Category Archives: Human Genetics

About 20 percent of cancers are familial and genetic. Breast, prostate, ovaries, colon, rectum, pancreases and some type of brain cancers have a genetic connection and run from one generation to the next. Blood cancer, which is common in some families, can occur during childhood, after puberty or at later stages of life. Bilateral renal and eye cancers also have genetic links and can occur in younger people and adults. But genetics are not the only factor. A large number of cancers occur because of environmental factors, eating habits, infection and lifestyle. Therefore, any planning around cancer treatment must take them into account.

Worryingly, the federal and provincial health departments have no strategy for prevention, diagnosis, treatment and terminal management of patients with malignancies. To understand cancer and its management in Pakistan, it is important to know some basic facts about the disease and the challenges confronted by health planners in our country.

Potential causes

Eating habits play an important role in many types of cancers. Cancer of the oesophagus is more common in Quetta and some parts of Balochistan and Khyber Pakhtunkhwa, where people prefer having hot food and drinks because of the cold weather. Cancer of the mouth and throat are more common among consumers of paan, gutka and betel nut in Karachi. In recent years, these cancers are becoming more common in rural Sindh where gutka and different kinds of paan masalas are spreading like an epidemic. In some parts of Khyber Pakhtunkhwa, Balochistan and along the Saraiki belt in Punjab, smoked meat is a part of regular diet which can cause stomach cancer. People eating lots of overcooked and burnt meat in barbecues are also prone to cancer. Prostate cancer is more common in men who eat too many dairy products, especially among the cattle farming community. Of course, smoking cigarettes, beerri and huqqa is also associated with lung cancer. And in Pakistan, smoking is one of the major causes of early lung cancer and death, particularly in males.

Lifestyle is also implicated in different kinds of cancers. The lack of a good nights sleep and high levels of stress cause a failure of the immune system, causing the body to lose its ability to fight the early development of cancers. Lack of exercise can also put one in danger. People with low physical activity and high consumption of heavy food have extra insulin in their bodies which is another known cause of cancer. Obesity is another important factor, especially when it comes to cancer among young people. Cancer risk can be reduced by losing weight and increasing physical activity.

To win the battle against cancer, it is imperative that we understand the enemy and develop policies accordingly

Infection is also a major cause of cancer in humans and responsible for thousands of deaths in Pakistan every year. Human papillomavirus (HPV), Epstein-Barr virus, herpes, HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with different kind of cancers in the cervix, the anogenital area, the skin, the nasopharynx and the liver.

About 15 percent of the Pakistani population is infected with HBV and HCV. These viruses can lead to liver cancer and even deaths in our relatively young population.

Recently, a UN summit on environment and climate has highlighted the risk to life on earth, which may vanish if world leaders dont do anything about global warming. A polluted environment causes cancer. Polycyclic aromatic hydrocarbons(PAH) are the chemicals from industrial waste present in the outer environment which attach to fine carbon particles and their inhalation causes lung cancer.

Additionally, there are other PAH-type chemicals associated with cancers in industrial countries despite strict environmental regulations. Polluting the body with benzene, food preservatives, nitrates, pesticides and some cosmetics are associated with certain types of cancers. High levels of chlorine in water can also cause cancer with long-term drinking, especially among children. Long-term UV radiation causes cancer in farmers working on fields. Electromagnetic radiation and x-rays are also responsible for cancer. Non-protective x-rays of abdomen in young girls during puberty can cause ovarian and breast cancer.

A time for change

It is about time we had a national policy to fight cancer in Pakistan. Health planners should think about cancer and its management in light of peoples lifestyles and their exposure to chemicals. Familial cancers are another big challenge and it is important to create awareness about these among the masses for early detection, diagnosis and management. Teaching about familial cancer in school and using media for awareness can lead to early detection, thereby decreasing instances of cancer-related deaths in a high-risk population. Nowadays, it is possible to diagnose cancer of the breast, ovaries, colon, rectum and prostate at early stages. Early detection makes curative treatment possible.

Of course, the government should also strictly enforce measures to discourage use of cigarettes, gutka, betel nuts and paan masalas. It should go without saying that children should not have any access to these cancerous materials. A massive campaign is required to create awareness about cancer of the mouth, tongue, larynx, nasopharynx, mandible, nose and lungs. These cancers are preventable and by their prevention it is possible to save millions of rupees that would be spent in treatment. There is also a need for carrying out electronic and social media preventive campaigns regarding cancer-causing eating habits in different parts of country.

Health planners should also accept their failure in prevention and control of HBV and HCV and redouble their efforts to remedy this. A vaccine is available for the prevention of HBV which should be provided to every citizen of Pakistan.

Presently, the federal health ministry is also trying hard to initiate a plan for safe blood banking and the use of disposable syringes in hospitals and the community. There is also a need to create awareness about safe shaving at barber shops, the use of the same miswaak in the mosque and sharing of blades during azadar in Moharram.

Furthermore, policymakers must recognise that cervical cancer in women is 100 percent preventable because of a vaccine against the cancer-causing virus. Every girl in the country should get vaccinated at the age of 11/13 to eradicate this cancer from the community.

A healthy and hygienic lifestyle is a preventive measure against different viral infections. Clean drinking water should be another high priority for health planners. In our country we have no policy regarding cancer-causing chemicals and industrial waste. Our environment is polluted with chemicals, our rivers are used as reservoirs for industrial waste, our vegetables are grown in river beds laden with cancer-causing chemicals.

