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Background: Androgen deprivation therapy (ADT) improves outcomes in men undergoing definitive radiotherapy for prostate cancer but carries significant toxicities. Clinical parameters alone are insufficient to accurately identify patients who will derive the most benefit, highlighting the need for improved patient selection tools to minimize unnecessary exposure to ADT's side effects while ensuring optimal oncological outcomes. The ArteraAI Prostate Test, incorporating a multimodal artificial intelligence (MMAI)-driven digital histopathology-based biomarker, offers prognostic and predictive information to aid in this selection. However, its clinical utility in real-world settings has yet to be measured prospectively., Methods: This multicentre implementation trial aims to collect real-world data on the use of the previously validated Artera MMAI-driven prognostic and predictive biomarkers in men with intermediate-risk prostate cancer undergoing curative radiotherapy. The prognostic biomarker estimates the 10-year risk of metastasis, while the predictive biomarker determines the likely benefit from short-term ADT (ST-ADT). A total of 800 participants considering ST-ADT in conjunction with curative radiotherapy will be recruited from multiple Australian centers. Eligible patients with intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network, will be asked to participate. The primary endpoint is the percentage of patients for whom testing led to a change in the shared ST-ADT recommendation, analyzed using descriptive statistics and McNemar's test comparing recommendations before and after biomarker testing. Secondary endpoints include the impact on quality of life and 5-year disease control, assessed through linkage with the Prostate Cancer Outcomes Registry. The sample size will be re-evaluated at an interim analysis after 200 patients., Discussion: ASTuTE will determine the impact of a novel prognostic and predictive biomarker on shared decision-making in the short term, and both quality of life and disease control in the medium term. If the biomarker demonstrates a significant impact on treatment decisions, it could lead to more personalized treatment strategies for men with intermediate-risk prostate cancer, potentially reducing overtreatment and improving quality of life. A potential limitation is the variability in clinical practice across different centers inherent in real-world studies., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12623000713695p. Registered 5 July 2023., Competing Interests: Declarations. Ethics approval and consent to participate: Central ethical approval was obtained from St Vincent’s Human Research Ethics Committee (HREC 2023/ETH01630) in 2023. Local ethical and governance approval has been obtained from all participating sites. The study is being conducted in accordance with the Declaration of Helsinki, the National Health and Medical Research Council (NHMRC) National Statement on Ethical Conduct in Human Research 2007, and the NHMRC Australian Code for Responsible Conduct of Research. All participants are providing written informed consent. Consent for publication: Not applicable. Competing interests: Prof Tim Showalter is Chief Medical Officer of Artera®. The authors; EW, MN, MG, JdL, SR, MD, JMac, TL, BW, SS, MC, KH, and JMar are employed by GenesisCare, which has a commercial relationship with ArteraAI., (© 2025. The Author(s).)

Background: In response to the dual public health emergencies of COVID-19 and the overdose crisis, the Government of British Columbia (BC) introduced risk mitigation prescribing, or prescribed safer supply. In the context of colonialism and racism, Indigenous people are disproportionately impacted by substance use harms and experience significant barriers to receiving care, particularly those living in rural and remote communities. As part of a larger provincial evaluation, we sought to assess the implementation of risk mitigation prescribing as experienced by Indigenous people who use drugs (IPWUD) in Northern BC., Methods: We used the Consolidated Framework for Implementation Research and the First Nations Perspective on Health and Wellness as conceptual frameworks to guide the study. In partnership with people with lived/living experience, we conducted 20 qualitative interviews with IPWUD. Data were supplemented by four interviews with health planners and analyzed thematically., Results: Participants reported limited implementation of risk mitigation prescribing in Northern BC, with unique regional challenges and innovative facilitators to access. Analysis of supplementary health planner data was consistent with the experiences of IPWUD and together provided a comprehensive picture of implementation in Northern BC. Four themes emerged: 1) Northern socio-politico-cultural barriers to implementation (outer setting), 2) rural and remote healthcare delivery challenges (inner setting), 3) adaptability of risk mitigation prescribing on Northern wellness (intervention characteristics), and 4) Northern ingenuity, relationality and champions facilitating access (implementation process)., Conclusions: Implementation and access to risk mitigation prescribing in Northern BC was limited, with region-specific applicability challenges and a health service delivery model that was not able to sufficiently meet the unique service needs of IPWUD. Demonstrating Northern ingenuity, peer groups, harm reduction community champions, and telehealth services were identified as stopgap measures that promoted access and reduced inequitable implementation within the region., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier B.V.)

