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Contents
Schizophrenia Alzheimer’s Disease and Anti-Psychotics Stem cell Research Viagra for Heart Passive Immunization for Alzheimer’s Disease Approval for Generic Pain Medication Vaccine against Hepatitis A Pharmaceutical Industry: Pfizer India to Lead in Heart Disease: The Indian Gene Monoclonal Antibodies in India Drugs in Japan: Novartis Center for Compassion and Altruism Research and Education Schizophrenia Schizophrenia is a lifelong disease affecting about 1 percent of the world's population. Before today's antipsychotic drugs were developed, patients generally were hospitalized, sometimes for life. Current drugs generally can halt or lessen the hallucinations, delusions and aggression patients suffer, but they don't help most patients with other symptoms, including depression, lack of drive or energy, and impaired memory and attention. Those symptoms make it difficult for patients to hold a job or maintain relationships, and many people with schizophrenia end up homeless or imprisoned. Johnson & Johnson sells the former blockbuster schizophrenia drug Risperdal, which together with two related medicines brought in $4.7 billion in 2007 - roughly 8 percent of total global sales. But Risperdal lost patent protection last summer and generic competition cut sales by 61 percent in 2008's third quarter. A newer, long-acting injected version called Risperdal Consta hasn't picked up much of the slack, and a successor drug called Invega hasn't been a success either. So, Johnson & Johnson has made an unusual $10 million deal with Vanderbilt University, whose researchers will work on development of a potential new schizophrenia treatment, all the way up to creating a compound ready for testing in people. The Vanderbilt-J&J partnership appears to be more extensive than historical university-industry collaborations. Instead of just identifying the research target, or mechanism that an eventual drug would alter, the point at which many university collaborations stop, Vanderbilt's team will test many compounds to find the best one and try to fine tune it to boost effectiveness and limit side effects. Existing drugs block dopamine. Under the collaboration, Vanderbilt University scientists instead will target another important neurotransmitter, glutamate. Vanderbilt University Medical Center has opened a laboratory devoted to advancing the understanding and treatment of diverse brain disorders including autism, ADHD, schizophrenia and Alzheimer’s disease. The Vanderbilt Laboratory for Neurobehavior, which officially opened January 15, 2009, allows scientists to research the complex roles of genes, as well as the impact of drugs, in how the brain supports learning, memory, attention, emotion and social behavior. The 9,000-square-foot lab dwarfs the prior space dedicated to neurobehavioral research in animal models at Vanderbilt. The new lab is supported by the Center for Molecular Neuroscience, the Vanderbilt Kennedy Center for Research on Human Development and the National Institutes of Health. New treatments are needed in this therapeutic area. The U.S. Food and Drug Administration (FDA) has been reviewing SAPHRIS(TM) (asenapine) sublingual tablets in the acute treatment of schizophrenia in adults and in the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults as monotherapy. Schering-Plough acquired asenapine in November 2007 through its acquisition of Organon BioSciences, which developed the antipsychotic agent. Alzheimer’s Disease and Anti-Psychotics Alzheimer's disease is the most common cause of dementia and causes symptoms including aggression, delusions and hallucinations. Previous studies have shown anti-psychotic drugs, which can help control the aggression and hallucinations for a few months raise the risk of death in older patients with dementia. There are other side effects, including respiratory problems and stroke. Anti-psychotic drugs commonly used to treat Alzheimer's disease may double a patient's chance of dying within a few years, suggests a new study that adds to concerns already known about such medications. Newer anti-psychotic drugs are no safer than older ones for the risk of suddenly dying from a heart problem, says a study that finds they roughly double that hazard. Experts aren't sure how the anti-psychotics increase patients' risk of dying. But they think the drugs could be damaging to the brain and their sedative effects make patients less able to exercise and more susceptible to deadly infections. The research was published Friday in the medical journal, Lancet Neurology. According to the research findings published in Aging Cell (Vol. 7: 506-515, 2008) and Journal of Neuroscience (Vol. 28: 