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Extrication

In order to improve the outcomes for patients who have experienced traumatic injury, a pioneering research is being carried out by the researchers from the University of Birmingham. This study is a part of the major £10 million study is known as the ˜Golden Hour' study.

The Golden Hour study was launched in the year 2014 and is carried out over a four year period. The term ˜golden Hour' refers to the first 60 minutes from the time a person suffers a traumatic injury. This time is very crucial as a prompt and right medical analysis and treatment during this period is an important factor for the patient's survival. The aim of the study is to understand what happens to the immune system in this 60 minutes window. Insights into the happening can play a big role in managing such cases.

The study is being led by Professor Janet Lord and Professor Tony Belli from the University of Birmingham’s Institute of Inflammation and Ageing and the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre (NIHR SRMRC) respectively. A key piece of the research of the ongoing Golden Hour study was published in PLOS Medicine on 18th July 2017.

It is seen that the major and instant cause of the death after a severe trauma is hemorrhage remarked Lead author Dr. Jon Hazeldine, a Research Fellow at the University of Birmingham However, in some cases where the victim dies later complications like multi-organ dysfunction or sepsis are the causes of death. It means that the individual’s immune response to injury greatly influences the chances of developing these fatal conditions.

He added that in most studies that have studied the immune response to trauma, blood samples taken after hospital admission have been analyzed. So, there is no information about the immune status of the patient right after the injury and how it might have any influence on the outcome for the patient.

Dr Hazeldine further adds that the aim of the study is to comprehensively assess the ultra-early immune response to trauma. The exploratory analysis then needs to be carried out to find its relationship with the development of multiple organ dysfunction syndromes.

An important part of the research was the blood sampling and analysis operation working 24 hours a day in collaboration with West Midlands Ambulance Service and Midlands Air Ambulance. Paramedics who are specially trained in taking blood samples from such patients are immediately sent to the scene of such major traumas.

Professor Janet Lord explained that even before this study, it was known that a few days after major trauma the immune system is much suppressed, and it makes the patient very prone to infections and sepsis. However, it wasn't known how soon it happens. This study has now revealed that the changes to the immune system happen fast. In fact, within minutes of a traumatic injury, the levels of many immune cells and molecules are altered in the patient. It is also interesting to note that in some cases these immune cells and molecules increase than normal and in some cases they decrease.

Professor Janet Lord added that it was known that after a traumatic injury activation of the immune system happened and also compensatory response starts in a bid to dampen down the inflammation. This study showed us that these processes don't happen sequentially but simultaneously.

As a part of their study, the composition and function of immune cells and concentrations of cytokines, in blood samples acquired within one hour from 89 adults who suffered traumatic injuries was analyzed. Again blood samples were taken at four to 12 hours and 48 to 72 hours post-injury and were analyzed.

Professor Tony Belli explained that it was seen that many characteristics of the immune reaction observed in the first hour were different from those seen at later time points. Also, a link between natural killer T cell numbers in the hour after trauma and the eventual development of multiple organ dysfunction syndromes was found.

The researchers are now hopeful that their findings will help them to develop a test to determine which patients have a response that makes them likely to get to sepsis or multiorgan failure. This test will help in identifying such cases so that treatment can be started early.

References

https://medicalxpress.com/news/2017-07-complex-immune-hour-traumatic-injury.html

https://www.sciencedaily.com/releases/2017/07/170718142919.htm

 

 

 

A new study by the researchers at the University Of Virginia School Of Medicine has suggested that aggressive combination treatments for high blood pressure that are intended to protect the kidneys may actually be doing harm to the organs.

The researchers made this observation when they were studying some strange lesions in mice that have lost the ability of produce the enzyme renin. Similar lesions are also seen in patients suffering from high blood pressure. Their study revealed that the lesions were caused by the renin cells. In some treatments for high blood pressure, renin cells are targeted and that might give rise to the lesions.

