DAILY NEWS BULLETIN LEADING HEALTH, POPULATION AND FAMILY WELFARE STORIES OF THE Day Tuesday

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1 DAILY NEWS BULLETIN LEADING HEALTH, POPULATION AND FAMILY WELFARE STORIES OF THE Day Tuesday Global Guidelines Indian doctors oppose new diabetes norms (The Times of India: ) MUMBAI: A new set of global guidelines on managing diabetes that aim to replace those followed for over three decades has stirred up a row within the medical community. Doctors in India feel the norms, which recommend relaxing blood sugar targets, will not only lead to serious complications in diabetics but also confusion in treatment protocol. They advise that these should be ignored for Indians. The controversial norm relates to relaxing the long-term blood sugar target, hemoglobin A1C (HbA1c) which, via a blood test, gives an estimate of a person s blood sugar level average over the past few months. Generally, an HbA1c of 6.5% indicates diabetes. There were over 72 million cases of diabetes in India in 2017, according to International Diabetes Federation. Haven't been to Mainland China in Chandigarh yet? American College of Physicians, an organisation of internal medicine physicians, has recommended recently in the medical journal, Annals of Internal Medicine, that clinicians should aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes as against the traditional 6.5 to 7% which has been followed over decades. The recommendation is leading to a conflict in views amongst doctors, with certain associations opposing it. Doctors here say the guideline of lowering the blood sugar target cannot be binding and should be ignored as diabetes in India is more aggressive, and, hence, riddled

2 with complications. They say these recommendations should not be applicable here as India has its own three advisory bodies the ICMR (Indian Council of Medical Research), RSDDI (Research Society For The Study of Diabetes in India) and API (Association of Physicians of India) which are more tuned in to Indian cases. Anoop Misra, chairman of Delhi-based Fortis-C-DOC (Centre of Excellence For Diabetes, Metabolic Diseases and Endocrinology), said, In reality, Indian physicians continue to follow US-based guidelines, hence ACP guidelines may have substantial impact in India. If blood sugar control is loosened (as advised by ACP), more patients in India will suffer from complications, the burden of which is already high. We should ignore these, and stick to previous time-tested glycosylated hemoglobin limit of control of 7%. Others concur the guidelines cannot be standardized because of several differences in lifestyle, physiology and food habits. Dr Shashank Joshi, endocrinologist and diabetologist who consults at Mumbai s Lilavati Hospital, said, Asian Indians who develop diabetes are insulin-resistant and have different phenotype (observable characteristics, physiological properties, or behavior) compared to those in the western world. None of the North American or European guidance are applicable for Indians, Chinese or Asian geographies. Also, since Asians consume more carbohydrates, their response to medicines and doses is different. Says Dr Rajeev Chawla, president-elect of RSSDI 2018 and senior consultant diabetologist, Pharmacotherapy using oral or injectable agents may be used in addition to lifestyle modification therapies to achieve a target glycosylated hemoglobin target of less than 7% for all diabetics as far as possible to prevent complications. The RSSDI is the largest organisation of doctors in Asia engaged in diabetes care with over 7,000 members. The guidelines were first released in 2015 and revised in January 2018 based on Indian evidence. Patent Law Govt not using patent law effectively: Pharma body (The Times of India: ) The Indian Pharmaceutical Alliance, an association of 20 top Indian pharma companies that account for 80% of the country s exports and 46% of the domestic market, has submitted a report to the government that says that public health safeguards in the patent law were not being used effectively.

3 The IPA pointed out that an analysis of patent filings between 2007 and 2012 had shown that a third of the patentees got away with not disclosing whether a patent was being used or not and a third were defective or incomplete. In a report submitted to the Indian Patents Office and the Department of Industrial Policy and Promotion, the IPA referred to an ongoing case in the Delhi high court seeking directions to the government to compel patentees and licensees to declare information on the working of their patent as required under the Patent Act. The IPA report pointed out that many subsections in the Act were introduced to safeguard public health, prevent abuse of patent rights and ensure that patents contributed to dissemination of technology. It added that compulsory licences were a mechanism to ensure availability of medicines at reasonable prices especially where patents were not being used. The use of compulsory licence was not unusual as there were 100 instances of their use between 2001 and 2016, of which six were in the developed world, submitted the IPA. These licences were largely for HIV (73), cancer (12) and other diseases (15). So far, India has issued just one compulsory licence in early Neither has India ever revoked a patent for non-working, nor has the government granted compulsory licence for government use or for any public health imperative. IPA pointed out that the law empowered the controller of patents to demand information from patentees and licensees annually on how much the patent was being worked commercially. Such information was crucial to assess the balance between incentivising innovation and promoting public health by ensuring adequate availability of medicines at a reasonable price, IPA said. The alliance demanded that the patents controller place patent filings in the public domain and make them available under the RTI Act so that civil society and NGOs could assess the extent to which patents were being worked commercially. Just as the controller s office had made filings for 2012, 2013 public in a searchable database, it ought to digitize all filings and make them available in a searchable database, it added. The alliance urged the government to ensure that patent filing was done properly and that required forms were complete so that the controller could assess how the patent was being used to decide on granting or revoking compulsory licences and patents.

