Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

The neglected spectrum of COVID-19 pandemic - postpartum depression among COVID-19 infected South-Indian women - a cohort study.

The study aims to explore the burden of postpartum depression among COVID-19-infected mothers and stressor factors. A single-centre observational cohort study was conducted in South India to evaluate postpartum depression among 106 COVID-19-infected women who delivered from December 2020 to May 2021. Also, stressor factors related to COVID-19 infection were figured out to analyse their role in depression. Almost half of the COVID-19-infected mothers had a global EPDS score ≥ 10 and were at risk of depression during the pandemic. The depressive symptoms were not confined to the immediate postpartum period, but significantly impacted mothers until 6 months following childbirth. SYNOPSIS: COVID-19 infection not only affects the physical well-being but also adversely affects the mental health of the infected persons. Postpartum mothers who require the utmost care and support, are facing social deprivation due to the COVID-19 pandemic. This triggers the already fragile mental state of postpartum women and may worsen the level of depression.

A 3D-Printable, Low-Cost Obturator for Less Invasive Gynecologic Brachytherapy.

The purpose of this report is to design, develop, and evaluate a cost-effective applicator for interstitial brachytherapy (ISBT) to minimize patient morbidity and facilitate access to curative radiation treatment for gynecologic cancers, especially in low-resource settings. A computer-aided design and prototype were developed of a proposed applicator that incorporates 44 slotted channels to gently guide needles, with or without a tandem, through the vaginal canal, effectively eliminating the need for transcutaneous needle insertions typically employed during ISBT of advanced gynecologic cancer and thus reducing the risk of vaginal laceration and bladder or rectal injury. The tested prototype was developed using AutoCAD software (Autodesk, San Francisco, CA) and 3D printed in Accura Xtreme Gray material using stereolithography. Small-scale iterative tests using a gelatin phantom were conducted on this prototype to confirm the efficacy of the applicator through inter-operator usability, needle stability, and needle arrangement. A promising prototype was developed aimed at addressing key issues with traditional perineum-based templates to facilitate ISBT, including being able to cover bulky tumors with parametrial extension reliably, decrease the risk of tissue or organ injury, and treat women with a prior hysterectomy. Results of preclinical testing demonstrated that the applicator met its purpose, suggesting that it may facilitate ISBT without the morbidity typically associated with the procedure, especially by addressing concerns associated with implementing the procedure in low-resource settings. The applicator shows substantial promise in the treatment of advanced gynecologic cancer. While further testing remains necessary to confirm its translatability to the clinical setting, the applicator appears capable of meeting its design objectives, representing its potential for improving upon current methods.

RefZ facilitates the switch from medial to polar division during spore formation in Bacillus subtilis.

During sporulation, Bacillus subtilis redeploys the division protein FtsZ from midcell to the cell poles, ultimately generating an asymmetric septum. Here, we describe a sporulation-induced protein, RefZ, that facilitates the switch from a medial to a polar FtsZ ring placement. The artificial expression of RefZ during vegetative growth converts FtsZ rings into FtsZ spirals, arcs, and foci, leading to filamentation and lysis. Mutations in FtsZ specifically suppress RefZ-dependent division inhibition, suggesting that RefZ may target FtsZ. During sporulation, cells lacking RefZ are delayed in polar FtsZ ring formation, spending more time in the medial and transition stages of FtsZ ring assembly. A RefZ-green fluorescent protein (GFP) fusion localizes in weak polar foci at the onset of sporulation and as a brighter midcell focus at the time of polar division. RefZ has a TetR DNA binding motif, and point mutations in the putative recognition helix disrupt focus formation and abrogate cell division inhibition. Finally, chromatin immunoprecipitation assays identified sites of RefZ enrichment in the origin region and near the terminus. Collectively, these data support a model in which RefZ helps promote the switch from medial to polar division and is guided by the organization of the chromosome. Models in which RefZ acts as an activator of FtsZ ring assembly near the cell poles or as an inhibitor of the transient medial ring at midcell are discussed.

