Leptin regulation of the p53-HIF1α/PKM2-aromatase axis in breast adipose stromal cells: a novel mechanism for the obesity-breast cancer link.

BACKGROUND/OBJECTIVES: Obesity (body mass index (BMI)⩾30 kg m-2) is associated with an increased risk of estrogen-dependent breast cancer after menopause. Levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis, are elevated in breast tissue of obese women. Recently, the regulation of aromatase by the p53-hypoxia-inducible factor-1α (HIF1α)/pyruvate kinase M2 (PKM2) axis was characterized in adipose stromal cells (ASCs) of women with Li-Fraumeni Syndrome, a hereditary cancer syndrome that predisposes to estrogen-dependent breast cancer. The current study aimed to determine whether stimulation of aromatase by obesity-associated adipokine leptin involves the regulation of the p53-HIF1α/PKM2 axis. SUBJECTS/METHODS: Human breast ASCs were used to characterize the p53-HIF1α/PKM2-aromatase axis in response to leptin. The effect of pharmacological or genetic modulation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), p53, Aha1, Hsp90, HIF1α and PKM2 on aromatase promoter activity, expression and enzyme activity was examined. Semiquantitative immunofluorescence and confocal imaging were used to assess ASC-specific protein expression in formalin-fixed paraffin-embedded tissue sections of breast of women and mammary tissue of mice following a low-fat (LF) or high-fat (HF) diet for 17 weeks. RESULTS: Leptin-mediated induction of aromatase was dependent on PKC/MAPK signaling and the suppression of p53. This, in turn, was associated with an increase in Aha1 protein expression, activation of Hsp90 and the stabilization of HIF1α and PKM2, known stimulators of aromatase expression. Consistent with these findings, ASC-specific immunoreactivity for p53 was inversely associated with BMI in breast tissue, while HIF1α, PKM2 and aromatase were positively correlated with BMI. In mice, HF feeding was associated with significantly lower p53 ASC-specific immunoreactivity compared with LF feeding, while immunoreactivity for HIF1α, PKM2 and aromatase were significantly higher. CONCLUSIONS: Overall, findings demonstrate a novel mechanism for the obesity-associated increase in aromatase in ASCs of the breast and support the study of lifestyle interventions, including weight management, which may reduce breast cancer risk via effects on this pathway.

The prevalence of abnormal ECG in trained sportsmen.

BACKGROUND: Competitive sports training causes structural and conductive system changes manifesting by various electrocardiographic alterations. We undertook this study to assess the prevalence of abnormal ECG in trained Indian athletes and correlate it with the nature of sports training, that is endurance or strength training. METHODS: We evaluated a standard resting, lying 12 lead Electrocardiogram (ECG) in 66 actively training Indian athletes. Standard diagnostic criteria were used to define various morphological ECG abnormalities. RESULTS: 33/66 (50%) of the athletes were undertaking endurance training while the other 33 (50%) were involved in a strength-training regimen. Overall 54/66 (81%) sportsmen had significant ECG changes. 68% of these changes were considered as normal training related features, while the remaining 32% were considered abnormal. There were seven common training related ECG changes-Sinus Bradycardia (21%), Sinus Arrhythmia (16%), 1st degree Atrioventricular Heart Block (6%), Type 1 2nd-degree Atrioventicular Heart Block (3%), Incomplete Right bundle branch block (RBBB) (24%), Early Repolarization (42%), Left Ventricular Hypertrophy (LVH) (14%); while three abnormal ECG changes--T-wave inversion (13%), RBBB(4%), Right ventricular hypertrophy (RVH) with strain (29%) were noted. Early repolarization (commonest change), sinus bradycardia, and incomplete RBBB were the commoner features noticed, with a significantly higher presence in the endurance trained athletes. CONCLUSION: A high proportion of athletes undergoing competitive level sports training are likely to have abnormal ECG recordings. Majority of these are benign, and related to the physiological adaptation to the extreme levels of exertion. These changes are commoner during endurance training (running) than strength training (weightlifting).

Utilising BC observations to estimate CO contributions from fossil fuel and biomass burning in the Central Himalayan region.

