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Dimethandrolone, a Potential Male Contraceptive Pill, is Primarily Metabolized by the Highly Polymorphic UDP-Glucuronosyltransferase 2B17 Enzyme in human Intestine and Liver

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Drug Metabolism and Disposition 2022年第12期50卷 1493-1500页

作者： Sharma, Sheena Ahire, Deepak Basit, Abdul Lajoie, Maria Wang, Christina Lee, Min S. Blithe, Diana L. Amory, John K. Singh, Dilip K. Heyward, Scott Prasad, Bhagwat Department of Pharmaceutical Sciences Washington State University Spokane WA United States The Lundquist Institute Harbor UCLA Medical Center Torrance CA United States Contraceptive Development Program Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda MD United States Department of Medicine University of Washington School of Medicine Seattle WA United States BioIVT Halethorpe MD United States

Dimethandrolone undecanoate (DMAU), an oral investigational male hormonal contraceptive, is a prodrug that is rapidly converted to its active metabolite, dimethandrolone (DMA). Poor and variable oral bioavailability of DMA after DMAU dosing is a critical challenge to develop it as an oral drug. The objective of our study was to elucidate the mechanisms of variable pharmacokinetics of DMA. We first identified DMA metabolites formed in vitro and in vivo in human hepatocyte incubation and serum samples following oral DMAU administration in men, respectively. The metabolite identification study revealed two metabolites, DMA-glucuronide (DMA-G;major) and the androstenedione analog of DMA (minor), in the hepatocyte incubations. After oral DMAU administration, only DMA-G was detected in serum, which was >100-fold compared with DMA levels, supporting glucuronidation as the major elimination mechanism for DMA. Next, 13 clinically relevant UDP-glucuronosyltransferase (UGT) enzymes were tested for their involvement in DMA-G formation, which revealed a major role of UDP-glucuronosyltransferase 2B17 (UGT2B17) isoform with a smaller contribution of UGT1A9 in DMA-G formation. These data were confirmed by dramatically higher DMA glucuronidation rates (>200- and sevenfold) in the high versus the null UGT2B17-expressing human intestinal and liver microsomes, respectively. Since human UGT2B17 is a highly variable enzyme with a 20%–80% gene deletion frequency, the in vitro data suggest a major role of UGT2B17 polymorphism on the first-pass metabolism of DMA. Further, considering DMA is a selective and sensitive UGT2B17 substrate, it could be used as a clinical probe of UGT2B17 activity. © 2022 American Society for Pharmacology and Experimental Therapy. All rights reserved.

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NASA's development of Advanced Space Suits for Lunar Exploration 27

NASA's Development of Advanced Space Suits for Lunar Explora...

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27th IAA Symposium on human Exploration of the Solar System at the 75th International Astronautical Congress, IAC 2024

作者： McFarland, Shane M. Chullen, Cinda Sipila, Stephanie Pressure Garment System Team Deputy Lead for Technology Development NASA Parkway HoustonTX77058/EC5 United States Space Suit and Crew Survival Systems Branch Crew and Thermal Systems Division NASA Parkway HoustonTX77058/EC5 United States Extravehicular Activ. and Human Surface Mobility Program Technology Integration Partnerships Office NASA Parkway HoustonTX77058/DT United States

ISBN: (纸本)9798331312107

Significant work has been completed recently at NASA's Johnson Space Center in the Space Suit and Crew Survival Systems Branch to design and mature an advanced exploration Extra-Vehicular Activity (EVA) architecture. This effort culminated in the exploration Extra-vehicular Mobility Unit (xEMU) space suit, which was completed in 2022 and tested extensively through 2023, including human performance, cycle life performance and thermal vacuum testing. An overview of the xEMU design and test campaign is provided, as well as its value as the government reference design supporting the transition to EVA commercial services for the Artemis program. Lastly, a development roadmap is discussed which outlines NASA's identified strategy to enable the next generation of exploration EVA hardware for sustaining-class lunar and Mars missions. Copyright © (2024) by International Astronautical Federation. All rights reserved.

