In the pancreas, various types of beta cells produce insulin, which aids in blood sugar regulation. According to Weill Cornell Medicine researchers, losing a particularly productive type of beta cell may contribute to the development of diabetes.
Loss of productive pancreatic cells can contribute to Diabetes: Study(Unsplash)
Dr. James Lo, associate professor of medicine at Weill Cornell Medicine, and colleagues measured gene expression in individual beta cells collected from mice in the study, which was published March 16 in Nature Cell Biology, to determine how many different types of beta cells exist in the pancreas. The researchers discovered four distinct beta cell types, one of which stood out. Cluster 1 beta cells produced more insulin than other beta cells and appeared to be better at metabolising sugar. The study also found that the loss of these beta cells may contribute to type 2 diabetes.
“Before this, people thought a beta cell was a beta cell, and they just counted total beta cells,” said Dr. Lo, who is also a member of the Weill Center for Metabolic Health and the Cardiovascular Research Institute at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center. “But this study tells us it might be important to subtype the beta cells and that we need study the role of these special cluster 1 beta cells in diabetes.”
Drs. Doron Betel, Jingli Cao, Geoffrey Pitt and Shuibing Chen at Weill Cornell Medicine teamed up with Dr. Lo to carry out the study.
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The investigators used a technique called single-cell transcriptomics to measure all the genes expressed in individual mouse beta cells and then used that information to group them into four types. The cluster 1 beta cells had a unique gene expression signature that included high expression of genes that help cellular powerhouses called mitochondria to break down sugar and power them to secrete more insulin. Additionally, they could distinguish the cluster 1 beta cells from the other beta cell types by its high expression of the CD63 gene, which enabled them to use the CD63 protein as a marker for this specific beta cell type.
“CD63 expression provided us a way to identify the cells without destroying them and allowed us to study the live cells,” he said.
When the team looked at both human and mouse beta cells, they found that cluster 1 beta cells with high CD63 gene expression produce more insulin in response to sugar than the three other types of beta cells with low CD63 expression.
“They are very high-functioning beta cells,” Dr. Lo said. “We think they may carry the bulk of the workload of producing insulin, so their loss might have profound impacts.”
In mice fed an obesity-inducing, high-fat diet and mice with type 2 diabetes, the numbers of these insulin-producing-powerhouse beta cells decreased.
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“Because the numbers of cluster 1/high CD63 cells went down, you may have less insulin production, which may play a major role in diabetes development,” he said.
Transplanting beta cells with high CD63 production into mice with type 2 diabetes restored their blood sugar levels to normal. But removing the transplanted cells caused high blood sugar levels to return. Transplanting low CD63 production beta cells into the mice didn’t restore blood sugar to normal levels. The transplanted low CD63 beta cells instead appeared dysfunctional.
The discovery may have important implications for the use of beta cell transplants to treat diabetes, Dr. Lo said. For example, it may be better to transplant only high CD63- beta cells. He noted that it might also be possible to transplant fewer of these highly productive cells. Dr. Lo’s team also found that humans with type 2 diabetes had lower levels of high CD63 beta cells compared to those without diabetes.
Next, Dr. Lo and his colleagues would like to find out what happens to the high CD63-producing beta cells in mice with diabetes and how to keep them from disappearing.
“If we can figure out how to keep them around longer, surviving and functional, that could lead to better ways to treat or prevent type 2 diabetes,” he said.
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They would also like to study how existing diabetes treatments affect all types of beta cells. GLP-1 agonists, which help increase the release of insulin in people with diabetes, interact with high and low CD63-producing beta cells.
“Our study also shows that GLP-1 agonists might also be a way to get the low CD63-producing beta cells to work better,” Dr. Lo said.
This story has been published from a wire agency feed without modifications to the text. Only the headline has been changed.