The cost of inaction

Some of these points may sound like stating the obvious, but doing this work is of the utmost importance. Cancer treatment is very expensive and there are a few trained cancer surgeons, competent oncologists, radiologist and dedicated nursing staff available in Pakistan. A group of Karachi doctors started the City Tumour Board Karachi in March 2010, which meets every alternate Sunday to provide free consultation to cancer patients from the experts in the field. Other cities should have this kind of arrangement for the patients who are not able to afford treatment in private hospitals.

Most teaching hospitals provide services for cancer patients but lack human resources, medicine and modern radiotherapy units. ThePakistan Atomic Energy Commission(PAEC)has 18 centres in different cities of Pakistan providing free services to patients, but they confront a financial crisis with an increasing number of patients each year. In Karachi, KIRAN, the cancer treatment centre of PAEC, treats more than 6,000 cancer patients without any charges.

Unfortunately, there is also no recognition of palliative care (care for terminally ill patients and their families) in our country. Health planners should invest in the training of oncology nurses and palliative care technicians who can help doctors in the management of cancer patients as is being done in developed countries. And the Pakistan Nursing council should come forward with the plans for training of these health cadets.

Clearly, we have our work cut out for us.

The writer is ex-Secretary General of Pakistan Medical Association

Published in Dawn, EOS, January 5th, 2020

Originally posted here:
HEALTH: CANCER CARE AND POLICIES - DAWN.com

DNA with rainbow colors behind (CC0 NeedPix)

New scientific discoveries mean that parents can do some selection regarding the sexual orientation of their children. They can determine a little bit about the probability their child will be homosexual and abort if they dont like those odds. It seems that sexual orientation has certain genetic factors but is not determined. I think this creates a conundrum for many who support abortion and in-vitro fertilization, but also think discriminating against homosexuals is wrong. Aborting people because they are more likely to be homosexuals is extreme discrimination. I will list the science, a bit of the Chinese and American cultural reactions, and then note a Catholic response.

The Genetic Literacy Project reported:

In October 2018, geneticist Andrea Ganna and his team at the Broad Institute reported that their review of markers across the entire genome of more than 493,000 test participants identified 4 genome-wide significant loci for homosexual behavior, with many more loci identified for partner count (meaning lifetime number of sexual partners) in heterosexuals. These results led researchers to estimate that 8-20% of variation in non-heterosexual behavior could be attributed to common genetic variants (those most likely to be detected through GWAS) found in this study. Some these genes display curious overlap with others that affect biological processes such as smell and hormone production, hinting at complex cross-genome relationships between sexual preference and other phenotypes. Previous twin and family studies had already suggested that about40 percentof our sexual orientation is genetically heritable.

The significance of these results isnt their confirmation of a genetically heritable component to homosexuality, but rather their identification of some of the specific gene variants involved. Scientists need to know which variants, or SNPs (single-nucleotide polymorphisms) are associated with which phenotypic traits to employ such technologies as PGD (preimplantation genetic diagnosis) and gene editing to alter the genetic makeup of future children. Identifying the SNPs associated with homosexual behavior means that manipulating the genetics of sexual orientation could one day become possible.

The reaction here is vastly different in the West and the East. In the USA, testing to eliminate homosexual babies is unlikely to take hold but this will likely become a standard part of pre-implantation diagnosis done in IVF cases. The Genetic Literacy Project notes how this is received in the West:

In the United States, the political and party divisions that separate the conservative-religious right from the social-justice left do not prevent them from agreeing on the issue of gene-editing technologies, albeit for very different reasons. Typically, conservatives are afraid of playing God, while liberals are more focused on worsening inequality or harming vulnerable minority groups.

The article goes on to note how homosexuality is no longer stigmatized in North America or Europe.

GLP also notes the attitude in China, which are quite different

With no law prohibiting selectionagainstorforspecific sexual preferences yet in place, it remains possible that prospective parents may one day be able to choose or alter a future childs sexual preferences.

With strong growth in preimplantation genetic diagnosis procedures and no laws directly prohibiting selection of sexual orientation, its possible that Chinese parents could soon begin deciding their childs likely sexual preferences. The implications of this lie deep within the cultural context, as here homosexuality was banned for most of the 20thcentury. After legalization in 1997, it was finally removed from the official list of mental illnesses in 2001. Still, many taboos against homosexuals remain, and the status of LGBT culture is semi-underground. []

Unlike in American culture where fears of eugenics and an elite genetic class still linger after experiences from the first half of the 20thcentury, PGD [Pre-Implantation Diagnosis] in China has little stigma attached. The practice is being widely adopted across the country, and this continues to accelerate.

First of all, abortion is always wrong. There is no moral reason to directly kill an innocent baby in the womb or tiny zygote before implantation. We were all zygotes.

Second, using abortion for discrimination adds a layer of nastiness. This is why the Church has been doubly against sex-selective abortions. The catechism speaks out about discriminating against persons who have homosexual tendencies in 2358:

They [men and women who have deep-seated homosexual tendencies] must be accepted with respect, compassion, and sensitivity. Every sign of unjust discrimination in their regard should be avoided. These persons are called to fulfill Gods will in their lives and, if they are Christians, to unite to the sacrifice of the Lords Cross the difficulties they may encounter from their condition.

The latter part of that reminds us to call these people to live Christian chastity.It is important to note that all humans are genetically predisposed to certain sins more than others and this varies per person. Some are more prone to anger or gluttony. We should not use this either to consider homosexuality different or use a genetic predisposition to change the moral code.

We Catholic should speak out about the intrinsic discrimination in any form of PGD as we should respect the humanity of each human conceived.

Hopefully, this never comes to the USA or Canada. Hopefully, it helps to humanize the unborn so people realize that an unborn baby is a person. If we will avoid this for homosexuality, why not also avoid it for other issues like Downs Syndrome?

Note: Please support me via Patreon so I can write more on the Catholic approach to genetic bioethics. If you cant give monthly, a one-time Christmas gift would be appreciated.

