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Background: Pregnancy associated anxiety and depression is very well known for its prevalence. Pandemic like COVID-19 all the more is additive to the levels of anxiety and depression during pregnancy, especially for mothers who are concerned about feto-maternal wellbeing. This study makes an effort to analyze the health-related behavior changes and psychological impact of pregnant women after COVID-19 outbreak. Methods: Cross sectional, questionnaire-based study conducted on pregnant ladies visiting labor room and out-patients department RIMS, Ranchi from April 2020 to September 2020. Results: Most patients were primigravida and turned up only in third trimester. Pregnancy complications like heart disease, GDM, jaundice, PIH were present in 28% of participants. 48% participants had no family income during pandemic. The 92% women wore masks, 80% practiced social distancing, 72% practiced frequent handwashing, 72% practiced frequent handwashing during pandemic, 80% had no regular antenatal check-up. Almost 64% participants showed mild to moderate anxiety, 34% had moderate depression and 40% had moderate stress. Four percentages had severe anxiety, 2% had severe depression and 12% had severe stress. Usage of mask was inversely related to GAD7 scores, but had no correlation with EPDS scores. Rest parameters like frequent handwashing, social distancing, stressful behavior, not going out and frequent handwashing were directly related to GAD 7 and EPDS score. Conclusions: Mental health and preventive behavior of respondents could be attributed to socio demographic, social, situational, economic status, family conditions and perception of severity of Covid19.

There is a strong rationale for investigating nutritional interventions with docosahexaenoic acid (DHA) in cancer prevention and therapy; however, the effects of DHA on ovarian cancer (OC) have not...

Metformin is being actively repurposed for the treatment of gynecologic malignancies including ovarian cancer. We investigated if metformin induces analogous metabolic changes across ovarian cancer cells. Functional metabolic analysis showed metformin caused an immediate and sustained decrease in oxygen consumption while increasing glycolysis across A2780, C200, and SKOV3ip cell lines. Untargeted metabolomics showed metformin to have differential effects on glycolysis and TCA cycle metabolites, while consistent increased fatty acid oxidation intermediates were observed across the three cell lines. Metabolite set enrichment analysis showed alpha-linolenic/linoleic acid metabolism as being most upregulated. Downstream mediators of the alpha-linolenic/linoleic acid metabolism, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were abundant in all three cell lines. EPA was more effective in inhibiting SKOV3 and CaOV3 xenografts, which correlated with inhibition of inflammatory markers and indicated a role for EPA-derived specialized pro-resolving mediators such as Resolvin E1. Thus, modulation of the metabolism of omega-3 fatty acids and their anti-inflammatory signaling molecules appears to be one of the common mechanisms of metformin’s antitumor activity. The distinct metabolic signature of the tumors may indicate metformin response and aid the preclinical and clinical interpretation of metformin therapy in ovarian and other cancers.

Despite recent advances in diagnosis and treatment, ovarian cancer (OC) is the most lethal gynecological malignancy and improving the efficacy of chemotherapy is of great interest. This study increases our understanding of how dietary intervention with docosahexaenoic acid (DHA)-a supplement proven safe for human consumption – enhances the anti-cancer effects of conventional chemotherapy. Our results demonstrated synergistic cell killing by DHA and carboplatin in OC cell lines. Furthermore, DHA supplementation alone and in combination with carboplatin significantly reduced OC growth in a high-grade serous OC patient-derived xenograft mouse model. Carboplatin administered intraperitoneally significantly reduced tumor growth in DHA-fed mice compared to mice on the control diet. Intravenous carboplatin administration in combination with DHA reduced tumor growth similarly to carboplatin or DHA monotherapies. The DHA-induced reduction in tumor growth in this model was associated with increased tumor necrosis and improved survival. As such, our findings provide a strong rationale to move to clinical trials that will determine whether DHA supplementation enhances the efficacy and tolerance of cytotoxic chemotherapy in patients with OC.

