On the evolution of variation in sexual reproduction through the prism of eukaryotic microbes.

Almost all eukaryotes undergo sexual reproduction to generate diversity and select for fitness in their population pools. Interestingly, the systems by which sex is defined are highly diverse and can even differ between evolutionarily closely related species. While the most commonly known form of sex determination involves males and females in animals, eukaryotic microbes can have as many as thousands of different mating types for the same species. Furthermore, some species have found alternatives to sexual reproduction and prefer to grow clonally and yet undergo infrequent facultative sexual reproduction. These organisms are mainly invertebrates and microbes, but several examples are also present among vertebrates suggesting that alternative modes of sexual reproduction evolved multiple times throughout evolution. In this review, we summarize the sex-determination modes and variants of sexual reproduction found across the eukaryotic tree of life and suggest that eukaryotic microbes provide unique opportunities to study these processes in detail. We propose that understanding variations in modes of sexual reproduction can serve as a foundation to study the evolution of sex and why and how it evolved in the first place.

Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans.

We recently reported transposon mutagenesis as a significant driver of spontaneous mutations in the human fungal pathogen Cryptococcus deneoformans during murine infection. Mutations caused by transposable element (TE) insertion into reporter genes were dramatically elevated at high temperatures (37° vs. 30°) in vitro, suggesting that heat stress stimulates TE mobility in the Cryptococcus genome. To explore the genome-wide impact of TE mobilization, we generated transposon accumulation lines by in vitro passage of C. deneoformans strain XL280α for multiple generations at both 30° and at the host-relevant temperature of 37°. Utilizing whole-genome sequencing, we identified native TE copies and mapped multiple de novo TE insertions in these lines. Movements of the T1 DNA transposon occurred at both temperatures with a strong bias for insertion between gene-coding regions. By contrast, the Tcn12 retrotransposon integrated primarily within genes and movement occurred exclusively at 37°. In addition, we observed a dramatic amplification in copy number of the Cnl1 (Cryptococcus neoformans LINE-1) retrotransposon in subtelomeric regions under heat-stress conditions. Comparing TE mutations to other sequence variations detected in passaged lines, the increase in genomic changes at elevated temperatures was primarily due to mobilization of the retroelements Tcn12 and Cnl1. Finally, we found multiple TE movements (T1, Tcn12, and Cnl1) in the genomes of single C. deneoformans isolates recovered from infected mice, providing evidence that mobile elements are likely to facilitate microevolution and rapid adaptation during infection.

Emerging role of microRNAs as regulators of protein kinase C substrate MARCKS and MARCKSL1 in cancer.

MicroRNAs (miRNAs) have emerged as pivotal regulators of gene expression, playing essential roles in diverse cellular processes, including the development and progression of cancer. Among the numerous proteins influenced by miRNAs, the MARCKS/MARCKSL1 protein, a key regulator of cellular cytoskeletal dynamics and membrane-cytosol communication, has garnered significant attention due to its multifaceted involvement in various cancer-related processes, including cell migration, invasion, metastasis, and drug resistance. Motivated by the encouraging early clinical success of peptides targeting MARCKS in several pathological conditions, this review article delves into the intricate interplay between miRNAs and the MARCKS protein in cancer. Herein, we have highlighted the latest findings on specific miRNAs that modulate MARCKS/MARCKSL1 expression, providing a comprehensive overview of their roles in different cancer types. We have underscored the need for in-depth investigations into the therapeutic feasibility of targeting the miRNA-MARCKS axis in cancer, taking cues from the successes witnessed in related fields. Unlocking the full potential of miRNA-mediated MARCKS regulation could pave the way for innovative and effective therapeutic interventions against various cancer types.

Inhibition of leukotriene-B4 signalling-mediated host response to tuberculosis is a potential mode of adjunctive host-directed therapy.

