MNEMONIC

Deep tendon reflexes: root supply
"1,2,3,4,5,6,7,8":
S1-2: ankle
L3-4: knee
C5-6: biceps, supinator
C7-8: triceps

MNEMONIC

Carpal tunnel syndrome causes:
MEDIAN TRAP:
Myxoedema
Edema premenstrually
Diabetes
Idiopathic
Agromegaly
Neoplasm
Trauma
Rheumatoid arthritis
Amyloidosis
Pregnancy
 Mnemonic fits nicely since median nerve is trapped.

MEDICINE IN KITCHEN.........

Ginger Compounds May Be Effective in Treating Asthma Symptoms, Study Suggests

May 19, 2013 — Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the spicy root also may have properties that help asthma patients breathe more easily.

The results of the study will be presented at the ATS 2013 International Conference.

Asthma is characterized by bronchoconstriction, a tightening of the bronchial tubes that carry air into and out of the lungs. Bronchodilating medications called beta-agonists (β-agonists) are among the most common types of asthma medications and work by relaxing the airway smooth muscle (ASM) tissues. This study looked at whether specific components of ginger could help enhance the relaxing effects of bronchodilators.

"Asthma has become more prevalent in recent years, but despite an improved understanding of what causes asthma and how it develops, during the past 40 years few new treatment agents have been approved for targeting asthma symptoms," said lead author Elizabeth Townsend, PhD, post-doctoral research fellow in the Columbia University Department of Anesthesiology. "In our study, we demonstrated that purified components of ginger can work synergistically with β-agonists to relax ASM."

To conduct their study, the researchers took human ASM tissue samples and caused the samples to contract by exposing them to acetylcholine, a neurotransmitting compound that causes bronchoconstriction. Next, the researchers mixed the β-agonist isoproterenol with three separate components of ginger: 6-gingerol, 8-gingerol or 6-shogaol. Contracted tissue samples were exposed to each of these three mixtures as well as unadulterated isoproterenol and the relaxation responses were recorded and compared.

At the conclusion of their study, the researchers found that tissues treated with the combination of purified ginger components and isoproterenol exhibited significantly greater relaxation than those treated only with isoproterenol; of the three ginger components, 6-shogaol appeared most effective in increasing the relaxing effects of the β-agonist.

Once they were able to demonstrate that the ginger components enhanced the relaxing effects of the β-agonist, they turned their attention to learning why. First, the researchers wanted to determine if the ginger components might work by affecting an enzyme called phosphodiesterase4D (PDE4D). Previous studies have shown that PDE4D, which is found in the lungs, inhibits processes that otherwise help relax ASM and lessen inflammation. Using a technique called fluorescent polarization, they found that all three components significantly inhibited PDE4D.

Next, the study looked at F-actin filaments, a protein structure which previous studies have shown plays a role in the constriction of ASM, and found that 6-shogaol was effective in speedily dissolving these filaments.

"Taken together, these data show that ginger constituents 6-gingerol, 8-gingerol and 6-shogaol act synergistically with the β-agonist in relaxing ASM, indicating that these compounds may provide additional relief of asthma symptoms when used in combination with β-agonists," Dr. Townsend noted."By understanding the mechanisms by which these ginger compounds affect the airway, we can explore the use of these therapeutics in alleviating asthma symptoms."

Dr. Townsend and her colleague, Dr. Charles Emala, hope future studies will enable them to gain a better understanding of the cellular mechanisms that facilitate ASM relaxation and to determine whether aerosol delivery of these purified constituents of ginger may have therapeutic benefit in asthma and other bronchoconstrictive diseases.

                                        courtesy:science daily
.

mnemonic

Brachial plexus: numbers of each section
It is the same backwards and forwards:
5-3-2-3-5:
5 Rami
3 Trunks
2 Divisions
3 Cords
5 Terminal nerves

mnemonic

Brachial plexus: branches of posterior cord
STAR:
Subscapular [upper and lower]
Thoracodorsal
Axillary
Radial

HERE IS ANOTHER REASON TO ADOPT HEALTHIER LYFSTYLE............

Healthy Lifestyle Choices Mean Fewer Memory Complaints

 — Research has shown that healthy behaviors are associated with a lower risk of Alzheimer's disease and dementia, but less is known about the potential link between positive lifestyle choices and milder memory complaints, especially those that occur earlier in life and could be the first indicators of later problems.

To examine the impact of these lifestyle choices on memory throughout adult life, UCLA researchers and the Gallup organization collaborated on a nationwide poll of more than 18,500 individuals between the ages of 18 and 99. Respondents were surveyed about both their memory and their health behaviors, including whether they smoked, how much they exercised and how healthy their diet was.

As the researchers expected, healthy eating, not smoking and exercising regularly were related to better self-perceived memory abilities for most adult groups. Reports of memory problems also increased with age. However, there were a few surprises.

Older adults (age 60-99) were more likely to report engaging in healthy behaviors than middle-aged (40-59) and younger adults (18-39), a finding that runs counter to the stereotype that aging is a time of dependence and decline. In addition, a higher-than-expected percentage of younger adults complained about their memory.

"These findings reinforce the importance of educating young and middle-aged individuals to take greater responsibility for their health -- including memory -- by practicing positive lifestyle behaviors earlier in life," said the study's first author, Dr. Gary Small, director of the UCLA Longevity Center and a professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA who holds the Parlow-Solomon Chair on Aging.

Published in the June issue of International Psychogeriatrics, the study may also provide a baseline for the future study of memory complaints in a wide range of adult age groups.

For the survey, Gallup pollsters conducted land-line and cell phone interviews with 18,552 adults in the U.S. The inclusion of cell phone-only households and Spanish-language interviews helped capture a representative 90 percent of the U.S. population, the researchers said.

"We found that the more healthy lifestyle behaviors were practiced, the less likely one was to complain about memory issues," said senior author Fernando Torres-Gil, a professor at UCLA's Luskin School of Public Affairs and associate director of the UCLA Longevity Center.

In particular, the study found that respondents across all age groups who engaged in just one healthy behavior were 21 percent less likely to report memory problems than those who didn't engage in any healthy behaviors. Those with two positive behaviors were 45 percent less likely to report problems, those with three were 75 percent less likely, and those with more than three were 111 percent less likely.

Interestingly, the poll found that healthy behaviors were more common among older adults than the other two age groups. Seventy percent of older adults engaged in at least one healthy behavior, compared with 61 percent of middle-aged individuals and 58 percent of younger respondents.

In addition, only 12 percent of older adults smoked, compared with 25 percent of young adults and 24 percent of middle-aged adults, and a higher percentage of older adults reported eating healthy the day before being interviewed (80 percent) and eating five or more daily servings of fruits and vegetables during the previous week (64 percent).

According to the researchers, older adults may participate in more healthy behaviors because they feel the consequences of unhealthy living and take the advice of their doctors to adopt healthier lifestyles. Or there simply could be fewer older adults with bad habits, since they may not live as long.

While 26 percent of older adults and 22 percent of middle-aged respondents reported memory issues, it was surprising to find that 14 percent of the younger group complained about their memory too, the researchers said.

