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Previous research has demonstrated that the Reaching Married Adolescents intervention (RMA) was associated with changes in inequitable gender norms, intimate partner violence (IPV), and modern contraceptive use. This study seeks to understand if changes in inequitable gender norms mediate the RMA intervention's effects on contraceptive use and intimate partner violence (IPV). A four-arm cluster randomized control trial was conducted to evaluate effects of the RMA intervention (household visits, small groups, combination, control) on married adolescent girls and their husbands in Dosso, Niger (baseline: 1042 dyads; 24m follow-up: 737 dyads; 2016-2019). Mediation was assessed using inverse odds ratio weighting. In the small group intervention, of the total effect on IPV prevalence (8% reduction), indirect effects via inequitable gender norms is associated with a 2% decrease (95% CI: -0.07, 0.12) and direct effects with a 6% decrease (95% CI: -0.20, -0.02). For household visits, of the total effect on contraceptive use (20% increase), the indirect effect accounts for an 11% decrease (95% CI: -0.18, -0.01) and direct effect, a 32% increase (95% CI: 0.13, 0.44); similar to findings for the combination arm. This experimental evidence informs the value of changing underlying social norms to reduce IPV and increase contraception use., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Purpose: This study aims to (1) devise a classification system to categorize and manage ballistic fractures of the knee, hip, and shoulder; (2) assess the reliability of this classification compared to current classification schemas; and (3) determine the association of this classification with surgical management., Methods: We performed a retrospective review of a prospectively collected trauma database at an urban level 1 trauma centre. The study included 147 patients with 169 articular fractures caused by ballistic trauma to the knee, hip, and shoulder. Injuries were selected based on radiographic criteria from plain radiographs and CT scans. The AO/OTA classification system's reliability was compared to that of the novel ballistic articular injury classification system (BASIC), developed using a nominal group approach. The BASIC system's ability to guide surgical decision-making, aiming to achieve stable fixation and minimize post-traumatic arthritis, was also evaluated., Results: The BASIC system was created after analysing 73 knee, 62 hip, and 34 shoulder fractures. CT scans were used in 88% of cases, with 44% of patients receiving surgery. The BASIC classification comprises five subgroups, with a plus sign indicating the need for soft tissue intervention. Interrater reliability showed fair agreement for AO/OTA (k = 0.373) and moderate agreement for BASIC (k = 0.444). The BASIC system correlated strongly with surgical decisions, with an 83% concurrence in treatment choices based on chart reviews., Conclusions: Conventional classification systems provide limited guidance for ballistic articular injuries. The BASIC system offers a pragmatic and reproducible alternative, with potential to inform treatment decisions for knee, hip, and shoulder ballistic injuries. Further research is needed to validate this system and its correlation with patient outcomes., Level of Evidence: Level III, Diagnostic Study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high., Objectives: The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak., Methods: We analysed the outputs of two independent population-based surveys conducted at the end of the 2014-2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design., Results: Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23-0.52) and 0.12/10,000 person-days (95%CI: 0.05-0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area., Conclusion: Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.

Background: Autistic women are at high risk of developing restrictive eating disorders (REDs), such as anorexia nervosa., Aims: This study provides an overview of the clinical characteristics of autistic women with REDs to (i) enhance understanding of increased risk, and (ii) support the identification of autistic women in eating disorder services., Method: We compared self-reported autistic and disordered eating characteristics of: autistic participants with REDs (Autism + REDs; n = 57); autistic participants without REDs (Autism; n = 69); and women with REDs who are not autistic (REDs; n = 80). We also included a group of women with high autistic traits (HATs) and REDs, but no formal autism diagnosis (HATs + REDs; n = 38)., Results: Autism + REDs participants scored similarly to Autism participants in terms of autistic characteristics and to REDs participants in terms of experiencing traditional disordered eating symptoms. Autism + REDs participants were distinguished from both groups by having more restricted and repetitive behaviours and autism-specific eating behaviours related to sensory processing, flexibility and social differences. HATs + REDs participants showed a similar pattern of scores to Autism + REDs participants, and both also presented with high levels of co-occurring mental health difficulties, particularly social anxiety., Conclusion: The presentation of autistic women with REDs is complex, including both traditional disordered eating symptoms and autism-related needs, as well as high levels of co-occurring mental health difficulties. In eating disorder services, the REDs presentation of autistic women and those with HATs should be formulated with reference to autism-specific eating behaviours and co-occurring difficulties. Treatment adaptations should be offered to accommodate autistic characteristics and related needs.

Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cascades. To enable systematic exploration of how receptor valency and geometry affect signaling outcomes, we designed cyclic homo-oligomers with up to 8 subunits using repeat protein building blocks that can be modularly extended. By incorporating a de novo-designed fibroblast growth factor receptor (FGFR)-binding module into these scaffolds, we generated a series of synthetic signaling ligands that exhibit potent valency- and geometry-dependent Ca 2+ release and mitogen-activated protein kinase (MAPK) pathway activation. The high specificity of the designed agonists reveals distinct roles for two FGFR splice variants in driving arterial endothelium and perivascular cell fates during early vascular development. Our designed modular assemblies should be broadly useful for unraveling the complexities of signaling in key developmental transitions and for developing future therapeutic applications., Competing Interests: Declaration of interests L.S., D.B., N.I.E., T.S., A.E., A.F., W.Y., D.R.H., B.C., H.R.-B., A.P., R.L.R., G.B., and D.C.E. are coinventors on a patent application that has been filed by the University of Washington., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In Finland the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We performed a genome-wide association study for orofacial clefts, which include CL/P and CP, in the Finnish population. We identified rs570516915, a single nucleotide polymorphism that is highly enriched in Finns and Estonians, as being strongly associated with CP ( P = 5.25 × 10 -34 , OR = 8.65, 95% CI 6.11-12.25), but not with CL/P ( P = 7.2 × 10 -5 ), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland ( P = 8.82 × 10 -28 ) and Estonia ( P = 1.25 × 10 -5 ). The risk allele of rs570516915 disrupts a conserved binding site for the transcription factor IRF6 within a previously characterized enhancer upstream of the IRF6 gene. Through reporter assay experiments we found that the risk allele of rs570516915 diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6 , suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.

Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine., Competing Interests: Conflict of interest X.W., J.G-M, B.H., and D.B. are co-inventors on an International patent (Serial 63/570,567) filed by the University of Washington covering molecules and their uses described in this manuscript. A.R., X.W., and D.B. are co-founders of Lila Biologics and own stock or stock options in the company. All other authors declare no competing interests.