Heart disease is no longer a man’s disease alone – it is the leading cause of death in women globally, more than all the cancers combined yet in women, it is still under recognized and under treated often leading to suboptimal care and poor outcomes, majority of which are preventable. Heart disease may be considered by some to be more of a problem for men however, it’s the common cause of death for both women and men and some heart disease risk factors and symptoms in women can differ from those in men.
Heart disease risk factors and symptoms of a heart attack in women (Photo by engin akyurt on Unsplash)
In an interview with HT Lifestyle, Dr Teffy Jose, Consultant Cardiology at Aster Medcity in Kochi, shared, “Most common is a heart attack due to blockage which had formed inside a major coronary artery (coronary artery disease). However, women often have chest pain with no evidence of blockage in major coronary arteries – Ischemia with No Obstructive Coronary Artery disease (INOCA) due to disease in smaller blood vessels(microvascular disease). Women are also prone to spontaneous dissections or spasm in coronary arteries and stress induced weakness of the heart (stress cardiomyopathy). Women, especially those with rheumatological diseases can have involvement of their heart valves.”
What are the risk factors?
Dr Teffy Jose revealed, “Women at mid-life near or after menopause are at the highest risk. The hormone estrogen raises the level of HDL (good) cholesterol and helps to keep the arteries flexible. After menopause, drop in estrogen levels occur leading to higher risk of heart disease. Traditional risk factors like high blood pressure, diabetes, high cholesterol levels especially bad cholesterol and smoking are the most important risk factors for heart disease in both men and women.”
She added, “Women with diabetes are more likely to develop heart disease than men with diabetes. 3-fold risk of fatal coronary artery disease is seen in them as compared to non-diabetic women. Emotional stress and depression affect women’s hearts adversely. Also, this may make it more difficult to follow a healthy lifestyle and adhere to the recommended treatments. Additional risk factors include family history of heart disease, obesity and physical inactivity, rheumatological diseases, pregnancy complications such as high blood pressure or diabetes in pregnancy.”
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Dr Ravindranath Reddy DR, HOD and Senior Consultant Interventional Cardiologist at BGS Gleneagles Global Hospital in Bengaluru, said, “Several traditional risk factors for coronary artery disease, such as high cholesterol, hypertension, diabetes, smoking, and obesity, affect both women and men, but these traditional risk factors tend to cause more severe disease in women than in men.” Other risk factors that may play a bigger role in the development of heart disease in women include –
• Diabetes: Women with diabetes are two to four times more likely to develop heart disease than men with diabetes and have an increased risk of having a silent heart attack.
• Hypertension: Women over age 60 are more likely than men to have hypertension but less likely to have it managed well.
• Smoking: Women who smoke are three times more likely to have a heart attack compared with men who smoke.
• Dyslipidemia: A low level of HDL cholesterol (“good” cholesterol) is more closely linked with coronary heart disease for women than for men.
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• Emotional stress and depression: Women are more likely to experience psychosocial stress and depression, which may play an important role in developing cardiovascular diseases.
• Physical Inactivity: In general, regular exercises are not routinely practiced by women. Lack of physical activity is a major risk factor for heart disease.
• Menopause: Low levels of estrogen after menopause increase the risk of developing disease in smaller blood vessels.
• Pregnancy complications: Pregnancy-associated hypertension, Gestational diabetes greatly raises a person’s risk of developing hypertension, diabetes later in life, which are responsible for developing cardiovascular diseases.
• Peripartum cardiomyopathy: In this condition, which is encountered during pregnancy and the peripartum period, cardiac muscle becomes weak, and chambers get dilated, leading to severe congestive heart failure.
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• Family history of early heart disease: This appears to be a greater risk factor in women than in men.
• Autoimmune diseases: Rheumatoid arthritis, lupus, and other autoimmune diseases, which are more commonly seen in women, may increase the risk of heart disease.
• Obesity: Women face a higher risk of obesity when they go through menopause. They’re also more likely to gain abdominal (belly) fat, which is linked to a higher risk for heart disease.
