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1.
Psychol Sex ; 15(2): 170-192, 2024.
Article in English | MEDLINE | ID: mdl-38800743

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic and associated shelter-in-place ordinances passed in the first year of the pandemic rapidly limited access to in-person social interactions, raising concerns of diminishing social support and community cohesion while psychological stressors increased. For LGBTQIA+ people, connectedness to the LGBTQIA+ community is known to buffer against the harmful effects of stressors and decrease risks for poor psychological and behavioral health outcomes. The current study uses qualitative cross-sectional and trajectory analysis methods to characterize how LGBTQIA+ people's perceptions of community connectedness shifted during the first year of the pandemic. A convenience sample of LGBTQIA+-identified people in the U.S. completed an initial online survey in September 2020 (n = 298 and a follow-up survey in September 2021 (n = 129). The survey included changes in connectedness to the LGBTQIA+ community since the pandemic's beginning. Thus, we used both cross-sectional (between-person analyses) and longitudinal trajectory (within-person analyses) qualitative approaches to understanding changes in LGBTQIA+ people's sense of connection to the LGBTQIA+ community across the first two years of the COVID-19 pandemic. Eight cross-cutting themes (related to identity shifts/exploration, disconnection, online connections, and increased awareness of social justice issues) were identified and then organized within each level of the Social-Ecological Model of LGBTQIA+ wellbeing (i.e., the individual-, couple-, interpersonal-, organizational-, community-, and chronosystem- level). Given the importance of social support for LGBTQIA+ wellbeing, more longitudinal research is needed to determine whether these changes persist after the resolution of the acute phase of the pandemic.

2.
Respir Care ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688544

ABSTRACT

BACKGROUND: The bag-valve-mask (BVM) or manual resuscitator bag is used as a first-line technique to ventilate patients with respiratory failure. Volume-restricted manual resuscitator bags (eg, pediatric bags) have been suggested to minimize overventilation and associated complications. There are studies that both support and caution against the use of a pediatric resuscitator bag to ventilate an adult patient. In this study, we evaluated the ability of pre-hospital clinicians to adequately ventilate an adult manikin with both an adult- and pediatric-size manual resuscitator bag without the assistance of an advanced airway or airway adjunct device. METHODS: This study was conducted at an international conference in 2022. Conference attendees with pre-hospital health care experience were recruited to ventilate an adult manikin using a BVM for 1 min with both an adult and pediatric resuscitator bag, without the use of adjunct airway devices, while 6 ventilatory variables were collected or calculated: tidal volume (VT), breathing frequency, adequate breaths (VT > 150 mL), proportion of adequate breaths, peak inspiratory pressure (PIP), and estimated alveolar ventilation (EAV). RESULTS: A total of 208 participants completed the study. Ventilation with the adult-sized BVM delivered an average VT of 290.4 mL compared to 197.1 mL (P < .001) when using the pediatric BVM. PIP with the adult BVM was higher than with the pediatric BVM (10.6 cm H2O vs 8.6 cm H2O, P < .001). The median EAV with the adult bag (1,138.1 [interquartile range [IQR] 194.0-2,869.9] mL/min) was markedly greater than with the pediatric BVM (67.7 [IQR 0-467.3] mL/min, P < .001). CONCLUSIONS: Both pediatric- and adult-sized BVM provided lower ventilation volumes than those recommended by professional guidelines for an adult. Ventilation with the pediatric BVM was significantly worse than with the adult bag when ventilating a simulated adult subject.

3.
Phys Rev Lett ; 132(14): 143402, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38640397

ABSTRACT

We report on the observation of spontaneously drifting coupled spin and quadrupolar density waves in the ground state of laser driven Rubidium atoms. These laser-cooled atomic ensembles exhibit spontaneous magnetism via light mediated interactions when submitted to optical feedback by a retroreflecting mirror. Drift direction and chirality of the waves arise from spontaneous symmetry breaking. The observations demonstrate a novel transport process in out-of-equilibrium magnetic systems.

