Selective ER-ß agonists alleviate neuronal deficits in insulin-resistant estrogen-deficient rats.

OBJECTIVE: The present study aimed to determine the effect of estrogen receptor (ER) agonists on depression and memory impairment in insulin-resistant ovariectomized (OVX) rats. METHODS: Rats underwent bilateral ovariectomy, and low-dose streptozotocin (STZ) and a high-fat diet (58% fat, 25% protein, and 17% carbohydrates as a percentage of kilocalories) were administered to induce an estrogen-deficient insulin-resistant state. After 1 week of STZ administration, rats were treated with 17ß-estradiol (17ßE2) and selective ER-α (propylpyrazoletriol) and ER-ß (diarylpropionitrile) agonists (10 µg/kg subcutaneously). Memory was evaluated using the Morris water maze and depression using the forced swim test. RESULTS: Treatment with selective ER-ß agonist and 17ßE2 but not with selective ER-α agonist significantly modulated the neurobehavioral deficits in insulin-resistant OVX rats. These neurobehavioral parameters were further correlated with brain-derived neurotrophic factor (BDNF) levels and acetylcholinesterase (AChE) activity. Selective ER-ß agonist and 17ßE2 significantly modulated BDNF levels and AChE activity in insulin-resistant OVX rats. Significant increases in estradiol and uterine weight were observed in 17ßE2-treated rats, but selective ER agonists did not show any effect. CONCLUSION: ER-ß agonist can be an effective strategy for the mitigation of memory loss and depression in an estrogen-deficient insulin-resistant state without all of the deleterious feminizing effects that occur with the use of 17ßE2.

Lactobacillus plantarum MTCC 9510 supplementation protects from chronic unpredictable and sleep deprivation-induced behaviour, biochemical and selected gut microbial aberrations in mice.

AIM: Here, we evaluated any beneficial effects of a potential probiotic bacterial strain (Lactobacillus plantarum MTCC 9510) in two different stress paradigms in mice. METHODS AND RESULTS: Lactobacillus plantarum MTCC 9510 (2 × 1010 CFU per mice) was supplemented to male Swiss albino mice either subjected to chronic unpredictable mild stress or sleep deprivation (SD) stress. Various behavioural and biochemical tests along with selected gut bacterial abundances were determined. Lactobacillus plantarum MTCC 9510 supplementation prevented stress-induced behavioural despair (depression, anxiety, learning and memory, stereotypic behaviour), oxidative stress markers and inflammatory cytokines in brain and serum. Its supplementation also improved gut and blood brain barrier integrity. It also affected caecal short-chain fatty acids along with the promotion of Lactobacillus sp. and reduction in Enterobacteriaceae abundances. We also observed that two different stresses variably affected various behavioural and biochemical changes but L. plantarum MTCC 9510 supplementation most effectively prevented all these changes. CONCLUSION: We provide evidence that positive modulation of the selected beneficial gut microbial population could serve as a viable strategy to neutralize day-to-day and SD stress-induced pathological alterations. SIGNIFICANCE AND IMPACT OF THE STUDY: Therapeutic potential of this/other probiotic strains in tackling the deleterious neurobiological effects on exposure to various stress-related conditions can be explored.

A novel cobiotic-based preventive approach against high-fat diet-induced adiposity, nonalcoholic fatty liver and gut derangement in mice.

