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Coronary-pulmonary artery fistulas (CPAFs) are rare entities that can cause significant left-to-right shunting and complicate routine coronary artery bypass grafting. There are no best practice guidelines and a scarcity of reports regarding concomitant treatment of CPAF with coronary artery disease. We present a case of bilateral CPAFs in a 60-year-old man with symptomatic coronary artery disease treated successfully with coronary artery bypass, epicardial ligation, and transpulmonary closure of CPAF with patch reconstruction. This case highlights the importance of optimal myocardial protection and complete closure of the fistula to prevent risk of coronary steal.

Purpose: Current therapies for proliferative diabetic retinopathy (PDR) do not specifically target VEGF-independent, cell-type–specific processes that lead to vision loss, such as inflammatory pathways. This study aimed to identify targetable cell types and corresponding signaling pathways by elucidating the single-cell landscape of the vitreous of patients with PDR. Design: Case series. Subjects: Vitreous and peripheral blood obtained from 5 adult patients (6 eyes) undergoing pars plana vitrectomy for vision-threatening PDR. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on vitreous cells obtained from diluted cassette washings during vitrectomy from 6 eyes and peripheral blood mononuclear cells (PBMCs, n = 5). Droplet-based scRNA-seq was performed using the Chromium 10x platform to obtain single-cell transcriptomes. Differences in tissue compartments were analyzed with gene ontology enrichment of differentially expressed genes and an unbiased ligand–receptor interaction analysis. Main Outcome Measures: Single-cell transcriptomic profiles of vitreous and peripheral blood. Results: Transcriptomes from 13 675 surgically harvested vitreous cells and 22 636 PBMCs were included. Clustering revealed 4 cell states consistently across all eyes with representative transcripts for T cells (CD2, CD3D, CD3E, and GZMA), B cells (CD79A, IGHM, MS4A1 (CD20), and HLA-DRA), myeloid cells (LYZ, CST3, AIF1, and IFI30), and neutrophils (BASP1, CXCR2, S100A8, and S100A9). Most vitreous cells were T cells (91.6%), unlike the peripheral blood (46.2%), whereas neutrophils in the vitreous were essentially absent. The full repertoire of adaptive T cells including CD4+, CD8+ and T regulatory cells (Treg) and innate immune system effectors (i.e., natural killer T cells) was present in the vitreous. Pathway analysis also demonstrated activation of CD4+ and CD8+ memory T cells and ligand–receptor interactions unique to the vitreous. Conclusions: In the first single-cell transcriptomic characterization of human vitreous in a disease state, we show PDR vitreous is primarily composed of T cells, a critical component of adaptive immunity, with activity and proportions distinct from T cells within the peripheral blood, and neutrophils are essentially absent. These results demonstrate the feasibility of liquid vitreous biopsies via collection of otherwise discarded, diluted cassette washings during vitrectomy to gain mechanistic and therapeutic insights into human vitreoretinal disease. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Context: Adolescent phase is a very crucial period in one’s life, much emotional and psychological support is needed for an adolescent to bloom into a responsible adult. But unfortunately adolescents do not get the support or they fail to seek support due to lack of awareness. Government of India, to address this issue has established dedicated adolescent friendly health services (AFHS). This study estimates the utilisation of adolescent friendly health clinics in a rural area of Maharashtra. Aims: Aim is to the study the utilisation of adolescent friendly health services and its various determinants in a rural area of Maharashtra. Objectives: Objectives of this study were to assess the sociodemographic profile of study participants, to study the utilisation of adolescent friendly health services among them and to determine the factors associated with utilisation of adolescent friendly health services. Settings and Design: A community based cross-sectional study was conducted among 290 late adolescents from a rural area of Maharashtra from October 2022 to December 2022. Methods and Material: With the help of data from Gram panchayat about residing adolescents in the rural field practice area of tertiary care hospital, all late adolescents were included in this study after obtaining informed consent. Data was collected with and Statistical analysis was done using ‘Open Epi Info’ software. Results: Out of 290 adolescents, 35% (102) were aware of adolescent friendly health clinics (AFHS), 20% (58) utilised AFHS, the significant sociodemographic components for utilisation were found to be females (AOR: 2.161,95% CI: 1.088-4.295), Bauddha religion (AOR: 2.465,95% CI: 0.585-10.383), socioeconomic class I and II- B.G Prasad classification (AOR: 1.544,95% CI: 0.786-3.030), higher secondary education (AOR: 8.025,95% CI: 1.434-44.916) and Government schooling (AOR:0.389,95% CI: 0.080-1.889). Conclusions: Though initiatives are taken from the Government to lend a helping hand to the adolescents, awareness and utilisation seems to be minimal.

