Lead and calcium crosstalk tempted acrosome damage and hyperpolarization of spermatozoa: signaling and ultra-structural evidences.

BACKGROUND: Exposure of humans and animals to heavy metals is increasing day-by-day; thus, lead even today remains of significant public health concern. According to CDC, blood lead reference value (BLRV) ranges from 3.5 µg/dl to 5 µg/dl in adults. Recently, almost 2.6% decline in male fertility per year has been reported but the cause is not well established. Lead (Pb2+) affects the size of testis, semen quality, and secretory functions of prostate. But the molecular mechanism(s) of lead toxicity in sperm cells is not clear. Thus, present study was undertaken to evaluate the adverse effects of lead acetate at environmentally relevant exposure levels (0.5, 5, 10 and 20 ppm) on functional and molecular dynamics of spermatozoa of bucks following in vitro exposure for 15 min and 3 h. RESULTS: Lead significantly decreased motility, viable count, and motion kinematic patterns of spermatozoa like curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency and maximum amplitude of head lateral displacement even at 5 ppm concentration. Pb2+ modulated intracellular cAMP and Ca2+ levels in sperm cells through L-type calcium channels and induced spontaneous or premature acrosome reaction (AR) by increasing tyrosine phosphorylation of sperm proteins and downregulated mitochondrial transmembrane potential. Lead significantly increased DNA damage and apoptosis as well. Electron microscopy studies revealed Pb2+ -induced deleterious effects on plasma membrane of head and acrosome including collapsed cristae in mitochondria. CONCLUSIONS: Pb2+ not only mimics Ca2+ but also affects cellular targets involved in generation of cAMP, mitochondrial transmembrane potential, and ionic exchange. Lead seems to interact with Ca2+ channels because of charge similarity and probably enters the sperm cell through these channels and results in hyperpolarization. Our findings also indicate lead-induced TP and intracellular Ca2+ release in spermatozoa which in turn may be responsible for premature acrosome exocytosis which is essential feature of capacitation for fertilization. Thus, lead seems to reduce the fertilizing capacity of spermatozoa even at 0.5 ppm concentrations.

Monitoring of minerals level in dialysate during hemodialysis treatment of kidney patients using LIBS technique.

Chronic kidney patients may have difficulties in blood filtration to eliminate the waste from the blood and to maintain the level of the minerals in the blood. Hemodialysis (HD) is an artificial way to remove the waste from the blood of a kidney patient and to maintain the proper mineral level in the blood. Reverse osmosis (RO) water having less total dissolved solids (TDS) < 50 ppm is used to prepare dialysis fluid/dialysate in dialysis with two chemicals (electrolytes and salts such as sodium bicarbonate). To check the purity of RO water from various RO machines used to prepare dialysate, which is vital for the safety of the patient, the laser-induced breakdown spectroscopy (LIBS) technique has been used. Also, the amount of replacement of electrolytes/minerals between the blood of the patient and dialysate after dialysis has been checked/determined for two different machines: hemodialysis machine (HDM) and on-line hemo-dia filtration machine (on-line HDF machine). It is observed that the proper amount of electrolytes (Na, Ca, and Mg) are maintained/normalized (depending upon patient's need), excess K is removed, and excess urea and creatinine is removed continuously from the blood of a patient during dialysis treatment which is essential for the better health of a kidney patient. Our results show that the RO water used in on-line HDF machine is purer (i.e., ultrapure); therefore, the quality of life of a kidney patient may be better if dialysis is performed with the on-line HDF machine. The experimental results also show that the filtration capacity of the dialyzer decreases after reusing it many times for dialysis treatment.

The Deadly Duo of Hypertension and Diabetes in India: Further Affirmation from a New Epidemiological Study.