Go here to see the original:
Aborting Babies Because They're Gay: Coming Soon to China - Patheos

DetailsCategory: DNA RNA and CellsPublished on Thursday, 26 December 2019 15:57Hits: 327

NEW YORK, NY, USA I December 26, 2019 I Prevail Therapeutics Inc. (Nasdaq: PRVL) (Prevail or the Company), a biotechnology company developing potentially disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases, today announced that the U.S. Food and Drug Administration (FDA) has notified Prevail that the Companys Investigational New Drug (IND) application for PR001 for the treatment of neuronopathic Gaucher disease (nGD) patients is now active and that Prevail may proceed with initiating its proposed clinical trial. As previously reported, Prevails IND for PR001 for the treatment of nGD had been put on clinical hold by the FDA, and this clinical hold has now been removed.

The Companys planned Phase 1/2 clinical trial for nGD patients will commence at a dose higher than originally proposed. Prevail submitted nonclinical data in which no PR001-related safety events or adverse findings were observed, supporting the initiation of the Phase 1/2 clinical trial at this higher dose.

Prevail is activating a Phase 1/2 clinical trial for Type 2 Gaucher disease patients and expects to initiate patient dosing during the first half of 2020. Type 2 Gaucher disease is the more severe form of nGD, which presents in infancy and involves rapidly progressing neurodegeneration leading to death in infancy or early childhood. The Company also plans to initiate a Phase 1/2 clinical trial for Type 3 Gaucher disease patients in the second half of 2020, under the same nGD IND. Type 3 Gaucher disease is a form of nGD that typically presents in childhood and involves multiple neurological manifestations.

We are pleased to now have an active IND for PR001 for the nGD indication and look forward to initiating a Phase 1/2 clinical trial in the first half of 2020, said Asa Abeliovich, M.D., Ph.D., Founder and Chief Executive Officer of Prevail. Patients with nGD have the most severe form of Gaucher disease and a significant unmet need for therapies to treat their neurological manifestations. We believe PR001 has tremendous potential to help patients suffering from this devastating disease.

Prevail is also developing PR001 for Parkinsons disease patients with a GBA1 mutation (PD-GBA). The Company has an active IND for PR001 for the treatment of PD-GBA and the PROPEL Phase 1/2 clinical trial for PD-GBA patients is now recruiting.

About Neuronopathic Gaucher DiseaseGaucher disease is a lysosomal storage disorder caused by mutations in the glucocerebrosidase gene GBA1, leading to multi-organ pathology. Patients with severe mutations in the GBA1 gene can present with neuronopathic Gaucher disease, also termed Type 2 or Type 3 Gaucher disease. Type 2 Gaucher disease presents in infancy and involves rapidly progressive neurodegeneration leading to death in infancy or early childhood. Type 3 Gaucher disease typically presents in childhood and can involve neurological manifestations such as gaze and motor abnormalities and seizures. There are no therapies approved by the FDA for the treatment of neuronopathic Gaucher disease.

About Prevail TherapeuticsPrevail is a gene therapy company leveraging breakthroughs in human genetics with the goal of developing and commercializing disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases. The company is developing PR001 for patients with Parkinsons disease with a GBA1 mutation (PD-GBA) and neuronopathic Gaucher disease; PR006 for patients with frontotemporal dementia with GRN mutation (FTD-GRN); and PR004 for patients with certain synucleinopathies.

Prevail was founded by Dr. Asa Abeliovich in 2017, through a collaborative effort with The Silverstein Foundation for Parkinsons with GBA and OrbiMed, and is headquartered in New York, NY.

SOURCE: Prevail Therapeutics

Continued here:
Prevail Therapeutics Announces IND Active for PR001 for Treatment of Neuronopathic Gaucher Disease | DNA RNA and Cells | News Channels -...

Piragathesh Subramanian wears many hats.

As evident from his email signature, which takes up about one third of my phone screen, Piragathesh is a representative for international students at the Columbia Universitys General Studies Students Council, the president of the Columbia-Barnard Reflect, and thats on top of his double major as a fifth year student in Neuroscience and Behaviour & Pre-Medicine at Columbia University.

All at the age of 26.

What is perhaps also atypical of Pira (and also a reflection of changing educational trends) is that he went to university through the polytechnic route, which is still relatively unconventional. He said:

In fact, when I first started out in Republic Polytechnic, both my secondary school teachers and Republic Polytechnic [lecturers] did mention that the path towards medicine from a polytechnic route was either non-existent or very difficult.

When I told my colleagues about him, one of them said, Wah, hes really smart.

The cut-off Grade Point Average of past polytechnic students who enter local universities vary each year, but for the popular courses, they usually hover between 3.6 and 3.8 (out of four).

For even more prestigious Ivy League institutions like Columbia, its higher. Pira managed to get in with a perfect GPA score of 4.0, which he managed to sustain throughout his time in Republic Polytechnic no mean feat.

He might seem like your typical Asian overachiever, but Pira tells me, over email, that being in the medical field was not what he originally wanted.

He had (literally) sky-high ambitions to be a pilot.

Since young, I have been fascinated with planes and the idea of flying, he wrote. Having parents who worked for Singapore Airlines probably factored into that childhood dream.

However, that dream changed when Pira encountered the wonders of life sciences in Dunman Secondary. That shifted my interest towards medicine, he wrote.

For most, going to junior college is the conventional (and more direct) route to take if one wishes to pursue medicine. But it was not for Pira, who did not like taking tests.

Back in the day there was an emphasis on school bandings and how O Level scores tend to affect a schools placement.