The Himalayan region is adversely affected by the increasing anthropogenic emissions from the adjacent Indo-Gangetic plain. However, source apportionment studies for the Himalayan region that are crucial for estimating CO concentration, are grossly insufficient, to say the least. It is in this context that our study reported here assumes significance. This study utilizes five years (2014-2018) of ground-based observations of eBC and multiple linear regression framework (MLR) to estimate CO and segregate its fossil fuel and biomass emission fractions at a high-altitude (1958 m) site in the Central Himalayas. The results show that MERRA2 always underestimates the observed CO; MOPITT has a high monthly difference ranging from -32% to +57% while WRF-Chem simulations underestimate CO from February to June and overestimate in other months. In contrast, CO estimated from MLR replicates diurnal and monthly variations and estimates CO with an r2 > 0.8 for 2014-2017. The CO predicted during 2018 closely follows the observed variations, and its mixing ratios lie within ±17% of the observed CO. The results reveal a unimodal diurnal variation of CO, COff (ff: fossil fuel) and CObb (bb: biomass burning) governed by the boundary layer evolution and upslope winds. COff has a higher diurnal amplitude (39.1-67.8 ppb) than CObb (5.7-33.5 ppb). Overall, COff is the major contributor (27%) in CO after its background fraction (58%). CObb fraction reaches a maximum (28%) during spring, a period of increased agricultural and forest fires in Northern India. In comparison, WRF-Chem tracer runs underestimate CObb (-38% to -98%) while they overestimate the anthropogenic CO during monsoon. This study thus attempts to address the lack of continuous CO monitoring and the need to segregate its fossil fuel and biomass sources, specifically over the Central Himalayas, by employing a methodology that utilizes the existing network of eBC observations.

Vaccination saves lives: a real-time study of patients with chronic diseases and severe COVID-19 infection.

OBJECTIVES: This study aims to describe the demographic and clinical profile and ascertain the determinants of outcome among hospitalized coronavirus disease 2019 (COVID-19) adult patients enrolled in the National Clinical Registry for COVID-19 (NCRC). METHODS: NCRC is an on-going data collection platform operational in 42 hospitals across India. Data of hospitalized COVID-19 patients enrolled in NCRC between 1st September 2020 to 26th October 2021 were examined. RESULTS: Analysis of 29 509 hospitalized, adult COVID-19 patients [mean (SD) age: 51.1 (16.2) year; male: 18 752 (63.6%)] showed that 15 678 (53.1%) had at least one comorbidity. Among 25 715 (87.1%) symptomatic patients, fever was the commonest symptom (72.3%) followed by shortness of breath (48.9%) and dry cough (45.5%). In-hospital mortality was 14.5% (n = 3957). Adjusted odds of dying were significantly higher in age group ≥60 years, males, with diabetes, chronic kidney diseases, chronic liver disease, malignancy and tuberculosis, presenting with dyspnoea and neurological symptoms. WHO ordinal scale 4 or above at admission carried the highest odds of dying [5.6 (95% CI: 4.6-7.0)]. Patients receiving one [OR: 0.5 (95% CI: 0.4-0.7)] or two doses of anti-SARS CoV-2 vaccine [OR: 0.4 (95% CI: 0.3-0.7)] were protected from in-hospital mortality. CONCLUSIONS: WHO ordinal scale at admission is the most important independent predictor for in-hospital death in COVID-19 patients. Anti-SARS-CoV2 vaccination provides significant protection against mortality.

Gastric teratoma presenting as melena in the newborn: A case report.

Melena is reported in 1 of 350 to 400 new-borns. Significant upper gastrointestinal bleeding in a neonate with an antenatally diagnosed abdominal mass has not been reported before. This case highlights an unusual presentation of a gastric teratoma and proposes a probable embryological explanation for the site of occurrence.

COVID-19 appropriate behavior in India: Time to invest for the benefits in future.