4 Male birth control pill Male birth control pill taken once a day shows success (The Times of India: ) A new birth control pill for men with a hormonal component has shown efficacy and safety in preventing pregnancies when used once daily for a month. The study was presented yesterday (18th of March 2018) at the ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Illinois. The study with the new pill was tested on 83 men. It contains dimethandrolone undecanoate, or DMAU. The pill contains the activities of male hormone testosterone and also a female hormone progestin. It is to be taken once a day. DMAU is developed by the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, that also sponsored this study. Stephanie Page, M.D., PhD, professor of medicine at the University of Washington, Seattle, Washington led the study. She explained that many men would opt for a once daily pill that provides them with reversible contraception rather than go in for topical gels or long acting injections of DMAU that would provide longer term contraception. She explained that testosterone preparations till date have not shown success as male contraceptives because they can lead to liver inflammation. These testosterone pills are also cleared easily and rapidly from the body. This means at least twice daily pills are recommended. DMAU on the other hand contains undecanoate, a long-chain fatty acid that delays its exit from the body and allows for a single daily dose. The pills need to be taken with food to be effective, she said. The study started off with 100 men of whom 83 completed the study. The men were aged between 18 and 50 and were all healthy. The study was conducted at the University of Washington Medical Center and at Harbor-UCLA Medical Center in Torrance, CA with assistance from Christina Wang, MD, professor of medicine at the University of California, Los Angeles and Arthi Thirumalai, MD, Assistant professor of medicine at the University of Washington. The participants were given three different doses of DMAU - 100, 200, and 400 mg. they were given two different formulations inside the capsules - one with powder and one with castor oil/ benzyl benzoate. Five persons in each group received a placebo and 12 to 15 men received the DMAU pills. The pills were taken for 28 days once daily with food. At the end of the study the 83 men gave their blood samples for testing hormone levels as well as cholesterol levels. This had been done once at baseline as well. Results showed at men who were given 400mg of DMAU showed marked suppression of their testosterone levels. This led to effective contraception. Page explained that although the blood levels of

5 the male hormones dipped, there were no symptoms of testosterone deficiency or excess. These men however gained weight slightly, developed mild acne and showed mild decrease in HDL cholesterol. Their liver functions and kidney functions were however normal and the drug was deemed safe. There were no changes in the EKG results or vital signs with this drug use. Mood and sexual functions too remained unaltered with this pill, Page said. She added that this study paves the way for further longer term studies with larger populations of men to prove that taking DMAU each day regularly can block the production of sperm and provide contraception.

6 Male birth control pill (The Asian Age: )

7 Male birth control pill (Dainik Jagran: ) Diabetes drug (The Asian Age: )

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9 Male Fertility (The Asian Age: )

10 Tuberculosis Maharashtra shows the way on how to tackle tuberculosis including a daily drug regimen and cash transfers (The Times of India: ) India has taken major strides to fight tuberculosis (TB), which remains the country s largest infectious killer. Under the auspices of Prime Minister Narendra Modi, the central government in its new National Strategic Plan for TB, has recognised TB elimination as the foremost priority, committing unprecedented funds for the programme, including Rs 600 crore towards nutritional support for patients. States with a high TB burden such as Maharashtra have a crucial role to play in ensuring effective implementation of these strategies. In 2017, Maharashtra reported 2,14,102 new TB cases of which 9,172 were cases of drug resistant TB (DR-TB). However, the Maharashtra government has undertaken innovative strategies using latest technologies and engaging with the private sector to expand provision of free diagnosis and treatment to all patients. A call centre provides easy access to private providers to notify TB cases, and in turn offers patients counselling and adherence support. The project which was piloted in Mumbai and Nagpur, resulted in a dramatic increase in notification of TB cases and will now be scaled up to other cities in Maharashtra. Furthermore, a mass awareness campaign TB Harega Desh Jeetega, with the iconic Amitabh Bachchan as its ambassador, was launched by the Municipal Corporation of Greater Mumbai (MCGM) in 2014 and was subsequently adopted by the central government. The widely popular campaign was disseminated across the country through various mediums. Last year, based on WHO s recommendations, Maharashtra shifted from an intermittent to a daily drug regimen. A new anti-tb drug, Bedaquiline, was introduced as part of the DR-TB treatment regimen in Maharashtra and has shown successful results. CBNAAT machines were made available for all TB patients through district hospitals and government medical colleges to augment the state s capacity for timely and accurate diagnosis of DR-TB. We understand that delay in diagnosis increases risk of transmission, and therefore my health staff has intensified active case finding efforts across all districts. Additionally, to improve patient tracking and follow-ups, technology based adherence solutions such as 99 DOTS have been rolled out across Maharashtra. Patients call in a toll free helpline with unique numbers printed on the back of the medicine sleeves after taking