Gamma delta (γδ) T cells kill transformed cells, and increased circulating γδ T cells levels correlate with improved outcome in cancer patients; however, their function within the breast tumor microenvironment (TME) remains controversial. As tumors progress, they begin to express stem-cell associated proteins, concomitant with the emergence of therapy resistant metastatic disease. For example, invasive breast cancers often secrete the embryonic morphogen, NODAL. NODAL has been shown to promote angiogenesis, therapy resistance and metastasis in breast cancers. However, to date, little is known about how this secreted protein may interact with cells in the TME. Herein we explore how NODAL in the TME may influence γδ T cell function. We have assessed the proximity of γδ T cells to NODAL in a cohort of triple negative breast tumors. In all cases in which γδ T cells could be identified in these tumors, γδ T cells were found in close proximity to NODAL-expressing tumor cells. Migration of γδ and αβ T cells was similar toward MDA-MB-231 cells in which NODAL had been knocked down (shN) and MDA-MB-231 scrambled control cells (shC). Furthermore, Vδ1 γδ T cells did not migrate preferentially toward conditioned medium from these cell lines. While 24-h exposure to NODAL did not impact CD69, PD-1, or T cell antigen receptor (TCR) expression on γδ T cells, long term exposure resulted in decreased Vδ2 TCR expression. Maturation of γδ T cells was not significantly influenced by NODAL stimulation. While neither short- nor long-term NODAL stimulation impacted the ability of γδ T cells to kill MCF-7 breast cancer cells, the absence of NODAL resulted in greater sensitivity of targets to γδ T cell cytotoxicity, while overexpression of NODAL conferred resistance. This appeared to be at least in part due to an inverse correlation between NODAL and surface MICA/B expression on breast cancer target lines. As such, it appears that NODAL may play a role in strategies employed by breast cancer cells to evade γδ T cell targeting, and this should be considered in the development of safe and effective γδ T cell immunotherapies.

Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast cancer cells NANOG, SNAIL and NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), whereby translation of a subset of these isoforms is stimulated under hypoxia. This leads to accumulation of corresponding proteins which induce plasticity and “fate-switching” toward stem-cell like phenotypes. Surprisingly, we observed that mTOR inhibitors and chemotherapeutics induce translational activation of a subset of NANOG, SNAIL and NODAL mRNA isoforms akin to hypoxia, engendering stem cell-like phenotypes. Strikingly, these effects can be overcome with drugs that antagonize translational reprogramming caused by eIF2α phosphorylation (e.g. ISRIB). Collectively, our findings unravel a hitherto unappreciated mechanism of induction of plasticity of breast cancer cells, and provide a molecular basis for therapeutic strategies aimed at overcoming drug resistance and abrogating metastasis.

Mechanistic studies contribute greatly to our understanding of γδ T cell (γδTc) biology, aiding development of these cells as immunotherapeutic agents. The antibody blocking assay is an accepted method to determine the receptors involved in γδTc killing of tumour targets. Effectors and/or targets are pre-incubated with microgram quantities of monoclonal antibodies (mAb), often described by commercial sources to be useful for blocking assays. We and others have used such assays extensively in the past, correlating decreases in cytotoxicity against specific targets with involvement of the blocked receptor(s). However, we wondered whether other mechanisms might be at play beyond cytotoxicity inhibition. Indeed, administration of certain “blocking” mAb to the γδ T cell antigen receptor (γδTCR) induced γδTc death. Upon further investigation, we discovered that γδTc underwent apoptosis triggered by incubation with mAb to the γδTCR. This effect was specific, as no apoptosis was observed when αβ T cells (αβTc) were incubated with these mAb. Apoptosis was further potentiated by the presence of interleukin (IL)-2, often included in cytotoxicity assays; however, exogenous interleukin-2 (IL-2) did not contribute significantly to γδTc cytotoxicity against breast cancer cell lines. Here, we have investigated the usefulness of four mAb for use in blocking assays by assessing blocking properties in conjunction with their propensity to induce apoptosis in cultured primary human γδTc. We found that the 5A6.E9 clone was usually a better alternative to the commonly used B1 (or B1.1) and 11F2 clones; however, some variability in susceptibility to apoptosis induction was observed among donor cultures. Thus, viability assessment of primary effector cells treated with mAb alone should be undertaken in parallel with cytotoxicity assays employing blocking antibodies, in order to account for cytotoxicity reduction caused by effector cell death. Previous findings should be reassessed in this light.