It put him under a lot of pressure and while he managed to score decently for his O levels, the entire experience made him realise one thing: That the conventional A level route was not for him:

I was keen on pursuing medicine and wanted to (take) a different route. I wanted to study subjects that catered to my interest.

Deciding against junior colleges, Pira turned to local polytechnics. He decided a Diploma in Biomedical Science would bring him closer to his dream of being a medical professional.

Back in 2010, only four polytechnics offered biomedical courses and each of them had their own areas of specialisation with amazing levels of research in their respective fields, according to Pira.

It was a tough choice, but in the end, he chose to enrol in Republic Polytechnic at 17 years old because he felt that its approach to biomedicine is more holistic, which best suited his learning needs.

To me, Republic Polytechnic felt like the ideal option as they had a biomedical programme that focuses on various medical topics and they organised their modules in a (complementary manner each semester).

The course is comprehensive. Students study human anatomy, gain insights into the molecular and physiological basis of different diseases (as well as their treatment) and even perform research and laboratory diagnostics.

Pira also liked that RPs Biomedical Science Diploma offers students the choice of two specialisation options: the Biomedical Research track and the Medical Technology track.

He chose the former where he delved into neurobiology, genomics, oncology, microbiology, among others.

I found the modules to be very interesting, he added.

However, his choice was met with some initial resistance from relatives and friends who saw Republic Polytechnic as an underperforming school for academically weaker students.

However, that was not the case. Many of my Republic Polytechnic peers are doing very well in their respective fields, he wrote.

Pira said that these stereotypes were disheartening, especially after he decided to choose Republic Polytechnic.

However, despite the criticisms, I took all the information that Ive heard with a pinch of salt and focused my efforts on what needed to be achieved, he said.

So what did he enjoy during his time at Republic Polytechnic?

Aside from the polytechnics dynamic approach to academics, as well as the rigour of handling challenges and difficult situations, Pira appreciated how RPs Problem-based Learning and hands-on approach encouraged him to identify new solutions for current medical conditions.

I was also fortunate to be allowed to undertake internships at both the National University Hospital Surgical Centre and the Genome Institute of Singapore.

During his internship, Pira experienced first-hand working with a breast cancer team.

The team comprised the Human Genetics Team from the Genome Institute of Singapore, the Surgery Team from the National University Hospital and the Epidemiological Team from the National University of Singapores School of Public Health.

One of the most important things that Pira picked up during that 15-week internship was the inter-personal skills through speaking with medical workers, allied health professionals, and patients, especially the terminally ill.

I learned that human compassion is very important in the field of medicine. Patients need to be comforted with a sense of assurance, care, and positiveness; as a result, I do believe that as a doctor besides having to diagnose and cure illness, I should empathise (with patients) and help build their spirits.

Aside from his internships, Pira also had the chance to take part in extra-curricular activities.

For one, he took part in the first ever Singapore Youth Model Parliament where he was assigned the portfolio for the Minister of State for Health and Member of Parliament of Tampines-Changkat GRC.

It was here that I realised what attributes and knowledge one had to harness to become a good leader. I was empowered with self-confidence to meet challenges and had opportunities to sharpen my oratorical skills when I addressed audiences.

Piras time at Republic Polytechnic would not have been complete without his lecturers. One lecturer in particular, Dr Ventris De Souza, Piras genomics lecturer, left a lasting impact on him.

I did not do well in my first exam, he wrote.

I remember approaching her and she (sat down) with me and guided me in understanding concepts about genomics. [WIth her] her guidance, I was able to ace that module with flying colors.

And it was this belief from his lecturers that drove Pira to try his best.

My [lecturers] believed that I would be able to set a certain precedence by entering a medicine-based programme from a polytechnic route. This motivation and drive from my teachers and peers has allowed me to become Republic Polytechnics first ever-Ivy League student who is pursuing Neuroscience and behaviour, pre-medicine and human rights.

Dr Ventris dedication is just one of the many examples of Republic Polytechnic lecturers who go beyond their call of duty for students.

What I can say is, I stand upon the shoulders of giants and my success was due to my lecturers guidance, added Pira, who regularly returns back to Singapore to catch up with this school friends and mentors.

It was because of their encouragement, I was able to carry out my passions, he wrote, adding that their motivation helped him to achieve a SAT score of 2290/2400 in 2014, and the rest is history.

Pira will be graduating from Columbia University in 2020, before he starts medicine in 2021. He shares that he will be returning to Singapore when he finishes his studies in 2025.

Reading Piras story made me think about how there is no such thing as a fixed education route. His story is a testament to how people can still succeed when they take the path less travelled.

Choose your own path, Pira advised. There is no such thing as the right education path. Everyone has their own needs and wants. Therefore do not be afraid to choose an academic route that suits you.

If youre interested, you can read about Republic Polytechnics Diploma in Biomedical Science course here. You can also find information on other courses at Republic Polytechnic here.

Republic Polytechnic will also be holding Admissions Talks for the Joint Admissions Exercise on the following dates:

11 Jan 2020 (Sat), 11am & 4pm14 Jan 2020 (Tue), 7pm 9pm

Click here to sign up.

Top image by Piragathesh Subramanian. Quotes were edited for clarity.

See the original post here:
S'porean RP graduate-turned-Ivy League pre-med once told that poly students won't make it into medicine - Mothership.sg

Weve all been there. Youre prepping your meals, counting calories and hitting the gym with gusto. Then, you step on the scale to see that your weight has boomeranged back to the same old number. What happened?

Theres actually a scientific explanation for why the human body always seems to revert to its previous weight. Say hello to the set point theory. You can think of your set point as your natural body weight or the number that it usually hovers around on the scale. Both genetics and environmental factors contribute to a persons set point.