10330-10338, 2008), apolipoprotein D or ApoD shows protective and reparative role in neurodegenerative diseases, which suggests interesting avenues for preventing and slowing the progression of neurodegenerative diseases such as Alzheimer's, stroke, dementia, Parkinson's and multiple sclerosis, to name a few. Stem cell Research Patients reported greater ability to walk and more movement in their joints after a transplant of their own bone marrow cells. Their condition continued to improve for up to two years after the pioneering procedure, doctors found. Last year experts predicted that stem cell therapy could be used to "cure" the crippling neurological disease, which affects about 85,000 people in Britain, within 15 years. Sufferers experience fatigue, difficulty walking or speaking and pain. Caused by damage to myelin, a protective sheath around the body's central nervous system, there is no known cure for MS and few successful treatments. Stem cells have become increasingly important in medical research for their ability to turn themselves into any kind of cell. Previous research had suggested that they had the ability to help the body to rebuild myelin damaged by MS. The findings, published in the Lancet Neurology medical journal, showed that 81 per cent of patients had significant improvements to their disability. By injecting stem cells directly into the brain, scientists have successfully reversed neural birth defects in mice whose mothers were given heroin during pregnancy (Molecular Psychiatry, 2008; Journal of Neurochemistry, 2008). Even though most of the transplanted cells did not survive, they induced the brain's own cells to carry out extensive repairs. Transplanted stem cells have previously shown promise in reversing brain damage caused by strokes, as well as by neurological diseases like Parkinson's, Alzheimer's, and Huntington's. But their use in treating birth defects is relatively new. In recent years, a handful of research teams have been developing stem-cell-based therapies for rodents with real or simulated birth defects in the brain. Viagra for Heart The erectile dysfunction drug sildenafil amplifies the effects of a heart-protective protein, according to a report published in the Journal of Clinical Investigation online Jan. 5. Sildenafil, more widely known as Viagra prescribed for Erectile Dysfunction (ED) and also marketed as Revatio for pulmonary arterial hypertension, has already been shown to improve heart function. It may have value in either treating or preventing heart damage due to chronic high blood pressure. The key, investigators say, is sildenafil's effects on a single protein, RGS2, newly identified in the latest study as an essential link in the chain reactions that initially protect the body's main blood-pumping organ from spiraling into heart failure. RGS2 is stimulated by an enzyme, called protein kinase G, whose action is, in turn, raised by countering the activity of another enzyme, phosphodiesterase 5 (PDE5A). Sildenafil's ability to block PDE5A was shown in 2005 to be responsible for blunting hypertrophy due to high blood pressure in mice and offsetting similar, adrenaline-stimulated heart stress in people. PDE5A is involved in the breakdown of a key molecule, cyclic guanosine monophosphate, which helps control stresses and limit overgrowth in the heart. PDE5A is also the biological pathway blocked in the penis by sildenafil to promote the relaxation of blood vessels and maintain erections. RGS2 acts like a short-term reset mechanism in the heart, recoupling G proteins that if left alone stimulate the heart's response to high blood pressure resulting in a cascade of reactions known as Gq signaling leading to scar tissue formation, hypertrophy and heart failure. Currently, physicians use ACE inhibitors and ARB inhibitors to block Gq signaling. These classes of drugs are the most common treatment for heart failure, which afflicts more than 5 million Americans, killing over a quarter million of them each year. Passive Immunization for Alzheimer’s Disease Alzheimer's disease (AD) is a progressive and fatal brain disease for which there is no cure. It destroys brain cells, causing problems with memory, thinking and behavior severe enough to affect work, lifelong hobbies and social life. According to the Alzheimer's Association, as many as 5 million Americans are living with AD, which is the sixth-leading cause of death in the United States. Delivering monoclonal antibodies directed against beta-amyloid that accumulates in the brains of individuals with AD is called "passive immunization," since the body is receiving the antibodies, rather then generating the antibodies itself. Several innovator pharmaceutical companies, such as