Evaluate patent ductus arteriosus (PDA) morphology changes in the preterm neonate undergoing transcatheter PDA closure (TCPC). We propose the type F ductus is associated with lower corrected gestational age (CGA) and improved TCPC outcomes. Retrospective review of premature neonates undergoing TCPC at a large volume institution from November 2020 to November 2023. Two independent cardiologists blindly reviewed angiograms to classify the PDA as one of the 6 published morphologies. Procedural characteristics and outcomes were compared for two cohorts of TCPC patients constituting the type F and the non-type F ductus; statistical significance set at p-value < 0.05. 104 TCPC neonates met inclusion criteria; these were categorized as type F (n = 44) and non-type F (n = 60) ductal morphology. Patients with type F ductal morphology was associated with African American race (p = 0.007), lower procedural/chronological age (p < 0.001), weight (p = 0.002), and CGA (p < 0.001). Procedural length was significantly shorter in the type F group (41 vs 57 min; p < 0.01). Unsuccessful TCPC (n = 2) and device embolization (n = 2) events all occurred in patients with a non-type F ductal morphology. The CGA cut off < 34 weeks represents a good predictor of having a type F ductus (sensitivity 0.93, specificity 0.67). Younger chronological and CGA are associated with type F ductal morphology. At this institution, a type F ductus was associated with a shorter TCPC procedure time and demonstrated a lower complication rate. This data may prompt consideration of earlier TCPC referral. However, determining ideal TCPC timing in premature neonates is multifactorial and requires a multidisciplinary review team., Competing Interests: Declarations. Conflict of interest: Dr. Ligon is a proctor and education consultant for Abbott Vascular, Inc.; Dr. Ligon is also a consultant for B. Braun Interventional Systems, Inc. No other authors have any financial relationships to disclose., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these 2 interventions., Objective: A systematic review and network meta-analysis was conducted to compare the efficacy and acceptability of these 2 interventions in treating MDD., Data Sources: Six databases and registry platforms for the clinical trial were systematically searched to identify the eligible double-blinded, randomized controlled trials published between 2015 and 2022., Data Exaction: Two authors selected independently the placebo-controlled trials of antidepressants and microbiota-targeted interventions (prebiotics, probiotics, and synbiotics) used for the treatment of MDD in adults (≥18 years old). Standardized mean differences (SMDs) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO no. CRD42020222305)., Results: Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. When all trials were considered, compared with placebo, SMDs of interventions ranged from -0.16 (95% credible interval: -0.30, -0.04) for venlafaxine to -0.81 (-1.06, -0.52) for escitalopram. Probiotics were superior to brexpiprazole (SMD [95% credible interval]: -0.42 [-0.68, -0.17]), cariprazine (-0.44 [-0.69, -0.24]), citalopram (-0.37 [-0.66, -0.07]), duloxetine (-0.26, [-0.51, -0.04]), desvenlafaxine (-0.38 [-0.63, -0.14]), ketamine (-0.32 [-0.66, -0.01]), venlafaxine (-0.47 [-0.73, -0.23]), vilazodone (-0.37 [-0.61, -0.12]), vortioxetine (-0.39 [-0.63, -0.15]), and placebo (-0.62 [-0.86, -0.42]), and were noninferior to other antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants., Conclusion: Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD., Systematic Review Registration: PROSPERO registration no. CRD42020222305., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Little is known of the epidemiology of musculoskeletal injuries (MSKIs) in US Air Force Special Warfare (AFSPECWAR) Tactical Air Control Party trainees. The purpose of this longitudinal retrospective cohort study was to (1) report the incidence and type of MSKI sustained by AFSPECWAR trainees during and up to 1 year following training, (2) identify factors associated with MSKI, and (3) develop and present the MSKI classification matrix used to identify and categorise injuries in this study., Methods: Trainees in the Tactical Air Control Party Apprentice Course between fiscal years 2010-2020 were included. Diagnosis codes were classified as MSKI or non-MSKI using a classification matrix. Incidence rates and incidence proportion for injury types and regions