Abstract Background Children exposed prenatally to alcohol or cannabinoids individually can exhibit growth deficits and increased risk for adverse birth outcomes. However, these drugs are often co-consumed and their combined effects on early brain development are virtually unknown. The blood vessels of the fetal brain emerge and mature during the neurogenic period to support nutritional needs of the rapidly growing brain, and teratogenic exposure during this gestational window may therefore impair fetal cerebrovascular development. Study Design To determine whether prenatal polysubstance exposure confers additional risk for impaired fetal-directed blood flow, we performed high resolution in vivo ultrasound imaging in C57Bl/6J pregnant mice. After pregnancy confirmation, dams were randomly assigned to one of four groups: drug-free control, alcohol-exposed, cannabinoid-exposed or alcohol-and-cannabinoid-exposed. Drug exposure occurred daily between Gestational Days 12–15, equivalent to the transition between the first and second trimesters in humans. Dams first received an intraperitoneal injection of either cannabinoid agonist CP-55,940 (750 µg/kg) or volume-equivalent vehicle. Then, dams were placed in vapor chambers for 30 min of inhalation of either ethanol or room air. Dams underwent ultrasound imaging on three days of pregnancy: Gestational Day 11 (pre-exposure), Gestational Day 13.5 (peri-exposure) and Gestational Day 16 (post-exposure). Results All drug exposures decreased fetal cranial blood flow 24-hours after the final exposure episode, though combined alcohol and cannabinoid co-exposure reduced internal carotid artery blood flow relative to all other exposures. Umbilical artery metrics were not affected by drug exposure, indicating a specific vulnerability of fetal cranial circulation. Cannabinoid exposure significantly reduced cerebroplacental ratios, mirroring prior findings in cannabis-exposed human fetuses. Post-exposure cerebroplacental ratios significantly predicted subsequent perinatal mortality (p = 0.019, area under the curve, 0.772; sensitivity, 81%; specificity, 85.70%) and retroactively diagnosed prior drug exposure (p = 0.005; AUC, 0.861; sensitivity, 86.40%; specificity, 66.7%). Conclusions Fetal cerebrovasculature is significantly impaired by exposure to alcohol or cannabinoids, and co-exposure confers additional risk for adverse birth outcomes. Considering the rising potency and global availability of cannabis products, there is an imperative for research to explore translational models of prenatal drug exposure, including polysubstance models, to inform appropriate strategies for treatment and care in pregnancies affected by drug exposure.

Abstract Quiescence in stem cells is traditionally considered as a state of inactive dormancy or with poised potential. Naive mouse embryonic stem cells (ESCs) can enter quiescence spontaneously or upon inhibition of MYC or fatty acid oxidation, mimicking embryonic diapause in vivo. The molecular underpinning and developmental potential of quiescent ESCs (qESCs) are relatively unexplored. Here we show that qESCs possess an expanded or unrestricted cell fate, capable of generating both embryonic and extraembryonic cell types (e.g., trophoblast stem cells). These cells have a divergent metabolic landscape comparing to the cycling ESCs, with a notable decrease of the one-carbon metabolite S-adenosylmethionine. The metabolic changes are accompanied by a global reduction of H3K27me3, an increase of chromatin accessibility, as well as the de-repression of endogenous retrovirus MERVL and trophoblast master regulators. Depletion of methionine adenosyltransferase Mat2a or deletion of Eed in the polycomb repressive complex 2 results in removal of the developmental constraints towards the extraembryonic lineages. Our findings suggest that quiescent ESCs are not dormant but rather undergo an active transition towards an unrestricted cell fate.

Abstract Background Prenatal alcohol (ethanol) exposure (PAE) results in brain growth restriction, in part, by reprogramming self-renewal and maturation of fetal neural stem cells (NSCs) during neurogenesis. We recently showed that ethanol resulted in enrichment of both proteins and pro-maturation microRNAs in sub-200-nm-sized extracellular vesicles (EVs) secreted by fetal NSCs. Moreover, EVs secreted by ethanol-exposed NSCs exhibited diminished efficacy in controlling NSC metabolism and maturation. Here we tested the hypothesis that ethanol may also influence the packaging of RNAs into EVs from cell-of-origin NSCs. Methods Sex-specified fetal murine iso-cortical neuroepithelia from three separate pregnancies were maintained ex vivo, as neurosphere cultures to model the early neurogenic niche. EVs were isolated by ultracentrifugation from NSCs exposed to a dose range of ethanol. RNA from paired EV and cell-of-origin NSC samples was processed for ribosomal RNA-depleted RNA sequencing. Differential expression analysis and exploratory weighted gene co-expression network analysis (WGCNA) identified candidate genes and gene networks that were drivers of alterations to the transcriptome of EVs relative to cells. Results The RNA content of EVs differed significantly from cell-of-origin NSCs. Biological sex contributed to unique transcriptome variance in EV samples, where > 75% of the most variant transcripts were also sex-variant in EVs but not in cell-of-origin NSCs. WGCNA analysis also identified sex-dependent enrichment of pathways, including dopamine receptor binding and ectoderm formation in female EVs and cell-substrate adhesion in male EVs, with the top significant DEGs from differential analysis of overall individual gene expressions, i.e., Arhgap15, enriched in female EVs, and Cenpa, enriched in male EVs, also serving as WCGNA hub genes of sex-biased EV WGCNA clusters. In addition to the baseline RNA content differences, ethanol exposure resulted in a significant dose-dependent change in transcript expression in both EVs and cell-of-origin NSCs that predominantly altered sex-invariant RNAs. Moreover, at the highest dose, ~ 73% of significantly altered RNAs were enriched in EVs, but depleted in NSCs. Conclusions The EV transcriptome is distinctly different from, and more sex-variant than, the transcriptome of cell-of-origin NSCs. Ethanol, a common teratogen, results in dose-dependent sorting of RNA transcripts from NSCs to EVs which may reprogram the EV-mediated endocrine environment during neurogenesis.

Summary: Prenatal alcohol exposure (PAE) impairs recovery from cerebrovascular ischemic stroke in adult rodents. Since the gut becomes dysbiotic following stroke, we assessed links between PAE and enteric portal inflammation. Adult control and PAE rat offspring received a unilateral endothelin-1-induced occlusion of the middle cerebral artery. Post-stroke behavioral disabilities and brain cytokines were assessed. Mesenteric adipose and liver transcriptomes were assessed from stroke-exposed and stroke-naive offspring. We identified, in the liver of stroke-naive animals, a moderate correlation between PAE and a gene network for inflammatory necroptosis. PAE inhibited the acute-phase brain inflammatory cytokine response to stroke. Post-stroke neurological function was correlated with an adipose gene network associated with B-lymphocyte differentiation and nuclear factor κB (NF-κB) signaling and with a liver pro-inflammatory gene network. Collectively, PAE inhibits brain inflammation but results in an inflammatory signature in enteric portal tissues after stroke, suggesting that PAE persistently and adversely impacts the gut-brain axis following adult-onset disease.

