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Background: Sexual dysfunction is common for adults receiving chronic haemodialysis; however, renal nurses seldom discuss this topic with patients., Objectives: This study aimed to identify renal nurses' attitudes towards providing sexual healthcare and to determine their confidence in discussing sexual dysfunction with adults who are receiving haemodialysis., Design: An online cross-sectional study., Participants: Renal nurses across Australia and New Zealand (n = 65) who were members of the Renal Society of Australasia provided direct care to adults receiving haemodialysis., Measurements: Two questionnaires measuring (1) the frequency of sexual health discussions, levels of knowledge and competence, barriers to discussing sexual dysfunction and views on accountability (Van Ek survey) and (2) communication, practical knowledge, and attitude (sexual health educator for professionals scale) were used. Demographic characteristics were also collected., Results: Most participants were females (60%) with postgraduate qualifications (61.4%). The average nephrology nursing experience was 13.10 ± 9.14 years. Most renal nurses identified as having positive attitudes (77.2%) about providing sexual healthcare and were confident in communicating with patients about sexual concerns (42.9%), although many nurses (64.35%) rarely did so. Less than one-half (48.6%) indicated feeling competent to discuss sexual dysfunction, and less than one-third (30%) had sufficient knowledge about sexual dysfunction. Barriers were lack of practical training (74.2%) and insufficient time (57.1%). Younger nurses (≤45 years old) and male nurses were significantly more confident in discussing sexual health matters., Conclusions: Overall, renal nurses had positive attitudes towards discussing sexual health concerns with patients however they rarely did so., (© 2024 The Author(s). Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Background: Compared with conventional cigarettes, electronic cigarettes are less harmful in some studies. However, recent research may indicate the opposite. This study aimed to determine whether e-cigarette use is related to myocardial health in adults in the U.S., Methods: This study used data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a cross-sectional survey of adult US residents aged 18 years or older. We examined whether e-cigarette use was related to myocardial infarction byapplying a logistic regression model to calculate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: The final analytical sample included 198,530 adults in the U.S. Logistic regression indicated that U.S. adults who reported being former and some days of e-cigarette use had 23% and 52% greater odds of ever having an MI, respectively, than did those who reported never using e-cigarettes (OR = 1.23, 95% CI 1.08-1.40, p = 0.001; OR = 1.52, 95% CI 1.10-2.09, p = 0.010)., Conclusions: The results suggest that former and someday users of e-cigarettes probably have increased odds of myocardial infarction in adults in the U.S. Further research is needed, including long-term follow-up studies on e-cigarettes, since it is still unknown whether they should be discouraged., (© 2024. The Author(s).)

Aims: The survival of inoculated Escherichia coli on Fuji apples in Washington State orchards was studied, considering evaporative cooling, canopy location, year, and region, with the examination of sunlight exposure and inoculation levels in year 2., Methods and Results: Rifampicin-resistant E. coli was applied to Fuji apples. Initial concentrations for the high-inoculation study were 7.4 ± 0.3 log10 CFU per apple and 3.4 ± 0.3 log10 CFU per apple for the low-inoculation study. Enumeration of E. coli was conducted at 0, 2, 10, 18, 34, 42, 58, 82, 106, and 154 h after inoculation. Results were analyzed using Tukey's honest significance difference test and a log-linear model. Log-linear, Weibull, and Biphasic models characterized E. coli die-off patterns for high and low inoculations. The application of evaporative overhead cooling water did not significantly influence E. coli survival on Fuji apples; inoculation level and sunlight exposure were significant factors in a log-linear model. E. coli decreased by 5.5 ± 1.3 and 3.3 ± 0.4 log10 CFU per apple for high and low inoculated apples, respectively, by 154 h. The Biphasic model best explained the die-off pattern for high and low-inoculated Fuji apples., Conclusions: Overhead evaporative cooling, a useful fruit quality practice, did not impact the survival of generic E. coli on Fuji apple surfaces. The significant impact of sunlight exposure and inoculation levels on die-off highlights the importance of ultraviolet radiation in risk reduction and the need for various inoculum concentrations in preharvest field studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: Domestic abuse (DA) and suicidal ideation (SI) are prevalent and often co-occur. Numerous practical and psychosocial barriers inhibit help-seeking, including accessibility and confidentiality concerns. Early intervention and referral are essential for both DA and SI. Pharmacies are accessible and may be perceived as a discreet venue for a DA and SI response service. There is a growing body of literature about the role of community pharmacy teams in suicide prevention and assisting domestic abuse victims globally. Whilst there have been some interventions in UK pharmacies to support domestic abuse victims and encouragement of staff training in suicide prevention, there is currently no commissioned service for DA and/or SI in pharmacies in the UK., Objective: To assess public acceptability of a novel response service in community pharmacy for people in danger from domestic abuse and/or suicidal ideation., Methods: Data collection consisted of an online public survey running for 6 weeks and qualitative interviews with pharmacy customers. Descriptive statistics were used to present the survey results and interviews were audio recorded, transcribed verbatim and then analysed using the Framework Analysis method and NVivo 11., Results: The majority of 501 survey respondents and all 12 customer interview participants were supportive of offering a response service for DA and/or SI in community pharmacy. Participants emphasised the need for appropriate staff training and support. They considered it an ethical and accessible approach and the majority said that they would recommend such a service to family or friends, and use it themselves if needed. However, awareness of the service was low and marketing materials were considered insufficiently clear., Conclusions: There is strong public support and acceptability for a response service covering both suicidal ideation and domestic abuse in community pharmacies. Further research is required to develop appropriate marketing materials., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Although guidelines exist for identifying mixtures, these measures often occur at the end-point of analysis and are protracted. To facilitate early mixture detection, we integrated a high-resolution melt (HRM) mixture screening assay into the qPCR step of the forensic workflow, producing the integrated Quantifiler TM Trio-HRM assay. The assay, when coupled with a prediction tool, allowed for 75.0% accurate identification of the contributor status of a sample (single source vs. mixture). To elucidate the limitations of the developed qPCR-HRM assay, developmental validation studies were conducted assessing the reproducibility and samples with varying DNA ratios, contributors, and quality. From this work, it was determined that the integrated Quantifiler TM Trio-HRM assay is capable of accurately identifying mixtures with up to five contributors and mixtures at ratios up to 1:100. Further, the optimal performance concentration range was found to be between 0.025 and 0.5 ng/µL. With these results, evidentiary-like DNA samples were then analyzed, resulting in 100.0% of the mixture samples being accurately identified; furthermore, every time a sample was predicted as a single source, it was true, giving confidence to any single-source calls. Overall, the integrated Quantifiler TM Trio-HRM assay has exhibited an enhanced ability to discern mixture samples from single-source samples at the qPCR stage under commonly observed conditions regardless of the contributor's sex.

Reducing disparities is vital for equitable access to precision treatments in cancer. Socioenvironmental factors are a major driver of disparities, but differences in genetic variation likely also contribute. The impact of genetic ancestry on prioritization of cancer targets in drug discovery pipelines has not been systematically explored due to the absence of pre-clinical data at the appropriate scale. Here, we analyze data from 611 genome-scale CRISPR/Cas9 viability experiments in human cell line models to identify ancestry-associated genetic dependencies essential for cell survival. Surprisingly, we find that most putative associations between ancestry and dependency arise from artifacts related to germline variants. Our analysis suggests that for 1.2-2.5% of guides, germline variants in sgRNA targeting sequences reduce cutting by the CRISPR/Cas9 nuclease, disproportionately affecting cell models derived from individuals of recent African descent. We propose three approaches to mitigate this experimental bias, enabling the scientific community to address these disparities., (© 2024. The Author(s).)

