Common Hematological Reference Indices Among Healthy Reproductive Age Indian Women-Data Subset from Nationwide Study.

Despite the negative implications on women's health, pregnancy, and fetal outcomes, population-based studies on hematological indices among reproductive age women in India have received inadequate attention. This study aimed to generate normative ranges for various hematological parameters among these women. After ethics approval, apparently healthy (n = 5884) women (aged 18-40 years) were recruited from six eco-geographic zones of India. After various exclusions (n = 5412), including women having anemia, data of clinically, and biochemically healthy women (n = 472) was analysed to generate centiles (2.5 and 97.5th) and correlations. The mean age and mean BMI of women was 29.3 ± 6.5 years and 23.25 ± 3.26 kg/m2 with BP of 112.26 ± 8.9/74.04 ± 6.7 mmHg. The reference intervals for hemoglobin (12-15.1 gm/dl), RBC (3.68-5.55 millions/µl), WBC (4.1-11.26*109/L), platelet count (1.32-4.42*105/µl), and erythrocyte sedimentation rate (4.35-41.65 mm/hr) were different from currently used reference values (p < 0.05). However, these haematological indices did not vary among various age categories, geographical zones, ethnicities and rural or urban origins. Pearson's correlation revealed a statistically significant association between ESR, WBC, monocytes, and platelets with homeostasis model assessment of insulin resistance (HOMA-IR). Women with HOMA-IR > 2 displayed a statistically significant differences in parameters like MCV, ESR, eosinophil and platelet counts as compared to the women with HOMA-IR < 2. This study provides a pioneering reference data of hematological indices among women of reproductive age in India. Despite the small sample size results can be extrapolated to the national population given the representative sampling of various geographical zones. This may pave way for future comprehensive large-scale studies on the subject. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01714-6.

Association of TCF7L2 Gene Variant (rs12255372) with Polycystic Ovary Syndrome and its Effect Modification of the Disease Phenotype.

Polycystic ovary syndrome (PCOS) and type-2 diabetes mellitus (T2DM) share common genetic features. Transcription factor 7-like-2 (TCF7L2) is consistently studied T2DM susceptibility locus. However, limited studies on TCF7L2 have failed to demonstrate any link with the PCOS risk. Therefore, we investigated the association of TCF7L2 polymorphic variant (rs12255372) with the PCOS risk. We recruited 120 PCOS cases, diagnosed as per Rotterdam 2003 criteria, and an equal number of age-matched controls. Besides a detailed clinical assessment, subjects underwent biochemical and hormonal profiling. Genotyping for rs12255372 was done by PCR-RFLP. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of genotype-phenotype correlations. The PCOS cases reported fewer menstrual cycles per year and exhibited signs of hyperandrogenism. The heterozygous genotype of rs12255372 was strongly associated with the PCOS risk (OR = 2.00; 95%CI: 1.07-3.76). Unlike controls, only 3 cases harbored TT genotype, and the PCOS risk persisted in the dominant model (GT + TT) as well. Moreover, we found a synergistic effect modification by the variant genotype in the subjects who had family histories of T2DM, hirsutism, or menstrual irregularities. We report a significant association of the TCF7L2 polymorphic variant rs12255372 with the PCOS risk.

Behavioural changes, DNA damage and histological alterations in Labeo rohita fingerlings in response to organic-coated silver nanoparticles.