Alcohol exposure in adulthood can result in inflammation, malnutrition, and altered gastroenteric microbiota, which may disrupt efficient nutrient extraction. Clinical and preclinical studies have documented convincingly that prenatal alcohol exposure (PAE) also results in persistent inflammation and nutrition deficiencies, though research on the impact of PAE on the enteric microbiota is in its infancy. Importantly, other neurodevelopmental disorders, including autism spectrum and attention deficit/hyperactivity disorders, have been linked to gut microbiota dysbiosis. The combined evidence from alcohol exposure in adulthood and from other neurodevelopmental disorders supports the hypothesis that gut microbiota dysbiosis is likely an etiological feature that contributes to negative developmental, including neurodevelopmental, consequences of PAE and results in fetal alcohol spectrum disorders. Here, we highlight published data that support a role for gut microbiota in healthy development and explore the implication of these studies for the role of altered microbiota in the lifelong health consequences of PAE.

Background: Fetal alcohol spectrum disorders (FASD) are often characterized as a cluster of brain-based disabilities. Though cardiovascular effects of prenatal alcohol exposure (PAE) have been documented, the vascular deficits due to PAE are less understood, but may contribute substantially to the severity of neurobehavioral presentation and health outcomes in persons with FASD.Methods: We conducted a systematic review of research articles curated in PubMed to assess the strength of the research on vascular effects of PAE. 40 pertinent papers were selected, covering studies in both human populations and animal models.Results: Studies in human populations identified cardiac defects, and defects in vasculature, including increased tortuosity, defects in basement membranes, capillary basal hyperplasia, endarteritis, and disorganized and diminished cerebral vasculature due to PAE. Preclinical studies showed that PAE rapidly and persistently results in vasodilation of large afferent cerebral arteries, but to vasoconstriction of smaller cerebral arteries and microvasculature. Moreover, PAE continues to affect cerebral blood flow into middle-age. Human and animal studies also indicate that ocular vascular parameters may have diagnostic and predictive value. A number of intervening mechanisms were identified, including increased autophagy, inflammation and deficits in mitochondria. Studies in animals identified persistent changes in blood flow and vascular density associated with endocannabinoid, prostacyclin and nitric oxide signaling, as well as calcium mobilization.Conclusion: Although the brain has been a particular focus of studies on PAE, the cardiovascular system is equally affected. Studies in human populations, though constrained by small sample sizes, did link pathology in major blood vessels and tissue vasculature, including brain vasculature, to PAE. Animal studies highlighted molecular mechanisms that may be useful therapeutic targets. Collectively, these studies suggest that vascular pathology is a possible contributing factor to neurobehavioral and health problems across a lifespan in persons with a diagnosis of FASD. Furthermore, ocular vasculature may serve as a biomarker for neurovascular health in FASD.

Sesame (Sesamum indicum L.) is a drought tolerant oilseed crop with the highest oleic acid content, which is yet to be explored for its hybrid vigour. Therefore, present study was carried at Sri Karan Narendra Agriculture University, Jobner, Jaipur, Rajasthan during 2019–20 and 2020–21 to study the combining ability for 11 seed yield and its attributing traits in 10 parents and their 45 crosses in sesame. The effects of general combining ability and specific combining ability on morpo-biochemical attributes of cultivars were studied utilizing half-diallel cross. The experiment was conducted using randomized blocks design (RBD) with 3 replications under different environmental conditions. Significant variations were detected among parents for all of the recorded attributes and the F1 generation also showed significant differences for all recorded attributes. The GCA (General Combining Ability)/SCA (Specialized Combining Ability) variance ratio was found to be less than one, indicating that non-additive gene action predominated for all tested attributes. The parents RT–346, TKG–22, RT–372 and RT–351 emerged as good general combiners for seed yield per plant and its attributes in all environmental conditions. The crosses RT–346 × RT–351, TKG–22 × RT–372, RT–372 × RT–351 and RT–103 × RT–351 emerged as good specific cross combinations for seed yield and oil content. Incorporating F1 hybrids with a high SCA and parents with a high GCA into multiple crossings could also to be a beneficial strategy for improving seed production and oil content in sesame.

Abstract Prenatal opioid exposure (POE) is commonly associated with neonatal opioid withdrawal syndrome (NOWS), which is characterized by a broad variability in symptoms and severity. Currently there are no diagnostic tools to reliably predict which infants will develop severe NOWS, while risk stratification would allow for proactive decisions about appropriate clinical monitoring and interventions. The aim of this prospective cohort study was to assess if extracellular microRNAs (miRNAs) in umbilical cord plasma of infants with POE could predict NOWS severity. Participants (n = 58) consisted of pregnant women receiving medications for opioid use disorder and their infants. NOWS severity was operationalized as the need for pharmacologic treatment and prolonged hospitalization (≥ 14 days). Cord blood miRNAs were assessed using semi-quantitative qRT-PCR arrays. Receiver operating characteristic curves and area under the curve (AUC) were estimated. The expression of three miRNAs (miR-128-3p, miR-30c-5p, miR-421) predicted need for pharmacologic treatment (AUC: 0.85) and prolonged hospitalization (AUC: 0.90). Predictive validity improved after two miRNAs (let-7d-5p, miR-584-5p) were added to the need for pharmacologic treatment model (AUC: 0.94) and another two miRNAs (let-7b-5p, miR-10-5p) to the prolonged hospitalization model (AUC: 0.99). Infant cord blood extracellular miRNAs can proactively identify opioid-exposed neonates at high-risk for developing severe NOWS.