Disabled-1 (Dab1) plays a key role in reelin-mediated neuronal migration during brain development. Tyrosine phosphorylation of Dab1 at two YQXI and two YXVP motifs recruits multiple SH2 domains, resulting in activation of a wide range of signaling cascades. However, the molecular mechanisms underlying the coordinated regulation of Dab1 downstream effectors remain poorly understood. Here, we show that alternative splicing results in inclusion of different combinations of YQXI and YXVP motifs in Dab1 isoforms during development. Dab1 variants with partial or complete loss of YQXI motifs are preferentially expressed at early developmental stages, whereas the commonly studied Dab1 is predominantly expressed at late developmental stages. Expression of Dab1 variants in 293T and Neuro2a cells reveals reduced levels or absence of tyrosine phosphorylation in variants that have lost one or both YQXI motifs. We further demonstrate that Dab1 variants differ in their abilities to activate Src and recruit distinct SH2 domains involved in specific downstream signaling pathways. We propose that coordinated expression of specific Dab1 isoforms in different populations of cells in the developing brain contributes to precise neuronal migration by modulating the activity of subsets of Dab1 downstream effectors.

Presentation of uterine prolapse is a normal event in a pregnant woman which can be pre-existent or else manifest in the course of pregnancy. Complications resulting from prolapse of uterus vary from minor cervical infection to spontaneous abortion to preterm labour, maternal and fetal mortality, acute retention of urine and urinary tract infection. Authors of this paper have studied a case of a pregnant lady who presented to the emergency department with prolapse and her line of management which was executed. This was a case report study and management were done as per standard obstetrical guidelines. Patient was counselled at the time of discharge. Implementation of conservative treatment modalities throughout pregnancy with prolapse and their application in accordance of severity of uterine prolapse and patient’s preference may be sufficient to achieve an uneventful pregnancy, normal and spontaneous vaginal delivery.

Neuronal injury may cause an irreversible damage to cellular, organ and organism function. While preventing neural injury is ideal, it is not always possible. There are multiple etiologies for neuronal injury including trauma, infection, inflammation, immune mediated disorders, toxins and hereditary conditions. We describe a novel laser application, utilizing femtosecond laser pulses, in order to connect neuronal axon to neuronal soma. We were able to maintain cellular viability and demonstrate that this technique is universal as it is applicable to multiple cell types and media.

The levels of endogenous deoxyribonucleotides in plants are greatly affected by the absence of the micronutrient boron. Described here is a high-performance liquid chromatographic assay for quantitating deoxyribonucleoside di- and triphosphates in tomato root tip tissues under boron-sufficient and boron-deficient conditions. The extraction procedure consists of (a) removing phenols from the tomato root tips by grinding frozen tissue in 6% trichloroacetic acid containing polyvinylpolypyrrolidone, (b) neutralizing the extract with freon-amine, (c) selective degradation of ribonucleotides with periodate, followed by (d) treatment with rhamnose and methylamine prior to injection of the deoxyribonucleotides into an anion-exchange column. Results indicate that the eight deoxyribonucleoside di- and triphosphates can be reproducibly resolved and quantified. By this extraction procedure, column life was extended to more than 70 runs per cartridge. This assay technique can be used with less than 500 mg of fresh root tip tissue and allows quantitation of plant deoxyribonucleotides in the picomole range.

The chromatographic separation and quantitation of nucleotides in tomato root tips are seriously impaired by the presence of phenols, which greatly increase in the absence of boron. However, when polyvinylpolypyrolidone is added to the 6% trichloroacetic acid homogenizing solution and the mixture is shaken on ice for 30 min, there is a decrease in phenol concentration such that nucleotides can be separated and quantified on anion-exchange Partisil SAX10 columns after neutralization with freon—amine. This treatment extends column life to more than 70 analyses per cartridge. Such a technique is unique in that it can be used with less than 500 mg of root tip tissue and allows quantitation of plant nucleotides in the picomol range.