were calculated. Measures were compared for differences between those who did and did not sustain an MSKI during training. A Cox proportional hazards model was used to identify factors associated with MSKI., Results: Of the 3242 trainees, 1588 (49%) sustained an MSKI during training and the cohort sustained MSKIs at a rate of 16 MSKI per 100 person-months. Overuse/non-specific lower extremity injuries predominated. Differences were seen in some baseline measures between those who did and did not sustain an MSKI. Factors retained in the final Cox regression model were age, 1.5-mile run times and prior MSKI., Conclusion: Slower run times and higher age were associated with an increased likelihood of MSKI. Prior MSKI was the strongest predictor of MSKI during training. Trainees sustained MSKIs at a higher rate than graduates in their first year in the career field. The MSKI matrix was effective in identifying and categorising MSKI over a prolonged (12-year) surveillance period and could be useful for future injury surveillance efforts in the military or civilian settings. Findings from this study could inform future injury mitigation efforts in military training environments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The subfield of rural queer studies and the concept of lesbian earth encourage scholars to explore the significance of rural place, nature, and climate change in queer texts. Alison Bechdel's graphic memoir, Fun Home: A Family TragicComic , presents nature as a source of familial conflict, creativity, and mutual support and as under threat due to strip mining. The climate change novel, 2 Degrees, focuses intensely on the realities of climate change and lesbian relations with the earth. These two texts are drastically different, yet they both convey a lesbian earth sensibility, featuring main characters who practice an open, vulnerable, interdependent stance with themselves and the more-than-human world.

The presentation and investigation of a levopositioned caudal vena cava, a rare congenital vascular abnormality seen mainly in Bernese Mountain Dogs, which resulted in ureteral compression, hydronephrosis and hydroureter. Surgical transection, transposition and anastomosis were performed to reposition the circumcaval ureter. A 19-month-old male neutered Bernese Mountain Dog was presented with a 13-month history of vague signs including intermittent abdominal pain, inappetence and diarrhoea, which were poorly responsive to medical management. Abdominal ultrasound revealed left-sided hydronephrosis and hydroureter. Further investigation included abdominal computed tomography and pre- and post-intravenous iodinated contrast, which revealed a levopositioned caudal vena cava with associated ureteral displacement to a circumcaval position, resulting in ureteral compression and proximal dilation affecting both the proximal ureter and the left kidney. The patient was also found to have concomitant gall bladder agenesis. Surgery was performed to transect, transpose and anastomose the ureter in a normal anatomical position, and the patient made an excellent clinical recovery. All gastrointestinal signs resolved within 2 weeks of surgery and remained resolved 12 months later. Follow-up ultrasound and pyelography were performed at 4-month post-surgery, revealing a mild improvement in the hydronephrosis and hydroureter. Although rare, circumcaval ureter should be considered a differential in dogs presenting with hydroureter and hydronephrosis, especially Bernese Mountain Dogs., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Knowledge gaps about how the ocean melts Antarctica's ice shelves, borne from a lack of observations, lead to large uncertainties in sea level predictions. Using high-resolution maps of the underside of Dotson Ice Shelf, West Antarctica, we reveal the imprint that ice shelf basal melting leaves on the ice. Convection and intermittent warm water intrusions form widespread terraced features through slow melting in quiescent areas, while shear-driven turbulence rapidly melts smooth, eroded topographies in outflow areas, as well as enigmatic teardrop-shaped indentations that result from boundary-layer flow rotation. Full-thickness ice fractures, with bases modified by basal melting and convective processes, are observed throughout the area. This new wealth of processes, all active under a single ice shelf, must be considered to accurately predict future Antarctic ice shelf melt.