Objective: To conduct a meta-analysis of randomized controlled trials (RCTs) on the effects of atropine eye drop in slowing myopia progression. Methods: A systematic search of relevant articles was done through a computerized search on PubMed, Medline, Cochrane Library, and Google Scholar on June 16, 2022. A supplementary search was done on ClinicalTrials.gov on the same date. After thorough search and analysis, seven relevant RCTs, double-masked with atropine eye drop as intervention arm and placebo as control arm, were selected for meta-analysis. Jadad scoring was used to evaluate the quality of RCTs. The outcome measurements included in the present meta-analysis are mean changes in the spherical equivalent (SE) of myopic error, and mean changes in axial length (AL) during the study period. Result: Pooled summary effect size, calculated by random effect model, for SE of myopia progression was 1.08 with 95% confidence interval (CI) (0.31–1.86) which was statistically significant (P-value = 0.006). Pooled summary effect size, calculated by random effect model, for axial length was − 0.89 with 95% CI (−1.48 to − 0.30) which was statistically significant (P-value = 0.003). Conclusion: In summary, atropine was demonstrated to be effective in controlling myopia progression in children. Both outcome measures, mean SE changes and mean AL elongation responded to atropine intervention compared to placebo.

Circulating miRNAs the in blood are promising biomarkers for predicting pregnancy complications and adverse birth outcomes. Previous work identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following prenatal alcohol exposure and regulated epithelial-mesenchymal transition in the placenta. Here we show that a single intravascular administration of pooled murine-conserved HEamiRNAs to pregnant mice on gestational day 10 (GD10) attenuates umbilical cord blood flow during gestation, explaining the observed intrauterine growth restriction (IUGR), specifically decreased fetal weight, and morphometric indices of cranial growth. Moreover, RNAseq of the fetal portion of the placenta demonstrated that this single exposure has lasting transcriptomic changes, including upregulation of members of the Notch pathway (Dll4, Rfng, Hey1), which is a pathway important for trophoblast migration and differentiation. Weighted gene co-expression network analysis also identified chemokine signaling, which is responsible for regulating immune cell-mediated angiogenesis in the placenta, as an important predictor of fetal growth and head size. Our data suggest that HEamiRNAs perturb the expression of placental genes relevant for angiogenesis, resulting in impaired umbilical cord blood flow and subsequently, IUGR.

Accumulating evidence indicates that extracellular vesicles (EVs) mediate endocrine functions and also pathogenic effects of neurodevelopmental perturbagens like ethanol. We performed mass-spectrometry on EVs secreted by fetal murine cerebral cortical neural stem cells (NSCs), cultured ex-vivo as sex-specific neurosphere cultures, to identify overrepresented proteins and signaling pathways in EVs relative to parental NSCs in controls, and following exposure of parental NSCs to a dose range of ethanol. EV proteomes differ substantially from parental NSCs, and though EVs sequester proteins across sub-cellular compartments, they are enriched for distinct morphogenetic signals including the planar cell polarity pathway. Ethanol exposure favored selective protein sequestration in EVs and depletion in parental NSCs, and also resulted in dose-independent overrepresentation of cell-cycle and DNA replication pathways in EVs as well as dose-dependent overrepresentation of rRNA processing and mTor stress pathways. Transfer of untreated EVs to naïve cells resulted in decreased oxidative metabolism and S-phase, while EVs derived from ethanol-treated NSCs exhibited diminished effect. Collectively, these data show that NSCs secrete EVs with a distinct proteome that may have a general growth-inhibitory effect on recipient cells. Moreover, while ethanol results in selective transfer of proteins from NSCs to EVs, the efficacy of these exposure-derived EVs is diminished.

We report a finding of a pigmented chorioretinal scar with acute retinal necrosis (ARN) caused by herpes simplex virus 2 (HSV-2) infection rather than toxoplasma, creating an initial diagnostic dilemma. A 53-year-old functionally monocular male presented with painless floaters and blurry vision in his seeing eye over a period of 4 days. An exam demonstrated anterior chamber (AC) reaction, vitritis, multifocal patches of whitening, and an occlusive retinal vasculitis. A superior pigmented chorioretinal scar with overlying contracted vitreous was noted in the periphery with no adjacent retinal whitening. The patient was treated for both ARN and toxoplasma chorioretinitis until PCR study of the vitreous and AC returned positive for HSV-2 and negative for toxoplasmosis. Management consisted of a dual therapy regimen of both oral and intravitreal antiviral agents as well as oral corticosteroids. The patient’s clinical course was complicated by rhegmatogenous retinal detachment within 2 weeks after symptom onset, requiring pars plana vitrectomy with silicone oil and intraoperative intraocular incubation with foscarnet. We review emerging evidence for pigmented chorioretinal scars in ARN specifically caused by HSV-2, as well as diagnostic and treatment dilemmas in the management of ARN and ARN detachments.

The dielectric interpretation of crystal ionicity evolved by Phillips and Van Vechten (P.V.V) has been utilized to evaluate various ground state properties for broad range of semiconductors and insulators. Although, the relevance of P.V.V dielectric theory has been restricted to only simple ANB8-N structured compounds, which have a particular bond. Levine has broadened P.V.V. theory of ionicity to multiple bond and complex crystals and evaluated many bond parameters for ternary tetrahedral semiconductors. Some other researchers have extended Levine’s work with a concept of ionic charge product and nearest neighbour distance to binary and ternary tetrahedral crystals to evaluate the ground state properties. In this paper, a new hypothesis of average atomic number of the elements in a compound has been used to understand the some electronic and optical properties such as ionic gap (Ec), average energy gap (Eg), crystal ionicity (fi), electronic susceptibility (χ), and dielectric constant (ϵ) of ternary tetrahedral (AIIBIV and AIBIII) semiconductors. A reasonably acceptable agreement has been noticed between our evaluated values and other researchers reported values.

The concept of ionicity has been developed by Phillips and Van Vechten from the dielectric analysis of the semiconductors and insulators to evaluate various bond parameters of binary tetrahedral (AIIBVI and AIIIBV) semiconductors. In this paper, an advance hypothesis of average atomic number of the elements in a compound has been used to evaluate intrinsic electronic and optical parameters such as ionic gap (Ec), average energy gap (Eg), crystal ionicity (fi) and dielectric constant (ϵ) of binary tetrahedral semiconductors.