Basically, the theory holds the body uses different regulatory mechanisms to defend a default weight range. When you take in less calories, for example, the body fights the deficit by slowing your metabolism and boosting your appetite. Though set point theory hasnt been fully validated yet, it may make dieting difficult not just in terms of losing weight, but actively keeping it off.

There are some ways to outsmart this pesky biological tendency, though. Some studies suggest losing just 5 to 10 percent of your body weight at a time. By losing weight gradually, you can potentially lower your bodys set point.

Read more:

When Dieting, Should We Be Fasting or Grazing?

The Biggest Factor Behind Obesity May Be One We Don't Want to Hear

Breakfast Might Not Be So Essential After All

See the original post here:
Do Our Bodies Have Weight 'Set Points' They Always Revert To? - Discover Magazine

From the cradle to the grave

There is evidence to suggest that the unique microbiome of each person starts to take shape even while we are still growing in the womb. From birth and throughout life, it continues to develop and evolve, influenced by genetics, as well as environmental factors such as diet, nutrition and exposure to drugs such as antibiotics.

It is estimated that an average adult carries about two kilograms worth of microbes in their gut. In fact, the number of these organisms often outnumber our own cells. Most of the time, we may be carrying more microbial genes than human genes in our bodies. The latter aid in digestion and help produce essential vitamins (such as vitamins B and K) and maintain a healthy gut by preventing overgrowth and invasion by disease-causing microbes. But increasingly, research is finding that there is more to our microbiomes than just promoting gut health: It can impact weight, immunity, mood, behaviour, energy and overall wellness.

Some experts claim that up to 90 percent of diseases can be traced back in some way to the gut and the health of the microbiome. The gut microbiome, and its diversity, has been shown to influence many conditions not traditionally considered microbe related from whether a person develops obesity, heart disease, asthma or diabetes, to neurological conditions such as Parkinsons disease and dementia, to development of cancer, right down to how well we respond to chemotherapy and vaccines.

A new frontier

Microbiome research is an exploding field of science growing at an exponential rate. New knowledge is being added almost daily. The organisms being discovered have names not found in textbooks, being unknowable to us a mere few years ago. Unlike their disease-causing counterparts, they live symbiotically within the host and are not found in clinical specimens. But advances in genetic analysis technology have propelled the exploration of this new frontier of science.

Researchers have now identified more than 10,000 species of microbes living in and on the human body. The next challenge is to tease out and define the apparent associations between the microbiome, health and disease and develop ways to manipulate it to improve health, as we have done with antibiotics and probiotics.

The more diverse, the better

It remains to be defined how exactly the microbiome exerts its health consequences on the host or what makes a healthy microbiome. Experts agree that diversity is a good thing when it comes to gut microbes. The diversity of the travellers we carry appears instrumental in the development of a robust immune system. Association with disease is usually observed when this diversity is reduced or lost. Diet is a major influence on this diversity by dictating the environment in which certain microbes can take up long-term residence within the gut. For example, diets high in saturated fats, which are linked to conditions such as diabetes and heart disease,are also thought to reduce microbial diversity.

How you can influence your microbiome

Here are a few tips to cultivate as much diversity as possible in your gut microbiome:

Increase your fibre intake

Dietary fibre usually comes from plant-based food ingredients that are not broken down by enzymes in the gastrointestinal tract. Most adults should aim to have 25 35 grams of fibre in their diet every day. Fibre supports the growth and diversity of the microbiome and has the added benefits of lowering your risk of heart disease, diabetes and colon cancer.

Eat a wide and seasonal range of fruits, nuts and vegetables

The variety and the types of fibres found within different fruits and vegetables are thought to support different microbial species, thereby contributing to the overall diversity.

Include fermented foods in your diet

Fermented foods such as pickled vegetables, staples of the Burmese dinner tables everywhere, have been shown to be beneficial in improving the diversity of the microbiome and gut function. Other fermented foods include yoghurt, kimchi, soybean-based products such as soy sauce and tempeh.

Avoid artificial sweeteners.

Artificial sweeteners such as saccharin, sucralose or aspartame may be sold as sugar substitutes or are found in sugar-free beverages. These are marketed as a healthier no-calorie alternative to natural sugars, but they have been shown to disrupt the gut microbiome.

Avoid antibiotics and non-essential medicines

Antibiotics may be life-saving when taken for the right reasons. But taken unnecessarily, they indiscriminately wipe out many beneficial microbes, reducing the diversity of the microbiome with effects lasting up to years. Dangerous and pathogenic bacteria may flourish in absence of the microbiome diversity which may result in serious illness. Even non-antibiotic medications may alter gut microbiome by altering the colonic environment so best to play it safe and only take them when necessary.

Dr Thel Khin Hla is a doctor with the Myanmar Oxford Clinical Research Unit in Yangon.

Read the original here:
The travellers within us - Myanmar Times

Madagascar, the worlds fourth-largest island, is a global biodiversity hotspot. Andrea Baden

The island of Madagascar off the southeastern coast of Africa hosts at least 12,000 plant species and 700 vertebrate species, 80% to 90% of which are found nowhere else on Earth.

Isolated for the last 88 million years and covering an area approximately the size of the northeastern United States, Madagascar is one of the worlds hottest biodiversity hotspots. Its island-wide species diversity is striking, but its tropical forest biodiversity is truly exceptional.

Sadly, human activities are ravaging tropical forests worldwide. Habitat fragmentation, over-harvesting of wood and other forest products, over-hunting, invasive species, pollution and climate change are depleting many of these forests native species.

Among these threats, climate change receives special attention because of its global reach. But in my research, I have found that in Madagascar it is not the dominant reason for species decline, although of course its an important long-term factor.

