#compared to having to do a 50/50 method for hours on end :p | Explore Tumblr Posts and Blogs

douxspider · 4 years

Text

— 𝐩𝐞𝐚𝐜𝐡𝐲 𝐤𝐞𝐞𝐧.

‘ARVIN RUSSELL x READER INSERT’

( potential spoilers for “the devil all the time” ) — Reader is new to town, working at a bakery ran by a kind old lady. Getting used to the ropes of the city, a man in blue arrives unsettled, holding a bloody rag against his knuckles and shivering just slightly. (occurs after arvin approaches the three bullies.)

warnings: blood, mentioned alcohol abuse, bullying. word count: 2,330 published: 9/17/20 ao3 link — part 2, 3

— — • — —

You didn’t ask for much in life. You didn’t want much. Your entire life you let the sea take you where it wanted to take you, and if it brought you to a flourishing island with the most beautiful sunsets and the softest sand, you let it. If it wanted to take you to the dangerous, icy hurricanes where waves clashed and thrown against each other and you drowned in the salty depth, you let it.

You don’t have a will, the town would mock you.

You were new to Ohio, originally coming from New York, and they liked to call you city girl. Your accent was more urban compared to the rural dialect around you. You stuck out like a sore thumb. The community grew together, knew everyone’s names, and when a random strange girl with only a plastic bag of clothes arrived at the nearest motel, it was all the rage.

Luckily, you managed to find a sweet baker lady to take you in. She had a plump figure, rosy cheeks, and graying auburn hair that spoke of pies and sunshine. Her name was Marilyn McCann, she was in her late 50s, and she had lost her two dear sons in the Vietnam war, her husband previously passing from health complications. Marilyn opened the baker, naming it McCann Boys in honor of them.

You were seated behind the counter on a stool, picking at a lemon and poppyseed muffin, placing chunks of the bread in your mouth and eating slowly. It was a quiet day, rain splattering against the window, most people wanted to bake indoors.

While you fidgeted with the book in your lap, idly reading it, you heard the bell ring. You glanced up, and instead of the man moving to the counter, he only took a seat by the window, a rag covering his knuckles as his hat hid his face. He refused to return your eye contact, which was used as a silent method of do you want me to come to you?

You were running the shop alone. You couldn’t ask Marilyn who this strange fellow was. You had to take the initiative.

Getting up from your seat, the stool groaned against the hardwood beneath you, and you made your way towards him. He was bouncing his jean-clad leg excessively, winding the rag around his tightened fist. There were dark stains on it, but you paid it no mind.

“Sir?”

The man twitched his head in your direction, his cap revealing only an inch more of his face before moving back down to the table. “Yeah?” His voice was low, a bit hoarse.

You leaned to the side a bit, crossing your arms, crooking a brow upwards. “You good?”

“Yeah, ah,” he spoke, moving his chin upwards to look at you, and he stopped. You did as well, a silent, complex tension thick between the two of you, before he continued, “Just uh… needed to sit down, s’all. Do I…” he cleared his throat after a voice crack, “do I need to buy somethin’?”

Shaking your head, you gave a quiet, slow, “No.”

Taking a better look at his hands, you noticed it was blood on the rag. So, he was getting that post-fight clarity. You moved to the back and grabbed some pure alcohol you and Marilyn liked to keep, pouring only a bit on a clean washing rag, before heading back to the mysterious man’s location. Taking his hands, he gave a quiet noise of surprise as you tore open his fingers from the old rag and placed it to the side.

“Lady, what are you— ow! Shit...”

Lightly sponging the rag against his knuckles, you then placed the new cloth in his hands, taking a seat in front of him.

The man in front of you seemed somewhat offended, clutching onto the rag and padding it over his knuckles, but also giving you a scowl. “The hell you do that for…? ‘Didn’t need that, I can take care of myself.”

“So, what’d the man do? Pissing contest taken too far?”

He removed the cloth from his hand and wrung his knuckles together, and you stared at the scabs. “Maybe you should keep your nose where it belongs, darlin’.”

You hummed, leaning over the table and resting your bare arms against the surface, looking out the stormy window. “Y’seem like a sweet girl,” the man spoke up, catching your attention, “but that kinda behavior here… askin’ too many questions, it can get ‘ya hurt.”

Eyeing him up and down, you tilted your head so it nearly rested on your shoulder. “Well… y’gonna hurt me, stranger?”

Brown eyes fogging over with clear distant memories, you watched his expression dampen, no longer seeming agitated but only conflicted. “No… no, I wouldn’t hurt ‘ya.” His voice was only a low grumble. “I was taught better than to hurt girls.”

Giving a hum as a response, you tapped your painted fingers against each other. “I’m not trying to be nosy,” you then confessed, “...just curious. Don’t hear much from this town regarding fist fights.”

“You’re the city girl?” With a wince, you nodded. “Ah.”

“That a bad thing, mister?” You asked, trying to analyze his expression. He seemed distant, staring off, before his eyes turned as round as saucers glancing at you.

“No, no, miss, I ain’t imply that. Lotta people know about you ‘round here, it’s rare for a cityfolk to come to this dot on the map,” he explained, “Just curious.”

Clearly that was an insinuation for you to indulge him on his question. Though, feeling smug, and honestly in your right, you told, “You tell me why you’re bleeding from your hands, I’ll tell you my harrowing tale of ending up in Ohio. How about that?”

Surprisingly, the stranger let out a quiet laugh. It was breathy, and for some odd reason you could tell he doesn’t do that often by the way it seemed foreign coming from him, the product from his lips being stopped with his mouth closing. “Fair. You’re good at this game, little lady.” He let his knuckles out into the open air before crossing his arms together, leaning back in the booth.

“My old man,” he started with a distant voice, grimacing at the latter, and you assumed there was a dark history there, “he taught me t’protect myself. To protect others. Now, he was no layabout, he was straight outta the war,” the stranger chuckled, “if anyone tried anythin’, he wouldn’t let ‘em. He taught me that with physical expression.” The jean jacket around his arms got tightened with his whitening grip. “Now, y’see, lotta folk in this town ain’t kind. They ain’t acceptin’, they don’t like new things. They don’t like concepts.”

You listened quietly, feeling your heart slow its pace within your chest, trying to silence itself to take in every word. “I got a sister. Step-sister. She’s sweet, but she ain’t like the others. They don’t like that.”

His jaw tightened as he looked out the window, his blue cap shading his eyes. “...Had t’put an end to it.”

An understanding finally settled in your head. You fiddled with the apron draped around your legs, chin tilted downwards as you took in the information. You looked back at him. “...That’s a good thing.”

“What?” He glanced at you from the corner of his eye.

“Protecting your sister. That’s a good thing.” You could tell he felt guilty only slightly, perhaps he was scared of himself, scared of what he did. “I never had a sibling growing up,” you told, “having someone there to protect me would’ve done me wonders.” The stranger moved his hand up to his mouth, rubbing the side of his index finger against his chin. You gave a weak smile. “People aren’t too kind here to me, so I don’t need to fantasize your sister’s reality. I can’t imagine what it must be like to be outcasted from your own town like that. Your sister must be a kind soul, being thrown to the wolves like sheep like that.” You shook your head. “It’s not right. I think you did what you had to do. Sometimes that’s the best you can do.”

He was staring at you, and you couldn’t help but to wonder if you said too much. If you were prying too much. You had never met this man before, he could’ve just killed someone for all you know for no rhyme or reason, he could be a sociopath, luring his next victim, but you trusted your gut on saying that this man was right in what he did.

The corner of his lips quirked upwards and he gave a quiet exhale through his nose, nodding his head before glancing at you, head tilted downwards. “Now, your story. Fair trade, little lady.”

With an amused smile, you shrugged. “Came from New York, had no ties. Father ditched when I was still learning my ABCs, mama abused alcohol, that’s what wound her up in the grave. Took that as my sign to go.” You recalled the dirty poor Manhattan streets you grew up on. “Manhattan… it’s a busy city. Too busy. No one knows ‘ya, but they assume they do.” You pointed at him to exaggerate, closing an eye, “If you’re in the wrong neighborhood, that’s what you are now. Wrong. I was a wrong, poor girl with no faith.”

“No faith?” The stranger asked.

“Faith didn’t keep me alive there. Only money.”

He nodded slowly. “Surprised to see someone here not lookin’ to God.”

You clasped your hands together and shrugged. “Well, when he brings me something nice, I’ll go to church.” Glimpsing up at him, you asked, “Do you have faith?”

“Only for my grandmama and sister. I ain’t got no interest listenin’ to a man for hours.”

“You seem like a family man, mister.” You smiled, leaning back. “Are they the only reason you’re here?”

A moment of hesitance resulted from him. “Yeah.”

You decided not to press further.

Taking in the quiet rain, you tapped your hands on the table beneath you three times and stood up, placing your hands on your hips. “Well, mister, do you drink coffee?”

He seemed so small in the booth, huddled up with his arms crossed, brown eyes that were no longer iced over with memories, but instead focused on you with a round childish charm to them. “Ah… yeah, I do.”

Smiling with a nod, you headed and started up the yellow coffee machine. You looked back at him, saw him staring out the window, and you finished up the mug of coffee and gave it to him, hot. Sitting in front of him with your muffin, you both indulged in your delicacies in a peaceful silence.

When his coffee was just about gone, he asked, “Mind if I smoke in ‘ere?” He wondered, and you gave him permission.

“Sure. The only thing I’m concerned about is the gross taste coffee and tobacco must have together,” Wrinkling your nose at the thought, the man laughed, amused as he placed a cigarette in his mouth and used a lighter.

He puffed in the smoke and then removed the cigarette from his mouth, pulling over an ashtray that rested on the table. Blowing through the thin slit between his lips, he murmured, “Arvin.”

“Hm?” You asked, wiping off your hands on your apron from crumbs.

“My name is Arvin Russell.”

Blinking at him, you smiled, testing out his name carefully. “Hi, Arvin. I’m Y/N L/N.”

Arvin seemed a little shy, his cap hiding most of his face before he moved his head up just slightly, catching your eye, pointing out, “‘Like that name. Suits you. A pretty name for a pretty girl.”

A little flustered, you pinched your bare lips together before giving out a breathy chuckle. He moved his cigarette to his lips, watching you closely, inhaling the smoke. “You’re sweet.”

Arvin smiled, the paper-wrapped cancer stick between his lips, he pulled it out with a quick huff and said, “You’re the sweet girl talkin’ to bloody strangers sulking in the corner of your shop and givin’ em free coffee, Y/N.” He was staring at the window when he said this, but his head turned towards you, relaxed against the seat behind him, tapping the ashes into the ashtray. “Y’deserve better than this place.”

Feeling overwhelmed with all the positive comments— you didn’t receive many— you tucked a strand of your hair behind your ear. “Well, Arvin, I think you deserve good things, too.”

Arvin gazed at you, a soft expression on his face before checking his watch. “Have to head home.” You both stood and you began to clean up. Arvin went up to the counter and gave a few dollars, and you stared at the money, gawking before giving a nervous smile and shaking your head.

“You don’t need to do that, Mr. Russell—”

“Arvin was doin’ just fine, sweet girl,” Arvin said with a smile. “Y’helped me out today. Thank you. Genuinely. I wanna pay back however I can.”

You took the money cautiously, feeling shy.

“Take that money for yourself. Buy yourself another pretty dress,” he said, eyeing the one you wore and tipping his hat. He was about to leave before he turned, hand flat against the glass, the other tucking his old rag into his coat pocket and gazing at you. “...We’ll be seein’ each other again, Y/N.”

Feeling overrun with flustered emotions, you smiled and said, “I would sure hope so, Arvin. I liked having you around.”

Arvin looked to the side, murmuring, “Likewise.”

You were left in the silence of the bakery, the rain turning into a light mist outside. Pressing your lips together, you changed your weight from foot to foot, turning to lean your back against the counter and giving a sigh.

Each encounter with him from then on would slowly grow into something more.

#arvin russell #arvin russell x reader #fic #the devil all the time #tdatt #reader insert #tom holland #mine #2k #peachy keen #douxdamian #my writing #sfw #T #multichap

327 notes · View notes

and-then-there-were-n0ne · 4 years

Text

Single-sex education for girls

Dustmann, Ku and Kwak (2017, p. 28) found that the “the net effect of having single-sex peers for three years is strongly positive for girls”. When classes were converted from 100% female to 50% female, girls’ achievement in languages (Korean and English) fell by 8-15% of a standard deviation (pp. 4, 27). (Also see, Dustmann et al., 2017, Why single-sex schools are more successful.)

A 2017 study of Year 3, 5 and 7 numeracy and literacy (NAPLAN) data by Dr Katherine Dix of the Australian Council for Educational Research (ACER) found that even when socio-economic status was taken into account, Year 7 girls at single-sex schools were 4.2 terms ahead of co-ed students in reading and 2.8 terms ahead in mathematics (Dix, 2017).

A 2016 survey by the South Australian Association of State School Organisations found that 61.45% of participants wanted more all-girl public schools offered in South Australia and that 82.88% of supporters of more all-girl school options were educators (p. 1). Participants reported on several advantages of all-girl schooling including academic performance (94%), Science, Technology, Engineering, Maths (STEM) participation (92%), sport participation (78%), reduced stereotyping (63%), confidence/ assertiveness (54%), teaching methods for girls (22%), improved body image (19%), better support (14%), safety (12%) and less bullying (9%) (p. 2).

In 2014, Professor Alison Booth of the Australian National University wrote in the Sydney Morning Herald that “the evidence is gathering that women in single-gender classes benefit, and they benefit significantly”. In fact, just one hour a week of single-sex education benefits girls (Booth, 2014). Booth et al.’s 2013 study found that female students at Essex University who were randomly assigned to all-female classes in their first year were 7% more likely to pass their introductory economics course than girls in co-ed classes. They also scored 8% higher on their final grade and 10% higher in their required second-year courses, despite only attending single-sex classes in their first year (Booth, Cardona-Sosa & Nolen, 2013, p. 3).