Ariel Gomez, MD, who is the director of UVA’s Child Health Research Center, remarked that in order to treat hypertension, inhibitors of the renin angiotensin system are being used for quite a while and they are considered largely safe. He added that their research on mice have indicated that the complete lack of renin causes vascular lesions. Now that poses a question whether long-term and aggressive use of compounds that completely demolish the renin angiotensin system cause any problems in humans. More research into the subject is needed to find a definitive answer.

What is Renin’s Role in Managing Blood Pressure?

The role of the hormone renin in the body is to regulate blood pressure. The cells that produce renin also play a vital role in blood vessels creation during the developmental phase in the womb. When these cells were blocked from producing renin in adult mice, it led to the creation of obstructive vascular lesions in the kidneys. It seemed like the blood vessel now created by renin cells were defective, disorganized and directionless and didn't carry out the functions they were meant to. Gomez added that typically arteries are thin and let blood pass through it. But, that was not the case when renin production was blocked. The lesions were filled with non-functional cells.

Researcher Maria Luisa S. Sequeira-Lopez, MD said that their study led them to think, whether stopping the cells from carrying out their routine function extended over long periods of time was having an undesirable and unintended side effect in patients with high blood pressure. She added that since renin plays an important part during pregnancy, renin inhibition is avoided during pregnancy as it can have unwanted effects in the development of the baby.

Questioning the Combination

Gomez and Sequeira-Lopez made clear that not all hypertension drugs have this effect on the kidney. Only certain less common combination treatments that work by completely blocking the whole renin-angiotensin system need to be reevaluated as they chronically stimulate renin cells to accumulate inappropriately to form lesions in the kidney. Together with low blood pressure, kidney structure can be severely affected. High blood pressure patients should ask their doctors before stopping taking their prescribed medications as it can lead to worse problems.

The next thing to do in the research process is to delve deeper into their findings so that they can have a better understanding of the whole thing. Also, they have to find out if what happens in mice also holds true in humans.

Gomez added that they need to find out whether it is necessary or not to use dual combinations of drugs that over-activate renin cells plus they need to know how low and how fast blood pressure should be lowered. Once that's done, the effects this combination treatment has in individuals needed to be looked at and analyzed.

In case the findings are found to apply to humans also, they will have to work on finding how exactly it happens “ as in what molecules are activated, and how to act on those molecules to prevent the overgrowth of the vessels. Gomez added that physicians might then need to exercise control and use their judgment wisely before treating hypertension using full-blown inhibition.

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References

https://medicalxpress.com/news/2017-07-aggressive-blood-pressure-treatments-kidney.html

https://www.sciencedaily.com/releases/2017/07/170718142913.htm

 

 

Wheelchair

A recent research has suggested that if one is on a long-term prescription of opioid medication, tapering the dose can help in improving pain and function and will also boost the quality of life. So, in this case, less is actually better for you.

Dr. Joseph Frank, a primary care physician at Denver’s Veterans Affairs Medical Center and the lead author of the new study said that almost 10 million Americans resort to long-term opioid medications in order to manage chronic pain. Oxycodone (Oxycontin, Percocet) and hydrocodone (Vicoprofen) are all included in Opioid medications. Doctors prescribe these medications over extended periods in order to treat a variety of chronic pain conditions, like arthritis or low back pain.

Frank remarked that there are ongoing nationwide efforts to reduce the usage of opioid drugs. Such efforts will have an impact people who have been prescribed these drugs for long term use for chronic pain management. But, there is not much known about the benefits and risks associated with reducing long-term opioid therapy. If a person has been taking them for a long time and then stops suddenly, it is likely that he will suffer from unpleasant withdrawal symptoms.

The report on this research was published online recently in the Annals of Internal Medicine.

Tamara Haegerich, of the U.S. Centers for Disease Control and Prevention, added that the withdrawal symptom when opioids are reduced or discontinued too quickly for people who were using them over prolonged period include drug craving, anxiety, insomnia, abdominal pain, and tremor. She added that one size fits all approach will not apply here and there be a need to customize the tapered dose according to patient goals and concerns.