Treatment of tuberculosis (TB) is faced with several challenges including the long treatment duration, drug toxicity and tissue pathology. Host-directed therapy provides promising avenues to find compounds for adjunctively assisting antimycobacterials in the TB treatment regimen, by promoting pathogen eradication or limiting tissue destruction. Eicosanoids are a class of lipid molecules that are potent mediators of inflammation and have been implicated in aspects of the host response against TB. Here, we have explored the blood transcriptome of pulmonary TB patients to understand the activity of leukotriene B4, a pro-inflammatory eicosanoid. Our study shows a significant upregulation in the leukotriene B4 signalling pathway in active TB patients, which is reversed with TB treatment. We have further utilized our in-house network analysis algorithm, ResponseNet, to identify potential downstream signal effectors of leukotriene B4 in TB patients including STAT1/2 and NADPH oxidase at a systemic as well as local level, followed by experimental validation of the same. Finally, we show the potential of inhibiting leukotriene B4 signalling as a mode of adjunctive host-directed therapy against TB. This study provides a new mode of TB treatment along with mechanistic insights which can be further explored in pre-clinical trials.

National and regional prevalence of gestational diabetes mellitus in India: a systematic review and Meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is frequently misdiagnosed during pregnancy. There is an abundance of evidence, but little is known regarding the regional prevalence estimates of GDM in India. This systematic review and meta-analysis aims to provide valuable insights into the national and regional prevalence of GDM among pregnant women in India. METHODS: We conducted an initial article search on PubMed, Scopus, Google Scholar, and ShodhGanga searches to identify quantitative research papers (database inception till 15th June,2022). This review included prevalence studies that estimated the occurrence of GDM across different states in India. RESULTS: Two independent reviewers completed the screening of 2393 articles, resulting in the identification of 110 articles that met the inclusion criteria, which collectively provided 117 prevalence estimates. Using a pooled estimate calculation (with an Inverse square heterogeneity model), the pooled prevalence of GDM in pregnant women was estimated to be 13%, with a 95% confidence interval (CI) ranging from 9 to 16%.. In India, Diabetes in Pregnancy Study of India (DIPSI) was the most common diagnostic criteria used, followed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and World Health Organization (WHO) 1999. It was observed that the rural population has slightly less prevalence of GDM at 10.0% [6.0-13.0%, I2=96%] when compared to the urban population where the prevalence of GDM was 12.0% [9.0-16.0%, I2 = 99%]. CONCLUSIONS: This review emphasizes the lack of consensus in screening and diagnosing gestational diabetes mellitus (GDM), leading to varied prevalence rates across Indian states. It thoroughly examines the controversies regarding GDM screening by analyzing population characteristics, geographic variations, diagnostic criteria agreement, screening timing, fasting vs. non-fasting approaches, cost-effectiveness, and feasibility, offering valuable recommendations for policy makers. By fostering the implementation of state-wise screening programs, it can contribute to improving maternal and neonatal outcomes and promoting healthier pregnancies across the country.

Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii.

Deletion of native centromeres in the human fungal pathogen Cryptococcus deuterogattii leads to neocentromere formation. Native centromeres span truncated transposable elements, while neocentromeres do not and instead span actively expressed genes. To explore the epigenetic organization of neocentromeres, we analyzed the distribution of the heterochromatic histone modification H3K9me2, 5mC DNA methylation and the euchromatin mark H3K4me2. Native centromeres are enriched for both H3K9me2 and 5mC DNA methylation marks and are devoid of H3K4me2, while neocentromeres do not exhibit any of these features. Neocentromeres in cen10Δ mutants are unstable and chromosome-chromosome fusions occur. After chromosome fusion, the neocentromere is inactivated and the native centromere of the chromosome fusion partner remains as the sole, active centromere. In the present study, the active centromere of a fused chromosome was deleted to investigate if epigenetic memory promoted the re-activation of the inactive neocentromere. Our results show that the inactive neocentromere is not re-activated and instead a novel neocentromere forms directly adjacent to the deleted centromere of the fused chromosome. To study the impact of transcription on centromere stability, the actively expressed URA5 gene was introduced into the CENP-A bound regions of a native centromere. The introduction of the URA5 gene led to a loss of CENP-A from the native centromere, and a neocentromere formed adjacent to the native centromere location. Remarkably, the inactive, native centromere remained enriched for heterochromatin, yet the integrated gene was expressed and devoid of H3K9me2. A cumulative analysis of multiple CENP-A distribution profiles revealed centromere drift in C. deuterogattii, a previously unreported phenomenon in fungi. The CENP-A-binding shifted within the ORF-free regions and showed a possible association with a truncated transposable element. Taken together, our findings reveal that neocentromeres in C. deuterogattii are highly unstable and are not marked with an epigenetic memory, distinguishing them from native centromeres.