• Polycystic ovary syndrome (PCOS): PCOS raises a person’s cardiovascular disease risk. People with PCOS often develop individual risk factors such as diabetes, high blood pressure, high cholesterol, and sleep apnea.
• Oral contraceptive therapy: Use of oral contraceptive pills may raise a person’s risk for cardiovascular disease.
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• Menopause: Estrogen helps reduce a person’s risk of cardiovascular disease but menopause and surgical menopause cause estrogen levels to drop. As a result, a person faces a higher risk for developing cardiovascular diseases.
Symptoms of a heart attack:
Dr Teffy Jose said, “The most common symptom in both men and women is classical chest pain or discomfort which may spread along one or other arm. However, women may experience a wider spectrum of symptoms which may or may not be associated with chest discomfort. This may include jaw, neck or back pain, shortness of breath, nausea or vomiting, upper abdominal discomfort, palpitation, excess sweating, giddiness or fainting or extreme fatigue. Sometimes, a heart attack may be silent especially in elderly or diabetic.”
Talking about what needs to be done for your heart, she suggested, “Women of all ages should take their heart health seriously. Get annual check ups to assess heart health risks. Living a healthy lifestyle reduces your risk of heart disease. Regular moderate intensity aerobic physical exercise of at least 150 minutes /week like walking, swimming or cycling keeps the heart healthy. Including short bursts of jogging or brisk walking in your regular walk gives the additional boost of interval training. Find ways to relax like yoga or meditation and seek help from a professional when stressed out. Eat balanced diet, get at least 7-8 hours of sleep and maintain a healthy weight. Quit smoking and limit your alcohol intake.”
She opined, “In general, treatment of heart disease in men and women is same including medications, angioplasty, or coronary artery bypass surgery. Become knowledgeable about your numbers of blood pressure, blood sugar, blood cholesterol with strict adherence to lifestyle modifications and guideline directed therapy. Recognizing symptoms and risks, making lifestyle changes and getting timely care can save a woman’s life and thus the family and society at large.”
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According to Dr Ravindranath Reddy, the most common heart attack symptom in women is the same as in men: chest pain, pressure, or discomfort that lasts more than a few minutes or comes and goes. However, chest pain is not always severe or even the most noticeable symptom, particularly in women. Women are more likely than men to have heart attack symptoms unrelated to chest pain, such as:
Mumbai: India has set an ambitious goal to eliminate TB by 2025 five years ahead of the global goal of 2030, but several years of progress made in the elimination of tuberculosis (TB) have come undone due to the disruption caused by the ongoing COVID-19 pandemic. For the first time in over a decade, mortality due to TB has increased worldwide, and there are indicators that the incidence may have increased as well. The disruptions caused by COVID caused individuals to avoid contact with healthcare, and this delayed health-seeking and stigma have possibly contributed to the same.
The COVID-19 pandemic has “reversed years of progress made in the fight to end TB,” says the World Health Organisation (WHO). COVID-19 and TB are both infections that affect the lungs. COVID-19 being an acute infection that also affects the immune system can result in the reactivation of latent infections including TB. The prevalence of TB among COVID-19 patients is 0.37 – 4.47 per cent in different studies. The WHO estimates that these COVID-19-related disruptions in access to TB care could cause an additional half a million TB deaths. During the lockdown, in the first quarter of 2020, reporting of TB cases was reduced by 26 per cent as reported by the health authorities. This has been a major setback for the National TB Elimination Programme.
The pandemic has not only been a disruptor but also an enabler, one of the key learnings from COVID was the impact of technology in accelerating equitable access to quality healthcare. The tremendous scale-up of genome sequencing and knowledge sharing enabled greater and faster discoveries, including the democratisation of molecular diagnostics like RT-PCR, which before COVID was held by a few multinational companies. It is also evident that bacterial infections like TB and fungal infections, which are known to be secondary to viral infections, can become difficult to treat in absence of accurate diagnostics, especially with the increase in drug resistance. It is also clear that no health problem can be related to only a ‘poor world’ problem. In the era of global travel, infectious diseases, and antimicrobial resistance is indeed a global issue, which can potentially derail any success made in other health conditions.