Background: Addressing threats to the nursing and public health workforce, while also strengthening the skills of current and future workers, requires programmatic solutions. Training programs should be guided by frameworks, which leverage nursing expertise and leadership, partnerships, and integrate ongoing evaluation., Purpose Statement: This article provides a replicable framework to grow, bolster, and diversify the nursing and public health workforces, known as the Nurse-led Equitable Learning (NEL) Framework for Training Programs. The framework has been applied by several multipronged, federally funded training programs led by investigators embedded in an academic nursing institution., Methods: The NEL framework focuses on: (1) increasing equitable access to the knowledge, skills, and competencies needed to prepare a diverse workforce to deliver effective interventions; (2) fostering academic-practice linkages and community partnerships to facilitate the deployment of newly gained knowledge and skills to address ongoing and emerging challenges in care delivery; and (3) continuously evaluating and disseminating findings to inform expansion and replication of programs., Results: Ten programs using this framework have successfully leveraged $18.3 million in extramural funding to support over 1000 public health professionals and trainees. Longitudinal evaluation efforts indicate that public health workers, including nurses, are benefiting from the programs' workplace trainings, future clinicians are being rigorously trained to identify and address determinants of health to improve patient and community well-being, and educators are engaging in novel pedagogical opportunities to enhance their ability to deliver high quality public health education., Conclusions: Training programs may apply the NEL framework to ensure that the nursing and public health workforces achieve equitable, sustainable growth and deliver high quality evidence-based care., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The limited blood supply and intrinsic healing capacity of the meniscus contributes to suboptimal tissue regeneration following injury and surgical repair. Biologic augmentation techniques have been utilized in combination with isolated meniscal repair to improve tissue regeneration. Several innovative strategies such as Platelet-Rich Plasma (PRP), fibrin clots, mesenchymal stem cells (MSCs), bone marrow stimulation, meniscal scaffolds, and meniscal wrapping, are being explored to enhance repair outcomes. This article provides a comprehensive review of recent findings and conclusions regarding biologic augmentation techniques., Recent Findings: Studies on PRP reveal mixed outcomes, with some suggesting benefits in reducing failure rates of isolated meniscal repair, while others question its efficacy. Fibrin clots and PRF (Platelet-rich fibrin), although promising, show inconsistent results and lack sufficient evidence for definitive conclusions. MSCs demonstrate potential in preclinical studies, but clinical trials have been limited and inconclusive. Bone marrow stimulation appears effective in certain contexts, but its broader applicability remains uncertain. Meniscal scaffolds, including CMI (Collagen Meniscal Implants) and Actifit (polyurethane scaffolds), show encouraging short- and mid-term outcomes but have not consistently surpassed traditional methods in the long term. Meniscal wrapping is infrequently studied but demonstrates positive short-term results with certain applications. The review reveals a diverse range of outcomes for biologic augmentation in meniscal repair. While certain techniques show promise, particularly in specific scenarios, the overall efficacy of these methods has yet to reach a consensus. The review underscores the necessity for standardized, high-quality research to establish the definitive effectiveness of these biologic augmentation methods., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adult humans cannot regenerate the enamel-forming cell type, ameloblasts. Hence, human induced pluripotent stem cell (hiPSC)-derived ameloblasts are valuable for investigating tooth development and regeneration. Here, we present a protocol for generating three-dimensional induced early ameloblasts (ieAMs) utilizing serum-free media and growth factors. We describe steps for directing hiPSCs toward oral epithelium and then toward ameloblast fate. These cells can form suspended early ameloblast organoids. This approach is critical for understanding, treating, and promoting regeneration in diseases like amelogenesis imperfecta. For complete details on the use and execution of this protocol, please refer to Alghadeer et al. 1 ., Competing Interests: Declaration of interests A.A., A.P.P., J.M., and H.R.-B. are co-inventors on a patent application entitled “A Method to Direct the Differentiation of Human Induced Pluripotent Stem Cells into Early Ameloblasts” (PCT/US2022/053517 filed 12/20/2022)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Foot-and-mouth disease (FMD) outbreaks affecting Asiatic black bears ( Ursus thibetanus ) and a Malayan sun bear ( Helarctos malayanus ) were previously reported in 2011 in two housing facilities at a Vietnamese bear rescue centre. In this study, demographic data of all animals housed in the centre at the time of the outbreaks ( n  = 79) were collected. Blood samples drawn from 23 bears at different timepoints were tested for FMDV-specific antibodies targeting using a non-structural protein (NSP) ELISA and by virus neutralisation test (VNT). The relationship between seroconversion and clinical signs was explored and epidemic curves and transmission diagrams were generated for each outbreak, where FMD cases were defined as animals showing FMD clinical signs. Outbreak-specific attack rates were 18.75 and 77.77%, with corresponding basic reproduction numbers of 1.11 and 1.92, for the first and second outbreaks, respectively. Analyses of risk factors showed that after adjusting for sex there was strong evidence for a decrease in odds of showing clinical signs per year of age. All samples collected from bears before the outbreak tested negative to NSP and VNT. All cases tested positive to VNT following onset of clinical signs and remained positive during the rest of the follow up period, while only 6 out of 17 cases tested positive to NSP after developing clinical signs. Six animals without clinical signs were tested post outbreaks; five seroconverted using VNT and three animals were seropositive using NSP ELISA. This study provides initial epidemiological parameters of FMD in captive bears, showing that FMDV is easily spread between bears in close proximity and can cause clinical and subclinical disease, both of which appear to induce rapid and long-lasting immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ludi, Baker, Sanki, De Jong, Maryan, Walker, King, Gubbins, Limon and Officer.)

In the United States, the growing number of people experiencing homelessness has become a socioeconomic crisis with public health ramifications, recently exacerbated by the COVID-19 pandemic. We hypothesized that the environmental surveillance of flood control infrastructure may be an effective approach to understand the prevalence of infectious disease. From December 2021 through July 2022, we tested for SARS-CoV-2 RNA from two flood control channels known to be impacted by unsheltered individuals residing in upstream tunnels. Using qPCR, we detected SARS-CoV-2 RNA in these environmental water samples when significant COVID-19 outbreaks were occurring in the surrounding community. We also performed whole genome sequencing to identify SARS-CoV-2 lineages. Variant compositions were consistent with those of geographically and temporally matched municipal wastewater samples and clinical specimens. However, we also detected 10 of 22 mutations specific to the Alpha variant in the environmental water samples collected during January 2022-one year after the Alpha infection peak. We also identified mutations in the spike gene that have never been identified in published reports. Our findings demonstrate that environmental surveillance of flood control infrastructure may be an effective tool to understand public health conditions among unsheltered individuals-a vulnerable population that is underrepresented in clinical surveillance data., Competing Interests: The authors declare no competing financial interest.