11 their doses. This allows programme staff to review adherence and support those who miss their doses. Along with free diagnosis and treatment we also recognised the importance of addressing social determinants of TB such as malnutrition, which is both a cause and effect of TB. I am happy to share that Maharashtra is one of the first states in the country that introduced schemes to provide nutrition support to TB patients. Under these schemes my government has set aside Rs 15 crore to provide nutritious food like pulses, rice, peanuts, jaggery and wheat flour to patients with multi-drug resistant (MDR) TB for two years across 22 municipal corporations. We are also contributing Rs 47 crore towards cash transfers to all TB patients, and incentives for treatment providers and supporters across the state. Finally, TB elimination requires a multi-pronged approach with the participation of every sector. With the new Corporate Social Responsibility strategy in place, MCGM is partnering with donors to encourage CSR funding towards awareness, nutrition, infection control, and community engagement initiatives. Our success with eliminating diseases like smallpox and polio is now proof that when political leadership, government officials, grassroots level functionaries and civil society synergise efforts, no health challenge is unsurmountable. I would like to share my appreciation of the incessant efforts of my ministers and secretaries of health and medical education, mission director, state TB programme personnel right up to the TB health visitor, extended ecosystem of healthcare providers and chemists who are making every effort to ensure that our aim to eliminate TB is realised. I feel privileged to lead this movement against TB in every village, town and city of Maharashtra. World TB Day falls this week. I assure Maharashtra s unflinching support to the fight against TB. TB Harega Desh Jeetega!

12 Tobacco Use Punjab to ban hookah bars (The Hindu: ) The Cabinet on Monday approved amendment to the Cigarette and Other Tobacco Products Act. Move aimed at reducing tobacco use The Punjab government has decided to impose a permanent ban on hookah bars in the State, instead of issuing temporary orders against them every two months. The move is aimed at reducing the use of tobacco in various forms. The State Cabinet, in a meeting held here on Monday, approved an amendment to the Cigarette and Other Tobacco Products (Prohibition of Advertisement and Regulation of Trade and Commerce, Production, Supply and Distribution) Act, 2003 (COTPA 2003), for the prevention and control of diseases caused by the use of tobacco products. Presidential nod The amendment would result in a complete ban on the running of hookah bars in the State. The proposed amendment will be placed before the Legislative Assembly and, after being passed by the House, will be reserved for the assent of the President of India, read an official statement. At present, Section 144 of CrPC is promulgated against all hookah bars in all the districts of the States for two months, with extension required at the end of the period. The Cabinet has also decided to introduce a Bill for regularisation of unauthorised colonies, plots and buildings in the Budget Session that is slated to start from Tuesday (March 20). The Cabinet cleared the decks for its members to pay their own income tax beginning March The draft amendment bills for relevant changes to 'The East Punjab Ministers' Salaries Act, 1947, and 'The Salaries and Allowances of Deputy Ministers, Punjab Act, 1956,' will be presented in the Budget session, the statement added. It was also decided that MBBS doctors will now get their full salaries, including all allowances, during probation period. The Cabinet has decided to do away with the condition of basic pay only for newly appointed medical officers in the Health and Family Welfare Department, read the statement.

13 India s first womb transplant Recipient of womb suffers abortion (Hindustan Times: ) PUNE: Recipient of India s first womb transplant will have to undergo a second embryo transfer after suffering an abortion. According to doctors, the 21-yearold from Solapur, who underwent an embryo transfer in February this year, remained pregnant for five weeks but suffered an abortion in the sixth week. Dr Shailesh Puntambekar, medical director of Pune s Galaxy Care Laparoscopy Institute (GCLI), where the uterine transplant and embryo transfer was performed, said, The first recipient of the womb transplant underwent an embryo transfer in the first week of February. A pregnancy test was conducted after 14 days which showed she was still carrying the baby. The tests were positive for the first five weeks and the hormonal levels were also positive. This showed that the uterus was responsive, which is a good sign. Unfortunately, during the sixth week there was an abortion. Doctors said normally embryo transfer-led pregnancy is successful during the third attempt. One of the reasons could be the recipient was prescribed immunosuppressants during the transplant, which may have led to the abortion, said Dr Puntambekar. He said the woman will undergo embryo transfer for the second time in the last week of March. Doctors at a Pune hospital had conducted two uterine transplants on May 18 and May 19 last year. The first recipient was the 21-year-old woman from Solapur who was born without a uterus. The second transplant was successfully performed on a 24-yearold woman from Baroda who was suffering from Asherman s Syndrome (scar tissue in the uterus). In the last week of March, the woman from Solapur will undergo an embryo transfer for the second time while the woman from Baroda for the first time, said Dr Puntambekar. He said that one more uterine transplant was performed on January 26. There are two women, a 24-year-old and a 25-year-old, who are likely to undergo uterine transplants in the first week of April, he said.