Purpose: Age of menopause has been associated with the risk of developing glaucoma; however, it is unclear if the onset of menopause is directly associated with the development of glaucoma. Our objective was to determine if there is an association between the age at diagnosis of menopause and glaucoma., Methods: This retrospective, case-only analysis was performed using the Veterans Affairs (VA) Corporate Data Warehouse of female veterans from 2000 to 2019. Women with both menopause and glaucoma diagnoses were matched based on covariates. The two matched cohorts were early menopause-early comparative (EM-EC; n = 1075) and late menopause-late comparative (LM-LC; n = 1050) women. We used a Pearson correlation to examine the linear relationship between age at diagnosis of menopause and glaucoma. Afterward, we used a multivariate linear regression model with age at diagnosis of glaucoma serving as the outcome variable to account for the covariates., Results: We found that EM women developed glaucoma 6.0 years (interquartile range [IQR], 5.1-6.5) earlier than the EC group (P < 0.001), and LM women developed glaucoma an average of 5.2 years (IQR, 4.8-5.7) later than the LC group (P < 0.001). There was a modest linear relationship between the age of menopause and glaucoma diagnoses in the EM-EC (r = 0.40) and LM-LC (r = 0.46) cohorts. In our multivariate analysis, age at diagnosis of menopause was the largest factor related to age at diagnosis of glaucoma while accounting for our covariates. Our models predicted a 0.67-year delay in age at diagnosis of glaucoma with each additional premenopausal year., Conclusions: This case-only analysis elucidates a temporal association between menopause and glaucoma, highlighting the need to characterize the role of menopause in the onset of glaucoma for women.

Purpose: Hormonal therapy (HT) has been suggested to lower the risk of developing glaucoma. Our goal was to investigate the association between HT use and the onset of glaucoma diagnosis in postmenopausal women., Methods: This retrospective case-only study included female veterans with open-angle glaucoma from VA records between 2000 to 2019. Propensity score matching was used to match HT (n = 1926) users to untreated (n = 1026) women on multiple covariates (e.g., age of menopause, BMI, blood pressure, antihypertensive medications, and a co-morbidity index). A simple linear regression was used to evaluate the impact of HT duration on the age of glaucoma diagnosis, and multivariate linear regression analysis was used to determine which factors contributed to the age at diagnosis of glaucoma., Results: We found a linear relationship between the age at diagnosis of glaucoma and menopause in women with (r = 0.54) and without HT (r = 0.57) use. HT users tended to have a later diagnosis of glaucoma. Our multivariate analysis found that 0-2 years, 2-5 years, and >5 years of HT use were associated with a 2.20 [confidence interval (CI), 1.64, 2.76], 3.74 [CI, 3.02, 4.46], and 4.51 [CI, 3.84, 5.18] years later diagnosis of glaucoma. An interaction (-0.009 [-0.015, -0.003]) was observed between HT duration and age of menopause diagnosis, with the impact of HT decreasing for later menopause ages., Conclusions: Longer duration of HT use was associated with a later diagnosis of glaucoma in postmenopausal women in this case-only analysis. The impact of HT may be modulated by menopausal age, although further study is needed. The findings support a protective role of estrogen in glaucoma pathogenesis.

Abstract: Neutrophil NETosis is a unique form of cell death, characterized by the release of decondensed chromatin and antimicrobial contents to the extracellular space, which is involved in inflammation and thrombosis. However, the role of NETosis in the pathogenesis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) and how a targeted therapy affects the accumulation of neutrophil extracellular traps (NETs) under flow remain unknown. Flow cytometry demonstrated that the percentage of neutrophils undergoing NETosis in whole blood from patients with iTTP on admission was significantly increased, with a concurrent decrease in the capacity of inducible NETosis by shigatoxin. After therapy, the percentage of H3Cit+MPO+ neutrophils was significantly reduced, with an improvement in inducible NETosis in these patients. Additionally, little to no NET and thrombus formation was detected underflow in the whole blood from patients with iTTP when platelet counts were very low, but the NET and thrombus formation was dramatically increased following therapy when platelet counts rose to ≥50 × 109/L or were restored to normal with donor platelets. Similarly, there was no thrombus or NET accumulation under flow in the whole blood from vwf-/- mice, but NET accumulation was significantly higher in Adamts13-/- mice than in wild-type mice. Finally, recombinant ADAMTS13 or caplacizumab (or anfibatide) prevented NET and thrombus formation under flow in whole blood from patients with iTTP or from Adamts13-/- mice. These results indicate that neutrophil NETosis and NET formation depend on platelets and von Willebrand factor (VWF) in iTTP, and a targeted therapy such as recombinant ADAMTS13 or caplacizumab may prevent NET and thrombus formation under flow in iTTP., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Isolation of an unusual organism, Achromobacter xylosoxidans , from 2 cardiac surgical patients on the same day prompted an investigation to search for cases and cause. An extensive review demonstrated a pseudo-outbreak related to practices to conserve laboratory saline due to short supply resulting from supply chain shortage from the coronavirus disease 2019 pandemic., Competing Interests: Mary Ellen Scales currently works as an independent infection prevention consultant with paid services to the Massachusetts Department of Public Health. Sarah Haessler served as a Society for Healthcare Epidemiology of American (SHEA) Board Member from 2020 to 2022., (© The Author(s) 2024.)