Evidence shows tablet-based interactive distraction (TBID) is effective as a preoperative anxiolytic in pediatric patients. TBID involves age-appropriate video games that have been preloaded onto a tablet (TAB) and subsequently given to a pediatric patient before the administration of anesthesia. The purpose of this study is to provide a comprehensive analysis of previous studies that have investigated the use of TBID to minimize preoperative anxiety. The literature criteria for this systematic review included randomized controlled trials and prospective studies that used TBID as a method to reduce preoperative anxiety in pediatric patients aged 1-12 years. Data extraction concentrated on the patient population to which the TABs were introduced, the method of TAB administration, how anxiety was evaluated, who completed the evaluations, and the results of each publication. This chosen data set is to systematically understand if TBID is effective and to identify the most practical ways to implement TBID. Collected data from the selected publications were entered into a table. For this systematic review, 27 publications from 2006 to 2023 were screened for eligibility. These studies were selected using a combination of MeSH terms and a Title-Abstract filter in PubMed, Embase, and Scopus. These data represented 475 total patients (T) and 249 patients who implemented TAB use. The other 226 patients were used as various control groups. The outcome of each study is summarized and placed into a table. This study is expected to provide an overall assessment of the effectiveness of TBID and proposed guidelines for clinicians to incorporate TAB use into preoperative protocols. The time to give the TAB to the children impacts its efficiency. This review accentuates the effectiveness of utilizing TBID to mitigate preoperative anxiety in pediatric patients based on a comprehensive analysis of multiple prior studies conducted in diverse healthcare settings, including pediatric hospitals and surgical centers. TAB use demonstrated an effective reduction in perioperative anxiety, emergence of delirium, and time to discharge, increasing parental satisfaction compared to midazolam. These results are likely replicable across a broader range of clinical settings, provided the intervention parameters, such as the timing of TAB introduction and the personalization of content to patient interests, are carefully adapted to each situation. The anxiety evaluations of patients using TBID varied based on the evaluator. Therefore, future research should analyze if perceived anxiety in patients using TABs is consistent or not among the evaluators. The impact of this TBID review has the potential to set a new benchmark for managing pediatric preoperative anxiety, with significant implications for healthcare quality and patient satisfaction., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Aplanalp et al.)

Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and labor. Although the specific triggers for their release in utero remain unclear, it is thought that they may contribute to the initiation of parturition by influencing cellular stress mechanisms that make the fetal membranes (FMs) more susceptible to rupture. DAMPs induce inflammation in many different tissue types. Indeed, they precipitate the subsequent release of several proinflammatory cytokines that are known to be key for the weakening of FMs. Previously, we have shown that in vitro stretch of human amnion epithelial cells (hAECs) induces a cellular stress response that increases high-mobility group box-1 (HMGB1) secretion. We have also shown that cell-free fetal DNA (cffDNA) induces a cytokine response in FM explants that is fetal sex-specific. Therefore, the aim of this work was to further investigate the link between stretch and the DAMPs HMGB1 and cffDNA in the FM. These data show that stretch increases the level of cffDNA released from hAECs. It also confirms the importance of the sex of the fetus by demonstrating that female cffDNA induced more cellular stress than male fetuses. Our data treating hAECs and human amnion mesenchymal cells with HMGB1 show that it has a differential effect on the ability of the cells of the amnion to upregulate the proinflammatory cytokines and propagate a proinflammatory signal through the FM that may weaken it. Finally, our data show that sulforaphane (SFN), a potent activator of Nrf2, is able to mitigate the proinflammatory effects of stretch by decreasing the levels of HMGB1 release and ROS generation after stretch and modulating the increase of key cytokines after cell stress. HMGB1 and cffDNA are two of the few DAMPs that are known to induce cytokine release and matrix metalloproteinase (MMP) activation in the FMs; thus, these data support the general thesis that they can function as potential central players in the normal mechanisms of FM weakening during the normal distension of this tissue at the end of a normal pregnancy.

Introduction: Lactic acid is well studied in the trauma population and is frequently used as a laboratory indicator that correlates with resuscitation status and has thus been associated with patient outcomes. There is limited literature that assesses the association of initial lactic acid with post-operative morbidity and hospitalization costs in the orthopedic literature. The purpose of this study was to assess the association of lactic acid levels and alcohol levels post-operative morbidity, length of stay and admission costs in a cohort of operative lower extremity long bone fractures, and to compare these effects in the ballistic and blunt trauma sub-population., Methods: Patients presenting as trauma activations who underwent tibial and/or femoral fixation at a single institution from May 2018 to August 2020 were divided based on initial lactate level into normal, (< 2.5) intermediate (2.5-4.0), and high (> 4.0). Mechanism of trauma (blunt vs. ballistic) was also stratified for analysis. Data on other injuries, surgical timing, level of care, direct hospitalization costs, length of stay, and discharge disposition were collected from the electronic medical record. The primary outcome assessed was post-operative morbidity defined as in-hospital mortality or unanticipated escalation of care. Secondary outcomes included hospital costs, lengths of stay, and discharge disposition. Data were analyzed using ANOVA and multivariate regression., Results: A total of 401 patients met inclusions criteria. Average age was 34.1 ± 13.0 years old, with patients remaining hospitalized for 8.8 ± 9.5 days, and 35.2% requiring ICU care during their hospitalization. Patients in the ballistic cohort were younger, had fewer other injuries and had higher lactate levels (4.0 ± 2.4) than in the blunt trauma cohort (3.4 ± 1.9) (p = 0.004). On multivariate regression, higher lactate was associated with post-operative morbidity (p = 0.015), as was age (p < 0.001) and BMI (p = 0.033). ISS, ballistic versus blunt injury mechanism, and other included laboratory markers were not. Lactate was also associated with longer lengths of stay, and higher associated direct hospitalization cost (p < 0.001) and lower rates of home disposition (p = 0.008)., Conclusion: High initial lactate levels are independently associated with post-operative morbidity as well as higher direct hospitalization costs and longer lengths of stay in orthopedic trauma patients who underwent fixation for fractures of the lower extremity long bones. Ballistic trauma patients had significantly higher lactate levels compared to the blunt cohort, and lactate was not independently associated with increased rates of post-operative morbidity in the ballistic cohort alone., Level of Evidence: III., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Purpose of Review: Postinfectious inflammatory arthritis can result from various pathogens, including bacteria, viruses, fungi, and parasites. Prompt identification and treatment of acute infection is vital, but some cases progress to chronic arthritis despite successful treatment of infection. Postinfectious inflammatory arthritis varies from mild, self-limited arthralgia to severe, refractory arthritis, necessitating ongoing disease-modifying treatment. This review explores the spectrum of postinfectious inflammatory arthritis to provide insights into effective management., Recent Findings: Research continues regarding the benefit of antimicrobial therapy, beyond treatment of the acute infection, to diminish the severity of postinfectious inflammatory arthritis. Following treatment of acute infection, most cases are self-limited so treatment is symptomatic. However, a difficult-to-predict fraction of cases develop chronic postinfectious inflammatory arthritis that can be challenging to manage. Recently, as more biologic, and targeted synthetic DMARDs have become available, treatment options have expanded., Summary: In this article, we use the term 'postinfectious inflammatory arthritis' rather than 'reactive arthritis' because it describes a broader spectrum of diseases and emphasizes the common pathogenesis of a postinfectious inflammatory process. We summarize the conventional therapies and recent management developments for the most frequently encountered postinfectious inflammatory arthritides., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Laboratory outreach programs for K-12 students in the United States from 2020 to 2022 were suspended or delayed due to COVID-19 restrictions. While Southern Nevada also observed similar closures for onsite programs, we and others hypothesized that in-person laboratory activities could be prioritized after increasing vaccine doses were available to the public and masking was encouraged. Here, we describe how the Laboratory of Neurogenetics and Precision Medicine at the University of Nevada Las Vegas (UNLV) collaborated with administrators from a local school district to conduct training activities for high school students during the COVID-19 pandemic. The Science Education for the Youth (SEFTY) program's curriculum was constructed to incorporate experiential learning, fostering collaboration and peer-to-peer knowledge exchange. Leveraging neuroscience tools from our UNLV laboratory, we engaged with 117 high school applicants from 2021 to 2022. Our recruitment efforts yielded a diverse cohort, with >41% Pacific Islander and Asian students, >9% African American students, and >12% multiracial students. We assessed the impact of the SEFTY program through pre- and postassessment student evaluations, revealing a significant improvement of 20.3% in science proficiency ( p  < 0.001) after participating in the program. Collectively, our laboratory curriculum offers valuable insights into the capacity of an outreach program to actively foster diversity and cultivate opportunities for academic excellence, even in the challenging context of a global pandemic., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Ghani et al.)

