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Abstract Background Patients with diabetes on dialysis experience wide variations in glucose levels and an increased risk of hypoglycaemia. Due to the inaccuracies of HbA1c in dialysis patients, JBDS-IP and KDIGO recommend the use of continuous glucose monitoring (CGM). We conducted a systematic review to examine the current evidence for CGM use and its impact on clinical outcomes in patients with diabetes on dialysis. Methods A search of MEDLINE(R) ALL, Ovid Emcare, Journals@Ovid Full Text and Embase databases were conducted. Clinical or observational trials in adults with Type 1(T1D) or Type 2 (T2D) diabetes on dialysis and CGM intervention reporting on glycaemic outcomes were included. Results Of the 936 citations identified, 49 duplicates were removed. 887 citations were screened by title and abstract. 9 full texts were reviewed and a further 7 excluded due to duplications or failure to meet to selection criteria. Data was extracted for 2 studies, both prospective before-and-after interventional studies with no control group. Joubert et al. (2015) showed results for 15 participants with T1D. Mean CGM glucose level decreased from 8.37mmol/L at baseline to 7.7mmol/L at the end of the CGM period (p 10mmol/L decreased from 41 to 30% (p

Adequate control of thyroid function is crucial for optimal pregnancy outcomes and neurodevelopment of the offspring, and testing for thyroid function is ideally performed using manufacturer- and gestation-specific reference ranges. While universal screening for thyroid dysfunction is not recommended, targeted case finding of women at risk of thyroid disease during pregnancy is advised. A number of controversies continue to fuel debate including: (i) the target range for thyroid stimulating hormone (TSH) in women with subfertility planning pregnancy, (ii) management of mild thyroid hypofunction before and during pregnancy, (iii) the treatment of thyroid peroxidase (TPO) antibody-positive euthyroid women with levothyroxine, (iv) the optimal choice of antithyroid treatment in women with hyperthyroidism. A significant body of evidence has accumulated in recent years, including large systematic reviews and meta-analyses of observational studies determining effects of thyroid dysfunction on pregnancy and fetal outcomes. In addition, outcomes from important randomised trials continue to inform current guidance on how to best care for women with thyroid dysfunction before and during pregnancy.

Abstract Background Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration PROSPERO CRD42021272686.

Rice followed by wheat is the dominant cropping system in the middle Indo-Gangetic plains (IGP). Lower productivity (4.8 t ha−1) of this cropping system in Bihar, compared to the national average (6.8 t ha−1) due to several climate- and production-related issues, is a matter of concern for the farmers and the policymakers. Keeping all these in view, an experiment with rice–wheat cropping system was carried out during 2020–21 and 2021–22 in 17 adopted villages of 13 districts of Bihar under the Project “Climate Resilient Agriculture Program (CRAP)” to evaluate the feasibility of early transplanting of rice in the month of June with the aim of achieving higher system productivity by early harvesting of rice and subsequent timely sowing of wheat before 15 November with the provision of assured irrigation. In this study, the concept of an innovative community irrigation approach and single-phase 3-hp submersible pump was employed. Long-duration rice variety (150 days) Rajendra Mahsuri-1 was sown during 20–25 May in the nursery and transplanted through puddling operation during 15–20 June in 17 locations. Under delayed conditions, the nursery sowing and transplanting window were 10–15 June and 10–15 July, respectively. Timely sown rice grown with the provision of a community irrigation system achieved a grain yield of 5.2 t ha−1 and 85.8% higher water productivity, compared to late-sown crops. Following the harvest of rice, the HD-2967 variety of wheat was planted in the first fortnight of November and harvested in the first week of April, yielding 4.9 t ha−1 with the application of 2–3 irrigations based on soil type and evaporative demand. Timely harvesting of wheat facilitated farmers of the region to take an additional crop of summer green gram. With an assured irrigation system and shifting planting dates and thereby managing climatic risks, the overall productivity of the rice–wheat cropping system was achieved to the tune of 10.1 t ha−1 with a cropping intensity of 300% for better adaptation and sustainable production.