Abstract Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs ( ex miRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed ex miRNAs with clinically-relevant effect sizes (Cohen’s d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of ex miRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered ex miRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant ex miRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition.

Abstract Most persons with fetal alcohol spectrum disorders (FASDs) remain undiagnosed or are diagnosed in later life. To address the need for earlier diagnosis, we previously assessed miRNAs in the blood plasma of pregnant women who were classified as unexposed to alcohol (UE), heavily exposed with affected infants (HEa), or heavily exposed with apparently unaffected infants (HEua). We reported that maternal miRNAs predicted FASD-related growth and psychomotor deficits in infants. Here, we assessed whether fetal sex influenced alterations in maternal circulating miRNAs following prenatal alcohol exposure (PAE). To overcome the loss of statistical power due to disaggregating maternal samples by fetal sex, we adapted a strategy of iterative bootstrap resampling with replacement to assess the stability of statistical parameter estimates. Bootstrap estimates of parametric and effect size tests identified male and female fetal sex-associated maternal miRNA responses to PAE that were not observed in the aggregated sample. Additionally, we observed, in HEa mothers of female, but not male fetuses, a network of co-secreted miRNAs whose expression was linked to miRNAs encoded on the X-chromosome. Interestingly, the number of significant miRNA correlations for the HEua group mothers with female fetuses was intermediate between HEa and UE mothers at mid-pregnancy, but more similar to UE mothers by the end of pregnancy. Collectively, these data show that fetal sex predicts maternal circulating miRNA adaptations, a critical consideration when adopting maternal miRNAs as diagnostic biomarkers. Moreover, a maternal co-secretion network, predominantly in pregnancies with female fetuses, emerged as an index of risk for adverse birth outcomes due to PAE.

This paper presents a comparison of several artificial intelligence (AI) based binary classifiers for detecting the integrity of data obtained from Internet of Things (IoT) enabled wearable sensors. Detecting the integrity of data at the network edge facilitates the elimination of corrupted or unusable data, which translates to a lower amount of data stored and transmitted. This reduces the storage and power requirements of IoT devices without a reduction in functionality. In this work, we explore several machine learning-based classifiers to check the integrity of electrocardiogram (ECG) data. The feature vectors are derived from low complexity kurtosis and skewness based Signal Quality Indices (SQIs). From the experiments, it is found that a bagged ensemble of 3 neural networks achieves the highest detection accuracy of 99.47%. We also estimated the complexity and power consumed by the various classifier implementations and classifier fusion implementations. The energy consumed by the ensemble classifier was estimated to be around 0.039 nJ.

This paper aims to reduce the power consumption of electrocardiography based wearable healthcare devices, by introducing power reduction approaches and considerations at system level design, where we have the highest potential to influence power. It focuses, in particular, on algorithm design and implementation, data acquisition, and transmission under constrained resources. A thorough investigation of the suitability of nine existing algorithms for on-sensor QRS feature detection is conducted, with respect to metrics such as sensitivity, positive predictivity, power consumption, parameter choice and time delay. Optimisation of data acquisition on CPU-based IoT systems is performed, and the current consumption is reduced by a factor of 3 using a combination of direct memory access (DMA) list approach and low-level register manipulations for task delegation. The acquisition data rate, sampling rate, buffer and batch size are also optimised. To reduce the power consumption by data transmission, the effect of on-sensor versus off-sensor processing is investigated. While focusing on CPU-based systems with experiments performed on a generic low-power wearable platform, the design optimisation and considerations proposed in this work could be extended to custom designs and allow further investigation into QRS detection algorithm optimisation for wearable devices.

Background: An acute respiratory disease (COVID-19), caused by a novel coronavirus (SARS-CoV-2,), has been declared a pandemic by WHO. A surgery on COVID-19 patients not only involves a risk of spread of the disease but also there is a serious concern for the patient's surgical outcomes and resources requirement. Aim: The retrospective study is aimed to provide a protocol for pre-operative testing of SARS CoV-2 using RT-PCR in the patient undergoing cardio-thoracic surgeries. Material and Methods: To analyze the impact of pre-operative testing of SARS- CoV-2 using RT-PCR in the patient undergoing elective cardio-thoracic surgeries. The patient who underwent surgical interventions during the COVID-19 lockdown period was divided into two phases. Phase I (without COVID-19 RT-PCR testing) and Phase II (with pre-operative COVID-19 RT-PCR testing). The retrospective comparison between the two study groups was done using Student t-test, Mann–Whitney U, and Chi square (χ2) test depending upon the clinical variable to be analyzed. Results: During the early phase (phase I), 26 patients underwent cardio-thoracic surgery without COVID-19 RT-PCR test. Whereas, during phase II, all patients were tested for COVID-19 using RT-PCR, preoperatively and a total of 64 surgeries were performed during this phase. One patient planned for CABG was positive on RT-PCR for COVID-19 and was sent to the quarantine ward. The difference in the pre-operative hospital stay between two groups was found to be statistically significant and a significant decrease in the number of PPE kits used, during the phase I. Conclusion: All asymptomatic patients should be tested for COVID-19 using RT-PCR prior to cardio-thoracic surgeries not only to contain the disease but to avoid potential implications of COVID-19 on the perioperative course, without added financial implications.