We read with great interest the article "the deadly duo of hypertension and diabetes in India: further affirmation from a new epidemiological study" by Metri et al.1 They rightly pointed out that the prevalence of hypertension in Indian patients with type 2 diabetes patients is high and therefore early screening and management of hypertension should be included in the treatment of patients with type 2 diabetes. We wish to share our study findings on the prevalence of hypertension in newly onset diabetes mellitus (DM). We find that the prevalence of hypertension in all males and females with DM was 44.59, 44.34, and 45.16%, respectively.2.

Impact of metformin therapy on health-related quality of life outcomes in tuberculosis patients with diabetes mellitus in India: A prospective study.

OBJECTIVE: To assess the impact of metformin use on health-related quality of life (HRQoL) in tuberculosis (TB) patients who are presented with type 2 diabetes mellitus (T2DM). METHODOLOGY: In this community-based prospective study, TB patients attending Hakeem Abdul Hameed Centenary Hospital, New Delhi (India) and had comorbidity of T2DM between April 2018 and July 2019 were enrolled. Patients were divided into metformin users and metformin non-users on the basis of the presence of metformin in their routine as antidiabetic drug(s). HRQoL was determined using a validated TB-specific tool (Dhingra and Rajpal-12 scale ie, DR-12) consists of symptom and socio-psychological and exercise adaptation domains. The HRQoL scores were compared at pretreatment (1st visit), end of intensive phase (2nd visit) and end of treatment (3rd visit) between the two groups. RESULTS: A total of 120 patients were enrolled, of which 24 were excluded as they did not respond at follow-up visits. Among the metformin users (n = 48) the mean age of patients was 47.56 years and 62.50% was males. Among the metformin non-users (n = 48), the mean age of patients was 49.02 years and 54.10% was males. The baseline characteristics were similar in both groups except for the substance used history (P = .025), literacy level (P = .048) and BMI (P = .028). Metformin users demonstrated significant improvement in symptom scores (2nd visit: P < .001; 3rd visit: P = .001) and socio-psychological and exercise adaptation scores (2nd visit: P < .0001; 3rd visit: P < .0001) as compared with metformin non-users at 2nd visit and 3rd visit. Overall, scores were also found to be significantly improved in metformin users (2nd visit: P < .001; 3rd visit: P = .001). CONCLUSION: Metformin therapy exerted favourable effects on HRQoL in patients with TB and T2DM and can be recommended as an adjuvant antitubercular drug in TB patients with co-morbidity of T2DM, unless contraindicated.

A novel signal sequence negative multimeric glycosomal protein required for cell cycle progression of Leishmania donovani parasites.

Expression of the intracellular form amastigote specific genes in the Leishmania donovani parasite plays a major role in parasite replication in the macrophage. In the current work, we have characterized a novel hypothetical gene, Ld30b that is specifically transcribed in the intracellular stage of the parasite. The recombinant Ld30b protein exists as a pentamer in solution as identified by native-PAGE and size exclusion gel chromatography. Structural analysis using circular dichroism and molecular modeling indicate that Ld30b belongs to family of cAMP-dependent protein kinase type I-alpha regulatory subunit. Co-localization immunofluorescence microscopy and western blot analyses (using anti-Ld30b antibody and anti-hypoxanthine-guanine phosphoribosyl transferase, a glycosome marker) on the isolated parasite glycosome organelle fractions show that Ld30b is localized in glycosome, though lacked a glycosome targeting PTS1/2 signal in the protein sequence. Episomal expression of Ld30b in the parasite caused the arrest of promastigotes and amastigotes growth in vitro. Cell cycle analysis using flow cytometry indicates that these parasites are arrested in 'sub G0/G1' phase of the cell cycle. Single allele knockout of Ld30b in the parasite similarly attenuated its growth by accumulation of cells in the S phase of cell cycle, thus confirming the probable importance of appropriate level of protein in the cells. Studying such intracellular stage expressing genes might unravel novel regulatory pathways for the development of drugs or vaccine candidates against leishmaniasis.

Land use change: A key ecological disturbance declines soil microbial biomass in dry tropical uplands.