As a part of their research review, Frank and his fellow colleague analyzed 67 studies that focussed on reducing or discontinuing opioid therapy prescribed for chronic pain management. About 40 of these studies specifically delved into how people fared when the dose of the opioid medication was reduced. The good news is that most people reported having found some improvement in pain severity, function, and quality of life.

However, the quality of evidence in the studies was not very high. The researchers still emphasized on the need of cutting back on opioid medication. There are several important risks associated with opioid medication like addiction and overdose. Also, there are other problems like an increased risk of fractures, heart attack, sleep issues, mood swings, and libido problems associated with it.

The risks increase with an increase in dose. One remedy is to taper the doses or stopping them altogether. But, that too is not devoid of issues as it can lead to illegal substance use or even suicide. So, ideally, the tapering of opioid dose should be gradual and should be supported by other non-opioid care.

Mindfulness meditation and cognitive behavioral therapy, a type of psychotherapy are some of the non-opioid treatment that might be needed.

Dr. Harshal Kirane, Director of addiction services at Staten Island University Hospital in New York City remarked that identifying effective non-opioid approaches to chronic pain management is of significant importance. Kirane is not a part of the research team but added that medication-assisted therapies which involve agents such as methadone and buprenorphine can also help opioid tapering.

Among the various ways tapering of opioid dose can be done, the basic is to lower a patient’s daily dose by 10 percent every five to seven days explained Kirane. This need to be done until the patient is off the medication completely, or re-establishes a lower baseline regimen. Abruptly stopping opioids is likely to give withdrawal syndromes or will make the person highly vulnerable to relapse back to opioid use.

Opioid prescribing has widely occurred without an adequate risk assessment in the last two decades. Kirane added that by aiding individuals to develop healthy skills and habits to deal with chronic pain, the opioid epidemic can be handled.

References

https://medicalxpress.com/news/2017-07-easing-opioid-dose-pain-quality.html

http://www.philly.com/philly/health/topics/HealthDay724681_20170718_Easing_Opioid_Dose_May_Improve_Pain_and_Quality_of_Life.html

 

 

Baby

The primate brain has an organized set of a map for each of senses “ be it touch, sight or hearing. Researchers have known for a while that these maps are categorized into designated area that responds to different types of stimuli in each of the senses in adults. However, there has been a lot of ambiguity if this organization is innate or develops over time.

Through a study, the Harvard Medical School researchers Michael Arcaro and Margaret Livingstone tried to find the answer to it and their research seems to suggest that the answer could be both. The study was published recently in eLife and it says that a primitive blueprint of an organization is present in the brains of primates within few days of birth. With age and experience, it gradually gets filled in. The findings of the study explain some characteristics of neurodevelopmental disorders like autism, like avoidance of certain visual stimuli, and stress the importance of correcting visual deficits in infants early to ensure normal brain development.

Livingstone and Arcaro in their new study have tried to gain a better understanding of the organization of the visual system. As a part of their research, the brain activity of four 10 days young macaques was monitored with the aid of a functional magnetic resonance scanner as they viewed various images, including scenes and faces. But, there were some hindrances to their work. As the macaques were swaddled, they would doze off to sleep. So, the researchers were able to get only a small amount of data of the time when the monkeys were awake. A huge chunk of the data from the magnetic resonance scans was collected when they were asleep.

In order to ensure that the data from the sleeping time is not wasted, Arcaro, who is also a postdoctoral fellow in Livingstone’s lab, decided to analyze it anyway. His study of the data led to a surprising finding. He found that even when the animals were asleep with their eyes shut, many parts of the visual system would turn on in conjunction with each other. These findings point to a functional organization that connects all of these visual areas in the brain.

Over the next several years, the researchers continued to work on the same macaques. They carried out scans as the animals grew mature and stayed awake longer. Their research revealed that the primitive maps present at the time of birth were still there are very gradually filled in and became more sophisticated. It now had the ability to respond to specific stimuli that absent in their early days.

During the early days of the macaques, the visual system activity was already somewhat organized into ventral and dorsal streams. When the animals get older, these areas are key to object recognition and visually guided actions, respectively, But, there were certain things that were missing in the early days like – they lacked clusters of neurons in the fusiform gyrus, a structure linked to recognition. But, as they were about 200 days old, such neuronal selectivity arose.