关键词： NASA

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Effectiveness of a short-Term soy nutrition education intervention on nutrition knowledge and self-efficacy scores of rural elderly Zambian women

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Nutrition and Healthy Aging 2023年第1期8卷 97-108页

作者： Mukherjee, Upasana Dawson, John A. Chalwe, Joseph Musonda Oldewage-Theron, Wilna Youth and Families Program Unit College of Agriculture Human and Natural Resource Sciences Washington State University Extension Pullman WA United States Department of Nutritional Sciences College of Human Sciences Texas Tech University Lubbock TX United States Department of Economics Applied Statistics and International Business New Mexico State University Las Cruces NM United States Department of Health Sciences Faculty of Applied and Computer Sciences Vaal University of Technology Vanderbijlpark South Africa Department of Sustainable Food Systems and Development Faculty of Natural and Agricultural Sciences University of the Free State Bloemfontein South Africa

BACKGROUND: Women are at most risk for chronic diseases which can be prevented by healthy dietary choices. Evidence exists that nutrition education interventions (NEIs) are effective in educating community-dwelling women to modify their behavior for better health outcomes. OBJECTIVES: The objectives of this study were to implement a need-based, tailored NEI and evaluate its effectiveness in improving nutrition and soy knowledge and self-efficacy of participants in the intervention group compared to a control group. METHODS: A quasi-experimental pre-post-study design was used in a convenience sample of 149 women from the copper belt region of Zambia. The health belief model (HBM) informed the NEI, which consisted of six lessons, three cooking demonstrations, and an illustrative recipe book. Nutrition and soy knowledge scores and self-efficacy scores were evaluated using validated and reliable questionnaires. Data were analyzed using IBM SPSS software, version 26, and mean change scores in knowledge and self-efficacy were compared between the intervention and control groups. RESULTS: The average improvement in the scores for total nutrition knowledge and all six sub-sections of knowledge was significantly higher in the intervention group compared to the control group. The mean total self-efficacy score for the intervention group improved significantly (p=5.7767e-20) from a pre-intervention score of 29.9±7.4 to 57.3±7.0 after the implementation of the NEI. No significant improvement (p=0.904) in the control group was observed. CONCLUSIONS: A short-Term, multi-component NEI was effective in improving the nutrition and soy knowledge and soy cooking self-efficacy of the participants in the intervention group. © 2023-The authors. Published by IOS Press.

关键词： attitudes knowledge Nutrition education self-efficacy women Zambia

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Completion of 6-mo isoniazid preventive treatment among eligible under six children:A cross-sectional study,Lagos,Nigeria

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World Journal of Clinical Cases 2023年第1期11卷 104-115页

作者： Victor Abiola Adepoju Ademola Adelekan Aderonke Agbaje Femi Quaitey Tobi Ademola-Kay Ann Uduak Udoekpo Olusola Daniel Sokoya Department of HIV and Infectious Diseases Jhpiego NigeriaFederal Capital TerritoryAbuja 900918Nigeria Department of Research Bluegate Research InstituteIbadan 211271Oyo StateNigeria Clinical Services Institute of Human Virology of NigeriaAbuja 900918Nigeria Department of HIV and Infectious Diseases Jhpiego NigeriaUyo 520108AkwaIbomNigeria Adolescent and Youth Care Youth Development and Empowerment InitiativeLagos 23401Nigeria Monitoring and Evaluation Jhpiego NigeriaUyo 520108AkwaIbomNigeria Lagos State Tuberculosis Buruli Ulcer and Leprosy Control ProgramIkeja 100001LagosNigeria