Land use changes such as transformation of natural landscapes, forest degradation and increase in croplands due to human activities are considered amongst the most influential ecological disturbances affecting soil, ecosystems and environmental sustainability. The previous works from India are limited to show that soil disturbances influence abiotic and biotic factors along a rural-urban gradient. However, variations in soil microbial biomass (SMB) -C, -N and -P quantity due to land use changes at different soil depths across different land use types remain poorly understood on comparative ground. We investigated the impact of land use types on soil properties and SMB -C, -N and -P levels across different soil depths (0-10, 10-20 and 20-30 cm) in dry tropical uplands. Four land use types/covers (natural forest, mixed forest, savanna and agriculture land) were selected. The present study is based on two hypotheses: i) different land use types affect SMB levels in top surface soil (0-10 cm), but have less effects in deeper soil profiles (20-30 cm); and ii) SMB levels in top surface soil are highest in natural forest, followed by mixed forest and then savanna and agriculture lands. ANOVA showed significant differences in SMB values due to land use covers (P < 0.001), soil depths (P < 0.001) and land use types × soil depths interaction (P < 0.001). Although, there had no effect of land use types on SMB levels in deeper soil profiles (20-30 cm) but soil parameters (soil pH, soil moisture, soil temperature, total-N, C/N ratio and organic-C) significantly affect SMB levels in top surface (0-10 cm) soil. The study suggests that SMB may be considered as a key indicator of soil fertility index, while land use practices are a major cause for loss of microbial community composition/biomass in dry tropical upland soil.

Changes in microbial community structure and yield responses with the use of nano-fertilizers of nitrogen and zinc in wheat-maize system.

The growing popularity of nano-fertilization around the world for enhancing yield and nutrient use efficiency has been realized, however its influence on soil microbial structure is not fully understood. The purpose of carrying out this study was to assess the combined effect of nano and conventional fertilizers on the soil biological indicators and crop yield in a wheat-maize system. The results indicate that the at par grain yield of wheat and maize was obtained with application of 75% of recommended nitrogen (N) with full dose of phosphorus (P) and potassium (K) through conventional fertilizers along with nano-N (nano-urea) or nano-N plus nano-Zn sprays and N100PK i.e. business as usual (recommended dose of fertilizer). Important soil microbial property like microbial biomass carbon was found statistically similar with nano fertilizer-based management (N75PK + nano-N, and N75PK + nano-N + nano-Zn) and conventional management (N100PK), during both wheat and maize seasons. The experimental data indicated that the application of foliar spray of nano-fertilizers along with 75% N as basal is a sustainable nutrient management approach with respect to growth, yield and rhizosphere biological activity. Furthermore, two foliar sprays of nano-N or nano-N + nano-Zn curtailed N requirement by 25%, furthermore enhanced soil microbial diversity and the microbial community structure. The specific microbial groups, including Actinobacteria, Bacteroidia, and Proteobacteria, were present in abundance and were positively correlated with wheat and maize yield and soil microbial biomass carbon. Thus, one of the best nutrient management approaches for sustaining productivity and maintaining sound microbial diversity in wheat-maize rotation is the combined use of nano-fertilizers and conventional fertilizers.

Screening of Chronic Kidney Disease in Adults: A 10 years' Experience in North Indian City on World Kidney Day.

Chronic kidney disease (CKD) is a complex disease that is asymptomatic in its early stages. Its delayed recognition may predispose patients to adverse outcomes. Early detection and management of kidney disease through screening programs is widely recommended. In the present study, we conducted a screening program at a hospital set up on World Kidney Day for 10 years to detect patients with CKD. The current study constituted 1324 apparently healthy adults, aged >18 years. Information on age, sex, height, weight, history of diabetes mellitus (DM) and hypertension (HTN), and familial history of kidney disease was recorded. Systolic and diastolic blood pressure, random blood sugar; urinalysis, and serum creatinine (Cr) levels were measured. The study outcome was the presence of CKD. Binary logistic regression analysis was applied to find the predictors of CKD. The median age of the study subjects was 40 years. CKD was found in 35.6% of subjects. Age, DM, HTN, and abnormal Cr levels were associated with increasing risk of CKD. The main objective of the present study was to identify the extent of risk relative to the co-factors of CKD and thereby target those who are potentially modifiable, like DM, to intervene at the earliest possible stage to treat the current disease condition and prevent the future health impairment.