The COVID-19 pandemic gave an opportunity to adopt many appropriate changes in the behavior of the people in India. The major gears of those behavior changes were the enforcement by the government, fear, motivation (self and induced), and self-experiences or realizations with time. If those changes are fitted in the Trans-Theoretical Model, Indian people have passed through the "Pre-Contemplation" to "Action" stage of behavior changes during different phases of this pandemic. Frequent hand hygiene, maintaining physical distancing, use of face mask, cough etiquettes, avoid greetings through physical contacts, fear in spitting and urination at public places, refrain from gatherings and avoiding outside food are some of the examples of those appropriate behaviors which were enforced or learnt during the COVID pandemic. The continuous lockdown made people understand the difference between "want" and "need," the importance of local production, and the significance of social media and technology in routine life. The work-from-home strategy gave a chance to appreciate the work--life balance in a more applied way. The first-ever lifetime experience of unbelievable rejuvenating nature because of lack of human play taught people to appreciate nature. Although the current focus is on responding to the pandemic and on coping with its immediate effects, yet this is the time when there is an urgent need to create an enabling environment to support and sustain these COVID-19 appropriate behaviors (maintenance stage) to reap the maximum benefits out of them. Sustaining these appropriate behaviors is also important considering the bimodal distribution of the COVID-19 and possibility of advent of the second wave of COVID-19 in near future.

AFLP-based genetic diversity assessment of commercially important tea germplasm in India.

India has a large repository of important tea accessions and, therefore, plays a major role in improving production and quality of tea across the world. Using seven AFLP primer combinations, we analyzed 123 commercially important tea accessions representing major populations in India. The overall genetic similarity recorded was 51%. No significant differences were recorded in average genetic similarity among tea populations cultivated in various geographic regions (northwest 0.60, northeast and south both 0.59). UPGMA cluster analysis grouped the tea accessions according to geographic locations, with a bias toward China or Assam/Cambod types. Cluster analysis results were congruent with principal component analysis. Further, analysis of molecular variance detected a high level of genetic variation (85%) within and limited genetic variation (15%) among the populations, suggesting their origin from a similar genetic pool.

Prolonged persistence of SARS-CoV-2 in the upper respiratory tract of asymptomatic infected individuals.

BACKGROUND: Duration of persistence of SARS-CoV-2 in the upper respiratory tract of infected individuals has important clinical and epidemiological implications. AIM: We aimed to establish the duration and risk factors for persistence of SARS-CoV-2 in the upper respiratory tract of asymptomatic infected individuals. METHODS: Data of repeat rRT-PCR (real-time reverse transcription-polymerase chain reaction) test done for SARS-CoV-2 infected individuals at our institute at Jodhpur, India were analysed from 19 March to 21 May 2020. Duration of virus persistence was estimated with parametric regression models based on weibull, log-normal, log-logistic, gamma and generalized gamma distributions. Factors associated with prolonged viral persistence were analysed with the best-fitting model. RESULTS: Fifty-one SARS-CoV-2 infected individuals with repeat rRT-PCR test were identified with 44 asymptomatics. The asymptomatic individuals had median virus persistence duration of 8.87 days (95% CI: 7.65-10.27) and 95 percentile duration of 20.70 days (95% CI: 16.08-28.20). The overall median virus persistence including both symptomatic and asymptomatic individuals was found to be 9.18 days (95% CI: 8.04-10.48). Around one-fourth asymptomatics (10/44) demonstrated SARS-CoV-2 persistence beyond 2 weeks. Age <60 years and local transmission were found to be significantly associated with longer virus persistence among asymptomatic individuals on univariate regression but not in multivariate analysis. CONCLUSION: Recommended home isolation duration for SARS-CoV-2 infected individuals in India should be extended from 17 days to at least 3 weeks. Prolonged persistence of SARS-CoV-2 in a considerable proportion of asymptomatic individuals merits attention with regard to ensuring universal infection prevention precautions irrespective of symptomatic status.

Intra- and Inter-observer Variability in Different Methods of Measuring Carpal Collapse.

Introduction: Carpal collapse of wrist occurs in disorders like rheumatoid arthritis and Kienbock's disease. Three techniques have been described to measure carpal collapse. First, the carpal height ratio (CHR), measured by dividing carpal height by 3rd metacarpal length. Second, the revised carpal height ratio (RCH ratio), measured by dividing carpal height by length of capitate. Third, capitate radius distance (CR index), measured by shortest distance between distal edge of radius and the proximal edge of capitate. The index publications describe good reliability of all these but which method out of the three is best in terms of intra- and inter-observer variability is not known. The purpose of this study was to find out which method had the least inter- and intra-observer variability for determining carpal collapse. Materials and Methods: Fifty normal wrist postero-anterior radiographs were studied by three assessors who measured CHR, RCH ratio and CR index separately. The measurements were repeated after one month by all the three observers. The results were then statistically analysed. Results: The p-value was <0.001 in all the three assessors in CR index meaning that the intra-observer variability was least in CR index. For the inter-observer variability intra class coefficient of 0.9 indicated that the CR index has the least variability. Conclusion: CR index is the most reproducible method to measure carpal collapse. The method which provides accurate measurement of carpal collapse will allow better staging of carpal disorders.