The introduction of AlphaFold 2 1 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design 2-6 . Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.2.3 7,8 . Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework., (© 2024. The Author(s).)

Using spin-echo nuclear magnetic resonance in the model transverse field Ising system TmVO_{4}, we show that low frequency quantum fluctuations at the quantum critical point have a very different effect on ^{51}V nuclear spins than classical low-frequency noise or fluctuations that arise at a finite temperature critical point. Spin echoes filter out the low-frequency classical noise but not the quantum fluctuations. This allows us to directly visualize the quantum critical fan and demonstrate the persistence of quantum fluctuations at the critical coupling strength in TmVO_{4} to high temperatures in an experiment that remains transparent to finite temperature classical phase transitions. These results show that while dynamical decoupling schemes can be quite effective in eliminating classical noise in a qubit, a quantum critical environment may lead to rapid entanglement and decoherence.

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D 3 formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D 3 1000 IU (STD1000), (2) micellar Vitamin D 3 1000 IU (LMD1000), (3) standard Vitamin D 3 2500 IU (STD2500), and (4) micellar Vitamin D 3 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5-60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D 3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D 3 concentrations than the STD1000 group (iAUC(30-60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH) 2 D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D 3 (LipoMicel ® ), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.

Objective Evaluating an artificial intelligence (AI) tool (AIATELLA, version 1.0; AIATELLA Oy, Helsinki, Finland) in interpreting cardiac magnetic resonance (CMR) imaging to produce measurements of the aortic root and valve by comparison of accuracy and efficiency with that of three National Health Service (NHS) cardiologists. Methods AI-derived aortic root and valve measurements were recorded alongside manual measurements from three experienced NHS consultant cardiologists (CCs) over three separate sites in the northeast part of the United Kingdom. The study utilised a comprehensive dataset of CMR images, with the intraclass correlation coefficient (ICC) being the primary measure of concordance between the AI and the cardiologist assessments. Patient imaging was anonymised and blinded at the point of transfer to a secure data server.  Results The study demonstrates a high level of concordance between AI assessment of the aortic root and valve with NHS cardiologists (ICC of 0.98). Notably, the AI delivered results in 2.6 seconds (+/- 0.532) compared to a mean of 334.5 seconds (+/- 61.9) by the cardiologists, a statistically significant improvement in efficiency without compromising accuracy. Conclusion AI's accuracy and speed of analysis suggest that it could be a valuable tool in cardiac diagnostics, addressing the challenges of time-consuming and variable clinician-based assessments. This research reinforces AI's role in optimising the patient journey and improving the efficiency of the diagnostic pathway., Competing Interests: AIATELLA has filed for a patent related to the method utilised by the AI tool to determine key landmarks and produce measurements from medical imaging. Patent application 20235369 - Finland - Machine Learning Based Landmark or Segment Detection From Medical Image Data.. Jack Parker is the CEO and co-founder of AIATELLA. He holds a majority shareholding in the company. James Coey is an unpaid advisor to AIATELLA., (Copyright © 2024, Parker et al.)

In contrast to traditional randomized controlled trials, embedded pragmatic clinical trials (ePCTs) are conducted within healthcare settings with real-world patient populations. ePCTs are intentionally designed to align with health system priorities leveraging existing healthcare system infrastructure and resources to ease intervention implementation and increase the likelihood that effective interventions translate into routine practice following the trial. The NIH Pragmatic Trials Collaboratory, funded by the National Institutes of Health (NIH), supports the conduct of large-scale ePCT Demonstration Projects that address major public health issues within healthcare systems. The Collaboratory has a unique opportunity to draw on the Demonstration Project experiences to generate lessons learned related to ePCTs and the dissemination and implementation of interventions tested in ePCTs. In this article, we use case studies from six completed Demonstration Projects to summarize the Collaboratory's experience with post-trial interpretation of results, and implications for sustainment (or de-implementation) of tested interventions. We highlight three key lessons learned. First, ineffective interventions (i.e., ePCT is null for the primary outcome) may be sustained if they have other measured benefits (e.g., secondary outcome or subgroup) or even perceived benefits (e.g., staff like the intervention). Second, effective interventions-even those solicited by the health system and/or designed with significant health system partner buy-in-may not be sustained if they require significant resources. Third, alignment with policy incentives is essential for achieving sustainment and scale-up of effective interventions. Our experiences point to several recommendations to aid in considering post-trial sustainment or de-implementation of interventions tested in ePCTs: (1) include secondary outcome measures that are salient to health system partners; (2) collect all appropriate data to allow for post hoc analysis of subgroups; (3) collect experience data from clinicians and staff; (4) engage policy-makers before starting the trial., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: The 2022 Australian winter was the first time that COVID-19, influenza and respiratory syncytial virus (RSV) were circulating in the population together, after two winters of physical distancing, quarantine and borders closed to international travellers. We developed a novel surveillance system to estimate the incidence of COVID-19, influenza and RSV in three regions of Queensland, Australia., Design: We implemented a longitudinal testing-based sentinel surveillance programme. Participants were provided with self-collection nasal swabs to be dropped off at a safe location at their workplace each week. Swabs were tested for SARS-CoV-2 by PCR. Symptomatic participants attended COVID-19 respiratory clinics to be tested by multiplex PCR for SARS-CoV-2, influenza A and B and RSV. Rapid antigen test (RAT) results reported by participants were included in the analysis., Setting and Participants: Between 4 April 2022 and 3 October 2022, 578 adults were recruited via their workplace. Due to rolling recruitment, withdrawals and completion due to positive COVID-19 results, the maximum number enrolled in any week was 423 people., Results: A total of 4290 tests were included. Participation rates varied across the period ranging from 25.9% to 72.1% of enrolled participants. The total positivity of COVID-19 was 3.3%, with few influenza or RSV cases detected. Widespread use of RAT may have resulted in few symptomatic participants attending respiratory clinics. The weekly positivity rate of SARS-CoV-2 detected during the programme correlated with the incidence of notified cases in the corresponding communities., Conclusion: This testing-based surveillance programme could estimate disease trends and be a useful tool in settings where testing is less common or accessible. Difficulties with recruitment meant the study was underpowered. The frontline sentinel nature of workplaces meant participants were not representative of the general population but were high-risk groups providing early warning of disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: gustatory ability is a marker of health not routinely tested in the medical practice. The current study wants to assess whether taste strips can be useful to monitor taste function from home., Methods: we performed simple sensory tests in lab setting vs. unassisted testing at home, and compared the results with self-reports ability to taste and smell. Using paper strips impregnated with sweet, bitter, salty, or sour tastants, and with two trigeminal stimuli (capsaicin, tannins) in high and low concentrations, we assessed gustatory and trigeminal function in 74 participants (47 women) in the lab, where paper strips were administered by an experimenter, and in 77 participants (59 women) at home, where they self-administered the test., Results: we found that high (but not low) concentration taste strips are correctly identified by vast majority of participants. On average, taste identification, intensity and pleasantness scores did not differ for the 8 taste strips, while identification of capsaicin was significantly better in the lab. Taste identification scores correlated with intensity ratings in both settings (r = 0.56, in the lab, r = 0.48, at home, p < 0.005). Self-rated taste ability correlated with self-rated smell ability (r = 0.68, and r = 0.39, p ≤ 0.005), but not with scores in the strips test., Conclusion: home testing with impregnated taste strips is feasible, and can be used for telemedical purposes., (© 2024. The Author(s).)