Prevalence of Obesity in Newly Onset Diabetes Mellitus and Its Relationship with Uric Acid: An Indian Cross-Sectional Study.

Introduction: Prevalence of obesity is high in diabetes mellitus (DM) and is associated with hyperuricemia (HU), hypertension, metabolic syndrome, cardiovascular disease and dyslipidemia. In obesity, elevated serum uric acid (SUA) has been shown to be associated in many studies from different countries, but data from India are lacking. The aim of the present study is to know the prevalence of obesity and to know the relationship between obesity and SUA in newly onset DM. Methods: In this cross-sectional study from India, 402 consecutive newly onset diabetic patients (male: 284; female: 118) were enrolled. All patients were grouped into four based on BMI (body mass index): underweight (<18.5 kg/m2), normal weight (18.5-23 kg/m2), overweight (>23-27.5 kg/m2), and obese (>27.5 kg/m2). All participants were grouped into four quartiles based on SUA (Q1: <4.23; Q2: ≥4.24-5.19; Q3: ≥5.20-6.16; Q4: >6.16). Results: The mean age, BMI and SUA of the participants were 46.20±0.52 years, 26.35±0.21 kg/m2 and 5.24±0.007 mg/dl, respectively. Overall prevalence of generalized obesity, central obesity and hyperuricemia (HU) were 35.07%, 85.82% and 13.43%, respectively. The prevalence of generalized obesity increased across the SUA quartile. A multinomial logistic regression analysis showed that serum uric acid level was independently associated with generalized obesity (p<0.001). Conclusion: This first report from India shows a significant positive association between SUA and generalized obesity among newly onset DM. Therefore, routine estimation of SUA is recommended in newly onset DM to prevent and treat HU and its related complications.

Optimizing polyhalite (POLY-4) use in the maize-wheat system: A comparative case study from upper and Trans Indo-Gangetic plains of India.

Increasing complexity in crop nutrient requirement in intensive crop production systems needs alternate multi-nutrient sources. Polyhalite (POLY-4) which contains 14% K2O along withcalcium (17% CaO), magnesium (6% MgO), and sulfur (19% S) can be a possible recourse in this regard. In maize-wheat systems, it was evaluated for productivity, profitability, nutrient usage, and nutrient use efficiency under Indo-Gangetic plain (IGP) zones for consecutive two years (2018-19 and 2019-20). The results revealed that 150% K through POLY-4 produced the maximum maize grain yield under the Trans Indo-Gangetic plains (TGP). The maize grain yield increased by 20.8% and 26.2% under 100% K (POLY-4) and 150% K (POLY-4) over No-K, respectively. But statistically, 100% K (POLY-4) stands similar with both 150% K (POLY-4) and 150% K through muriate of potash (MOP) and equivalent. The trends were noticed under upper Indo-Gangetic plain zones (UGP) also. Similarly, the maximum wheat grain yield (6.12 and 6.29 t/ha under TGP and UGP, respectively) was obtained under 150% K (POLY-4), and remained statistically at par with 100% K (POLY-4), but significantly higher than 150% K (MOP). Under both agro-ecologies i.e. TGP and UGP, the highest system productivity was obtained with recommended N, P, and 150% K application through POLY-4. The added return over NPK remained highest with 150% K (POLY-4) for both maize and wheat. However, higher partial factor productivity for N and S, agronomic, physiological, and translocation efficiencies were noticed under 150% K (POLY-4), and remained at par with 100% K (POLY-4). Increased system yield, added returns, partial factor productivity, agronomic, physiological, and translocation efficiencies under 100% K through POLY-4 (along with recommended N and P) proved its effectiveness as multi-nutrient source for the maize-wheat system under TGP and UGP.