Alcohol use disorder (AUD) is one of the most common preventable mental health disorders and can result in pathology within the CNS, including the cerebellum. Cerebellar alcohol exposure during adulthood has been associated with disruptions in proper cerebellar function. However, the mechanisms regulating ethanol-induced cerebellar neuropathology are not well understood. High-throughput next generation sequencing was performed to compare control versus ethanol-treated adult C57BL/6J mice in a chronic plus binge model of AUD. Mice were euthanized, cerebella were microdissected, and RNA was isolated and submitted for RNA-sequencing. Down-stream transcriptomic analyses revealed significant changes in gene expression and global biological pathways in control versus ethanol-treated mice that included pathogen-influenced signaling pathways and cellular immune response pathways. Microglial-associated genes showed a decrease in homeostasis-associated transcripts and an increase in transcripts associated with chronic neurodegenerative diseases, while astrocyte-associated genes showed an increase in transcripts associated with acute injury. Oligodendrocyte lineage cell genes showed a decrease in transcripts associated with both immature progenitors as well as myelinating oligodendrocytes. These data provide new insight into the mechanisms by which ethanol induces cerebellar neuropathology and alterations to the immune response in AUD.

Background: The prevalence of genito-anal injuries in victims of sexual assault depends on several factors. Forensic examination, documentation of injuries and preparing report thus becomes challenging for healthcare providers as the presence or absence of injuries aids in the subsequent laying of charges against the accused. This paper aims to determine the pattern of genito-anal injuries and factors associated with the laying of charges against the accused. Methods: A cross-sectional study of victims of sexual assault (n = 440) was conducted between 2014 and 2017 in a specialized tertiary care center in a Metropolitan city in India. The results were expressed as proportion and percentage. Chi-squared test was used to analyse data using SPSS version 23.0. Results: There was no statistically significant association between reporting within 72 h of sexual assault and the arrest of the accused. Vaginal and anal bleeding were present in 4.1% cases and 2.7% cases respectively. Genital and anal injuries were present only in 30.9% of cases. The most common genito-anal injury was laceration (72.08%). Posterior fourchette injury (most common site) was present in 27.94% of cases. Extra genital injuries were found in 24.09% of victims. The most common extra genital injury was abrasion (26.42%). Intoxicants were found in the blood of 4.8% of victims and spermatozoa/semen was found in swabs from 3.6% of victims. In this study 25.9% of perpetrators were arrested, out of which 84.37% of adult victim’s cases and 94.23% of minor ( 0.05) and were dropped from the model. The odds ratio (OR) for charge-laying associated with the age of the victim 18 years age and 18 years of age did not appear to have any influence over the arrest. A notable finding was a high proportion (75.51% in 18 years) of cases where an arrest was effected in adults and child sexual assault cases where no injuries were described. Conclusion: This study shows the pattern of genito-anal injuries and factors associated with the laying of charges in sexual assault cases in a developing country. It should be noted that most of those exposed to sexual assault do not have visible genito-anal injuries. We report that age is significantly associated with the presence of genito-anal injuries. However, it is important to note that the presence of injuries does not prove rape, neither its absence disproves the act. The information gathered by a meticulous forensic examination does make a difference in the legal outcome for cases of sexual assault.

Modified Reynolds-Darcy equation for ferrofluid lubricated squeeze-film bearing, made by flat circular porous upper and flat circular impermeable lower discs, is derived. The ferrofluid is controlled by oblique variable magnetic field (VMF) and VMF is important because of its advantage of generating maximum field at the required active contact zone. The porous matrix is considered because of its advantageous property of self-lubrication. Moreover, the validity of the Darcy’s law is assumed in the porous matrix. Expression for dimensionless film pressure p in terms of Bessel function by considering the effect of existence of pressure difference at the film-porous interface is obtained. The expression for dimensionless load-carrying capacity W is also obtained. The effects of dimensionless radial parameter, inverse of the dimensionless film thickness parameter (h0 / h) , magnetization parameter and squeeze velocity are studied on p, whereas the effects of the inverse of the dimensionless film thickness parameter and magnetization parameter and squeeze velocity are studied on W. Moreover, the effect of dimensionless pressure difference P at the film-porous interface is studied on Wn (which is the term because of existence of the pressure difference at the film-porous interface). The results show that p increases for smaller values of radial parameter, larger values of magnetization parameter and when (h0 / h) ≤ 12, whereas W increases for larger values of magnetization parameter and when (h0 / h) ≤ 12. The squeeze velocity have no effects on the variation of p and W. Moreover, the results for Wn show that it increases with the increase of P.

Summary: Prenatal alcohol exposure (PAE) results in cerebral cortical dysgenesis. Single-cell RNA sequencing was performed on murine fetal cerebral cortical cells from six timed pregnancies, to decipher persistent cell- and sex-specific effects of an episode of PAE during early neurogenesis. We found, in an analysis of 38 distinct neural subpopulations across 8 lineage subtypes, that PAE altered neural maturation and cell cycle and disrupted gene co-expression networks. Whereas most differentially regulated genes were inhibited, particularly in females, PAE also induced sex-independent neural expression of fetal hemoglobin, a presumptive epigenetic stress adaptation. PAE inhibited Bcl11a, Htt, Ctnnb1, and other upstream regulators of differentially expressed genes and inhibited several autism-linked genes, suggesting that neurodevelopmental disorders share underlying mechanisms. PAE females exhibited neural loss of X-inactivation, with correlated activation of autosomal genes and evidence for spliceosome dysfunction. Thus, episodic PAE persistently alters the developing neural transcriptome, contributing to sex- and cell-type-specific teratology.

Liquid K_(1-x) Rb_x binary alloys with various thermodynamical proportions of participating elements are investigated. The properties of thermodynamic interest are included in the study. The internal energy (Fint), Helmholtz free enrgy (FH) and the entropy (S) have been calculated in a concentration range from X=0.0 to X=1.0 increasing in a step of 0.1 in the present work. Apart from the internal energy (Fint), various contributions to this energy are also calculated and separately depicted in the present article. A variational approach has been adopted for the present calculation. A single potential with a set of two parameters is used for the calculation of all properties of the alloys. Static Hartree local field function (H) is used to consider screening effect. Various local field correction functions are used to take into account the exchange and correlation effect. Comparison with experimental data at some concentration shows the good agreement with the presently obtained data. With the help of current results, the applied model potential found very suitable with individual parameters for thermodynamical study. As the present results provide the data even where minimum availability of the experimental findings, it can serve as a data base for the future calculation which deals with thermodynamics of the liquid alloys. Present results allow one to get proportion based tuned properties of the K_(1-x) Rb_x for different requirements.