Dynamic genome plasticity during unisexual reproduction in the human fungal pathogen Cryptococcus deneoformans.

Genome copy number variation occurs during each mitotic and meiotic cycle and it is crucial for organisms to maintain their natural ploidy. Defects in ploidy transitions can lead to chromosome instability, which is a hallmark of cancer. Ploidy in the haploid human fungal pathogen Cryptococcus neoformans is exquisitely orchestrated and ranges from haploid to polyploid during sexual development and under various environmental and host conditions. However, the mechanisms controlling these ploidy transitions are largely unknown. During C. deneoformans (formerly C. neoformans var. neoformans, serotype D) unisexual reproduction, ploidy increases prior to the onset of meiosis, can be independent from cell-cell fusion and nuclear fusion, and likely occurs through an endoreplication pathway. To elucidate the molecular mechanisms underlying this ploidy transition, we identified twenty cell cycle-regulating genes encoding cyclins, cyclin-dependent kinases (CDK), and CDK regulators. We characterized four cyclin genes and two CDK regulator genes that were differentially expressed during unisexual reproduction and contributed to diploidization. To detect ploidy transition events, we generated a ploidy reporter, called NURAT, which can detect copy number increases via double selection for nourseothricin-resistant, uracil-prototrophic cells. Utilizing this ploidy reporter, we showed that ploidy transition from haploid to diploid can be detected during the early phases of unisexual reproduction. Interestingly, selection for the NURAT reporter revealed several instances of segmental aneuploidy of multiple chromosomes, which conferred azole resistance in some isolates. These findings provide further evidence of ploidy plasticity in fungi with significant biological and public health implications.

Serratiopeptidase Attenuates Lipopolysaccharide-Induced Vascular Inflammation by Inhibiting the Expression of Monocyte Chemoattractant Protein-1.

Lipopolysaccharide (LPS) has potent pro-inflammatory properties and acts on many cell types including vascular endothelial cells. The secretion of the cytokines MCP-1 (CCL2), interleukins, and the elevation of oxidative stress by LPS-activated vascular endothelial cells contribute substantially to the pathogenesis of vascular inflammation. However, the mechanism involving LPS-induced MCP-1, interleukins, and oxidative stress together is not well demonstrated. Serratiopeptidase (SRP) has been widely used for its anti-inflammatory effects. In this research study, our intention is to establish a potential drug candidate for vascular inflammation in cardiovascular disorder conditions. We used BALB/c mice because this is the most successful model of vascular inflammation, suggested and validated by previous research findings. Our present investigation examined the involvement of SRP in vascular inflammation caused by lipopolysaccharides (LPSs) in a BALB/c mice model. We analyzed the inflammation and changes in the aorta by H&E staining. SOD, MDA, and GPx levels were determined as per the instructions of the kit protocols. ELISA was used to measure the levels of interleukins, whereas immunohistochemistry was carried out for the evaluation of MCP-1 expression. SRP treatment significantly suppressed vascular inflammation in BALB/c mice. Mechanistic studies demonstrated that SRP significantly inhibited the LPS-induced production of proinflammatory cytokines such as IL-2, IL-1, IL-6, and TNF-α in aortic tissue. Furthermore, it also inhibited LPS-induced oxidative stress in the aortas of mice, whereas the expression and activity of monocyte chemoattractant protein-1 (MCP-1) decreased after SRP treatment. In conclusion, SRP has the ability to reduce LPS-induced vascular inflammation and damage by modulating MCP-1.

Antibiotic resistance, biofilm formation, and virulence genes of Streptococcus agalactiae serotypes of Indian origin.