Abbott, Wyeth, Elan, Pfizer, Lilly, Genentech etc., are investing heavily in developing antibodies (passive immunization) and vaccines (active immunization) for AD. Approval for Generic Pain Medication Sun Pharmaceutical Industries Ltd., established in 1983 and headquartered in India, received several ANDA approvals from FDA. Approval was received for generic hydocodone bitartate with acetaminophen (APAP) tablets. The approval for Hydrocodone with APAP is the first approval for products based on controlled substances. Hydrocodone with APAP is a narcotic analgesic indicated in the treatment of relief of moderate to moderately severe pain of acute, chronic, or post-operative types. This is a Schedule III drug, regulated partly by the Controlled Substance Act of 1940 in the US. Approvals have been received for ten generic versions of these tablets containing Hydrocodone and APAP in the following strengths; 5/325 mg, 7.5/325 mg, 10/325 mg, 5/500 mg, 7.5/500 mg, 10/500 mg, 7.5/650 mg, 10/650 mg, 10/660 mg and 7.5/750 mg. Hydrocodone + APAP Bioequivalent to strengths approved - 5/500 mg Vicodin 5 /500 mg tablets of Abbott Laboratories 7.5/500 mg Hydrocodone with APAP 7.5 /500 mg tablets of Mikart Inc 10/500 mg Lortab 10/500 mg of UCB Pharma, Inc. 7.5/750 mg Vicodin ES tablets 7.5/ 750mg of Abbott Laboratories 7.5/650 mg Hydrocodone with APAP tablets 7.5/650 mg of Mikart Inc. 10/650 mg Hydrocodone with APAP 10 /650 mg tablets of Mikart Inc 10/660 mg Hydrocodone with APAP 10/660 mg of Mallinckdrodt, Inc 5/325 mg Norco tablets, Hydrocodone with APAP 5/325 mg, from Watson Laboratories 7.5/325 mg Norco tablets, Hydrocodone with APAP 7.5/ 325 mg, from Watson Laboratories 10/325 mg Norco tablets, Hydrocodone with APAP 10/325 mg, from Watson Laboratories. These strengths have annual sales of approximately USD 540 million in the US which includes branded as well as generic products. Approval was also received for generic Aredia®, pamidronate disodium for injection USP, generic Lopid ®, gemfibrozil tablets, USP, and generic Phenargan®, promethazine hydrochloride tablets. Generic Lopid contains gemfibrozil 600 mg, a cholesterol reducing agent and has annual sales of about USD 44 million in the US. Generic Aredia® is indicated in the treatment of hypercalcemia of malignancy, paget's disease, osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma. Approval has been received for two strengths- 30 mg/ vial and 90 mg/ vial. Genericand branded Aredia® has sales of approximately USD 20 million in the US. In addition, approval was received for generic Phenargan tablets. promethazine hydrochloride USP. Generic Phenargan is an antihistamine/ antiemetic and is available as 12.5 mg, 25 mg and 50 mg tablets bioequivalent to generic Promethazine hydrochloride from Sandoz, Inc. Generic Phenargan® has sales of approximately USD 50 million in the US. These products, to be manufactured at multiple facilities of Sun Pharma (together with its subsidiaries) in India and US, will reach market shortly. Vicodin ® is a registered trademark of Abbott Laboratories. Lopid® is a registered trademark of Pfizer Pharmaceuticals Ltd. Aredia® is a registered trademark of Novartis Pharmaceutical Corporation Phenargan® is a registered trademark of Wyeth Pharmaceuticals. Meanwhile, Abbott Laboratories fired 200 sales representatives preparing to market a new abuse-resistant pain pill after the company stopped plans to introduce the drug this year. The drugmaker said in October that the drug, an extended release form of Vicodin, failed to gain U.S. Food and Drug Administration approval. The company hasn’t released details of the so-called complete response letter from the FDA. Vicodin is in a class of powerful pain medications under scrutiny by U.S. regulators and doctors because of increasing abuse rates and a fear the drugs may lose their effectiveness when given over a long period of time. Abbott said its extended release form, Vicodin CR, would be the first in the hydrocodone class of narcotics to provide relief for 12 hours. Other hydrocodone drugs sell for less than $1 a dose and must be taken every four to six hours. If approved, the drug may face skepticism from insurers, who would be reluctant to pay for a more expensive version of a drug that has had generic competition for years. A spokeswoman for Abbott, “Based on the delay in the market availability of Vicodin CR, Abbott is reducing the number of staff supporting our pain-care business.” King Pharmaceuticals Inc., which bought Alpharma Inc. for $1.3 billion in December, is gaining one of a half-dozen companies racing to sell the first long-acting painkillers modified to deter potentially fatal misuse. By buying Alpharma and investing in its own pain