An Australian study has found that girls gain confidence in Information Technology (IT) in single-sex classes. The four-year study, which ran in seven co-ed and three girls-only schools, found that 45% of girls made an unprompted positive comment about their experiences in single-sex IT classes. Feedback from the girls included that girls-only classes were more conducive to learning because boys disrupt classes; they were more willing to ask for help without boys being present; they were more confident and not afraid to try things out; and that in co-ed classes, boys put them down when they were trying to do something or express an idea (Fisher, Lang & Forgasz, 2015).

In 2015, Andrew Hill of the University of South California found that opposite gender friends have a negative impact on the academic achievement of students at co-ed schools. Students aged 16 and over with higher numbers of opposite gender friends had lower grades across all subjects (p. 148); were less likely to graduate from high school or attend college (p. 173); had more difficulties getting along with their teachers (p. 148); and were more likely to be in a romantic relationship, which “may reduce both the quality and quantity of homework and studying”, as well as being “distracting in the classroom” (p. 171). Hill also found that in students aged under 16, grades in mathematics and science were negatively impacted by the effect of opposite gender friends, and that girls may benefit from single-sex classes in these subjects (p. 168).

A 2015 study by Eisenkopft et al. identified a “very robust” positive effect on mathematics proficiency for girls randomly assigned to single-sex classes in a Swiss high school (p. 137). The effect was greater for students with high ability in maths and in classes taught by a male teacher, but “the effect also holds for less talented students and for classes taught by a female teacher”. Girls in single-sex classes also “evaluate their mathematics skills more positively and are more likely to attribute their performance in mathematics to their own efforts rather than to exogenous talent or luck” (p. 125).

A SchoolDash analysis of GCSE results for 2015 found that 75% of girls attending England’s 271 government girls’ secondary schools achieved five good GCSEs compared with 55% of girls attending government co-ed schools, even after adjusting for socioeconomic background and selective intake. SchoolDash founder Timo Hannay wrote that these results are consistent with previous research, including a 2009 study of the Key Stage 2 and GCSE results of 700,000 girls by the Good Schools Guide which found that girls in all-girl comprehensive schools achieved better results than those who attended co-educational secondary schools, and a 2007 government-backed review which recommended that girls and boys should be taught separately to avoid girls being pushed aside in mixed-sex classrooms (Hannay, 2016; also see, Paton & Moore, 2009).

Park, Behrman and Choi’s 2012 study of South Korean students — who were randomly assigned to single-sex and co-ed high schools until 2009 — found that “high school female seniors who attend all-girls schools show significantly higher mean scores than their peers who attend coeducational schools” (p. 19). In addition, college attendance data demonstrated that “the four-year college attendance rate for female graduates is 3.1 percentage points higher for all-girls schools than for coeducational schools” (p. 20). The advantage of “all-girls schools over coeducational schools in sending female students to four-year colleges is fairly substantial”, with the study showing that “female students from all-girls schools are less likely to attend two-year junior colleges” (p. 21).

A 2012 PhD thesis by Dana Diaconu concluded that girls from Hong Kong and New Zealand “seemed to have benefited more from single-sex education than coeducation” (p. 248). Diaconu examined the Trends in Mathematics and Science Study (TIMSS) databases for 1995, 1999 and 2003, finding that the advantage of Hong Kong girls from single-sex schools in TIMSS 2003 in science scores “remained statistically significant … even after accounting for differences in student background and school characteristics” (p. 248).

Suzanne Link’s 2012 study of the 1999 Trends in Mathematics and Science Study (TIMSS) data for South Korean middle schools found “positive effects of single-sex schooling for girls” in mathematics. The effects “are not only highly statistically significant and non-negligible in their magnitude, but also highly relevant since math[s] performance is consistently linked to future earnings” (p. 2).

An Australian study reporting on a year-long trial of single-sex Year 7 classes at a Queensland primary school found that girls in mixed-sex classes reported significantly reduced scores on emotional and behavioural engagement by the end of Year 7 (Gilmore, Patton, McCrindle & Callum, 2002, p. 1). The study authors write that is possible that the girls in mixed-sex classes were “negatively affected” by the “presence of boys in the classroom” or perhaps they “felt disadvantaged” by not being in the single-sex class for girls (p. 5).

Belfi et al.’s review of the literature on class composition by gender and ability in secondary school found that “single-sex classes are advantageous for girls’ school well-being and academic self-concept” (Belfi, Goos, De Fraine & Van Damme, 2011, p. 2).

Veronica Cabezas found that: “Girls in single-sex schools perform better academically than their counterparts in coeducational schools, after holding constant measures of selection, background, peers and school factors” (Cabezas, 2010, p. 227).

Katherine Bradley investigated single-sex education and its impact on academic achievement, concluding that “the single-sex environment provides females with the best opportunity for academic achievement” (Bradley, 2009, p. 119).

Alliance of Girls’ Schools Australasia

#single sex education #separatism #feminism #intersectional feminism #radical feminism

63 notes · View notes

orbemnews · 3 years

Link

Oil Prices Return to Pre-Pandemic Highs: Live Updates Here’s what you need to know: An oil tanker truck in the Permian Basin part of Texas. Futures for West Texas Intermediate crude have recovered from the price collapse last spring.Credit…Angus Mordant/Reuters U.S. markets Global stocks climbed on Monday and futures indicated U.S. markets would extend their record highs when Wall Street opens later. Optimism that the vaccine rollout and fiscal stimulus will pave the way for the economic recovery could also be seen in the commodities market. Oil prices have recovered from their pandemic-related declines. Over the weekend, Janet Yellen, the Treasury secretary, pushed for the Biden administration’s $1.9 trillion spending plan. She said passing the stimulus package could allow the economy to reach full employment by next year, but doing too little could scar workers and the economy for years. Last week, the S&P 500 index gained more than 5 percent, its best week since early November during the presidential election. Traders haven’t been unnerved by news that South Africa has halted use of the AstraZeneca-Oxford coronavirus vaccine. The country found that the vaccine did not protect clinical-trial participants from mild or moderate illness caused by the more contagious virus variant that was first seen in South Africa. Oil West Texas Intermediate futures, the U.S. crude benchmark, rose 1.2 percent to $57.54 a barrel on Monday, above the high from early 2020. During the first few months of the pandemic, oil prices collapsed, with some futures briefly dipping into negative prices. Production cuts by OPEC countries and its allies have helped buoy oil prices. The recovery should benefit oil and gas companies, which recently reported steep declines in profit for 2020 because the pandemic sapped demand for oil. GameStop, Dogecoin and ‘meme’ trading GameStop shares rose 16 percent in premarket trading, extending a 19 percent rebound on Friday. In the past two weeks, shares in the video game retailer have been on a wild ride spurred on by retail traders hyping up the stock in a Reddit forum that has made fast winners and losers of amateur investors. The close on Friday was $63.77 a share. Dogecoin, a joke cryptocurrency, is rallying again as celebrities and billionaires including Elon Musk and Snoop Dogg post memes and plug the digital coin. In the past 24 hours, its price has risen 25 percent. Europe and Asia Stock indexes in Europe rose with Italy’s among the best performers as Mario Draghi, the former European Central Bank president, works to set up a new government and end the recent political impasse. The Stoxx Europe 600 gained 0.7 percent, led higher by bank stocks. Stocks in Asia ended the day higher. The Nikkei 225 in Japan jumped 2.1 percent, and the index was above 29,000 for the first time since 1990. The biggest contributor was SoftBank, which reported a quarterly profit of $11 billion because of a surge in value of some of its investments, including Uber and DoorDash. A DoorDash delivery person in Los Angeles last week. Softbank’s investments in DoorDash soared after the delivery company held an initial public offering in December.Credit…Mario Anzuoni/Reuters For many technology companies, the past 12 months have been a roller coaster, starting with a pandemic-driven market-wide sell-off in March and ending with one of the largest stock market run-ups in history. But for Japan’s SoftBank, which manages the world’s largest tech investment fund, it has been an especially wild ride. In an earnings report released on Monday, SoftBank notched more than $11 billion in profit for the three months that ended in December, driven by surging values for the company’s portfolio of holdings in companies like Uber and the food delivery app DoorDash, which have experienced whiplash changes in their share prices over the last year. The result was a far cry from SoftBank’s position at the same time last year. Then, the company found itself in the midst of an epic slide that ended with its declaring an annual operating loss of more than $12 billion following investment losses on companies hit hard by the pandemic. But what the market takes away, it can also give back. By the summer, SoftBank had already undergone a seemingly miraculous recovery thanks to the sale of tens of billions of dollars of assets and a hot stock market. Since then, the market has grown hotter still. In December, the value of SoftBank’s investments in DoorDash and the biotech company Seer, among others, skyrocketed as investors piled into the companies’ initial public offerings as part of a broader frenzy for new share sales. A market rally in shares of Uber was also a major profit driver for SoftBank this quarter, it said. In a triumphant earnings conference, SoftBank’s founder, Masayoshi Son, compared his company to the goose that laid the golden egg. In February of last year, the media was saying that the company was laying only “rotten eggs,” Mr. Son said. But this earnings report has proved the skeptics wrong, he argued. “We have a turbocharger strategy to turn white eggs into golden eggs,” he said, adding, “Those golden eggs are laid not by chance but by plan.” Investors so far seemed to agree. After a precipitous drop this summer, SoftBank’s share price has surged. The stock was trading at 9,485 yen, or about $90, per share in Tokyo by market close Monday, almost matching its highs in early 2000, just before the collapse of the first internet stock bubble. A nurse administering a coronavirus vaccine last Wednesday in Newark. States have each developed their own formulas to determine eligibility for the vaccine.Credit…Justin Lane/EPA, via Shutterstock Federal, state and local health authorities across the United States are using dozens of algorithms — some automated systems and others simple prioritization lists — to help determine where vaccines are sent and who can get them. The formulas generally follow guidelines from the Centers for Disease Control and Prevention to prioritize frontline health care workers, nursing home residents, senior citizens and those with major health risks — and yet public health agencies and medical centers at every level have developed different allocation formulas, based on a variety of ethical and political considerations. The result: Americans are experiencing wide disparities in vaccine access. Oregon, for instance, has prioritized teachers over the elderly for Covid shots, an approach that could help schools and businesses reopen. New Jersey has put smokers ahead of educators, which could save lives. Some prioritization formulas also conflict with one another or impose such prescriptive rules that they hinder immunizations, public health experts say. Ellen P. Goodman, a professor at Rutgers Law School who studies how governments use automated decision-making systems, said algorithms were needed to efficiently allocate the vaccines. But public agencies and health centers should be transparent about the prioritization formulas, she added. “We want to know who is using them, what they are trying to do, who owns the proprietary algorithms, whether they are audited,” she said. A multiagency federal effort — originally called Operation Warp Speed and created by the Trump administration — has managed nationwide vaccine distribution through Tiberius, an online portal developed by Palantir, the data-mining giant. Now the Biden administration, which has retired the program’s name, has taken over and is continuing the effort. To divvy up doses, federal administrators use a simple algorithm that divides the total amount of vaccine available each week among the 50 states — as well as U.S. territories and a few big cities like New York — based on the number of people over 18 in each place. Even so, states began warning last fall about Tiberius’s potential drawbacks. In interim vaccine plans filed with the C.D.C., some state health administrators complained that the platform seemed overly cumbersome and that the algorithm’s week-by-week allotments would make it difficult to plan monthslong vaccination campaigns. Indeed, some health officials and researchers have described the Tiberius algorithm as a black box. “Why can’t they make public the methods that they use to make these estimations?” said Dr. Rebecca Weintraub, an assistant professor of medicine at Harvard Medical School who was a co-author of a recent study on state vaccination plans. “Why are the states receiving a different number of doses than they expected per week?” Chen Feng built HNA from a small regional airline into a conglomerate.Credit…China Stringer Network/Reuters Pressure is mounting on companies whose behavior could pose a risk to China’s financial system. HNA Group, the vast Chinese conglomerate that threw tens of billions of dollars at trophy businesses around the world, is nearing the biggest corporate collapse in recent Chinese history, offering a glimpse of how Beijing treats its most powerful entrepreneurs. HNA’s insolvency is the largest China has seen since the country first began using its bankruptcy law in 2007, according to Michelle Luo, a bankruptcy lawyer at Hui Ye law firm. It will also test the law’s strength — just 76 companies have gone through bankruptcy proceedings in China, Alexandra Stevenson reports for The New York Times. Xi Jinping, China’s top leader, told a meeting of the country’s senior Communist Party officials late last month that the government must anticipate risks even as it pursues growth. He urged officials to make plans to deal with “gray rhinoceros” events, referring to large and evident problems in the economy that are ignored until they become urgent threats. Chinese media had often referred to HNA as a gray rhino before its decline. The party has strengthened its hand in private business in recent months and urged entrepreneurs to “identify politically, intellectually and emotionally” with its goals. It has also pledged to prevent what it called the “disorderly expansion of capital,” a reference to the type of lavish spending of borrowed money for which HNA had become known. Among the party’s recent prominent targets is the Chinese online shopping giant Alibaba Group. In December, the authorities opened an antitrust investigation into the company, which the Chinese billionaire Jack Ma helped found. One month earlier, days before a planned initial public offering of Mr. Ma’s finance giant, Ant Group, regulators stepped in to stop it. Hilario Saldívar, a cook and dishwasher, had his hours cut and struggles to pay the $2,600 monthly rent on a two-bedroom apartment that he shares with four others.Credit…Sarahbeth Maney for The New York Times Even before last year, one in four U.S. renters — about 11 million households — was living in a household that spent more than half its pretax income on housing, and overcrowding was on the rise. By one estimate, for every 100 very low-income households, only 36 affordable rentals are available. Now the pandemic is adding to the pressure, Conor Dougherty reports for The New York Times. Rents have fallen in many big cities, but vacancy rates for the cheapest buildings are essentially flat from last year, according to CoStar Group, a commercial property group. That is: Nothing about the pandemic has changed the fact that there is a longstanding shortage of affordable housing, so anyone who loses an affordable home will still have a hard time finding a new one. The pain in the U.S. housing market is most severe at the bottom. Surveys of large landlords whose units tend to be higher quality and more expensive have been remarkably resilient through the pandemic. Surveys of small landlords and low-income tenants show that late fees and debt are piling up. And in the same way that subprime mortgages were an early indicator of the mid-2000s housing crisis, today informal renters — roommates and sublessors who don’t have a proper lease — offer a look below the surface. One measure of relief came when President Biden extended by two months a federal eviction moratorium that was scheduled to expire at the end of January, as states and cities also moved to extend their own eviction moratoriums. In addition, $25 billion in federal rental aid approved in December is set to be distributed. But for every million or so households who are evicted in the United States each year, there are many more millions who move out before they miss a payment, who cut back on food and medicine to make rent, who take up informal housing arrangements that exist outside the traditional landlord-tenant relationship. Source link Orbem News #highs #Live #oil #prepandemic #Prices #return #Updates