BACKGROUND: Group B Streptococcus (GBS) is a causative agent of various infections in newborns, immunocompromised (especially diabetic) non-pregnant adults, and pregnant women. Antibiotic resistance profiling can provide insights into the use of antibiotic prophylaxis against potential GBS infections. Virulence factors are responsible for host-bacteria interactions, pathogenesis, and biofilm development strategies. The aim of this study was to determine the biofilm formation capacity, presence of virulence genes, and antibiotic susceptibility patterns of clinical GBS isolates. RESULTS: The resistance rate was highest for penicillin (27%; n = 8 strains) among all the tested antibiotics, which indicates the emergence of penicillin resistance among GBS strains. The susceptibility rate was highest for ofloxacin (93%; n = 28), followed by azithromycin (90%; n = 27). Most GBS strains (70%; n = 21) were strong biofilm producers and the rest (30%; n = 9) were moderate biofilm producers. The most common virulence genes were cylE (97%), pavA (97%), cfb (93%), and lmb (90%). There was a negative association between having a strong biofilm formation phenotype and penicillin susceptibility, according to Spearman's rank correlation analysis. CONCLUSION: About a third of GBS strains exhibited penicillin resistance and there was a negative association between having a strong biofilm formation phenotype and penicillin susceptibility. Further, both the strong and moderate biofilm producers carried most of the virulence genes tested for, and the strong biofilm formation phenotype was not associated with the presence of any virulence genes.

Dot-ELISA based on recombinant Hypodermin C of Przhevalskiana silenus for field diagnosis of goat warble fly infestation.

Goat warble fly infestation (GWFI) is an economically important myiasis caused by larvae of Przhevalskiana silenus (Diptera, Oestridae), prevalent in countries of the Mediterranean Basin and Indian subcontinent. GWFI is characterized by the presence of subcutaneous warbles at the lumbar and sacral region of dorsum in the infested animal. The early larval instars (L1 and L2) remain inaccessible to physical detection due to their small size and subcutaneous presence thus causing hindrance in the diagnosis. The objective of present study was to develop a field applicable early diagnostic intervention for GWFI monitoring and prophylactic management for effective control of the disease. Recombinant Hypodermin C (rHyC) antigen of P. silenus was expressed in Escherichia coli. The purified protein was used for optimizing dot-ELISA in a checkerboard titration using goat warble fly infested serum as known positive. The optimized assay was further tested for lower temperature (18°C) and incubation time (30 min). The optimized assay was assessed for inter-rater reliability and field samples. The optimized conditions require 188 ng of protein/dot, 1:800 dilution of serum sample, 1:4000 dilution of anti-goat IgG conjugate and 5% skim milk powder in phosphate buffer saline as blocking buffer. The assay was found to have a diagnostic sensitivity and specificity of 97.3% and 95.8%, respectively. The inter-rater reliability of dot ELISA with rHyC indirect ELISA was found to be almost perfect with a Cohen's kappa index of 0.973. Further testing at ambient temperature (18°C) and shorter incubation steps (30 min) supported suitability of the assay for field diagnosis of GWFI. The present study provides the first report of a sensitive and specific dot-ELISA for early diagnosis of GWFI which is rapid and cost effective. The test may provide an effective field applicable tool for sustainable control of GWFI.

Probing plasmon-induced surface reactions using two-dimensional correlation vibrational spectroscopy.

Surface plasmon resonance (SPR) has the ability to drive catalytic conversion of the reactant molecules via the production of hot electrons, which in general requires high activation energy. The reactions driven by these hot electrons are critical and essential in various heterogeneous surface catalytic reactions. However, there is a need to understand the dynamics of surface reactions and the underlying mechanism, which are influenced by several factors such as the constitution of the nanoparticle, exposure time, and reaction conditions to name a few. However, the effect of solvent in stabilizing the electron-hole pair, the orientation, and the surface coverage of the analyte are poorly understood due to the limitations of current methods. To get deeper insights into the reaction dynamics, we have demonstrated the combined utility of plasmon-enhanced Raman spectroscopy and Two-dimensional correlation spectroscopy (2DCOS) to study the plasmon-driven conversion of 4-nitrothiophenol on the surface of plasmonic nanoparticles. Interestingly, this combined technique provided us with previously unobservable results regarding surface catalysis by conventional spectroscopic analysis alone. Specifically, for the first time, 2DCOS provided critical insights in bridging the gap in our understanding of the interplay of solvent effect, orientation, and surface packing of the analyte molecules. It was observed that certain species like 4,4-dimercaptoazobenzene (DMAB) or 4-aminothiophenol (4-ATP) can be selectively formed based on the ordered or disordered phases of the analytes on the surface, thus paving the way to precisely control light-driven reactions through operando spectroscopy.

Implementing a quality improvement initiative for private healthcare facilities to achieve accreditation: experience from India.