Silver nanoparticles (AgNPs) have garnered significant global attention from researchers due to their unique physicochemical properties and wide-ranging applications in industry and medicine. However, their release into aquatic ecosystems has raised concerns regarding potential ecotoxicological consequences. The present study investigated the effects of polyvinyl pyrrolidone-coated silver nanoparticles on Labeo rohita fingerlings, focusing on behavioural reactions, genotoxic effects, histological changes and bioaccumulation. L. rohita fingerlings were exposed to polyvinyl pyrrolidone-coated silver nanoparticles with sizes ranging from 18 to 29 nm for 7 days at concentrations of 100, 200, 400 and 800 ug/l. The nanoparticle zeta potential was found to be extremely negative, measuring - 55.5 mV for 18 nm and - 31.4 mV for 29 nm. Behavioural abnormalities, including respiratory distress, reduced responsiveness and erratic swimming, were observed in exposed groups compared to controls, with severity increasing with higher nanoparticle concentrations. Genotoxicity assessment revealed significantly higher DNA damage in kidney cells compared to gill cells. Histological examination of gill tissues showed clogging in primary and secondary lamellae, along with distorted anatomy, necrosis and vacuolar atrophy in peripheral tubules of the kidneys. The kidneys exhibited greater nanoparticle accumulation than the gills with prolonged exposure. Moreover, 18 nm AgNPs induced more pronounced DNA damage and histological alterations in the kidney and gill tissues compared to 29 nm nanoparticles. This study elucidates the critical role of monitoring AgNPs in aquatic systems, providing essential data on their behaviour and environmental impacts. The findings highlight the need for improved detection techniques and effective management of AgNP contamination. Future research should focus on developing more sensitive analytical methods, understanding long-term ecological effects and exploring innovative remediation strategies.

Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. OBJECTIVES: This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. MATERIALS AND METHODS: A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. RESULTS: Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. CONCLUSION: Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.

Development of highly discriminatory SCoT- and CBDP-based SCAR fingerprint for authentication of Indian senna (Senna alexandrina Mill.) formerly Cassia angustifolia Vahl.).

Introduction: Indian senna (Senna alexandrina Mill.) (formerly Cassia angustifolia Vahl.) is an important medicinal plant of the family Fabaceae. The leaves and pods of Indian senna yield sennosides and rhein-based laxative. Adulteration of Indian senna is a serious issue as with most of the medicinal plants used in the Indian systems of traditional medicine. The bulk of dried leaves and pods of morphologically related species, such as Cassia fistula, Senna occidentalis, Senna sophera, and Senna tora, is usually mixed with those of the Indian senna, and the admixture is used in laxative-based formulations. The present investigation is a modest attempt at developing species-specific start codon targeted (SCoT) polymorphism- and CAAT-box-derived polymorphism (CBDP)-based sequence-characterized amplified region (SCAR) markers for the identification and authentication of Indian senna and four adulterant species (C. fistula, S. occidentalis, S. sophera, and S. tora species). Methods: In this study, genomic DNA extracted from 44 accessions of Indian senna and four adulterant species was subjected to SCoT and CBDP PCR. The polymorphic amplicons were identified, eluted, ligated, and transformed into Escherichia coli DH5 α strain. PCR, restriction analysis, and DNA sequencing confirmed the transformed recombinant plasmid clones. Results: Post-sequencing, the sequence of the primary SCoT and CBDP primers was analyzed and extended into the unique signature sequence of the concerned accessions. This resulted in development of one SCoT-44- and two CBDP-25-based SCARs. SCoT-44 SCAR produced a signature amplicon of 287 bp for accession DCA120, and CBDP-25 SCAR yielded signature amplicons of 575 and 345 bp for accessions DCA13 and DCA119, respectively. The developed SCAR markers were validated across 48 samples (44 accessions of Indian senna and 4 adulterant species) and produced distinct amplicons in Indian senna only, while no such amplicon was observed in the other four adulterant species. Discussion: The information generated using these markers have been faithfully converted to single-locus, unequivocal, highly reproducible, and informative sequence-based SCAR markers. These markers will enable discrimination of individual plants on the basis of unique sequence-specific amplicons, which could be used as diagnostic markers to settle issues pertaining to the true identity of Indian senna.

Experimental study on the quasi-static and dynamic tensile behaviour of thermally treated Barakar sandstone in Jharia coal mine fire region, India.