Background: RASopathies are a group of disorders characterized by pathogenic mutations in the Ras/mitogen-activated protein kinase (Ras/MAPK) signaling pathway. Distinct pathogenic variants in genes encoding proteins in the Ras/MAPK pathway cause Noonan syndrome (NS) and neurofibromatosis type 1 (NF1), which are associated with increased risk for autism spectrum disorder and attention-deficit/hyperactivity disorder., Methods: This study examined the effect of RASopathies (NS and NF1) on human neuroanatomy, specifically on surface area (SA), cortical thickness (CT), and subcortical volumes. Using vertex-based analysis for cortical measures and Desikan region of interest parcellation for subcortical volumes, we compared structural T1-weighted images of children with RASopathies (n = 91, mean age = 8.81 years, SD = 2.12) to those of sex- and age-matched typically developing children (n = 74, mean age = 9.07 years, SD = 1.77)., Results: Compared with typically developing children, RASopathies had convergent effects on SA and CT, exhibiting increased SA in the precentral gyrus, decreased SA in occipital regions, and thinner CT in the precentral gyrus. RASopathies exhibited divergent effects on subcortical volumes, with syndrome-specific influences from NS and NF1. Overall, children with NS showed decreased volumes in striatal and thalamic structures, and children with NF1 displayed increased volumes in the hippocampus, amygdala, and thalamus., Conclusions: Our study reveals the converging and diverging neuroanatomical effects of RASopathies on human neurodevelopment. The convergence of cortical effects on SA and CT indicates a shared influence of Ras/MAPK hyperactivation on the human brain. Therefore, considering these measures as objective outcome indicators for targeted treatments is imperative., (Published by Elsevier Inc.)

Sexual assault sample processing, despite recent funding and research efforts, remains time-consuming, labourious, and inefficient. These limitations, combined with the prevalence of sexual assaults, have prompted the need to develop a cheaper, quicker, and more robust method for separating victim and perpetrator contributions within sexual assault evidence so that analysts can keep pace with submissions and cases can be resolved in a timely manner. Thus, this study examined the use of a combined enzymatic and alkaline approach for differential cell lysis-with the goal of developing a quick, cheap, and more efficient DNA isolation method. Quantification results for this assay revealed that (72.0 ± 18.3)%, (15.8 ± 14.2)%, and (29.5 ±  23.7)% of total DNA were retained in sperm fractions for neat semen, neat vaginal, and semen-vaginal mixture eluates, respectively. Short tandem repeat (STR) analysis of mixture samples processed with this technique exhibited sperm fraction DNA profiles with mean male-to-female ratios of 1.74:1, which was a 3.01 ± 2.30-fold improvement in male-to-female ratios and led to the recovery of 5.90 ± 7.80 unshared male contributor alleles in sperm fractions that were otherwise undetected in unseparated controls. Overall, this study presented a modified differential lysis approach using prep GEM™ and sodium hydroxide treatments that can accomplish cell elution and fractional lysis within 25 min. Future studies should investigate alternative "non-sperm" cell lysis methods to enhance lysis efficiency and minimize the potential for inhibition, as well as the optimization and automation of this technique., Key Points: Traditional sexual assault sample processing methods are time-consuming and inefficient.This modified differential lysis method produces lysates with sufficient DNA yield and quality.A combined technique using enzymatic and alkaline lysis can accomplish fractional separation.Lysis with prep GEM and NaOH absent purification is compatible with downstream processes., (© The Author(s) 2024. Published by OUP on behalf of the Academy of Forensic Science.)

Germline pathogenic variants in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway are the molecular cause of RASopathies, a group of clinically overlapping genetic syndromes. RASopathies constitute a wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies in nearly all the major body systems. With increasing global recognition of these conditions, the 8th International RASopathies Symposium spotlighted global perspectives on clinical care and research, including strategies for building international collaborations and developing diverse patient cohorts in anticipation of interventional trials. This biannual meeting, organized by RASopathies Network, was held in a hybrid virtual/in-person format. The agenda featured emerging discoveries and case findings as well as progress in preclinical and therapeutic pipelines. Stakeholders including basic scientists, clinician-scientists, practitioners, industry representatives, patients, and family advocates gathered to discuss cutting edge science, recognize current gaps in knowledge, and hear from people with RASopathies about the experience of daily living. Presentations by RASopathy self-advocates and early-stage investigators were featured throughout the program to encourage a sustainable, diverse, long-term research and advocacy partnership focused on improving health and bringing treatments to people with RASopathies., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

With the awakening of female consciousness, women's participation in sports has gradually gained autonomy and agency. However, Chinese women still face numerous restrictions in combat sports, hindering the development of this industry. Based on years of practice and research experience in the field, we summarize some general and specific issues, such as stigmatization and the constraints of traditional Chinese thinking. These issues need attention and consideration in the pursuit of gender equality in sports in the future., 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., (© 2024 Li, Li, Li, Zhang, Wang, Green and Zhang.)