Introduction: Transitioning into the role of a mother encompasses many physical and psychosocial changes, affecting the way a woman may function. Maternal health is an emerging area of practice for occupational therapists, and therefore, screening and assessment tools to support work in this area are needed. The Barkin Index of Maternal Functioning (BIMF) is a quantitative outcome measure that is used by health professionals to assess maternal functioning. Currently, its ability to measure occupational performance is unclear., Methods: Utilising a mixed methods design, this study analysed the extent to which the BIMF assesses maternal function from an occupational perspective. Thirteen first-time mothers with a baby 12 months of age or younger participated in the study. Results from the BIMF were compared with themes developed from semi-structured qualitative interviews that explored the occupational experiences of first-time mothers., Findings: Seven themes were developed from the interviews. The BIMF addressed three themes, including changes to engagement in basic activities of daily living and leisure, transitioning into motherhood, emotions, self-efficacy, and social support. However, four themes were not captured by the BIMF, including changes to partner relationships, identity shift, influence of 'person' factors, and changes to social experiences in early motherhood., Conclusion: Findings suggest that a new tool with a holistic perspective of mothers as occupational beings is needed to be able to identify occupational performance issues and the potential need for occupational therapy support. This study identified key experiences of occupational performance for new mothers., (© 2024 The Authors. Australian Occupational Therapy Journal published by John Wiley & Sons Australia, Ltd on behalf of Occupational Therapy Australia.)

Introduction: Problem-solving skills (PSS) help to provide a systematic approach to dealing with and managing complex problems. The overall aim of this study was to assess the acceptability and feasibility of developing and adapting a prison-based PSS  workbook for adults within a medium- and low-secure hospital., Method: We used the Medical Research Council framework in our participatory mixed methods study incorporating an adapted survey (to identify what types of problems people experience in secure hospitals), a series of three interactive workshops (to co-produce two case study examples for a workbook) and we gathered feedback from patients and hospital staff on the acceptability and feasibility of the workbook. Data from the survey were used to inform the case study examples, and the feedback from patients and hospital staff was descriptively summarised and the results consolidated., Results: In total, 82 (51%) patients took part in the survey; 22 patients and 49 hospital staff provided feedback on the workbook. The survey results indicated that patients regularly experience problems while in the hospital. Patients reported problems relating to restrictions of freedom and boredom. The workshops produced two case studies for the workbooks, with mainly positive patient and staff feedback. More work is required to improve the visual representation of the characters in the case studies, the amount and content of the language and the mechanism of the intervention delivery., Conclusion: The adaptation process proved acceptable and feasible to both patients and staff. The co-production methodology for the workbook and feedback from patients and staff was an effective way of iteratively refining the materials to ensure that they were both meaningful and acceptable to staff and patients. Subsequent work is required to develop the workbook and evaluate the feasibility of the intervention delivery, recruitment rates, uptake and adherence to the PSS using a randomised controlled trial., Patient or Public Contribution: At each stage of the project consultation with patients and/or hospital staff was involved., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: The major changes in the timing of meals during Ramadan may be challenging for hypothyroid patients on levothyroxine. We aimed to study the effect of Ramadan fasting on thyroid functions in hypothyroid patients taking levothyroxine., Methods: We did a comprehensive search of 8 databases for Randomized controlled studies (RCTs) and observational studies investigating the effect of Ramadan fasting on thyroid functions in hypothyroid individuals taking levothyroxine. Relevant data was extracted and analyzed. Mean difference (MD) and standard deviation (SD) were used to evaluate the continuous data. Risk ratios (RR) with a 95% confidence interval were used for outcomes constituting dichotomous data. National Institutes of Health (NIH) tools were used to assess the risk of bias., Results: Fourteen studies met our inclusion criteria, 3 RCTs, and 11 observational studies, all designed as pre-post studies. Ramadan fasting was associated with a statistically significant increase in TSH in patients who were euthyroid before Ramadan (MD = -0.76 [95% CI; -1.27, -0.25]). However, free thyroxine (FT4) was found to be stable (MD = 0.01, [95% CI; -0.03, 0.06]). All timing points were associated with a significant increase in TSH levels after Ramadan, pre-iftar (MD = -0.69 [95% CI; -1.03, -0.36]), post-iftar (MD = -0.76 [95% CI; -1.12, -0.39]), and pre-suhoor (MD = -1.19 [95% CI; -2.18, -0.19])., Conclusion: TSH increases significantly after Ramadan. No timing point has superiority in maintaining thyroid control. However, choosing the timing should be individualized according to the patient's preference to guarantee the most possible compliance., (© 2023. The Author(s).)

Tissue repair is significantly compromised in the aging human body resulting in critical disease conditions (such as myocardial infarction or Alzheimer's disease) and imposing a tremendous burden on global health. Reprogramming approaches (partial or direct reprogramming) are considered fruitful in addressing this unmet medical need. However, the efficacy, cellular maturity and specific targeting are still major challenges of direct reprogramming. Here we describe novel approaches in direct reprogramming that address these challenges. Extracellular signaling pathways (Receptor tyrosine kinases, RTK and Receptor Serine/Theronine Kinase, RSTK) and epigenetic marks remain central in rewiring the cellular program to determine the cell fate. We propose that modern protein design technologies (AI-designed minibinders regulating RTKs/RSTK, epigenetic enzymes, or pioneer factors) have potential to solve the aforementioned challenges. An efficient transdifferentiation/direct reprogramming may in the future provide molecular strategies to collectively reduce aging, fibrosis, and degenerative diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Keshri, Detraux, Phal, McCurdy, Jhajharia, Chan, Mathieu and Ruohola-Baker.)