In the present study, the effect of mild to high-temperature regimes on the quasi-static and dynamic tensile behaviours of Barakar sandstone from the Jharia coal mine fire region has been experimentally investigated. The experimental work has been performed on Brazilian disk specimens of Barakar sandstone, which are thermally treated up to 800 °C. The quasi-static and dynamic split tensile strength tests were carried out on a servo-controlled universal testing machine and Split Hopkinson Pressure Bar (SHPB), respectively. Microscopic and mineralogical changes were studied through a petrographic investigation. The experimental results suggest the prevalence of both, static and dynamic loading scenarios after 400 °C. Up to 400 °C, the quasi-static and dynamic tensile strengths increased due to the evaporation of water, which suggests a strengthening effect. However, beyond 400 °C, both strengths decreased significantly as newly formed thermal microcracks became prevalent. The dynamic tensile strength exhibits strain rate sensitivity up to 400 °C, although it shows a marginal decline in this sensitivity beyond this temperature threshold. The Dynamic Increase Factor (DIF) remained constant up to 400 °C and slightly increased after 400 °C. Furthermore, the characteristic strain rate at which the dynamic strength becomes twice the quasi-static strength remains consistent until reaching 400 °C but steadily decreases beyond this temperature. This experimental study represents the first attempt to validate the Kimberley model specifically for thermally treated rocks. Interestingly, the presence of water did not have a significant impact on the failure modes up to 400 °C, as the samples exhibited a dominant tensile failure mode, breaking into two halves with fewer fragments. However, as temperature increased, the failure behaviours became more complex due to the combined influence of thermally induced microcracks and the applied impact load. Cracks initially formed at the centre and subsequently, multiple shear cracks emerged and propagated in the loading direction, resulting in a high degree of fragmentation. This study also demonstrates that shear failure is not solely dependent on the loading rate but can also be influenced by temperature, further affecting the failure mode of the sandstone.

Descriptive spectrum of thiamine deficiency in pregnancy: A potentially preventable condition.

OBJECTIVE: Pregnancy, a nutritionally demanding situation in terms of macro- and micronutrient supply owing to heightened maternal, placental, and fetal needs, significantly affects thiamine reserves. Thiamine deficiency during pregnancy and the postpartum period, presenting with varied manifestations and outcomes, is a relatively common condition in our population. The study aimed to understand the various manifestations and outcomes of acute thiamine deficiency in pregnant and postpartum women, emphasizing the significance of early recognition and thiamine therapy to prevent serious complications during pregnancy and after childbirth. METHODS: This prospective study conducted in a tertiary care center in North India enrolled consecutive pregnant and postpartum women presenting with clinical features consistent with thiamine deficiency disorders, such as thiamine deficiency-related neuropathy, high-output heart failure, heart failure with reduced ejection fraction, Wernicke's encephalopathy, gastric beriberi, and thiamine-responsive acute pulmonary hypertension. In addition to capturing medical history including drug intake, dietary consumption, and comorbidities, women underwent brief relevant clinical examinations and laboratory assessments, including whole-blood thiamine levels. Response to intravenous thiamine supplementation was also monitored. RESULTS: Data of 31 women (12 pregnant, 19 postpartum) with a diagnosis of acute thiamine deficiency and a mean age of 28.88 ± 2.69 years were analyzed. The mean thiamine level was 1.28 ± 0.44 µg/dL with mean blood lactate of 3.46 ± 3.33. The most common presentation was gastric beriberi (n = 10), followed by paraparesis (n = 6), high-output heart failure (n = 6), acute pulmonary hypertension, heart failure with reduced ejection fraction (n = 3 each), and an acute confusional state (n = 2). All patients responded to thiamine challenge. CONCLUSION: In the context of borderline thiamine status, particularly in our population with endemic thiamine deficiency and heightened demand for thiamine during pregnancy and the peripartum period, the deficiency can have varied and serious manifestations of dry and wet beriberi. Early recognition of the clinical features and thiamine therapy can be life-saving. There is a need for validated clinical criteria owing to the non-availability of thiamine testing in resource-limited settings.

Thiamine deficiency-related neuropathy: A reversible entity from an endemic area.