4.
Adv Physiol Educ ; 48(2): 254-259, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38328812

ABSTRACT

In response to COVID-19, educators rapidly pivoted to new and innovative ways of delivering lecture material. The ability to host synchronous lectures on platforms like Zoom gave students continued access to classroom material in the face of an ongoing pandemic. The purpose of this study was to investigate the differences in exam scores between students attending a physiology class (PHSL3051) synchronously via Zoom or asynchronously by viewing recorded lectures posted after class. Students in PHSL3051 were evaluated with four unit exams and one cumulative final exam. Although pooled analysis of all students showed that synchronous lecture viewing positively predicted exam scores, this positive association was even larger when the data were analyzed by gender and ethnicity. For female-identified students and students of color (SOC), attending lectures synchronously was associated with average scores on every unit exam that were higher by 2.7-7.4 percentage points. Moreover, the greater a student's synchronous participation in the course throughout the semester, the better that student's performance on the cumulative final exam was likely to be. These data highlight the need to better understand how different groups of undergraduate students select and respond to different assessment methods used in the same course, which may have long-term effects on their overall performance at 4-year institutions.NEW & NOTEWORTHY This study examined the relationship between lecture attendance (synchronous or asynchronous) and exam scores throughout the semester. Although everyone in the course benefited from synchronous lecture attendance, our data indicated that students of color (SOC) and female-identified students benefited most. SOC and female-identified students who participated synchronously had even higher mean scores on all exams within the course compared with SOC and female-identified students who participated asynchronously by watching recordings of the same lectures.


Subject(s)
COVID-19 , Curriculum , Humans , Female , Students
5.
Sci Rep ; 14(1): 158, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38168495

ABSTRACT

Movement of resources was essential to the survival and success of early complex societies. The sources and destinations of goods and the means of transportation - be it by boats, carts and/or foot - can often be inferred, but the logistics of these movements are inherently more difficult to ascertain. Here, we use strontium isotopic analysis to test hypotheses about the role of animal and animal-powered transport in medium and long-distance movement and exchange, using the Indus Civilization as a case study. Across the wide geographical spread of the Indus Civilisation, there is strong evidence for long-distance exchange of raw materials and finished objects and this process is presumed to involve boats and animal-driven transport, although there is little evidence as to the relative importance of each mode of movement. Strontium isotopic analysis of animal remains from four sites analysed for this study combined with results from nine other sites indicates limited long-distance animal movement between different geological zones within the Indus Civilisation. These findings suggest that individual animals primarily moved short- or medium-distances, though there are several significant exceptions seen in some pigs and cattle found at two large urban sites. We infer that long-distance transport of goods, be it raw materials, finished objects, other goods, or the animals themselves, could have occurred through the use of boats and waterways, by traction animals moving over long distances that did not end up in the archaeological record, and/or by different animals participating in many short to medium-distance movements.


Subject(s)
Hoof and Claw , Animals , Cattle , Swine , Strontium Isotopes , Archaeology , Transportation , Civilization , Movement
6.
J Shoulder Elbow Surg ; 33(2): 417-424, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37774829

ABSTRACT

BACKGROUND: The ability to do comparative effectiveness research (CER) for proximal humerus fractures (PHF) using data in electronic health record (EHR) systems and administrative claims databases was enhanced by the 10th revision of the International Classification of Diseases (ICD-10), which expanded the diagnosis codes for PHF to describe fracture complexity including displacement and the number of fracture parts. However, these expanded codes only enhance secondary use of data for research if the codes selected and recorded correctly reflect the fracture complexity. The objective of this project was to assess the accuracy of ICD-10 diagnosis codes documented during routine clinical practice for secondary use of EHR data. METHODS: A sample of patients with PHFs treated by orthopedic providers across a large, regional health care system between January 1, 2016, and December 31, 2018, were retrospectively identified from the EHR. Four fellowship-trained orthopedic surgeons reviewed patient radiographs and recorded the Neer Classification characteristics of displacement, number of parts, and fracture location(s). The fracture characteristics were then reviewed by a trained coder, and the most clinically appropriate ICD-10 diagnosis code based on the number of fracture parts was assigned. We assessed congruence between ICD-10 codes documented in the EHR and radiograph-validated codes, and assessed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for EHR-documented ICD-10 codes. RESULTS: There were 761 patients with unilateral, closed PHF who met study inclusion criteria. On average, patients were 67 years of age and 77% were female. Based on radiograph review, 37% were 1-part fractures, 42% were 2-part, 11% were 3-part, and 10% were 4-part fractures. Of the EHR diagnosis codes recorded during clinical practice, 59% were "unspecified" fracture diagnosis codes that did not identify the number of fracture parts. Examination of fracture codes revealed PPV was highest for 1-part (PPV = 0.66, 95% confidence interval [CI] 0.60-0.72) and 4-part fractures (PPV = 0.67, 95% CI 0.13-1.00). CONCLUSIONS: Current diagnosis coding practices do not adequately capture the fracture complexity needed to conduct subgroup analysis for PHF. Conclusions drawn from population studies or large databases using ICD-10 codes for PHF classification should be interpreted within this limitation. Future studies are warranted to improve diagnostic coding to support large observational studies using EHR and administrative claims data.