Arcaro explained that the brain sets a system by creating a map this early into which more information can be added in set places with experience. Since the evidence of the organization is present even in the early dates, it is most likely that it is there from before birth.

Since humans and monkeys are quite linked genetically; the findings will have some implications for humans also. An inability of the maps to later incorporate and respond to stimuli such as faces as is seen in neurodevelopmental disorders can be explained by the theory that these maps do not evolve normally with experience Livingstone added.

While it is known that the earliest visual experiences are key to child’s perceptual development, the new findings of the study further reiterate the importance of promptly correcting any visual deficits present at birth, not just to prevent blindness but also for the proper development of higher visual and cognitive functions.

References

https://medicalxpress.com/news/2017-07-blueprint-adult-visual-birth.html

https://www.sciencedaily.com/releases/2017/07/170718131032.htm

 

Zika virus

Researchers at UC Berkeley and Humabs BioMed, a private biotechnology company have developed a new test “ an antibody-based assay – to differentiate Zika infections from infections from another virus of the same family like dengue and West Nile viruses. This new test is said to be the best till date as it is simple in nature, highly effective, and low-cost too.

Known to cause severe congenital birth defects, Zika is a mosquito-borne disease. There already exist tests that can detect Zika virus infection. But, these tests have some limitations which often renders them useless. Either these tests need to be carried out shortly after infection or they do not fare well in differentiating Zika from other flaviviruses. Because of their limited ability in detecting Zika virus  – there have been hindrances to determine the prevalence of Zika virus infections, the cases of congenital Zika syndrome and the frequency of neurological complications associated with Zika virus infections.

The article with results from the study was published online recently in the journal Proceedings of the National Academy of Sciences.

The newly developed assay is very promising with high sensitivity of 91.8 percent and specificity of 95.9 percent for identifying Zika virus infections. The licensing process of the assay is underway and the researchers are hopeful that the test will be available to the medical community soon. The research that led to the assay was funded, in part, by grants from National Institutes of Health.

Eva Harris, study co-author, and UC Berkeley professor in the Division of Infectious Diseases and Vaccinology at the School of Public Health remarked that there was an urgent need for a serological method to differentiate dengue virus from Zika virus infections. This is the first of its kind to have such high sensitivity and specificity in dengue-endemic regions.

The proprietary CellClone discovery technology of the Humabs BioMed lab was applied to generate a new human antibody to the Zika virus, which was then used by the company to develop the assay. The premise of the assay is a well-established approach that is used to detect viral infection. However, what gives this assay the edge over others is the use of new antibody and protocol which further fortifies the two key assay metrics – superior sensitivity and specificity.

As a part of the development process, the assay was implemented in five countries. There it was tested using a large number of clinical samples from travelers and patients living in areas with a high level of exposure to Zika virus and other flaviviruses.

The study data reveals that the new assay was robust with high sensitivity and specificity. When performed on a control group of 540 patients infected with other flavivirus and on patients infected with Zika virus, the specificity of the assay was found to be 95.9 percent.

What played a big role in the development of this assay was the use of detailed patient samples from Harris’s collaborative studies in Nicaragua. Not only the sample included multiple, longitudinal samples from Zika patients, some of which had prior exposure to dengue virus and some not, but also there were samples from dengue patients who were infected once or more with different types of the dengue virus. The variety in the sample was a big plus. The samples were collected over a 14-year study of a cohort of children whose previous viral infection histories were well documented. Since, there is a chance that prior dengue virus infections can cross-react and confound many current Zika antibody-based assays, a thoroughly analyzed pool of patient samples was a key contributor towards the successful development of the assay as it removed the chances of cross-reactivity.

Davide Corti, senior vice president and chief scientific officer of Humabs BioMed remarked that the results of the assay speak for itself. It is highly effective in detecting both recent and past Zika virus infections and it also has the ability to discriminate Zika from other flavivirus infections. He added that they were hopeful that in days to come it will become a simple, effective and low-cost solution for Zika surveillance programs, prevalence studies and clinical intervention trials in flavivirus-endemic areas.