"Memory issues were to be expected in the middle-aged and older groups, but not in younger people," Small said. "A better understanding and recognition of mild memory symptoms earlier in life may have the potential to help all ages."

Small said that, generally, memory issues in younger people may be different from those that plague older generations. Stress may play more of a role. He also noted that the ubiquity of technology -- including the Internet, texting and wireless devices that can result in constant multi-tasking, especially with younger people -- may impact attention span, making it harder to focus and remember.

Small noted that further study and polling may help tease out such memory-complaint differences. Either way, he said, the survey reinforces the importance, for all ages, of adopting a healthy lifestyle to help limit and forestall age-related cognitive decline and neurodegeneration.

                                    courtesy:science daily

NEW ANTIDEPRESSANT WITHOUT SIDE EFFECTS..............

Ketamine Cousin Rapidly Lifts Depression Without Side Effects, Study Suggests

 — GLYX-13, a molecular cousin to ketamine, induces similar antidepressant results without the street drug side effects, reported a study funded by the National Institute of Mental Health (NIMH) that was published last month inNeuropsychopharmacology.

Major depression affects about 10 percent of the adult population and is the second leading cause of disability in U.S. adults, according to the World Health Organization. Despite the availability of several different classes of antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs), 30 to 40 percent of adults are unresponsive to these medications. Moreover, SSRIs typically take weeks to work, which increases the risk for suicide.

Enter NMDA (N-methyl-D-aspartate) receptor modulators. In the 1970s, researchers linked the receptors to learning and memory. Biotech and pharmaceutical companies in the 1980s attempted to apply chemical blockers to these receptors as a means to prevent stroke. But blocking these receptors led to the opposite effect -- --the rise of cardiovascular disease. Research in the field dampened until a glutamate receptor antagonist already approved for anesthesia, and known on the streets as "Special K," ketamine, made headlines in the early 2000s. Human clinical studies demonstrated that ketamine can ward off major and bipolar depressive symptoms within 2 hours of administration and last for several days. Ketamine is fraught with serious side effects including excessive sleepiness, hallucinations, and substance abuse behavior.

"Ketamine lit the field back up," said Joseph Moskal, Ph.D., a molecular neurobiologist at Northwestern University and senior study author. "Our drug, GLYX-13, is very different. It does not block the receptor ion channel, which may account for why it doesn't have the same side effects."

Moskal's journey with GLYX-13 came about from his earlier days as a Senior Staff Fellow in NIMH's Intramural Research Program. While at NIMH, he created specific molecules, monoclonal antibodies, to use as new probes to understand pathways of learning and memory. Some of the antibodies he created were for NMDA receptors. When he moved to Northwestern University, Moskal converted the antibodies to small protein molecules. Composed of only four amino acids, GLYX-13 is one of these molecules.

Previous electrophysiological and conditioning studies had suggested that GLYX-13, unlike ketamine, enhanced memory and learning in rats, particularly in the brain's memory hub or hippocampus. GLYX-13 also produced analgesic effects. Using several rat behavioral and molecular experiments, Moskal's research team tested four compounds: GLYX-13, an inactive, "scrambled" version of GLYX-13 that had its amino acids rearranged, ketamine, and the SSRI fluoxetine.

Results of the Study

GLYX-13 and ketamine produced rapid acting (1 hour) and long-lasting (24 hour) antidepressant-like effects in the rats. Fluoxetine, an SSRI that typically takes from 2-4 weeks to show efficacy in humans, did not produce a rapid antidepressant effect in this study. As expected, the scrambled GLYX-13 showed no antidepressant-like effects at all. The researchers observed none of the aforementioned side effects of ketamine in the GLYX-13-treated rats.

Protein studies indicated an increase in the hippocampus of the NMDA receptor NR2B and a receptor for the chemical messenger glutamate called AMPA. Electrophysiology studies in this brain region showed that GLYX-13 and ketamine promoted long-lasting signal transmission in neurons, known as long-term potentiation/synaptic plasticity. This phenomenon is essential in learning and memory. The researchers propose how GLYX-13 works: GLYX-13 triggers NR2B receptor activation that leads to intracellular calcium influx and the expression of AMPA, which then is responsible for increased communication between neurons.

These results are consistent with data from a recent Phase 2 clinical trial, in which a single administration of GLYX-13 produced statistically significant reductions in depression scores in patients who had failed treatment with current antidepressants. The reductions were evident within 24 hours and persisted for an average of 7 days. After a single dose of GLYX-13, the drug's antidepressant efficacy nearly doubled that seen with most conventional antidepressants after 4-6 weeks of dosing. GLYX-13 was well tolerated and it did not produce any of the schizophrenia-like effects associated with other NMDA receptor modulating agents.

Significance

NMDA receptors need a molecule each of the amino acid chemical messengers glutamate and glycine to become activated. Moskal speculates that GLYX-13 either directly binds to the glycine site on the NMDA receptor or indirectly modulates how glycine works with the receptor. Resulting activation of more NMDA and AMPA receptors leads to an increase in memory, learning -- and antidepressant effects. By contrast, ketamine only blocks the NMDA receptor, but also increases the activity of the AMPA receptor. Knowledge of these mechanisms could lead to the development of more effective antidepressants.

What's Next

GLYX-13 is now being tested in a Phase 2 repeated dose antidepressant trial, where Moskal and his colleagues at Naurex, Inc., a biotechnology company he founded, hope to find in humans the optimal dosing for the drug. They also want to see if this molecule, and others like it, regulate other NMDA receptor subtypes -- there are over 20 of them -- and whether it will work on other disorders, such as schizophrenia, attention-deficit hyperactivity disorder, and autism.

"One could call NMDA modulators such as GLYX-13 'comeback kids,'" said Moskal. "A toolkit that I developed in 1983 is now setting the stage in 2013 for the development of possible new therapeutics that may provide individuals suffering from depression with a valuable new treatment option."
                                                  courtesy:science daily

Probiotics Prevent Diarrhea Related to Antibiotic Use, Review Shows

 — Probiotic supplements have the potential to prevent diarrhea caused by antibiotics, according to a new Cochrane systematic review. The authors studied Clostridium difficile (C. difficile) infections in patients taking antibiotics and found symptoms of diarrhea were substantially reduced when patients were also treated with probiotics.

Antibiotics disturb the beneficial bacteria that live in the gut and allow other harmful bacteria like C. difficile to take hold. Although some people infected with C. difficile show no symptoms, others suffer diarrhea or colitis. The so-called "good bacteria" or yeast in probiotic foods and supplements may offer a safe, low-cost way to help prevent C. difficile-associated diarrhea (CDAD). This finding is important because CDAD is expensive to treat.

CDAD cases were reported in 23 trials involving 4,213 adults and children. Probiotics taken in conjunction with antibiotics reduced the number of people who suffered diarrhea by 64%. Only 2% of participants who took probiotics had CDAD compared to nearly 6% of those who took placebo. In 26 trials reporting on adverse events, there were fewer adverse events in the group taking probiotics.