drugs, King has positioned itself to lead a market that may reach $3 billion by 2015. Purdue Pharma LP, maker of OxyContin, also is working to develop painkillers that are resistant to abuse. Vaccine against Hepatitis A Hepatitis A infections, usually transmitted via contaminated food and water, can cause debilitating illness. Protection afforded by the hepatitis A vaccine may last more than a decade, a new study shows. In fact, antibodies against hepatitis A virus persist for up to 27 years after vaccination, report investigators from the Centers for Disease Control and Prevention in Atlanta and the Alaska Native Tribal Health Consortium in Anchorage, in the Journal of Infectious Diseases. Pharmaceutical Industry: Pfizer As the low hanging fruit has been exhausted, the innovative drug development became tougher due to tough FDA regulations and generic competition – the innovative pharmaceutical industry, in general, is in trouble. Pfizer’s research labs have failed to be innovative and produce enough new medicines to replace drugs losing patent protection, led by the Lipitor cholesterol pill, the world’s best-selling medicine with $12.7 billion in 2007 sales. As a matter of act, Lipitor and Viagra were acquired, but not developed, by Pfizer, which has become an industry-wide practice – acquire companies and layoff workers. Pfizer has fired more than 14,000 workers since 2006, after acquiring various innovative companies that developed blockbuster drugs. Pfizer has reshaped its research division, which includes 10,000 people and a budget of $7.5 billion a year. The company has a total workforce of 83,000. As it focuses on developing medicines to treat cancer, brain disorders and pain, Pfizer has begun firing 800 researchers, or 8 percent of its science staff, in January. The research cuts add to firings of 1,200 scientists last year with the closing of Pfizer’s Ann Arbor, Michigan, laboratory. Pfizer is also trimming its U.S. sales operation to save money as top-selling products lose patent protection. Pfizer Inc. also wants to get rid of 100 experimental medicines for conditions ranging from obesity to high cholesterol by selling them to rivals. Pfizer is halting early-stage development of medicines for heart failure, high cholesterol and obesity to focus on so-called more- profitable diseases. Pfizer plans to seek U.S. regulatory approval for 15 to 20 drugs from 2010 to 2012 and will have as many as 28 drugs in the final stages of human tests this year, three times the number in 2005. Pfizer would focus on six areas of medicine: cancer, Alzheimer’s disease, schizophrenia, pain, inflammation and diabetes. These disease areas have the biggest growth potential and the best possibility of medical advances, the company said last year. Pfizer Inc is to buy Wyeth in a deal valued at about $68 billion. It would diversify Pfizer into vaccines and injectable biologic medicines by adding Wyeth's big-selling Prevnar vaccine for childhood infections and Enbrel rheumatoid arthritis treatment. Aside from Enbrel, for which Wyeth shares rights with Amgen, and Prevnar, Wyeth also is developing experimental Alzheimer's disease drugs which could be a major opportunity. Pfizer is going to slash more than 8,000 Jobs. Other possible preys for Pfizer were Bristol-Myers Squibb or biotech giant Amgen Inc. Biogen Idec has also been mentioned as a possible Pfizer target. Pfizer became the world's largest drug-maker with its purchase in 2000 of Warner-Lambert and the $60 billion acquisition three years later of Pharmacia. Pfizer exemplifies the overriding problem for many large not-so-innovative-drug-makers, which have struggled to produce new blockbusters to replace those on which they lose exclusivity. India to Lead in Heart Disease: The Indian Gene Heart disease is the number one killer in the world and India is particularly badly hit, with the problem set to intensify in coming years. The World Health Organization estimates that by 2010, India will have 60% of the world's heart patients. A gene mutation that almost guarantees the development of heart disease is carried by 60m Indians, researchers at Center for Cellular and Molecular Biology, Hyderabad, say. Around 4% people from the Indian Continent (South Asia) have the mutation, which increases the risk of heart disease seven-fold, the scientists from India, Britain and the United States, in Nature Genetics, said 4 percent of people. The researchers first identified the mutation in the heart protein gene MYBPC3 five years ago in two Indian families with cardiomyopathy - a disease causing deterioration of the heart muscle. It would be easy to test people at a young age for the gene. However, all that doctors could do would be to offer healthy