Multicellular organisms are constantly subjected to pathogens that might be harmful. Although insects lack an adaptive immune system, they possess highly effective anti-infective mechanisms. Bacterial phagocytosis and parasite encapsulation are some forms of cellular responses. Insects often defend themselves against infections through a humoral response. This phenomenon includes the secretion of antimicrobial peptides into the hemolymph. Specific receptors for detecting infection are required for the recognition of foreign pathogens such as the proteins that recognize glucans and peptidoglycans, together referred to as PGRPs and βGRPs. Activation of these receptors leads to the stimulation of signaling pathways which further activates the genes encoding for antimicrobial peptides. Some instances of such pathways are the JAK-STAT, Imd, and Toll. The host immune response that frequently accompanies infections has, however, been circumvented by diseases, which may have assisted insects evolve their own complicated immune systems. The role of ncRNAs in insect immunology has been discussed in several notable studies and reviews. This paper examines the most recent research on the immune regulatory function of ncRNAs during insect-pathogen crosstalk, including insect- and pathogen-encoded miRNAs and lncRNAs, and provides an overview of the important insect signaling pathways and effector mechanisms activated by diverse pathogen invaders.

Abstract Objective True identity and specific set of markers to enrich endometrial stem cells still remains elusive. Present study was undertaken to further substantiate that very small embryonic-like stem cells (VSELs) are the true and elusive stem cells in adult mice endometrium. Methods This was achieved by undertaking three sets of experiments. Firstly, SSEA-1+ and Oct-4 + positive VSELs, sorted from GFP mice, were transplanted into the uterine horns of wild-type Swiss mice and GFP uptake was studied within the same estrus cycle. Secondly, uterine lumen was scratched surgically and OCT-4 expressing stem/progenitor cells were studied at the site of injury after 24–72 h. Thirdly, OCT-4 expression was studied in the endometrium and myometrium of adult mice after neonatal exposure to estradiol (20 µg/pup/day on days 5–7 after birth). Results GFP + ve VSELs expressing SSEA-1 and Oct-4 engrafted and differentiated into the epithelial cells lining the lumen as well as the glands during the estrus stage when maximum remodeling occurs. Mechanical scratching activated tissue-resident, nuclear OCT-4 positive VSELs and slightly bigger ‘progenitors’ endometrial stem cells (EnSCs, cytoplasmic OCT-4) which underwent clonal expansion and further differentiated into luminal and glandular epithelial cells. Neonatal exposure to endocrine disruption resulted in increased numbers of OCT-4 positive VSELs/EnSCs in adult endometrium. Discussion Results support the presence of functionally active VSELs in adult endometrium. VSELs self-renew and give rise to EnSCs that further differentiate into epithelial cells under normal physiological conditions. Also, VSELs are vulnerable to endocrine insults. To conclude VSELs are true and elusive uterine stem cells that maintain life-long uterine homeostasis and their dysregulation may result in various pathologies. Graphical Abstract

Abstract Follicle stimulating hormone (FSH) is secreted by the anterior pituitary and acts on the germ cells indirectly through Granulosa cells in ovaries and Sertoli cells in the testes. Extragonadal action of FSH has been reported but is still debated. Adult tissues harbor two populations of stem cells including a reserve population of primitive, small-sized, pluripotent very small embryonic-like stem cells (VSELs) and slightly bigger, tissue-specific progenitors which include ovarian stem cells (OSCs) in ovaries, spermatogonial stem cells (SSCs) in testes, endometrial stem cells (EnSCs) in uterus and hematopoietic stem cells (HSCs) in the bone marrow. Data has accumulated in animal models showing FSHR expression on both VSELs and progenitors in ovaries, testes, uterus and bone marrow and eventually gets lost as the cells differentiate further. FSH exerts a direct action on the stem/progenitor cells via alternatively spliced FSHR-3 rather than the canonical FSHR-1. FSH stimulates VSELs to undergo asymmetrical cell divisions to self-renew and give rise to the progenitors that in turn undergo symmetrical cell divisions and clonal expansions followed by differentiation into specific cell types. Excessive self-renewal of VSELs results in cancer and this explains ubiquitous expression of embryonic markers including nuclear OCT-4 along with FSHR in cancerous tissues. Focus of this review is to compile published data to support this concept. FSHR expression in stem/progenitor cells was confirmed by immuno-fluorescence, Western blotting, in situ hybridization and by quantitative RT-PCR. Two different commercially available antibodies (Abcam, Santacruz) were used to confirm specificity of FSHR expression along with omission of primary antibody and pre-incubation of antibody with immunizing peptide as negative controls. Western blotting allowed detection of alternatively spliced FSHR isoforms. Oligoprobes and primers specific for Fshr-1 and Fshr-3 were used to study these alternately-sliced isoforms by in situ hybridization and their differential expression upon FSH treatment by qRT-PCR. To conclude, stem/progenitor cells in adult tissues express FSHR and directly respond to FSH via FSHR-3. These findings change the field of FSH-FSHR biology, call for paradigm shift, explain FSHR expression on cancer cells in multiple organs and provide straightforward explanations for various existing conundrums including extragonadal expression of FSHR.