"In the short-term, taking probiotics in conjunction with antibiotics appears to be a safe and effective way of preventing diarrhea associated with Clostridium difficile infection," said lead researcher Bradley Johnston of The Hospital for Sick Children Research Institute in Toronto, Canada. "The introduction of some probiotic regimens as adjuncts to antibiotics could have an immediate impact on patient outcomes, especially in outbreak settings. However, we still need to establish the probiotic strains and doses that provide the best results, and determine the safety of probiotics in immunocompromised patients."

Although taking probiotics in combination with antibiotics helped to prevent CDAD, it did not reduce the number of people who were infected with C. difficile. "We think it's possible that probiotics act to prevent the symptoms of C. difficile infection rather than to prevent the infection itself," said Johnston. "This possibility needs to be investigated further in future trials, which should help us to understand more about how probiotics work."
                                                    courtesy:science daily

Hormone Levels May Provide Key to Understanding Psychological Disorders in Women

 — Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.

The results suggest a monthly window of opportunity that could potentially be targeted in efforts to prevent common mental health problems developing in women. The research is the first to show a potential link between psychological vulnerability and the timing of a biological cycle, in this case ovulation.

A common symptom of mood and anxiety problems is the tendency to experience repetitive and unwanted thoughts. These 'intrusive thoughts' often occur in the days and weeks after a stressful experience.

In this study, the researchers examined whether the effects of a stressful event are linked to different stages of the menstrual cycle. The participants were 41 women aged between 18 and 35 who had regular menstrual cycles and were not using the pill as a form of contraception. Each woman watched a 14-minute stressful film containing death or injury and provided a saliva sample so that hormone levels could be assessed. They were then asked to record instances of unwanted thoughts about the video over the following days.

"We found that women in the 'early luteal' phase, which falls roughly 16 to 20 days after the start of their period, had more than three times as many intrusive thoughts as those who watched the video in other phases of their menstrual cycle," explains author Dr Sunjeev Kamboj, Lecturer in UCL's Department of Clinical, Educational and Health Psychology. "This indicates that there is actually a fairly narrow window within the menstrual cycle when women may be particularly vulnerable to experiencing distressing symptoms after a stressful event."

The findings could have important implications for mental health problems and their treatment in women who have suffered trauma.

"Asking women who have experienced a traumatic event about the time since their last period might help identify those at greatest risk of developing recurring symptoms similar to those seen in psychological disorders such as depression and post-traumatic stress disorder (PTSD)," said Dr Kamboj.

"This work might have identified a useful line of enquiry for doctors, helping them to identify potentially vulnerable women who could be offered preventative therapies," continued Dr Kamboj.

"However, this is only a first step. Although we found large effects in healthy women after they experienced a relatively mild stressful event, we now need to see if the same pattern is found in women who have experienced a real traumatic event. We also need further research to investigate how using the contraceptive pill affects this whole process."

                                       courtesy:science daily

STUDIES ON TO DEFEAT HIV.............

Promising Strategy to Help Vaccines Outsmart HIV

 — A new discovery at Oregon Health & Science University highlights an ingenious method to ensure the body effectively reacts when infected with the highly evasive HIV virus that causes AIDS. The same team of researchers has been utilizing this unique approach to develop its own HIV vaccine candidate, which has so far shown promising results in animal studies.

This latest research finding will be published in the May 24, 2013, edition of the journal Science.

"A major challenge in developing an effective HIV vaccine is figuring out how to target this evasive virus," said Dr. Louis Picker, M.D., associate director of the OHSU Vaccine and Gene Therapy Institute, where the work was conducted.

CD8+ "cytotoxic" T cells are an important component of the immune system and are particularly important for pathogens, like HIV, that easily evade antibodies. They serve as sentries within the body that detect and destroy virus-infected cells, accomplishing this function by recognizing short viral peptides on the surface of infected cells. T-cells are designed to be quite frugal in the number of different viral peptides they recognize, typically responding to just a handful of such peptides. This is a problem for control of HIV, which is able to able change its peptides and thus escape T cells responses that do not target the relatively few functionally critical peptides that can't change without debilitating the virus. In the vast majority of HIV infections, the few viral peptides recognized by T cells are not the vulnerable ones, and the virus escapes.

Therefore, the strategy that Dr. Picker and his colleagues adopted was to try to develop a vaccine to increase the number of viral peptides that T cells would recognize, reasoning that increasing this "recognition breadth" would allow T cells to more effectively respond to HIV.

The researchers found that cytomegalovirus or CMV, a common virus already carried by a large percentage of the population, may hold the key. Their studies in the non-human primate model of HIV, called SIV, found that a modified version of CMV engineered to express SIV proteins generates SIV-specific T cells that recognize three-fold as many SIV peptides as T cell generated by conventional vaccines and SIV itself. Moreover, these responses were entirely different from conventional responses, such that even viruses that had previously escaped natural responses would still be vulnerable. In effect, the hunters of the body were provided with a much better targeting system to help them find and destroy an elusive enemy.

Picker and his colleagues believe an HIV vaccine equipped with a modified CMV vector might be able to both prevent infection (prophylactic vaccine) and effectively battle the virus even if applied post-infection in individuals with infections suppressed by anti-retroviral therapy. Moving forward, the research team hopes to utilize this new information to create customized CMV vectors with a broad ability to identify several components of HIV and then incorporate this component into an effective vaccine.

"We hope we can begin clinical trials in human patients within a few years," explained Dr. Picker. "This new information gives us a much clearer roadmap for effectively targeting the disease which to this point has found ways to evade the human immune system."

National Institutes of Health (P01 AI094417, RO1 AI060392, RO1 AI059457, P51 OD 011092 and contract #HHSN261200800001E), the Bill & Melinda Gates Foundation and the International AIDS Vaccine Initiative funded this research.

OHSU and paper authors Drs. Picker, Hansen, Früh and Nelson have a significant financial interest in TomegaVax, Inc., a company that may have a commercial interest in the results of this research and technology. The potential individual and institutional conflicts of interest have been reviewed and managed by OHSU.
                           courtesy:science daily

PROVNG D OLDEST SAYING WRONG-"AADAKKE BARLILLA ANDRE ANGALA DONKU".........

How Playing Surfaces Affect Athletic Performance, Injury Potential

 — A group of University of Rhode Island students have been jumping up and down for weeks on a variety of playing surfaces in a study to evaluate how each affects athletic performance and injury potential.

Disa Hatfield, URI assistant professor of kinesiology, said little is known about whether athletes perform better or are more susceptible to injury on the various surfaces.

"People make decisions all the time that amount to spending thousands of dollars to buy artificial turf or to plant one kind of grass or another, but those decisions are based mostly on cost," Hatfield said. "We think this study will answer a lot of important questions, especially about injury risk."

Hatfield and her students are testing four surfaces -- a hard metal plate, artificial turf like that used in many National Football League stadiums, and grass planted on either a sandy loam soil or on peat soil.

The surfaces are being tested using 42 volunteer subjects who are asked to jump in five different ways to measure the height of each jump, the power they produce, and their landing pattern. According to Hatfield, jumping height and power directly correlate to athletic performance.

The volunteers are also filmed so the researchers can examine the angles of their legs, knees and ankles as they land to analyze injury risk.

"We expect performance to be a little better on the artificial turf, but we may also get more ankle and knee movements on the landing because of the harder impact," she said.