Background: In recent years, overdoses involving illicit cocaine, methamphetamine, and other stimulants have increased in the U.S. The unintentional consumption of stimulants containing illicit fentanyl is a major risk factor for overdoses, particularly in Massachusetts and Rhode Island. Understanding the drug use patterns and strategies used by people who use stimulants (PWUS) to prevent overdose is necessary to identify risk and protective factors for stimulant-involved overdoses. Mixed-methods research with people who distribute drugs (PWDD) can also provide critical information into the mechanisms through which fentanyl may enter the stimulant supply, and the testing of drug samples can further triangulate PWUS and PWDD perspectives regarding the potency and adulteration of the drug supply. These epidemiological methods can inform collaborative intervention development efforts with community leaders to identify feasible, acceptable, and scalable strategies to prevent fatal and non-fatal overdoses in high-risk communities., Methods: Our overall objective is to reduce stimulant and opioid-involved overdoses in regions disproportionately affected by the overdose epidemic. To meet this long-term objective, we employ a multi-pronged approach to identify risk and protective factors for unintentional stimulant and opioid-involved overdoses among PWUS, and use these findings to develop a package of locally tailored intervention strategies that can be swiftly implemented to prevent overdoses. Specifically, this study aims to [1] Carry out mixed-methods research with incarcerated and non-incarcerated people who use or distribute illicit stimulants to identify risk and protective factors for stimulant and opioid-involved overdoses; [2] Conduct drug checking to examine the presence and relative quantity of fentanyl and other adulterants in the stimulant supply; and [3] Convene a series of working groups with community stakeholders involved in primary and secondary overdose prevention in Massachusetts and Rhode Island to contextualize our mixed-methods findings and identify multilevel intervention strategies to prevent stimulant-involved overdoses., Discussion: Completion of this study will yield a rich understanding of the social epidemiology of stimulant and opioid-involved overdoses in addition to community-derived intervention strategies that can be readily implemented and scaled to prevent such overdoses in two states disproportionately impacted by the opioid and overdose crises: Massachusetts and Rhode Island., Competing Interests: Competing interests The authors declare that they have no competing interests.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G&#95;{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G&#95;{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Background: Turner syndrome (TS) and Noonan syndrome (NS) are distinct genetic conditions with highly similar physical and neurodevelopmental phenotypes. TS is caused by X chromosome absence, whereas NS results from genetic mutations activating the Ras-mitogen-activated protein kinase signaling pathway. Previous neuroimaging studies in individuals with TS and NS have shown neuroanatomical variations relative to typically developing individuals, a standard comparison group when initially examining a clinical group of interest. However, none of these studies included a second clinical comparison group, limiting their ability to identify syndrome-specific neuroanatomical phenotypes., Methods: In this study, we compared the behavioral and brain phenotypes of 37 girls with TS, 26 girls with NS, and 37 typically developing girls, all ages 5 to 12 years, using univariate and multivariate data-driven analyses., Results: We found divergent neuroanatomical phenotypes between groups, despite high behavioral similarities. Relative to the typically developing group, TS was associated with smaller whole-brain cortical surface area (p ≤ .0001), whereas NS was associated with smaller whole-brain cortical thickness (p = .013). TS was associated with larger subcortical volumes (left amygdala, p = .002; right hippocampus, p = .002), whereas NS was associated with smaller subcortical volumes (bilateral caudate, p ≤ .003; putamen, p < .001; pallidum, p < .001; right hippocampus, p = .015). Multivariate analyses also showed diverging brain phenotypes in terms of surface area and cortical thickness, with surface area outperforming cortical thickness at group separation., Conclusions: TS and NS have syndrome-specific brain phenotypes, despite their behavioral similarities. Our observations suggest that neuroanatomical phenotypes better reflect the different genetic etiologies of TS and NS and may be superior biomarkers relative to behavioral phenotypes., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic brought increases in economic shocks due to poor health and lost employment, which reduced economic well-being, especially in households with children. The American Rescue Plan Act of 2021 expanded Child Tax Credit (CTC) payments to include eligibility for the lowest income households, boosted benefit levels, and provided monthly advance payments to households with children. Using Census Household Pulse Survey respondent data from January 2021 to July 2022, we evaluated the association between these advance CTC monthly payments and food insufficiency among households with children experiencing health- or employment-related economic shocks (defined as missed work due to COVID-19/other illness or COVID-19-related employer closure/layoff/furlough). Using a triple difference design, we found that the advance CTC was associated with greater reductions in food insufficiency among households with children experiencing economic shocks both compared with households without children and with households with children not experiencing economic shocks. Permanently expanding the advance CTC could create resilience to economic shocks during disease outbreaks, climate disasters, and recessions., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

The AlphaFold Database Protein Structure Database (AlphaFold DB, https://alphafold.ebi.ac.uk) has significantly impacted structural biology by amassing over 214 million predicted protein structures, expanding from the initial 300k structures released in 2021. Enabled by the groundbreaking AlphaFold2 artificial intelligence (AI) system, the predictions archived in AlphaFold DB have been integrated into primary data resources such as PDB, UniProt, Ensembl, InterPro and MobiDB. Our manuscript details subsequent enhancements in data archiving, covering successive releases encompassing model organisms, global health proteomes, Swiss-Prot integration, and a host of curated protein datasets. We detail the data access mechanisms of AlphaFold DB, from direct file access via FTP to advanced queries using Google Cloud Public Datasets and the programmatic access endpoints of the database. We also discuss the improvements and services added since its initial release, including enhancements to the Predicted Aligned Error viewer, customisation options for the 3D viewer, and improvements in the search engine of AlphaFold DB., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Superapps (ie apps that integrate the features of multiple applications for a more convenient user experience) have become pervasive among Internet users. This case study examines a recent disruption to one such application: KakaoTalk - the most widely used messaging application in South Korea. Specifically, the case study examines a fire incident at the SK C&C data centre, which caused an extended outage for one of South Korea's leading tech companies - Kakao Corp. The review of this event reveals how ineffective disaster readiness resulted in inadequate fire response, leading to serious ripple effects across the data centre. During the outage, cyber-security threats rose. As a result of these disruptions, Kakao users turned to competitor apps, resulting in changing market dynamics. This case study highlights the unforeseen costs and socio-economic influences caused by such interruptions, highlighting the importance of holistic risk management strategies.

Background: Systemic mastocytosis (SM) is a rare and potentially severe hematologic disorder characterized by the clonal proliferation of mast cells (MCs) into various organs. The clinical manifestations of advanced SM are caused by the uncontrolled release of cytokines and vasoactive amines from MC and disease-induced organ dysfunction. Patients with SM typically present with symptoms such as flushing, pruritus, diarrhea, and headaches, but outcomes following active treatment have not been well characterized. In this study, the clinical characteristics, treatment patterns, and natural history of an SM patient cohort diagnosed and treated within a community hematology network in the United States is described., Methods: We identified 105 patients who were diagnosed and managed in one of 19 community hematology clinics up to an index date of 1 October 2022. Data collection included patient and disease characteristics, baseline biochemistry and hematology, SM diagnostic criteria being met, biomarkers tested, CD2 and/or CD25 expression in MCs as well as serum tryptase levels at presentation. Data abstraction also included supportive care drugs and anticancer therapy used, treatment response, reason for discontinuation, and overall survival by disease subtype., Results: A total of 105 SM patients were identified who met the inclusion criteria. The specific SM subtypes were indolent (47.6%), aggressive (9.5%), SM with an associated hematological neoplasm (19.0%), MC leukemia (1.9%), and subtype not documented (21.9%). Regardless of subtype, approximately 62% of patients did not receive SM-directed active therapy. Only 26% of patients with indolent systemic mastocytosis (ISM) received treatment compared to 65.6% with advanced subtypes. Relative to ISM cohort, the relative risk of death in patients with the advanced SM subtypes was approximately 15 times greater (hazard ratio = 15.0; 95% confidence interval: 3.3 to 66.5)., Conclusions: SM patients present with multiple underlying symptoms, within various disease subtypes that are difficult to diagnose in a timely manner. As a result, many patients do not receive active drug therapy for their disease. Therefore, greater disease awareness is required as well as new tools for earlier disease detection., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DP, KM, and TG are employees and shareholders of the sponsor (Blueprint Medicines Corporation).