Subject(s)
Humeral Fractures , International Classification of Diseases , Female , Humans , Male , Databases, Factual , Electronic Health Records , Reproducibility of Results , Retrospective Studies , Aged
7.
Stem Cell Reports ; 18(12): 2498-2514, 2023 12 12.
Article in English | MEDLINE | ID: mdl-37995702

ABSTRACT

Brain organoid methods are complicated by multiple rosette structures and morphological variability. We have developed a human brain organoid technique that generates self-organizing, single-rosette cortical organoids (SOSR-COs) with reproducible size and structure at early timepoints. Rather than patterning a 3-dimensional embryoid body, we initiate brain organoid formation from a 2-dimensional monolayer of human pluripotent stem cells patterned with small molecules into neuroepithelium and differentiated to cells of the developing dorsal cerebral cortex. This approach recapitulates the 2D to 3D developmental transition from neural plate to neural tube. Most monolayer fragments form spheres with a single central lumen. Over time, the SOSR-COs develop appropriate progenitor and cortical laminar cell types as shown by immunocytochemistry and single-cell RNA sequencing. At early time points, this method demonstrates robust structural phenotypes after chemical teratogen exposure or when modeling a genetic neurodevelopmental disorder, and should prove useful for studies of human brain development and disease modeling.


Subject(s)
Induced Pluripotent Stem Cells , Pluripotent Stem Cells , Humans , Induced Pluripotent Stem Cells/metabolism , Brain , Cell Differentiation , Organoids
8.
J Emerg Manag ; 21(5): 439-452, 2023.
Article in English | MEDLINE | ID: mdl-37932946

ABSTRACT

As coronavirus disease 2019 (COVID-19) spread within the United States, the challenge of responding to a large-scale health crisis was compounded as the federal government struggled to deliver a unified response. Decision-making powers for pandemic protocols were passed to individual states, whose responses were heavily influenced by their administrations' partisan political leanings. This study explores differences in the transparency of COVID-19 information on university websites and the restrictiveness of the measures they implemented by examining university messaging in all-Republican and all-Democrat controlled states. This study employs a quantitative content analysis of a census of websites (N = 265) from public universities located in states with government trifectas. The data reveal that masking, vaccination, and testing measures were significantly more restrictive among universities located in Democratic trifectas than in Republican trifectas. Additionally, universities in Democratic trifectas communicated more transparently, such that they were more likely to have a direct link to COVID-19 information on their homepages. The results indicate that universities in states where a single political party holds power implemented COVID-19 protocols that reflected the political -viewpoints on the health and economic responses to the pandemic. This finding offers important evidence that both governments and public universities based their public health decisions on political factors.


Subject(s)
COVID-19 , Humans , United States , Universities , Pandemics , Politics , Public Policy
9.
Nanoscale ; 15(43): 17609-17620, 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37876284

ABSTRACT

Sacrificial templates present an effective pathway for gaining high-level control over nanoscale reaction products. Atomic layer deposition (ALD) is ideally suited for such approaches due to its ability to replicate the surface topography of a template material through the deposition of an ultrathin conformal layer. Herein, metal nanostructures are demonstrated as sacrificial templates for the formation of architecturally complex and deterministically positioned oxide nanoshells, open-topped nanobowls, vertically standing half-shells, and nanorings. The three-step process sees metal nanocrystals formed in periodic arrays, coated with an ALD-deposited oxide, and hollowed out with a selective etch through nanopores formed in the oxide shell. The procedure is further augmented through the use of a directional ion beam that is used to sculpt the oxide shells into bowl- and ring-like configurations. The functionality of the so-formed materials is demonstrated through their use as substrate-confined nanoreactors able to promote the growth and confinement of nanomaterials. Taken together, the work expands the design space for substrate-based nanomaterials, creates a platform for advancing functional surfaces and devices and, from a broader perspective, advances the use of ALD in forming complex nanomaterials.

