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The equine chorionic girdle is comprised of specialized invasive trophoblast cells that begin formation approximately 25 days after ovulation (day 0) and invade the endometrium to become endometrial cups. These specialized trophoblast cells transition from uninucleate to differentiated binucleate trophoblast cells that secrete the glycoprotein hormone equine chorionic gonadotropin (eCG; formerly known as pregnant mare serum gonadotropin or PMSG). This eCG has LH-like activity in the horse but variable LH- and FSH-like activity in other species and has been utilized for these properties both in vivo and in vitro. To produce eCG commercially, large volumes of whole blood must be collected from pregnant mares, which negatively impacts equine welfare due to repeated blood collections and the birth of an unwanted foal. Attempts to produce eCG in vitro using long-term culture of chorionic girdle explants have not been successful beyond 180 days, with peak eCG production at 30 days of culture. Organoids are three-dimensional cell clusters that self-organize and can remain genetically and phenotypically stable throughout long-term culture (i.e., months). Human trophoblast organoids have been reported to successfully produce human chorionic gonadotropin (hCG) and proliferate long-term (>1 year). The objective of this study was to evaluate whether organoids derived from equine chorionic girdle maintain physiological functionality. Here we show generation of chorionic girdle organoids for the first time and demonstrate in vitro production of eCG for up to 6 weeks in culture. Therefore, equine chorionic girdle organoids provide a physiologically representative 3D in vitro model for chorionic girdle development of early equine pregnancy.

Cluster of differentiation 47 (CD47) plays an important role in the pathophysiology of various diseases including atherosclerosis but its role in neointimal hyperplasia which contributes to restenosis has not been studied. Using molecular approaches in combination with a mouse vascular endothelial denudation model, we studied the role of CD47 in injury-induced neointimal hyperplasia. We determined that thrombin-induced CD47 expression both in human aortic smooth muscle cells (HASMCs) and mouse aortic smooth muscle cells. In exploring the mechanisms, we found that the protease-activated receptor 1-Gα protein q/11 (Gαq/11)–phospholipase Cβ3–nuclear factor of activated T cells c1 signaling axis regulates thrombin-induced CD47 expression in HASMCs. Depletion of CD47 levels using its siRNA or interference of its function by its blocking antibody (bAb) blunted thrombin-induced migration and proliferation of HASMCs and mouse aortic smooth muscle cells. In addition, we found that thrombin-induced HASMC migration requires CD47 interaction with integrin β3. On the other hand, thrombin-induced HASMC proliferation was dependent on CD47’s role in nuclear export and degradation of cyclin-dependent kinase–interacting protein 1. In addition, suppression of CD47 function by its bAb rescued HASMC efferocytosis from inhibition by thrombin. We also found that vascular injury induces CD47 expression in intimal SMCs and that inhibition of CD47 function by its bAb, while alleviating injury-induced inhibition of SMC efferocytosis, attenuated SMC migration, and proliferation resulting in reduced neointima formation. Thus, these findings reveal a pathological role for CD47 in neointimal hyperplasia.

Background There is an increasing need for Mental Health Promotion (MHP) among adolescents, especially in developing countries with limited resources and rapid socio-demographic transition. With the growing burden of mental health problems among adolescents (suicide, depression) and their preferences to seek help from their peers, improving Mental Health Literacy (MHL) and behaviours for First Aid in Mental Health (MH-FA) becomes crucial to promote their mental health. Methods Schools are ideal settings for reaching the vulnerable adolescents. The proposed study evaluates the effectiveness of a classroom-based teacher-led integrated school mental health intervention called SUMS (MHP + MHL + MH-FA). The study will involve a pragmatic, cluster-randomised waitlist-controlled design to evaluate the effectiveness of SUMS intervention using schools as unit-of-randomisation. The study will be conducted in Srinivaspura taluka (Sub-district) of Kolar district (administrative unit of health) of Karnataka in collaboration with a multi-disciplinary expert team from NIMHANS (National Institute of Mental Health And Neuro Sciences), Bangalore-India and Department of Education, Government of Karnataka, India. A total of 8 schools (400 students studying in 6–8 grade) from Srinivaspura taluka will be randomised into intervention and waitlist control group. The intervention group will receive SUMS intervention through 10–15 h of classroom sessions. The primary outcome is the improvement in positive mental health literacy, as measured by the Mental Health-Promoting Knowledge (MHPK-10) scale. Changes in MH-FA knowledge and intentions, Mental health stigma, help-seeking and resilience are assessed as secondary outcomes. Data will be collected at baseline, 6-weeks, 6-months and 12-months post-intervention. The waitlist-control schools will receive the interventions at the end of the 12-month follow-up assessment in intervention-schools. Discussion This is the first study to integrate Mental Health Literacy with Mental Health Promotion and behaviours for First Aid in Mental Health to promote mental health well-being among adolescent school children in India. With a need to build a more substantial evidence base on School Mental Health Promotion approaches in developing countries, the study findings will have implications for implementing and operationalising Health and Wellness Ambassador initiative in India. Trial registration Clinical Trials Registry - India, CTRI/2019/07/020394. Registered prospectively on 29 July 2019. (ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=35724&EncHid=&userName=sums).