Introduction: Immediate postpartum (IPP) Long Acting Reversible Contraception (LARC) is effective in reducing short birth spacing, which is highest among minoritized and younger women with lower socioeconomic status. The structural barrier of cost for pregnant people who desire IPP LARC insertion was alleviated in 2016 when New York State provided statewide reimbursement for Medicaid recipients., Methods: Analyses of existing electronic medical records (EMR) were conducted on women who received IPP LARC between 3/2/17 and 9/2/19 at two hospitals after a term delivery, defined as gestational age 37 0/7 weeks or greater. Descriptive and bivariate statistics, including chi-square tests and Fischer's exact tests, based on cell sizes, were calculated using SAS (version9.4)., Results: Prior to the study period, IPP LARC was not placed in these hospitals. After reimbursement policy changes, electronic medical record data identified 501 women with full term delivery and IPP LARC placed, of which the majority were single (82.8%), Black (49.1%), and had public insurance (Medicaid and Medicaid Managed Care) (79.2%)., Discussion: Removing structural economic barriers for people using public insurance may increase health equity in contraceptive access and choice., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: We investigated neuropsychiatric outcomes in children with Noonan syndrome and addressed limitations in previous research with a focus on prepubertal children, comparison to typically developing children, comprehensive neuropsychiatric evaluation, and controlling for overall cognitive abilities., Method: Forty-five children with Noonan syndrome (mean = 8 years 6 months, SD = 2 years 2 months; 29 females) and 40 typically developing children (mean = 8 years 9 months, SD = 2 years; 22 females) were evaluated with objective, parent-report, and psychiatric interview measures., Results: Children with Noonan syndrome demonstrated elevated symptoms across attention-deficit/hyperactivity disorder (ADHD) (attention, hyperactivity, and inhibition), autism spectrum disorder (ASD) (maintaining social relationships, behavioral rigidity, and sensory sensitivity), and oppositional defiant disorder (ODD) (aggression) symptom clusters relative to typically developing children (all p < 0.05). Group differences in nearly all parent-report measures were significant after accounting for variations in intellectual functioning, suggesting that increased neurodevelopmental symptoms are not simply driven by overall intelligence. Twenty out of 42 children with Noonan syndrome met criteria for ADHD, eight out of 42 for ODD, and 11 out of 43 demonstrated clinically significant symptoms seen in children with ASD., Interpretation: Children with Noonan syndrome are at increased risk for a range of ADHD, ASD, and ODD associated symptoms. A dimensional approach reveals significant ASD symptoms in Noonan syndrome that do not emerge when using the currently accepted categorical diagnostic approach., What This Paper Adds: Neuropsychiatric disorders occur in more than half of children with Noonan syndrome. Children with Noonan syndrome demonstrate highly variable neurodevelopmental symptom profiles. Children with Noonan syndrome display variable impairments in attention, hyperactivity, and inhibition. Specific social concerns include behavioral rigidity, transitions, and difficulties maintaining social relationships. Children with Noonan syndrome display variably elevated levels of aggression and emotional dysregulation., (© 2023 Mac Keith Press.)

Key Words: Breast cancer, mastectomy, breast conserving surgery, post-mastectomy reconstruction, older women, quality of life., 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., (© 2023 Published by Elsevier Ltd.)

The gustatory, olfactory, and trigeminal systems are anatomically separated. However, they interact cognitively to give rise to oral perception, which can significantly affect health and quality of life. We built a Supervised Learning (SL) regression model that, exploiting participants' features, was capable of automatically analyzing with high precision the self-ratings of oral sensitivity of healthy participants and patients with chemosensory loss, determining the contribution of its components: gustatory, olfactory, and trigeminal. CatBoost regressor provided predicted values of the self-rated oral sensitivity close to experimental values. Patients showed lower predicted values of oral sensitivity, lower scores for measured taste, spiciness, astringency, and smell sensitivity, higher BMI, and lower levels of well-being. CatBoost regressor defined the impact of the single components of oral perception in the two groups. The trigeminal component was the most significant, though astringency and spiciness provided similar contributions in controls, while astringency was most important in patients. Taste was more important in controls while smell was the least important in both groups. Identifying the significance of the oral perception components and the differences between the two groups provide important information to allow for more targeted examinations supporting both patients and healthcare professionals in clinical practice., (© 2023. Springer Nature Limited.)

Low-cost air quality monitors are growing in popularity among both researchers and community members to understand variability in pollutant concentrations. Several studies have produced calibration approaches for these sensors for ambient air. These calibrations have been shown to depend primarily on relative humidity, particle size distribution, and particle composition, which may be different in indoor environments. However, despite the fact that most people spend the majority of their time indoors, little is known about the accuracy of commonly used devices indoors. This stems from the fact that calibration data for sensors operating in indoor environments are rare. In this study, we sought to evaluate the accuracy of the raw data from PurpleAir fine particulate matter monitors and for published calibration approaches that vary in complexity, ranging from simply applying linear corrections to those requiring co-locating a filter sample for correction with a gravimetric concentration during a baseline visit. Our data includes PurpleAir devices that were co-located in each home with a gravimetric sample for 1-week periods (265 samples from 151 homes). Weekly-averaged gravimetric concentrations ranged between the limit of detection (3 μg/m 3 ) and 330 μg/m 3 . We found a strong correlation between the PurpleAir monitor and the gravimetric concentration (R>0.91) using internal calibrations provided by the manufacturer. However, the PurpleAir data substantially overestimated indoor concentrations compared to the gravimetric concentration (mean bias error ≥ 23.6 μg/m 3 using internal calibrations provided by the manufacturer). Calibrations based on ambient air data maintained high correlations (R ≥ 0.92) and substantially reduced bias (e.g. mean bias error = 10.1 μg/m 3 using a US-wide calibration approach). Using a gravimetric sample from a baseline visit to calibrate data for later visits led to an improvement over the internal calibrations, but performed worse than the simpler calibration approaches based on ambient air pollution data. Furthermore, calibrations based on ambient air pollution data performed best when weekly-averaged concentrations did not exceed 30 μg/m 3 , likely because the majority of the data used to train these models were below this concentration., Competing Interests: Declaration of interests 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.

