Utilisation of adolescent reproductive and sexual health services in a rural area of West Bengal: A mixed-method study

Introduction: Despite policy actions and strategic efforts for improving the reproductive and sexual health of adolescents by promoting the uptake of adolescent reproductive and sexual health (ARSH) services, the utilisation rate remains significantly low, especially in rural areas of India. This study aimed to assess the utilisation of these services by adolescents in rural West Bengal and its associated determinants. Methods: This mixed-method study was conducted from May to September 2021 in the Gosaba rural block of South 24 Parganas, West Bengal. Quantitative data were collected from 326 adolescents using a pre-tested structured questionnaire. Qualitative data were collected via four focus group discussions among 30 adolescents and key-informant interviews among six healthcare workers. Quantitative data were analysed using SPSS, while qualitative data were analysed thematically. Results: Ninety-six (29.4%) adolescents had utilised ARSH services at least once during adolescence. The factors associated with non-utilisation of ARSH services were younger age, female sex, increasing reproductive health stigma and decreasing parent–adolescent communication related to sexual health. Qualitative exploration revealed that unawareness regarding services, perceived lack of privacy and confidentiality at healthcare facilities and disruption of services post-emergence of the COVID-19 pandemic were some major barriers to ARSH service utilisation. Conclusion: A multi-component strategy, including promotion of adolescent-friendly health clinics, community support interventions associated with motivation and counselling of parents regarding the importance of adolescent reproductive health, is needed to improve the utilisation of ARSH services. Necessary steps to correct the deficiencies at the facility level should also be prioritised

Sperm Motility Regulatory Proteins: A Tool to Enhance Sperm Quality

Sperm forward motility is an essential parameter in mammalian fertilization. Studies from our laboratory have identified and characterized a few unique sperm motility regulatory proteins/glycoproteins from the male reproductive fluids and mammalian blood serum. The purified sperm motility-initiating protein (MIP) from caprine epididymal plasma as well as the forward motility-stimulating factor (FMSF) and motility-stimulating protein (MSP) from buffalo and goat serum, respectively, have high efficacy to initiate or increase motility in nonmotile or less motile sperm. Antibody of sperm motility inhibitory factor (MIF-II) has the high potential to enhance sperm vertical velocity and forward motility by increasing intracellular cyclic adenosine monophosphate (cAMP) level. The appearance and disappearance of D-galactose–specific lectin and its receptor along the epididymis has been reported to be involved in motility regulation in spermatozoa. A novel synthetic cryopreservation method and role of lipid to protect membrane damage during cryopreservation have been demonstrated. Motility-promoting proteins may be extremely useful for improving cattle breeding and breeding of endangered species, thereby helping in enhanced production of animal products as well as in the conservation of animals. Isolated proteins and developed cryopreservation technology may also be beneficial in human infertility clinics to increase the chance of fertilization

Microfluidic Chip for Molecular Amplification of Influenza A RNA in Human Respiratory Specimens

A rapid, low cost, accurate point-of-care (POC) device to detect influenza virus is needed for effective treatment and control of both seasonal and pandemic strains. We developed a single-use microfluidic chip that integrates solid phase extraction (SPE) and molecular amplification via a reverse transcription polymerase chain reaction (RT-PCR) to amplify influenza virus type A RNA. We demonstrated the ability of the chip to amplify influenza A RNA in human nasopharyngeal aspirate (NPA) and nasopharyngeal swab (NPS) specimens collected at two clinical sites from 2008–2010. The microfluidic test was dramatically more sensitive than two currently used rapid immunoassays and had high specificity that was essentially equivalent to the rapid assays and direct fluorescent antigen (DFA) testing. We report 96% (CI 89%,99%) sensitivity and 100% (CI 95%,100%) specificity compared to conventional (bench top) RT-PCR based on the testing of n = 146 specimens (positive predictive value = 100%(CI 94%,100%) and negative predictive value = 96%(CI 88%,98%)). These results compare well with DFA performed on samples taken during the same time period (98% (CI 91%,100%) sensitivity and 96%(CI 86%,99%) specificity compared to our gold standard testing). Rapid immunoassay tests on samples taken during the enrollment period were less reliable (49%(CI 38%,61%) sensitivity and 98%(CI 98%,100%) specificity). The microfluidic test extracted and amplified influenza A RNA directly from clinical specimens with viral loads down to 103 copies/ml in 3 h or less. The new test represents a major improvement over viral culture in terms of turn around time, over rapid immunoassay tests in terms of sensitivity, and over bench top RT-PCR and DFA in terms of ease of use and portability

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

Structural and Functional Analysis of the Host Parasite Interaction Network Using Plasmodium as Case Study

Parasitic diseases caused by protozoan pathogens results into millions of deaths per year in addition to substantial suffering and socioeconomic decline worldwide. Active research for understanding host–parasite infection biology in order to develop improved therapeutics is of prime importance due to lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host–parasite interactions. A top-down system analysis protocol has been developed to construct and analyze large scale protein-protein interaction network using various graph theoretical approaches to identify highly interacting hub and central proteins. Further, an in-silico knock-out (KO) approach is implemented to isolate important interacting proteins (IIPs), which in principle can elicit significant impact on the integrity of the interaction networks. This network biology protocol is applied on Plasmodium falciparum interactome to identify a small set of proteins as important interacting proteins (IIPs), which not only play crucial role in intra-pathogen network integrity, stage specificity but also interact with various human proteins involved in multiple metabolic pathways within the host cell. These IIPs could be used as potential drug targets in malarial research. Stage specific metabolic network was also constructed for P. falciparum followed by its analysis at intra-pathogen and host-pathogen condition. Similar network analysis approach was used to study an interaction network of deregulated set of gene in mutant P53 condition in order to identify important hub proteins. Analysis of important interactions at the molecular level is also crucial. In a case study, an E3 ubiquitin ligase (COP1) mediated regulation of adipocyte triglyceride lipase (ATGL) protein was studied using molecular modeling and docking techniques. In another case study Inhibition of DNA topoisomerase by SQDG was studied. Origin and evolution of DNA-(C5)-methyltransferase was studied across the tree of life. This large scale phylogenetic study elucidated gradual complexity in the DNMT and other methyltransferase genes

A New Mode of Interaction of Carboxylic Acids with Some N-phenylbenzohydroxamates of Copper(II), Cobalt(II) & Nickel(II)

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Intermittent dosing with vemurafenib in BRAF V600E-mutant melanoma: review of a case series

The selective BRAF inhibitors, vemurafenib and dabrafenib, yield high response rates and improved overall survival in patients with BRAF V600E-mutant metastatic melanoma. Acquired drug resistance and drug toxicity are key challenges when using these drugs. We investigated whether vemurafenib toxicity could successfully be managed with intermittent dosing, and if its therapeutic efficacy could be maintained on intermittent dosing. Six patients with BRAF V600E-mutated metastatic melanoma were treated with an intermittent dosing regimen of vemurafenib. In three patients, toxicities were successfully managed with an intermittent dosing regimen. In the other three patients, intolerable toxicities continued on intermittent dosing. Our experience shows that intermittent dosing can successfully manage vemurafenib toxicities where continuous dosing at a reduced dose does not. Intermittent treatment improves drug tolerability and can achieve or maintain melanoma shrinkage. We recommend that in clinical practice, intermittent dosing should be considered as an alternative to dose reduction/termination in the management of vemurafenib toxicity