10.
J Prev Alzheimers Dis ; 10(4): 875-885, 2023.
Article in English | MEDLINE | ID: mdl-37874110

ABSTRACT

BACKGROUND/OBJECTIVES: CAN-THUMBS UP is designed as a comprehensive and innovative fully remote program to 1) develop an interactive and compelling online Brain Health Support Program intervention, with potential to positively influence dementia literacy, self-efficacy and lifestyle risk factors; 2) enroll and retain a community-dwelling Platform Trial Cohort of individuals at risk of dementia who will participate in the intervention; 3) support an open platform trial to test a variety of multidomain interventions that might further benefit individuals at risk of dementia. This manuscript presents the Brain Health Support Program Study protocol. DESIGN/SETTING: Twelve-month prospective multi-center longitudinal study to evaluate a fully remote web-based educational intervention. Participants will subsequently be part of a Platform Trial Cohort and may be eligible to participate in further dementia prevention clinical trials. PARTICIPANTS: Three hundred fifty older adults who are cognitively unimpaired or have mild cognitive impairment, with at least 1 well established dementia risk factor. INTERVENTION: Participants engage in the Brain Health Support Program intervention for 45-weeks and complete pre/post intervention measures. This intervention is designed to convey best available evidence for dementia prevention, consists of 181 chapters within 8 modules that are progressively delivered, and is available online in English and French. The program has been developed as a collaborative effort by investigators with recognized expertise in the program's content areas, along with input from older-adult citizen advisors. MEASUREMENTS: This study utilizes adapted remote assessments with accessible technologies (e.g. videoconferencing, cognitive testing via computer and mobile phone, wearable devices to track physical activity and sleep, self-administered saliva sample collection). The primary outcome is change in dementia literacy, as measured by the Alzheimer's Disease Knowledge Scale. Secondary outcomes include change in self-efficacy; engagement using the online program; user satisfaction ratings; and evaluation of usability and acceptance. Exploratory outcomes include changes in attitudes toward dementia, modifiable risk factors, performance on the Neuropsychological Test Battery, performance on self-administered online cognitive assessments, and levels of physical activity and sleep; success of the national recruitment plan; and the distribution of age adjusted polygenic hazard scores. CONCLUSIONS: This fully remote study provides an accessible approach to research with all study activities being completed in the participants' home environment. This approach may reduce barriers to participation, provide an easier and less demanding participant experience, and reach a broader geography with recruitment from all regions of Canada. CAN-THUMBS UP represents a Canadian contribution to the global World-Wide FINGERS program (alz.org/wwfingers).


Subject(s)
Alzheimer Disease , Brain , Aged , Humans , Canada , Longitudinal Studies , Prospective Studies
11.
JACC CardioOncol ; 5(3): 343-355, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37397080

ABSTRACT

Background: Remote ischemic conditioning (RIC) has been beneficial in laboratory studies of anthracycline cardiotoxicity, but its effects in patients is not established. Objectives: The authors studied the effect of RIC on cardiac biomarkers and function during and after anthracycline chemotherapy. Methods: The ERIC-Onc study (Effect of Remote Ischaemic Conditioning in Oncology Patients; NCT02471885) was a randomized, single-blind, sham-controlled study of RIC at each chemotherapy cycle. The primary endpoint was troponin T (TnT) during chemotherapy and up to 1 year. Secondary outcomes included cardiac function, major adverse cardiovascular events (MACE), and MACE or cancer death. Cardiac myosin-binding-protein C (cMyC) was investigated in parallel with TnT. Results: The study was prematurely halted after the evaluation of 55 patients (RIC n = 28, sham n = 27). Biomarkers increased from baseline to cycle 6 of chemotherapy for all patients (median TnT 6 [IQR: 4-9] ng/L to 33 [IQR: 16-36)] ng/L; P ≤ 0.001; cMyC 3 (IQR: 2-5) ng/L to 47 (IQR: 18-49) ng/L; P ≤ 0.001). Mixed-effects regression analysis for repeated measures showed no difference in TnT between the 2 groups (RIC vs sham, mean difference 3.15 ng/L; 95% CI: -0.04 to 6.33; P = 0.053), or cMyC (RIC vs sham, mean difference 4.17 ng/L; 95% CI: -0.12 to 8.45; P = 0.056). There were more MACE and cancer deaths in the RIC group (11 vs 3; HR: 0.25; 95% CI: 0.07-0.90; P = 0.034), with more cancer deaths (8 vs 1; HR: 0.21; 95% CI: 0.04-0.95; P = 0.043) at 1 year. Conclusions: TnT and cMyC significantly increased during anthracycline chemotherapy with 81% having a TnT ≥14 ng/L at cycle 6. RIC did not affect the rise in biomarkers, but there was a small increase in early cancer deaths, possibly related to the greater proportion of patients with metastatic disease randomized to the RIC group (54%vs 37%). (Effect of Remote Ischaemic Conditioning in Oncology Patients [ERIC-ONC]; NCT02471885).