BACKGROUND: High-fat diets (HFDs) induce systemic inflammation, gut microbial derangements and disturb metabolic homeostasis, resulting in weight gain, insulin resistance and nonalcoholic fatty liver (NAFL). Numerous antioxidants and prebiotic/probiotics per se may prevent HFD-associated comorbidities, but there are no reports related to their combination. OBJECTIVE: In the present study, we aim to evaluate a cobiotic combination of lycopene (antioxidant) and isomalto-oligosaccharides (IMOs, a prebiotic) for prevention of HFD-induced alterations. DESIGN: Male Swiss albino mice were fed either normal pellet diet (NPD) or HFD and lycopene (5 and 10 mg kg(-1)), IMOs (0.5 and 1 g kg(-1)) or their combination for 12 weeks. Systemic adiposity, glucose tolerance, insulin sensitivity, feeding regulators in hypothalamus, hepatosteatosis and liver inflammation, cecal short chain fatty acids (SCFAs), serum inflammatory cytokines, gut morphology and alterations in selected gut microbes were studied. RESULTS: Lycopene, IMOs and their combination prevented weight gain, adiposity, improved adipose tissue fat mobilization and reduced insulin resistance. Hypothalamic orexigenic and anorectic genes have also been modulated by these treatments. Dietary interventions prevented NAFL-like symptoms and improved glucose homeostasis. Improvement in selected gut microbial abundance and SCFA concentration along with reduced systemic inflammation, metabolic endotoxemia and improved ileal and colonic health were observed in mice supplemented with lycopene, IMOs and their combination. Interestingly, cobiotic combination synergistically improved many of the HFD-induced alterations. CONCLUSION: The present work provide evidence that new approach based on cobiotic combination (antioxidant plus prebiotic) can be employed to develop novel class of functional foods for their application against HFD-associated pathological complications.

Competency based medical education as an accelerator to end tuberculosis (End TB) in India.

Tuberculosis is a major public health challenge in India and has been targeted for elimination. The National Tuberculosis Elimination Program (NTEP), in its all-previous forms has been one of the leading national health programs with the institutionalized engagement of medical colleges. This article outlines the mechanisms for medical college engagement in NTEP and discusses how the recent adoption of competency based medical education (CBME) for graduate medical education provides an opportunity for strengthening medical college participation in NTEP. The authors propose that for an accelerated progress towards 'End TB' in India, there is need for scaling up faculty development programs, focusing upon operational and implementation research, adopting a practical approach in designing curriculum for graduate medical teaching and creation of online repository of training material as well as the data bank of post-graduate theses, and other published and unpublished research work. Alongside, these efforts need to be supplemented by the professional associations of medical specialties and the governments through organizing annual national scientific and policy forum; and the capacity building of postgraduate students and faculty members in operational research, amongst others. The adoption of CBME has-arguably- created an opportunity for innovations at medical college level to support End TB. The learnings could also be utilized for enhanced engagement of medical colleges in other national health programs. India's experience on medical college engagement in tuberculosis elimination could serve as a 'good practice' for TB endemic countries in other parts of the world.

Effect of sesamol on the pathophysiological changes induced by surgical menopause in rodents.

OBJECTIVE: Estrogen deprivation after menopause is associated with increased oxidative stress. The present study was designed to study the role of sesamol (3,4-methylenedioxyphenol), a phenolic antioxidant and anti-inflammatory molecule, in oxidative stress-induced changes in three major affected organ systems, the central nervous system, the cardiovascular system and the skeletal system in ovariectomized rats, a widely used animal model of menopause. DESIGN: Animals were divided into eight different groups (n = 6-8). Five groups underwent ovariectomy; starting from the 2nd day of ovariectomy, three of these groups received sesamol (2, 4, 8 mg/kg) and the fourth group was administered α-tocopherol (100 mg/kg) orally for 7 weeks. The fifth ovariectomized group did not receive any drug treatment. Rats in the naïve (non-operated) and sham-operated groups did not receive any drug treatment, while the eighth group consisted of naïve animals which were treated for 7 weeks with only sesamol 8 mg/kg orally daily. After 7 weeks, animals were subjected to testing of behavioral paradigms (elevated plus maze and Morris water maze for assessment of anxiety and memory, respectively) 24 h after the last dose. After behavioral studies, animals were sacrificed for various biochemical estimations. RESULT: Administration of sesamol (2, 4, 8 mg/kg orally) to ovariectomized rats for 7 weeks significantly and dose-dependently improved memory, attenuated anxiety, decreased oxidative stress in brain, improved the serum lipid profile and reduced serum tumor necrosis factor-α levels when compared with ovariectomized control rats. Similar protective effects were observed in the case of the skeletal system studies. Sesamol increased the bone ash content and the mechanical stress parameters in treated groups. CONCLUSION: The results emphasize the involvement of oxidative stress and inflammation in the development of ovariectomy-induced pathophysiological changes and point towards the therapeutic potential of sesamol in menopausal pathologies.