BACKGROUND AND PURPOSE: Despite thiamine deficiency being a lesser-known entity in modern times, beriberi in various forms, including thiamine deficiency-related neuropathy, remains endemic in Kashmir due to the consumption of polished rice as a staple food. This observational study investigates cases of peripheral neuropathy of unknown etiology and their potential responsiveness to thiamine administration. METHODS: This prospective study enrolled adult patients presenting to the emergency department with weakness consistent with thiamine deficiency-related neuropathy and conducted a therapeutic challenge with thiamine on 41 patients. Response to thiamine therapy was monitored based on subjective and objective improvements in weakness and power. Patients were divided into thiamine responders (n = 25) and nonresponders (n = 16) based on their response to thiamine therapy and nerve conduction studies. RESULTS: Most of the baseline characteristics were similar between responders and nonresponders, except the responders exhibited lower thiamine levels and higher partial pressure of oxygen and lactate levels compared to nonresponders. All patients had a history of consuming polished rice and traditional salt tea. Although weakness in the lower limbs was present in both groups, nonresponders were more likely to exhibit weakness in all four limbs. Clinical improvement was observed within 24 h, but proximal muscle weakness persisted for an extended period of time. CONCLUSIONS: Thiamine deficiency-related neuropathy presents with predominant lower limb weakness, exacerbated by vomiting, poor food intake, psychiatric illness, and pregnancy. Thiamine challenge should be followed by observation of clinical and biochemical response.

Etiology and incidence of infection in Mechanically Ventilated Medical Intensive Care Unit Patients in a Tertiary Care Hospital

Introduction@#Intensive care unit (ICU) patients are at the greatest risk of acquiring nosocomial infections, partly because of their serious underlying disease, but also by exposure to life-saving invasive procedures. Hospital-acquired infections increase patient morbidity, increase the length of hospital stay and hospital costs, and also increases mortality rate. The basic knowledge of organisms infecting ICU patients is very important to empirically select appropriate antibiotics, so that the most likely infecting organisms are addressed.@*Objective@#The aim of the study was to find out the etiologic agents causing infection in medical intensive care unit patients.@*Results@#In our study of 289 patients, 180 (62.3%) showed a growth of organism during the stay in ICU. The most common site of infection was the respiratory tract in 138 patients (47.8%) with 60 patients (20.8%) showing Acinetobacter baumannii.

In silico designing of multiepitope-based-peptide (MBP) vaccine against MAPK protein express for Alzheimer's disease in Zebrafish.

Understanding the role of the mitogen-activated protein kinases (MAPKs) signalling pathway is essential in advancing treatments for neurodegenerative disorders like Alzheimer's. In this study, we investigate in-silico techniques involving computer-based methods to extract the MAPK1 sequence. Our applied methods enable us to analyze the protein's structure, evaluate its properties, establish its evolutionary relationships, and assess its prevalence in populations. We also predict epitopes, assess their ability to trigger immune responses, and check for allergenicity using advanced computational tools to understand their immunological properties comprehensively. We apply virtual screening, docking, and structure modelling to identify promising drug candidates, analyze their interactions, and enhance drug design processes. We identified a total of 30 cell-targeting molecules against the MAPK1 protein, where we selected top 10 CTL epitopes (PAGGGPNPG, GGGPNPGSG, SAPAGGGPN, AVSAPAGGG, AGGGPNPGS, ATAAVSAPA, TAAVSAPAG, ENIIGINDI, INDIIRTPT, and NDIIRTPTI) for further evaluation to determine their potential efficacy, safety, and suitability for vaccine design based on strong binding potential. The potential to cover a large portion of the world's population with these vaccines is substantial-88.5 % for one type and 99.99 % for another. In exploring the molecular docking analyses, we examined a library of compounds from the ZINC database. Among them, we identified twelve compounds with the lowest binding energy. Critical residues in the MAPK1 protein, such as VAL48, LYS63, CYS175, ASP176, LYS160, ALA61, LEU165, TYR45, SER162, ARG33, PRO365, PHE363, ILE40, ASN163, and GLU42, are pivotal for interactions with these compounds. Our result suggests that these compounds could influence the protein's behaviour. Moreover, our docking analyses revealed that the predicted peptides have a strong affinity for the MAPK1 protein. These peptides form stable complexes, indicating their potential as potent inhibitors. This study contributes to the identification of new drug compounds and the screening of their desired properties. These compounds could potentially help reduce the excessive activity of MAPK1, which is linked to Alzheimer's disease.

Biogenic silver nanoparticles: Synthesis, applications and challenges in food sector with special emphasis on aquaculture.