BACKGROUND Nigeria is one of the thirty high burden countries with significant contribution to the global childhood tuberculosis *** annual risk for children could be as high as 4%particularly in high tuberculosis(TB)prevalent ***(INH)Preventive Therapy has been shown to prevent TB incidence but data on its implementation among children are *** To determine the completion of INH among under six children that were exposed to adults with smear positive pulmonary TB in Lagos,*** This was a hospital-based retrospective cross-sectional review of 265 medical records of eligible children<6 years old enrolled for INH across 32 private hospitals in Lagos,*** study took place between July and September *** was collected on independent variables(age,gender,type of facility,TB screening,dose and weight)and outcome variables(INH outcome and proportion lost to follow up across months 1-6 of INH treatment).RESULTS About 53.8%of the participants were female,95.4%were screened for TB and none was diagnosed of having *** participants’age ranged from 1 to 72 mo with a mean of 36.01±19.67 mo,and 40.2%were between the ages of 1-24 *** 155(59.2%)of the 262 participants initiated on INH completed the six-month ***,107(41.0%)children were lost to follow-up at the end of the sixth *** the cumulative 107 loss to follow-up while on INH,largest drop-offs were reported at the end of month 2,52(49%)followed by 20(19%),17(16%),11(10.2%)and 7(6.5%)at months 3,4,5 and 6 *** analysis showed that there was no significant association between age,gender,type of facility and completion of INH treatment(P>0.005).CONCLUSION This study demonstrated suboptimal INH completion rate among children with only 6 out of 10 children initiated on INH who completed a 6-mo treatment in Lagos,*** huge drop-offs in the first 2 mo of INH calls for innovative strategies such as the use of 60-d INH calen

关键词： Isoniazid Child Tuberculosis Treatment Outcome Completion Latent tuberculosis Dosage

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Investigating resilience of international students at a public university in Southern Taiwan and its implications for the New Southbound Policy

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International Journal of Educational development 2024年 106卷

作者： Radiamoda, Rohaiba B. Chuang, Hsueh-Hua Pernia, Ronald A. Borazon, Elaine Q. International Graduate Program of Education and Human Development (IGPEHD) National Sun Yat-sen University Kaohsiung Taiwan Political Science Program College of Social Sciences University of the Philippines Cebu Cebu City Philippines Institute of Political Science National Sun Yat-sen University Kaohsiung Taiwan

While the initiative behind Taiwan's New Southbound Policy is largely driven by economic, political and academic priorities, this study promotes strengthening the psychological dimension of the policy to support its increasing international student population. The current study examines how optimism and emotional regulation predicts resilient behavior among a sample of international students in Taiwan. Empirical results from regression analysis showed that there is a positive association between optimism and resilience, while mediation analyses reported that optimism is also a partial mediator between emotion regulation and resilience, which nuances their relationship. The findings bear significant policy implications to Taiwan's educational development initiative. © 2024 Elsevier Ltd

关键词： Emotion dysregulation International students New Southbound Policy Optimism Resilience Taiwan

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STIGMA: Single-cell tissue-specific gene prioritization using machine learning (vol 111, pg 338, 2024)

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AMERICAN JOURNAL OF human GENETICS 2024年第3期111卷 618-618页

作者： Balachandran, Saranya Prada-Medina, Cesar A. Mensah, Martin A. Glaser, Juliane Kakar, Naseebullah Nagel, Inga Pozojevic, Jelena Audain, Enrique Kircher, Martin Sreenivasan, Varun K. A. Spielmann, Malte Institute of Human Genetics University Hospital Schleswig-Holstein University of Lübeck and Kiel University Lübeck Germany Human Molecular Genetics Group Max Planck Institute for Molecular Genetics 14195 Berlin Germany Institut für Medizinische Genetik und Humangenetik Charité - Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin Augustenburger Platz 1 13353 Berlin Germany BIH Charité Digital Clinician Scientist Program BIH Biomedical Innovation Academy Anna-Louisa-Karsch-Strasse 2 10178 Berlin Germany RG Development & Disease Max Planck Institute for Molecular Genetics 14195 Berlin Germany Department of Biotechnology BUITEMS Quetta Pakistan Institute of Medical Genetics Carl von Ossietzky University 26129 Oldenburg Germany DZHK e.V. (German Center for Cardiovascular Research) Partner Site Hamburg/Kiel/Lübeck Department of Congenital Heart Disease and Pediatric Cardiology University Hospital of Schleswig-Holstein 24105 Kiel Germany Development and Disease Max Planck Institute for Molecular Genetics 14195 Berlin Germany