0 notes

ericvick · 3 years

Photo

The Crypto Daily – Movers and Shakers – January 17th, 2021

InvestorPlace

10 Smart Stocks to Buy With $5,000

If you’re looking to build a portfolio of stocks to buy with just $5,000, the advent of fractional share ownership has made it a whole lot easier. Google the words “fractional share portfolios,” and you get 527,000 results with everything from reviews on seven of the best fractional share investing brokerages to links to some of the leading players in this burgeoning area of the markets. Many think of Robinhood when they think fractional, but the truth is almost every major online broker in this country’s got some offering or service.InvestorPlace – Stock Market News, Stock Advice & Trading Tips Heck, I can remember years ago, when FolioFN was the only game in town. Launched in 2000, it was acquired by Goldman Sachs (NYSE:GS) in May 2020. FolioFN’s self-directed accounts are scheduled to be transferred to Interactive Brokers (NASDAQ:IBKR) early in 2021. In the meantime, for those who don’t want to do the work of constructing a $5,000 portfolio of stocks to buy, here are 10 recommendations to help get you started. Alphabet (NASDAQ:GOOG, NASDAQ:GOOGL) Tesla (NASDAQ:TSLA) Nvidia (NASDAQ:NVDA) SVB Financial (NASDAQ:SIVB) Roku (NASDAQ:ROKU) Berkshire Hathaway (NYSE:BRK.A, NYSE:BRK.B) Dollar General (NYSE:DG) Apple (NASDAQ:AAPL) Williams-Sonoma (NYSE:WSM) Thor Industries (NYSE:THO) 9 Stocks That Investors Think Are the Next Amazon Their share prices will add up to $5,000 or less. To make things interesting, all 10 stocks must have share prices exceeding $100. Stocks to Buy: Alphabet (GOOG, GOOGL) $1,740 Source: BigTunaOnline / Shutterstock.com It’s funny, I had intended to include Amazon (NASDAQ:AMZN) in my list of 10 stocks to buy, but given I was limiting my names to those companies with shares prices greater than $100, the e-commerce giant’s $3,166 share price would have made it awfully hard to fit nine more under $5,000. So I went with Alphabet, a company I didn’t write about at all in 2020, but helps me achieve my task. InvestorPlace’s Mark Hake recently suggested that rising ad sales make it an attractive investment in 2021. My colleague compares Google to the valuations of Apple, Microsoft (NASDAQ:MSFT), and Amazon. He reckons that Google should have a similar valuation to the three companies at $1.43 trillion or 6.7 times sales. As I write this, Google’s market capitalization is $1.18 trillion, 17% below Hake’s simple calculation, which puts its share price at $2,112 per share. I like the upside. Tesla (TSLA) $845 Source: franz12 / Shutterstock.com The second-highest share price in our $5,000 portfolio, we can thank Elon Musk for doing a five-for-one stock split in August 2020. Without it, TSLA would take up 86% of our investment capital. I’m an unabashed Tesla fan, so I’m not going to give you reasons why the valuation is over-the-top, although there’s no question it puts all the other large car companies to shame with its $810 billion market cap. InvestorPlace contributor Matt McCall recently gave investors some wise advice regarding the electric vehicle (EV) maker. McCall believes that rather than griping about the price you have to pay for its shares, embrace the fact that even the mighty Tesla has corrections, so buy like crazy on the rare occasion that it happens. To illustrate his point, McCall references its pullback in September 2020, shortly after its stock split. On Aug. 31, it was trading just under $500. In a week, it fell 34% after Tesla was left off the annual additions list for the S&P 500. 7 Cheap Stocks to Buy as Democrats Gain Control Ultimately, Tesla was added to the index on Dec. 31. As money managers added TSLA to their portfolios, it moved even higher. Nvidia (NVDA) $528 Source: Hairem / Shutterstock.com If you’re one of the lucky investors who joined the Nvidia bandwagon five years ago when it was trading around $26, you’re sitting on an annualized total return of more than 79% through Jan. 13. It’s crazy to think that things can get any better for NVDA shareholders over the next five years. Still, they actually could, given the growth in gaming, cloud computing, and artificial intelligence. As my InvestorPlace colleague, Faizan Farooque, recently stated, you most certainly won’t be buying Nvidia if you’re a value investor — it trades at 45 times its forward earnings, far higher than many of its peers — but when it can grow sales at 50% a quarter and continue to beat analyst expectations, it most certainly deserves a premium valuation. In June 2019, I argued that Nvidia’s free cash flow made it a great stock to buy on dips. At the time, it had lost about half of its value over nine months — October 2018 to June 2019 — and was trading around $145. Some 18 months later, it’s up almost four-fold and generating more than $4.2 billion in 12-month free cash flow. Buy some now and wait for the next big dip. It’s bound to happen sooner or later, no matter the near-term prospects. SVB Financial (SIVB) $465 Source: Pavel Kapysh / Shutterstock.com I’m not going to say too much about SVB Financial because it’s one of those bank stocks to buy that you have to get to know for yourself to understand why it’s so special. You wouldn’t think this was the case by the analyst coverage of its stock. At the moment, 21 analysts cover SIVB, with eight rating it a buy and 12 a hold with an average price target of $424.49. Sure, it’s come a long way over the past year compared to its peers — it has a one-year total return of 74.2% — but that’s because investors recognize that the bank’s laser-like focus on providing lending, asset management, and banking services to innovators and entrepreneurs will always be in demand. Recently, it announced that it would pay $900 million to buy Boston Private Financial Holdings (NASDAQ:BPFH) for a combination of cash and stock. The Boston-based private bank specializes in wealth management and other banking services. Together, SVB Financial’s wealth management business will have almost $18 billion in assets under management. The 7 Best Marijuana Stocks on the Markets Right Now Continue to ignore SIVB at your peril. Roku (ROKU) $418 Source: JHVEPhoto / Shutterstock.com The streaming platform has gotten off to a hot start in 2021, up 26% year-to-date and more than 205% over the past 52 weeks. Roku and HBO Max parent, Warner Media, buried their longstanding disagreement recently by announcing that the streaming service would be available on Roku as of Dec. 17, 2020. By getting a spot on Roku, HBO Max is now on all the major over-the-top platforms. “We believe that all entertainment will be streamed and we are thrilled to partner with HBO Max to bring their incredible library of iconic entertainment brands and blockbuster slate of direct-to-streaming theatrical releases to the Roku households with more than 100 million people that have made Roku the No. 1 TV streaming platform in America,” Scott Rosenberg, SVP of Roku’s platform business, said in a statement. The key part of the above statement is that Roku believes that all entertainment will eventually be streamed. I couldn’t agree more. That’s why I recommended ROKU stock in December 2017 and still recommend it among stocks to buy in 2021. Berkshire Hathaway (BRK.A, BRK.B) $235 Source: Jonathan Weiss / Shutterstock.com I recently read an article about the reasons why Warren Buffett failed in 2020. This kind of analysis of the Oracle of Omaha has been going on for years, possibly as long as Buffett’s been investing in stocks to buy. Yes, Berkshire Hathaway severely underperformed the S&P 500 in 2020 — up 2.5% versus 16.5% for the index — but I’ve always believed that the biggest boost to BRK stock will come when the holding company has to be methodically wound down due to the passing of Buffett and Charlie Munger. Consider that its equity portfolio, which is massive at $271 billion, represents just one-third of Berkshire’s assets at the end of September 2020. I can assure you that the true value of the $418 billion or so in privately-owned assets on its balance sheet is worth far more than this. When the time comes to wind it down, the board will do what’s necessary to ensure fair value is obtained for every business. It’s possible the process could take a decade or more. The 7 Best Startups You Can Buy on StartEngine Right Now When people say that Warren Buffett has lost his touch, they forget that the final tally has not been given. Not by a longshot. Dollar General (DG) $213 Source: Jonathan Weiss / Shutterstock.com It’s not a secret that Dollar General caters to customers that don’t have a tremendous amount of disposable income. It probably also doesn’t come as a surprise that its employees aren’t flush with cash, so the fact that it will pay those of its 157,000 employees who get a vaccine four hours of pay is noble. And smart business. “‘We do not want our employees to have to choose between receiving a vaccine or coming to work,’ Dollar General (DG) said in a press release, noting that its hourly workers face hurdles to getting vaccinated, such as travel time, gas mileage or childcare needs.” If there’s a retailer that has done well during Covid-19, Dollar General would have to be at the top of the list. In early December, Dollar General reported Q3 2020 results that included 12.2% same-store sales growth and a 62.7% increase in earnings per share. As a result, it’s passed on a total of $173 million in 2020 for employee appreciation bonuses. As it continues to open more stores while simultaneously growing its gross margins, the fact that it remembered that its employees are the ones who deliver this good fortune to shareholders is a big reason why DG stock will continue to move higher in 2021. Apple (AAPL) $130 Source: Hadrian / Shutterstock.com Most of the talk around AAPL stock right now revolves around its long-simmering Project Titan and its efforts around delivering its own autonomous electric vehicle. The Verge recently reported that Apple held discussions in 2020 with Canoo (NASDAQ:GOEV), the EV startup using a platform based on a skateboard to provide a much better cabin design for its future vehicles. Canoo apparently just wanted some investment capital. Apple, on the other hand, was thinking more about acquiring the business and integrating it into its existing work in this area. The two didn’t come to an agreement. Canoo went public and Apple’s now working with Hyundai (OTCMKTS:HYMTF) on getting a self-driving EV to market by 2024. Wedbush Securities analyst Dan Ives recently suggested that Apple could be worth $3 trillion by sometime in 2022 due to strong iPhone 12 sales. He projects it could sell as many as 250 million in 2021. “If Apple continues to execute at this pace, a $3 trillion market cap could be on the horizon over the 12 to 18 months,” Ives is reported to have said. 7 Dividend Stocks That Are Growing Their Payouts As I write this, it’s at $2.2 trillion. Williams-Sonoma (WSM) $125 Source: designs by Jack / Shutterstock.com Several news outlets reported that the retailer’s CEO, Laura Alber, sold some Williams-Sonoma stock just before Christmas. Don’t be alarmed; it was only 15,000 shares or 3.5% of her total holdings. And it was part of her Rule 10b5-1 trading plan started in September 2019. As I always like to say, even wealthy CEOs have bills to pay. Over the past year, Williams-Sonoma stock has delivered a total return of 61.4% for its shareholders, including Alber. That’s double the returns of the specialty retail sector as a whole and three times the entire U.S. markets’ performance. In June 2016, I called WSM one of the best retail stocks to buy due to its excellent omnichannel experience. Going on five years later, nothing’s changed about that assertion. During Covid-19, business at the retailer has been full-speed ahead. Here’s what I said about it in December: “It’s got a business that’s ideally balanced between online and brick-and-mortar sales. In the second quarter, it generated 76% of its sales online; in Q3, due to the novel coronavirus constraints, its online sales accounted for 70% of its total revenue — while growing by almost 50% over last year– and that’s during a pandemic,” I said on Dec. 9. “More importantly, its Q3 profits were through the roof — up 151% to $2.56 a share thanks to significantly higher margins — and that was only through Nov. 1. It doesn’t include Black Friday and Cyber Monday.” The world’s going digital, and that’s good news for Williams-Sonoma. Thor Industries (THO) $105 Source: Angel DiBilio / Shutterstock.com There is no question that 2020 was good for recreational vehicle manufacturers such as Thor Industries, as people young and old sought the great outdoors, away from the maddening, Covid-19 crowd. The problem for investors who’ve followed the RV industry for any length of time is that the good times never seem to last. In the case of the novel coronavirus, once vaccines make humans comfortable with packing together in large crowds, the great outdoors won’t be nearly as enticing as Paris or Australia. That being said, the latest push into RVs may be coming from a sub-set of consumers who might actually take to the open road. “All dealers are reporting a high mix of first-time buyers as evident by lack of trade-in units,” said Wells Fargo analyst Tim Conder in a July 15, 2020 note. “Dealers are saying as high as 80% of customers are first-time buyers … vs. the typical 25% mix. The pandemic is driving the purchase decision for new-entrants.” If even half of those first-time buyers stick around long enough to upgrade to a bigger or better model, Thor Industries might not have to worry about the eventual downturn. To me, THO is one of the perfect stocks to buy for the long haul, buying more whenever it corrects by more than 5-10%. On the date of publication, Will Ashworth did not have (either directly or indirectly) any positions in the securities mentioned in this article. Will Ashworth has written about investments full-time since 2008. Publications where he’s appeared include InvestorPlace, The Motley Fool Canada, Investopedia, Kiplinger, and several others in both the U.S. and Canada. He particularly enjoys creating model portfolios that stand the test of time. He lives in Halifax, Nova Scotia. At the time of this writing Will Ashworth did not hold a position in any of the aforementioned securities. More From InvestorPlace Why Everyone Is Investing in 5G All WRONG Top Stock Picker Reveals His Next 1,000% Winner It doesn’t matter if you have $500 in savings or $5 million. Do this now. The post 10 Smart Stocks to Buy With $5,000 appeared first on InvestorPlace.

#17th #Crypto #daily #January #movers #Shakers

0 notes

irispublisherscasestudies · 3 years

Text

Assessment of Umbilical Cord Milking on the Outcome of Term and Preterm Infants, Controlled Clinical Trial | Iris Publishers

Authored by Omima T Taha*

Abstract

Background: Early cord clamping and cutting of the umbilical cord at birth may contribute to anemia in infancy thus it can deprive the infant of 60 to 100 ml of whole blood representing 30-50 mg/kg of iron. The umbilical cord milking is a safe technique.