As a primatologist and lemur specialist, I study how human pressures affect Madagascars highly diverse and endemic signature species. In two recent studies, colleagues and I have found that in particular, the ruffed lemur an important seed disperser and indicator of rainforest health is being disproportionately impacted by human activities. Importantly, habitat loss is driving ruffed lemurs distributions and genetic health. These findings will be key to helping save them.

Madagascar has lost nearly half (44%) of its forests within the last 60 years, largely due to slash-and-burn agriculture known locally as tavy and charcoal production. Habitat loss and fragmentation runs throughout Madagascars history, and the rates of change are staggering.

This destruction threatens Madagascars biodiversity and its human population. Nearly 50% of the countrys remaining forest is now located within 300 feet (100 meters) of an unforested area. Deforestation, illegal hunting and collection for the pet trade are pushing many species toward the brink of extinction.

In fact, the International Union for Conservation of Nature estimates that 95% of Madagascars lemurs are now threatened, making them the worlds most endangered mammals. Pressure on Madagascars biodiversity has significantly increased over the last decade.

In a newly published study, climate scientist Toni Lyn Morelli, species distribution expert Adam Smith and I worked with 19 other researchers to study how deforestation and climate change will affect two critically endangered ruffed lemur species over the next century. Using combinations of different deforestation and climate change scenarios, we estimate that suitable rainforest habitat could be reduced by as much as 93%.

If left unchecked, deforestation alone could effectively eliminate ruffed lemurs entire eastern rainforest habitat and with it, the animals themselves. In sum, for these lemurs the effects of forest loss will outpace climate change.

But we also found that if current protected areas lose no more forest, climate change and deforestation outside of parks will reduce suitable habitat by only 62%. This means that maintaining and enhancing the integrity of protected areas will be essential for saving Madagascars rainforest habitats.

In a study published in November 2019, my colleagues and I showed that ruffed lemurs depend on habitat cover to survive. We investigated natural and human-caused impediments that prevent the lemurs from spreading across their range, and tracked the movement of their genes as they ranged between habitats and reproduced. This movement, known as gene flow, is important for maintaining genetic variability within populations, allowing lemurs to adapt to their ever-changing environments.

Based on this analysis, we parsed out which landscape variables including rivers, elevation, roads, habitat quality and human population density best explained gene flow in ruffed lemurs. We found that human activity was the best predictor of ruffed lemurs population structure and gene flow. Deforestation alongside human communities was the most significant barrier.

Taken together, these and other lines of evidence show that deforestation poses an imminent threat to conservation on Madagascar. Based on our projections, habitat loss is a more immediate threat to lemurs than climate change, at least in the immediate future.

This matters not only for lemurs, but also for other plants and animals in the areas where lemurs are found. The same is true at the global level: More than one-third (about 36.5%) of Earths plant species are exceedingly rare and disproportionately affected by human use of land. Regions where the most rare species live are experiencing higher levels of human impact.

Scientists have warned that the fate of Madagascars rich natural heritage hangs in the balance. Results from our work suggest that strengthening protected areas and reforestation efforts will help to mitigate this devastation while environmentalists work toward long-term solutions for curbing the runaway greenhouse gas emissions that drive climate change.

Already, nonprofits are working hard toward these goals. A partnership between Dr. Edward E. Louis Jr., founder of Madagascar Biodiversity Partnership and director of Conservation Genetics at Omahas Henry Doorly Zoo, and the Arbor Day Foundations Plant Madagascar project has replanted nearly 3 million trees throughout Kianjavato, one region identified by our study. Members of Centre ValBios reforestation team a nonprofit based just outside of Ranomafana National Park that facilitates our ruffed lemur research are following suit.

At an international conference in Nairobi earlier this year, Madagascars president, Andry Rajoelina, promised to reforest 40,000 hectares (99,000 acres) every year for the next five years the equivalent of 75,000 football fields. This commitment, while encouraging, unfortunately lacks a coherent implementation plan.

Our projections highlight areas of habitat persistence, as well as areas where ruffed lemurs could experience near-complete habitat loss or genetic isolation in the not-so-distant future. Lemurs are an effective indicator of total non-primate community richness in Madagascar, which is another way of saying that protecting lemurs will protect biodiversity. Our results can help pinpoint where to start.

[ Like what youve read? Want more? Sign up for The Conversations daily newsletter. ]

Original post:
Lemurs are the world's most endangered mammals, but planting trees can help save them - The Conversation US

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq:SGEN) today announced it has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tucatinib. This NDA requests FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting. The submission is based on the results of HER2CLIMB, a randomized pivotal trial comparing tucatinib added to trastuzumab and capecitabine versus trastuzumab and capecitabine alone. HER2CLIMB trial results were presented on December 11, 2019 at the 2019 San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

Tucatinib was recently granted Breakthrough Therapy designation by the FDA in combination with trastuzumab and capecitabine, for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. This designation was based on data from the HER2CLIMB trial.

Todays submission marks another important milestone for Seattle Genetics and tucatinib, and a potential advance for patients with either locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases, said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. We look forward to working with the FDA on the review of this application.

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab, and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline, and confirmed objective response rate. Safety data were evaluated throughout the study.

