FETOMATERNAL OUTCOME OF GESTATIONAL DIABETES MELLITUS IN PRIMIGRAVIDA DELIVERED AT TERTIARY CARE HOSPITAL

Objective: To determine the Prevalence of gestational diabetes mellitus (GDM) in primigravida and their feto-maternal outcome who delivered at tertiary care hospital in western Rajasthan. Methods: A retrospective chart review study will be conducted on primigravida delivered at the department of Obstetrics and Gynaecology, MDM Hospital Dr. S. N. Medical College, Jodhpur, Rajasthan, India from May 2022 to December 2022. Results: The prevalence of GDM in primigravida was 6.42%, maximum occurrence between 34 and 36 weeks of gestation (53.3%). 8.8% of GDM patients had a preterm delivery, out of these 8 women polyhydramnios were seen in 4 women. 49% had lower segment cesarean section and 3% had instrument delivery. preeclampsia was seen in 25.56%, urinary tract infection in 10%, preterm labor was seen in 8.89%, premature rupture of membrane was seen in 5.56% of the study population. 10% of babies were low birth weight. The incidence of congenital anomalies was seen in 6.6%. Intrauterine death was seen in 2 babies who had congenital anomalies. Conclusion: GDM is associated with adverse complications in both the mother and fetus

Cell wall-associated Mycobacterium tuberculosis rRv3083 protein stimulates macrophages through toll-like receptor-2 (TLR2)

Aims and objectives: Characterization of proteins associated with the mycobacterial cell wall is critical to understanding bacterial survival and immune modulation in the host. A variety of mycobacterial products are able to recognize and activate mammalian toll-like receptors (TLRs) mediating the secretion of antibacterial effector molecules. Mycobacterium tuberculosis MymA Rv3083 protein is a cell wall-associated protein which is up-regulated upon infection of macrophages. The objective of the present study is to understand the role of Rv3083 protein as a TLR agonist and its contribution in activating macrophages. Methods: The MymA (Rv3083) gene was cloned and expressed. The purified 55.5kDa recombinant protein was used to stimulate phorbol myristate acetate (PMA) differentiated THP-1 macrophage cell line. Cell surface markers of Rv3083 stimulated THP-1 cells were done using flow cytometry for TLR2, TLR4, HLA-DR and co-stimulatory molecules CD40, CD64 and CD80. Cytokines TNF-α, IL-10 and IL-12 were assayed in the culture supernatant using ELISA. Results: Stimulation of THP-1 macrophages for 48 and 72 h with rRv3083 protein resulted in significantly increased expression of TLR2. A significant up-regulation was also seen in the expression of co-stimulatory molecules CD40, CD80 and antigen-presenting molecule HLA-DR on THP-1 cells. These macrophages also produced a significant quantity of proinflammatory TH1 cytokines TNF-α and IL-12, but not IL-10 at 48 and 72 h post-stimulation. Conclusion: The cell wall-associated M. tuberculosis rRv3083 protein acts as an agonist of TLR2 and thereby activates macrophages to produce a TH1 immune response. Acknowledgements: The financial support of OSDD-CSIR and the research fellowships of ICMR to I. Saraav and S. Singh is duly acknowledged

Ectopic eruption of maxillary central incisor through abnormally thickened labial frenum: An unusual presentation

Ectopic eruption is a deviation from the normal eruption pattern, making the tooth erupt out of its normal position, and possibly causing resorption of adjacent primary teeth. A wide range of etiological factors may be responsible for ectopic eruption of the teeth, so their management depends on the correction of the established etiological factor. The present case report describes an unusual case of ectopically erupted central incisor encased within an abnormally thickened labial frenum, which was treated by orthodontic repositioning of the ectopically erupting tooth after frenectomy

PMN-MDSCs Enhance CTC Metastatic Properties through Reciprocal Interactions via ROS/Notch/Nodal Signaling