14 Water crisis Water crisis to intensify in India: Unesco report (Hindustan Times: ) Says population growth, climate change will add to scarcity across country NEWDELHI: A new report released by the United Nations Educational, Scientific and Cultural Organization (Unesco) ahead of World Water Day on March 22 shows that the water crisis will be intensifying across India by Central India is staring at deepening water scarcity that means withdrawal of 40% of the renewable surface water resources. Experts say the already stressed groundwater resources will face greater pressure in the coming years. The already stressed ground water resources will face even greater pressure in north India. SK Sarkar, who heads the water resources division at policy think-tank TERI, said that groundwater depletion was extremely severe in Punjab, Haryana and Delhi. Ground water depletion carries with it the risk of salinity, he said. South and central India will experience high levels of risk from poor water quality in its river basins by The report relies on a study done by the International Institute for Applied Systems Analysis for its estimations in future scenarios. Contamination is not only a problem with surface water resources but also groundwater, according to SWA Naqvi, a scientist at the Council of Scientific & Industrial Research (CSIR) and NIO director, There is metallic contamination but also contamination from improper disposal of human excreta, he said. There is growing evidence to show that because of dumping of faecal matter in the ground either because of open defecation or soak-pits toilets with improper disposal of faecal matter - leads to contamination of groundwater aquifers with E-coli bacteria, according to experts. The Unesco report said that over 2 billion people worldwide do not have access to safe drinking water but almost twice that number of people do not have access to safe sanitation. The demand for water is expected to increase by almost one-third by 2050 compared to 2010 levels. China, India, United States, Russia and Pakistan are the largest consumers of water at present and they will continue to be top water guzzlers in The report attributed the water scarcity to population growth and climate change, which were not just fuelling water scarcity but also flooding in areas that are not historically flood-prone.

15 According to the report,the number of people exposed to flood risk surged from 1.2 billion to day to 1.6 billion in 2050, and assets valued at US $45 trillion will also be at risk. The report recommends nature-based solution that mimic nature, citing the example of smallscale water harvesting structure in Rajasthan that quenched the water demand of 1,000 villages. Another example of this is the underground taming of floods for irrigation (UTFI) project, that is being piloted in the Ganga river basin. UTFI is a way of managing both flooding and drought because the method entails channelising excess flow during the wet season for the recharge of aquifers, thus curbing flooding downstream. Economic Survey Economic Survey : At Rs 3.3 lakh, Delhi s per capita income second highest in the country (The Indian Express: ) Delhi's per capita income, at Rs 3,29,093, is the second highest in the country, the report maintains. In , the per capita income was Rs 3,00,793 Delhi s per capita income, at Rs 3,29,093, is the second highest in the country, the report maintains (File) The Delhi government has pegged at per cent the tax collection growth in the fiscal. In , as the economy reeled under the impact of the global slowdown and demonetisation, tax collection growth had slumped to 3.03 per cent. As per the Economic Survey report of , tabled in the Delhi Assembly on Monday, tax collection in the capital had fallen sharply in However, this year, the city s revenue surplus has come down to 0.80 per cent (Budget Estimate or BE) of the Gross State Domestic Product (GSDP) as compared to the 1.58 per cent in In , total tax collection has been projected at Rs 38,700 crore as against Rs 31,139 crore in Delhi s per capita income, at Rs 3,29,093, is the second highest in the country, the report maintains. In , the per capita income was Rs 3,00,793. The survey has revealed that all component in the tax revenue had grown this year as compared to last year. However, the first dip after the implementation of the GST was in October. Attributing