lifestyle advice involving healthy food habits and exercise. Patients with the mutant gene appear healthy throughout the early part of their lives, but the abnormal protein manufactured from the gene slowly accumulates. After they turn 45 or so, the abundance of the abnormal protein triggers cardiomyopathy or other symptoms. The team found only three people who had two copies of the abnormal gene. Two of them developed severe heart disease before the age of 3. CCMB director Dr Lalji Singh said that the defect could be detected very early during pregnancy through a pre-natal diagnosis. If parents choose, a fetus having two copies of defective gene (homozygous) could be aborted after genetic counseling. Interestingly, this genetic defect is present only in the people of the Indian Continent (~ 2 billion) including Afghanistan, India, Pakistan, Sri Lanka, Indonesia and Malaysia but not in other countries. While virtually absent among peoples from other parts of the world, the deadly genetic variant is equally spread across most of India's regions, its social castes, as well as its language and religious groups. In a follow-up sampling of more than 2,000 indigenous individuals from 26 countries across five continents, the telltale mutation showed up in Pakistan, Sri Lanka, Malaysia and Indonesia, but nowhere else. The dangerous did not die out over the course of evolution, as usually happens to maladapted genes, because the harmful effects are felt mainly late in life after people have had their children and passed on their genes, so the mutation is essentially invisible to natural selection. Selected native populations from the following countries were studied: South Africa, Namibia, Kenya, Democratic Republic of Congo, Central African Republic, Nigeria, Senegal, Algeria, Israel, Italy, France, Orkney Island, Pakistan, India, Sri Lanka, Andaman, Malaysia, Indonesia, New Guinea, Boungainville, Australia, Cambodia, China, Japan, Russia, Mexico, Colombia and Brazil. Selected local and native Tribes/castes studied in various states within Indian Union: ANDHRA PRADESH: Goud, Kolma, Yanadi, Chenchu, Siddi (African settlers), Erkula, Thotti, Gowda, Muslims, Velama, Padmashali, Sagara, Sugali, Madiga, Lambadi, and Vysyas. TAMIL NADU: Marvar, Kallar, Irulas, Kurumba, Agamudaiyar, Paniyan, Toda, Kota, Baduga, Chakkiliar, Khani, Malayali, Parayar, Paliyar, Malaikurvar, Kondareddy, Arundathi, Lingayath, and Anglo-Indian. KERALA: Oorali, Kattunayakkan, Kurcha, Kuruman, Muslims, Malayan, Ulladan, and Karimbala, KARNATAKA: Halakki and Kunabi, MAHARASTRA: Mahadekoli, Thakar, Parsi (Iranian descent) and Katkari, GUJARAT: Rathwa, Koli, Tadvi, Girasia, Vatika Gond and Bhils. MADHYA PRADESH: Bhilala, Barela, Kol, Bhil, Gond, Mawasi, Sahariya, Keer, Korku and Baiga. KASHMIR: Pandits UTTRANCHAL: Tharus and Buxas UTTAR PRADESH: Brahmin, Sidhi, Muslim, Haburra, Chipi, lakodiga, Rajput, Diwari, Yadava, Saharia, Rohidas, Kori and Lodhe PUNJAB: Ramgarhia RAJASTHAN: Bheels, Meena and Meghwa CHATTISGARH: Sathnami, Santhal, Gond, and Kanwar, Bhist and Bhotia. ORISSA: Oraon, Kissan, Dhurva, Bonda and Gadaba. BIHAR: Oraon. JHARKAND: Ho, Munda and Oraon. NAGALAND: Chakhesang-Naga, Ao-Naga and Naga-Sema. ARUNACHAL PRADESH: Nyshi MIZORAM: Mizo, ANDAMAN ISLANDS: Great Andamanese, Nicobarese and Onges. Monoclonal Antibodies in India Intas Biopharmaceuticals Limited (IBPL), India’s leading biotechnology company, signed a Memorandum of Understanding (MoU) with Government of Gujarat for setting up a separate manufacturing facility for Monoclonal Antibodies (MAbs), a recombinant mammalian platform product. The company will invest Rs 160 crores towards setting up a manufacturing facility at Sanand near Ahmedabad. The facility, dedicated for Monoclonal Antibodies, will undertake large-scale manufacturing of the recombinant product with a capacity of 5000L in phases. In the area of Research & Development pertaining to recombinant products, the company is developing Novel Drug Delivery System for proteins, a cloning facility, introducing novel production platforms, developing MAbs and recombinant products (cytokines, hormones and blood factors). The company, in a planned and phase-wise manner, will screen technologies / new molecules and identify the most promising ones, prioritizing them on the basis of their business potential and compatibility. IBPL is planning to generate clones for commercial production of protein using state-of-the-art technologies to improve yields, quality as well as adopting novel expression systems with an objective to build Intellectual Property over the long run. MAbs has strong potential of generating IP in terms of patents and could provide a novel platform for delivery of many of the