Hemophagocytic lymphohistiocytosis secondary to infections:a tertiary care experience

Background: Hemophagocytic lymphohistiocytosis is an uncommon complication of various conditions. It is characterized by immune dysregulation and massive cytokine release causing multiorgan dysfunction. It is classified as primary and secondary to various etiologies like infections, malignancies and autoimmune disease. As it has high mortality, clinician awareness is important for early diagnosis and improved outcome. Aim of the study was to study the etiologies, clinical manifestations, complications and laboratory features in patients diagnosed with infection associated hemophagocytic syndrome (IAHS).Methods: We have done retrospective analysis of all cases diagnosed to have Infection Associated Hemophagocytic Syndrome (IAHS) between March 2012 to November 2015 in a 1000 bedded tertiary care hospital in south India.Results: Total five cases detected. Most of the cases are related to tropical infections (80%). All of them presented with fever, cytopenias and organomegaly. Ferritin and Triglycerides were elevated in all patients. Bone marrow hemophagocytosis was observed in 80% of cases. Diagnostic protocol of HLH 2004 was followed. Only 20% survival observed.Conclusions: IAHS is a rare fulminant complication associated with diagnostic and therapeutic challenges because of overlapping clinical features with sepsis. Increased physician awareness, early diagnosis and therapeutic interventions may improve survival

Clinical profile of sickle cell syndromes: experience at a tertiary care centre in South India

Background: Sickle cell syndromes are commonly encountered inherited haematological disorders regarding which sparse published data are available from Telangana State. Methods: Prospective study of 55 patients diagnosed to have sickle cell syndromes at our tertiary care teaching hospital in Hyderbad, Telangana State, South India. Results: Their mean age was 19.9 (range 3-48) years; there were 35 males. Consanguinity was noted in 31%. History of cholecystectomy was evident in 5 cases. Blood transfusions were received in the past in 52% of cases. Symptoms at presentation were jaundice (85%), pain (80%), fatiguability (60%), pallor (30%), dyspnoea (29%), lump abdomen (7%) and leg ulcer (3%). Acute chest syndrome was seen in 10.9% cases. Physical examination revealed pallor (90%), icterus (80%) hepatomegaly (49%) and splenomegaly (41%). Mean haemoglobin at presentation was 8.3 g/dL. Sickle cells were seen in peripheral smear in 51%. Sickling test was positive in all after induction. Characterization of haemoglobin by high performance liquid chromatography revealed homozygous sicke cell anaemia was evident in 22/ 43 (51.2%), sickle thalassemia in 16/43 (37.2 %) and sickle cell trait in 5/43 (11.6 %). Conclusions: Sickle cell disease should be considered in the differential diagnosis while evaluating patients presenting with anaemia and skeletal pains. Prompt recognition and management improves survival and eventual prognosis in these patients

महिषासुर: मिथक व परंपराएं

इक्कसवीं सदी के दूसरे दशक में भारत में महिषासुर आंदोलन द्विज संस्कृति के लिए चुनौती बनकर उभरा। इसके माध्यम से आदिवासियों, पिछड़ों और दलितों के एक बड़े हिस्से ने अपनी सांस्कृतिक दावेदारी पेश की। लेकिन यह आंदोलन क्या है, इसकी जड़ें समाज में कहां तक फैली हैं, बहुजनों की सांस्कृतिक परंपरा में इसका क्या स्थान है, मौजूदा लोक-जीवन में महिषासुर की उपस्थिति किन-किन रूपों में है, इसके पुरातात्विक साक्ष्य क्या हैं? गीतों-कविताओं व नाटकों में महिषासुर किस रूप में याद किए जा रहे हैं और अकादमिक-बौद्धिक वर्ग को इस आंदोलन ने किस रूप में प्रभावित किया है, उनकी प्रतिक्रियाएं क्या हैं? आदि प्रश्नों पर विमर्श हमें एक ऐसी बौद्धिक यात्रा की ओर ले जाने में सक्षम हैं, जिससे हममें अधिकांश अभी तक अपरिचित रहे हैं। क्या महिषासुर दक्षिण एशिया के अनार्यों के पूर्वज थे, जो बाद में एक मिथकीय चरित्र बन कर बहुजन संस्कृति के प्रतीक पुरुष बन गए? क्या यह बहुत बाद की परिघटना है, जब माकण्डेय पुराण, दुर्गासप्तशती जैसे ग्रंथ रच कर, एक कपोल-कल्पित देवी के हाथों महिषासुर की हत्या की कहानी गढ़ी गई? इस आंदोलन की सैद्धांतिकी क्या है? प्रमोद रंजन द्वारा संपादित किताब “महिषासुर: मिथक व परंपराएं” में लेखकों ने उपरोक्त प्रश्नों पर विचार किया है तथा विलुप्ति के कगार पर खड़े असुर समुदाय का विस्तृत नृवंशशास्त्रीय अध्ययन भी प्रस्तुत किया है। इस पुस्तक में समकालीन भारतीय साहित्य में महिषासुर पर लिखी गई कविताओं व गीतों का प्रतिनिधि संकलन भी है तथा महिषासुर की बहुजन कथा पर आधारित एक नाटक भी प्रकाशित है। समाज-विज्ञान व सांस्कृतिक विमर्श के अध्येताओं, सामाजिक-राजनीतिक कार्यकर्ताओं, साहित्य प्रेमियों के लिए यह एक आवश्यक पुस्तक है