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1, 2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal, and gastric cancers. HER2 mediates cell growth, differentiation, and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is progression-free survival per RECIST criteria. Secondary endpoints include overall survival, objective response rate, and duration of response. The trial is being conducted in North America and is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic, or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST criteria. Progression-free survival, duration of response, overall survival, and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

About Seattle Genetics

Seattle Genetics, Inc. is a global biotechnology company that discovers, develops, and commercializes transformative medicines targeting cancer to make a meaningful difference in peoples lives. ADCETRIS (brentuximab vedotin) and PADCEV (enfortumab vedotin-ejfv) use the companys industry-leading antibody-drug conjugate (ADC) technology designed to bring a powerful medicine directly to cancer cells. ADCETRIS is approved for the treatment of several types of CD30-expressing lymphomas, and PADCEV is approved to treat adults with metastatic urothelial cancer. In addition, investigational agent tucatinib, a small molecule tyrosine kinase inhibitor, is in late-stage development for HER2-positive metastatic breast cancer, and in clinical development for metastatic colorectal cancer. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland, and the European Union. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

Forward Looking Statements

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting; the therapeutic potential of tucatinib, including its possible efficacy, safety and therapeutic uses and anticipated development activities including ongoing and future clinical trials. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that the New Drug Application submission based on the HER2CLIMB trial may not be accepted for filing by, or ultimately approved by, the FDA in a timely manner or at all or with the requested label; the difficulty and uncertainty of pharmaceutical product development; the risk of adverse events or safety signals; and the possibility of disappointing results in ongoing or future clinical trials despite earlier promising clinical results. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the companys Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

References:

Read the original here:
Seattle Genetics Announces Submission of Tucatinib New Drug Application to the U.S. FDA for Patients with Locally Advanced or Metastatic HER2-Positive...

R. Arama says the shaar will discuss how far we have to go in our personal efforts to secure what we find productive and fend off what is damaging. Lack in such effort (aside from reducing the odds life will go as we want) also leads to less providence for a person.

We will see more of what he means in the course of the shaar, but I want to be sure we notice it already: R. Arama thinks part of the calculus for how much providence a person merits is how much effort the person him/herself invests. Heaven helps those who help themselves, for real.

He opens with Bereishit Rabbah 76, where R. Pinhas quotes R. Aybo: Yaakov and Moshe were each afraid at certain junctures (Yaakov at the beginning of Parshat Vayishlach, when he hears Esav is headed his way with 400 men; Moshes is inferred from Hashem telling him not to fear Og). Their fear begs explanation, given verses where they were told they were chosen by Hashem and were promised divine protection. Their fear tells R. Aybo that the righteous have no ironclad promises in this world (whatever the promises mean, and they clearly mean something, they do not guarantee safety in this world).

The Four Causes

Free will is part of the reason. As groundwork for his presentation of free will, R. Arama lists four causes of human events: providence, human action, the stars and chance [scientific determinists of various sorts used to deny the role of chance, although I think the random elements in quantum physics have restored its place]. The least obvious of those is human action, considering providence could run the world without any help.

Three arguments show him humans must have some free will. First, unless the human intellect has freedom to exercise its powers, it would be futile to have given it to humans (and it is unthinkable Hashem would act futilely). Second, reward and punishment assumes free will. Finally, the Torah also requires us to take steps to avoid accidents, such as by building a maakeh, a fence around elevated spaces, and Hashem told the Jews to stay inside the night of makkat bechorot, the plague of the first born.

As political philosophy has shown (he says), effort only makes sense if it has some ability to succeed. Even where many people fail (Niddah 70b speaks of many trying, to no avail, in a particular situation), or their efforts are self-destructive (as with Yosefs brothers, he says), effort does often help, proving life is not ruled completely by Providence, the stars (what we today would call natural cause and effect), and chance.

Our Actions Shape Our Providence

In addition to a role for free will, R. Arama cites verses to show Heaven reacts according to how we act. Someone who always makes good choices will certainly receive providential aid, to the point s/he will barely need to try. As Tehillim 37:23 says, Hashem guides the steps of those whose path Hashem likes.

On the flip side, no matter how good ones birth circumstances (he says a good astrological sign, we would say good genetics and environment), if s/he chooses poorly, Hashem will break the persons pride, regardless of his/her efforts. As Yeshayahu 44:25 says, Hashem can overthrow peoples wisdom, foil their various plans.

During Avshaloms rebellion in II Shmuel 17, Hashem prevented Achitophels advice from being accepted, to preserve Davids monarchy, despite Achitophels great wisdom, his ideas always being the best ones.

Those are at the extremes, howeverpeople who are fully good or evil. For people in the middle range, providence does not tip the scales, the role of chance and the stars becomes significant, leaving room for personal effort to have a real impact. Its why Mishlei 10:4 could say effort helps people become rich, and Mishlei 19:3 that a persons evil ruins his path.

Efforts Also Help Interpret Life

Lack of effort where effort is appropriate constitutes a sin, phrases such as be-chol mishlach yadecha and asher taaseh (in Devarim 15:10 and 18), everything you put your hand to and all you do (implying we are supposed to put our hand to things, supposed to do).

Because most of us are in that category, the Torah gives advice on how to make the proper efforts, for example in building a maakeh. Those of enough merits do not need protection, and those on the other extreme will not be able to avoid Hashems punishment. Practical advice in the Torah is aimed at the large middle.

Rabbi Dr. Gidon Rothstein has served in the community rabbinate and in educational roles at the high school and adult level. He is an author of Jewish fiction and nonfiction, most recently Were Missing the Point: Whats Wrong With the Orthodox Jewish Community and How to Fix It. He lives in Bronx, New York, with his wife and three children.

See original here:
Balancing Human Effort and Divine Intervention - Jewish Link of Bronx, Westchester and Connecticut

During the first All-University meeting of the academic year, on Sept. 3, East Stroudsburg University presented the annual Distinguished Professor Awards and the inaugural Innovator & Entrepreneur of the Year award.

The Distinguished Professor Award the highest honor for ESU faculty to receive is presented based on outstanding contributions to the academic life of the university and its reputation. The award of Distinguished Professor is conferred upon an individual by ESU President Marcia G. Welsh, Ph.D., in recognition of exceptional achievements in teaching, research/scholarship/creative activities, and service.