16 the dip in tax collection in to the refunds made under various heads, Principal Secretary (Finance) SN Sahai said, The refunds dated back to 10 years in some cases. Maintaining that the projected growth rate of per cent was one of the best among states with economy as vast as that of Delhi, he said that the revenue surplus has slumped due to the rise in expenditure under many heads, including payment of salaries following the recommendations of the 7th Pay Commission. The survey states, All components in the tax revenue showed a higher growth rate during (BE) except for other taxes on goods & services, which have show a lesser growth of 9.66 per cent as compared to per cent in It also states that there was fiscal deficit of Rs crore in the year (prov) as compared to fiscal surplus of Rs crore in Stamps & Registration Fees registered negative annual growth of 8.39 per cent during (Prov) as compared to the growth of 20.8% during due to the global economic slowdown, which adversely affected the collection under the head, it reads. The survey showed that the projected GSDP growth in is per cent and the state s economy is likely to attain the size of Rs 6,86,017 crore. The advance estimate of GSDP of Delhi at constant prices during was recorded at Rs 5,56,800 crore at a growth of 8.14 per cent as compared to What survey highlights * The advance estimate of GSDP of Delhi at current prices during is likely to attain level of `6,86,017 cr, at a growth of 11.22% over * As per advance estimate, per capital income of Delhi at current prices during estimated at `3,29,093 as compared to `3,00,793 in * Tax collection registered a growth of 3.03% in (Prov.) as compared to growth of 13.61% in Tax collection for is budgeted with a growth of 19.33% over the previous year Diet/Nutrition A big breakfast could aid weight loss, glucose control (Medical News Today: ) You may have heard that breakfast is "the most important meal of the day," and a new study helps to support this. It found that eating a big breakfast and reducing lunch and dinner size may be key for people looking to lose weight and improve their blood glucose levels.

17 Researchers suggest that three meals per day starting with a big breakfast could promote weight loss and better glucose control. Led by researchers from Tel Aviv University in Israel, the study found that adults who were obese and had type 2 diabetes lost more weight and had better blood glucose levels after 3 months when they had a high-energy breakfast every day. Lead study author Dr. Daniela Jakubowicz, who is a professor of medicine at Tel Aviv University, and colleagues recently presented their results at ENDO 2018, the annual meeting of the Endocrine Society, held in Chicago, IL. Obesity is a leading risk factor for type 2 diabetes; excess weight makes it more difficult for the body to use insulin the hormone that regulates blood glucose levels effectively. According to the Obesity Society, it is estimated that around 90 percent of adults who have type 2 diabetes are overweight or obese. In terms of treating obesity and type 2 diabetes, switching to a more healthful diet is often the first port of call. But, as Dr. Jakubowicz notes, it's not always what and how much we eat that might cause problems; it's also the time of day at which we eat. "Our body metabolism changes throughout the day," as Dr. Jakubowicz explains. "A slice of bread consumed at breakfast leads to a lower glucose response and is less fattening than an identical slice of bread consumed in the evening." With this in mind, Dr. Jakubowicz and colleagues sought to find out more about how the timing of food intake influences weight loss and blood glucose levels. Bdiet led to weight loss, reduced hunger The scientists enrolled 29 adults, of whom 18 were male and 11 were female, to their study. Subjects were aged 69, on average, and all of them had obesity and type 2 diabetes. The team randomly assigned each of the adults to two different diet groups for a total of 3 months. One group followed the "Bdiet," and this consisted of three meals per day: a large breakfast; a medium-sized lunch; and a small evening meal. The other group followed the "6Mdiet," which consisted of six small meals spaced throughout the day, plus three snacks. How weight loss makes us hungrier New research explains how weight loss may make us more hungry. The researchers tested the subjects' blood glucose levels every 2 weeks during the study. They also used continuous glucose monitoring to measure overall glucose levels, as well as spikes in blood glucose throughout the study.

18 The researchers found that subjects in the Bdiet group lost an average of 5 kilograms after 3 months, while those who followed the 6Mdiet gained an average of 1.4 kilograms. Hunger and cravings for carbohydrates also increased among subjects in the 6Mdiet group, but these reduced significantly for subjects who followed the Bdiet. The effects on blood glucose levels The scientists found that the fasting glucose levels of subjects in the Bdiet group fell by an average of 54 milligrams per deciliter (mg/dl) from 161 mg/dl to 107 mg/dl after 3 months, while fasting glucose levels of the 6Mdiet diet group fell by just 23 mg/dl, from 164 mg/dl to 141 mg/dl. Upon looking at overall mean glucose levels, the team found that these dropped by 29 mg/dl in the first 14 days from 167 mg/dl to 138 mg/dl for subjects who followed the Bdiet, while they fell just 9 mg/dl among the 6Mdiet diet group, from 171 mg/dl to 162 mg/dl. At 3 months, overall mean glucose levels decreased by 38 mg/dl in the Bdiet group from 167 mg/dl to 129 mg/dl compared with a reduction of 17 mg/dl in the 6Mdiet diet group, from 171 mg/dl to 154 mg/dl. Mean glucose levels during sleep did not reduce at all for those subjects who followed the 6Mdiet diet, but subjects in the Bdiet group experienced a reduction of 24 mg/dl from 131 mg/dl to 107 mg/dl at 3 months. Those who adhered to the Bdiet also required less insulin during the study period, with a reduction in 20.5 units each day. Subjects who followed the 6Mdiet diet, however, needed more insulin, with an increase of 2.2 units every day. Meal timing offers benefits in itself Notably, the study also revealed that participants adhering to the Bdiet experienced a significant decrease in overall blood sugar levels in as little as 14 days, even when the subjects themselves showed no weight loss. According to the researchers, this finding indicates that the timing of meals itself can help with blood glucose management, though weight loss can help to enhance the benefits. Overall, the team concludes that three meals each day with breakfast being the biggest may be of great benefit to people with obesity and type 2 diabetes. "This study shows," says Dr. Jakubowicz, "that, in obese, insulin-treated type 2 diabetes patients, a diet with three meals per day, consisting of a big breakfast, average lunch, and small dinner, had many rapid and positive effects compared to the traditional diet with six small meals evenly distributed throughout the day." These "positive effects" included "better weight loss, less hunger, and better diabetes control while using less insulin."