Hatfield said that many people, especially women, experience knee valgus -- their knees cave inward upon landing -- which is associated with a high risk of anterior cruciate ligament (ACL) injury.

"When we see knee valgus to a certain degree, that's a serious risk factor for injury," she said.

The study is particularly timely because of increasing concern, especially in the NFL, about the high prevalence of injuries on artificial turf.

"The problem is that maintaining artificial turf is much cheaper and easier than maintaining live grass. The cost factor is much less," she said. "But I'm hoping that we'll be able to show a decreased injury risk on natural surfaces, which have a higher capacity to absorb impacts."

While the professional athletic venues may be one driver of the research, Hatfield believes her data will be equally useful to recreational venues where the majority of amateur and recreational athletes exercise and compete.

"Most of those venues aren't going to be investing in an artificial surface, but they will want to know what we learn about the differences between soil types," Hatfield said. "There is some speculation that because sand is denser and doesn't bend as much, injury potential will be higher, but there is no research yet to verify that."

Hatfield will spend the summer and fall analyzing the data that is being collected this spring, and she hopes to have results to report at the end of the year.

Her research was funded in part by the New England Regional Turfgrass Foundation and with guidance from turfgrass scientists W. Michael Sullivan at URI and Jason Henderson at the University of Connecticut.

                                 courtesy:science daily

First Drug to Significantly Improve Heart Failure Mortality in Over a Decade

 — Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality in over a decade and should be added to standard treatment, according to lead author Professor Svend Aage Mortensen (Copenhagen, Denmark).

Heart Failure 2013 is being held from 25-28 May in Lisbon, Portugal. It is the main annual meeting of the Heart Failure Association of the European Society of Cardiology (1).

Coenzyme Q10 (CoQ10) occurs naturally in the body and is essential to survival. CoQ10 works as an electron carrier in the mitochondria, the powerhouse of the cells, to produce energy and is also a powerful antioxidant. It is the only antioxidant that humans synthesise in the body.

CoQ10 levels are decreased in the heart muscle of patients with heart failure, with the deficiency becoming more pronounced as heart failure severity worsens. Statins are used to treat many patients with heart failure because they block the synthesis of cholesterol, but these drugs also block the synthesis of CoQ10, which further decreases levels in the body.

Double blind controlled trials have shown that CoQ10 improves symptoms, functional capacity and quality of life in patients with heart failure with no side effects. But until now, no trials have been statistically powered to address effects on survival.

The Q-SYMBIO study (2) randomised 420 patients with severe heart failure (New York Heart Association (NYHA) Class III or IV) to CoQ10 or placebo and followed them for 2 years. The primary endpoint was time to first major adverse cardiovascular event (MACE) which included unplanned hospitalisation due to worsening of heart failure, cardiovascular death, urgent cardiac transplantation and mechanical circulatory support. Participating centres were in Denmark, Sweden, Austria, Slovakia, Poland, Hungary, India, Malaysia and Australia.

CoQ10 halved the risk of MACE, with 29 (14%) patients in the CoQ10 group reaching the primary endpoint compared to 55 (25%) patients in the placebo group (hazard ratio=2; p=0.003). CoQ10 also halved the risk of dying from all causes, which occurred in 18 (9%) patients in the CoQ10 group compared to 36 (17%) patients in the placebo group (hazard ratio=2.1; p=0.01).

CoQ10 treated patients had significantly lower cardiovascular mortality (p=0,02) and lower occurrence of hospitalisations for heart failure (p=0.05). There were fewer adverse events in the CoQ10 group compared to the placebo group (p=0.073).

Professor Mortensen said: "CoQ10 is the first medication to improve survival in chronic heart failure since ACE inhibitors and beta blockers more than a decade ago and should be added to standard heart failure therapy."

He added: "Other heart failure medications block rather than enhance cellular processes and may have side effects. Supplementation with CoQ10, which is a natural and safe substance, corrects a deficiency in the body and blocks the vicious metabolic cycle in chronic heart failure called the energy starved heart."

CoQ10 is present in food, including red meat, plants and fish, but levels are insufficient to impact on heart failure. CoQ10 is also sold over the counter as a food supplement but Professor Mortensen said: "Food supplements can influence the effect of other medications including anticoagulants and patients should seek advice from their doctor before taking them."

Patients with ischaemic heart disease who use statins could also benefit from CoQ10 supplementation. Professor Mortensen said: "We have no controlled trials demonstrating that statin therapy plus CoQ10 improves mortality more than statins alone. But statins reduce CoQ10, and circulating CoQ10 prevents the oxidation of LDL effectively, so I think ischaemic patients should supplement statin therapy with CoQ10."

                            courtesy:science daily

A NEW RAY OF HOPE TO GRANDPARENTS..........

Drug Reverses Alzheimer's Disease Deficits in Mice

 — An anti-cancer drug reverses memory deficits in an Alzheimer's disease mouse model, University of Pittsburgh Graduate School of Public Health researchers confirm in the journalScience.

In new research, scientists confirm that an anti-cancer drug reverses memory deficits in an Alzheimer's disease mouse model. (Credit: © fergregory / Fotolia)

The research, funded by the National Institutes of Health's National Institute on Aging and Alzheimer's Association, reviewed previously published findings on the drug bexarotene, approved by the U.S. Food and Drug Administration for use in cutaneous T cell lymphoma. The Pitt Public Health researchers were able to verify that the drug does significantly improve cognitive deficits in mice expressing gene mutations linked to human Alzheimer's disease, but could not confirm the effect on amyloid plaques.

"We believe these findings make a solid case for continued exploration of bexarotene as a therapeutic treatment for Alzheimer's disease," said senior author Rada Koldamova, M.D., Ph.D., associate professor in Pitt Public Health's Department of Environmental and Occupational Health.

Dr. Koldamova and her colleagues were studying mice expressing human Apolipoprotein E4 (APOE4), the only established genetic risk factor for late-onset Alzheimer's disease, or APOE3, which is known not to increase the risk for Alzheimer's disease, when a Case Western Reserve University study was published last year stating that bexarotene improved memory and rapidly cleared amyloid plaques from the brains of Alzheimer's model mice expressing mouse Apolipoprotein E (APOE). Amyloid plaques consist of toxic protein fragments called amyloid beta that seem to damage neurons in the brain and are believed to cause the associated memory deficits of Alzheimer's disease and, eventually, death.

Bexarotene is a compound chemically related to vitamin A that activates Retinoic X Receptors (RXR) found everywhere in the body, including neurons and other brain cells. Once activated, the receptors bind to DNA and regulate the expression of genes that control a variety of biological processes. Increased levels of APOE are one consequence of RXR activation by bexarotene. The Pitt researchers began studying similar compounds a decade ago.

"We were already set up to repeat the Case Western Reserve University study to see if we could independently arrive at the same findings," said co-author Iliya Lefterov, M.D., Ph.D., associate professor in Pitt Public Health's Department of Environmental and Occupational Health. "While we were able to verify that the mice quickly regained their lost cognitive skills and confirmed the decrease in amyloid beta peptides in the interstitial fluid that surrounds brain cells, we did not find any evidence that the drug cleared the plaques from their brains."