Digital technologies facilitating TB diagnosis
Online consultations have made access to doctors easier, especially when distances have been prohibitive. Rapid turnaround times, with new-age diagnostics tools, have made treatment initiation quicker. Tests such as radiographs can be digitised and reported remotely. All of these also dependent on internet connections, ease of transporting specimens and overall access, and a lot of work needs to be done to make these universal.
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As there are two forms of TB, pulmonary, which affects the lungs and extrapulmonary which affects the other organs. There is a wide range of tests available for diagnosis. This spectrum ranges from the visualisation of the bacteria in a specimen to the demonstration of the DNA and whole genome sequencing of the bacterial genome. There are supplementary tests like ADA, IGRAs and other simple blood tests like ESR, that can be used to assist in the diagnosis of extrapulmonary TB. “The complexities of clinical presentations and the wide range of diagnostic tests available highlight the role of artificial intelligence (AI) and machine learning (ML) tools to support the National Tuberculosis Elimination Programme. Selection of the right test/s for the prevailing clinical situation and the appropriate interpretation of the test results is vital,” remarked Dr Rohini Kelkar, Senior Consultant, Infectious Diseases, Clinical Microbiology and MolecularMicrobiology, Metropolis Healthcare Ltd.
With widespread growth in the area of digital technologies to facilitate TB diagnosis. Timely medical intervention with the help of telemedicine has changed the scenario, especially in rural areas. “Mobile diagnostic labs equipped with digital diagnostic tools have paved the way to enhanced access to healthcare facilities. Moreover, rapid molecular testing kits can detect the presence of drug-resistant strains with high precision in diagnosing TB. Using digital X-rays with computer-aided detection (CAD) also reduces the chances of human error and therefore misdiagnosis,” voiced Raghavendra Goud Vaggu, Global CEO, EMPE Diagnostics.
Speaking on the role of digital technologies aiding in TB detection, Anirvan Chatterjee, Co-Founder and CEO, HaystackAnalytics, shared, “AI in radiology, rapid molecular assays and compressive screening for drug resistance using genome sequencing are the current disruptions which will upend the entire paradigm of TB diagnosis and treatment. Genomics provides the opportunity to enable personalised treatment for every TB case, basis which there is expected to be a reduction in the incidence of drug resistance TB, which will be critical for TB elimination. With access to whole genome sequencing in the public and private health sectors, nationwide, the existing infrastructure will be able to provide these tests for all strata of society.”
Challenges in diagnosing TB
TB remains one of the world’s top infectious killers and has aptly been labelled ‘Captain of the men of death’. Without a rapid and accurate diagnosis, it can be mistaken for other conditions. TB mimics several conditions including cancer, hence a high degree of suspicion is required.
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TB diagnosis is exacerbated by a multitude of challenges. While the stigma attached to the disease continues to be a significant contributor among people failing or delaying seeking timely medical help, there are other significant challenges as well. “Another challenge faced are the time-consuming tests. As the growth of the bacteria on culture remains the ‘gold standard’ for diagnosis followed by testing the growth on culture for susceptibility to different antimicrobials. This is referred to as phenotypic testing. These tend to be time-consuming because Mycobacterium tuberculosis the organism that causes TB is extremely slow growing,” shared Dr Kelkar.
Sharing his views on the challenges in diagnosing TB, Dr Lancelot Pinto, Consultant Pulmonologist and Epidemiologist, PD Hinduja Hospital & MRC, Mahim, “A majority of patients with the disease seek help in the private sector. Diagnosis and treatment in the private sector are often non-standardised. The quality of care often tends to be suboptimal. There is a need for education of private practitioners to recognise the disease early, ask for newer molecular tests which have significantly higher accuracy than the conventional sputum smear microscopy, and start treatment as soon as the diagnosis is made. The overreliance on chest radiography and under-utilisation of molecular tests for diagnosis are often the single leading cause of diagnostic delays. Multidrug-resistant tuberculosis, which is a significant contributor to the burden of disease can only be recognised if appropriate testing is done, and practitioners need to be educated about the same.”