19 "A diet with adequate meal timing and frequency has a pivotal role in glucose control and weight loss." Breast Cancer Breast cancer: Obesity may hinder some treatments (Medical News Today: ) Obesity may be the reason that some cancers become resistant to drugs intended to stop the formation of new blood vessels that fuel tumor growth, according to recent research led by Massachusetts General Hospital in Boston. Could obesity prevent some cancer treatments from working correctly? In a paper now published in the journal Science Translational Medicine, the researchers explain how obesity and molecular factors linked to it may promote resistance to antiangiogenic inhibitors in breast cancer. Anti-angiogenic therapy which is designed to prevent the growth of blood vessels that feed tumors is showing mixed results in people with breast and other cancers. It is also well known that obesity raises the risk of many types of cancer, including breast cancer. The new study is the first to show a link between these two "observations." It also offers some molecular targets that might improve response to treatment with anti-angiogenic inhibitors. "Collectively," explains lead study author Dr. Joao Incio, of the Department of Radiation Oncology at Massachusetts General Hospital, "our clinical and preclinical results indicate that obesity fuels resistance to anti-vascular endothelial growth factor therapy in breast cancer via production of several inflammatory and pro-angiogenic factors, depending on the subtype of cancer." "Targeting these resistance factors," he continues, "may rejuvenate the use of anti-angiogenic therapy in breast cancer treatment." Angiogenesis and its inhibition

20 Angiogenesis is a natural process in the body that repairs and grows blood vessels. Some chemical signals stimulate the process and some chemical signals inhibit it. Levels of these are normally kept in balance so that blood vessels are made only when and where necessary. These processes also play a key role in cancer. Without a dedicated blood supply, tumors cannot grow and spread. However, they do so because they also generate chemical signals that trigger angiogenesis, resulting in the growth of blood vessels that keep them fed with oxygen and nutrients. Breast cancer: Body fat, not weight, poses major risk Learn how even women of a normal weight may be at increased risk of invasive breast cancer if they have high levels of body fat. Angiogenesis inhibitors are drugs that are designed to interfere with the chemical signals involved in angiogenesis. One of these drugs blocks vascular endothelial growth factor (VEGF), a signaling molecule that triggers growth of new blood vessels when it binds to proteins on cell surfaces. However, Dr. Incio and his colleagues found that obesity "promotes resistance to VEGF inhibitor therapy" by altering chemical signals in tumors. They note that it increases "interleukin-6 [IL-6] and possibly also fibroblast growth factor 2 [FGF-2] in the tumor microenvironment." The team also discovered with the help of "mouse models of cancer with and without obesity" that resistance to VEGF inhibitors may be overcome by using the "appropriate combination therapy." Obesity, anti-vegf therapy in breast cancer The researchers started their investigation by analyzing the results of a clinical trial that tested the anti-vegf drug bevacizumab, with and without chemotherapy, in 99 people with breast cancer. Promising results from early clinical trials had led to the accelerated approval of the drug for the treatment of metastatic breast cancer in the United States. But approval was then withdrawn after subsequent studies found no evidence of benefit to long-term survival. The trial that Dr. Incio and his colleagues investigated had shown that bevacizumab only benefited a small percentage of people. When the researchers analyzed the trial data, they found that people whose body mass index (BMI) was 25 or higher that is, if they fell into the overweight or obese category had larger tumors when they were diagnosed. On average, these people had tumors that were 33 percent bigger than those whose BMI was under 25.