Aquaculture, a rapidly expanding global food sector faces challenges like pathogenic infections, water quality management and sustainability. Silver nanoparticles (AgNPs) have emerged as promising tools in aquaculture due to their antimicrobial, antiviral and antifungal properties. AgNPs offer alternatives to traditional antimicrobial agents. Their small size and unique physicochemical properties enhance antimicrobial activity, effectively inhibiting pathogen growth and reducing disease incidence in aquatic organisms. Additionally, AgNPs can improve water quality by catalyzing the removal of pollutants, heavy metals and nutrients, reducing environmental impacts. Despite their potential benefits, several challenges and knowledge gaps exist in the utilization of AgNPs in aquaculture. Addressing challenges related to regulation, sustainability and environmental impact will be crucial for realizing their full potential in the industry. Therefore, the present review aims to provide insight into the role of AgNPs, its challenges in aquaculture and also highlights key areas for future research.

Gene expression profiling and physiological adaptations of pearl spot (Etroplus suratensis) under varying salinity conditions.

Eutroplus suratensis (Pearl spot) is naturally found in estuarine environments and has been noted to have a high salinity tolerance. By examining the impact of various salinity levels on the growth and survival of pearl spot, the present study aims to enhance aquaculture profitability by assessing their adaptability and physiological adjustments to changes in salinity and determining their potential to acclimate to a broad range of salinity regimes. Results revealed no mortality in the control group (0 ppt), and in 15, 25 and 35 ppt treatment groups. However, the remaining groups (45, 60, and 75 ppt) showed differing levels of mortality with 44 % mortality observed in the 45 ppt group and 100 % mortality in both the 60 and 75 ppt groups. The expression analysis showed that liver IGF-1 mRNA expression increased by 2.6-fold at 15 ppt, and HSP70 mRNA expression in the liver also showed a significant increase with rising salinity levels. In addition, OSTF1 expression exhibited an increase at 15 ppt, whereas SOD and CAT expression reached their highest levels at 25 ppt. At 15 ppt, the expression of NKA mRNA increased significantly by 2.8-fold. The study's overall findings suggested that utilizing a salinity level of 15 ppt for pearl spot production could be viable for profitable aquaculture.

Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome.

Introduction: Polycystic Ovary syndrome (PCOS) affects the health of many women around theworld. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis. Methods: Eighteen mature parkes strain mice (4-5 weeks old) weighing18-21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kgbw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days. Results: In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice. Discussion: Quercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn't act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS.

Prevalence, Regional Variations, and Predictors of Overweight, Obesity, and Hypertension Among Healthy Reproductive-Age Indian Women: Nationwide Cross-Sectional Polycystic Ovary Syndrome Task Force Study.

BACKGROUND: A clear understanding of the anthropometric and sociodemographic risk factors related to BMI and hypertension categories is essential for more effective disease prevention, particularly in India. There is a paucity of nationally representative data on the dynamics of these risk factors, which have not been assessed among healthy reproductive-age Indian women. OBJECTIVE: This cross-sectional polycystic ovary syndrome (PCOS) task force study aimed to assess the anthropometric and sociodemographic characteristics of healthy reproductive-age Indian women and explore the association of these characteristics with various noncommunicable diseases. METHODS: We conducted a nationwide cross-sectional survey from 2018 to 2022 as part of the Indian Council of Medical Research-PCOS National Task Force study, with the primary aim of estimating the national prevalence of PCOS and regional phenotypic variations among women with PCOS. A multistage random sampling technique was adopted, and 7107 healthy women (aged 18-40 years) from 6 representative geographical zones of India were included in the study. The anthropometric indices and sociodemographic characteristics of these women were analyzed. Statistical analysis was performed to assess the association between exposure and outcome variables. RESULTS: Of the 7107 study participants, 3585 (50.44%) were from rural areas and 3522 (49.56%) were from urban areas. The prevalence of obesity increased from 8.1% using World Health Organization criteria to 40% using the revised consensus guidelines for Asian Indian populations. Women from urban areas showed higher proportions of overweight (524/1908, 27.46%), obesity (775/1908, 40.62%), and prehypertension (1008/1908, 52.83%) categories. A rising trend of obesity was observed with an increase in age. Women aged 18 to 23 years were healthy (314/724, 43.4%) and overweight (140/724, 19.3%) compared with women aged 36 to 40 years with obesity (448/911, 49.2%) and overweight (216/911, 23.7%). The proportion of obesity was high among South Indian women, with 49.53% (531/1072) and 66.14% (709/1072), using both World Health Organization criteria and the revised Indian guidelines for BMI, respectively. BMI with waist circumference and waist-to-height ratio had a statistically significant linear relationship (r=0.417; P<.001 and r=0.422; P<.001, respectively). However, the magnitude, or strength, of the association was relatively weak (0.3<|r|<0.5). Statistical analysis showed that the strongest predictors of being overweight or obese were older age, level of education, wealth quintile, and area of residence. CONCLUSIONS: Anthropometric and sociodemographic characteristics are useful predictors of overweight- and obesity-related syndromes, including prehypertension, among healthy Indian women. Increased attention to the health of Indian women from public health experts and policy makers is warranted. The findings of this study can be leveraged to offer valuable insights, informing health decision-making and targeted interventions that mitigate risk factors of overweight, obesity, and hypertension. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/23437.