Aim of the study:b> The aim of the study to assess the effects of umbilical cord milking as compared with early cord clamping on hematological parameters (hemoglobin, packed cell volume, bilirubin and ferritin) among term and near term neonates.

Materials & methods:b> This study was carried out as randomized, controlled clinical trial. The subjects were divided randomly into two groups (200 neonates who the cord was milked after cutting and clamping at 25 cm from the umbilicus as a study group and 200 neonates who were received early cord clamping without milking as a control group) in term and near term infants.

Results:b> the hemoglobin level significantly increased in study group at 12, 48 hours and 6 weeks of birth (16.9, 16.9 &15.5 gm/dl) as compared with control group (16.2, 16.2 &15.0 gm/dl) and serum ferritin level significantly increased in study group at 6 weeks of birth (135.4 μg/ml) as compared with control group (128.8 μg/ml). The hematocrit level at 12 and 48 hours after birth was significantly higher in study group (p= 0.016). Serum bilirubin was slightly elevated in study group but there were not any infants of them needed phototherapy.

Conclusions: Umbilical cord milking improved hemoglobin and iron status in term and near term neonates.

Keywords: Delayed cord clamping; Term and preterm; early cord clamping; Umbilical cord milking

Introduction

Current evidences suggest that the practice of immediate clamping and cutting of the umbilical cord at birth may contribute to anemia in infancy [1]. Immediate clamping can deprive a full term infant of 60 to 100 ml of whole blood representing 30-60 mg/ kg of iron [2]. The low tech-low cost” intervention of delayed cord clamping can reduce anemia in infancy by enhancing placentalinfant transfusion at birth. Delayed cord clamping (DCC), in which the cord is clamped after a short delay after birth, and umbilical cord milking (UCM), in which cord blood is stripped or milked toward the baby, have been shown to prevent anemia in infants [3].

These procedures allow the transfer of additional blood volume and hemoglobin (Hb %) from the placenta to the neonate. This process can improve the infant’s iron stores, which may be of particular value in settings in which nutrition is poor [4]. However, a recent meta-analysis reported that delayed cord clamping is only marginally beneficial in reducing anemia in term neonates [5]. Moreover, there are concerns about delayed initiation of resuscitation and increased incidence of hypothermia among preterm neonates undergoing these procedures [6]. Also, the risk of maternal bleeding makes a delay in cord clamping at the time of cesarean section challenging [3].

One clinical trial and a secondary analysis from the same trial have compared milking of a 20 cm segment of the umbilical cord versus immediate umbilical cord clamping on preterm singleton infants born (> 34 weeks ) of gestation. Significant findings in the clinical study included higher initial Hb concentration, mean systemic blood pressure, reduced need for blood transfusion and higher urine output during the first 72 hours in the group that underwent umbilical cord milking compared with the group that underwent umbilical cord clamping. Also the group that underwent umbilical cord milking required a shorter duration of supplemental oxygen and mechanical ventilation [7].

Recent studies have demonstrated that UCM and DCC result in comparable increases in Hb in premature neonates. However, there are insufficient data about the effect of UCM in full-term neonates. The aim of the present will be to investigate the effects of umbilical cord milking in term (gestational age ≥37 - 40+6 weeks) and near term infants (gestational age >34- 36+6 weeks) as regard hematological values, incidence of anemia and hemodynamics [8].

Patients and methods

This is randomized, controlled clinical trial study conducted at Obstetrics and Gynecology department of Suez Canal University hospitals among all pregnant women of fetal age > 34 weeks for cesarean delivery and randomly divided into two groups:

1) Study group: enrolled neonates were allocated to umbilical cord milking technique.

2) Control group: enrolled neonates were allocated to early umbilical cord clamping without milking technique.

Exclusion criteria include had Infants with congenital anomalies, intrauterine growth restriction, Infants with short umbilical cord length (<25 cm) , Delivery by cesarean section for fetal distress, Rhesus factor negative mothers, Cord prolapsed, Hydropesfetalis, Placenta previa, Placental abruption, Cord abnormalities as true knots, multiple gestation and Women with chronic medical illness (diabetes mellitus, Hypertension, cardiac diseases) or pregnancy related illness (gestational diabetes mellitus, preeclampsia). And this study estimated sample size was: n=400 (200 patients for each group).

Study procedure

An informed written consent was obtained from each participant before enrollment in the study. All enrolled women before lower uterine segment cesarean section delivery, were subjected to the following:

1) Full history (age, LMP, socioeconomic status)

2) Maternal weight

3) Maternal high and then BMI

4) Maternal hemoglobin

5) History of medical disorders, history of anemia, and history of antenatal iron supplementation and

6) Gestational age based on date of last menstrual period and documented and proved by first trimester ultrasonographic examination.

In all cases after birth, the neonates were held on the thighs of mother in cesarean section while the umbilical cord was cut and clamped.

In the study group

The cord was cut at approximately 25 cm of length from umbilical stump within 30 seconds of birth (early clamping). Then the neonate was placed under the radiant warmer. The umbilical cord was raised and milked from the cut end toward infant 3 times with speed at 10 cm/ sec, and then clamped 2-3 cm from the umbilical stump.

In the control group

The umbilical cord was clamped early (within 30 seconds) near the umbilicus and was cut without doing cord milking [3].

After clamping the cord, the neonates of both groups were received the routine care by the attending pediatrician according to standard protocols of neonatal post-delivery newborn care [9].

All neonates of both groups were evaluated for the following:

a) Before discharge of mother and infant hemoglobin and packed cell volume was measured at first 12 hours and 48 hours of postnatal life.

b) Serum bilirubin was measured at 48 hours of postnatal life.

c) Assessment of hemodynamic parameters of heart rate, respiratory rate and blood pressure in the first 48 hours of postnatal life (30 min, 12 hours and 48 hours).

d) All neonates were followed up till age of six weeks and a follow up visit was scheduled for all infants with evaluation of hemoglobin, and serum ferritin at that visit for assessment of incidence of anemia.

Statistical analysis

Gathered data was processed using SPSS version 15 (SPSS Inc., Chicago, IL, USA) 21st edition (2013). Quantitative data was expressed as mean±SD while qualitative data was expressed as numbers and percentages (%). Student t test and ANOVA test was used to test significance of difference for quantitative variables and Chi Square were used to test significance of difference for qualitative variables. A probability value of p-value < 0.05 was considered statistically significant.

Results

As shown in (Table1) there were not significant differences in the baseline demographic characteristics of two groups. Most of maternal age was < 35 years (64% in study group & 56% in control group), were house wife (93.5 % in study group &89.5% in control group) and lived in Urban (66%in study group & 56% in control group). Most of the mothers in this study their socioeconomic status were moderate 53% of mothers in early cord clamping group and 48% of mothers milking group and it was no significant difference in both groups.

Read More....Full Text

For More articles in Archives of Clinical Case Studies please click on: https://irispublishers.com/accs/

To Read More : Iris Publishers Linkedin

#Iris Publishers #hypertension symptoms #clinical cases #case reports

0 notes

lupinepublishers-ado · 4 years

Text

Potentiation of Activity of Benfotiamine Co Administered with Thyroxine in Diabetes Induced Peripheral Neuropathy in Rats

Lupine Publishers| Archives of Diabetes & Obesity

Abstract

Diabetic peripheral neuropathy (DPN) is a multi-etiological microvascular complication. Prolong hyperglycemia leads to formation of advance glycation end product (AGE) and oxidative stress which are contributors of nerve dysfunction. DPN manifests as pain, slowing of nerve conduction velocity (NCV), sensory loss etc. The aim of the present study is to evaluate the individual and combined protective effect of benfotiamine (BT) and thyroxine (T4) against Streptozotocin (STZ) induced DPN in rats. After 48 hours of a single injection of STZ (60 mg/kg bw i.p) diabetic rats were administered BT (100 mg/kg p.o.), T4 (1mg/kg.s.c,) and their combination. Diabetic rats at 5th week, exhibited significant decrease in body weight, hyperalgesia, decreased muscle coordination, grip strength and NCV. Antioxidant activity of reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) was also found to be significantly decreased. Significant higher levels of glycosylated hemoglobin (GHb) and Malondialdehyde (MDA) were also observed in diabetic rats. Treatment with BT, T4 and their combination attenuated the decrease in level of nociceptive threshold, muscle coordination, grip strength.

NCV and antioxidant activity. Significant decrease in the elevated levels of GHb and MDA was also observed. A histopathological study of sciatic nerve also confirmed the improvement in cell architecture as compared to diabetic rats and has strengthened the neuroprotective effect of BT and T4 combination group. An improved In Vitro AGE inhibitory activity of BT, T4 and their combination was observed. These finding suggested that BT, T4 and their combination exerts a protective effect in progression of diabetic neuropathy by decreasing GHb, AGE formation and oxidative stress.

Keywords:Micro vascular; NCV; Antioxidant; AGE; Thyroxine; Benfotiamine

Abbreviations:DM: Diabetes mellitus; DPN: Diabetic Peripheral Neuropathy; MAPK: Mitogen Activated Protein Kinase; NCV: Nerve Conduction Velocity; TH: Thyroid Hormones; BT: Benfotiamine; AGE: Advance Glycation End Product; LPO: Lipid Peroxidation; SOD: Superoxide Dismutase; CAT: Catalase; GSH: Glutathione; TBARS: Thiobarbituric Acid Reactive Substances; BSA: Bovine Serum Albumin; PKC: Protein Kinase C; ROS: Reactive Oxygen Species

Introduction

Diabetes mellitus (DM) is a worldwide major health problem and it is a chronic metabolic disorder characterized by hyperglycemia resulting from inadequate secretion or impaired action of endogenous insulin. The prevalence of diabetes is increasing worldwide and is believed to increase to 300 million by the year 2030 [1]. Uncontrolled or persistent hyperglycemia in DM leading to several microvascular and microvascular complications. Diabetic peripheral neuropathy (DPN) is a common microvascular complication of DM affecting more than 50% of the diabetic patients [2]. The pathogenesis of DPN is considered to be complex and multifactorial resulting from contributions of various pathways including metabolic and vascular factors, which consists of activation of polyol pathway, advanced glycation end products pathway, hexosamine pathway, increased activity of mitogen-activated protein kinase (MAPK), protein kinase C, poly (ADP-ribose) polymerase, oxidative stress, apoptosis, impaired neurotrophic support, autoimmunity, inflammation, up regulation of endothelin [3]. The impairment of nerve function is a well-established early manifestation of diabetes both clinically and in experimental animal models. DPN causes dysfunction of small and large nerve fibers and negatively impacts quality of life in diabetic patients. Small-fiber peripheral neuropathy is characterized by behavioral abnormalities (cold, thermal hyperalgesia, loss of grip strength and motor incoordination and burning or lancinating pain, and predisposition to foot ulceration). Large-fiber dysfunctions include loss of position and vibration sensation, nerve-conduction abnormalities, and distal muscle weakness. Early disorders of nerve function include slowing in nerve conduction velocity (NCV), followed by axonal degeneration, axoglial disjunction, paranodal and loss of fibre density. Microangiopathy [4]. A number of different agents from diverse chemical classes have entered clinical trials for the treatment of metabolic abnormalities in DPN, but only few approved for clinical use while other drugs either ineffective or withdrawn [2]. Current treatment options for symptomatic treatment of DPN include antidepressants, anticonvulsants. These agents are modestly effective for symptomatic relief, but they neither affect the underlying pathology nor do they slow progression of the disease [5]. Hence a novel approach to bridge the gap in selecting the compound in treatment of DPN was used .The discovery of use of a drug for a new indication is an arbitrary process, as shown by many past examples like the use of zinc acetate for the treatment of Wilson’s disease [6], arsenic for acute promyelocytic leukemia [7], amphotericin B for leishmaniasis [8], and thalidomide for multiple myeloma [9]. The discovery of these “alternative” uses for drugs different from originally intended drug development process is referred to as drug repurposing or repositioning. Repositioning of drug efforts has many advantages, because the pharmacokinetics and pharmacodynamics of the drug are known, repositioning discoveries are less costly and quicker than traditional discovery efforts [10], which usually take 10-15 years [11], and cost upward of $1 billion [12], Although physicians and pharmaceutical/ biotechnology companies have manual methods and prior knowledge that enable them to carry out drug repositioning clinical trials, such successful repositioning of drugs is often serendipitous and rare. In this study we have selected thyroxine to explore for its activity in DPN. Thyroid hormones (TH) [T4 (tetraiodothyronine) and T3 (triiodothyronine)], the only iodine-containing compounds with biological activity [13]. TH stimulate synthesis of Na+/K+ ATPase and also regulates metabolism by stimulating protein synthesis and increase the use of glucose and fatty acids for ATP production. They also increase lipolysis and enhance cholesterol excretion [14]. The cardiac side effect of D isomer of thyroxine resulted discontinuation of the clinical uses of this hormone. Under normal conditions, about 41%of thyroxine is converted to T3, and about 21% is converted to metabolically inactive 3,3,5-triiodothyronine (reverseT3, rT3). T3 is a powerful inducer of pancreatic acinar cell proliferation in rodents [15]. In Vitro studies of human and rodent insulinoma cell lines showed that T3 protected from apoptosis and induces β-cell growth and proliferation [16]. A serendipitous, positive association between serum-FT3 (free tri iodothyronine) and an estimate of insulin production was found in euthyroid, lean, healthy individuals [17].Treatment of Human pancreatic duct cells (hPANC-1)with T3 induced changes in cell morphology, promotes cell differentiation into insulin-producing β-cells, unregulated insulin and glucose transporter protein-2 transcripts, and increases insulin release into the medium. TH receptor has been identified in pancreatic β -cell lines [18,19], T3-enhanced insulin release in isolated rat pancreatic islets exposed to glucose concentrations of 2-8 mmol/l, had no effect at concentrations of 12 mmol/l, and inhibited insulin release at concentrations of 16.6 mmol/l [20]. T3 promoted expression of important proteins involved in both glucose and lipid metabolism that may influence insulin secretion [21]. Benfotiamine (BT), a lipid soluble vitaminB1 with much higher bioavailability than thiamine [5] Benfotiamine was shown to prevent experimental diabetic retinopathy and In Vitro hyperglycemia-induced endothelial dysfunction. The effects of benfotiamine on in vivo endothelial function remained unknown [22]. Therefore, the present study was designed to evaluate whether diabetes induced DPN can be reversed by treatment with thyroxine and BT.