21 In addition, tissue samples from people who had more body fat revealed that their tumors had a smaller blood supply, which is known to reduce the effects of chemotherapy. Further examination showed that people with a higher BMI had higher circulating levels of two molecules: IL-6, which promotes inflammation, and FGF-2, which promotes angiogenesis. There was also evidence that these factors were present in fat cells and adjacent cells in the tumors. The role of IL-6 and FGF-2 in mouse models In the next stage of the study, the researchers sought to confirm these findings in mouse models of breast cancer, both with and without obesity. They used two models: one of breast cancer that is positive for the estrogen receptor (ER), and the other of triple-negative breast cancer. They found, in the case of the obese mice, that the tumor microenvironments which contained many fat cells and had reduced levels of oxygen responded poorly to anti-vegf treatment. Morever, at a molecular level, responses differed depending on the breast cancer subtype. For example, in obese mice with ER-positive breast cancer, the fat cells and some types of immune cell had higher levels of several pro-inflammation and pro-angiogenic molecules including IL-6. The researchers found that when they blocked IL-6 in the ER-positive obese mice, the animals' responses to anti-vegf therapy improved and matched that of the lean mice. Obese mice with triple-negative breast cancer, on the other hand, showed higher levels of FGF-2 but not of IL-6. In their case, blocking FGF-2 raised their response to treatment to that of the lean mice. Blocking either of those molecules in lean mice with either type of breast cancer did not improve their response to anti-vegf treatment. "This is the first study to propose that markers such as body mass index could help personalize anti-vegf therapy, with blockade of molecules like IL-6 or FGF-2 for overweight or obese cancer patients." Dr. Joao Incio The researchers note that there are several inhibitors of the two pathways are already available. For example, to inhibit FGF-2 in their experiments, they used the widely used diabetes drug metformin, which has been showing promise in slowing the growth of some cancers.

22 Neuroscience Targeting these brain cells may aid weight loss (Medical News Today: ) A new study in mice investigating a brain region that controls the animals' impulses to "feed or flee" may have implications for obesity and anxiety in humans, according to its authors. What controls hunger? Researchers investigate. We know that both too much and too little food can be bad for us. Too little? Stunted growth. Too much? Obesity. The latter can also open the door to diabates, cardiovascular disease, and cancer. Studies show that the brain mechanisms that are involved in feeling hungry are highly complex. For instance, it seems that the nerve signals telling us when it is acceptable to eat are also fired from the same neurons that tell us when to run from danger. This finding has led scientists to consider whether investigating this mechanism further might provide clues to new treatment targets for obesity or psychiatric conditions that are linked to anxiety. The researchers behind the new study from Imperial College London in the United Kingdom set out to examine this brain mechanism, particularly in regard to a region of the brain called the ventromedial hypothalamus (VMH), which has been a subject of interest in obesity research for a long time. 'Control switch' for feed-or-flee mechanism In their study which has now been published in the journal Cell Reports the researchers used mice with neurons that had been genetically modified to be stimulated by a laser light. This modification allows scientists to toggle brain regions "off" and "on" by focusing the laser on the required area. When they did this to the VMH, they discovered that a group of cells called SF1 act as a "control switch" for the feed-or-flee mechanism. Can't keep the weight off? This may be why If you're struggling to stay slim, these brains cells may be to blame. SF1 cells are normally very active when mice are anxious such as when they explore a new environment but the researchers found that SF1 activity "dampens down" when the mice approach food.

23 The researchers say that SF1 effectively switches the activity of the VMH from defensive behavior to "need to feed" when the animals discover food. But when the animals' guards were dropped while feeding, the VMH switched back to defensive after eating. Further investigation showed that the researchers could manipulate SF1 activity in the mice. By making the mice more stressed, they found that they could switch the VMH back to defensive mode, which prevented the mice from being hungry. When the team administered drugs to the mice to increase activity in their SF1 neurons, the animals were less likely to want food and stored less fat. Dampening down SF1 activity made the mice feel less anxious, but it also made them eat more and put on more weight. "We have shown for first time," says study co-author Dominic Withers, of Imperial College London's Institute of Clinical Sciences, "that activity in this small population of brain cells acutely changes food intake. That hadn't been shown before." Eating disorders and stress in humans Withers and team believe that their findings could be relevant for studies of eating disorders and stress in human subjects. "There's a long-standing recognition," he says, "that things like obesity are associated with altered anxiety states and altered emotions and depression, so it is a bit of a chicken and egg as to which came first." Withers believes that small-molecule drugs targeting the SF1 neurons or other relevant "fine control mechanisms" in the brain may have greater potential than some existing treatments. These are less precise in targeting and therefore have a greater risk of creating unintended adverse effects. "At the moment we're only in the foothills of discovering how the brain works, particularly the appetite regulatory circuits. But when you start combining these new tools in the lab, we're really moving into a revolution in brain science." Dominic Withers World Happiness Day (Hindustan: )