Additional studies are being carried out to further simplify the assay protocol.

References

https://medicalxpress.com/news/2017-07-distinguishes-zika-similar-viral-infections.html

https://www.sciencedaily.com/releases/2017/07/170718124718.htm

 

 

No smoking

One of the leading causes of preventable death in the United States is tobacco. Ironically most tobacco users start using it during youth, even though it is widely known that use of tobacco products in any form is injurious to health.

A report published in Morbidity and Mortality Weekly Report recently revealed that there was a marked decrease in the number of middle and high school students in the US using tobacco. In the year 2015, this number of students using tobacco was said to be 4.7 million and it dropped to 3.9 million in 2016 as cited in a report from the US Centers for Disease Control and Prevention (CDC) and the US Food and Drug Administration's (FDA's) Center for Tobacco Products.

As a part of the survey, students were asked to fill in questionnaires from the National Youth Tobacco Survey. The aim of the survey was to find out the recent trend of tobacco use among youth. If a student had used a tobacco product in the last 30 days, he was counted as a tobacco user. The tobacco products that were included in the survey included e-cigarettes, cigarettes, cigars, smokeless tobacco, pipe tobacco, hookah (a water pipe used to smoke tobacco), and bidis (small, flavored cigarettes wrapped in a leaf).

As per the data received, it is noted that there has been a sharp decline in the use of electronic cigarettes among the students in the year 2016. The data from the prior years show that for quite a long time the use of e-cigarettes was showing an upward trend. The 17% drop in the use of e-cigarettes is a welcome sign. But, there is a long way to go as e-cigarettes still remain quite popular among the youth.

In a statement CDC Acting Director Anne Schuchat remarked that far too many young people are still using tobacco products, so prioritizing proven strategies to protect our youth from this preventable health risk must continue. It is likely that all the tobacco prevention and control strategies from all levels of government is showing some results and has contributed to the reduction in usage. But the authors of the report also stressed that continued surveillance was needed to determine if the trend continues.

The comprehensive strategies that can help in preventing and reducing the use of tobacco products in all from among American youths include:

–    Creation of smoke-free policies that include e-cigarettes.

–    Social media campaigns that spread awareness among kids about the risk of tobacco use.

–    Imposing taxes on tobacco products to increase its price.

–    Awareness about secondhand smoke and e-cigarette aerosol.

–    Putting some restriction on the advertisement and promotion of tobacco products.

–    Increasing the minimum age for tobacco product purchase to 21 years.

FDA Commissioner Scott Gottlieb opined that even though the latest numbers are encouraging, it is critical that the work is continued to ensure this downward trend continues over the long term across all tobacco products.

The data collected from the survey also point towards another disturbing trend “ the usage of more than one type of tobacco. In the year 2016, 2 or more types of tobacco products were used by 47.2% of high school tobacco users and 42.4% of middle school tobacco users. The data is raising a concern as the use of more than one type of tobacco product increases the symptoms of nicotine dependence.

As per the federal regulations since August 8, 2016, it is illegal to sell e-cigarettes, cigars, hookah tobacco, and pipe tobacco to anyone under 18 in person and online.

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References

https://medicalxpress.com/news/2017-06-tobacco-students-sharply.html

https://www.cancer.org/latest-news/tobacco-use-drops-among-middle-and-high-school-students.html

76

Hairlose

Studies show that anxiety is the one of most common causes of hair loss.

 

Anxiety and hair loss have a rather simple and yet complex relationship. Anxiety can, in some cases, trigger hair loss. In other cases, it can make already existing hair loss more severe and make it more difficult to control.

 

There are many symptoms of anxiety and a very common one is hair loss. It has often been found that those who live in constant fear of losing their hair may actually start to lose it by giving themselves so much stress and anxiety that their hair may actually fall out.