The Pitt researchers postulate that the drug works through a different biological process, perhaps by reducing soluble oligomers which, like the plaques, are composed of the toxic amyloid beta protein fragments. However, the oligomers are composed of smaller amounts of amyloid beta and, unlike the plaques, are still able to "move."

"We did find a significant decrease in soluble oligomers," said Dr. Koldamova. "It is possible that the oligomers are more dangerous than the plaques in people with Alzheimer's disease. It also is possible that the improvement of cognitive skills in mice treated with bexarotene is unrelated to amyloid beta and the drug works through a completely different, unknown mechanism."

In the Pitt experiments, mice with the Alzheimer's gene mutations expressing human APOE3 or APOE4 were able to perform as well in cognitive tests as their non-Alzheimer's counterparts 10 days after beginning treatment with bexarotene. These tests included a spatial test using cues to find a hidden platform in a water maze and a long-term memory test of the mouse's ability to discriminate two familiar objects following introduction of a third, novel object.

Bexarotene treatment did not affect the weight or general behavior of the mice. The drug was equally effective in male and female mice.

                                      courtesy:science daily

MNEMONIC

CHF: causes of exacerbation
A SMITH PEAR:
Anemia
Salt/ Stress/ Stopping meds
MI
Infection/ Ischemia
Thyroid (high/low)
HTN
Pericarditis
Endocarditis (valve disease)
Arrhythmia
Rx (beta blocker, etc)

Murmurs: innocent murmur features 
8 S's:
Soft
Systolic
Short
Sounds (S1 & S2) normal
Symptomless
Special tests normal (X-ray, EKG)
Standing/ Sitting (vary with position)
Sternal depression

MNEMONIC

CHF: causes of exacerbation [ID 3059]
A SMITH PEAR:
Anemia
Salt/ Stress/ Stopping meds
MI
Infection/ Ischemia
Thyroid (high/low)
HTN
Pericarditis
Endocarditis (valve disease)
Arrhythmia
Rx (beta blocker, etc)

now parents need not stop thier children from playing videogames...........!!!!!!!!!

New Study Recommends Using Active Videogaming ('exergaming') to Improve Children's Health

May 17, 2013 — Levels of physical inactivity and obesity are very high in children, with fewer than 50% of primary school-aged boys and fewer than 28% of girls meeting the minimum levels of physical activity required to maintain health. Exergaming, using active console video games that track player movement to control the game (e.g., Xbox-Kinect, Wii), has become popular, and may provide an alternative form of exercise to counteract sedentary behaviors. In a study scheduled for publication in The Journal of Pediatrics, researchers studied the effects of exergaming on children.

Dr. Louise Naylor and researchers from The University of Western Australia, Liverpool John Moores University, and Swansea University evaluated 15 children, 9-11 years of age, who participated in 15 minutes each of high intensity exergaming (Kinect Sports -- 200m Hurdles), low intensity exergaming (Kinect Sports -- Ten Pin Bowling), and a graded exercise test (treadmill). The researchers measured energy expenditure. They also measured the vascular response to each activity using flow-mediated dilation (FMD), which is a validated measure of vascular function and health in children.

They found that high intensity exergaming elicited an energy expenditure equivalent to moderate intensity exercise; low intensity exergaming resulted in an energy expenditure equivalent to low intensity exercise. Additionally, although the low intensity exergaming did not have an impact on FMD, high intensity exergaming significantly decreased FMD, suggesting that the latter may improve vascular health in children. High intensity exergaming also increased heart rate and the amount of energy burned. Participants reported similar enjoyment levels with both intensities of exergaming, which indicates that children may be equally likely to continue playing the high intensity games.

According to Dr. Naylor, "Higher intensity exergaming may be a good form of activity for children to use to gain long-term and sustained health benefits." These findings also support the growing notion that high intensity activity is beneficial for children's health, and high intensity exergaming should be considered a means of encouraging children to become more active.

                                                   courtesy:science daily

STAY AWAY FROM ROADS:YOUR KIDNEYS ARE AT RISK!!!!!!!!!!!

Living Close to Major Road May Impair Kidney Function

 — The authors base their findings on more than 1100 adults who had sustained a stroke between 1999 and 2004 and had been admitted to hospital in the greater Boston area of Massachusetts in the US.

---

On admission, each patient's serum creatinine was measured. This is a by-product of muscle metabolism and is filtered out of the body by the kidney, known as the glomerular filtration rate or GFR. The GFR is therefore an indicator of the health of the kidneys and how well they are working.

Half the patients lived within 1 km of a major road, with the rest living between 1 and 10 km away.

After taking account of influential factors, such as age, sex, race, smoking, underlying conditions, treatment for heart conditions, and neighbourhood affluence, those patients who lived closest to a major road had the lowest GFR.

Those who lived 50 metres away had a GFR that was 3.9 ml/minute/1.73 m² lower than those who lived 1000 metres away. This difference is comparable to a reduction in GFR associated with being 4 years older.

The authors calculate that a reduction in proximity to a major road from 1000 metres to 50 metres may be associated with a 4% higher rate of cardiovascular death and a 1% increased risk in death from all causes.

"There is growing evidence that living near major roadways contributes to the incidence of vascular disease, and adverse prognosis among patients with prevalent cardiovascular disease," write the authors.

Air pollution caused by traffic is associated with an increased risk of stroke and heart attack, as a result of inflammation, artery narrowing as a result of plaque build-up, and changes to peripheral arteries.

The kidneys are highly susceptible to the build-up of arterial plaque, write the authors: "If causal, these results imply that exposures associated with living near a major roadway contribute to reduced renal function, an important risk factor for cardiovascular events."

                                                 courtesy:science daily

Brain Frontal Lobes Not Sole Center of Human Intelligence, Comparative Research Suggests

May 13, 2013 — Human intelligence cannot be explained by the size of the brain's frontal lobes, say researchers.

Research into the comparative size of the frontal lobes in humans and other species has determined that they are not -- as previously thought -- disproportionately enlarged relative to other areas of the brain, according to the most accurate and conclusive study of this area of the brain.

It concludes that the size of our frontal lobes cannot solely account for humans' superior cognitive abilities.

The study by Durham and Reading universities suggests that supposedly more 'primitive' areas, such as the cerebellum, were equally important in the expansion of the human brain. These areas may therefore play unexpectedly important roles in human cognition and its disorders, such as autism and dyslexia, say the researchers.

The study is published in the Proceedings of the National Academy of Sciences (PNAS) today.

The frontal lobes are an area in the brain of mammals located at the front of each cerebral hemisphere, and are thought to be critical for advanced intelligence.

Lead author Professor Robert Barton from the Department of Anthropology at Durham University, said: "Probably the most widespread assumption about how the human brain evolved is that size increase was concentrated in the frontal lobes.

"It has been thought that frontal lobe expansion was particularly crucial to the development of modern human behaviour, thought and language, and that it is our bulging frontal lobes that truly make us human. We show that this is untrue: human frontal lobes are exactly the size expected for a non-human brain scaled up to human size.

"This means that areas traditionally considered to be more primitive were just as important during our evolution. These other areas should now get more attention. In fact there is already some evidence that damage to the cerebellum, for example, is a factor in disorders such as autism and dyslexia."