13.
J Hosp Infect ; 138: 60-73, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37290689

ABSTRACT

Bone marrow transplant and haemato-oncology patients are at risk of healthcare-associated infections due to waterborne pathogens. We undertook a narrative review of waterborne outbreaks in haemato-oncology patients from 2000 to 2022. Databases searched included PubMed, DARE and CDSR, and were undertaken by two authors. We analysed the organisms implicated, sources identified and infection prevention and control strategies implemented. The most commonly implicated pathogens were Pseudomonas aeruginosa, non-tuberculous mycobacteria and Legionella pneumophila. Bloodstream infection was the most common clinical presentation. The majority of incidents employed multi-modal strategies to achieve control, addressing both the water source and routes of transmission. This review highlights the risk to haemato-oncology patients from waterborne pathogens and discusses future preventative strategies and the requirement for new UK guidance for haemato-oncology units.


Subject(s)
Cross Infection , Waterborne Diseases , Humans , Waterborne Diseases/epidemiology , Cross Infection/epidemiology , Health Facilities , Disease Outbreaks , Water Supply , Water Microbiology
15.
Hum Reprod Open ; 2023(3): hoad021, 2023.
Article in English | MEDLINE | ID: mdl-37304815

ABSTRACT

STUDY QUESTION: Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)? SUMMARY ANSWER: Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids. WHAT IS KNOWN ALREADY: SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids. STUDY DESIGN SIZE DURATION: In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology. PARTICIPANTS/MATERIALS SETTING METHODS: A cohort of 19 women aged 38-52 years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI). MAIN RESULTS AND THE ROLE OF CHANCE: Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (P = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (P = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (P = 0.17). LIMITATIONS REASONS FOR CAUTION: The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected. WIDER IMPLICATIONS OF THE FINDINGS: The imaging protocol that we have developed represents a generic paradigm for measuring the volume of the uterus and uterine fibroids that can be readily incorporated in future studies of medical treatments of HMB. In the present study, SPRM-UPA failed to produce a significant reduction in the volume of the uterus or the total volume of fibroids (which were present in approximately half of the patients) after either two or three 12-week courses of treatment. This finding represents a new insight in respect of the management of HMB using treatment strategies that target hormone-dependence. STUDY FUNDING/COMPETING INTERESTS: The UPA Versus Conventional Management of HMB (UCON) trial was funded by the EME Programme (Medical Research Council (MRC) and National Institutes of Health Research (NIHR)) (12/206/52). The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council, National Institute for Health Research, or Department of Health and Social Care.Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. H.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (All paid to Institution) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc., and Myovant Sciences GmbH. H.C. has received royalties from UpToDate for an article on abnormal uterine bleeding. L.W. has received grant funding from Roche Diagnostics (Paid to Institution). All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: The study reported here is an embedded mechanism of action study (no comparator) within the UCON clinical trial (registration ISRCTN: 20426843).