* Context.-Machine learning applications in the pathology clinical domain are emerging rapidly. As decision support systems continue to mature, laboratories will increasingly need guidance to evaluate their performance in clinical practice. Currently there are no formal guidelines to assist pathology laboratories in verification and/or validation of such systems. These recommendations are being proposed for the evaluation of machine learning systems in the clinical practice of pathology. Objective.-To propose recommendations for performance evaluation of in vitro diagnostic tests on patient samples that incorporate machine learning as part of the pre-analytical, analytical, or post-analytical phases of the laboratory workflow. Topics described include considerations for machine learning model evaluation including risk assessment, predeployment requirements, data sourcing and curation, verification and validation, change control management, human-computer interaction, practitioner training, and competency evaluation. Data Sources.-An expert panel performed a review of the literature, Clinical and Laboratory Standards Institute guidance, and laboratory and government regulatory frameworks. Conclusions.-Review of the literature and existing documents enabled the development of proposed recommendations. This white paper pertains to performance evaluation of machine learning systems intended to be implemented for clinical patient testing. Further studies with real-world clinical data are encouraged to support these proposed recommendations. Performance evaluation of machine learning models is critical to verification and/or validation of in vitro diagnostic tests using machine learning intended for clinical practice. (Arch Pathol Lab Med. 2024;148:e335-e361; doi: 10.5858/arpa.2023-0042-CP), Institution of machine learning (ML) in the pathology clinical domain has gained momentum and is rapidly advancing. As ML-based clinical decision support (CDS) systems continue to mature, laboratories will increasingly [...]

Investigation of thermodynamic of liquid binary alloys using pseudopotential theory is reported. The potential suggested by Fiolhais et al. with its individual parameters is used for the entire calculation. A transferability of the potential from the solid to liquid medium is achieved for the presently reported binary alloy. The internal energy components, Helmholtz free energy, entropy, and total energy at various proportions of the participating alkali metals are included in the study. The comparison with the other data has been shown in the present article. Exchange and correlation effect is also tested with the help of various local field correction functions. BIBECHANA 18 (2) (2021) 1-8

Summary: How ubiquitous transcription factors (TFs) coordinate temporal inputs from broadly expressed epigenetic factors to control cell fate remains poorly understood. Here, we uncover a molecular relationship between p53, an abundant embryonic TF, and WDR5, an essential member of the MLL chromatin modifying complex, that regulates mouse embryonic stem cell fate. Wild-type Wdr5 or transient Wdr5 knockout promotes a distinct pattern of global chromatin accessibility and spurs neuroectodermal differentiation through an RbBP5-dependent process in which WDR5 binds to, and activates transcription of, neural genes. Wdr5 rescue after its prolonged inhibition targets WDR5 to mesoderm lineage-specifying genes, stimulating differentiation toward mesoderm fates in a p53-dependent fashion. Finally, we identify a direct interaction between WDR5 and p53 that enables their co-recruitment to, and regulation of, genes known to control cell proliferation and fate. Our results unmask p53-dependent mechanisms that temporally integrate epigenetic WDR5 inputs to drive neuroectoderm and mesoderm differentiation from pluripotent cells. : How ubiquitous chromatin-associated proteins and transcription factors (TFs) regulate cell fate determination is poorly understood. Li et al. show that regulation of the broadly expressed TF p53 by the chromatin-associated protein WDR5 is required for neuroectoderm versus mesoderm lineage determination in mouse embryonic stem cells (ESCs). Keywords: WDR5, p53, chromatin, cell fate, embryonic stem cells, differentiation, retina, neuroectoderm, mesoderm, cardiomyocyte

QS-21 is a potent vaccine adjuvant currently sourced by extraction from the Chilean soapbark tree. It is a key component of human vaccines for shingles, malaria, coronavirus disease 2019 and others under development. The structure of QS-21 consists of a glycosylated triterpene scaffold coupled to a complex glycosylated 18-carbon acyl chain that is critical for immunostimulant activity. We previously identified the early pathway steps needed to make the triterpene glycoside scaffold; however, the biosynthetic route to the acyl chain, which is needed for stimulation of T cell proliferation, was unknown. Here, we report the biogenic origin of the acyl chain, characterize the series of enzymes required for its synthesis and addition and reconstitute the entire 20-step pathway in tobacco, thereby demonstrating the production of QS-21 in a heterologous expression system. This advance opens up unprecedented opportunities for bioengineering of vaccine adjuvants, investigating structure-activity relationships and understanding the mechanisms by which these compounds promote the human immune response.

Integrating the health-care enterprise (IHE) is an international initiative to promote the use of standards to achieve interoperability among health information technology systems. The Pathology and Laboratory Medicine domain within IHE has brought together subject matter experts, electronic health record vendors, and digital imaging vendors, to initiate development of a series of digital pathology interoperability guidelines, called “integration profiles” within IHE. This effort begins with documentation of common use cases, followed by identification of available data and technology standards best utilized to achieve those use cases. An integration profile that describes the information flow and technology interactions is then published for trial use. Real world testing occurs in “connectathon” events, in which multiple vendors attempt to connect their products following the interoperability guidance parameters set forth in the profile. This paper describes the overarching set of integration profiles, one of which has been published, to support key digital pathology use cases.