 

Hair Loss Is Still Hair Loss

 

If you have thinning hair and a receding hair line, you should see a doctor or a hair specialist in order to control it. However, anxiety is the enemy of your hair. It can lead to conditions that might trigger hair loss, and that will certainly make living with (or without) hair loss far more stressful.

 

Poor, Anxious Hair…

 

Hair loss is never the only symptom of anxiety, or for that matter, anxiety is not the only reason for hair loss. It swings both ways. It is also observed as being very rare for hair loss to happen if your anxiety isn’t severe. Make sure that you get a better understanding of its root cause before acting upon any plan of action. The key issue that strikes common between anxiety and hair loss is stress. Anxiety is understood in many ways, as a long term and persistent stressful behavior. While technically, stress and anxiety are two very separate conditions and even continuous and hypertension and stress on their own can lead to many of the same symptoms. The reality is that anyone dealing with anxiety and stress is putting themselves at severe risk of contracting hair fall and receding hair line.

 

 

 

Stress and anxiety

 

Stress in many cases is the main trigger behind conditions that lead to hair loss. These include:

 

  • Alopecia Areata “ Sudden hair loss in the form of large clumps of hair from around your scalp
  • Telogen Effluvium “ More than the normal amount of hair falls out. It occurs when your body tells more hairs to stop growing than usual
  • Trichotillomania “ This is a serious medical condition caused by stress and anxiety. The person pulls out hairs without even realizing it

 

Treating the root cause

Not all anxiety-related hair loss is permanent.

 

If stress and anxiety are the reasons for your hair loss then reducing anxiety and relaxing more can help bring your hair back.

 

However, there’s always a catch, isn’t there? We have to remember that not all hair comes back after it’s lost regardless of the cause. Considering that your hair loss was natural and not caused by anxiety at all, no matter what, you need to make sure of two very important things.

 

Firstly, you are addressing your anxiety issues to reduce further anxiety related hair loss and secondly, to reduce the anxiety you experience because of your lost hair.

 

Life – (Anxiety+Stress)= Hair Gain

 

Anxiety is just a form of stress. However, when it gets out of hand, it may take our hair with it. It not only affects the way you feel and behave but clearly also has a huge impact on your physical health and appearance. Many people even notice with an increase in hair loss, a deterioration of skin, increased muscle tension and risen levels of skin sebum. But is it all just anxiety?

 

Many observations of the physical symptoms of anxiety sufferers can ensure us that hair loss is certainly not a guaranteed result of prolonged stress or anxiety. In fact, many sufferers may go for years without even showing any major impact on their hair line.

However, stress and anxiety do have an impact on our physical health — but to what extent is an arguable topic.

 

References

 

http://archderm.jamanetwork.com/article.aspx?articleid=526620

http://europepmc.org/abstract/MED/8591973

 

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Drug resistant bacterial infections are the cause of death of about 700,000 people each year. Combating such drug resistant bacteria is important to the future of medical research. In a major step toward it, the life scientists at UCLA have found that combinations of three different antibiotics can overcome bacteria’s resistance to antibiotics. The report on the study was published recently in the journal Royal Society Interface. It reveals that this combination seem to work even if none of the three antibiotics on their own”or even two of the three together”is effective.

As a part of this study, E.coli was grown in a laboratory and the samples were then treated combinations of one, two and three antibiotics from a group of 14 drugs. The aim was to study how effective is every single combination of this drug to kill the bacteria. The biologists found that some combinations were successful is killing 100% of the bacteria, including 94 of the 364 three-drug groupings the researchers tested.

Pamela Yeh, the paper’s senior author and a UCLA assistant professor of ecology and evolutionary biology opined that the success rate could have been even higher if higher doses of the drugs were tested by the researchers.

A sophisticated framework created by Elif Tekin, the paper’s lead author and a UCLA graduate student, enabled the scientists in determining when adding a third antibiotic was producing new desired effects that couldn’t be achieved by combinations of just two drugs. Tekin opined that three antibiotics combination changes the dynamic. So far scientists didn’t explore the idea of three-drug combinations, but this study shows that it can have really beneficial effects.