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25 Sex Ratio (Dainik Jagran: )

26 ह ड ^Ȳ ȣड ȡ [क ȣ ɇऔर खन क पतल करन ȡ ȣदव ए ख त ɇत Ʌलग च ट क नजरअ द ज करन पड़ सकत ह ȡ ȣ(dainik Bhaskar: ) ȡ [क ȣ ɇऔर खन क पतल करन ȡ ȣदव ए ख त ɇत Ʌलग च ट क नजरअ द ज करन पड़ सकत ह ȡ ȣ पर च ट लगन क ब द \ È ` ã ȣऔर È ज स ǕǾ ह ज त ɇ@ Ǒ य ȣ क Ǖ ǽ ] Ʌन आए, त यह ȣȳसमझन Ȣ ȡǑ f ȣ खतर स ब हर ह कई ब र इस च ट क छह ȣ ȯऔर एक स ल क ब द भ Ǒ ȡ ǾǕ ह ज त ɇ@ख सकर ऐस ल ग ज Ǒ क ȣ ɇऔर खन पतल करन ȡ ȣदव ए ल रह ɇय कम ` Ĩ क Í ȯ` Û Ʌइसक सबस \ खतर ह त ह ȡ ȣओप ड Ʌहर ȣ ȯ7 स 8 ȣ ऐस आत ɇǔ Û Ʌच ट लगन क ȣ ɉब द सर Ʌच ट ȧग भ रत क पत चलत ह ȯ ȧभ ष Ʌइस Þɬ Ǘ ȣ Ȫ Ȫ ȡकहत ɇ@यह कहन ह आरएमएल ɅÛ ǗȪ [ ȣ ȡ [ Ʌ क ह ड ड. एलएन ǕÜ ȡक ड. ǕÜ ȡन बत य ऐस क स Ʌ Ȫ ɉ Ʌ ȡ Ǿ ȡ ȧबह त Ǿ ह त ह ^ f म गलव र क ओप ड और ȡ Ʌ ȣ ɉ, Ǖ, आम जनत और ȨÈ ɉक f अव यरन स ĤȪĒ ȡ रख ज एग ड. ǕÜ ȡन बत य ज Í ȯछ ट ह त ɇउनक Ħȯ और è क ब च ग प ह त ह यह Þ È ȨǑ Ȳ क खतर ह त ह 45 क ब द Ĥȡ ǙǓ Ǿ स Ħȯ और è क ब च Ʌअपन आप ग प आन लगत ह ऐस Ʌयह Þ È Ȩ ह न पर तम म तरह ȧ ȯ ȡǓ ȡȲ ǕǾ ह त ɇ@ ^ f Ǿ ȣह क ई भ च ट लगन क ब द एक ब र ȨÈ स Ǿ ȡ [ Ʌ@ख सकर तब जब ȣ क च ट लगन क ब द [और ज ब न Ʌलडख़ड़ हट Ǒ ȡ_ द ȣह ह ड ^Ȳ ȣड आज कई ब र च ट क 6 ȣ ȯऔर 1 स ल ब द भ Ǒ ȡ ǾǕ ह ज त ɇ 45 स \ ` Ĩ क å è और Í ɉक Ʌच ट लगन पर रहन ȡǑ f \ [

27 ȡ Ǿ ȡ ȣȳह न बढ़ रह ह ड ^Ȳ ȣक ȣ एलएनज प क ȯ h ड. [न बत य f È Ȣ Ʌ ȧवजह स भ Ï ȡ ȡ ह ड ^Ȳ ȣक क स बढ़ रह ɇ@इस र कन क एक ȣउप य ह य व ओ क ȡ Ǿ ȡज ए वह ह लम ट लग कर ȣब इक चल ए य क र Ĝȡ^ करत È स ट ȯã Ǿ ब ध Ǒ क ई f È Ȣ Ʌ Ʌ घ यल ह त भ ह, त उस त र त उपच र क f ȣ ȧ \ è ȡ पह च य ज ए ȡ समय स घ यल क इल ज ǕǾ ह सक ऐस ^ f È ɉ Ï ȡ ȡ \ è ȡ ɉ Ʌह ड ^Ȳ ȣ क ȡ [फ ल रहत ɇ@क छ ऐस ȣह ल ह ^ Ʌ Ȣक प चव म जल पर म जद 50 ब ड क ह ड ^Ȳ ȣ ȡ [हम श फ ल रहत ह ह ड ^Ȳ ȣक नजर अ द ज ȣȳकरन ȡǑ समय पर और ȡǑ ȣइल ज कर न