Clinical exome and genome sequencing have revolutionized the understanding of human disease genetics. Yet many genes remain functionally uncharacterized, complicating the establishment of causal disease links for genetic variants. While several scoring methods have been devised to prioritize these candidate genes, these methods fall short of capturing the expression heterogeneity across cell subpopulations within tissues. Here, we introduce single-cell tissue-specific gene prioritization using machine learning (STIGMA), an approach that leverages single-cell RNA-seq (scRNA-seq) data to prioritize candidate genes associated with rare congenital diseases. STIGMA prioritizes genes by learning the temporal dynamics of gene expression across cell types during healthy organogenesis. To assess the efficacy of our framework, we applied STIGMA to mouse limb and human fetal heart scRNA-seq datasets. In a cohort of individuals with congenital limb malformation, STIGMA prioritized 469 variants in 345 genes, with UBA2 as a notable example. For congenital heart defects, we detected 34 genes harboring nonsynonymous de novo variants (nsDNVs) in two or more individuals from a set of 7,958 individuals, including the ortholog of Prdm1, which is associated with hypoplastic left ventricle and hypoplastic aortic arch. Overall, our findings demonstrate that STIGMA effectively prioritizes tissue-specific candidate genes by utilizing single-cell transcriptome data. The ability to capture the heterogeneity of gene expression across cell populations makes STIGMA a powerful tool for the discovery of disease-associated genes and facilitates the identification of causal variants underlying human genetic disorders.

关键词： gene prioritzation single-cell sequencing congenital limb malformations congenital heart disease pseudotime gene expression congenital diseases

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Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease

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Translational Neurodegeneration 2024年第1期13卷 963-979页

作者： Chen-Pei Lin Irene Frigerio John G.J.M.Bol Maud M.A.Bouwman Alex J.Wesseling Martin J.Dahl Annemieke J.M.Rozemuller Ysbrand D.van der Werf Petra J.W.Pouwels Wilma D.J.van de Berg Laura E.Jonkman Amsterdam UMC Department of Anatomy and NeurosciencesLocation Vrije Universiteit AmsterdamDe Boelelaan 11171081 HV AmsterdamThe Netherlands Amsterdam Neuroscience Brain imagingAmsterdamThe Netherlands Center for Lifespan Psychology Max Planck Institute for Human Development14195 BerlinGermany Leonard Davis School of Gerontology University of Southern CaliforniaLos AngelesCA 90089USA Amsterdam UMC Department of PathologyLocation Vrije Universiteit AmsterdamDe Boelelaan 1117AmsterdamThe Netherlands Amsterdam Neuroscience NeurodegenerationAmsterdamThe Netherlands Amsterdam Neuroscience CompulsivityImpulsivity and Attention ProgramAmsterdamThe Nether-lands Amsterdam UMC Department of Radiology and Nuclear MedicineLocation Vrije Universiteit AmsterdamDe Boelelaan 1117AmsterdamThe Netherlands

Background Degeneration of the locus coeruleus(LC)noradrenergic system contributes to clinical symptoms in Alzheimer’s disease(AD)and Parkinson’s disease(PD).Diffusion magnetic resonance imaging(MRI)has the potential to evaluate the integrity of the LC noradrenergic *** aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and *** Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD,14 PD,and 8 control brain *** anisotropy(FA)and mean diffusivity were derived from the LC,and from tracts between the LC and the anterior cingulate cortex,the dorsolateral prefrontal cortex(DLPFC),the primary motor cortex(M1)or the *** tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase(DBH)to quantify noradrenergic cell density and fiber *** comparisons and correlations between outcome measures were performed using linear regression and partial *** The AD and PD cases showed loss of LC noradrenergic cells and *** the cortex,the AD cases showed increased DBH+immunoreactivity in the DLPFC compared to PD cases and controls,while PD cases showed reduced DBH+immunoreactivity in the M1 compared to *** FA within the LC was found for AD,which was correlated with loss of noradrenergic cells and fibers in the *** FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group,whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control *** tract alterations were not correlated with cortical DBH+*** In AD and PD,the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC,rat

关键词： Locus coeruleus Noradrenergic degeneration Alzheimer’s disease Parkinson’s disease Diffusion MRI Post-mortem Histopathology