BACKGROUND: The Manyata program is a quality improvement initiative for private healthcare facilities in India which provided maternity care services. Under this initiative, technical assistance was provided to selected facilities in the states of Uttar Pradesh, Jharkhand and Maharashtra which were interested in obtaining 'entry level certification' under the National Accreditation Board for Hospitals and Healthcare Providers (NABH) for provision of quality services. This paper describes the change in quality at those Manyata-supported facilities when assessed by the NABH standards of care. METHODS: Twenty-eight private-sector facilities underwent NABH assessments in the three states from August 2017 to February 2019. Baseline assessment (by program staff) and NABH assessment (by NABH assessors) findings were compared to assess the change in quality of care as per NABH standards of care. The reported performance gaps from NABH assessments were then also classified by thematic areas and suggested corrective actions based on program implementation experience. RESULTS: The overall adherence to NABH standards of care improved from 9% in the baseline assessment to 80% in the NABH assessment. A total of 831 performance gaps were identified by the NABH assessments, of which documentation issues accounted for a majority (70%), followed by training (19%). Most performance gaps could be corrected either by revising existing documentation or creating new documentation (62%), or by orienting facility staff on various protocols (35%). CONCLUSION: While the adherence of facilities to the NABH standards of care improved considerably, certain performance gaps remained, which were primarily related to documentation of facility policies and protocols and training of staff, and required corrective actions for the facilities to achieve NABH entry level certification.

Centromere scission drives chromosome shuffling and reproductive isolation.

A fundamental characteristic of eukaryotic organisms is the generation of genetic variation via sexual reproduction. Conversely, significant large-scale genome structure variations could hamper sexual reproduction, causing reproductive isolation and promoting speciation. The underlying processes behind large-scale genome rearrangements are not well understood and include chromosome translocations involving centromeres. Recent genomic studies in the Cryptococcus species complex revealed that chromosome translocations generated via centromere recombination have reshaped the genomes of different species. In this study, multiple DNA double-strand breaks (DSBs) were generated via the CRISPR/Cas9 system at centromere-specific retrotransposons in the human fungal pathogen Cryptococcus neoformans The resulting DSBs were repaired in a complex manner, leading to the formation of multiple interchromosomal rearrangements and new telomeres, similar to chromothripsis-like events. The newly generated strains harboring chromosome translocations exhibited normal vegetative growth but failed to undergo successful sexual reproduction with the parental wild-type strain. One of these strains failed to produce any spores, while another produced ∼3% viable progeny. The germinated progeny exhibited aneuploidy for multiple chromosomes and showed improved fertility with both parents. All chromosome translocation events were accompanied without any detectable change in gene sequences and thus suggest that chromosomal translocations alone may play an underappreciated role in the onset of reproductive isolation and speciation.

Long transposon-rich centromeres in an oomycete reveal divergence of centromere features in Stramenopila-Alveolata-Rhizaria lineages.

Centromeres are chromosomal regions that serve as platforms for kinetochore assembly and spindle attachments, ensuring accurate chromosome segregation during cell division. Despite functional conservation, centromere DNA sequences are diverse and often repetitive, making them challenging to assemble and identify. Here, we describe centromeres in an oomycete Phytophthora sojae by combining long-read sequencing-based genome assembly and chromatin immunoprecipitation for the centromeric histone CENP-A followed by high-throughput sequencing (ChIP-seq). P. sojae centromeres cluster at a single focus at different life stages and during nuclear division. We report an improved genome assembly of the P. sojae reference strain, which enabled identification of 15 enriched CENP-A binding regions as putative centromeres. By focusing on a subset of these regions, we demonstrate that centromeres in P. sojae are regional, spanning 211 to 356 kb. Most of these regions are transposon-rich, poorly transcribed, and lack the histone modification H3K4me2 but are embedded within regions with the heterochromatin marks H3K9me3 and H3K27me3. Strikingly, we discovered a Copia-like transposon (CoLT) that is highly enriched in the CENP-A chromatin. Similar clustered elements are also found in oomycete relatives of P. sojae, and may be applied as a criterion for prediction of oomycete centromeres. This work reveals a divergence of centromere features in oomycetes as compared to other organisms in the Stramenopila-Alveolata-Rhizaria (SAR) supergroup including diatoms and Plasmodium falciparum that have relatively short and simple regional centromeres. Identification of P. sojae centromeres in turn also advances the genome assembly.