The scientists argue that many of our high-level abilities are carried out by more extensive brain networks linking many different areas of the brain. They suggest it may be the structure of these extended networks more than the size of any isolated brain region that is critical for cognitive functioning.

Previously, various studies have been conducted to try and establish whether humans' frontal lobes are disproportionately enlarged compared to their size in other primates such as apes and monkeys. They have resulted in a confused picture with use of different methods and measurements leading to inconsistent findings.

                                              courtesy:science daily

New Drug Reverses Memory Deficits and Slows Alzheimer's in Mice

May 13, 2013 — A drug developed by scientists at the Salk Institute for Biological Studies, known as J147, reverses memory deficits and slows Alzheimer's disease in aged mice following short-term treatment. The findings, published May 14 in the journal Alzheimer's Research and Therapy, may pave the way to a new treatment for Alzheimer's disease in humans.

---

Marguerite Prior, Salk Institute, is a research associate in Salk's Cellular Neurobiology Laboratory. (Credit: Photo: Courtesy of the Salk institute for Biological Studies)          

"J147 is an exciting new compound because it really has strong potential to be an Alzheimer's disease therapeutic by slowing disease progression and reversing memory deficits following short-term treatment," says lead study author Marguerite Prior, a research associate in Salk's Cellular Neurobiology Laboratory.

Despite years of research, there are no disease-modifying drugs for Alzheimer's. Current FDA-approved medications, including Aricept, Razadyne and Exelon, offer only fleeting short-term benefits for Alzheimer's patients, but they do nothing to slow the steady, irreversible decline of brain function that erases a person's memory and ability to think clearly.

According to the Alzheimer's Association, more than 5 million Americans are living with Alzheimer's disease, the sixth leading cause of death in the country and the only one among the top 10 that cannot be prevented, cured or even slowed.

J147 was developed at Salk in the laboratory of David Schubert, a professor in the Cellular Neurobiology Laboratory. He and his colleagues bucked the trend within the pharmaceutical industry, which has focused on the biological pathways involved in the formation of amyloid plaques, the dense deposits of protein that characterize the disease. Instead, the Salk team used living neurons grown in laboratory dishes to test whether their new synthetic compounds, which are based upon natural products derived from plants, were effective at protecting brain cells against several pathologies associated with brain aging. From the test results of each chemical iteration of the lead compound, they were able to alter their chemical structures to make them much more potent. Although J147 appears to be safe in mice, the next step will require clinical trials to determine whether the compound will prove safe and effective in humans.

"Alzheimer's disease research has traditionally focused on a single target, the amyloid pathway," says Schubert, "but unfortunately drugs that have been developed through this pathway have not been successful in clinical trials. Our approach is based on the pathologies associated with old age-the greatest risk factor for Alzheimer's and other neurodegenerative diseases-rather than only the specificities of the disease."

To test the efficacy of J147 in a much more rigorous preclinical Alzheimer's model, the Salk team treated mice using a therapeutic strategy that they say more accurately reflects the human symptomatic stage of Alzheimer's. Administered in the food of 20-month-old genetically engineered mice, at a stage when Alzheimer's pathology is advanced, J147 rescued severe memory loss, reduced soluble levels of amyloid, and increased neurotrophic factors essential for memory, after only three months of treatment.

In a different experiment, the scientists tested J147 directly against Aricept, the most widely prescribed Alzheimer's drug, and found that it performed as well or better in several memory tests.

"In addition to yielding an exceptionally promising therapeutic, both the strategy of using mice with existing disease and the drug discovery process based upon aging are what make the study interesting and exciting," says Schubert, "because it more closely resembles what happens in humans, who have advanced pathology when diagnosis occurs and treatment begins." Most studies test drugs before pathology is present, which is preventive rather than therapeutic and may be the reason drugs don't transfer from animal studies to humans.

Prior and her colleagues say that several cellular processes known to be associated with Alzheimer's pathology are affected by J147, including an increase in a protein called brain-derived neurotrophic factor (BDNF), which protects neurons from toxic insults, helps new neurons grow and connect with other brain cells, and is involved in memory formation. Postmortem studies show lower than normal levels of BDNF in the brains of people with Alzheimer's.

Because of its broad ability to protect nerve cells, the researchers believe that J147 may also be effective for treating other neurological disorders, such as Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS), as well as stroke, although their study did not directly explore the drug's efficacy as a therapy for those diseases.

The Salk researchers say that J147, with its memory enhancing and neuroprotective properties, along with its safety and availability as an oral medication, would make an "ideal candidate" for Alzheimer's disease clinical trials. They are currently seeking funding for such a trial.

                            courtesy:science daily

MNEMONIC

Atrial fibrillation: causes
A S#!T:
Alcohol
Stenosis (mitral valve)
Hypertension
Infarction/ Ischaemia
Thyrotoxicosis

Apex beat: abnormalities found on palpation, causes of impalpable
HILT:
Heaving
Impalpable
Laterally displaced
Thrusting/ Tapping
If it is impalpable, causes are COPD:
COPD
Obesity
Pleural, Pericardial effusion
Dextrocardia

MNEMONIC

Muscles: potentially absent ones
 Muscles which may be absent but may be important:
5 P's:
Palmaris longus [upper limb]
Plantaris [lower limb]
Peroneus tertius [lower limb]
Pyramidalis [anterior abdominal wall]
Psoas minor [posterior abdominal wall]

MNEMONIC

Bicipital groove: attachments of muscles near it
"The lady between two majors":
Teres major attaches to medial lip of groove.
Pectoralis major to lateral lip of groove.
Latissimus (Lady) is on floor of groove, between the 2 majors

MNEMONIC

Anterior forearm muscles: superficial group
There are five, like five digits of your hand.                                    
Place your thumb into your palm, then lay that hand palm down on your other arm,
Your 4 fingers now show distribution: spells PFPF [pass/fail, pass/fail]:
Pronator teres
Flexor carpi radialis
Palmaris longus
Flexor carpi ulnaris
Your thumb below your 4 fingers shows the muscle which is deep to the other four: Flexor digitorum
superficialis.

DENGUE VIRUS SPECIAL FEATURE REVEALED: HOPE THIS HELPS TO SAVE CHILDREN...........

Discovery Points to New Approach to Fight Dengue Virus

Apr. 11, 2013 — Researchers have discovered that rising temperature induces key changes in the dengue virus when it enters its human host, and the findings represent a new approach for designing vaccines against the aggressive mosquito-borne pathogen.

The researchers found that the dengue virus particles swell slightly and take on a bumpy appearance when heated to human body temperature, exposing "epitopes," or regions where antibodies could attach to neutralize the virus.

The discovery is significant because it could help to explain why vaccines against dengue have been ineffective, said Michael G. Rossmann, Hanley Distinguished Professor of Biological Sciences at Purdue University.

Scientists have been designing vaccines targeting the virus's smooth appearance found at the cooler temperatures of mosquitoes and ticks.

"The bumpy form of the virus would be the form present in humans, so the optimal dengue virus vaccines should induce antibodies that preferentially recognize epitopes exposed in that form," Rossmann said.