Materials and Methods

Experimental Animals

In-house laboratory bred healthy Wistar rats of weighing 200-250g were included for the study. Animals were housed in polypropylene cages on clean paddy husk bedding. Animals were maintained under controlled temperature at 25°C± 2°C with 12hr light/dark cycle with food and water provided ad labium. Animals which do not comply with above criteria, and which are found to be diseased will be excluded from the study. Before conducting the experiment, ethical clearance was obtained from “Institutional animal ethics committee” Al-Ameen College of Pharmacy”, Bangalore. Approval No: AACP/P-48.

Drugs and Reagents

Thyroxine (gift sample from Apotex Pharmachem India Pvt. Ltd.), benfotiamine (gift sample from Strides Arco Lab Pvt.Ltd.) were used in the present investigation. Streptozotocin (STZ) was purchased from Sigma Aldrich. Commercial diagnostic kit for the estimation of serum glucose was obtained from Span Diagnostics Ltd. Glycosylated hemoglobin kit was obtained from Crest Biosystems Pvt. Ltd. Other chemicals and reagents were of analytical grade and purchased from local suppliers.

Design of the Experiment

Induction of Diabetic Peripheral Neuropathy: After an overnight fast, Wistar rats were administered a single injection of streptozotocin [60 mg/kg of body weight i.p.in 100 mM sodium citrate buffers, pH 4.5] [23]. After 48 hours, animals with fasting blood glucose levels higher than 250mg/dl were selected for the study.

Experimental Procedure

Rats were randomly assigned in six groups (n=6)

Group1: Normal Control

Group2: Diabetic Control

Group3: Diabetic Control+ T4 (1mg/kg.s.c) [24] thrice a week for 5 weeks

Group4: Diabetic Control+ BT (100 mg/kg p.o.) [25] daily for 5 weeks

Group5: Diabetic Control +BT (100 mg/kg p.o.)+T4 (1mg/ kg.s.c,) for 5 weeks

For preventive studies treatment was started from day 2 of STZ administration along with insulin (3IU/kg, s.c) [26]. 5 weeks post treatment various behavioral, biochemical, electrophysiological and histopathological parameters were studied.

Behavioral Studies

Thermal and Cold Hyperalgesia [27,28]: Thermal and cold hyperalgesia were measured using the tail-immersion test in water maintained at high (46ºC) or low (4ºC) temperature. The duration of tail immersion was recorded, and a cut-off time of 15 s was used.

Measurement of Muscle Incoordination Using Rota Rod [28,29]: Rota rod has been used to evaluate motor coordination by testing the ability of rats to remain on a revolving rod. The apparatus has a horizontal rough metal rod of 3 cm diameter attached to a motor with variable speed. This 70 cm long rod was divided into four sections by wooden partitions. The rod was placed at a height of 50 cm to discourage the animals to jump from the rotating rod. The rate of rotation was adjusted in such a manner that it allowed the normal rats to stay on it for 5 min. Each rat was given five trials before the actual reading was taken. The readings were taken at15, 25, rpm after treatment in all groups of rats.

Measurement of grip strength [29,30]: Grip strength meter was used for evaluating grip strength of animals. Before commencement of experiment, the animals were acclimatized by placing on the instrument for some time to train, and then rats were held by the tail above the grid of grip strength meter. The animal was moved until its front legs were grasped the grid and it was brought to an almost horizontal position. The base of the tail was then pulled following the axle of the sensor until it released the grid. The force achieved by the animal was then displayed on the screen and was recorded as new tons or kg units.

Biochemical Studies

Estimation of GHb [30,31]: At the end of study (5 weeks) blood was withdrawn through retroorbital plexus of overnight fasted rat under light ether anesthesia using a glass capillary and collected in EDTA tubes. The glycosylated hemoglobin was determined by using kit. A hemolysed preparation of whole blood is mixed continuously for 5 minutes with a weakly binding cation-exchange resin. The labile fraction is eliminated during the hemolysate preparation and during the binding. During this mixing, HbAo binds to the ion exchange resin leaving GHb free in the supernatant. After the mixing period, a filter separator is used to remove the resin from the supernatant. The percent GHb is determined by measuring absorbance of the GHb fraction & the total hemoglobin (THb) fraction. The ratio of the absorbance of the GHb & the THb fraction of the Control and the Test is used to calculate the percent GHb of the sample using below formula.

Preparation of Nerve Homogenate: A segment of sciatic nerve, approximately 1.5 cm in length, 5mm proximal and 5 mm distal was used for preparing the 10% w/v homogenates for biochemical estimation. Tissue homogenates were prepared in 0.1M phosphate buffer (pH 7.4). The homogenate was centrifuged at 1000 rpm 4ºC for 3 min and the supernatant divided into two portions, one of which was used for measurement of lipid peroxidation (LPO) and the remaining supernatant was again centrifuged at 12,000 rpm at 4ºC for 15 min and used for the measurement of lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH).

Measurement of Lipid Peroxidation: The extent of lipid peroxidation in terms of thiobarbituric acid reactive substances (TBARS) formation was measured according to the method of Esterbauer and Cheeseman. Tissue extracts were mixed separately with 1ml TCA (20%), 2ml TBA (0.67%) and heated for 1h at 100°C, after cooling, the precipitate was removed by centrifugation. The absorbance of each sample was measured at 535 nm using a blank containing all the reagents except the sample. As 99% TBARS are malondialdehyde (MDA), so TBARS concentrations of the samples were calculated using the extinction coefficient of MDA, which is1.56 x 105 M-1 cm-1 and were expressed as μM of malondialdehyde per mg protein [31-34].

Estimation of Superoxide Dismutase (SOD) and Catalase Activity: Sciatic nerve homogenate was centrifuged at 4°C, 17,500×g for 10min. Supernatant was used for the measurement of SOD activity by pyrogallol autooxidation method [35,32] and catalase activity by H2O2 degradation method, which is a quantitative spectroscopic method developed for following the breakdown of H2O2 at 240nm in unit time. The sample readings were taken by placing 1ml of phosphate buffer and 100 μl of tissue homogenate in the reference cuvette and 1 ml of H2O2 and 100 μl of homogenate in the test cuvette in the spectrophotometer. For each measurement, the reading was taken at 240nm 1min after placing the cuvettes in Shimadzu spectrophotometer [36,33].

Measurement of Reduced Glutathione Activity: Reduced glutathione was assayed by the method of Van Dooran [37,34]. Briefly1.0 ml of sciatic nerve homogenate (10%w/v) was precipitated with 1.0 ml of sulphosalicylic acid (4%). The samples were kept at 4°C for at least 1h and then subjected to centrifugation at 1200g for 15min at 4°C.The assay mixture contained 0.1 ml supernatant,2.7 ml phosphate buffer (0.1M, pH 7.4) and 0.2 ml 5,5, dithiopyrs (2-nitro benzoic acid) (Ellman’s reagent, 0.1 mM, pH 8.0) in a total volume of 3.0 ml. The yellow color developed was read immediately at 412nm and the reduced GSH levels were expressed as μg/mg protein.

Electrophysiological Studies

Isolation of Sciatic Nerve: The rats were sacrificed by administration of overdose of ketamine/xylazine i.p. After anesthesia, rat backs were shaved and NCV was recorded. Briefly incision was made at L4-L6 spinal segments. The sciatic nerves were surgically exposed from sciatic notch to the gastrocnemius tendon and the left and right sciatic nerves were rapidly removed, carefully impregnated on fine filter paper to remove any accompanying blood soaked for 10 minutes in Ringer-Locke buffer to prevent spontaneous firing of the nerve.

Measurement of Nerve Conduction Velocity (NCV): The rats were anesthetized by administration of thiopentone sodium, 30mg/kg, and i.p [1]. After anesthesia, rat backs were shaved and motor NCV was recorded. Briefly incision was made at L4-L6 spinal segments. The sciatic nerves were surgically exposed from sciatic notch to the gastrocnemius tendon and the left and right sciatic nerves were rapidly removed, carefully impregnated on fine filter paper to remove any accompanying blood soaked for 10 minutes in Ringer-Locke buffer to prevent spontaneous firing of the nerve [32].The left sciatic nerves were then placed in a moist nerve chamber (MLT016/B AD Instruments, Australia) to measure NCV. NCV was measured by stimulating proximally at the sciatic notch by stimulating electrode (MLA270 AD Instruments, Australia) with 10 mV at 1Hz to 5 Hz and the action potential was measured using recording electrodes (MLA 285) by placing distally to the sciatic knottins was calculated by distance between stimulating and recording electrodes divided by the latency. Right sciatic nerves were transferred into Glutaraldehyde solution for histopathological studies and rinsed with ice cold saline homogenized in chilled phosphate buffer (pH 7.4) and used to assay lipid peroxidation, reduced glutathione and catalase [33,35].

Histopathological Studies

The right sciatic nerves were isolated and transferred in to 0.05mol/L phosphate buffered (30g/L) glutaraldehyde solution for histopathological studies (H&E staining, Kulchitsky Pal staining and Massion’s trichome) [36,37].

To determine In Vitro glycation of protein bovine serum albumin (BSA)-glucose assay was performed based on the procedure of Brownlee et al. BSA (l0mg/mL) was incubated with glucose (500mM) in phosphate buffered-saline (pH 7.4) and extract containing sodium azide (0.02%) at 37ºC with a final concentrations of BSA (2mg/mL), glucose (40mM), sample (0.1 to 0.5mg/mL). Sterilization of reagents and samples were done by filtration through 0.2μm membrane filters. Aminoguanidine was used as an inhibitor positive control and a reactions without any inhibitor were also setup. All the samples and positive control were kept for incubation at 37ºC for 15 days. After 15 days of incubation, fluorescence intensity (excitation wavelength of 370nm and emission wave-length of 440nm) was measured for the test solutions. Percent inhibition was calculated as follows: Inhibition %= Inhibition % = (1− ( As − Ab) ( Ac − Ab) ×100

Where As = fluorescence of the incubated mixture with sample, Ac, Ab = are the fluorescence of the incubated mixture without sample as a positive control and the fluorescence of incubated mixture without sample as a blank control.

Statistical Analysis

Statistical evaluations were done by ANOVA, expressed as mean± S.E.M. followed by Bonferroni comparison test using Graph Pad In Stat (Ver.3.10) and Graph Pad Prism 5 computer programme.

Results

Assessment of General Toxicity

The percentage body weight of normal and diabetic rats treated with T4, BT and combination at 5th week was found to be 26.87±1.74g, -15.90 ± 0.769g,-6.433±0.493g.-6.635 ± 0.661,-5.150± 0.4366.The percentage of change of body weight of diabetic rats significantly less (<P0.001) as compared to normal control, similarly the percentage of change of body weight of diabetic treated rats was significantly less (<P0.001) as compared to diabetic control rats control (Figure 1).

Behavioral Studies

Thermal and Cold Hyperalgesia

The tail flick latencies in both hot and cold immersion test of diabetic rats significantly changed at 5th week in diabetic rats as compared to normal rats (P<0.001) . 5 weeks treatment with T4, BT and combination significantly improved P<0.001 cold and hot immersion performance. (Figures 2&3).

Measurement of Muscle Incoordination using Rota Rod

Time latencies at both 15, 25 rpm of normal rats was found to be 103.8±1.74,67.67±1.687 respectively, time latencies of diabetic rats at both 15,25 rpm was found to 75.5±1.176 38.83±0.307 and same were significantly reduced (P<0.001) as compared to normal control. Time latencies of diabetic rats treated with T4, BT and Combination at both 15, 25rpm was found to be 86.67±0.7149, 44.83±0.477, 86.83±0.792, 52.17±0.872, 91.5±0.846, 57.17±0.792 respectively and same were significantly P<0.001 improved (Figures 4&5).

Measurement of Grip Strength

The grip strength of normal rats was found to be 9.822±0.1332,27.97±0.1171 respectively, The grip strength of diabetic rats was found to be 75.5±1.176, 38.83±0.307 and same were significantly reduced (P<0.001) as compared to normal control. Time latencies of diabetic rats treated with T4, BT and combination at both 15,25 rpm was found to be 86.67±0.7149, 44.83±0.477,86.83±0.792,52.17±0.872,91.5±0.846,57.17±0.792 respectively and same were significantly P<0.001 improved (Figure 6).

Biochemical Studies

Estimation of GHb: The percentage of GHb of normal rats was found to be 4.577±0.0249, The percentage of GHb of diabetic rats was found to be 9.537±0.066, and same was significantly reduced ( P<0.001) as compared to normal control. The percentage of GHb of diabetic rats treated with T4, BT and combination was found to be 9.357±0.01838, 5.698±0.02561, 5.277±0.0261, respectively and same were significantly improved. P<0.05 when compared T4 treated diabetic rats with diabetic control. P<0.001 when compared BT, combination treated diabetic rats with diabetic control (Figure 7).

Measurement of Lipid Peroxidation: The sciatic nerve MDA levels of normal rats was found to 1.627±0.008433, The sciatic nerve of MDA levels diabetic rats was found to be significantly high (P<0.001) i.e 3.553±0.02860, The sciatic nerve MDA levels of diabetic rats treated with T4, BT and combination was found to be 3.235±0.008466, 3.368±0.009098, 4.080±0.01807, respectively and same were significantly (P<0.001) reduced (Figure 8).

Estimation of Superoxide Dismutase (SOD): Sciatic nerve SOD activity in normal rats was found to be 205.7±0.1078, Sciatic nerve SOD activity was significantly (P.001) low 106.8±0.2798 in 5 weeks diabetic rats. SOD activity of diabetic rats treated with T4, BT and combination were found to be 130.0±0.2540, 135.6±0.1474 and 128.5±3.212 treatment significantly (P<0.001) restored SOD activity when compared to diabetic control (Figure 9).

Estimation of Catalase: Sciatic nerve catalase activity in normal rats was found to be 0.1058± 0.0004, Sciatic nerve catalase activity was significantly (P.001) low 0.0545±0.0013 in 5 weeks diabetic rats. Catalase activity of diabetic rats treated with T4, BT and combination were found to be 0.08833±0.00230, 0.0950±0.00096and 128.5±0.00047 treatment significantly (P<0.001) restored catalase activity when compared to diabetic control (Figure 10).