WHAT IS KNOWN ON THE SUBJECT?: Major depressive disorder is the most prevalent of all mental illnesses. 10%-20% of patients with depression and 1% of the population overall have treatment-resistant depression (TRD). DBS is an emerging investigational treatment for TRD with documented clinical efficacy and safety. The framework of the recovery model includes both clinical and personal recovery. Personal recovery is a self-process in which hope, empowerment and optimism are embraced to overcome the impact of mental illness on one's sense of self. Although clinical and functional outcomes of DBS for TRD have been well documented in the previous studies, personal recovery as an outcome has been explored only in a handful of studies. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first qualitative study exploring personal recovery from DBS treatment specific to the target of subcallosal cingulate cortex in patients with TRD. Since the existing literature on personal recovery in DBS studies is limited, the contribution of this paper is crucial to this field. For individuals who responded to deep brain stimulation clinically, neither participants nor family believed it cured their depression, but rather there was a significant decrease in the severity of symptoms of depression. A holistic-oriented framework (that includes personal recovery) is significant for those individuals with TRD undergoing DBS. Personal and clinical recovery are two different constructs, and individuals may experience one or the other or both. The experience of participants who responded to deep brain stimulation recognized that the recovery from depression is a process of reconstructing self. This process involved a period of adjustment that evoked a deeper self-awareness, re-engagement with daily living and newfound gratitude in living. Individuals transitioned from an emotionally driven life to one where future goals were considered. Supportive relationships were instrumental in this process. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: A deep brain stimulation intervention for treatment-resistant depression offered individuals an opportunity for personal recovery where a reconstruction of self occurred. Personal recovery can be considered as an outcome in conjunction with clinical and functional outcomes in future DBS trials for TRD. The relevance of personal recovery in the prevention of relapses needs further investigation. To advocate for care and services that facilitate the process of recovery from depression, it is important to understand the personal dimensions and experience of recovery that may influence the process. To develop recovery-oriented interventions to help patients and families in recovery post-deep brain stimulation, further understanding of support and negotiating relationships during this life-altering experience is needed. ABSTRACT: Introduction Multiple trials of antidepressant treatments in patients with depression pose a major challenge to the mental health system. Deep brain stimulation (DBS) is an emerging and promising investigational treatment to reduce depressive symptoms in individuals with treatment-resistant depression (TRD). The clinical and functional outcomes of DBS for TRD have been well documented in previous studies; however, studies of personal recovery as an outcome of DBS specific to the target of subcallosal cingulate cortex in patients with TRD are limited. Aim To explore the processes of personal recovery in patients with treatment-resistant depression following subcallosal cingulate-deep brain stimulation. Method Participants were 18 patients with TRD who participated in the subcallosal cingulate (SCC)-DBS trial and 11 family members. They also participated in add-on individual cognitive behavioural therapy during the trial. A qualitative constructivist grounded theory approach was used to conceptualize the personal recovery process of patients and families. Results While every participant and their families' journey were unique following the deep brain stimulation intervention, a theoretical model of Balancing to Establish a Reconstructed Self emerged from the data. The themes underlying the model were (1) Balancing to Establish a Reconstructed Self: A Whole-Body Experience, (2) The Liminal Space in-between: Balancing with Cautious Optimism, (3) Hope: Transitioning from Emotion-Focussed Living to Goal-Oriented Planning and (4) Support: Negotiating Relationships. Discussion This is the first study examining recovery from patients' perspectives as an outcome of SCC-DBS intervention for TRD. The study shows that personal recovery is a gradual and continual process of reconstruction of the self, developing through supportive relationships. Clinical and personal recovery are two distinct constructs, and individuals may experience one or the other or both. Most patients who do respond clinically experience improvement in terms of having optimism and hope. Some patients, however, respond with significant symptom reduction but are not able to achieve personal recovery to experience joy or hope for improved quality of living. Implications for Practice Strategies for personal recovery for both patients and family need to be considered during and post deep brain stimulation intervention. Nurses working with these patients and families may benefit from education, training and support to assess and engage in conversations about their recovery process., (© 2023 The Authors. Journal of Psychiatric and Mental Health Nursing published by John Wiley & Sons Ltd.)

While the association of racial discrimination and internalizing symptoms in Black individuals is well established, we still have a limited understanding of mechanisms and contextual factors influencing this association, such as sleep and the family context. The present study examined sleep and fatigue as mediators underlying the relationship between racial discrimination and internalizing symptoms within Black adolescent-caregiver dyads. Using data from a larger survey study of risk and resilience in Black adolescents (M age = 14.36, 49.5% female) and their caregivers (M age = 39.25, 75.9% female), we used the Actor-Partner Interdependence Model extended Mediation (APIMeM) to test associations of racial discrimination, sleep factors, and internalizing symptoms among 179 dyads. Significant actor effects revealed that sleep disturbance and fatigue independently mediated the association of racial discrimination and internalizing symptoms among adolescents and caregivers. Additionally, partner effects were found, such that adolescents' experiences of discrimination were indirectly associated with their caregivers' internalizing symptoms via caregiver fatigue. No direct or indirect effects of caregiver experiences of discrimination on adolescent outcomes were found. The findings highlight the important role sleep and fatigue play in the link between racial discrimination and internalizing symptoms among Black adolescents and adults; and the role that the family context may play in this association. Mental health and sleep interventions for Black individuals should address the impact of racial discrimination on internalizing symptoms, with an emphasis on family-focused interventions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Per- and polyfluoroalkyl substances (PFAS) are a class of manufactured chemicals that have been extensively utilized worldwide. We hypothesize that the presence, uptake, and accumulation of PFAS in aquatic vegetation (AV) is dependent upon several factors, such as the physiochemical properties of PFAS and proximity to potential sources. In this study, AV was collected from eight locations in Florida to investigate the PFAS presence, accumulation, and spatiotemporal distribution. PFAS were detected in AV at all sampling locations, with a range from 0.18 to 55 ng/g sum (∑)PFAS. Individual PFAS and their concentrations varied by sampling location, time, and AV species. A total of 12 PFAS were identified, with the greatest concentrations measured in macroalgae. The average bioconcentration factor (BCF) among all samples was 1225, indicating high PFAS accumulation in AV from surface water. The highest concentrations, across all AV types, were recorded in the Indian River Lagoon (IRL), a location with a history of elevated PFAS burdens. The present study represents the first investigation of PFAS in naturally existing estuarine AV, filling an important gap on PFAS partitioning within the environment, as well as providing insights into exposure pathways for aquatic herbivores. Examining the presence, fate, and transport of these persistent chemicals in Florida's waterways is critical for understanding their effect on environmental, wildlife, and human health.

Background: Incontinence is common in hospitalised older adults but few studies report new incidence during or following hospitalisation., Objective: To describe prevalence and incidence of incontinence in older inpatients and associations with clinical outcomes., Design: Secondary analysis of prospectively collected data from consecutive consenting inpatients age 65 years and older on medical and surgical wards in four Australian public hospitals., Methods: Participants self-reported urinary and faecal incontinence 2 weeks prior to admission, at hospital discharge and 30 days after discharge as part of comprehensive assessment by a trained research assistant. Outcomes were length of stay, facility discharge, 30-day readmission and 6-month mortality., Results: Analysis included 970 participants (mean age 76.7 years, 48.9% female). Urinary and/or faecal incontinence was self-reported in 310/970 (32.0%, [95% confidence interval (CI) 29.0-35.0]) participants 2 weeks before admission, 201/834 (24.1% [95% CI 21.2-27.2]) at discharge and 193/776 (24.9% [95% CI 21.9-28.1]) 30 days after discharge. Continence patterns were dynamic within the peri-hospital period. Of participants without pre-hospital incontinence, 74/567 (13.1% [95% CI 10.4-16.1) reported incontinence at discharge and 85/537 (15.8% [95% CI 12.8-19.2]) reported incontinence at 30 days follow-up. Median hospital stay was longer in participants with pre-hospital incontinence (7 vs. 6 days, P = 0.02) even in adjusted analyses and pre-hospital incontinence was significantly associated with mortality in unadjusted but not adjusted analyses., Conclusion: Pre-hospital, hospital-acquired and new post-hospital incontinence are common in older inpatients. Better understanding of incontinence patterns may help target interventions to reduce this complication., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Interprofessional practice is increasingly cited as necessary in the delivery of high-quality nutrition and rehabilitation services. However, there is limited evidence available exploring the factors which influence interprofessional practice in subacute rehabilitation nutrition services. Our ethnographic study explored collaborative activities, influential factors and staff attitudes related to interprofessional practice in nutrition care. Fifty-eight hours of ethnographic field work were undertaken from September 2021-April 2022, across three subacute rehabilitation units, with a total of 165 patients, support persons and staff participating. Overall, 125 unique participants were observed and 77 were interviewed. We generated three themes through reflexive thematic analysis. First, the potential opportunities for interprofessional practice at mealtimes , as influenced by communication, role clarity and reciprocity. Second, hierarchy of nutrition roles and tasks impedes interprofessional practice, where the perceived lower importance of nutrition care to other clinical roles and physical therapies influences staff practice. Third, the mystery of nutrition care roles and systems in rehabilitation , which exposes gaps in the awareness of different team members regarding nutrition care roles and systems, hindering interprofessional practice. Our findings highlight the opportunity for embedded, innovative models of care and staff education to enhance interprofessional practice in nutrition and mealtimes.

