Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs

Chronic inflammatory diseases such as arthritis are characterized by dysregulated responses to pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α). Pharmacologic anti-cytokine therapies are often effective at diminishing this inflammatory response but have significant side effects and are used at high, constant doses that do not reflect the dynamic nature of disease activity. Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- or TNF-α-mediated inflammation in an autoregulated, feedback-controlled manner. Our results show that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system. The customization of intrinsic cellular signaling pathways in stem cells, as demonstrated here, opens innovative possibilities for safer and more effective therapeutic approaches for a wide variety of diseases

Learner’s perspectives on competency-based medical education in pharmacology at a tertiary care teaching hospital in South India

Background: Competency based medical education (CBME) was implemented recently in India. The study was conducted to evaluate the perspectives of undergraduate medical students towards CBME curriculum in pharmacology at a tertiary care medical college in South India.Methods: After the completion of the curriculum, feedback was taken in a semi-structured, validated questionnaire. It was based on Kirkpatrik’s level 1 model of evaluation. Majority of the questions were framed on a 5-point Likert's scale (1 being poor to 5 being excellent). Qualitative data was collected by open ended question on additional comments.Results: The response rate was 72.8%. Majority of the participants rated the theory classes, practical classes, small group discussions, self-directed learning, integration, and assessments as good and excellent. More than 80% participants rated role play as an innovative and worthwhile concept towards mastering prescription communication. They felt that role play ignites team work, and provides confidence. Close to 90% of the participants rated the overview on emergency use authorization, orientation on drug regulators, perspectives on hydroxychloroquine prophylaxis as effective and excellent. More than 85% participants felt that AETCOM provided them insight on ethical issues, patient communication, and perspective of doctors as caregivers. 9.8% (16) participants provided comments to open ended question for feedback.Conclusions: The study provided an insight of medical undergraduates towards CBME curriculum. Further studies can be designed to look into the effectiveness of teaching learning methods based on the performance of the students, perspective of faculties with focus faculty development, and role of various stakeholders

Trends in Private Equity and Venture Capital Investments with Special Focus on the Booming India Growth Story

Private Equity investments have restructured the trend of acquisitions and aided in valuecreation as against strategic buyers. Private equity’s growing involvement in many sectors is evenmore striking. The nature of investments of private equity firms and funds, the strategies employed,value creating practices, profitable exits are significantly different from that of other strategic andcorporate buyers. The paper deals with the above aspects. The paper is divided into two parts. Part Ideals with the basics of private equity investment structures and exits. Part II of the paper deals withthe private equity growth story in India. Private equity investments, proposed changes to regulations,sectoral growth, venture capital regulations as well as impact of the latest Union budget a thecredit crunch have been dealt with

Mental Health among Chicanos and Chicanas: Barriers to Mental Health Care, Consequences of Disparities, and Resources

Mexican Americans, or Chicanos and Chicanas, face many barriers to mental health care. This literature review was conducted by the Collective Corazón—a VCU student organization, mentored by Dr. Indira Sultanić, that addresses Latinx health equity through service and advocacy—in order to examine the underlying causes and consequences of disparities in mental health in Chicanos and Chicanas. Some of the barriers that affect mental health care in Mexican Americans are racial inequities and discrimination, the societal and/or cultural stigma associated with receiving care, language barriers, lack of health insurance, and legal status. Furthermore, among Chicanos, machismo culture is associated with an increased risk for depression and higher stress levels. Colorism has also been correlated with depression among Chicanos with darker skin phenotypes. Cultural identity also plays a role in mental health for Mexican Americans; a balance of Mexican and American culture is associated with a decreased risk for depression. Among Chicanas, there may be justified mistrust of healthcare systems and services due to historical events. The Latina paradox also has unintended health consequences; Latina women are not screened for prenatal depression as often as other ethnic groups. Lastly, are mental health resources for Latinx communities, like Therapy for Latinx and The Focus on You. However, this review argues that in order to reduce the mental health disparities that Chicanos and Chicanas face, there must be increased awareness of the disparities as well as changes in the healthcare system that address current inequities and barriers.https://scholarscompass.vcu.edu/uresposters/1408/thumbnail.jp

Hasil Belajar Kognitif IPA Fisika Siswa melalui Penerapan Strategi Bowling Campus di Kelas Viii6 SMPN 15 Pekanbaru