16.
Am Psychol ; 78(4): 589-600, 2023.
Article in English | MEDLINE | ID: mdl-37384510

ABSTRACT

Psychology has a long history of perpetuating scientific racism and pathologizing gender and sexually diverse individuals. The field has been criticized for the reproduction of racism, sexism, cissexism, and other social inequities. This intersectional epistemological exclusion has led to a lack of appreciation for the work of Black sexual and gender diverse (SGD) scholars within the field of psychology. To highlight and center the contributions of Black SGD scholars in the field, we conducted an in-depth literature search of the work of 62 Black SGD scholars whose names and curricula vitae were obtained through email listservs, Twitter, and snowball sampling. In analyzing the work of the scholars, a total of 34 Black SGD scholars met inclusion criteria and had their research included in our review. We summarize their major contributions to the field of psychology in this article. Implications of these scholars' works and their potential to help address the lack of visibility of Black SGD scholars in mainstream psychology journals are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Racism , Sexual Behavior , Humans , Knowledge , Sexism
17.
bioRxiv ; 2023 Apr 11.
Article in English | MEDLINE | ID: mdl-37090564

ABSTRACT

Neural tube defects (NTDs) including anencephaly and spina bifida are common major malformations of fetal development resulting from incomplete closure of the neural tube. These conditions lead to either universal death (anencephaly) or life-long severe complications (spina bifida). Despite hundreds of genetic mouse models having neural tube defect phenotypes, the genetics of human NTDs are poorly understood. Furthermore, pharmaceuticals such as antiseizure medications have been found clinically to increase the risk of NTDs when administered during pregnancy. Therefore, a model that recapitulates human neurodevelopment would be of immense benefit to understand the genetics underlying NTDs and identify teratogenic mechanisms. Using our self-organizing single rosette spheroid (SOSRS) brain organoid system, we have developed a high-throughput image analysis pipeline for evaluating SOSRS structure for NTD-like phenotypes. Similar to small molecule inhibition of apical constriction, the antiseizure medication valproic acid (VPA), a known cause of NTDs, increases the apical lumen size and apical cell surface area in a dose-responsive manner. This expansion was mimicked by GSK3ß and HDAC inhibitors; however, RNA sequencing suggests VPA does not inhibit GSK3ß at these concentrations. Knockout of SHROOM3, a well-known NTD-related gene, also caused expansion of the lumen as well as reduced f-actin polarization. The increased lumen sizes were caused by reduced cell apical constriction suggesting that impingement of this process is a shared mechanism for VPA treatment and SHROOM3-KO, two well-known causes of NTDs. Our system allows the rapid identification of NTD-like phenotypes for both compounds and genetic variants and should prove useful for understanding specific NTD mechanisms and predicting drug teratogenicity.

19.
Biol Psychol ; 179: 108564, 2023 04.
Article in English | MEDLINE | ID: mdl-37061084

ABSTRACT

Elevated irritability during adolescence predicts mental health issues in adulthood. Social interactions commonly elicit symptoms of irritability. Prior research has traditionally examined neural activity during the anticipation of, and immediate reaction to, social feedback separately in irritable adolescents. However, studies suggest that irritable adolescents demonstrate altered brain activation when anticipating feedback, and these alterations may have downstream effects on the neural activity when actually presented with feedback. Thus, the goal of this study was to characterize the influence of irritability on the relationship between brain function during anticipation and receipt of social feedback. We leveraged the Virtual School task to mimic social interactions using dynamic stimuli. Parallel region of interest (ROI) analyses tested effects of anticipatory bilateral amygdala (or dorsal anterior cingulate cortex; dACC) activation on the dACC (or bilateral amygdala) activation during receipt of peer feedback. Parallel exploratory whole-brain analyses were conducted to identify the effects of anticipatory bilateral amygdala or dACC activation on other regions during receipt of peer feedback. In ROI analyses, more vs. less irritable adolescents showed distinct relationships between anticipatory bilateral amygdala activation and dACC activation when receiving predictably mean feedback. Across both whole-brain analyses, anticipatory bilateral amygdala and dACC activation were separately associated with activation in socioemotional regions of the brain during subsequent feedback. These relationships were modulated by irritability, and the valence and predictability of the feedback. This suggests that irritable adolescents may engage in altered emotion processing and regulation strategies, depending on the valence and predictability of social feedback.


Subject(s)
Brain , Irritable Mood , Humans , Adolescent , Feedback , Irritable Mood/physiology , Gyrus Cinguli/physiology , Peer Group , Magnetic Resonance Imaging
20.
J Hosp Infect ; 135: 154-156, 2023 05.
Article in English | MEDLINE | ID: mdl-36870392
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