Purpose: To evaluate the use of resonant acoustic mixing (RAM) technology for homogenous blending of a morphologically challenging model API in low-dose concentrations (<0.1% w/w), and assess the potential for blend uniformity (BU) optimization., Methods: Caffeine (CAF) mixing was carried out using a LabRAM I benchtop mixer. Uniformity was assessed under a range of mixing conditions and sample preparation procedures in order to optimize system performance. The capacity for microscale mixing was evaluated from final parameters for 0.05% and 0.0125% CAF blends., Results: Upon optimization, RAM was able to accurately prepare homogeneous mixtures of <0.1% CAF in dilutions of up to 1 part per 8,000. Results from a 0.05% blend targeting 125 μg CAF dosage amounts revealed an AV score of 8.8 while a 0.0125% w/w blend accurately prepared 25 μg of CAF with 99.3% accuracy (98.7% label claim) and AV of 10.1. Microscale mixing in the 0.05% w/w blend was confirmed from plots of BU data against sample size demonstrating a slope of 0.05 within the range of 250-10 mg sample (125-5 μg CAF). L1 BU criteria only failed at the level of 2 μg CAF, despite target precision to 26 nanograms (98.7% label claim)., Conclusions: This study presents the first instance of a homogenously mixed <0.1% (w/w) blend using RAM technology and demonstrate the suitability for reproducible dosing of single-digit microgram drug amounts. Uniformity is documented for API amounts 60x smaller than a recent report has shown and 10,000x smaller than achieved previously with CAF., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Intimate partner violence (IPV) is a significant public health, human rights, and development issue. While existing evidence posits that addressing social norms is key to IPV prevention, successful IPV interventions that include a norms approach are limited in number and methodological rigor and rarely include a formal investigation of the diffusion of intervention impact. We contribute novel findings to this intellectual and programmatic space with evidence on a social and behavior change communication (SBCC) intervention (Change Starts at Home) in Nepal designed to prevent IPV and shift social norms towards greater gender equity., Methods: Participants included 442 married women across 13 communities assessed at three timepoints: before intervention (baseline), at the completion of the core couple's curriculum and edutainment (midline), and at the conclusion of the diffusion curriculum (endline). Generalized estimating equations with propensity-score adjustments were used to determine change in outcomes at midline and endline for two intervention conditions (direct beneficiary, N  = 173; and resident of the intervention community, ( N  = 178) relative to control ( N  = 91)., Results: IPV victimization significantly decreased in both intervention conditions at midline, with larger reductions in direct beneficiaries. At endline, direct beneficiaries had sustained reduction in IPV relative to control participants. Positive injunctive norms also significantly improved by midline for both intervention groups, whereas improvements in descriptive norms for intervention groups were matched by improvements in the control group at both midline and endline. Several secondary outcomes showed significant improvements for both intervention groups at midline and/or endline, including in-law violence, financial decision-making, communication, and relationship quality, with additional improvements for the direct beneficiaries in attitudes, leadership, GBV advocacy, and diffusion., Conclusion: This study sheds light on the effectiveness of the Change intervention, the role of addressing social norms in IPV prevention efforts, and the benefits of organized diffusion., Competing Interests: None., (© 2023 The Authors.)

Objective: To compare characteristics of patients ≥65 years presenting with idiopathic subglottic stenosis (iSGS) to patients diagnosed at <65 years. We hypothesize that the groups have similar comorbidities and disease courses., Data Sources: Medical records of patients treated for iSGS at a tertiary care institution from January 2005-September 2022., Review Methods: Patient demographics, time from symptom onset to diagnosis, medical history and comorbidities, and treatment modalities/intervals were recorded and analyzed. Characteristics of patients ≥65 and <65 years at presentation were compared using Chi-square analysis for non-numeric values and the Mann-Whitney U-test for numeric values., Results: One hundred seven patients with iSGS were identified and 16 (15%) were aged ≥65 years (mean age 72.6, 15 female) at presentation. These patients were compared to 91 patients aged <65 years (mean age = 47.6, 90 female). Patients ≥65 years had higher rates of type 2 diabetes mellitus (T2DM) (p = 0.004) and tobacco use (p = 0.004). There were no significant differences in body mass index, gastroesophageal reflux disease, hormone replacement therapy, time from symptom onset to presentation, or length of operative treatment intervals., Conclusion: Patients ≥65 years with iSGS have higher rates of tobacco use, suggesting that alterations in wound healing may play a role in the development of iSGS in this age group. Although rates of T2DM were higher in the elderly group, clinical significance may be limited given the overall higher rate of diabetes mellitus in the elderly population., Level of Evidence: 4 Laryngoscope, 133:3075-3079, 2023., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Gender norms have been posited to impact intimate partner violence (IPV), but there is scant evidence of the longitudinal association between community-level gender norms and IPV. Using longitudinal data on 3,965 married girls surveyed in India, we fitted mixed-effects ordinal and binary logistic regression models for physical IPV intensity and occurrence of sexual IPV. We found a 26% increase in the odds that women experience frequent physical IPV per one unit increase in greater community-level equitable gender norms. We did not find an association between community-level equitable gender norms and sexual IPV. Findings suggest that the relationship between gender norms and physical and sexual IPV differs, indicating the need for tailored interventions for different types of IPV., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Tooth enamel secreted by ameloblasts (AMs) is the hardest material in the human body, acting as a shield to protect the teeth. However, the enamel is gradually damaged or partially lost in over 90% of adults and cannot be regenerated due to a lack of ameloblasts in erupted teeth. Here, we use single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) to establish a spatiotemporal single-cell census for the developing human tooth and identify regulatory mechanisms controlling the differentiation process of human ameloblasts. We identify key signaling pathways involved between the support cells and ameloblasts during fetal development and recapitulate those findings in human ameloblast in vitro differentiation from induced pluripotent stem cells (iPSCs). We furthermore develop a disease model of amelogenesis imperfecta in a three-dimensional (3D) organoid system and show AM maturation to mineralized structure in vivo. These studies pave the way for future regenerative dentistry., Competing Interests: Declaration of interests A.A., S.H.-D., Y.T.Z., D.D.E., Y.W., A.P.P., H.Z., J.M., D.B., and H.R.-B. are co-inventors on a patent application entitled “Human IPSC Derived Ameloblasts and Uses Thereof” (PCT/US2022/053517 filed 12/20/2022 and published 7/6/2023)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Non-small cell lung cancer (NSCLC) patients, accounting for approximately 85% of lung cancer cases, are usually diagnosed in advanced stages. Traditional surgical resection and radiotherapy have very limited clinical benefits. The objective of this study was to develop and evaluate a targeted therapy, antibody-drug conjugate (ADC), for NSCLC treatment. Specifically, the CD276 receptor was evaluated and confirmed as an ideal surface target of NSCLC in the immunohistochemistry (IHC) staining of seventy-three patient tumor microarrays and western blotting analysis of eight cell lines. Our anti-CD276 monoclonal antibody (mAb) with cross-activity to both human and mouse receptors showed high surface binding, effective drug delivery and tumor-specific targeting in flow cytometry, confocal microscopy, and in vivo imaging system analysis. The ADC constructed with our CD276 mAb and payload monomethyl auristatin F (MMAF) showed high anti-NSCLC cytotoxicity to multiple lines and effective anti-tumor efficacy in both immunocompromised and immunocompetent NSCLC xenograft mouse models. The brief mechanism study revealed the integration of cell proliferation inhibition and immune cell reactivation in tumor microenvironments. The toxicity study did not detect off-target immune toxicity or peripheral toxicity. Altogether, this study suggested that anti-CD276 ADC could be a promising candidate for NSCLC treatment.