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Quantum Science and Technologies in K-12: Supporting Teachers to Integrate Quantum in STEM Classrooms

arXiv

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arXiv 2024年

作者： Holincheck, Nancy Rosenberg, Jessica L. Zhang, Xiaolu Butler, Tiffany N. Colandene, Michele Dreyfus, Benjamin W. College of Education and Human Development George Mason University FairfaxVA22030 United States Department of Physics and Astronomy George Mason University FairfaxVA22030 United States STEM Accelerator Program George Mason University FairfaxVA22030 United States

Quantum science and computing represent a vital intersection between science and technology, gaining increasing importance in modern society. There is a pressing need to incorporate these concepts into the K-12 curriculum, equipping new generations with the tools to navigate and thrive in an evolving technological landscape. This study explores the professional learning of K-12 teachers (n = 49) related to quantum concepts and pedagogy. We used open-ended surveys, field notes, workshop artifacts, and interviews to examine teachers’ perceptions of quantum and how they made connections between quantum and their curriculum. Our data reveal that most teachers were excited and interested in teaching quantum but were aware of potential barriers and concerns that might get in the way of teaching quantum. We found that teachers readily identified connections to math and science in their curriculum, but only a few made connections to computing. Enthusiasm for teaching quantum concepts was found in both elementary and secondary educators, suggesting a widespread recognition of its importance in preparing students for a future where quantum technology is a fundamental aspect of their lives and careers. © 2024, CC BY.

关键词： Teaching

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Counselor self-efficacy, multicultural competency, and perceived wellness among counselors in training during covid-19: a pre- and peri-analysis

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Journal of Counselor Leadership and Advocacy 2023年第2期10卷 99-111页

作者： Fakhro, Dania Rujimora, James Zeligman, Melissa Mendoza, Sarah Department of Counselor Education and School Psychology University of Central Florida Orlando FL United States Counseling Program Department of Health and Human Development Montana State University Bozeman MI United States

The COVID-19 pandemic disrupted how counselors-in-training (CITs) provided services to clients. The present cross-sectional causal-comparative study (N = 131) examined the differences between CIT (a) self-efficacy, (b) multicultural competence, and (c) perceived wellness pre- and during the pandemic. Independent samples t-tests and one-way between-groups multivariate analysis of variance (MANOVA) were used to explore group differences. Our findings suggest that CITs did not perceive significant negative impacts in these areas as a result of COVID-19. © 2023 Chi Sigma Iota.

关键词： Counselor self-efficacy counselors-in-training COVID-19 multicultural competence wellness

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Improving the Interaction of Autistic Children through Eye Tracking using Gamification Design Framework

Improving the Interaction of Autistic Children through Eye T...

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2021 International Conference on Computer System, Information Technology, and Electrical Engineering, COSITE 2021

作者： Azizah, Anfazul Faridatul Djunaidy, Arif Siahaan, Daniel Suhariadi, Fendy Institut Teknologi Sepuluh Nopember Department of Informatics Surabaya Indonesia Institut Teknologi Sepuluh Nopember Department of Information Systems Surabaya Indonesia Universitas Airlangga Doctoral Program in Human Resources Development - Postgraduate School Surabaya Indonesia

ISBN: (纸本)9781665425094

Tracking for autism (TFA) is an interactive game designed specifically to increase the interaction of autistic children. Although the exact cause of autism spectrum disorder (ASD) is unknown, so far there is no medical cure for ASD. Therefore, one of the efforts to respond to this issue is to focus on increasing the interaction of autistic children through game media. The current autistic game design has not been able to increase the interaction of autistic children, but only helps autistic children to interact. This study proposes a framework for designing interactive games for autistic children based on eye tracking and developing a new strategy to determine the increase in the interaction of autistic children from one level to another. The results of the initial investigation showed that there was an increase in the interaction of autistic children before and after using TFA games. The initial testing was using parameters such as viewing objects, eyes looking down, forward focus, and dilated pupils. Based on the results of the initial trial, the TFA Games was proven to be able to increase the level of interaction of autistic children. © 2021 IEEE.

关键词： Diseases

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