Pre-polycystic ovary syndrome and polymenorrhoea as new facets of polycystic ovary syndrome (PCOS): Evidences from a single centre data set.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex disorder with diverse metabolic implications. Diagnosis typically relies on oligo-amenorrhoea (OA), hyperandrogenism (HA), and polycystic ovarian morphology (PCOM). However, the role of polymenorrhoea in PCOS remains understudied. Additionally, limited information exists regarding metabolic disturbances in women with partial PCOS phenotypes that do not meet diagnostic criteria. This extensive database aims to provide substantial evidence on the metabolic implications of polymenorrhoea and partial PCOS phenotypes. DESIGN: Prospective observational study. PATIENTS AND MEASUREMENTS: In this single-centre study, 6463 women with PCOS-like characteristics and 3142 age-matched healthy women were included. The study compared clinical (anthropometry, modified Ferriman Gallwey [mFG] score), hormonal (serum testosterone), and metabolic (plasma glucose, serum lipids, insulin) characteristics between women diagnosed with PCOS, those with partial PCOS phenotypes, and the healthy control group RESULTS: In all, 5174 women met Rotterdam criteria for PCOS diagnosis, while 737 were classified as Pre-PCOS, including HA (n = 538), OA (n = 121), or PCOM (n = 78). Common clinical features included oligomenorrhoea (75.5%), hirsutism (82.9%), obesity (27.2%), hypertension (1.6%), metabolic syndrome (19.6%), and diabetes mellitus (5.6%). Women diagnosed with PCOS, HA only, and OA only exhibited higher average body mass index, plasma glucose levels (both fasting and 2 h after the oral glucose tolerance test), and lipid fractions in comparison to those with PCOM and the healthy controls. However, indices of insulin resistance were similar among women with PCOS, HA, PCOM, and OA, albeit higher than in the healthy controls. The polymenorrhoea subgroup (5.9%) had lower BMI and serum testosterone, but similar mFG score, plasma glucose, insulin, and lipid levels as the oligomenorrhoea subgroup. CONCLUSION: The metabolic disturbances observed in Pre-PCOS women highlight the need to reassess diagnostic criteria. Including the polymenorrhoea subcategory in PCOS criteria is recommended due to similar metabolic dysfunctions as the oligomenorrhoea group.

Efficacy of serum anti-mullerian hormone (AMH) levels for prediction of polycystic ovary syndrome (PCOS) and its association with clinical, biochemical and hormonal parameters.