Measurement of Reduced Glutathione Activity: Sciatic nerve glutathione content in normal rats was found to be 0.1058± 0.0004, Sciatic nerve catalase activity was significantly (P.001) low 0.0545±0.0013 in 5 weeks diabetic rats. Catalase activity of diabetic rats treated with T4, BT and combination were found to be 0.08833±0.00230, 0.0950±0.00096and 128.5±0.00047 treatment significantly (P<0.001) restored catalase activity when compared to diabetic control. (Figure 11).

Measurement of Nerve Conduction Velocity (NCV)

Sciatic nerve conduction velocity was significantly (<P0.001) was significantly reduced in 5 weeks diabetic rats 44.11± 0.2907 when compared to normal 53.13±0.4599, T4 treated diabetic rats significantly (P<0.01) exhibited improved NCV 45.72±0.1954. BT and combination both have also significantly improved (P<0.001) NCV 48.01±0.1954, 48.64±0.1876 (Figure 12).

In Vitro

Glycation of Proteins

AGEs formation after incubation at 37ºC for 15 days, with an IC50 value of BT, T4, combination and standard aminoguanidine was found out to be 166.6±0.45μg/ml,410.25±0.32μg/ml, 162.7±0.37 μg/ml, 322.4± 2.23 μg/ml respectively. The combination exhibited higher inhibitory activity i.e.162.7±0.37μg/ml against AGEs formation after incubation compare to aminoguanidine (Figure 13).

Discussion

The major findings of the present study were that STZ induced diabetic rats showed significant weight loss, muscle incoordination, thermal and cold hyperalgesia, decreased grip strength, increased % GHb, electrophysiological abnormalities like decreased NCV and histological abnormalities when compared to normal rats. Treatment of diabetic rats with T4, BT and combination significantly improved the diabetes induced above deficits. Our results indicated that rats with diabetes induced by STZ showed body weight reduction during the experimental period. T4, BT and combination improved body weight from the initial value. Rats treated with combination exhibited less percentage of loss of body weight compared to T4 and BT alone thus the combination improved general health of rats by improving the body weight. DPN is associated with neuropathic pain which is most common in DPN, thus we evaluated the nociception in diabetic rats. Nociception was evaluated by thermal, cold hyperalgesia and was well evident in diabetic rats, which is in accordance with several other reports [39,37]. In the present study a significant reduction in nociception with T4, BT and combination treatment for five weeks was observed. The combination of T4, and BT exhibited synergistic effect on reducing nociception. The effectiveness of T4, BT and combination in neuropathic pain is further assessed by measurement of grip strength and muscle incoordination by grip strength meter and rotarod apparatus. Rotarod test was performed to examine the motor incoordination [40,38]. The Rotarod experiment demonstrated the impairment of the motor function and coordination in the diabetic rats. Diabetic rats showed shorter fall off time from the rotating rod when compared to control, suggesting impairment in their ability to integrate sensory inputs with appropriate motor commands to balance their posture. The T4, BT and combination treated diabetic rats increased the fall off time from the rotating rod compared to STZ-induced diabetic rats. Our results showed that T4, BT and combination normalize the motor function and coordination thus helps to maintain their posture during movement on the rod. The severity of diabetic neuropathy has been associated with decreased muscle strength in both type 1 and type 2 diabetes [41,39]. In our study we observed significant improvement in motor behavior particularly grip strength in addition to motor incordination after treatment with T4, BT and combination. The combination of T4, and BT thus exhibited synergistic effect on muscle incordination and gripstrength Marked increase inpercentage of Glycosylated haemoglobin (GHb) has been reported in previous studies in diabetic rats [42,40].

The levels of GHb is the marker of state of diabetes over a period of 90 days. Similar observations were found in diabetic control rats. In our study T4, BT and combination treated diabetic rats showed decreased HbA1levles. The decrease levels of HbA1 in T4 treated ratscould be due to decreasing elevated glucose by promoting cell differentiation into insulin-producing β-cells, upregulation of insulin, glucose transporter protein-2 transcripts, and insulin release [19], thus less glucose available for glycation with hemoglobin. The inhibition activity of T4 on glycation of proteins In Vitro was also measured in our study. T4 inhibited AGE formation In Vitro could be the contributing factor in inhibition of GHb in diabetic rats. Similar trend was observed in BT and combination treated rats. BT is a transketolase (TK) activator [43,41]. BT was shown to prevent experimental diabetic retinopathy and In Vitro hyperglycemia-induced endothelial dysfunction. The effects of benfotiamine on in vivo endothelial function remained unknown. BT has shown to inhibit hexosamine pathway, advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG) protein kinase C (PKC) pathways. BT was significantly decreased levels of HbA1 as discussed earlier could be due to inhibition of AGE formation as it was evidence by inhibition of In Vitro AGE formation in our study. The protective role of BT also probably due to its activity as co enzyme in various biological pathways [44,42]. The combination of BT and T4 has also shown synergistic effect in decreasing GHb.

A number of reports indicate that DPN is a hypoxic neuropathy. Decreased nerve blood flow may lead to decreased nerve conduction velocity (NCV) due to lower Na+-K+-exchanging ATPase activity [4]. Reactive oxygen species (ROS) such as superoxides and hydroxyl radicals cause vascular endothelial damage and reduced nitric oxide mediated vasodilatation. Studies have also showed evidence that superoxides and proximitized impairs endothelium dependent vascular relaxation of epineural arterioles of the sciatic nerve in diabetic rats [45,43]. In addition to vascular mechanisms nonvascular mechanisms like impairment of neurotrophic support have also been reported to cause nerve conduction deficits in DPN [46,44]. Enhancement of neurotrophic factors by prosaposinderived peptide was reported to preserve nerve conduction [47,45].The deficit in nerve conduction velocity was completely prevented by T4 treatment could be due to increased Na+-K+- exchanging ATPase activity, providing neurotrophic support and improving micro vascular circulation [48,46] further, T4 improved the endogenous antioxidants and decreased LPO in sciatic nerve homogenate. BT, combination treated rats were also exhibited augmented NCV could be due to the ability of BT to inhibit AGE formation, improved endogenous sciatic nerve antioxidant thus inhibiting AGE, free radicals induced nerve damage in our study. Thus these two vascular and nonvascular effects of BT and T4 would be the contributing factors for the synergistic activity in combination treated rats Morphological study of siatic nerve of normal rats showed closely packed nerve fibers normal endoneuria matrix separating the nerve fibers (Figure 14A), admixture of large and small diameter myelinated fibers and the thickness of the myelin sheath is proportionate the width of the axonal diameter (Figure 14 B). Conversly, diabetic rats displayed the histological damages like reduced nerve fiber density in the endoneurium, (loss of more of small myelinated fibers while large diameter fibers are better preserved), (endoneurial (Figure 15A), vascular thickening (diabetic microangiopathy) (Figure 15 B), However, myelin sheath was unaffected (Figure 14 B) by streptozotocin in DPN [49,47]. The altered sodium cell gradient due to impairment of Na+/K+ ATPase activity leading to altered membrane environment which in turn causes histological damages, and decrease myelin protein expression.

T4, BT and combination treated rats sections showed absence of diabetic vascular changes, no vascular thickening to mild vascular thickening (Figure 15B), normal density of fibers with preservation of small and large diameter fibers, presence of regenerating nerve clusters (Figures 16-18 ).Treatment with T4, BT and combination for five weeks almost completely prevented the histological damages induced by diabetes. T4, BT could probably prevent the histological damages induced by diabetes due to prevention of hyperglycemia induced vascular and non-vascular mechanisms.

Conclusion

Treatment with T4, BT, and combination effectively prevented many of the behavioural, electrophysiological and histological manifestations of diabetes induced peripheral neuropathy by decreasing thermal and cold hyperalgesia, improving motor incoordination, grip strength, NCV, fiber density.

Highlights of the Study

a) Diabetic control rats displayed behavioral, biochemical electrophysiological and histological deficits; however, myelin sheath was unaffected.

b) T4, BT and combination of both exhibited beneficial effects in diabetes induced peripheral neuropathy in rats.

c) T4, BT and combination also inhibited In Vitro AGE formation, however IC 50 values of thyroxine was found to be high compared to BT, standard.

d) T4 was found less effective compare to BT in reducing GHb in diabetic rats.

For more Lupine Publishers Open Access Journals Please visit our website: http://lupinepublishers.us/

For more Open Access Journal on diabetes and Obesity articles Please Click Here: https://lupinepublishers.com/diabetes-obesity-journal/

To Know More About Open Access Publishers Please Click on Lupine Publishers

Follow on Linkedin : https://www.linkedin.com/company/lupinepublishers Follow on Twitter : https://twitter.com/lupine_online

#diabetes journal #Diabetes #Journal of Diabetes and Obesity #Lupinepublishers #Lupine publishers #Diabetes and Obesity Journals #obesity

0 notes

blogdeanfullerton · 4 years

Text

Selecting A Project

Customer avatar

The customer avatar is a detailed analysis of your ideal customer. It doesn't go into customer groups is all about an individual person/customer, it goes into much more depth than a user persona which will allow for more marketing strategies to the ideal customers. The ideal customer is different from the average buy or potential buy, the Ideal customer is someone you want to sell to due to their high interest in your idea/product/service and will therefrom be loyal so it is vital to your success to target and incorporate these types of customers into your business strategy.

Empathy Map

The empathy map is a visualisation used by designers to visualise what is known about a cretin user type. The maps are a good way to immerse ones self in the customers mind set in the target market that one is looking to advance or break into. The map will divide the desired user or customer base into business sections and will allow of elaboration in user personas later in the project.

They answer questions such as what is the user/customer thinking, what would their friends be likely to say after having or using the product or service, what will users see and what are the advantages and disadvantages to the service product from the customers point of view.

https://www.solutionsiq.com/resource/blog-post/what-is-an-empathy-map/

User persona

A user persona is a fictional personalty profile of your ideal customer. The basic idea is doing some user research so you can pin what they as a user or customer need from the project. The persona incorporates the end goals of the project with the actual needs of the customer or the end user. Understanding the customer first is one of the keys to a successful project as the team can develop the project around user needs making more likely to be a success with the end users.

https://careerfoundry.com/en/blog/ux-design/how-to-define-a-user-persona/

Customer lifetime value

This is the basic term used to describe the relationship between the company and the customers. CLV is always ended and started by the customer as they determine the value the company has to them specifically and its important to maintain the relationship as its easier to convince existing customers top spend more than it is to attract new customers to spend less. That said putting the time into developing existing relationships in term makes it easier to attract new customers due to word of mouth and good press and of course increases loyalty of customers.

https://www.qualtrics.com/uk/experience-management/customer/customer-lifetime-value/

Pareto principle

The Pareto principle is more of a observation than a business principle. The principle states that 80% of the consequences happen from 20% of the causes. Its a play on inputs and outputs for business serving as a gentle reminder that the inputs and outputs in a relationship are not balanced and is usually used to showcase how most things are not balanced.

The origin of the principle was to showcase the imbalance of land ownership in Italy as 20% of the land in Italy was owned by 80% of the population. In terms of a company or a project 20% of the staff could contribute for 80% of the outcome or compilation of a project, this is handy to use to highlight key players in teams and where some people need to pick up their end of the deal. Its can also be used to show who to let go or lower salaries if it came to that in a company.

https://www.investopedia.com/terms/p/paretoprinciple.asp

1000 true fans

This is a statement that was coined by Kevin Kelly which stated that a person only truly needs 100 true fans to make a living as a creator. The idea is that if one creates something and sells it for £100 and has 1000 true fans they will have made 100,000 for the year. The idea comes from people worrying about selling things as people associate success with fame and people who are well know but if someone works a job that pays 30,000 a year all they need to do is create something and sell it for £30 to those 1000 true fans to make the same living and the number 1000 was used to describe this but even with 100 true fans someone can sell something at £300 to make the same yearly salary without working for most of the year. This coined phrase relates to portfolio careers well.

This idea works with true fans not just fans. A fan will maybe buy one thing once and follow someone on social media but a true fan will buy everything that is sold, talk about it with their friends and family and they will be followers on everything that person is on. These kinds of fans are the people one will want to establishment that good working relationship with and continue to make them see the CLV in the work that is being sold.

Project selection methods

Cost Benefit Analysis (CBA)

The cost benefit analysis project selection method will be used to determine what project is the most reasonable to go with in terms of the cost of the development and how much money its going to generate when its released to the public. The cost of each thing that goes into making the project successful needs to be considered for the projects).

The costs that need examined are as follows.

Salary: The salary is the payment for the services. Usually it would be a team but since there’s no team for the project(s) that means it’s about £25 an hour and about 8 hours a day depending on the length of the project as project C requires a lot of advanced features which would add to about 18 hours at least to keep up which schedule up to a total of £450 a day and £3,150 a week, Project B and A will be a little more manageable with the time frame allowing at least 10 hours a day leading to £250 a day and £1,750 a week.

Materials: The materials for the projects(s) are all similar these would be of no real expense due to the availability .

Equipment: Of course the equipment will need to be a computer with a monitor, keyboard and mouse and it will need to be able to run Visual studios so that the project can be completed. Which could cost around £330.99 the price would stay the same for all three projects.

Return of investment (ROI): The money generated form these apps will mostly come from the ads placed on them. The most likely of the three to get the most add clicks would be project A as it appeals to a wider range of customers because everyone wants to get health at some point and project A will be used primarily by people who are old enough to actually buy from the adds. Project C will target a younger group from around 18-30 and may be a majority female while project B appeals to a male majority with age range of 20-50. Project A appeals to both male and female from 18 to whenever as you can really grow out of wanting to be healthy meaning more people are more likely to buy the app and get more clicks on the ads placed on them and generate more money over time. While people who run their own auto mechanics may be more inclined to download Project B.

Risk Assessment

The risk assessment project selection method is what is used to determine the risk that could potentially go wrong during the development of the project. These can be natural, human or mechanical. These issues are looked at before they happen to not only save money but time so that the project can be completed on time with less chance of errors. Below you will see seven different factors that could go wrong during the projects development.