Study of different concentric rings inside gallstones with LIBS.

Gallstones obtained from patients from the north-east region of India (Assam) were studied using laser-induced breakdown spectroscopy (LIBS) technique. LIBS spectra of the different layers (in cross-section) of the gallstones were recorded in the spectral region 200-900 nm. Several elements, including calcium, magnesium, manganese, copper, silicon, phosphorus, iron, sodium and potassium, were detected in the gallstones. Lighter elements, including carbon, hydrogen, nitrogen and oxygen were also detected, which demonstrates the superiority of the LIBS technique over other existing analytical techniques. The LIBS technique was applied to investigate the evolution of C(2) swan bands and CN violet bands in the LIBS spectra of the gallstones in air and an argon atmosphere. The different layers (dark and light layers) of the gallstones were discriminated on the basis of the presence and intensities of the spectral lines for carbon, hydrogen, nitrogen, oxygen and copper. An attempt was also made to correlate the presence of major and minor elements in the gallstones with the common diet of the population of Assam.

Prevalence and risk factors of chronic kidney disease in overweight and obese population in a tertiary care hospital in North India.

Obesity has already been a global epidemic, and its prevalence has been projected to grow by 40% in the next decade. Its increasing prevalence has implications on the epidemiology of chronic kidney disease (CKD), which, in turn, could impact the health system and thereby the society in an adverse manner. Lack of community-based screening programs can lead to missed or late detection of CKD. The current study aims to estimate the prevalence of CKD in overweight and obese general population attending a screening camp in a tertiary care hospital in a North Indian city. In this cross-sectional study, 103 overweight and obese people from a community attending a health camp were screened for serum creatinine, urine analysis, random blood sugar, and uric acid. Demographic and anthropometric parameters were noted. Binary logistic regression analysis was used to find the predictors of CKD in these patients. The median age of the participants was 43 years with a male predominance (68%). More than half (58.4%) of the participants were obese and the remaining 41.6% were overweight. The overall prevalence of CKD was 17.5%. Individuals with obesity and diabetes were more prone to develop CKD (odds ratio = 4.868 and 7.941, respectively). CKD was prevalent in individuals with obesity. Obesity and diabetes were the significant predictors for the development of CKD. All the overweight and obese individuals should be periodically screened for kidney diseases.

Chronic Kidney Disease among Middle-Aged and Elderly Population: A cross-sectional screening in a Hospital Camp in Varanasi, India.

Chronic kidney disease (CKD) is no longer considered just a health burden, but a major health priority owing to its high treatment costs and poor outcome. The lack of community-based screening programs has led to the detection of CKD patients at advanced stages. This study aims to estimate the prevalence of CKD and patterns of known risk factors among the general population (middle-aged and elderly) attending a screening camp in a community-based setting. The study participants constituted a part of the general population of Varanasi (aged ≥45 years) who volunteered in a screening camp that was organized as part of the World Kidney Day Initiative at Opal Hospital. Information on age, sex, height, weight, smoking and drug history, history of diabetes, hypertension, and family history of kidney disease was extensively interrogated, while laboratory investigations such as urinalysis and serum creatinine levels were recorded. More than three-fifths of the participants were middle-aged adults (i.e., 45-64 years) and the remaining 34.8% were elderly population, i.e., ≥65 years. The overall prevalence of CKD in the 198 studied participants was 29.3%. Higher number of participants (40.6%) of elderly population had CKD (P = 0.011). The serum creatinine, albuminuria, and estimated glomerular filtration rate levels were strongly associated with CKD (P <0.05). Our study suggests that elderly individuals are at risk with higher serum creatinine levels and would benefit from early detection of CKD to prevent disease progression and associated morbidity and mortality.