Whole-body physical exercise has been shown to promote retinal structure and function preservation in animal models of retinal degeneration. It is currently unknown how exercise modulates retinal inflammatory responses. In this study, we investigated cytokine alterations associated with retinal neuroprotection induced by voluntary running wheel exercise in a retinal degeneration mouse model of class B1 autosomal dominant retinitis pigmentosa, I307N Rho. I307N Rho mice undergo rod photoreceptor degeneration when exposed to bright light (induced). Our data show, active induced mice exhibited significant preservation of retinal and visual function compared to inactive induced mice after 4 weeks of exercise. Retinal cytokine expression revealed significant reductions of proinflammatory chemokines, keratinocyte-derived chemokine (KC) and interferon gamma inducible protein-10 (IP-10) expression in active groups compared to inactive groups. Through immunofluorescence, we found KC and IP-10 labeling localized to retinal vasculature marker, collagen IV. These data show that whole-body exercise lowers specific retinal cytokine expression associated with retinal vasculature. Future studies should determine whether suppression of inflammatory responses is requisite for exercise-induced retinal protection., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries. GWAS in 596,905 Million Veteran Program subjects identified 39 tinnitus loci, and identified genes related to neuronal synapses and cochlear structural support. Applying state-of-the-art analytic tools, we confirm a large number of shared variants, but also a distinct genetic architecture of tinnitus, with higher polygenicity and large proportion of variants not shared with hearing difficulty. Tissue-expression analysis for tinnitus infers broad enrichment across most brain tissues, in contrast to hearing difficulty. Finally, tinnitus is not only correlated with hearing loss, but also with a spectrum of psychiatric disorders, providing potential new avenues for treatment. This study establishes tinnitus as a distinct disorder separate from hearing difficulties., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Computerised hexapod-assisted orthopaedic surgery (CHAOS) is a method by which complex multiplanar, multilevel deformity can be corrected with a high degree of accuracy utilising minimally invasive techniques within a single operative event. This study's aim was to report the reliability, accuracy and magnitude of correction achieved, alongside patient-reported outcomes and risk factors for complications when using the CHAOS technique throughout the lower limb., Materials and Methods: Retrospective review of medical records and radiographs for consecutive patients who underwent CHAOS for lower limb deformity correction at a tertiary centre between 2012 and 2020., Results: There were 70 cases in 56 patients, with the site of surgery being the femur in 48 cases, proximal tibia in 17 and distal tibia in 5 cases. Multiplanar correction was performed in 43 cases, and multilevel osteotomy was undertaken in 23 cases. Fixation was undertaken with intramedullary nailing (IMN) in 49 cases and locked plates in 21.The maximum corrections were 40° rotation, 20° coronal angulation, 51° sagittal angulation and 62-mm mechanical axis deviation (MAD). Deformity correction was mechanically satisfactory in all patients bar one who was undercorrected requiring revision. The mean patient global impression of change (PGIC) score was 6.2 out of 7.Overall complication rate was 12/70 (17%). Complications from femoral surgery included two nonunions, one case of undercorrection, one case of stiffness, one muscle hernia and one pulmonary embolism. Complications from tibial surgery were one compartment syndrome, one pseudoaneurysm of the anterior tibial artery requiring stenting, one transient neurapraxia of the common peroneal nerve, one locking plate fatigue failure, one seroma and one superficial wound infection., Conclusion: Computerised hexapod-assisted orthopaedic surgery can be used for accurate correction of complex multilevel and multiplanar deformities of both the femur and tibia. The risk profile appears to differ between femoral and tibial surgeries, and also to that of traditional circular frame correction. Patients remain highly satisfied with both the functional and symptomatic outcomes., How to Cite This Article: French JMR, Filer J, Hogan K, et al . Computer Hexapod-assisted Orthopaedic Surgery for the Correction of Multiplanar Deformities throughout the Lower Limb. Strategies Trauma Limb Reconstr 2024;19(1):9-14., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2024; The Author(s).)