Study of factors leading to treatment delay in new sputum positive pulmonary tuberculosis patients and its impact on sputum conversion.

Our study was done to identify patient or health system related delay in diagnosis of treatment naïve sputum positive PTB patients and its impact on sputum conversion at 2 months. A total of 280 patients were enrolled and followed up for 2 months following which repeat sputum examination was done. Detailed clinical history was taken with emphasis on duration of symptoms, day of presentation, diagnosis and starting of therapy. The median(range) of delay in treatment initiation was 15 (0-82) days, most commonly because of delay due to the health system. Patients with positive sputum at the end of two months had significantly higher delay in treatment initiation (p < 0.05). Being remote (>5 km) from a health provider, being an unskilled labourer, and visiting a private practitioner were associated with delay in diagnosis. Eradication of tuberculosis in India requires training of health professionals, intersectoral cooperation and better public outreach.

Drug resistant tuberculosis among elderly: Challenges.

The article deals with challenges faced by the geriatric populations while on MDR treatment. Risk factors like tobacco use, low socio-economic status, previous disease, longer delays in seeking treatment and reduced mobility are some of the challenges while initiating MDR treatment. Other issues like drug-related adverse events and increased co-morbidity pose a major challenge while treating patients. Susceptibility among the geriatric age group includes various anatomical and physiological changes including nutritional deficiencies and co morbidities.

Evaluation of a new quality assessment strategy for blinded rechecking of random sputum smears for TB in Delhi, India.

This study was conducted at the New Delhi Tuberculosis Center, Delhi, India, from 1 January 2006 to 31 December 2007 to assess the feasibility of implementing random blinded rechecking (RBRC), a quality assurance strategy, and its impact on the performance of tuberculosis smear microscopy in Delhi, RBRC activities are carried out monthly at District Tuberculosis Centers (DTCs). Forty thousand five hundred and six slides were rechecked during the study period. RBRC, as a method of quality assurance was found to be feasible for a large application. The quality of sputum microscopy improved, with a significant reduction in the number of false positive and false negative errors in 2007 compared to 2006. The number of microscopy centers reporting high false errors decreased significantly in 2007.

Tuberculosis: Newer diagnostic tests: Applications and limitations.

A public health worry as is Tuberculosis (TB) has been making more than 10 million people globally suffer from its terror and causing more than 2 million people worldwide to lose their lives every year. Mankind is putting all its efforts, since the discovery of the causative bacilli, to come up with some dramatic improvements in providing high-quality TB diagnostic services. Nevertheless, it poses a challenge and many people with TB remain use only smear microscopy for diagnosis. In an environment where transmission is becoming easier by the day the challenge becomes burdensome once disease gets associated with drug resistance, HIV, other diseases, etc. It becomes of paramount importance to address this biggest public health challenge delivering timely diagnosis using advanced technologies. Initial microscopic examination forms the backbone of TB diagnosis since 100 years along with clinical confirmations. Newer advanced diagnostic tools coming into play are genotypic assays (LPA, CBNAAT, LAMP) that are rapid molecular tests, and culture methods (liquid culture media) with standard drug susceptibility testing assays. Program ideates to correlate these rapid molecular diagnostics with turn-around time (TAT) as low as around 2 hours, with conventional standard methods. These help in reinforcing the diagnostic capacities and also provide identification of drug resistance patterns for few most important first line and second line drugs. The present day developments have brought these tests to near-patient point of care. Culture tests (liquid culture media) are gold standard technique for the analysis of TB with its increased sensitivity and highest quality over all others. An on-going search under TB diagnostics is to find an efficient, reproducible, cost effective tool with minimal infrastructure requirements. This review conveys the advances made over the past decades in the diagnosis of the disease and drug resistance.