Moxifloxacin-Mediated Killing of Mycobacterium tuberculosis Involves Respiratory Downshift, Reductive Stress, and Accumulation of Reactive Oxygen Species.

Moxifloxacin is central to treatment of multidrug-resistant tuberculosis. Effects of moxifloxacin on the Mycobacterium tuberculosis redox state were explored to identify strategies for increasing lethality and reducing the prevalence of extensively resistant tuberculosis. A noninvasive redox biosensor and a reactive oxygen species (ROS)-sensitive dye revealed that moxifloxacin induces oxidative stress correlated with M. tuberculosis death. Moxifloxacin lethality was mitigated by supplementing bacterial cultures with an ROS scavenger (thiourea), an iron chelator (bipyridyl), and, after drug removal, an antioxidant enzyme (catalase). Lethality was also reduced by hypoxia and nutrient starvation. Moxifloxacin increased the expression of genes involved in the oxidative stress response, iron-sulfur cluster biogenesis, and DNA repair. Surprisingly, and in contrast with Escherichia coli studies, moxifloxacin decreased expression of genes involved in respiration, suppressed oxygen consumption, increased the NADH/NAD+ ratio, and increased the labile iron pool in M. tuberculosis. Lowering the NADH/NAD+ ratio in M. tuberculosis revealed that NADH-reductive stress facilitates an iron-mediated ROS surge and moxifloxacin lethality. Treatment with N-acetyl cysteine (NAC) accelerated respiration and ROS production, increased moxifloxacin lethality, and lowered the mutant prevention concentration. Moxifloxacin induced redox stress in M. tuberculosis inside macrophages, and cotreatment with NAC potentiated the antimycobacterial efficacy of moxifloxacin during nutrient starvation, inside macrophages, and in mice, where NAC restricted the emergence of resistance. Thus, NADH-reductive stress contributes to moxifloxacin-mediated killing of M. tuberculosis, and the respiration stimulator (NAC) enhances lethality and suppresses the emergence of drug resistance.

Estrogen-related receptor α is involved in angiogenesis and skeletal muscle revascularization in hindlimb ischemia.

Skeletal muscle ischemia is a major consequence of peripheral arterial disease (PAD) or critical limb ischemia (CLI). Although therapeutic options for resolving muscle ischemia in PAD/CLI are limited, the issue is compounded by poor understanding of the mechanisms driving muscle vascularization. We found that nuclear receptor estrogen-related receptor alpha (ERRα) expression is induced in murine skeletal muscle by hindlimb ischemia (HLI), and in cultured myotubes by hypoxia, suggesting a potential role for ERRα in ischemic response. To test this, we generated skeletal muscle-specific ERRα transgenic (TG) mice. In these mice, ERRα drives myofiber type switch from glycolytic type IIB to oxidative type IIA/IIX myofibers, which are typically associated with more vascular supply in muscle. Indeed, RNA sequencing and functional enrichment analysis of TG muscle revealed that "paracrine angiogenesis" is the top-ranked transcriptional program activated by ERRα in the skeletal muscle. Immunohistochemistry and angiography showed that ERRα overexpression increases baseline capillarity, arterioles and non-leaky blood vessel formation in the skeletal muscles. Moreover, ERRα overexpression facilitates ischemic neo-angiogenesis and perfusion recovery in hindlimb musculature of mice subjected to HLI. Therefore, ERRα is a hypoxia inducible nuclear receptor that is involved in skeletal muscle angiogenesis and could be potentially targeted for treating PAD/CLI.

Prevalence of collusion in cancer communications: A meta-analysis.