In healthy humans, taste sensitivity varies widely, influencing food selection and nutritional status. Chemosensory loss has been associated with numerous pathological disorders and pharmacological interventions. Reliable psychophysical methods are crucial for analyzing the taste function during routine clinical assessment. However, in the daily clinical routine, they are often considered too time-consuming. We used a supervised learning (SL) regression method to analyze with high precision the overall taste statuses of healthy controls (HCs) and patients with chemosensory loss, and to characterize the combination of responses that would best predict the overall taste statuses of the subjects in the two groups. The random forest regressor model allowed us to achieve our objective. The analysis of the order of importance of each parameter and their impact on the prediction of the overall taste statuses of the subjects in the two groups showed that salty (low-concentration) and sour (high-concentration) stimuli specifically characterized healthy subjects, while bitter (high-concentration) and astringent (high-concentration) stimuli identified patients with chemosensory loss. Although the present results require confirmation in studies with larger samples, the identification of such distinctions should be of interest to the health system because they may justify the use of specific stimuli during the routine clinical assessments of taste function and thereby reduce time and cost commitments.

Black Soldier fly (Hermetia illucens) larval (BSFL) frass was examined for its nutrient nitrogen, phosphate and potassium (N:P205:K2O), phytohormone and biogenic amine content, its plant growth promoting activity, and screened to test the hypothesis that bacteria characteristic of the genus Enterococcus (present in the biome of decaying catering waste and the larval gut) are excreted by BSFL in their frass. Frass plant growth promoting activity was measured by comparing the growth of winter wheat berry (Triticum aestivum) in frass treated soil to that of untreated (control) soil. The N:P205:K2O percent dry matter average, biogenic amine and phytohormone content of frass was determined by standard soil analysis, HPLC and HPLC/GC-MS methodologies, respectively. All were at too low of concentrations to account for its plant growth promoting activity. Frass added to soil induced a 11% increase in aerial mass and shoot length in treated plants over controls. Numerous colonies of Enterococci growing out on BEA (bile-esculin-agar) plates were detected in frass collected directly from larvae confirming the hypothesis that viable Enteroccoci are passing from the larval gut into their frass. Since a number of rhizobacteria, including Enterococci, have previously been identified as part of the larval gut biome, the passage of Enterococci from the larval gut into frass in the face of only trace N:P205:K2O percent dry matter averages, biogenic amine and phytohormone content is consistent with the hypothesis that Enterococci exhibiting rhizobacterial activity have a role in conferring to frass its plant growth promoting activity., Competing Interests: The author declares that no competing interests exist., (Copyright: © 2023 Terrence Green. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The RASopathies are genetic syndromes associated with pathogenic variants causing dysregulation of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway, essential for brain development, and increased risk for neurodevelopmental disorders. Yet, the effects of most pathogenic variants on the human brain are unknown. We examined: (1) How Ras-MAPK activating variants of PTPN11/SOS1 protein-coding genes affect brain anatomy. (2) The relationship between PTPN11 gene expression levels and brain anatomy, and (3) The relevance of subcortical anatomy to attention and memory skills affected in the RASopathies. We collected structural brain MRI and cognitive-behavioral data from 40 pre-pubertal children with Noonan syndrome (NS), caused by PTPN11 (n = 30) or SOS1 (n = 10) variants (age 8.53 ± 2.15, 25 females), and compared them to 40 age- and sex-matched typically developing controls (9.24 ± 1.62, 27 females). We identified widespread effects of NS on cortical and subcortical volumes and on determinants of cortical gray matter volume, surface area (SA), and cortical thickness (CT). In NS, we observed smaller volumes of bilateral striatum, precentral gyri, and primary visual area (d's < -0.8), and extensive effects on SA (d's > |0.8|) and CT (d's > |0.5|) relative to controls. Further, SA effects were associated with increasing PTPN11 gene expression, most prominently in the temporal lobe. Lastly, PTPN11 variants disrupted normative relationships between the striatum and inhibition functioning. We provide evidence for the effects of Ras-MAPK pathogenic variants on striatal and cortical anatomy as well as links between PTPN11 gene expression and cortical SA increases, and striatal volume and inhibition skills. These findings provide essential translational information on the Ras-MAPK pathway's effect on human brain development and function., (© 2023. The Author(s).)