Just like time and tide, embryonic development waits for no man but progresses forcefully to its completion, with just one exception. Diapause is an enigmatic, reversible, dormant halt that protects the developing embryo. Cancer cells have evolved to hijack many useful stem cell capabilities, and diapause is no exception. Recent work has revealed a diapause-like cancer cell state, prompting the quest for its key molecular regulators useful for cancer therapies. The present paper by Sun et al. 1 addresses this knowledge gap by revealing a key player in regulating the diapause-like cancer cell stage, the condensin protein SMC4., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Use of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients with preexisting tuberculosis (TB), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection can have serious consequences. Although various society guidelines recommend routine screening for these infections before initiating certain b/tsDMARDs, adherence to these recommendations varies widely. This quality improvement initiative evaluated local compliance with screening and assessed whether an automated computerized decision support system in the form of a best practice advisory (BPA) in the electronic health record could improve patient screening., Methods: Established patients with autoimmune rheumatic disease (ARD) aged 18 years or older with at least one visit to our rheumatology practice between October 1, 2017, and March 3, 2022, were included. When prescribing a new b/tsDMARD, clinicians were alerted via a BPA that showed the most recent results for TB, HBV, and HCV. Screening proportions for TB, HBV, and HCV before BPA initiation were compared with those of eligible patients after the BPA implementation., Results: A total of 711 patients pre-BPA and 257 patients post-BPA implementation were included in the study. The BPA implementation was associated with statistically significant improvement in screening for TB from 66% to 82% (P ≤ 0.001), HCV from 60% to 79% (P ≤ 0.001), hepatitis B core antibody 32% to 51% (P ≤ 0.001), and hepatitis B surface antigen from 51% to 70% (P ≤ 0.001)., Conclusion: Implementation of a BPA can improve infectious disease screening for patients with ARD who are started on b/tsDMARDs and has potential to improve patient safety., (© 2023 American College of Rheumatology.)

Background: The field of violence prevention research is unequivocal that interventions must target contextual factors, like social norms, to reduce gender-based violence. Limited research, however, on the social norms contributing to intimate partner violence or reproductive coercion exists. One of the driving factors is lack of measurement tools to accurately assess social norms., Methods: Using an item response modelling approach, this study psychometrically assesses the reliability and validity of a social norms measure of the acceptability of intimate partner violence to exert control over wife agency, sexuality, and reproductive autonomy with data from a population-based sample of married adolescent girls (ages 13-18) and their husbands in rural Niger (n = 559 husband-wife dyads) collected in 2019., Results: A two-dimensional Partial Credit Model for polytomous items was fit, showing evidence of reliability and validity. Higher scores on the "challenging husband authority" dimension were statistically associated with husband perpetration of intimate partner violence., Conclusions: This brief scale is a short (5 items), practical measure with strong reliability and validity evidence. This scale can help identify populations with high-need for social norms-focused IPV prevention and to help measure the impact of such efforts., (© 2023. The Author(s).)

» A multidisciplinary, integrated, and synergistic team approach to the unstable polytrauma patient is critical to optimize outcomes, minimize morbidity, and reduce mortality.» The use of Advanced Trauma Life Support protocols helps standardize the assessment and avoid missing critical injuries» Effective and open dialog with consulting specialists is paramount for effective team-based care.» Orthopaedic surgeons should play an important role in the rapid assessment of potentially life-threatening and/or limb-threatening injuries including pelvic ring disruption, open fractures with substantial blood loss, and dysvascular limbs., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A951)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Niger has the highest rate of adolescent fertility in the world, with early marriage, early childbearing and high gender inequity. This study assesses the impact of Reaching Married Adolescents (RMA), a gender-synchronized social behavioral intervention designed to improve modern contraceptive use and reduce intimate partner violence (IPV) among married adolescent couples in rural Niger., Methods: We conducted a four-armed cluster-randomized trial in 48 villages across three districts in Dosso region, Niger. Married adolescent girls (ages 13-19) and their husbands were recruited within selected villages. Intervention arms included home visits by gender-matched community health workers (CHWs) (Arm 1), gender-segregated, group discussion sessions (Arm 2), and both approaches (Arm 3). We used multilevel mixed-effects Poisson regression models to assess intervention effects for our primary outcome, current modern contraceptive use, and our secondary outcome, past year IPV., Results: Baseline and 24-month follow-up data were collected April-June 2016 and April-June 2018. At baseline, 1072 adolescent wives were interviewed (88% participation), with 90% retention at follow-up; 1080 husbands were interviewed (88% participation), with 72% retention at follow-up. Adolescent wives had higher likelihood of modern contraceptive use at follow-up relative to controls in Arm 1 (aIRR 3.65, 95% CI 1.41-8.78) and Arm 3 (aIRR 2.99, 95% CI 1.68-5.32); no Arm 2 effects were observed. Relative to those in the control arm, Arm 2 and Arm 3 participants were significantly less likely to report past year IPV (aIRR 0.40, 95% CI 0.18-0.88 for Arm 2; aIRR 0.46, 95% CI 0.21-1.01 for Arm 3). No Arm 1 effects were observed., Conclusions: The RMA approach blending home visits by CHWs and gender-segregated group discussion sessions is the optimal format for increasing modern contraceptive use and decreasing IPV among married adolescents in Niger. Trial registration This trial is retrospectively registered with ClinicalTrials.gov, Identifier NCT03226730., (© 2023. The Author(s).)