Diabetes related Quality of Life (QoL) and treatment satisfaction data is very scarce from India. The ayurpharmacoepidemiology study design was assumed to explore the definite situation of perceived QoL among Indian diabetics and to understand the possibilities of interventions provided in Ayurveda hospitals against diabetes by assessing treatment satisfaction among diabetics. Cross-sectional study involving 203 type 2 diabetes patients aged ≥ 25 years were assessed by self-administered Audit of Diabetes Dependent Quality of Life (ADDQoL-19) and Diabetes Treatment Satisfaction Questionnaire (DTSQc). Participants represented both male (68%) and female (32%) with mean age 55.31 (± 10.505 SD) years having age range of 56 years. Family history of diabetes revealed 20.68% paternal and 18.72% maternal diabetes. Mean duration of diabetes was 5.9384 (± 4.0148 SD) years with range of 6 months to 23.5 years. The mean ADDQoL [Average Weighted Impact (AWI)] score of the total participants were (-) 2.7753 where 98.03% participants perceived diabetes to impact negatively on their QoL. Mean DTSQ score was 28.0697. Association between ADDQoL (AWI) score and duration of diabetes showed no significant relationship (p=0.208) but strong evidence of diabetes complications was found significantly (p=0.017) related to ADDQoL (AWI) score. Negatively impact of Diabetes on QoL among Indians highlight lack of structured education, information programs and integrated diabetes health care model. The study widens the scope for future research opportunities involving ayurpharmacoepidemiological approach for monitoring psychosocial wellbeing and QoL with integrated therapeutic advances involving Ayurveda.

In perceptual decisions, subjects infer hidden states of the environment based on noisy sensory information. Here we show that both choice and its associated confidence are explained by a Bayesian framework based on partially observable Markov decision processes (POMDPs). We test our model on monkeys performing a direction-discrimination task with post-decision wagering, demonstrating that the model explains objective accuracy and predicts subjective confidence. Further, we show that the model replicates well-known discrepancies of confidence and accuracy, including the hard-easy effect, opposing effects of stimulus variability on confidence and accuracy, dependence of confidence ratings on simultaneous or sequential reports of choice and confidence, apparent difference between choice and confidence sensitivity, and seemingly disproportionate influence of choice-congruent evidence on confidence. These effects may not be signatures of sub-optimal inference or discrepant computational processes for choice and confidence. Rather, they arise in Bayesian inference with incomplete knowledge of the environment., A Bayesian framework based on partially observable Markov decision processes (POMDPs) not only predicts subjects’ confidence in a perceptual decision making task but also explains well-known discrepancies between confidence and choice accuracy as arising from incomplete knowledge of the environment.