AimWe aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.MethodsThis was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.ResultsOf 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).ConclusionIndividuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.

Objectives: We aim to study the prevalence of various lower urinary tract symptoms in women with overactive bladder (OAB). We also evaluated the impact of OAB on patient’s quality of life (QOL) through various validated self reporting questionnaires. Methods: An observational cross-sectional study was done where a total of 200 patients who were confirmed cases of OAB were included in the study. The patients were questioned using four structured well designed validated questionnaires and the data were recorded and analysed. Results: Age of patients ranged from 18 to 72 years. Urine frequency (99%) was the most commonly reported symptom followed by nocturia (91%) and urgency (89%). The mean scores for American urology association symptom index (AUASI) was 17, total bothersomeness score (TBS):30.17, urogenital distress inventory (UDI) - 6:58.75 and incontinence impact questionnaire (IIQ -7) was 75.95. Higher scores in IIQ-7 and UDI-6 correlated well with negative impact on quality of life and this association was found to be statistically significant. Conclusion: This study offers an introduction to the concept of QOL assessment using short form questionnaires for patient with symptoms of OAB. Many sufferers seek to manage their symptoms by adjusting to the problem instead of seeking treatment. This has not only puts a negative impact on the quality of life of women but also puts a financial burden on society especially in the developing countries.

Soils of Indian Konkan region, part of ecologically sensitive Western Ghats have been subjected to anthropogenic activities of late. This has endangered the ecological security through conspicuous losses in topsoil quality. The rationale of the present study was to map the soil properties and create management zones for ensuring food and nutritional security. The study was conducted in South Goa district of the state of Goa located in Konkan region. A total of 258 geo-referenced soil samples were collected and analyzed for pH, EC, SOC, available N, P, K and DTPA extractable micronutrients viz., Zn, Cu, Fe and Mn. Soil pH was found to be in acidic range. A wide variability existed in SOC content ranging from 0.12-5.85%. EC was mostly neutral with mean value 0.08±0.37 dSm-1, while available nitrogen (AN), available phosphorus (AP) and available potassium (AK) varied in range from 56.4-621.6 kg ha-1, 0.5-49.7 kg ha-1 and 31.5-786.2 kg ha-1 with mean values 211.2±76.9, 8.4±8.2 and 202.3±137.6 kg ha-1, respectively. A wide range was exhibited by cationic DTPA extractable Zn, Cu, Fe and Mn with mean values, 0.22±0.30, 0.44±0.60, 7.78±5.98 and 7.86±5.86 mg kg-1, respectively. Soil pH exhibited significant positive correlation with EC, AP AK and Zn and negative correlation with Fe and Cu. SOC exhibited significantly correlated with AN, AP, AK, Zn and Fe. Geo-statistical analysis revealed J-Bessel as best fit semivariogram model for pH, AP and AK; Rational Quadratic for EC, SOC, Zn and Mn; Hole effect for AN; Stable for Cu and K-Bessel for Fe for their spatial mapping. Four principal components showed eigenvalues more than one and cumulative variability of 59.38%. Three distinct soil management zones showing significant variation in soil properties were identified and delineated for wider scale management of soils. Precision nutrient management based on spatial variation and their mapping would enable refined agricultural and environmental management practices in the region.