Anti-mullerian hormone (AMH) has been proposed to add significance to diagnosis of PCOS in case of ambiguity. However, variable cutoffs of AHM among PCOS women have been reported. Using case-control design, this study investigated the diagnostic threshold of serum AMH levels among age matched 113 PCOS and 75 normo-ovulatory women and its correlation with clinical, hormonal and ultrasonographic parameters.PCOS was defined as per Rotterdam criteria 2003. Results depicted the mean serum AMH level to be significantly higher in PCOS group (7.84 ± 3.67vs. 3.23 ± 1.56 ng/mL) than controls. The AMH levels were positively(p = 0.001) associated with ovarian volume (r = 0.521) as well as number of ovarian follicles(r = 0.461). Further, serum AMH levels showed a positive correlation with luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (r = 0.206, p = 0.02), but no correlation significant with age, BMI,FG score and testosterone levels. As per receiver operating characteristic (ROC) curve, cut-off was worked out to be 3.76 ng/ml with 86.7% sensitivity and 62.7% specificity. The mean level of AMH were highest among PCOS women with phenotype A (12.67 ± 3.46 ng/ml) with least among PCOS women displaying phenotype B(7.28 ± 1.60 ng/ml) where there is absence of PCOM. In conclusion, serum AMH levels are highly predictive of PCOM and high LH/FSH ratio among PCOS women and may be a potent diagnostic marker of ovarian dysfunction either alone or in conjunction with other tools. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01058-4.

Biochemical and haematological abnormalities in severe acute organophosphorus poisoning / Anomalías bioquímicas y hematológicas en la intoxicación grave por organofosforados. Estudio prospectivo en un solo centro

Background: Organophosphorus insecticides are considered one of the commonest causes of morbidity and mortality due to poisoning worldwide. Severe organophosphorus poisoning can lead to multiple sometimes lethal metabolic and haematological abnormalities. Methods: A total of 141 OP poisoning patients were admitted during the study period and their blood samples were collected on admission and analysed for the biochemical abnormalities. Results: Out of 141 patients 76 were males (53.9%) and 65 were females (46.1%). Bradycardia with Pulse rate of less than 60 was seen in in 21 patients (14.7). Hypoxemia with oxygen saturation of less than 94% was seen in 32 (22.7%). leucocytosis with TLC o 11000 or more was seen in 19 patients (13.5%).101 patients (83.5%) had low serum choline esterase levels less than 1.5kU/L. Hypokalaemia with K+ of less than 3.5 was seen in 16 patients (9.9%). Five patients died out of 141 (3.5%). Hypoxemia Spo2 of less than 90% was seen in 3 (60%) patients who died and hypoglycaemia with blood glucose of less than 70mg/dl was seen in 2 out of 5 Patients (40%). Conclusions: low choline esterase levels less than 1.5kU/L was the most common abnormality indicating severe poisoning followed by hypoxemia. Both Hypoxemia and low acetylcholine esterase levels are bad prognostic signs and result in high mortality in organophosphorus poisoning. (AU)

Introducción: De entre todos los procesos de intoxicación, el envenenamiento por organofósforados se considera una de las causas más comunes de morbilidad y mortalidad en todo el mundo. La intoxicación grave por organofósforo puede provocar múltiples anomalías metabólicas y hematológicas, a veces letales. Métodos: Un total de 141 pacientes intoxicados por organofósforados fueron ingresados durante el periodo de estudio y sus muestras e sangre fueron recogidas al ingreso y analizadas para detectar las anomalías bioquímicas. Resultados: De los 141 pacientes, 76 eran varones (53,9%) y 65 mujeres (46,1%). Se observó bradicardia con una frecuencia de pulso inferior a 60 en 21 pacientes (14,7). Se observó hipoxemia con una saturación de oxígeno inferior al 94% en 32 (22,7%). Leucocitosis con un recuento total de leucocitos de 11.000 o más en 19 pacientes (13,5%). 101 pacientes (83,5%) tenían niveles bajos de colina esterasa sérica inferiores a 1,5 kU/L. Se observó hipopotasemia con K+ inferior a 3,5 en 16 pacientes (9,9%). Cinco pacientes fallecieron de un total de 141 (3,5%). Se observó hipoxemia Spo2 inferior al 90% en 3 (60%) pacientes que fallecieron e hipoglucemia con glucemia inferior a 70 mg/dl en 2 de 5 pacientes (40%). Conclusiones: Los niveles bajos de colinesterasa inferiores a 1,5 kU/L fueron la anomalía más frecuente que indicaba intoxicación grave, seguida de hipoxemia. La hipoxemia, la hipoglucemia y los niveles bajos de acetilcolinesterasa son signos de mal pronóstico y dan lugar a una elevada mortalidad en la intoxicación por organofosforados. (AU)

Normative range of various serum hormonal parameters among Indian women of reproductive age: ICMR-PCOS task force study outcome.