Diabetic cardiomyopathy (CM), occurring in the absence of hypertension, coronary artery disease, and valvular or congenital heart disease, is now recognized as a distinct, multifactorial disease leading to ventricular hypertrophy and abnormal myocardial contractility that correlates with an array of complex molecular and cellular changes. Animal models provide the unique opportunity to investigate mechanistic aspects of diabetic CM, but important caveats exist when extrapolating findings obtained from preclinical models of diabetes to humans. Indeed, animal models do not recapitulate the complexity of environmental factors, most notably the duration of the exposure to insulin resistance that may play a crucial role in the development of diabetic CM. Moreover, most preclinical studies are performed in animals with uncontrolled or poorly controlled diabetes, whereas patients tend to undergo therapeutic intervention. Finally, whilst type 2 diabetes mellitus prevalence trajectory mainly increases at 40- < 75 years (with a currently alarming increase at younger ages, however), it is a legitimate concern how closely rodent models employing young animals recapitulate the disease developing in old people. The aim of this review is to identify the current limitations of rodent models and to discuss how future mechanistic and preclinical studies should integrate key confounding factors to better mimic the diabetic CM phenotype., Competing Interests: Conflict of interest L.B. declares to have acted as SAB member of Sanofi, Novartis and International Aspirin Foundation and a Research Grant from AstraZeneca to the institution (unrelated to this work). LB and GV have founded two spinoff companies, Glycardial Diagnostics and Ivestatin Therapeutics (unrelated to this work). RAB reports speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche, outside the submitted work. The UMCG, which employs RAB has received research grants and/or fees from AstraZeneca, Abbott, Boehringer-Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche, outside the submitted work. GC, TD’H, MK and GAD are supported by the RHU-CARMMA Grant (ANR-15-RHUS-0003), the ANR-18-EURE-0011 Grant (EUR LIVE), the ANR-21-CE14-0031-01 Grant (DOXEPISEN), the RSE20003DDA Grant (FHU-SENEC), the FRM grants (EQU202003010186 and ENV202004011730). No others declared any conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Real-time surveillance of infectious diseases at schools or in communities is often hampered by delays in reporting due to resource limitations and infrastructure issues. By incorporating quantitative PCR and genome sequencing, wastewater surveillance has been an effective complement to public health surveillance at the community and building-scale for pathogens such as poliovirus, SARS-CoV-2, and even the monkeypox virus. In this study, we asked whether wastewater surveillance programs at elementary schools could be leveraged to detect RNA from influenza viruses shed in wastewater. We monitored for influenza A and B viral RNA in wastewater from six elementary schools from January to May 2022. Quantitative PCR led to the identification of influenza A viral RNA at three schools, which coincided with the lifting of COVID-19 restrictions and a surge in influenza A infections in Las Vegas, Nevada, USA. We performed genome sequencing of wastewater RNA, leading to the identification of a 2021-2022 vaccine-resistant influenza A (H3N2) 3C.2a1b.2a.2 subclade. We next tested wastewater samples from a treatment plant that serviced the elementary schools, but we were unable to detect the presence of influenza A/B RNA. Together, our results demonstrate the utility of near-source wastewater surveillance for the detection of local influenza transmission in schools, which has the potential to be investigated further with paired school-level influenza incidence data., Competing Interests: Declaration of competing interest Dr. Carolina Koutras is an employee of R-Zero Systems., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Recent national data suggests that less than 0.5% of NHS cataract patients undergo immediate sequential bilateral cataract surgery (ISBCS). Since ISBCS improves service efficiency, increasing its practice may help tackle the ever-growing burden of cataract in the UK, and reduce the COVID-19 cataract backlog. Surgeon attitudes are known to be a significant barrier to increasing the practice of ISBCS. However, little is known about patient perceptions of ISBCS., Methods: Patients at cataract clinics across three NHS hospital sites were recruited to complete an investigator-led structured questionnaire. Open-ended and closed-ended questions were used to assess awareness of ISBCS, willingness to undergo ISBCS and attitudes towards ISBCS., Results: Questionnaires were completed by 183 patients. Mean participant age was 70.5 (9.9) years and 58% were female. Forty-three percent were aware of ISBCS, chiefly via clinic staff. Just over a third would choose ISBCS if given the choice, and participants that perceived they were recommended ISBCS were more likely to opt for it. The most common motivator and barrier to uptake of ISBCS was convenience and the perceived risk of complications in both eyes respectively. Concerns related to the recovery period were common, including misunderstandings, such as the need to wear eye patches that obscure both eyes., Conclusions: Our study indicates that significantly more NHS patients would be willing to undergo ISBCS if given the choice. The reluctance of surgeons to recommend ISBCS and patient misunderstandings regarding the recovery period may be limiting its uptake., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

As a result of evolutionary selection, the subunits of naturally occurring protein assemblies often fit together with substantial shape complementarity to generate architectures optimal for function in a manner not achievable by current design approaches. We describe a "top-down" reinforcement learning-based design approach that solves this problem using Monte Carlo tree search to sample protein conformers in the context of an overall architecture and specified functional constraints. Cryo-electron microscopy structures of the designed disk-shaped nanopores and ultracompact icosahedra are very close to the computational models. The icosohedra enable very-high-density display of immunogens and signaling molecules, which potentiates vaccine response and angiogenesis induction. Our approach enables the top-down design of complex protein nanomaterials with desired system properties and demonstrates the power of reinforcement learning in protein design.

Purpose: To provide a biomechanical comparison between human dermal (HD) allograft and long head of biceps tendon (LHBT) autograft with and without posterior side-to-side suturing for superior capsule reconstruction., Methods: Eight fresh-frozen cadaveric shoulder specimens were tested in 5 conditions: (1) intact, (2) complete supraspinatus tear, (3) LHBT, (4) LHBT with side-to-side suturing, and (5) HD allograft with side-to-side suturing. Functional abduction force, superior translation of humeral head, translational range of motion, and rotational range of motion were tested at 0°, 30°, 60°, and 90° of abduction within each condition. Data were analyzed using analysis of variance with post-hoc Tukey testing for pairwise comparison, with a significance value set at .05., Results: Functional abduction force in the LHBT, LHBT + suture, and HD + suture conditions was significantly increased compared with the supraspinatus tear condition at abduction angles of 30° (P = .011, .001, and .017, respectively), 60° (P = .004, .001, and .002, respectively), and 90° (P = .013, .001, and .038, respectively). In addition, superior translation of the humeral head in the LHBT, LHBT + suture, and HD + suture conditions was significantly decreased compared with the tear condition at abduction angles of 30° (P = .03, .049, .03, respectively) and 60° (P = .02, .04, .03, respectively). All 3 reconstructive techniques were statistically identical to the intact rotator cuff condition in regard to translational and rotational range of motion., Conclusions: Superior capsule reconstruction with LHBT autograft without side-to-side suturing, LHBT with posterior side-to-side suturing, and HD allograft with posterior side-to-side suturing all equivalently restore functional abduction force and decrease superior translation of the humeral head after a complete supraspinatus tear., Clinical Relevance: Superior capsule reconstruction with long head of the biceps tendon autograft and human dermal allograft both restore functional abduction force and decrease superior translation of the humeral head, while displaying no losses in the range of motion in a cadaveric model., (Copyright © 2022 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Two-dimensional electronic spectroscopy (2DES) has recently been gaining popularity as an alternative to the more common transient absorption spectroscopy due to the combination of high frequency and time resolution of 2DES. In order to advance the reliable analysis of population dynamics and to optimize the time resolution of the method, one has to understand the numerous field matter interactions that take place at an early and negative time. These interactions have historically been discussed in one-dimensional spectroscopy as coherent artifacts and have been assigned to both resonant and non-resonant system responses during or before the pulse overlap. These coherent artifacts have also been described in 2DES but remain less well-understood due to the complexity of 2DES and the relative novelty of the method. Here, we present 2DES results in two model nanocrystal samples, CdSe and CsPbI 3 . We demonstrate non-resonant signals due to solvent response during the pulse overlap and resonant signals, which we assign to perturbed free induction decay (PFID), both before and during the pulse overlap. The simulations of the 2DES response functions at early and negative time delays reinforce the assignment of the negative time delay signals to PFID. Modeling reveals that the PFID signals will severely distort the initial picture of the resonant population dynamics. By including these effects in models of 2DES spectra, one is able to push forward the extraction of early time dynamics in 2DES.