Covid-19 and social stigma: Role of scientific community.

COVID-19 has led to stigma and discrimination among various groups of people in different populations. Healthcare workers caring for those affected by COVID-19,3 people who have recovered from COVID-19,4 those belonging to lower socioeconomic groups, those having particular religious and racial identities have all been at the receiving end of the discrimination. COVID-19 has led to reinforcement of preexisting stereotypes against various groups. For instance, in Italy, in weeks before the national lockdown started, a state of emergency was declared but everyday life was going on as always, the sentiment toward the Chinese community changed: their restaurants were left empty, more and more parents did not want their children to go to school if they had a Chinese classmate, and a high-profile politician said on TV that 'we have all seen them eat live mice'.

Lessons to be learnt from 100 year old 1918 influenza pandemic viz a viz 2019 corona pandemic with an eye on NTEP.

The article is about the 1918 H1N1 flu pandemic also called the "Spanish flu" which killed 50 million plus people worldwide, and the coronavirus pandemic (Covid-19) which has spread in the world at an alarming pace. As of now there are 11,327,790 cases and 532,340 deaths globally. Aim of this article is to draw conclusions and share knowledge from both the pandemics and apply these lessons in other health programmes.

Morbidity and mortality trends of Covid 19 in top 10 countries.

The present article highlights morbidity and mortality trends of Covid 19 in the last 3 months in top 10 countries of the world. In spite of efforts being undertaken, all countries are showing an increasing trend in terms of morbidity and mortality. The order of countries in terms of mortality and morbidity has changed in the last 3 months. Various efforts are being undertaken by WHO and other agencies world over including the vaccine development initiative.

Laboratory diagnosis of novel corona virus (2019-nCoV)-present and the future.

BACKGROUND: In December 2019 a novel coronavirus SARS-CoV-2 emerged in the Hunan seafood market in Wuhan, China, and soon became a global health problem. Since its outbreak, SARS-CoV-2 has had a major impact on clinical diagnostic laboratories. The scientific community has quickly risen to the occasion and reports of new developments have arrived at an unprecedented scale. At present, there is a growing list of over 400 SARC-CoV-2 diagnostic tests either in development or approved for clinical use. This presentation reviews the current laboratory methods available for testing COVID- 19 in microbiology laboratories and also provides an insight into the future diagnostics approaches. METHODS: Proper respiratory specimen collected at the appropriate time and from the right anatomical site is critical in the accurate and timely diagnosis of SARSCoV2. While oropharyngeal and nasopharyngeal swabs are recommended for the detection of early infection, other lower respiratory tract specimens like the sputum and bronchoalveolar lavage are used for late detection and monitoring of patients with severe COVID-19 pneumonia. RESULTS AND CONCLUSION: Real-time RT-PCR based molecular assay remains the test of choice for the etiological diagnosis of SARS-CoV-2 while serological tests are being introduced as supplementary tools. Finally, there is an urgent need for scaling up the diagnostic capacity by the introduction of reliable and accurate point-of-care tests which will assist in effective control of this outbreak. These assays can be used in the local hospitals and clinics bearing the burden of identifying and treating patients.

Benefits and limitations of serological assays in COVID-19 infection.

Accurate and rapid diagnostic tests are critical for achieving control of coronavirus disease 2019 (covid-19), a pandemic illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic tests for covid-19 fall into two main categories: molecular tests that detect viral RNA, and serological tests that detect anti-SARS-CoV-2 immunoglobulins. Reverse transcriptase polymerase chain reaction (RT-PCR), a molecular test, has become the gold standard for diagnosis of covid-19; however, this test has many limitations that include potential false negative results, changes in diagnostic accuracy over the disease course, and precarious availability of test materials. Serological tests have generated substantial interest as an alternative or complement to RT-PCR and other Nucleic acid tests in the diagnosis of acute infection, as some might be cheaper and easier to implement at the point of care. A clear advantage of these tests over RT-PCR is that they can identify individuals previously infected by SARS-CoV-2, even if they never underwent testing while acutely ill. Many serological tests for covid-19 have become available in a short period, including some marketed for use as rapid, point-of-care tests. The pace of development has, however, exceeded that of rigorous evaluation, and important uncertainty about test accuracy remains.