The findings are detailed in a research paper appearing online this week in Proceedings of the National Academy of Sciences.

The researchers used a technique called cryo-electron microscopy to see the three-dimensional structure of the virus at temperatures ranging from 28-37 degrees Celsius (37 degrees Celsius is 98.6 degrees Fahrenheit, or human body temperature). Findings showed that the virus has a smooth appearance while at the cooler temperatures found in mosquito or tick vectors, but then it morphs into the bumpy form at warmer temperatures before fusing to the host cell and delivering its genetic material.

"These findings were a big surprise," said Richard J. Kuhn, professor and head of Purdue's Department of Biological Sciences and director of the Bindley Bioscience Center. "No one expected to see the virus change its appearance as it moves from the mosquito to humans."

The paper was co-authored by postdoctoral researcher Xinzheng Zhang; lab manager Ju Sheng; postdoctoral researcher Pavel Plevka; Kuhn; Michael S. Diamond, a researcher at Washington University School of Medicine; and Rossmann.

Findings also could apply to related infections in the flavivirus family, which includes a number of dangerous insect-borne diseases such as West Nile, yellow fever, tick-borne encephalitis and Japanese encephalitis.

Dengue (pronounced DEN-gē) is a leading cause of serious illness and death among children in some Asian and Latin American countries, causing 50 million to 100 million infections per year. Globally, dengue has grown dramatically in recent decades, placing about half the world's population at risk of infection.

The researchers determined that the bumpy form of the virus is more efficient at infecting mammalian cells. The team was able to measure the virus's infectivity using a laboratory procedure where cells are infected in a culture dish. The bumpy shape is an intermediate stage before the virus becomes unstable, releasing its genetic material. The virus is made of subunit molecules that separate when the virus particle expands into its bumpy form, revealing exposed membrane surfaces between the subunits where antibodies might bind.

The work is funded by the National Institutes of Health and Purdue through university support for a structural biology electron microscope facility.

MDR BACTERIAS WILL NO MORE BE A PROBLEM TO TREAT.........!!!!!!!!!!!!

Discovery Holds Potential in Destroying Drug-Resistant Bacteria

May 7, 2013 — Through the serendipity of science, researchers at the University of Pittsburgh have discovered a potential treatment for deadly, drug-resistant bacterial infections that uses the same approach that HIV uses to infect cells.

The National Institutes of Health-supported discovery will be described in the June issue of the journalAntimicrobial Agents and Chemotherapy. It is especially promising in the development of a potential treatment for lung infections in people with cystic fibrosis.

"The discovery of this new antibiotic was an unexpected result of basic research on HIV proteins," said senior author Ronald Montelaro, Ph.D., professor and co-director of Pitt's Center for Vaccine Research (CVR). "As a result of studying these proteins, we discovered novel structures that turn out to work very well against bacterial infections, including the complicated bacterial populations in lung infections in cystic fibrosis patients."

Cystic fibrosis is a genetic disorder that leads to thick, viscous secretions in the lungs and other organs in about 30,000 children and adults in the United States, according to the Cystic Fibrosis Foundation. Lung infections resistant to antibiotics often are deadly for people with cystic fibrosis. About 80 percent of cystic fibrosis patients have at least one antibiotic-resistant infection in their lungs by age 18.

"Infections with progressively resistant bacteria in the lung shorten the lives of people with cystic fibrosis," said Joseph M. Pilewski, M.D., co-director of the Adult Cystic Fibrosis Center at UPMC. "What happens is the genetic defect predisposes patients to infections that drive the production of mucus that then blocks the airways and makes it difficult to breath."

Dr. Montelaro and his colleagues found that a particular sequence of amino acids on the tail end of HIV allow the virus to "punch into" and infect cells. The team manufactured a synthetic and more efficient version of this sequence -- called engineered cationic antimicrobial peptides, or "eCAPs" -- that laboratory tests have shown to rapidly destroy bacteria that are otherwise resistant to most standard antibiotics.

The eCAPs can be assembled in a laboratory setting from the amino acids arginine and tryptophan and manufactured to the shortest effective length, giving the resulting antibiotic treatment maximum potency while reducing costs.

The discovery was featured in April at two gatherings intended to put scientists in touch with business developers -- the BIO International Convention in Chicago, and the University Research & Entrepreneurship Symposium (URES) in Boston.

"At both symposia, we received a lot of interest from pharmaceutical-related companies," said co-author Jonathan Steckbeck, Ph.D., M.B.A., post-doctoral associate at CVR. "It was a particular honor to be recognized at URES as one of the year's 10 breakthroughs in life sciences."

Pitt has taken out several U.S. and international patents on this discovery.

"We have an unmet clinical need for treatment of hospital-acquired infections where the bacteria are extremely resistant to antibiotics," said co-author Yohei Doi, M.D., Ph.D., assistant professor of medicine in Pitt's School of Medicine. "We have patients with no treatment options left. The fact that these eCAPs are completely engineered puts them at an advantage because they can be manufactured easily, and they give us some hope for a quick-acting treatment in these dire circumstances."

Traditional antibiotics typically work by poisoning important metabolic processes after being taken up by the target bacteria, a process that may take hours, or days, to clear a bacterial infection. In contrast, the eCAPs are specifically attracted to the surface of target bacteria where they disrupt the bacterial membrane, causing death within seconds, or minutes.

Laboratory tests indicate that the eCAPs work well against biofilms, which are bacterial communities that develop very high levels of resistance to antibiotics by working together to protect the film's inner bacteria from traditional treatments. The eCAPs seem to push through the outer layers of biofilms to destroy the entire bacterial community.

"It's like a pin bursting a balloon; it's a very rapid action," said Dr. Montelaro. "While cystic fibrosis patients are our initial target and a very high-priority target, we also could look at infections associated with burns or indwelling medical devices, such as venous catheters. We could even look to the biodefense realm, in terms of a rapid, handheld nebulizer treatment that soldiers could use in the case of exposure to a bioterrorism agent."

Additional co-authors are Berthony Deslouches, M.D., Ph.D., and Jodi Craigo, Ph.D., both of Pitt's Center for Vaccine Research; and Timothy A. Mietzner, Ph.D., of the Lake Erie College of Osteopathic Medicine at Seton Hill.

                                                   courtesy:science daily

AMAZING!!!!!!!!!

Excessive Weight Gain During Pregnancy Increases Risk of Lacerations During Childbirth

May 7, 2013 — Excessive weight gain during pregnancy significantly increases the risk of lacerations during vaginal childbirth, according to a study conducted by researchers at Montefiore Medical Center. Among more than 1,000 women who participated in the study, 126 experienced a significant increase in their body mass index (BMI), both +1 and +2 category changes, according to the criteria established by the World Health Organization (WHO). Of those women, 85.5 percent experienced lacerations compared to 69 percent with no change in BMI category.

The study was presented today in New Orleans at the annual meeting of the American College of Obstetricians and Gynecologists.

"Excessive weight gain during pregnancy can result in larger babies, so we wanted to study whether there is increased risk for tears to the mother's vagina during delivery," said Diana Garretto, M.D., Department of Obstetrics & Gynecology and Women's Health, Montefiore Medical Center, and Instructor, Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine of Yeshiva University. "Our results were noteworthy -- when the mother gains too much weight, it causes increased risk for tears during delivery."