Background: The hormonal profile varies considerably with age, gender, ethnicity, diet or physiological state of an individual. Limited population-specific studies have studied the variations in hormonal parameters among apparently healthy women. We aimed to analyse the biological reference interval for various hormonal parameters in the reproductive-aged healthy Indian women. Methods: Out of 3877 participants that were clinically evaluated, 1441 subjects were subjected to laboratory investigations. All participants underwent a detailed clinical, biochemical and hormonal profiling. The hormone analysis was carried out at a single centre using a uniform methodology. Among the participants evaluated for biochemical and hormonal parameters, subjects that presented any abnormal profile or had incomplete investigations (n = 593) were excluded for further analysis. Findings: The mean age (±SD) of the subjects retained in the final analysis (n = 848) was 29.9 (±6.3) years. In the present study, the biological reference interval (2.5th-97.5th centile) observed were: serum T4: µg/dL (5.23-12.31), TSH: µg/mL (0.52-4.16) and serum prolactin: ng/mL (5.13-37.35), LH: mIU/mL (2.75-20.68), FSH: mIU/mL 2.59-15.12), serum total testosterone: ng/mL (0.06-0.68), fasting insulin: mIU/mL (1.92-39.72), morning cortisol: µg/dL (4.71-19.64), DHEAS:µg/dL (50.61-342.6) and SHBG: nmol/L (21.37-117.54). Unlike T4, TSH, LH, and E2, the biological reference interval for prolactin, FSH, testosterone, C-peptide insulin and DHEAS varied when the subjects were stratified by age (p < 0.05). The comparative analysis showed marginal differences in the normative ranges for the hormones analysed among different populations. Interpretation: Our first large composite data on hormonal measures will benefit future endeavours to define biological reference intervals in reproductive-aged Indian women. Funding: The study was financially supported by the grant-in-aid from ICMR vide file No:5/7/13337/2015-RBMH.

Hyperactive behaviour of growth differentiation factor- 15 (GDF-15) in conjunction with iron trafficking transporters and suppression of Nrf-2 gene in diabetes and metabolic syndrome.

Multiple parallel factors are frequently interrogated with various toxic radicals which are abundantly generated in the liver, heart, and pancreas in stress conditions. They are actively involved in the development of diabetes and metabolic aberrations. However, whether over-activation of GDF-15mRNA and influxes of iron-by-iron trafficking genes are directly suppressing the Nrf-2 gene in patients with diabetes and metabolic aberrations in context with undiagnosed individuals with diabetes and metabolic aberrations? Therefore, we have investigated inter and intra- related Zip8/14 mRNA, GDF-15mRNA, and Nrf-2 mRNA expressions in diabetes and metabolic syndrome as it is expected to be up to 134 million by 2045 in India. We recruited 120 subjects from the Department of Medicine, Endocrinology and Metabolic Clinic, All India Institute of Medical Sciences, New Delhi, India. Various investigations related to anthropometry, nutritional, hematological, biochemical, cytokine, and oxidative stress were measured in diabetes, metabolic syndrome, diabetes with metabolic aberration, and healthy controls. Relative expression of GDF-15, ZIP8, ZIP14, Nrf-2, and housekeeping genes was done in all subjects. Stress-responsive cytokines are highly expressed in patients with metabolic aberration with respect to body weight, IR, waist circumference, and fat mass. IL-1ß, TNF-α, and IL-6 levels were significantly higher in metabolic syndrome, whereas Adiponectin levels were profoundly lower side. MDA levels were significantly raised in diabetes with metabolic syndrome while SOD activities were lowered (p = 0.001). GDF-15 mRNA expression was 1.79-fold upregulated in group III as compared with Group I while 2-threefold down-regulation of Nrf-2 expression was observed in diabetes with metabolic aberration groups. Zip 8 mRNA expressions were downregulated (p = 0.014), and Zip 14 mRNA expressions were upregulated (p = 0.06) in diabetes and metabolic aberrations. The association of GDF-15 and Nrf-2 mRNA expression was found contradictory and highly interlinked with ROS. Zip 8/14mRNA expressions were also dysregulated in diabetes and metabolic-associated complications.