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Role of leptin on the expression of low density lipoprotein receptor

Background & objectives: Leptin resistance oriented hyperleptinaemia is a common problem in obese subjects in association with hypercholesterolaemia. The most common target for hypercholesterolaemia is impaired low density lipoprotein receptor (LDLR). This study was carried out to investigate whether any alteration in LDLR expression could explain the occurrence of hypercholesterolaemia in the event of hyperleptinaemia. Methods: Expression of LDLR and SREBP2 (sterol regulatory element binding protein 2) were examined in HepG2 cells by RT-PCR and Western blotting. JAK2 inhibitor II was used to verify the effect of JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway (common mediator for cytokine signaling). Co-localization of LDLR and insulin receptor (IR) was examined by confocal microscopy. Results: Leptin was found to reduce the expression of LDLR and its transcription factor SREBP2. On the other hand, a weak signal for stimulation of LDLR by leptin was noted to be mediated by JAK2 pathway. But the joint effect of the two signaling pathways kept LDLR only in depressed mode in presence of leptin. Confocal microscopy showed that LDLR made an intensively co-localized complex with insulin receptor in presence of leptin. Interpretation & conclusions: Our results show that though leptin stimulates LDLR expression very weakly through JAK-STAT signaling pathway, it mainly imposes inhibition on LDLR expression by inhibiting transcription factor SREBP2. The inter-association between LDLR and IR may be a reason to render LDLR functionally inactive in presence of leptin

Optimizing Groundnut (Arachis hypogaea L.) Yields: An Effect of Sowing Dates and Planting Densities in India Hot Arid Regions Under a Changing Climate

Groundnut (Arachis hypogaea L.) holds immense significance as an oilseed crop on a global scale. The growth and development of plants, along with crop productivity, are substantially impacted by the adverse effects of global climate change. In view of this, a research initiative was undertaken to investigate the effects of distinct sowing dates and planting densities on the yield and economic aspects of groundnut in the hot arid region of Rajasthan, India. The experiment, conducted over a span of three years during the kharif seasons of 2017, 2018, and 2019 at Swami Keshwanand Rajasthan Agricultural University, Bikaner, Rajasthan, India. The experimental design utilized a split-plot layout with four replications, comprising nine treatments. The main plot treatments involved three different sowing dates (15th May, 30th May, and 15th June), while the sub-plot treatments encompassed three planting densities (1.67 lakh, 2.50 lakh, and 3.33 lakh plants per hectare). Notably, the diverse sowing dates and planting densities exhibited notable effects on groundnut yield and economic viability. Comparative analysis revealed that sowing on May 30th, while statistically comparable to June 15th sowing, yielded the highest number of branches, pegs, pods per plant, kernel and pod yield, net return, and benefit-cost ratio. Interestingly, the highest haulm yield per hectare was achieved with the May 15th sowing, yet the harvest index improved progressively as sowing was delayed from May 15th to June 15th. However, the various sowing dates had no discernible effect on kernels per pod, seed index, and shelling percentage. Furthermore, employing a planting density of 1.67 lakh plants per hectare was resulted in the highest counts of branches, pegs, pods, kernels per pod, seed index, and shelling percentage. Remarkably, the elevation in planting density up to 2.50 lakh plants per hectare led to enhanced kernel and pod yields, harvest index, and net return. In an intriguing interaction between sowing dates and plant populations, the most favorable pod yield, kernel yield, and net return were recorded with a planting density of 2.50 lakh plants per hectare for the May 30th sowing. These findings underscore the significant effect of sowing date and planting density on yield attributes and ultimately on groundnut yield in the challenging hot arid region. Therefore, the timing of sowing and the density of planting play pivotal roles in enhancing groundnut productivity within this region, particularly in light of the changing climate conditions