INTRODUCTION: Collusion is the non-disclosure of information about diagnosis or prognosis, frequently encountered in cancer care and palliative services. Unraveling collusion is a skill and differences among communication techniques by Health Care Workers have maintained the process of non-disclosure to patients and caregivers. Identifying the prevalence of collusion in cancer care is required to improve the existing strategies across the world. METHODS: A systematic review of the literature from 1991 to 2020 in the English language was conducted with the protocol registration on PROSPERO ID (CRD 42021249216.) to identify the pooled prevalence of collusion. RESULTS: By using random effect model, the pooled prevalence estimate among patients for the diagnostic and prognostic collusion was 24.15, (95% CI [17.09; 32.96], Tou2 = 1.0801, I2  = 97.9%, Cochran's Q = 1058.22, df = 21, p-value < 0.001) and 37.92, (95% CI [22.46; 56.30], Tou2 = 1.9641, I2  = 98.6%, Cochran's Q = 944.26, df = 13, p-value < 0.001) respectively. There was no difference across subgroups with different types of setting for the interview, WHO regions and trend over the years. CONCLUSIONS: Substantial prevalence of collusion goes unnoticed in cancer care. A meaningful understanding of such a large prevalence requires inquiry into the existing communication paradigm in cancer care across the world. The findings also question the need of formulating uniform interview techniques and structured assessment tools or questionnaires in cancer care to improve the disclosure rates.

Dielectric response and proton transport in water confined in graphene oxide.

Graphene oxide (GO) membranes possess a hierarchical microstructure, with well-ordered crystalline lamellae combining to form a macroscopic membrane. Water can intercalate in GO either in the sub-nanometer interlayer spaces or in the gaps between the lamellae known as voids; distinguishing the contribution of these two has been challenging. Addressing this challenge, we systematically study various properties of GO membranes exposed to controlled humidity levels ranging from 0% to 90% RH. Thickness-dependent dynamic vapor sorption is used to quantify the water content under different humidity environments. Complementing the vapor sorption studies, the AC impedance response of the GO membrane is determined at different humidity values. Our findings suggest that (a) most water gets absorbed in interlayer spaces at low humidity (<25% RH), (b) the fraction of water in the void spaces increases with RH%, (c) the lower bound for the dielectric constant of confined water is estimated to be εwater > 17, and (d) the conductivity increases by 5 to 6 orders of magnitude over a narrow range of water content (13 wt% to 31 wt%). The rapid increase in conductivity over a narrow range of water content suggests a percolative process for the protons. The dielectric constant estimates suggest that confined water behaves distinctly differently in a hydrophilic environment than in a hydrophobic one.

BF3-etherate promoted facile access to vinyloxyimidazopyridines: a metal-free sustainable approach.

A convenient and metal-free synthesis of vinyloxyimidazopyridine derivatives has been attained via BF3.OEt2 promoted one-pot multicomponent approach. This procedure involves a facile coupling of 2-aminopyridine derivatives with arylglyoxal and alkyne derivatives. BF3.OEt2 complexation has successfully catalyzed the reaction at room temperature. Utilization of transition metal-free catalyst, mild reaction conditions, easy handling and operational simplicity are key features of developed process.

Improving quality of intrapartum and immediate postpartum care in public facilities: experiences and lessons learned from Rajasthan state, India.

BACKGROUND: In spite of considerable improvement in maternal and neonatal outcomes over the past decade in India, the current maternal mortality ratio and neonatal mortality rate are far from the Sustainable Development Goal targets due to suboptimal quality of maternity care. A package of interventions for improving quality of intrapartum and immediate postpartum care was co-designed with the Ministry of Health as the Dakshata program and implemented in public sector health facilities in selected districts in the state of Rajasthan of India since June 2015. This article describes the key strategies, interventions, results and challenges from four years of Dakshata program implementation. METHODS: We have conducted secondary analysis of program data (government data) collected from 202 public facilities across 20 districts of Rajasthan state. The data collected between June-August 2015 (baseline) and the data collected between May-August 2019 (latest) were analyzed. The data sources included: facility assessments, service statistics, monthly progress reports. RESULTS: During the period of program implementation, there were 17,94,249 deliveries accounting for 70% of institutional deliveries in intervention districts. As a result of the intervention, there was a notable increase in competency of health care providers, availability of essential resources, achievement of labour room standards and adherence to evidence-based clinical standards. We also observed reductions in the proportion of referrals for pre-eclampsia/eclampsia, postpartum hemorrhage and neonatal asphyxia by 11, 8 and 3 percentage points respectively. Similarly, data revealed a reduction in stillbirth rates in Dakshata intervention facilities (19.3 vs 15.3) compared to non-Dakshata facilities (21.8 vs 18). CONCLUSIONS: Our experience and findings indicate that the quality of intrapartum and immediate postpartum care can be improved in low- and middle-income countries with the approach presented in this paper.