The most common injuries to the vagina during labor occur at the vaginal opening, which may tear as the baby's head passes through. For successful vaginal delivery, the cervix must dilate to at least 10 centimeters. When a woman gains too much weight, the larger baby may increase the risk for laceration.

About 30 percent of women who maintained a normal BMI were laceration-free. Among women who became overweight during pregnancy, however, only 20 percent had no lacerations, and for women who were obese, just 9 percent went through delivery without a tear. Tears that occur in the posterior portion of the vagina can vary in severity. First degree lacerations, when the tear involves only the lining of the vagina, are the most common. A first degree tear doesn't usually bleed and may not require repair. A second degree laceration is when the tear extends into the submucosal tissues (the tissues just under the vaginal lining). Most second degree tears occur in the midline and extend towards the anus and require surgical repair.

More serious lacerations involve the deeper tissues, including the anal sphincter (third degree lacerations) or even the rectum and its lining (fourth degree lacerations). These lacerations are often difficult to repair and require surgery. Third and fourth degree tears are more likely to cause complications, including infection, bleeding, anal incontinence and increased pain.

A single institution retrospective chart review of 1,031 patients who delivered at term over seven months was performed. Patients were categorized into BMI classes at pre-pregnancy and term. Pre-pregnancy BMI categories are, according to WHO, normal weight -- 18-25, overweight -- 25-30, and obese -- 30 and above. Based on the 2009 IOM guidelines for appropriate weight gain during pregnancy, BMI was classified as underweight -- less than 23.5, normal weight -- 23.5-29.9, overweight -- 30-33, and obese -- greater than 33.5.
                                                      courtesy:science daily

NOW NO FEAR OF SIDE EFFECTS ANTI CANCER DRUGS!!!!!!!!

New Delivery for Cancer Drugs

May 7, 2013 — The protein tumor necrosis factor-alpha (TNF-alpha) is a powerful weapon in the arsenal to control cancer. Unfortunately, as is the case with many potent cancer therapies, the use of TNF-alpha as an anti-cancer therapy has been severely limited. "It was so toxic that it caused death," and researchers gave up on it, explains Scott McNeil, director of the Nanotechnology Characterization Lab at the Frederick National Laboratory for Cancer Research.

That was back in the 1990s. Today, TNF-alpha is a prime example of how to safely and effectively deliver toxic substances to cancer cells through the use of nanotechnology.

McNeil's lab, part of the federally funded research and development center operated by SAIC-Frederick for the National Cancer Institute, worked with a drug company to reformulate TNF-alpha by coupling it with gold nanoparticles. Using the nanotechnology-enhanced protein, it appears possible to safely inject up to three times the amount that had been lethal with previous versions. The modified drug has been through a Phase 1 clinical trial and is entering Phase 2.

In McNeil's lab, and for other scientists using nanotechnology for drug delivery, stories like this one are increasingly common. Researchers are looking to accelerate the development of potential nanotechnology drugs for cancer by exploring ways to reduce side effects and make treatments hit their targets more effectively. This can mean using nanotechnology to reformulate drugs that may have failed in previous clinical trials. In some cases, by attaching a nanoparticle to an existing drug, researchers may not only be able to lower its toxicity, but they may also see significant life expectancy gains for patients.

Many cancer drugs are approved based on how long they delay the progression of disease. Some drugs on the market "only improve life expectancy by maybe five weeks," says McNeil. He sees nanomedicine as a potential game-changer for cancer drugs in the future.

McNeil, both a chemist and biologist, has spent the majority of his career working in nanotechnology, but when he was asked to apply his expertise to find better drugs for cancer, he was skeptical. "My professional career was mostly military," says the former Army officer. "I was using nanotech for military applications at SAIC, using quantum dots to see if you scatter things, where they land. I got a call out of the blue in December of 2003 and the message was, 'We want to use nanotech for cancer applications.' I thought, 'What are they thinking? You are going to put a cadmium quantum dot in a human? There is no way!' I discounted it at first and I actually ignored the emails, hoping it would go away."

But it did not go away. In fact, much has changed in the last 10 years. Now, nanopharmaceuticals are beginning to demonstrate their capacity to place the drugs directly in the tumor, where they will do the most good, rather than let them roam freely in the body. A drug is attached to a nanoparticle, which is often a tiny little sphere. To put it in perspective, a nanometer is one billionth of a meter; the width of a single strand of hair is about 10,000 nanometers. The nanoparticle is small enough to flow through blood vessels and into a tumor, where the particle dissociates, and the drug is released. In the end, the goal of nanomedicine is that the only part of the body affected by the drug is the tumor, the area of need.

McNeil's Nanotechnology Characterization Lab was founded in 2004 in collaboration with the Food and Drug Administration and the National Institute of Standards and Technology. There is one thing the lab does not do: develop nanotechnology drugs. Instead, researchers there -- ranging in expertise from cancer biology and toxicology to chemistry, immunology, and physics -- help investigators from around the world create the best drugs possible. "We help investigators get from proof of concept, where they are generating a few tens of milligrams of material and get into clinical trials, where they are going to need kilograms of materials," say McNeil. "That translational research, as we call it, is absolutely germane to getting into clinical trials."

The majority of scientists who apply for assistance from the NCL are seeking FDA approval for their nanotech drugs but they don't have the resources to optimize their formula. The NCL can help. "We help them understand what is involved with their particle because they don't have the tools that we have to be able to characterize," says McNeil. "They may have a nice picture or cartoon of it but until they see our electron micrographs, they don't know what it looks like."

The Nanotechnology Characterization Lab serves two purposes. After a molecule has been through the NCL's assay cascade which consists of a set of tests that evaluate the preclinical toxicology, pharmacology, and efficacy of nanoparticles, the NCL is able to offer an evaluation. "The investigator is going to need $40 million dollars to get into Phase 2 trials. Investigators need to justify the investment. We help them generate data they need to further their work and then we serve as a third-party evaluation." That is crucial, McNeil says, for an investigator seeking funding. "A venture capital company can come to us and say, 'Well, what do you really think of this? Let's see your data, and explain it and defend it.' We, obviously, cannot endorse it but we can discuss the data in the context of what they are trying to do. That really holds a lot of weight."

Consider the example of Abraxane (paclitaxel), which was approved for use by the FDA in 2005. Abraxane, a variably toxic but widely prescribed cancer drug, has been enhanced by attaching it to a nanoparticle, thereby creating a new, targeted treatment. "Because of the size and the binding to a different receptor, that drug now has decreased toxicity compared to the former drug. For the nanoparticle-Abraxane conjugate toxicity is very marginal, at least for immunotoxicity and hypersensitivity," says McNeil.

Since 2005, the Nanotechnology Characterization Lab has characterized nearly 300 different particles. Six of them are in clinical trials. "Depending upon what community you are from, either that is a terrific ratio or that is a poor ratio," explains McNeil. "We view it as a super terrific ratio. A pharmaceutical company can make hundreds of thousands of different drugs and only about one out of 100,000 gets into clinical trials."
                                COURTESY:scince daily