Per- and polyfluoroalkyl substances (PFAS) are a group of manufactured chemicals that are resistant to degradation and thus persistent in the environment. The presence, uptake, and accumulation of PFAS is dependent upon the physiochemical properties of the PFAS and matrix, as well as the environmental conditions since the time of release. The objective of this study was to measure the extent of PFAS contamination in surface water and sediment from nine vulnerable aquatic systems throughout Florida. PFAS were detected at all sampling locations with sediment exhibiting greater PFAS concentrations when compared to surface water. At most locations, elevated concentrations of PFAS were identified around areas of increased human activity, such as airports, military bases, and wastewater effluents. The results from the present study highlight the ubiquitous presence of PFAS in vital Florida waterways and filled an important gap in understanding the distribution of PFAS in dynamic, yet vulnerable, aquatic environments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John Bowden reports financial support was provided by US Environmental Protection Agency., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Turner syndrome (TS) is a common sex chromosome aneuploidy in females associated with various physical, cognitive, and socio-emotional phenotypes. However, few studies have examined TS-associated alterations in the development of cortical gray matter volume and the two components that comprise this measure-surface area and thickness. Moreover, the longitudinal direct (i.e., genetic) and indirect (i.e., hormonal) effects of X-monosomy on the brain are unclear. Brain structure was assessed in 61 girls with TS (11.3 ± 2.8 years) and 55 typically developing girls (10.8 ± 2.3 years) for up to 4 timepoints. Surface-based analyses of cortical gray matter volume, thickness, and surface area were conducted to examine the direct effects of X-monosomy present before pubertal onset and indirect hormonal effects of estrogen deficiency/X-monosomy emerging after pubertal onset. Longitudinal analyses revealed that, whereas typically developing girls exhibited normative declines in gray matter structure during adolescence, this pattern was reduced or inverted in TS. Further, girls with TS demonstrated smaller total surface area and larger average cortical thickness overall. Regionally, the TS group exhibited decreased volume and surface area in the pericalcarine, postcentral, and parietal regions relative to typically developing girls, as well as larger volume in the caudate, amygdala, and temporal lobe regions and increased thickness in parietal and temporal regions. Surface area alterations were predominant by age 8, while maturational differences in thickness emerged by age 10 or later. Taken together, these results suggest the involvement of both direct and indirect effects of X-chromosome haploinsufficiency on brain development in TS., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Tarsal joint abnormalities have been observed in aged male mice on a C57BL background. This joint disease consists of calcaneal displacement, inflammation, and proliferation of cartilage and connective tissue, that can progress to ankylosis of the joint. While tarsal pathology has been described previously in C57BL/6N substrains, as well as in STR/ort and B10.BR strain, no current literature describes this disease occurring in C57BL/6J mice. More importantly the behavioral features that may result from such a change to the joint have yet to be evaluated. This condition was observed in older male mice of the C57BL/6J lineage, around the age of 20 weeks or older, at a frequency of 1% of the population. To assess potential phenotypic sequela, this study sought to evaluate body weight, frailty assessment, home cage wheel running, dynamic weight bearing, and mechanical allodynia with and without the presence of pain relief with morphine. Overall mice with tarsal injuries had significantly higher frailty scores (p< 0.05) and weighed less (p<0.01) compared to unaffected mice. Affected mice had greater overall touch sensitivity (p<0.05) and they placed more weight on their forelimbs (p<0.01) compared to their hind limbs. Lastly, when housed with a running wheel, affected mice ran for a shorter length of time (p<0.01) but tended to run a greater distance within the time they did run (p<0.01) compared to unaffected mice. When tested just after being given morphine, the affected mice performed more similarly to unaffected mice, suggesting there is a pain sensation to this disease process. This highlights the importance of further characterizing inbred mouse mutations, as they may impact research programs or specific study goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hemocyanins are multimeric oxygen transport proteins present in the blood of arthropods and molluscs, containing up to 8 oxygen-binding functional units per monomer. In molluscs, hemocyanins are assembled in decamer 'building blocks' formed of 5 dimer 'plates', routinely forming didecamer or higher-order assemblies with d5 or c5 symmetry. Here we describe the cryoEM structures of the didecamer (20-mer) and tridecamer (30-mer) forms of a novel hemocyanin from the slipper limpet Crepidula fornicata (SLH) at 7.0 and 4.7 Å resolution respectively. We show that two decamers assemble in a 'tail-tail' configuration, forming a partially capped cylinder, with an additional decamer adding on in 'head-tail' configuration to make the tridecamer. Analysis of SLH samples shows substantial heterogeneity, suggesting the presence of many higher-order multimers including tetra- and pentadecamers, formed by successive addition of decamers in head-tail configuration. Retrieval of sequence data for a full-length isoform of SLH enabled the use of Alphafold to produce a molecular model of SLH, which indicated the formation of dimer slabs with high similarity to those found in keyhole limpet hemocyanin. The fit of the molecular model to the cryoEM density was excellent, showing an overall structure where the final two functional units of the subunit (FU-g and FU-h) form the partial cap at one end of the decamer, and permitting analysis of the subunit interfaces governing the assembly of tail-tail and head-tail decamer interactions as well as potential sites for N-glycosylation. Our work contributes to the understanding of higher-order oligomer formation in molluscan hemocyanins and demonstrates the utility of Alphafold for building accurate structural models of large oligomeric proteins., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pasqualetto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Penile prosthesis surgery (PPS) is a commonly used treatment for erectile dysfunction (ED), either as first-line therapy or in cases refractory to other treatment options. In patients with a urologic malignancy such as prostate cancer, surgical interventions like radical prostatectomy (RP) as well as non-surgical treatments such as radiation therapy can all induce ED. PPS as a treatment for ED has high satisfaction rates in the general population. Our aim was to compare sexual satisfaction in patients with prosthesis implantation for ED following RP versus ED following radiation therapy for prostate cancer., Methods: A retrospective chart review from our institutional database was conducted to identify patients who underwent PPS at our institution from 2011 to 2021. Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire data at least 6 months from implant operative date available was required for inclusion. Eligible patients were placed in one of two groups depending on etiology of ED-following RP or prostate cancer radiation therapy. To prevent crossover confounding; patients with history of pelvic radiation were excluded from the RP group and patients with history of RP were excluded from the radiation group. Data were obtained from 51 patients in the RP group and 32 patients in the radiation therapy group. Mean EDITS scores and additional survey questions were compared between the radiation and RP groups., Results: There was a significant difference in mean survey responses for 8 of the 11 questions in the EDITS questionnaire between the RP group and the radiation group. Additional survey questions administered also found RP patients reported significantly higher rate of satisfaction with size of penis post-operatively versus the radiation group., Conclusions: These preliminary findings, while requiring large-scale follow-up, suggest that there is greater sexual satisfaction and penile prosthesis device satisfaction in patients undergoing IPP placement following RP versus radiation therapy for prostate cancer. Use of validated questionnaires should continue to be utilized in quantifying device and sexual satisfaction following PPS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-600/coif). RW is a consultant for Boston Scientific and Teleflex. The other authors have no conflicts of interest to report., (2023 Translational Andrology and Urology. All rights reserved.)

Introduction: Observational studies suggest both low and high iodine intakes in pregnancy are associated with poorer neurodevelopmental outcomes in children. This raises concern that current universal iodine supplement recommendations for pregnant women in populations considered to be iodine sufficient may negatively impact child neurodevelopment. We aim to determine the effect of reducing iodine intake from supplements for women who have adequate iodine intake from food on the cognitive development of children at 24 months of age., Methods and Analysis: A multicentre, randomised, controlled, clinician, researcher and participant blinded trial with two parallel groups. Using a hybrid decentralised clinical trial model, 754 women (377 per group) less than 13 weeks' gestation with an iodine intake of ≥165 µg/day from food will be randomised to receive either a low iodine (20 µg/day) multivitamin and mineral supplement or an identical supplement containing 200) µg/day (amount commonly used in prenatal supplements in Australia), from enrolment until delivery. The primary outcome is the developmental quotient of infants at 24 months of age assessed with the Cognitive Scale of the Bayley Scales of Infant Development, fourth edition. Secondary outcomes include infant language and motor development; behavioural and emotional development; maternal and infant clinical outcomes and health service utilisation of children. Cognitive scores will be compared between groups using linear regression, with adjustment for location of enrolment and the treatment effect described as a mean difference with 95% CI., Ethics and Dissemination: Ethical approval has been granted from the Women's and Children's Health Network Research Ethics Committee (HREC/17/WCHN/187). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals., Trial Registration Number: NCT04586348., Competing Interests: Competing interests: SW serves as a consultant at InovoBiologic, AB, Canada., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Black men in the United States have higher hypertension (HTN) prevalence than other groups, largely due to adverse social determinants of health, including poor healthcare access. The Community-to-Clinic Linkage Implementation Program (CLIP) is effective for HTN screening in Black-owned barbershops. However, its effect on HTN prevention among Black men is untested. Here, we describe the rationale and study protocol for the development and testing of a barbershop facilitation (BF) strategy, with trained Community Health Workers, to implement and scale CLIP for HTN prevention in Black men., Methods: The study is part of the American Heart Association (AHA)-funded RESTORE (Addressing Social Determinants to Prevent Hypertension) Health Equity Research Network. The study is tri-phasic: (i) pre-implementation-qualitative examination of factors affecting adoption of CLIP and development of BF strategy, (ii) implementation-cluster randomized control trial to test the effectiveness of CLIP with and without BF. We will partner with 20 barbershops and enroll 420 Black men with elevated blood pressure (BP)/Stage 1 HTN (2017 ACC/AHA HTN guidelines). Outcomes include reduction in BP, rate of CLIP adoption and linkage to care, and incidence of Stage 2 HTN. The study time frame is 12 months, (iii) post-implementation-we will evaluate program sustainability (6 months post-trial conclusion) and cost-effectiveness (up to 10 years)., Conclusions: This study harnesses community-based resources to address HTN prevention in Black men, who are more adversely impacted by HTN than other groups. It has major policy relevance for health departments and other stakeholders to address HTN prevention in Black communities., Clinicaltrials.gov Identifier: NCT05447962., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)