Efficacy of myo-inositol and d-chiro-inositol combination on menstrual cycle regulation and improving insulin resistance in young women with polycystic ovary syndrome: A randomized open-label study.

OBJECTIVE: To compare the effect of myo-inositol and d-chiro-inositol in combination (MI + DCI) with combined hormonal contraceptive (CHC) on menstrual cycle regulation in young Indian women with polycystic ovary syndrome (PCOS). METHODS: Seventy young women with PCOS aged 15-24 years with delayed cycles were randomized into two groups and were treated for 6 months with MI + DCI (550 + 150 mg, 3.6:1 ratio) twice a day and CHC (ethinyl estradiol 20 µg + drospirenone 3 mg) once a day. RESULTS: Spontaneous menses resumed in 28 (84.85%) young women on MI + DCI, compared with withdrawal bleeding in 34 (100%) on CHC. The mean cycle length reduced with both MI + DCI (124.54 ± 8.08 to 57.75 ± 3.00 days, P < 0.001) and CHC (105.88 ± 7.96 to 30.53 ± 2.95 days, P < 0.001). Regular menstrual cycles were established in 9 (27.27%) young women with MI + DCI (P = 0.001) and 30 (88.23%) with CHC (P < 0.001). Three months after stopping the treatment, 24 young women (85.71%) on MI + DCI and 25 (73.53%) on CHC continued to have spontaneous cycles. Anti-Müllerian hormone decreased with both the drugs (P = 0.001), whereas luteinizing hormone (P = 0.001) and testosterone (P = 0.04) decreased with CHC and homeostatic model assessment of insulin resistance (P < 0.001) with MI + DCI. CONCLUSION: Myo-inositol and d-chiro-inositol in combination (3.6:1 ratio) are effective in regularizing menstrual cycles and improving insulin resistance. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI/2018/03/012643). http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=20969&EncHid=&userName=myo-inositol.

The sigE gene is required for normal expression of heterocyst-specific genes in Anabaena sp. strain PCC 7120.

The filamentous cyanobacterium Anabaena (Nostoc) sp. strain PCC 7120 produces specialized cells for nitrogen fixation called heterocysts. Previous work showed that the group 2 sigma factor sigE (alr4249; previously called sigF) is upregulated in differentiating heterocysts 16 h after nitrogen step-down. We now show that the sigE gene is required for normal heterocyst development and normal expression levels of several heterocyst-specific genes. Mobility shift assays showed that the transcription factor NtcA binds to sites in the upstream region of sigE and that this binding is enhanced by 2-oxoglutarate (2-OG). Deletions of the region containing the NtcA binding sites in P(sigE)-gfp reporter plasmids showed that the sites contribute to normal developmental regulation but are not essential for upregulation in heterocysts. Northern RNA blot analysis of nifH mRNA revealed delayed and reduced transcript levels during heterocyst differentiation in a sigE mutant background. Quantitative reverse transcription-PCR (qRT-PCR) analyses of the sigE mutant showed lower levels of transcripts for nifH, fdxH, and hglE2 but normal levels for hupL. We developed a P(nifHD)-gfp reporter construct that showed strong heterocyst-specific expression. Time-lapse microscopy of the P(nifHD)-gfp reporter in a sigE mutant background showed delayed development and undetectable green fluorescent protein (GFP) fluorescence. Overexpression of sigE caused accelerated heterocyst development, an increased heterocyst frequency, and premature expression of GFP fluorescence from the P(nifHD)-gfp reporter.

Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut.

Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis.

Cyanobacterial heterocysts.

Many multicellular cyanobacteria produce specialized nitrogen-fixing heterocysts. During diazotrophic growth of the model organism Anabaena (Nostoc) sp. strain PCC 7120, a regulated developmental pattern of single heterocysts separated by about 10 to 20 photosynthetic vegetative cells is maintained along filaments. Heterocyst structure and metabolic activity function together to accommodate the oxygen-sensitive process of nitrogen fixation. This article focuses on recent research on heterocyst development, including morphogenesis, transport of molecules between cells in a filament, differential gene expression, and pattern formation.