This research aims at describe cognitive learning outcomes science of physics through the implementation strategy Bowling Campus on light subject at SMPN 15 Pekanbaru. The expected benefits of this research is for students implementation Bowling Campus strategy can improve the cognitive learning to become a better student. For teachers can be used as an alternative teaching strategies to improve the quality of science physics teaching. This research was conducted in SMP 15 Pekanbaru precisely in March 2015 until June 2015 in class VIII6 totaling 39 students. The design of the research is Pre-experimental design shapes One Shot Case study. From the research results obtained by the average value of absorption of students by 76.53% and categorized as good. Based on the average value of absorption was also found that the effectiveness of learning by applying Bowling Campus declared effective strategy. Based on 20 indicators of achievement of competencies in a given light material, 14 indicators declared complete with a percentage of 70%. It can be concluded that the application of Bowling Campus strategy can be used as an alternative in order to achieve the learning outcomes of cognitive learning better students in the classroom VIII6 SMP 15 Pekanbaru

Picking on the Same Person: Does Algorithmic Monoculture lead to Outcome Homogenization?

As the scope of machine learning broadens, we observe a recurring theme of algorithmic monoculture: the same systems, or systems that share components (e.g. training data), are deployed by multiple decision-makers. While sharing offers clear advantages (e.g. amortizing costs), does it bear risks? We introduce and formalize one such risk, outcome homogenization: the extent to which particular individuals or groups experience negative outcomes from all decision-makers. If the same individuals or groups exclusively experience undesirable outcomes, this may institutionalize systemic exclusion and reinscribe social hierarchy. To relate algorithmic monoculture and outcome homogenization, we propose the component-sharing hypothesis: if decision-makers share components like training data or specific models, then they will produce more homogeneous outcomes. We test this hypothesis on algorithmic fairness benchmarks, demonstrating that sharing training data reliably exacerbates homogenization, with individual-level effects generally exceeding group-level effects. Further, given the dominant paradigm in AI of foundation models, i.e. models that can be adapted for myriad downstream tasks, we test whether model sharing homogenizes outcomes across tasks. We observe mixed results: we find that for both vision and language settings, the specific methods for adapting a foundation model significantly influence the degree of outcome homogenization. We conclude with philosophical analyses of and societal challenges for outcome homogenization, with an eye towards implications for deployed machine learning systems.Comment: Published at NeurIPS 2022, presented at EAAMO 202

Potential Mechanisms Underlying TGF-β-mediated Complement Activation in Lung Fibrosis

While our previous studies suggest that limiting bleomycin-induced complement activation suppresses TGF-β signaling, the specific hierarchical interactions between TGF-β and complement in lung fibrosis are unclear. Herein, we investigated the mechanisms underlying TGF-β-induced complement activation in the pathogenesis of lung fibrosis. C57-BL6 mice were given intratracheal instillations of adenoviral vectors overexpressing TGF-β (Ad-TGFβ) or the firefly gene-luciferase (Ad-Luc; control). Two weeks later, mice with fibrotic lungs were instilled RNAi specific to receptors for C3a or C5a-C3ar or C5ar, and sacrificed at day 28. Histopathological analyses revealed that genetic silencing of C3ar or C5ar arrested the progression of TGF-β-induced lung fibrosis, collagen deposition and content (hydroxyproline, col1a1/2); and significantly suppressed local complement activation. With genetic silencing of either C3ar or C5ar, in Ad-TGFβ-injured lungs: we detected the recovery of Smad7 (TGF-β inhibitor) and diminished local release of DAF (membrane-bound complement inhibitor); in vitro: TGF-β-mediated loss of DAF was prevented. Conversely, blockade of the TGF-β receptor prevented C3a-mediated loss of DAF in both normal primary human alveolar and small airway epithelial cells. Of the 52 miRNAs analyzed as part of the Affymetrix array, normal primary human SAECs exposed to C3a, C5a or TGF-β caused discrete and overlapping miRNA regulation related to epithelial proliferation or apoptosis (miR-891A, miR-4442, miR-548, miR-4633), cellular contractility (miR-1197) and lung fibrosis (miR-21, miR-200C, miR-31HG, miR-503). Our studies present potential mechanisms by which TGF-β activates complement and promotes lung fibrosis

Obstetric emergencies during the COVID-19 lockdown period: a case series

Obstetric emergencies during COVID-19 pandemic pose an enormous challenge to the concerned obstetrician. Risk stratification during obstetric triage will guide in the initial assessment & planning of further management to reduce maternal and fetal morbidity and mortality rates. As the health system adapts to cope with this pandemic, special attention needs to be given to the several moral and ethical dilemmas that may occur during patient care