Not all antibiotics work the same way – all have their own mechanism to fight bacteria. For example: one class, which includes amoxicillin, kills bacteria by preventing them from making cell walls. There is another class which disrupts the tightly coiled DNA of bacteria and the one suppresses their ability to make proteins. There has been little research in the past which explored the effect of combinations of three antibiotics on bacteria. The recent study reveals that the effect could be more potent together than any two of them.

According to Van Savage, a co-author of the paper and a UCLA associate professor of ecology and evolutionary biology and of biomathematics, there is a general tendency among people that there is no need to understand interactions beyond pairs. But, this research reveals that that isn’t the case always. In order to determine which group of antibiotic would be most effective, combination of techniques from biology and mathematics were applied by the researchers.

Yeh said it is important to choose the three antibiotics systematically and rationally. This research also found that sometimes adding a third antibiotic makes the combination less potent also. So, with a systematic approach, the findings of this study could become one weapon to fight drug resistant bacteria. However, she also adds, overcoming drug resistance will require a full arsenal.

There are several other things that need to be done – we need to tackle this problem from all sides. There needs to be a policy in place to stop the overuse of antibiotics, doctors should take necessary caution when prescribing antibiotics, overuse of antibiotics in agriculture need to be addressed and researchers must work towards developing newer antibiotics. This research can contribute it its own way by better leveraging existing drugs.

Three-drug combinations will allow doctors to prescribe lower doses of each antibiotic, which could reduce side effects. In order to ensure that the benefits of this study are far reaching, researchers plan to make available open-access software that would let other scientists and clinicians decide which combinations of antibiotics will be most effective.

References:

http://newsroom.ucla.edu/releases/three-drug-combinations-could-help-counter-antibiotic-resistance-ucla-biologists-report

http://medicalxpress.com/news/2016-07-three-drug-combinations-counter-antibiotic-resistance.html

 

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MPS I is a rare inherited metabolic disorder caused by the deficiency of a key enzyme called alpha-L-iduronidase (IDUA). This enzyme plays a key role in breaking down complex sugars in cells and its deficiency results in abnormal accumulation of sugar debris and cell death. Presently, the only known treatments include bone marrow transplantation and intravenous enzyme replacement therapy. These treatments are only marginally effective and clinically impractical, especially when the disease enters the central nervous system. Researchers at the Perelman School of Medicine at the University of Pennsylvania are closer to finding a better way to treat children suffering from this rare disease. The findings of the study are published recently in the journal Molecular Genetics and Metabolism.


To help restore normal levels of IDUA, the researchers applied gene therapy in an ongoing preclinical trial and discovered that exposure to the human IDUA protein early in the life of an MPS I canine model increased immune tolerance to the foreign gene. Typically, dogs elicit a strong immune response to the human IDUA protein, and it makes it difficult to test if gene therapy is effective.

It was seen that the gene therapy could be tested without interference from an immune response in the dogs exposed to the human IDUA protein early in life. The researchers observed that when the gene was delivered to the brain in these dogs, there was a widespread expression of the enzyme and brain lesions that typically occur in MPS I patients were resolved.

Christian Hinderer, PhD, a senior research investigator working to complete his medical degree in the MD-PhD program at Penn remarked that their approach can test new human gene therapies in relevant animal models and may also have clinical applications for the prevention of immune responses to gene and protein replacement therapies.

The researchers worked with Plott hounds, in which MPS I naturally occurs. These dogs were originally used to develop Aldurazyme, a substance used in enzyme replacement therapy that breaks down the protein fragments left in cells.

MPS I is one of the 50 rare inherited disorders characterized by defects in the lysosomes – compartments within cells filled with enzymes to digest large molecules. When one of these enzymes is mutated, molecules that are supposed to be broken down by that enzyme accumulate within the cell and their fragments are not recycled.

MPS disorders symptoms include vision and hearing problems, hernias, and heart problems. It is estimated that in the United States 1 in 25,000 births will result in some form of MPS. The life expectancy of individuals suffering from MPS I vary, but those with the most severe form don’t live beyond 10 years.