Advances in the diagnosis of tuberculosis- Journey from smear microscopy to whole genome sequencing.

The laboratory plays an important role in diagnosing tuberculosis (TB) and the identification and drug sensitivity testing (DST) of Mycobacterium tuberculosis. With a timely diagnosis and treatment with appropriate anti-TB drugs, most people who develop TB can be cured and onward transmission of infection curtailed. For a long time, laboratories used only microscopy and conventional culture-based diagnosis, however these procedures are slow and may require 3-4 weeks to yield results. Given the increasing rate of drug resistance, it has been necessary to look for new and rapid diagnostic methods. Various molecular based diagnostic technologies became available in the beginning of early 90s, providing rapid detection, identification and DST of M. tuberculosis. Molecular technologies offer the greatest potential for laboratories because they have the highest sensitivity and specificity. The present article will review some of the new methodology that has been introduced in the clinical laboratory.

Awareness and perspectives on expansion of latent TB management among public-sector physicians and medical trainees in Delhi, India.

More than one in two healthcare workers (HCWs) in developing countries have latent tuberculosis infection (LTBI), an asymptomatic condition signifying persistent tubercular infection in absence of disease. OBJECTIVE: to evaluate the physician attitude towards LTBI preventive therapy and their perspectives regarding the potential expansion of latent TB management under the RNTCP. MATERIAL AND METHODS: We conducted a cross-sectional analysis among 60 participants of a continuing medical education program during October' 2019 in a medical college in Delhi, India. RESULTS: We enrolled a total of 30 medical officers, 15 resident doctors and 15 medical interns, comprising 27 (45%) males and 33 (55%) females. Only 9 (15%) participants were aware of existing RNTCP guidelines for programmatic management of LTBI. The median (IQR) self-rated willingness of the participants in receiving treatment for LTBI after confirmation of diagnosis on a 10 point continuous rating scale was 6 (5.8). The principal reason attributed to the treatment hesitancy were concerns over drug side effects 19 (31.7%), emergence of drug resistance 11 (18.3%) and the likelihood of reinfection 4 (6.7%). Support for expansion of preventive therapy among household TB contacts was varied, with maximum (41.2%) participants wanting it only for the comorbid patients. CONCLUSION: LTBI preventive treatment is associated with considerable side effects and lack of long-term benefits by a majority of Indian physicians despite significant personal health concerns in treating pulmonary TB cases.

A comparison of patient treatment pathways among multidrug-resistant and drug-sensitive TB cases in Delhi, India: A cross-sectional study.

BACKGROUND: The delay in the diagnosis and treatment initiation of patients with MDR-TB worsens individual prognosis and increases the risk of disease transmission in the community. These delays have been attributed to delay in treatment-seeking by the patient and shifting to multiple healthcare facilities before being tested and diagnosed through India's National Tuberculosis Elimination Program (NTEP). OBJECTIVE: to identify treatment pathways in patients with MDR-TB from the time of onset of symptoms and treatment seeking until diagnosis at a PMDT site and subsequent treatment initiation. We also compared these characteristics with those of patients with DS-TB. METHODS: We recruited a total of 168 patients with MDR-TB and DS-TB each, in Delhi. Data were analyzed using IBM SPSS Version 25. RESULTS: The mean (SD) patient delay for initial treatment-seeking was 20.9 (15.9) days in patients with MDR-TB, and 16.1 (17.1) days in patients with DS-TB (p < 0.001). The median time from visit to the first healthcare facility (HCF) until confirmation of MDR-TB diagnosis was 78.5 days, and until treatment initiation was 102.5 days. Among patients with DS-TB, the time interval from a visit to the first HCF until the initiation of ATT-DOTS was 61.5 days.. Patients diagnosed with DS-TB, whose first source of treatment was a private facility (n = 49), reported a significant delay in the initiation of ATT-DOTS (p < 0.001). CONCLUSIONS: Despite the introduction of universal drug sensitivity testing in individuals having presumptive MDR-TB, a significant delay in the diagnosis and initiation of effective MDR-TB treatment persists as a major public health challenge in India.