Detecting pulmonary TB, that is, TB infection in the lungs in adults is less of a challenge any longer, but there still exists some challenges in detecting paediatric TB and extrapulmonary TB (TB infection in organs other than lungs). However, these are likely to get resolved with current updates in the diagnostic systems. “The greatest challenge still is the availability of universal drug susceptibility test (Universal DST– testing to know among all available drugs which will work and which will not) for all patients. Current microbiological methods for drug susceptibility cannot be scaled, and remain unaffordable. Not only is the technology non-scalable, but it is also unreliable for several drugs and remains a high biohazardous workflow,” stated Chatterjee. He further added, contrary to this, whole genome sequencing is highly scalable, and with increased uptake can be as affordable as an RT-PCR test.
The other crucial aspect that needs immediate attention is the rising burden of drug-resistant TB strains, commenting on this Goud Vaggu added, “Drug-resistant TB strains are on the rise and this makes diagnosis and treatment complicated. In addition, co-infection with other illnesses can impede the treatment plan. Many times, the symptoms of TB overlap with that of other respiratory disorders, therefore, it is tricky to diagnose the disease solely based on symptoms.”
There are other ‘Mycobacteria’ referred to as Nontuberculous mycobacteria which can mimic TB. Sometimes infections of the lungs are caused by other bacteria (like nocardiosis) and fungi (histoplasmosis), present like TB. A wrong diagnosis can be disastrous to the patient, hence the need for strong laboratory diagnostic support. “The introduction of nucleic acid amplification tests (NAAT) has been a significant advance in the rapid diagnosis of tuberculosis. These tests are routinely used at most centres in the country. They identify the presence of the DNA of Mycobacterium tuberculosis and can further be used to identify genes indicating resistance to the drugs used for treatment,” observed Dr Kelkar.
Also, the symptoms of TB can often be non-specific. A prolonged cough, fever, weight loss, and loss of appetite can mimic multiple different diseases. Patients often shop from doctor to doctor and unless the prolonged nature of the symptoms is recognised, each doctor often treats the patient in isolation. This leads to misdiagnosis very often, multiple courses of antibiotics, and delays in diagnosis. To improve the diagnostics of TB, one needs to have a very low threshold for suspecting the disease, especially in a country such as India which is endemic for TB.
Dr Pinto added, “Newer molecular diagnostic tests have become cheaper over the years, more accessible, and have a quick turnaround time. Practitioners need to be sensitised about the superiority of such tests and should be incentivised and encouraged to ask for such newer molecular tests rather than conventional sputum microscopy. We need to improve access to such tests, even in rural India, if we want to eradicate the disease.”
Bridging the gap to limit the misdiagnosis of TB is non-negotiable. In several pockets, the extent of drug resistance is so high, the success of the TB elimination programme is being undermined. For every misdiagnosed TB case there are multiple secondary cases of drug-resistant TB, which means less number of drugs are available to treat the patient. “A therapy driven by universal DST is going to be critical for reducing misdiagnosis in TB. This will help in prescribing the right medication for the right drug resistance profile, hence earlier treatment and lesser transmission,” remarked Chatterjee.
Misdiagnosis of TB is a serious concern. False-negative results are a major player in leading to a diagnostic error. Misdiagnosis not only leads to delayed treatment, but it can also at times be fatal for the patient. Goud Vaggu stated, “The gap can be bridged with the use of AI and ML as these technologies enhance the accuracy of diagnosis. Healthcare professionals can evaluate the results of diagnostic tests such as X-rays or molecular tests with the help of AI, thus lowering the likelihood of a misdiagnosis. In addition, AI and ML have significantly contributed to the development of personalised medicine. These algorithms help in predicting the best treatment regimen for a particular population of patients.”