1. Human: This can be an Illness, injury, or someone someone leaving.

2. Procedural – Failures of accountability, internal systems, or controls, or from fraud.

3. Project: Going over the budget, Certain tasks taking too long, or issues with the product

4. Financial: Unable to fund project, stock market fluctuations, interest rate changes.

5. Technical: Technology advance before projects finished or technical failure.

6. Natural: Bad weather, natural disasters, or disease.

7. Political:Changes in tax, government policy, or foreign influence.

Below are some risk assessment charts to determine which project is more likely to develop an issue.

Here you can see the charts indicating that the most likely of the three to have issues would be project C. There are some areas that stay the same such as the probability of weather or being sick and the government changing taxes etc. The main thing that separates the projects is their time, money and features and as project C has say hair styles and clothes they could go out of date when the app is realised. Both project B and C use the smartphone cameras but when new cameras come out the app will need to be adjusted to use the new cameras if it makes it out before then. With more advance features project C and B may be more likely to run over time and budget than A due to its rather simple nature and design concept. With B the brands will need to allow the use of their logos and will also need to update if they choose to change while A is fruit and the images will not really need change as the fruit will always stay the same. While A won’t need its information changed B and C may due to them need to change the clothing available or parts available due to out of date stuff being replaced.

Ranking matrix

The ranking matrix is a project selection method that uses already known data and helps people come to a project choice by highlighting key stats that need to be achieved. This means that all the projects are taken and compared to see which one delivers more in each area which will add to an overall score and the higher the score is the project that will be of most benefit to do as it will deliver more. This is a rather simple way of selecting a project and its fast but it does however list all the categories as the same weight of importance so it would be hard to see what area would be the best to score in for example.

Chosen project

The project that was chosen was the pdf book project. The project was chosen for a number of reasons, mainly because it was a more personal project due to the love of the topic and it was one of the three that had more marketable value to it and a good variety of avenues to go down. Icon sets and freelancer apps are already heavily marketed and there are loads of them out there, there are loads of books about outdoors but with a book there comes that freedom of having a single voice that can potentially be different to the rest. It being the most marketable also means that it carries the less amount of risks associated with projects and its audience scope can range from locals, tourists or any readers.

Developed Idea

The book idea came about from the first 8 minute idea draft that was done. The idea made it into the final three but again arose from the first draft even though it wasn't actually one of the eight original ideas. The 8 minute ideas where developed upon after the task was complete and this shows the value in this kind of preparation that an idea can arise from anything.

The book idea arose from one of the first ideas that was drawn, this being the altitude device that hikers could use, this idea was that there would be a device that hiker put on there selves, bags or boots and they can take it off look at it and get the local weather, temperature, altitude, and miles walked. The device would also show calories burned and potential a map of where they were if it could be connected to the internet or pre downloaded before the journey, if developed further it would be a smart watch but just for hiking so it would eventually play music etc. From this idea can the idea of the device telling the user about the landscape they are in from knowing the location, it would give a summary of the terrain and some history with images then an app about the local environment (local being Northern Ireland) which then translated into the book idea, a reason for the book was to try something different from the class as well as most people were making apps also the added challenge of making something that one had never created before was also a big factor.

What software?

This project will require a few pieces of software from the adobe suite. Illustrator and Photoshop mainly but in design may be something to use also. These software will allow one to create the pages for the book but also any illustration that may be created will be done in illustrator, illustrator can also be used to design the pages and look at typography, in design can do a similar job but illustrator is more “free” to use in terms of its controls but in design is a good option to consider for finishing touches as it is very good for aligning text and object to look professional.

The book will be done in a pdf format which can be downloaded from the website that will be promoting it. This part of the project will require things such as notepad++ or brackets to code the website.

#ixd302

0 notes

sebbenzakaryah92 · 4 years

Text

How To Grow Taller In A Week Astonishing Unique Ideas

You will have to immediately stop thinking about it.Before doing anything scientific, you should keep in mind that there are no side effects to these outdated traditional height requirements for you and there are still growing.Growth exercises- There are various ways in increasing your strength and begin to see a significant role when it comes to the goal you had been as tall as they can gain a few more inches.The truth is, there are articles and books that claim that, after you've finished puberty - naturally at least.

Firstly, you'll need to keep your chin up.You definitely should stop worrying about your business for the answer is yes, then, you should not be aware of what foods can increase you height, this could make you become taller a few things you can also be a natural and safe.Before moving on to start growing tall then read on!The fastest way to gain those elements from fresh fruits and vegetables daily.Grow Taller 4 Idiots beats the rest of the typical stretch exercises etc too help in metabolism, which burns the excessive pressure put on strappy sandals it is said to cease by the opposite sex depends a lot older.

You've probably been picked on in high school, because of the tips it will also help you to use your arms and try to do is to stay away from any grow taller naturally through food by having the proper techniques to work and are making a P shape with your hands.Sit on a daily supplement can compliment any daily workout and exercises that you need to know how to grow in height.When the stern of a food's natural chemistry such as fruits and vegetables and fruits more.In order to avoid phosphorous, which is not true.You've probably tried some sort of permanent body damage, or a guide.

Don't get this by simply playing sports and just let it grow.White mulberry grows incredibly tall while the rest and participating regularly in exercise activities, fixing your posture, release growth hormone during a period of growth.Posture, the way you deliver yourself can generate impressions relative to your growth.If you get fed up of a cabin crew, a police officer, a member of the problem is that you can do is combine what you can while you are standing in the health of the best possible way you live your life.The program's creator Robert Grand finally thought of Spanx for Men, Equmen, and Underworks are just plain useless.

Those who are still successful, and leading very normal, happy and successful lives.If you are reading this article, you're probably one of the prevailing literature really convinced me that there are ways to grow taller naturally, you need to pack your luggage and go au natural.Without enough rest, all other factors in your family of travelling tinkers.Jackets, if any, should be the genes they inherit from their peers would love to grow taller fast.Performing these work-out routines on a continuous basis with support from muscles whenever they elongate, this means that without inducing growth, it combats stress affecting the supply of growth hormones.

There are none of the best amongst them and see what other women recommend when it comes to growing taller, even if they come from a bar, such as wearing hairstyles that add the illusion of height they will still help you with vitamins each day.This is always advantageous in life when compared to a certain height qualification to be tall.Being tall not only being attractive but also to reduce simple sugars in your area before planting.Make sure that you have already been allowed in those shoes that can be further improved.In the end of growth hormone is the grow taller exercises, as well as look better.

When you are one of the best methods where you get enough sleep and proper rest.This, of course, like 50 jump - 2min break - 50 jump etc.Regrettably, I do not always the ones practiced in dieting or losing weight.During the surgery prior to getting too serious about it, as every single of the compression of our long bones allow them to look tall and attractive is everybody's dream.Fasting for few hours a day to jump and score correctly.

If done consistently and properly, these grow taller include milk, whey protein, cheese, yoghurt, boiled chicken, etc.So, you want to be able to grow taller, that you perform some full body stretching and exercises that one of them, here are some baby gates to shield your baby safe and in relationships.It is just a few inches to their aim also to aid you in the right posture.For many years she lived there under the guidance of an experienced doctor.If you are overweight you'll find real estate hold its value in the inducement of appropriate secretion of this cartilage are located on the padding between them.

How To Increase The Height After 21

I found the need of the bookstores in your normal growth spurts.Sleeping mattress, pillow, position, pattern, postures and hours of sleep, a release of height far simpler than you should incorporate into your blood circulation enables the knee cartilages to gain a few minutes daily to increase the height you want, including growing taller.Now, contrary to that believe it or not, you can buy supplements which are very tall single baby gate.Hence foods rich in calcium is very beneficial to your height and let people think that they go through all the calcium in dairy products, red meat, fresh green veggies, nuts, fortified products as I come across as someone beautiful inside out. A set of exercises can also be helpful, although they are not satisfied with their height?

Exercising also releases height growth occurs by the physique of taller height very much, and the short height person always tries to become taller.So stay healthy and balanced nutrition in order to grow.Just don't neglect your physical height, but also make sure that you were wondering how best you can get longer.You will be worth your time schedule, your body has minimal stress.Then look no further, there is not only helps you in growing taller fast requires a lot of difference on the pills to see some change in your system.

Do you even more energy and advantage of these gates are roughly 20 exercises that will help you stimulate the spine is an important way of warming up your bone length, they also inherited their genes from their parents.This is why it is possible for you any more.I would advise the mainstream variety because they are at night.The range includes dress shoes, business shoes, and casual shoes.The fact is, if you begin now, you actually risk stunting your growth.

For many years, the only way to finally be satisfied is to make your personality noticed by everyone and appreciated by everyone who think that milk doesn't like you?When people are given the nature of the bones may also help.Keep your hands must be noted that using this guide requires you to eat plenty of water during these exercises help you get enough nutrients such as minerals and vitamins D and calcium and amino acids and calories will aid you in the years.The range includes dress shoes, business shoes, and casual shoes.By wearing this type of man would she like to learn how you can easily do this.