The hot phonon bottleneck has been under intense investigation in perovskites. In the case of perovskite nanocrystals, there may be hot phonon bottlenecks as well as quantum phonon bottlenecks. While they are widely assumed to exist, evidence is growing for the breaking of potential phonon bottlenecks of both forms. Here, we perform state-resolved pump/probe spectroscopy (SRPP) and time-resolved photoluminescence spectroscopy (t-PL) to unravel hot exciton relaxation dynamics in model systems of bulk-like 15 nm nanocrystals of CsPbBr 3 and FAPbBr 3 , with FA being formamidinium. The SRPP data can be misinterpreted to reveal a phonon bottleneck even at low exciton concentrations, where there should be none. We circumvent that spectroscopic problem with a state-resolved method that reveals an order of magnitude faster cooling and breaking of the quantum phonon bottleneck that might be expected in nanocrystals. Since the prior pump/probe methods of analysis are shown to be ambiguous, we perform t-PL experiments to unambiguously confirm the existence of hot phonon bottlenecks as well. The t-PL experiments reveal there is no hot phonon bottleneck in these perovskite nanocrystals. Ab initio molecular dynamics simulations reproduce experiments by inclusion of efficient Auger processes. This experimental and theoretical work reveals insight on hot exciton dynamics, how they are precisely measured, and ultimately how they may be exploited in these materials.

The identification of novel SARS-CoV-2 variants can predict new patterns of COVID-19 community transmission and lead to the deployment of public health resources. However, increased access to at-home antigen tests and reduced free PCR tests have recently led to data gaps for the surveillance of evolving SARS-CoV-2 variants. To overcome such limitations, we asked whether wastewater surveillance could be leveraged to detect rare variants circulating in a community before local detection in human cases. Here, we performed whole genome sequencing (WGS) of SARS-CoV-2 from a wastewater treatment plant serving Las Vegas, Nevada in April 2022. Using metrics that exceeded 100× depth at a coverage of >90 % of the viral genome, we identified a variant profile similar to the XL recombinant lineage containing 26 mutations found in BA.1 and BA.2 and three private mutations. Prompted by the discovery of this rare lineage in wastewater, we analyzed clinical COVID-19 sequencing data from Southern Nevada and identified two cases infected with the XL lineage. Taken together, our data highlight how wastewater genome sequencing data can be used to discover rare SARS-CoV-2 lineages in a community and complement local public health surveillance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To estimate the cost-effectiveness of single-use hydrophilic-coated intermittent catheters (HCICs) versus single-use uncoated intermittent catheters (UICs) for urinary catheterization., Methods: The evaluation took a UK national health service (NHS) perspective. The population of interest were people using intermittent catheters, with either a spinal cord injury or multiple sclerosis. A Markov model was developed that estimated costs and clinical evidence over the lifetime of a hypothetical cohort and applied health-related quality - of - life estimates. Model inputs were sourced from published evidence, including a network meta-analysis to inform the treatment effect (reduction in catheter-associated urinary tract infections [CAUTIs]), and were supported by expert opinion. The model outputs included per-patient lifetime costs, quality-adjusted life years (QALYs), and the incremental cost effectiveness ratio (ICER). Event counts were also produced., Results: Using HCICs instead of UICs could prevent seven CAUTI events per patient over a lifetime horizon (1.8 requiring secondary care). Overall, lifetime use of HCICs is £3,183 more expensive than use of UICs per patient. However, for these additional costs, 0.55 QALYs are gained. The ICER is £5,755 per additional QALY gained. Key drivers of the model results were identified and subject to sensitivity analyses. The results were found to be robust to parameter uncertainty., Conclusion: HCICs are likely to be a cost-effective alternative to UICs, a result driven by substantial reductions in the number of CAUTIs. Their adoption across clinical practice could avoid a substantial number of infections, freeing up resources in the NHS and reducing antibiotic use in urinary catheter users.

Following acute genotoxic stress, both normal and tumorous stem cells can undergo cell-cycle arrest to avoid apoptosis and later re-enter the cell cycle to regenerate daughter cells. However, the mechanism of protective, reversible proliferative arrest, "quiescence," remains unresolved. Here, we show that mitophagy is a prerequisite for reversible quiescence in both irradiated Drosophila germline stem cells (GSCs) and human induced pluripotent stem cells (hiPSCs). In GSCs, mitofission (Drp1) or mitophagy (Pink1/Parkin) genes are essential to enter quiescence, whereas mitochondrial biogenesis (PGC1α) or fusion (Mfn2) genes are crucial for exiting quiescence. Furthermore, mitophagy-dependent quiescence lies downstream of mTOR- and PRC2-mediated repression and relies on the mitochondrial pool of cyclin E. Mitophagy-dependent reduction of cyclin E in GSCs and in hiPSCs during mTOR inhibition prevents the usual G1/S transition, pushing the cells toward reversible quiescence (G0). This alternative method of G1/S control may present new opportunities for therapeutic purposes., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

When lockdown was announced in the United Kingdom, kitchen tables transformed into offices overnight, as many National Health Service (NHS) workers adapted to new ways of working from home. To respond to the developing situation, we established a programme of weekly 'Connections' meetings where staff could be together, remotely. This article describes the evolution of our Morning Connections and Oncology Connections virtual meetings, including the content of sessions, how they were evaluated and whether they met their intention to support colleagues during a particularly challenging time, both personally and professionally, for NHS staff.

The biological revolutions of computationally designed proteins, induced pluripotent stem cells (iPSCs), and the CRISPR-Cas9 system finally enables modifications that can spur deep understanding of spatial requirement of epigenetic information. This commentary describes the utility of a computationally designed protein, EED Binder (EB), when fused to dCas9 (EBdCas9) for identifying critical sites of PRC2 dependent histone H3K27me3 marks in the chromatin. By using EBdCas9 and gRNA, PRC2 function can be inhibited at specific loci, resulting in precise reduction of EZH2 and H3K27me3 marks, and in some (but not all) locations, activation of the gene and functional outcomes (such as regulation of cell cycle or trophoblast transdifferentiation). Interestingly, a functional TATA box located more than 500bp upstream of a TBX18 TSS was found to be repressed by PRC2, supporting the theory that epigenetic regulators control the repression of transcriptional elements on the promoter region. The EBdCas9 technology may provide a useful tool for controlling gene regulation through epigenomic control.