Objective: A major challenge in designing closed-loop brain-computer interfaces is finding optimal stimulation patterns as a function of ongoing neural activity for different subjects and objectives. Approach: To achieve goal-directed closed-loop neurostimulation, we propose "neural co-processors" which use artificial neural networks and deep learning to learn optimal closed-loop stimulation policies, shaping neural activity and bridging injured neural circuits for targeted repair and rehabilitation. The co-processor adapts the stimulation policy as the biological circuit itself adapts to the stimulation, achieving a form of brain-device co-adaptation. Here we use simulations to lay the groundwork for future in vivo tests of neural co-processors. We leverage a cortical model of grasping, to which we applied various forms of simulated lesions, allowing us to develop the critical learning algorithms and study adaptations to non-stationarity. Main results: Our simulations show the ability of a neural co-processor to learn a stimulation policy using a supervised learning approach, and to adapt that policy as the underlying brain and sensors change. Our co-processor successfully co-adapted with the simulated brain to accomplish the reach-and-grasp task after a variety of lesions were applied, achieving recovery towards healthy function. Significance: Our results provide the first proof-of-concept demonstration of a co-processor for adaptive activity-dependent closed-loop neurostimulation, optimizing for a rehabilitation goal. While a gap remains between simulations and applications, our results provide insights on how co-processors may be developed for learning complex adaptive stimulation policies for a variety of neural rehabilitation and neuroprosthetic applications., 45 pages, 19 figures. Submitted the IOP Journal of Neural Engineering

Introduction: There is an increasing body of evidence surrounding the importance of a T-cell mediated response to SARS-CoV-2 infection and after COVID-19 vaccination. In this internal feasibility study, we evaluated both the total antibody (IgA, IgM, and IgG) and T-cell responses in a cohort of COVID-19 convalescents and vaccinated individuals.Methods: Whole blood specimens were collected weekly from 12 subjects at different timepoints within/after the COVID-19 mRNA vaccination regimen and from 4 PCR-confirmed convalescent donors to measure durability of humoral and cell-mediated immune response. T-cell and Antibody responses were evaluated via the QuantiFERON SARS-CoV-2 Research Use Only (QFN SARS-CoV-2) assay which is an interferon gamma release assay (IGRA) and QIAreach Anti-SARS-CoV-2 Total (Anti-CoV-2) Test, respectively.Results: In a cohort of recently vaccinated individuals, subjects demonstrated robust total antibody and CD4+/CD8+ T-cell response to SARS-CoV-2 mRNA vaccines when followed for 2 months post 2nd dose. In most individuals, T-cell response declined between 1st and 2nd dose suggesting need for booster or completion of the 2-dose vaccine series. In a group of convalescent donors tested with QFN SARS-CoV-2 and Anti-CoV-2 tests, all patients had an antibody and T-cell response up to 1 year after natural infection.Conclusion: This small feasibility study demonstrates that QFN-SARS-CoV-2 test is able to identify CD4+ and CD8+ T-cell mediated responses in SARS-CoV-2 vaccinated subjects and those recovered from COVID-19, alongside a qualitative antibody response detectable via the QIAreach Anti-CoV2 Test.

Correlated binary data are prevalent in a wide range of scientific disciplines, including healthcare and medicine. The generalized estimating equations (GEEs) and the multivariate probit (MP) model are two of the popular methods for analyzing such data. However, both methods have some significant drawbacks. The GEEs may not have an underlying likelihood and the MP model may fail to generate a multivariate binary distribution with specified marginals and bivariate correlations. In this paper, we study multivariate binary distributions that are based on D-vine pair-copula models as a superior alternative to these methods. We elucidate the construction of these binary distributions in two and three dimensions with numerical examples. For higher dimensions, we provide a method of constructing a multidimensional binary distribution with specified marginals and equicorrelated correlation matrix. We present a real-life data analysis to illustrate the application of our results.

Background Cardiovascular disease (CVD) hospitalizations declined worldwide during the COVID-19 pandemic. It is unclear how shelter-in-place orders affected acute CVD hospitalizations, illness severity, and outcomes. Hypothesis COVID-19 pandemic was associated with reduced acute CVD hospitalizations (heart failure [HF], acute coronary syndrome [ACS], and stroke [CVA]), and worse HF illness severity. Methods We compared acute CVD hospitalizations at Duke University Health System before and after North Carolina's shelter-in-place order (January 1-March 29 vs. March 30-August 31), and used parallel comparison cohorts from 2019. We explored illness severity among admitted HF patients using ADHERE ("high risk": >2 points) and GWTG-HF (">10%": >57 points) in-hospital mortality risk scores, as well as echocardiography-derived parameters. Results Comparing hospitalizations during January 1-March 29 (N = 1618) vs. March 30-August 31 (N = 2501) in 2020, mean daily CVD hospitalizations decreased (18.2 vs. 16.1 per day, p = .0036), with decreased length of stay (8.4 vs. 7.5 days, p = .0081) and no change in in-hospital mortality (4.7 vs. 5.3%, p = .41). HF hospitalizations decreased (9.0 vs. 7.7 per day, p = .0019), with higher ADHERE ("high risk": 2.5 vs. 4.5%; p = .030), but unchanged GWTG-HF (">10%": 5.3 vs. 4.6%; p = .45), risk groups. Mean LVEF was lower (39.0 vs. 37.2%, p = .034), with higher mean LV mass (262.4 vs. 276.6 g, p = .014). Conclusions CVD hospitalizations, HF illness severity, and echocardiography measures did not change between admission periods in 2019. Evaluating short-term data, the COVID-19 shelter-in-place order was associated with reductions in acute CVD hospitalizations, particularly HF, with no significant increase in in-hospital mortality and only minor differences in HF illness severity.