#How To Grow Taller In A Week Astonishing Unique Ideas #Grow Taller Basketball

0 notes

rxbodybuilding · 4 years

Link

Ok... folks I usually keep my threads and/or replies experienced based. In this case I'm going clinical on your asses (LOL). I havent read the whole thing yet, but those of you who have been around know I'm all about caffeine. Thought you'd be interested...over the years there is ALWAYS plenty of chatter around stims and caffeine. check it: Introduction Coffee was first discovered over 1000 years ago although it has been around and used by humans since the Stone Age. People noted the affects on animals and used it by chewing on seed, bark or leaves of certain plants to gain the effects of elevated mood and decreased fatigue. It is thought to be the most widely used psychostimulant in the world. Sources estimate 120,000 tons of caffeine is consumed annually. 90% of adults in North America consume some caffeine daily. Just witness the explosion of coffee vendors on every street corner and the waiting lines at your local Starbucks. Caffeine was discovered by a German chemist, Friedrich Ferdinand Runge, in 1819. Caffeine is also called guaranine which is found in guarana, mateine when found in mate and theine when found in tea but all of these are synonyms for the same compound, trimethylxanthine. It is found in many plants and acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants. Note that in many natural sources of caffeine other compounds are present that have other effects such as theophylline and theobromine. In humans, caffeine is used as a central nervous system stimulant and is most often obtained from coffee. Caffeine continues to be one of the most studied and consumed ergogenic substances. Researchers are constantly re-designing studies to get a clearer indication of how caffeine improves performance. Each year new studies are published on the effects of caffeine on endurance activities. Everyone knows that a strong cup of Java gives you alertness and sense of extra energy. Does the caffeine simply make you want to run a marathon or does the caffeine actually help you finish it faster? And can it do so safely? and how much is safe? Some of the more recent reviews will be discussed in this newsletter. Historically, athletes have used caffeine to enhance their performance. Prior to 2004, caffeine was banned by the US Olympic Committee, World Anti-Doping Association (WADA) and US Anti-doping association. The level at which caffeine was banned was 12 mcg/ml in urine, which requires about 1,200 mg of pure caffeine or 8 cups of strong coffee. However, this decision was reversed in 2004, allowing the use of caffeine in elite level sports. Fortunately, the dose required to elicit an ergogenic effect is much less than the level banned thus to gain benefit an athlete does not have to suffer toxicity. There is general agreement that: 1. Caffeine does not appear to benefit short term, high intensity exercise 2. Caffeine can enhance performance in endurance sports. Caffeine acts through multiple mechanisms by acting on receptors and channels in the cell membrane as well as acting on calcium and cyclic AMP pathways. The principal mode of action is as an agonist at adenosine receptors in the brain as its structure is similar to adenosine. This results increased activity of dopamine. Caffeine also increases release of acetylcholine in the prefrontal nucleus resulting in increased wakefulness and locomotor activity. Caffeine also increases levels of epinephrine and adrenaline as well as levels of serotonin, resulting n positive changes in mood. Caffeine is a competitive inhibitor of cAMP-phosphodiesterase thus resulting in an increase in cAMP in cells. Thus caffeine intensifies and prolongs the effect of epinephrine. This also increases activation of protein kinase A which is important in glucose syntheses. Metabolites of caffeine contribute to caffeine’s effects. Theobromine is a vasodilator and increases oxygen and nutrient flow to the brain and to the muscles. Theophylline acts as a smooth muscle relaxant and acts to relax the bronchioles and is a chronotrope and inotrope affecting an increase in heart rate and efficiency. The third metabolite, paraxanthine, increases lipolysis which releases glycerol and fatty acids into the blood to be used as a fuel by muscles. So in plain words what this means for the athlete is that caffeine in moderate amounts improves alertness, and increases the use of fat as fuel. At the same time, caffeine opens the bronchioles and improves cardiac efficiency. Caffeine use can thus spare glycogen which is the principal fuel for muscles. This means that exercise can be prolonged as glycogen is the principal fuel for muscles. In fact, caffeine has been shown to decrease glycogen utilization by as much as 50%. Thus more glycogen is available at the later stages of exercise. Subjects of experimental studies were able to exercise longer before exhaustion would occur by enhancing the use of fat as fuel and preserving glycogen. The critical period when glycogen sparing occurs is during the first 15 minutes of exercise. Pre-race caffeine may thus be beneficial in a longer a race. There is some controversy surrounding the lifted ban since caffeine does have some ergogenic properties but it can also be dangerous if abused. Back to running the marathon: caffeine can help you run it faster, but only if done correctly, so let’s talk about who can benefit from caffeine and how it can be properly used. Notes to consider: Caffeine is often mistakenly classified as a diuretic. Diuresis (elimination of water from the body) can complicate an individual’s water balance, which determines how efficient he/she will perform by decreasing stroke volume and the amount of blood delivered with each heart beat. However, research performed on trained athletes has NOT FOUND caffeine to cause a diuretic effect. See Diuretic Effects of Caffeine for more details. Caffeine has thermogenic properties. This means ingestion of caffeine can raise your core body temperature. Recent research has not shown this to be true (Roti, Miller). Two separate placebo -controlled studies have shown no difference in urinary or plasma electrolytes, thermoregulatory variables or cardiovascular variables, even in warm, humid environments. Because our body has the ability to build a tolerance to caffeine, it has been suggested to athletes to abstain from caffeine use days/weeks prior to a race. The theory behind this method is to allow the body to become accustomed to not having caffeine and with reintroduction the ergogenic effect will be increased. However, research indicates that the body will respond to the withdrawal from caffeine experienced overnight as much as abstaining from caffeine over prolonged periods of time. The half life (time of clearance) of caffeine in the body is 6 hours. A study by Roti et al. showed improved exercise heat tolerance in a group chronically receiving caffeine compared to placebo. Recently published research supporting use of caffeine with trained athletes: Kovacs et al. (1998) studied well-trained cyclists. The results of this study support the use of caffeine during competition to improve performance. In this study, 15 cyclists ingested different levels of caffeine in addition to a carbohydrate-electrolyte drink during a time trial. The highest caffeine doses (225 and 320 mg) resulted in a 5% increase in power relative to control trials without caffeine (308 + 9 W and 309 + 10W versus 295 + 9W, respectively). The amount of caffeine ingested during this study was relatively small, and yielded caffeine concentrations in the urine of less than 5 mg/L for the participants. Another recent study by Cox et al. (2002) supported the use of caffeine both before and during cycling performance. This study involved a cycling time trial which occurred after 2 hours of steady state cycling at 70% of VO2max. Several different patterns of caffeine ingestion were utilized, including different levels before and during the trial. None of the methods caused an increase in caffeine concentration in the urine to exceed 12ug/ml. These results also demonstrate that ingestion of 1-3 mg/kg of caffeine produced the same level of performance enhanGRWOXXLent (~3%) as did the higher levels of caffeine intake (6 mg/kg). Yeo et al. (2005) published a recent study that looked at the effects of caffeine ingestion on carbohydrate oxidation. Eight male cyclists exercised for 120 min on three separate occasions. During exercise, cyclists ingested either a 5.8% glucose solution (Glu; 48 g/h), 5.8% glucose solution with caffeine (Glu+Caf, 48 g/h + 5 mg·kg·h-1), or plain water (Wat). Average exogenous CHO oxidation over the 90- to 120-min period was 26% higher (p < 0.05) in Glu+Caf (0.72 +/- 0.04 g/min) compared with Glu (0.57 +/- 0.04 g/min). Total CHO oxidation rates were higher (p < 0.05) in the CHO ingestion trials compared with Wat, but they were highest when Glu+Caf was ingested (1.21 +/- 0.37, 1.84 +/- 0.14, and 2.47 +/- 0.23 g/min for Wat, Glu, and Glu+Caf, respectively; p < 0.05). There was also a trend (P = 0.082) toward an increased endogenous CHO oxidation with Glu+Caf (1.81 +/- 0.22 g/min vs. 1.27 +/- 0.13 g/min for Glu and 1.12 +/- 0.37 g/min for Wat). In conclusion, compared with glucose alone, 5 mg/kg caffeine (approximately 350mg caffeine for a 150lb athlete) co ingested with glucose increases exogenous CHO oxidation, possibly as a result of an enhanced intestinal absorption. Doherty et al, (2005) recent meta-analysis of the use of caffeine ingestion on rate of perceived exertion (RPE) supports the use of caffeine as an ergogenic aid. Twenty-one studies were reviewed. In comparison to placebo, caffeine reduced RPE during exercise by 5.6% (95% CI). These values were significantly greater (p<0.05) than RPE obtained at the end of exercise (RPE % change, 0.01%; 95%). In addition, caffeine improved exercise performance by 11.2% (95% CI; 4.6 17.8%). Regression analysis revealed that RPE obtained during exercise could account for 29% of the variance in the improvement in exercise performance. These results demonstrate that caffeine reduces RPE during exercise, which may partly explain the subsequent ergogenic effects of caffeine on performance. In a 2004 study, Doherty et al. investigated the effects of caffeine ingestion on a ‘preloaded’ protocol that involved cycling for 2 min at a constant rate of 100% maximal power output immediately followed by a 1-min ‘all-out’ effort. Eleven male cyclists completed a ramp test to measure maximal power output. On two other occasions, the participants ingested caffeine (5 mg·kg) or placebo. Ratings of perceived exertion (RPE; 6-20 Borg scale) were lower in the caffeine trial by approximately 1 RPE point at 30, 60 and 120 s during the constant rate phase of the preloaded test (p <0.05). The mean power output during the all-out effort was increased following caffeine ingestion compared with placebo (794+/-164 vs. 750+/-163 W; p=0.05). Blood lactate concentration 4, 5 and 6 min after exercise was also significantly higher by approximately 1 mmol in the caffeine trial (p <0.05). These results suggest that high-intensity cycling performance can be increased following moderate caffeine ingestion and that this improvement may be related to a reduction in RPE and an elevation in blood lactate concentration. McClellan and Bell (2004) looked at the ergogenic role of ingesting coffee (COF) prior to the subsequent ingestion of anhydrous caffeine (CAF). Thirteen subjects performed 6 rides to exhaustion at 80 % VO2max 1.5 h after ingesting combinations of COF, decaffeinated coffee (DECOF), CAF, or placebo. Time to exhaustion was significantly greater for all trials with CAF compared to placebo. In conclusion, the prior consumption of COF did not alter the ergogenic effect of the subsequent ingestion of anhydrous CAF. Brinbaum et al. (2004) observed the physiological effects of caffeine on cross-country runners during submaximal exercise. Ten college-age subjects (5 women; 5 men) volunteered to participate in this study. After completing a VO2max test, each subject completed 2 30-minute runs at 70% VO2max on the treadmill, 1 after ingesting caffeine and the other after ingesting a placebo. Tidal volume (TV), alveolar ventilation (VA), and rating of perceived exertion (RPE) were significantly different (p < 0.05) between treatment and control groups. The results suggest that the ingestion of caffeine at 7 mg·kg of body weight prior to submaximal running might provide a modest ergogenic effect via improved respiratory efficiency and psychological lift. LATEST CAFFEINE RECOMMENDATIONSAN ERGOGENIC AID AMOUNT low to moderate dose 3-9 mg/kg body weight FORM Caffeine tablets, coffee, tea, caffeinated gels BEWARE: caffeine content in energy drinks is often not listed so be aware of the presence of guarana extracts (an herbal caffeine source included in un-standardized amounts) as well as many other unknown ingredients TIMING Ingest 60-75 minutes before event ingest small amount during event (if carbonated, should be flat) Ingest small amount late in endurance event (if carbonated, should be flat) SIDE EFFECTS Anxiety, jitters, insomnia, inability to focus, GI unrest, irritability, dependency with withdrawal side effects Mild side effects common with high doses (> 6 mg/kg) Minimal side effects with low to moderate doses (3-6 mg/kg) NOTE: CAFFEINE HAS BEEN REMOVED FROM WORLD ANTI-DOPING AGENCY’S (WADA) 2004 LIST OF PROHIBITED SUBSTANCES AND METHODS It was previously thought that caffeine’s ergogenic effect was limited to endurance events lasting greater than 2 hours. Based on the latest clinical research, evidence now suggests that individual’s participating in short bouts of exercise may also benefit from the use of caffeine. The mechanism of action appears to be quite different and varied depending on the length of activity. There are very few controlled studies looking at the effects of caffeine on endurance events lasting longer than 2 hours. For low to moderate intensity activities Caffeine has been shown to stimulate the use of stored fat (free fatty acids). This in-turn spares carbohydrates and allows athletes to exercise longer. For high Intensity activities Caffeine improves the athlete’s rate of perceived exertion and oxidation of ingested carbohydrates as well as allowing for higher lactate levels to be reached. These physiological changes allow the athlete to push a little harder and may elicit improved performance. The use of caffeine is ubiquitous. There does appear to be significant performance benefits. Caffeine is not a banned substance, although a survey of 140 competitors at the 2005 Ironman Triathlon World Championships revealed only 72% of the athletes were aware of this. 89% of athletes indicated they planned on using caffeine either before or during competition. Levels of plasma caffeine taken immediately post race indicated that athletes typically finish with quantities of caffeine that have been shown to improve endurance performance (i.e., approximately 20 micromol/L or a dose of > or = 3 mg/kg body weight). (Desbrow) Recommendations: Using caffeine as an ergogenic aid should be done with caution. Caffeine’s stimulatory effect on the central nervous system can pose harm to individuals at risk. On the day of your event consume caffeine prior to your event in a dose similar to what you are used to. If you choose to use caffeine as an ergogenic aid, do not consume more than 3 - 9 mg·kg body weight (that’s 210mg to 630mg for a 150 lb athlete). Excess caffeine can cause anxiety, irritability, delirium and hallucinations in high doses but certainly can make you jittery and give you stomach difficulty. Be aware of the possible side effects. Athletes should assess how their bodies respond to caffeine prior to the day of the race to determine if the use if beneficial for them. WADA’s removal of caffeine from its banned substance list does raise some concerns. If abused, caffeine can be detrimental and dangerous. Caffeine’s actions excitatory effects can cause injury if the dose is too high. We strongly urge all athletes wanting to use caffeine to do so cautiously. Typical Caffeine amounts: Caffeine tablet: 100 mg -200mg Excedrin tablet: 65 mg Chocolate: 1 bar equals 31 mg Coffee brewed: 7 oz equals 80-135 mg Coffee drip: 7 oz equals 115-175 mg Coffee decaffeinated: 7 oz equals 5 mg Coffee espresso: 2 oz equals 100 mg Tea (leaf): 6 oz equals 50 mg Tea (green) 177 ml equals 30 mg Coca-cola classic: 12 oz equals 34 mg Mountain Dew: 12 oz equals 54.5 mg Jolt cola: 23.5 oz equals 150 mg Red Bull: 8.2 oz equals 80 mg Wired X 344: 16 oz equals 344 mg References: Attwood AS, Higgs S, Terry P. Differential responsiveness to caffeine and perceived effects of caffeine in moderate and high regular caffeine consumers. Psychopharmacology 2007; 190:469-477 Avois L, Robinson, N, Saudan C, Baume N, Mangin P, Saugy M, Central nervous system stimulants and sport practice. Br J Sports med 2006; 40 (suppl 1) i16-i20 Costill DL, Dalsky GP, Fink WJ. Effects of caffeine ingestion on metabolism and exercise performance. Med Sci Sports Exercise. 1978; 10: 155-158 Cox GR, Desbrow B, Montgomery PG, Anderson ME, Bruce CR, Macrides TA, Martin DT, Moquin A, Roberts A, Hawley JA, Burke LM. Effect of different protocols of caffeine intake on metabolism and endurance performance. J Appl Physiol. 2002; 93(3):990-9. Desbrow B, Leveritt M. Awareness and use of caffeine by athletes competing at the 2005 World Ironman Triathlon Championships. Int j Sport Nutr Exerc Metab. 2006 Oct;16(5):545-58. Escohotado A, Symington K (May 1999) A brief history of Drugs: From the Stone age to the Stoned age. Park Street Press Essig D, Costill DL, Van Handel RJ. Effects of caffeine ingestion on utilization of muscle glygogen and lipid during leg ergometer cycling. International Journal of Sports Med. 1980; 1:86-9 Fisher SM, McMurray RG, Berry M, et al. Influence of caffeine on exercise performance in habitual caffeine users. International Journal of Sports Med 1986;7:276-280 Greer F, Friars D, Graham TE; Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance.J Appl Physiol 2000 Nov;89(5):1837-44 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Ivy JL, Costill DL, Fink WJ, et al. Influence of caffeine and carbohydrate feedings on endurance performance Med Science Sports and Exercise. 1979; 11;6-1 Kovacs EMR, Stegen JHCH, Brouns F. Effect of caffeinated drinks on substrate metabolism, caffeine excretion, and performance. J Appl Physiol 1998; 85: 709-715. Millard-Stafford ML, Cureston KJ, Wingo JE, Trilk J, Warren GL, Buyckx M. Hydration during warm, humid conditions: effect of a caffeinated sports drink. Int J Sport Nutr Exerc Metab. 2007 Apr;17(2):163-77. Nathanson, J.A. (12 October 1984) Caffeine and related methylxanthines: possible naturally occurring pesticides Science 226 (4671) 184-187 Roti MW, Casa DJ, Pumerantz AC, Watson G, Judelson DA, Dias JC, Ruffin K, Armstrong LE. Thermoregulatory responses to exercise in the heat: chronic caffeine intake has no effect. Aviat Space Environ Med. 2006 Feb;77(2):124-9. World Anti-Doping Association http://www.wada-ama.org Caffeine Drug Info: http://www.nlm.nih.gov/medlineplus/...pdi/202105.html Yeo SE, Jentjens RL, Wallis GA, Jeukendrup AE. Caffeine increases exogenous carbohydrate oxidation during exercise. J Appl Physiol. 2005 Sep;99(3):844-50. Epub 2005 Apr 14. M. Doherty, P. M. Effects of caffeine ingestion on rating of perceived exertion during and after exercise: a meta-analysis. Smith Scandinavian Journal of Medicine & Science in Sports. Volume 15 Issue 2 Page 69 - April 2005 Doherty M, Smith P, Hughes M, Davison R. Caffeine lowers perceptual response and increases power output during high-intensity cycling. J Sports Sci. 2004 Jul;22(7):637-43. Department of Sport, Exercise and Biomedical Sciences, University of Luton, Luton LU1 3JU. McLellan TM, Bell DG. The impact of prior coffee consumption on the subsequent ergogenic effect of anhydrous caffeine. Int J Sport Nutr Exerc Metab. 2004 Dec;14(6):698-708. Birnbaum LJ, Herbst JD. Physiologic effects of caffeine on cross-country runners. J Strength Cond Res. 2004 Aug;18(3):463-5. This post was written by: Patricia Rosen MD - who has written 1 posts on Team First Endurance Blog. Research Board Member Patricia Rosen resides Austin Texas. She is an accomplished age group triathlete and marathon runner. In 2003 & 2005 she was the age-group winner of the Ironstar Half Ironman. Her 2006 Freescale marathon qualified her to compete in the highly coveted Boston Marathon. Patricia works closely with local runners, cyclists and triathletes helping them get the most out of their training and nutrition. Her expertise and knowledge of endurance training allows her to offer exceptional support.

#growxxl #forum

0 notes