Abstract Background Very small embryonic-like stem cells (VSELs) exist in adult organs, express pluripotent markers and have the ability to differentiate into three germ layers in vitro. Testicular, ovarian and hematopoietic stem/progenitor cells express receptors for follicle stimulating (FSH) and ovarian hormones and are activated by them to undergo proliferation/differentiation. VSELs exist in mouse uterus and are regulated by physiological dose of estradiol (E) & progesterone (P) during endometrial growth, differentiation and regeneration/remodeling. In the present study, effects of daily administration of E (2 μg/day), P (1 mg/Kg/day) or FSH (5 IU/day) for 7 days on the endometrium and stem/progenitor cells was studied in bilaterally ovariectomized mice. Results E treatment resulted in hypertrophy whereas P resulted in hyperplasia and overcrowding of epithelial cells. FSH also directly stimulated the endometrial cells. Nuclear OCT-4A positive VSELs were visualized in ovariectomized (atrophied) endometrium and cytoplasmic OCT-4B positive epithelial, stromal and endothelial cells were observed after treatment. FSH treated uterine tissue showed presence of 4 alternately spliced FSHR isoforms by Western blotting. 3–5 μm VSELs with a surface phenotype of LIN-/CD45-/SCA-1+ were enumerated by flow cytometry and were found to express ER, PR, FSHR1 and FSHR3 by RT-PCR analysis. Differential effects of treatment were observed on pluripotent (Oct4A, Sox2, Nanog), progenitors (Oct-4, Sca-1), primordial germ cells (Stella, Fragilis) and proliferation (Pcna) specific transcripts by qRT-PCR analysis. FSH and P (rather than E) exerted profound, direct stimulatory effects on uterine VSELs. Asymmetric, symmetric divisions and clonal expansion of stem/progenitor cells was confirmed by co-expression of OCT-4 and NUMB. Conclusions Results confirm presence of VSELs and their regulation by circulatory hormones in mouse uterus. Stem cell activation was more prominent after P and FSH compared to E treatment. The results question whether epithelial cells proliferation is regulated by paracrine influence of stromal cells or due to direct action of hormones on stem cells. VSELs expressing nuclear OCT-4A are the most primitive and pluripotent stem cells, undergo asymmetric cell division to self-renew and differentiate into epithelial, stromal and endothelial cells with cytoplasmic OCT-4B. Role of follicle stimulating and steroid hormones on the stem cells needs to be studied in various uterine pathologies.

Multi-ratooning increases productivity and profitability of the sugarcane (Saccharum officinarum L.) production system, however the cane yields decline in subsequent ratoon crops owing to declining soil health. The present field experiment was conducted to assess the long-term effect of bio-manure addition on yield, soil quality and carbon sequestration in sugarcane plant-ratoon system during 2003-2013. It consisted of 10 treatments, viz. farmyard manure (FYM) (10 t/ha), biogas slurry (BS) (10 t/ha), sulphitation press mud cake (SPMC) (10 t/ha), vermi-compost (VC) (10 t/ha) alone and each in combination with Gluconacetobacter diazotrophicus (Gd), control and recommended dose of fertilizers (RDF). The plant and ratoon crops yields with farmyard manure, sulphitation press mud cake (SPMC), biogas slurry and vermi-compost added alone (10 t/ha) or with Gluconacetobacter diazotrophicus (Gd) were at par with RDF till the fourth ratoon crop. However, significant increase in ratoon crop yield with bio manures addition over RDF were recorded from fifth to ninth ratoon crop. Bio manure addition enhanced soil quality through increased SOC, infiltration rate (up to 47.5%), soil aggregates (up to 20.3%), soil microbial biomass carbon (SMBC) and microbial biomass nitrogen (SMBN) and decreased bulk density (up to 12.1%). The highest increase in SOC (72%), SMBC (413.86%) and SMBN (113.88%) were registered with SPMC + Gd addition. A two fold increase was recorded in average annual rate of soil carbon sequestration (1.05 to 1.97 t/ha/yr) against control (0.49 t/ha/yr). A linear relationship existed between SOC, carbon sequestration rate, cane yield and gross carbon input.