protein therapeutics. Drugs in Japan: Novartis Novartis AG said it has received approval in Japan to market four drugs to treat asthma, cancer, hypertension and blindness. The Swiss pharmaceuticals company said the approvals covered omalizumab, known as Xolair, for treating severe bronchial asthma in adult patients; nilotinib, or Tasigna, to treat certain forms of Philadelphia chromosome-positive chronic myeloid leukemia, a rare form of cancer; a new single-pill combination of valsartan - known as Diovan - and hydrochlorothiazide for high blood pressure treatment; and ranibizumab, or Lucentis, for patients with wet age-related macular degeneration, a form of blindness which affects about 20,000 people in Japan each year. Center for Compassion and Altruism Research and Education A new Center for Compassion and Altruism Research and Education has been launched at the Stanford University School of Medicine, with the aim of doing scientific research on the neural underpinnings of these thoughts and feelings. His Holiness the 14th Dalai Lama, Tenzin Gyatso, provided $150,000 in seed money for the center—the largest sum he has ever given for a scientific venture—and has agreed to return to Stanford for a future visit, according to Geshe Thupten Jinpa, a translator for the Dalai Lama. The center is the brainchild of Jim Doty, MD, a clinical professor of neurosurgery who recently returned to Stanford after a period of entrepreneurship, and neurologist William Mobley, MD, PhD, the John E. Cahill Family Professor in the School of Medicine. Doty is the director of the center, which is housed within the Stanford Institute for Neuro-Innovation and Translational Neurosciences. The impetus for the center began in November 2005, when the Dalai Lama visited Stanford for a dialogue with scientists and Buddhist scholars that was moderated by Mobley and focused on spiritual and scientific explorations of human experience in the areas of craving, suffering and choice. In March 2008, a delegation from Stanford flew to Seattle, where the Dalai Lama was attending a conference related to compassion. On hearing from the Stanford group about the goals of the planned center and the pilot studies under way, the Dalai Lama agreed to a return visit to Stanford and spontaneously volunteered the $150,000 donation to spur continuing exploration in this area. This event marked the transition from what was initially an informal gathering of like-minded scientists to the formal creation of the center by medical school Dean Philip Pizzo. Questions the center wishes to address include: -Is it possible to create a set of mental exercises that individuals can be taught to make them more compassionate without them having to spend thousands of hours in meditation (common for Buddhist monks)? - Is there an explanation for why a child becomes a bully? - Are there ways in which children or their parents can be taught to be more compassionate? - Can we create a set of exercises that will address the issue of “compassion fatigue” in clergy and hospital personnel? - Would such training benefit prison inmates to decrease violence and recidivism? - Is there a place for such training in the corporate environment to decrease the incidence of depression and anxiety in workers? The center is also sponsoring a symposium, slated for March, that will bring together a multidisciplinary group of scientists from around the world. Attendees will include philosophers, contemplative scholars, psychologists, developmentalists, primatologists, neuroeconomists and neuroscientists working in the area of compassion and altruism research. Doty brings a unique perspective on altruism to the center. At one point, he accumulated a $75 million fortune, part of which he committed as a multimillion-dollar pledge to Stanford University. But following the dot-com meltdown, Doty was $3 million in debt even after liquidating essentially all of his assets. To honor his charitable commitments, he sold his only remaining asset: stock in Accuray Inc., a publicly traded company he had previously headed as CEO. This allowed Doty to fulfill pledges of $5.4 million to the university and another $20 million to other charities. Part of his Stanford donation is being used to fund the center. Source: The primary sources cited above, BBC News, New York Times (NYT), Washington Post (WP), Mercury News, Bayarea.com, Chicago Tribune, CNN, USA Today, Intellihealthnews, Deccan Chronicle (DC), the Hindu, Hindustan Times, Times of India, AP, Reuters, AFP, Biospace etc. Notice: The content of the articles is intended to provide general information. Specialist advice should be sought about your specific circumstances. |
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