The current study examined micro RNA (miRNAs) clusters from the maternal plasma to determine their association with preterm birth (PTB) and infant birth outcomes. A subsample of 42 participants who spontaneously delivered either preterm (≤37 weeks) or term was selected from a parent sample of 515 pregnant Mexican American women. Plasma samples and prenatal data were collected at a single mid-gestation time point (22-24 weeks' gestation) and birth outcomes were obtained from medical records after delivery. Circulating miRNAs were analyzed by qPCR. When miRNAs were grouped according to chromosomal cluster rather than expression level, individual miRNAs correlated strongly with other individual miRNAs within their respective genomic locus. miRNAs from the c19mc cluster negatively correlated with c14mc miRNAs, and this relationship was more pronounced in PTB. Clusters c14mc was negatively associated with length of gestation; while the c19mc was positively associated with length of gestation and infant head circumference. Together, these findings suggest that groups of miRNAs from common chromosomal clusters, rather than individual miRNAs, operate as co-regulated groups of signaling molecules to coordinate length of gestation and infant outcomes. From this evidence, differences in cluster-wide expression of miRNAs are involved in spontaneous PTB.

In this paper I argue that the most fundamental goal of any public policy is to assist the realization of social good. I take it that the idea of social good has developed differently in different political and moral traditions, and focus my analysis on the interplay of liberalism, virtue ethics and the Capability Approach. I argue that the liberal conception of social good, as espoused by its leading exponents, is somewhat problematic, and that it fails to account for meaningful civic associations. Even though liberal thinkers often prioritize an individual’s freedom and autonomy, they do not provide us with concreto principles that can facilitate the realization of these goals. I draw upon the practical functioning of leading liberal democracies, including the United States, Canada and India, emphasizing the role of normative political constraints in policy making. I conclude that the liberal conception of social good stands in an acute need of a fresh principle that can rectify the above anomalies and reinvigorate its moral force, and that such a principle can probably be constructed with the help of Amartya Sen’s Capability Approach and Aristotle’s Virtue Theory.

Based on the Shliomis ferrofluid flow model (SFFM) and continuity equation for the film as well as porous region, modified Reynolds equation for lubrication of circular squeeze film bearings is derived by considering the effects of oblique radially variable magnetic field (VMF), slip velocity at the film–porous interface and rotations of both the discs. The squeeze film bearings are made up of circular porous upper disc of different shapes (exponential, secant, mirror image of secant and parallel) and circular impermeable flat lower disc. The validity of Darcy's Law is assumed in the porous region. The SFFM is important because it includes the effects of rotations of the carrier liquid as well as magnetic particles. The VMF is used because of its advantage of generating maximum field at the required active contact area of the bearing design system. Also, the effect of porosity is included because of its advantageous property of self-lubrication. Using Reynolds equation, general form of pressure equation is derived and expression for dimensionless load-carrying capacity is obtained. Using this expression, results for different bearing design systems (due to different shapes of the upper disc) are computed and compared for variation of different parameters.

Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3′UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.

Fetal alcohol spectrum disorders (FASD) are difficult to diagnose since many heavily exposed infants, at risk for intellectual disability, do not exhibit craniofacial dysmorphology or growth deficits. Consequently, there is a need for biomarkers that predict disability. In both animal models and human studies, alcohol exposure during pregnancy resulted in significant alterations in circulating microRNAs (miRNAs) in maternal blood. In the current study, we asked if changes in plasma miRNAs in alcohol-exposed pregnant mothers, either alone or in conjunction with other clinical variables, could predict infant outcomes. Sixty-eight pregnant women at two perinatal care clinics in western Ukraine were recruited into the study. Detailed health and alcohol consumption histories, and 2nd and 3rd trimester blood samples were obtained. Birth cohort infants were assessed by a geneticist and classified as unexposed (UE), heavily prenatally exposed and affected (HEa) or heavily exposed but apparently unaffected (HEua). MiRNAs were assessed in plasma samples using qRT-PCR arrays. ANOVA models identified 11 miRNAs that were all significantly elevated in maternal plasma from the HEa group relative to HEua and UE groups. In a random forest analysis classification model, a combination of high variance miRNAs, smoking history and socioeconomic status classified membership in HEa and UE groups, with a misclassification rate of 13%. The RFA model also classified 17% of the HEua group as UE-like, whereas 83% were HEa-like, at least at one stage of pregnancy. Collectively our data indicate that maternal plasma miRNAs predict infant outcomes, and may be useful to classify difficult-to-diagnose FASD subpopulations.

Hereditary, hormonal, and behavioral factors contribute to the development of breast cancer. Alcohol consumption is a modifiable behavior that is linked to increased breast cancer risks and is associated with the development of hormone-dependent breast cancers as well as disease progression and recurrence following endocrine treatment. In this study we examined the molecular mechanisms of action of alcohol by applying molecular, genetic, and genomic approaches in characterizing its effects on estrogen receptor (ER)-positive breast cancer cells. Treatments with alcohol promoted cell proliferation, increased growth factor signaling, and up-regulated the transcription of the ER target gene GREB1 but not the canonical target TFF1/pS2. Microarray analysis following alcohol treatment identified a large number of alcohol-responsive genes, including those which function in apoptotic and cell proliferation pathways. Furthermore, expression profiles of the responsive gene sets in tumors were strongly associated with clinical outcomes in patients who received endocrine therapy. Correspondingly, alcohol treatment attenuated the anti-proliferative effects of the endocrine therapeutic drug tamoxifen in ER-positive breast cancer cells. To determine the contribution and functions of responsive genes, their differential expression in tumors were assessed between outcome groups. The proto-oncogene BRAF was identified as a novel alcohol- and estrogen-induced gene that showed higher expression in patients with poor outcomes. Knock-down of BRAF, moreover, prevented the proliferation of breast cancer cells. These findings not only highlight the mechanistic basis of the effects of alcohol on breast cancer cells and increased risks for disease incidents and recurrence, but may facilitate the discovery and characterization of novel oncogenic pathways and markers in breast cancer research and therapeutics.