The reason why canine models are suitable for MPS I study is because dogs have similar CNS, heart, and brain features as humans with MPS I. Also, the canine brain is closer in size to humans and better recapitulates human disease. However, the problem is that these studies can be complicated by exaggerated immune responses against the human genes. In this study, the research team demonstrated that when dogs with a genetic deficiency of IDUA were exposed to the enzyme at an early stage, they were rendered immunologically tolerant to human IDUA.

An adeno-associated viral (AAV) vector was used by researchers to introduce normal human IDUA to glial and neuronal cells of the brain and spinal cord in dogs. It was aimed to treat the CNS manifestations of MPS I at the source. The researchers observed that after a single injection of the AAV9 vector into the spinal fluid, the enzyme expression exceeded normal levels in spinal fluid, and there was a complete reversal of the characteristic brain lesions of MPS I. The researchers are hopeful that these studies will help in the planning and design of first-in-human trials.

References:

http://medicalxpress.com/news/2016-07-human-gene-therapy-rare-metabolic.html

http://www.uphs.upenn.edu/news/News_Releases/2016/07/wilson/

 

 

 

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It is an established fact that circadian rhythm, which is our internal clock, regulates our eating and sleeping schedules. But, a new research study from the scientists at the University of Alberta reveals that our circadian rhythm has a much more important role to play than previously known. According to the new study, the results of which were published in the journal Current Biology, circadian rhythms have an important role in the normal development of an organism.

Co-author of the study Kirst King -Jones who is also an associate professor in the Department of Biological Sciences remarked that having this clock is an evolutionary advantage because it helps us to anticipate a change before it happens. Changes like temperature fluctuations, the approach of day or night, and nutrient availability can be anticipated by our biological clocks and thereby it helps in adjusting our physiological processes accordingly.

Francesca Di Cara, the study’s lead author explained that just like in insects, the circadian machinery is present in different tissues in mammals as well. To put it in layman language – there is one general master clock in the brain which controls the entire body- but, each tissue or organ also have a circadian rhythm in order to regulate different processes.

It is seen that in human patients who suffer from genetic disorders, the clock machinery is disrupted and the affected person exhibit a number of negative health consequences which includes abnormal sleep patterns, low energy levels, and impaired immune functions. It has also been noted that such disorders always affect both the central and tissue-specific clocks, which leads to one crucial question: what would happen if a single clock in a specific tissue were disrupted, leaving all other clocks intact?

In order to find an answer to this question, Di Cara and King-Jones examined fruit fly larvae whose circadian rhythms had been disrupted in a single tissue that produces steroid hormones. The effects were then compared with larvae whose rhythms had been disrupted in that single tissue as well as across the whole body.

The reason for selecting the steroid-producing tissue was that the communications between the master clock in the brain and the smaller tissue-specific clock happen through the release of hormones, including steroids and insulin. Another important about steroids is that they help in advancing the insect development through pulses that trigger the next developmental step in the insect’s life, such as the metamorphic transition from larva to pupa. The situation is similar to humans where sex steroids are involved in the onset of puberty.

The findings of their study were quite intriguing. It was found that when a specific circadian gene was disrupted across the whole body, it resulted in the fly becoming arrhythmic but was otherwise completely fine. But, when the same circadian gene was perturbed in just one tissue, it arrested the insect’s development at the larval stage. It is then unable to produce sufficient steroids to advance to the next life phase.

King -Jones remarked that the results are quite dramatic as these flies due as larvae and are unable to complete development. So, it means that when a single clock in a specific tissue stops working, it harms the body more than the situation when clocks throughout the body are damaged.

Di Cara remarked that with this study, a little bit of the interaction network in these insect steroid-producing cells has been explored. It is just the beginning of a series of studies that will define what is happening in the pituitary glands – as they are involved in the rhythmic regulation of certain steroids in humans.

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References:

http://medicalxpress.com/news/2016-08-circadian-rhythm-lot.html

https://www.ualberta.ca/science/science-news/2016/august/fruit-fly-study-shows-circadian-rhythm-does-a-lot-more-than-keep-time