An objective functional evaluation of the flexor carpi ulnaris set of triple tendon transfer in radial nerve palsy.

This study reports an objective assessment of postoperative function of 11 triple transfers for high radial palsies, using pronator teres for wrist extension, flexor carpi ulnaris for finger extension and palmaris longus for thumb extension. The mean follow-up was 3.3 years. Assessment was done by recording the active ranges of wrist motion, grip strength, wrist and finger strength and work simulation. The mean strength and range of wrist extension were 42% and 86%, respectively, of the contralateral wrist. Other measured movements were within the functional range and work simulation confirmed good restoration of function. The mean DASH score was 3.45, with no patient reporting any specific functional complaints. This study shows that even though the range of wrist motion and the strength of the wrist and fingers are less than normal, hand function remains good. We conclude that the flexor carpi ulnaris set of tendon transfer works well. LEVEL OF EVIDENCE: 3.

Seasonal, interannual, and long-term variabilities in biomass burning activity over South Asia.

The seasonal, interannual, and long-term variations in biomass burning activity and related emissions are not well studied over South Asia. In this regard, active fire location retrievals from the Moderate Resolution Imaging Spectroradiometer (MODIS), the retrievals of aerosol optical depth (AOD) from MODIS Terra, and tropospheric column NO2 from Ozone Monitoring Instrument (OMI) are used to understand the effects of biomass burning on the tropospheric pollution loadings over South Asia during 2003-2013. Biomass burning emission estimates from Global Fire Emission Database (GFED) and Global Fire Assimilation System (GFAS) are also used to quantify uncertainties and regional discrepancies in the emissions of carbon monoxide (CO), nitrogen oxide (NOx), and black carbon (BC) due to biomass burning in South Asia. In the Asian continent, the frequency of fire activity is highest over Southeast Asia, followed by South Asia and East Asia. The biomass burning activity in South Asia shows a distinct seasonal cycle that peaks during February-May with some differences among four (north, central, northeast, and south) regions in India. The annual biomass burning activity in north, central, and south regions shows an increasing tendency, particularly after 2008, while a decrease is seen in northeast region during 2003-2013. The increase in fire counts over the north and central regions contributes 24 % of the net enhancement in fire counts over South Asia. MODIS AOD and OMI tropospheric column NO2 retrievals are classified into high and low fire activity periods and show that biomass burning leads to significant enhancement in tropospheric pollution loading over both the cropland and forest regions. The enhancement is much higher (110-176 %) over the forest region compared to the cropland (34-62 %) region. Further efforts are required to understand the implications of biomass burning on the regional air quality and climate of South Asia.

Biodiversity of earthworm resources of arid environment.

Biodiversity of earthworms was studied in arid zone of Jodhpur district of Rajasthan. A total nine species of earthworms were recorded from different pedoecosystems of desert environment. These species were Pontoscolex corethrurus, Amynthas morrisi, Metaphire posthuma, Lampito mauritii, Perionyx sansibaricus, Ocnerodrilus occidentalis, Dichogaster bolaui, Octochaetona paliensis and Ramiella bishambari. They belonged to the families Glossoscolicidae, Megascolicidae, Ocnerodrilidae and Octochaetidae. The species P. sansibaricus, O. paliensis and P. corethrurus were reported for the first time from Rajasthan. The earthworm fauna of Jodhpur district were either exotic peregrine or native peregrine. Exotic species like A. morrisi and M. posthuma, and native peregrine species like L. mauritii were widely distributed in arid region. They appear to be better adapted to withstand drought conditions, as they have enteronephric meronephridia and excrete their urine into the guts for conservation of water in their bodies.