The Innovator and Entrepreneur of the Year Award, established in 2018, honors ESU faculty and staff for outstanding efforts in innovation/entrepreneurship and for exemplifying the definition of an ESU entrepreneur, which is someone who creates opportunities and implements solutions, for profit or not-for-profit, for the ESU community and beyond.

Distinguished Professor Award was presented to Terry L. Master, Ph.D. Master earned his Bachelor of Science in biology from Muhlenberg College in Allentown in 1976; a Master of Science in biology from ESU in 1980; and a Doctor of Philosophy from Lehigh University in 1989. He has been a faculty member in the department of biological sciences since 1989 and has taught 18 different courses and laboratories. Master has escorted ESU students on natural history tours to East Africa and the Galapagos Islands, in addition to teaching classes in Costa Rica since 1995. His areas of specialization are ornithology, behavioral ecology and predator-prey relationships.

In his 30 years at ESU, Master has mentored 30 graduate students and 13 undergraduate research students. Many of his students have been primary or co-authors on 34 peer-reviewed articles in 11 different journals, as well as various book chapters, technical reports and online publications. He has also edited a book on Avian Ecology and Conservation and has had several photographs published.

Master and his students have given nine international presentations, nine presentations at national conferences and 13 presentations at meetings of the National Council on Undergraduate Research. Together, they have also presented 84 times at regional, state and local meetings and he has been an invited speaker at a variety of national, regional, and local conferences. His research program and graduate students have been supported by over $1 million in grant funding. Dr. Master received the Earl Poole Award from the Pennsylvania Society for Ornithology in 2013 for his contributions to ornithology in Pennsylvania.

An active member of the campus and local communities, Master was interim department chair twice, has served on many departmental committees and is currently departmental graduate coordinator. Master chairs the statewide Ornithological Technical Committee that advises the Pennsylvania Game Commission on matters of avian conservation, and was a member of the both the Monroe County Open Space Advisory Council, which preserved 17,000 acres of open space in the county, and the Cherry Valley National Wildlife Refuge Study Team Partnership, responsible for establishing what will be a 20,000 acre refuge. He has given presentations and guided nature/birding field trips for 21 different conservation organizations in Delaware, New Jersey, and Pennsylvania.

Master also played a vital role in creation of the Schisler Museum of Wildlife and Natural History. He visited often with donors Arthur and Fannie Schisler 62 and worked in conjunction with Christine Langlois in facilities management, Howard Whidden in the department of biological sciences, Science and Technology Center architects, museum designers and exhibit fabricators to determine final museum, habitat diorama and signage designs and content.

He currently lives near Nazareth with his wife, Sally, their dog, Tica, and cat, Jimmy.

The second Innovator & Entrepreneur of the Year Award was given to Nicole Chinnici, director of the Dr. Jane Huffman Wildlife Genetics Institute and founder and CTO of Organtick LLC, a research and development company specializing in a three-step prevention model for personal, pet, and home tick protection. In her role as an ESU staff member and entrepreneur, Chinnici has led the research and development initiatives that have established ESU as a nationally-recognized center for tick testing and research.

In 2008, ESU's tick testing and research efforts were initiated by Jane Huffman, professor of biological sciences. Chinnici served as her protg beginning in 2012 and became director of the lab in 2017 following Huffman's untimely passing. Under Chinnici's leadership, several innovative and entrepreneurial achievements were realized that elevated and expanded ESU's role and recognition in tick testing and research, including rebranding LymeAide under the Cutter brand, testifying at joint hearings on the impact of Lyme disease with the Pennsylvania Department of Health and Human Resources, developing a childrens activity book to provide critical information on tick awareness and education for children, and winning the 2019 TecBridge non-collegiate business plan division for OrganTick LLC.

Chinnici worked closely with State Rep. Rosemary Brown (R-189) to raise tick awareness across the Commonwealth. Those efforts resulted in $1 million in allocations to ESU to create the PA Tick Research Lab that provides free tick testing to Pennsylvania residents. The Lab officially launched in April 2019, and to date has tested more than 5,000 ticks from all 67 Pennsylvania counties, and at least one tick from all 50 states. Efforts are ongoing to establish an annual line item appropriation from the Commonwealth to sustain the PA Tick Research Lab. The $1M allocation also supports the development of a robust database with analytic functions to identify the geographic location of the ticks tested and test results.

Chinnicis continued success with ESU tick research and testing is supported by the students she trains and works with daily and by the faculty, staff and business/community partners who share her passion for innovation and entrepreneurship. Her efforts are creating an entrepreneurial mindset at ESU that is enhancing the learning environment and creating ESU students who are world-class trained microbiologists with promising futures.

Applicants for the Innovator & Entrepreneur of the Year Award must submit a comprehensive application that addresses the impact of their activity (based on measurable outcomes), the projects alignment with ESUs strategic plan, and alignment with the definition of an ESU entrepreneur, creativity, sustainability and timeliness. Submissions are reviewed by a committee appointed by the president and representing faculty, staff, students, alumni and the greater community. Four finalists competed in a Shark Tank style platform, each giving a 10-minute presentation about their entrepreneurial projects followed by a question and answer segment with the judges. One award is presented each year. Individual and joint submissions are eligible.

For more information about the Distinguished Professor Award, contact the APSCUF office at 570-422-3278 or visit bit.ly/2NzBLJH. For more information about the Innovator and Entrepreneur of the Year Award contact the Office of the Provost at 570-422-3239.

See the original post here:
ESU awards Distinguished Professors and Innovator and Entrepreneur of the Year - Pocono Record