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In March 2018, Prime Minister Narendra Modi committed to eliminating TB in India by 2025. On World TB Day while inaugurating the One World TB Summit the PM once again emphasised the need for a collective approach to eliminating this age-old disease. The ongoing pandemic has undone years of progress made in TB elimination but deploying technology in detection, diagnosis and treatment could bolster the fight against TB. With increasing awareness through campaigns and advertisements the stigma related to the disease needs to be done away with as it remains one of the major deterrents in people seeking treatment infected by the disease.
Washington: According to study, normalising mindfulness practices can improve emotional well-being of a graduate student. The study was published in the journal, ‘PLoS One’
“Because of the state of graduate student mental health nationally, there’s a tangible need for a concrete intervention like this,” says Susan Hagness, a professor of electrical and computer engineering and one of the study’s co-authors. “How do we help our students develop resiliency and a really robust toolbox, both professional and personal, to flourish in an environment where there’s inevitably going to be stress? We’re getting the word out that investing in self-care is important, and it’s normal.”
Cultivated through practices such as meditation, yoga or prayer, mindfulness centers around being in the present moment in an open, non-judgmental, curious, accepting way. In recent years, corporate giants like Google, Intel, Nike, General Mills, Target and others have included mindfulness in employee development activities to reduce employee stress and burnout, and enhance their focus, creativity, job satisfaction and wellness.
The UW-Madison research included two studies involving a total of 215 participants across six academic semesters at UW-Madison (and the final four semesters concurrently at the University of Virginia). In the study, engineering graduate student cohorts participated in an hour-long, instructor-led mindfulness training program once a week for eight weeks. This “Mindful Engineer” curriculum was based on an existing Center for Healthy Minds training, “Cultivating Well-Being in the Workplace,” and drew on neuroscience-derived concepts described in The Emotional Life of Your Brain, a book co-authored by center founder Richard Davidson, a professor of psychology and psychiatry at UW-Madison.
Each weekly session built on the previous weeks’ content; students learned about the brain’s neuroplasticity and how it can be trained to change responses to emotions. They explored the six dimensions of emotional style (attention, self-awareness, resilience, outlook, social intuition and sensitivity to context) and learned strategies for creating and maintaining healthy mental and emotional habits. The graduate students also received training in mindfulness meditation and other contemplative practices, cognitive skills and techniques, and each session included time for meditation and cognitive exercises.
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In post-training surveys, students reported significantly improved emotional well-being, a more positive outlook, fewer negative emotions and increased mindfulness. Over the same period, the control groups (which received training at a later date) noted steady or decreased well-being. Mindfulness participants also reported they were better able to manage stress and anxiety, deal positively with setbacks, work more effectively with colleagues and focus on their research.
“What was beautiful is that we saw a really consistent pattern of results across all of the cohorts we did this study with,” says Pelin Kesebir, an honorary fellow with the Center for Healthy Minds and a study co-author.
Somewhat surprisingly, the researchers also found that engineering graduate students were open to mindfulness training and were not only highly satisfied with it, but also enjoyed the opportunity to connect with other graduate students.
“In the literature, there’s evidence that engineers are less likely to seek treatment for mental health issues — so our team wondered if engineers would engage with this,” says Wendy Crone, a professor of engineering physics and mechanical engineering and a study co-author. “The answer is that they did, and we had great cohorts throughout the project.”
The researchers say they’d like mindfulness training to be integrated into the graduate student experience in the future. In the meantime, they recommend the Healthy Minds Program app, which offers podcast-style lessons and seated and active meditations.
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And while the researchers focused on engineering graduate students, they note that adopting a mindfulness practice can be a positive step for anyone.
“Modest investments of your time can result in really significant benefits to your overall well-being,” says Hagness. “Small investments in self-care can have long-term rewards.”