Decomposition of kitchen waste amended with cow manure using an epigeic species (Eisenia fetida) and an anecic species (Lampito mauritii).

An epigeic (surface dweller) earthworm species Eisenia fetida and an anecic (deep burrower) earthworm species Lampito mauritii have been tested for decomposition of kitchen waste plus cow dung. Chemical analyses of worm-worked substrates by both species showed g/kg increases in nitrogen, phosphorus and potassium and decreases in C/N and C/P ratios after 150 days of vermicomposting. However, organic carbon matter showed reduction in their amounts for 3-4 months and afterwards slightly increased up to 150 days. E. fetida produced 0.27%, 156%, 41% and 38% increases in organic carbon, nitrogen, phosphorus, and potassium as well as 61% and 29% decreases in C/N and C/P ratios as compared to control after 150 days of earthworm inoculation. In contrast, L. mauritii produced 14%, 102%, 33% and 42% increases in organic carbon, nitrogen, phosphorus and potassium as well as 43% and 14% decreases in C/N and C/P ratios as compared to control after 150 days of earthworm activity. There was moderate mineralization and faster decomposition by E. fetida in comparison to moderate mineralization and moderate decomposition by L. mauritii. The average numbers of cocoons and adults produced were greater by E. fetida than by L. mauritii after 150 days. These results indicate E. fetida may be a better adapted species for decomposition of kitchen waste plus cow dung under tropical conditions.

Comparative studies on biomass production, life cycles and composting efficiency of Eisenia fetida (Savigny) and Lampito mauritii (Kinberg).

Comparative studies were performed to evaluate composting potential, biomass growth and biology of a non-native (Eisenia fetida) and an endemic (Lampito mauritii) species of earthworm in the semiarid environment of Jodhpur district of Rajasthan in India. Earthworms were reared in a mixed bedding material comprised of biogas slurry, cowdung, wheat straw, leaflitter, sawdust and kitchen waste. The percentage of organic carbon of the culture bedding material declined upto 105 days with E. fetida and 120 with L. mauritii. The percentage of nitrogen, phosphorous and potassium increased as a function of the vermicomposting period. In contrast, C/N and C/P ratios decreased day by day. Both species were effective for decomposition and mineralization of mixed bedding in the semiarid environment. A comparative assessment of biomass growth of E. fetida and L. mauritii was done under controlled laboratory conditions. The optimum temperature, moisture content and pH for E. fetida were 25 degrees C, 70% and 6.5, respectively. However, the optimum temperature, moisture content and pH for growth and development of L. mauritii were 30 degrees C, 60% and 7.5, respectively. The biology and reproductive rates of both species were also studied in the laboratory using mixed bedding. Cocoon production was higher for E. fetida than L. mauritii. The net reproductive rate was 9 per month in the case of E. fetida and 1 per month for L. mauritii. Fertilized eggs of E. fetida and L. mauritii developed into adults within 4 and 5 1/4 months, respectively. These observations indicate E. fetida may be a more efficient breeder than L. mauritii in the desert region of Rajasthan.

Value of clinico-psychiatric assessment in the diagnosis of chronic intractable pain in abdomen.

To evaluate the role of psychiatric illness in patients with chronic abdominal pain, 50 patients with this symptom were subjected to thorough clinical examination, detailed investigations and Goldberg's 60-item General Health Questionnaire. Those scoring 12 in this questionnaire were subjected to a detailed psychiatric evaluation. Sixteen (32%) patients had pure organic illnesses, 8 (16%) had organic illness with associated psychiatric factors and 26 (52%) had definite psychiatric illness. We conclude that chronic abdominal pain is often associated with psychiatric illness.

Control of hyperglycaemia and hyperlipidaemia by plant product.

A herbal powder consisting of Guargum, Methi, Tundika and Meshasringi was administered to thirty control and thirty NIDDM patients twice daily before principal meals for four weeks. Oral GTT showed improvement in both control and patient groups. Serum total and LDL cholesterol also fell significantly in both the groups after the trial period. Test meal of the herbal powder with D-Xylose excretion was otherwise normal. Follow up for upto two years did not reveal any long term side effect of the powder. This powder, therefore, can be effectively used to reduce postprandial blood glucose and LDL cholesterol in NIDDM patients as a long term measure.