There is an increasing demand for building an automated system where the individual load can be controlled and monitored through programmable logic controller (PLC) and supervisory control and data acquisition (SCADA). It serves to provide the required amount of electricity where and when needed for the smooth operation of the system. Automatic control and monitoring of electrical energy consumption can be beneficial as it provide the framework for a real-time decision. It provides the upper hand over the conventional system as it reduces human error and helps detect abnormal system behavior in less time. In this project, designing and development of a generalized prototype is done where the individual load is monitored and controlled in real-time using PLC and SCADA. This system provides automatic control when the load exceeds., {"references":["1.\tSasikala, S., Chitranjan, O. R., & Muthulakshmi, K. (2014). Implementation of Home Automation Safety Control Using Programmable Logic Controller. Middle-East Journal of Scientific Research, 20(4), 492-501.","2.\tKaur, K. (2014). Energy Management System using PLC and SCADA. IJERT.","3.\tMumtaz, F. (2015, December). Real-time, PLC based, energy monitoring system. In 2015 Annual IEEE India Conference (INDICON) (pp. 1-5). IEEE.","4.\tPawar, R., & Bhasme, N. R. (2016). Application of PLC's for Automation of Processes in Industries. Int. Journal of Engineering Research and Applications, 6(6), 53-59.","5.\tSujatha, S., Om Prakash, K. M., Kumar, M.R. (2016). Home Automation using PLCs. IJARE.","6.\tPuri, P. S. (2016). Advancement in home appliance automation using PLC. Int. Res. J. Eng. Technol, 3(6), 931-934.","7.\tThosar, S. S., Suradkar, M. M., Kawde, S., & Mate, N. H. (2018). Sanctioned Load Monitoring & Controlling by using PLC. IRJET.","8.\tGupta, M. K., Gupta, P. K., Giri, R. K., & Gupta, A. (2018). Smart electric control system using PLC & HMI. International Journal of Mechanical Engineering and Technology, 9(4), 548-555.","9.\thttps://engineerscommunity.com/t/introduction-to- plc/11273","10.\thttps://www.kavisatechsolutions.com/2020/09/delta- plc-wiring.html"]}

Serotonin receptor 4 (5-HT4R) plays an important role in regulating mood, anxiety, and cognition, and drugs that activate this receptor have fast-acting antidepressant (AD)-like effects in preclinical models. However, 5-HT4R is widely expressed throughout the central nervous system (CNS) and periphery, making it difficult to pinpoint the cell types and circuits underlying its effects. Therefore, we generated a Cre-dependent 5-HT4R knockout mouse line to dissect the function of 5-HT4R in specific brain regions and cell types. We show that the loss of functional 5-HT4R specifically from excitatory neurons of hippocampus led to robust AD-like behavioral responses and an elevation in baseline anxiety. 5-HT4R was necessary to maintain the proper excitability of dentate gyrus (DG) granule cells and cell type-specific molecular profiling revealed a dysregulation of genes necessary for normal neural function and plasticity in cells lacking 5-HT4R. These adaptations were accompanied by an increase in the number of immature neurons in ventral, but not dorsal, dentate gyrus, indicating a broad impact of 5-HT4R loss on the local cellular environment. This study is the first to use conditional genetic targeting to demonstrate a direct role for hippocampal 5-HT4R signaling in modulating mood and anxiety. Our findings also underscore the need for cell type-based approaches to elucidate the complex action of neuromodulatory systems on distinct neural circuits.