Intratumoral infiltration of myeloid-derived suppressor cells (MDSCs) is known to promote neoplastic growth by inhibiting the tumoricidal activity of T cells. However, direct interactions between patient-derived MDSCs and circulating tumors cells (CTCs) within the microenvironment of blood remain unexplored. Dissecting interplays between CTCs and circulatory MDSCs by heterotypic CTC/MDSC clustering is critical as a key mechanism to promote CTC survival and sustain the metastatic process. We characterized CTCs and polymorphonuclear-MDSCs (PMN-MDSCs) isolated in parallel from peripheral blood of metastatic melanoma and breast cancer patients by multi-parametric flow cytometry. Transplantation of both cell populations in the systemic circulation of mice revealed significantly enhanced dissemination and metastasis in mice co-injected with CTCs and PMN-MDSCs compared to mice injected with CTCs or MDSCs alone. Notably, CTC/PMN-MDSC clusters were detected in vitro and in vivo either in patients’ blood or by longitudinal monitoring of blood from animals. This was coupled with in vitro co-culturing of cell populations, demonstrating that CTCs formed physical clusters with PMN-MDSCs; and induced their pro-tumorigenic differentiation through paracrine Nodal signaling, augmenting the production of reactive oxygen species (ROS) by PMN-MDSCs. These findings were validated by detecting significantly higher Nodal and ROS levels in blood of cancer patients in the presence of naïve, heterotypic CTC/PMN-MDSC clusters. Augmented PMN-MDSC ROS upregulated Notch1 receptor expression in CTCs through the ROS-NRF2-ARE axis, thus priming CTCs to respond to ligand-mediated (Jagged1) Notch activation. Jagged1-expressing PMN-MDSCs contributed to enhanced Notch activation in CTCs by engagement of Notch1 receptor. The reciprocity of CTC/PMN-MDSC bi-directional paracrine interactions and signaling was functionally validated in inhibitor-based analyses, demonstrating that combined Nodal and ROS inhibition abrogated CTC/PMN-MDSC interactions and led to a reduction of CTC survival and proliferation. This study provides seminal evidence showing that PMN-MDSCs, additive to their immuno-suppressive roles, directly interact with CTCs and promote their dissemination and metastatic potency. Targeting CTC/PMN-MDSC heterotypic clusters and associated crosstalks can therefore represent a novel therapeutic avenue for limiting hematogenous spread of metastatic disease

Genome-Wide Association Study Implicates Testis-Sperm Specific <em>FKBP6</em> as a Susceptibility Locus for Impaired Acrosome Reaction in Stallions

<div><p>Impaired acrosomal reaction (IAR) of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR–affected and 37 control Thoroughbred stallions. A significant (<em>P</em><6.75E-08) genotype–phenotype association was found in horse chromosome 13 in FK506 binding protein 6 (<em>FKBP6</em>). The gene belongs to the immunophilins FKBP family known to be involved in meiosis, calcium homeostasis, clathrin-coated vesicles, and membrane fusions. Direct sequencing of <em>FKBP6</em> exons in cases and controls identified SNPs g.11040315G>A and g.11040379C>A (p.166H>N) in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44) and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine <em>FKBP6</em> was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for <em>FKBP6</em> up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that <em>FKBP6</em> relates to the IAR phenotype via regulatory or modifying functions. In conclusion, <em>FKBP6</em> was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. <em>FKBP6</em> genotyping is recommended for the detection of IAR–susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.</p> </div

Venn diagram of transcripts detected in stallion sperm and testes by microarray analysis (SNR ≥2).

<p>Venn diagram of transcripts detected in stallion sperm and testes by microarray analysis (SNR ≥2).</p

Equine <i>FKBP6</i> organization and splicing.

<p>(A) <i>FKBP6</i> genomic (left) and cDNA (right) according to ENSEMBL (<a href="http://www.ensembl.org/index.html" target="_blank">http://www.ensembl.org/index.html</a>); (B) <i>FKBP6</i> splice variants in stallion testis and sperm according to this study; (C) RT-PCR with combinations of <i>FKBP6</i> exon primers to determine alternative splicing in testis (T), normal sperm (S) and IAR sperm (I). Arrows show PCR products for alternative splice variants.</p