Distinguishing clinical and imaging features of nodular regenerative hyperplasia and large regenerative nodules of the liver.

AIM: Nodular regenerative hyperplasia (NRH) and large regenerative nodules (LRN) are distinct types of hepatocellular nodules that have been confused in the radiology literature. However, distinction is critical because their clinical significance is quite different. Our purpose was to review the clinical and imaging findings in a series of patients with NRH and LRN in order to identify distinguishing clinical and imaging features. MATERIALS AND METHODS: This was a retrospective case series. The clinical and imaging features were compared in 36 patients with pathological proof of NRH and 23 patients with pathological evidence of LRN. RESULTS: NRH and LRN have different predisposing factors and imaging findings. NRH is often associated with organ transplantation, myeloproliferative disease, or autoimmune processes. Livers with NRH typically do not have enhancing nodules; none of the present patients with NRH had enhancing liver masses. In contrast, LRN are often associated with Budd-Chiari syndrome. Enhancing liver masses were noted in 19 (83%) of the 23 patients with LRN. The p values for the comparisons were less than 0.001 for both enhancing liver masses and hepatic vein thrombosis. CONCLUSION: NRH and LRN can have distinct clinical presentations and imaging appearances. LRN often result in enhancing liver nodules, whereas NRH usually does not. Clinical and imaging information enables the distinction of LRN and NRH in many cases.

Medical therapy for rheumatic heart disease: is it time to be proactive rather than reactive?

Rheumatic Heart Disease (RHD) is well known to be an active inflammatory process which develops progressive calcification and leaflet thickening over time. The potential for statin therapy in slowing the progression of valvular heart disease is still controversial. Retrospective studies have shown that medical therapy is beneficial for patients with calcific aortic stenosis and recently for rheumatic valve disease. However, the prospective randomized clinical trials have been negative to date. This article discusses the epidemiologic risk factors, basic science, retrospective and prospective studies in valvular heart disease and a future clinical trial to target RHD with statin therapy to slow the progression of this disease. Recent epidemiological studies have revealed the risk factors associated with valvular disease include male gender, smoking, hypertension and elevated serum cholesterol and are similar to the risk factors for vascular atherosclerosis. An increasing number of models of experimental hypercholesterolemia demonstrate features of atherosclerosis in the aortic valve (AV), which are similar to the early stages of vascular atherosclerotic lesions. Calcification, the end stage process of the disease, must be understood as a prognostic indicator in the modification of this cellular process before it is too late. This is important in calcific aortic stenosis as well as in rheumatic valve disease. There are a growing number of studies that describe similar pathophysiologic molecular markers in the development of rheumatic valve disease as in calcific aortic stenosis. In summary, these findings suggest that medical therapies may have a potential role in patients in the early stages of this disease process to slow the progression of RHD affecting the valves. This review will summarize the potential for statin therapy for this patient population.

Journey of tuberculosis control in India.

NTP was pilot tested in Anantapur district of Andhra Pradesh during 1961 and thereafter the programme was launched throughout the country. In 1992, the Government of India together with the World Health Organization (WHO) and Swedish International Development Agency (SIDA) reviewed the National TB Programme and concluded that it suffered from managerial weakness, inadequate funding, over-reliance on x-ray, non-standard treatment regimens, low rates of treatment completion and lack of systematic information on treatment outcomes. Programme review showed that only 30% of patients were diagnosed and only 30% of those treated successfully. Based on the findings and recommendations of the review in 1992, the GOI evolved a revised strategy and launched the Revised National TB Control Programme (RNTCP).