Objectives: Responsive neurostimulation (RNS) is a relatively recent addition to the epilepsy surgery armory, gaining FDA approval in 2013 for use in adults with intractable focal epilepsy. Data for the use of RNS system in patients less than 18 years of age is limited. We aim to determine the safety and feasibility of RNS in children with refractory epilepsy., Methods: A retrospective chart review was conducted for all patients who underwent RNS implantation at an urban tertiary children's hospital. Demographics of the patients were obtained, including age at the time of implant, MRI findings, seizure onset zone identification, and RNS targets., Results: Out of a fourteen patient cohort, one patient had a post-operative complication of infection at surgical site requiring explantation. Thirteen out of 14 patients had immediate post-operative head imaging that was negative for hemorrhage, infarction, or skull fracture; one patient did not undergo head imaging. No patients reported a worsening clinical seizure frequency at a 6-month follow up visit. In the subset of patients who were implanted with RNS and did not undergo concurrent resections, there was a statistically significant reduction in the average number of long episodes at the most recent visit when compared to the 1-month post-operative visit (p = 0.0268)., Conclusions: RNS is a feasible and safe option for children as young as six years with refractory epilepsy when appropriate seizure focus identification has been performed with stereo CT and stereo EEG evaluations, and can be used in conjunction with other surgical epilepsy treatment modalities. Two canister RNS placement is achievable for patients with a broad epileptogenic network or multifocal seizure onset zones., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Despite the investment of public resources to fight staggering suicide rates among veterans, we know little about how veterans and service members in crisis communicate suicidal ideations, and what interventions they are willing to receive. We aim to identify communication and suicide intervention preferences of veterans and service members in times of crisis. Descriptive statistics were used to explore veterans communication of suicidal ideations. While 89.9% of participants indicated they were willing to speak to someone when having thoughts of suicide, less than 26% of participants indicated they were willing to bring up their thoughts with a crisis line or veterans organization. Rather, they indicate that family members (62.2%) and military friends (51.1%) would be their primary outreach. Logistic regression was used to determine whether or not preferred interventions varied by participant demographic characteristics. While the majority of participants indicated they were willing to allow intervention (88.6%), no one method was accepted by the majority of the population. The most accepted means of communication was to proactively contact a friend or family member about general life struggles (32.6%) or suicide-specific concerns (27.5%). Many participants were open to receiving resources (42.0%), suicide-specific mental health treatment (36.3%), and some sort of lethal means safety intervention (19.1%-26.4%). The age, marital status, and veterans status of participants significantly impacted what interventions they were willing to allow. We discuss the implications of these findings and the need for evidence-based, multimodal interventions in order to assist veterans in need., 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., (Copyright © 2023 Beatty, Richardson, Batten, Weintraub, Hogan and Hotle.)

Conventional dendritic cells (cDCs) are antigen-presenting cells (APCs) that play a central role in linking innate and adaptive immunity. cDCs have been well described in a number of different mammalian species, but remain poorly characterised in the chicken. In this study, we use previously described chicken cDC specific reagents, a novel gene-edited chicken line and single-cell RNA sequencing (scRNAseq) to characterise chicken splenic cDCs. In contrast to mammals, scRNAseq analysis indicates that the chicken spleen contains a single, chemokine receptor XCR1 expressing, cDC subset. By sexual maturity the XCR1 + cDC population is the most abundant mononuclear phagocyte cell subset in the chicken spleen. scRNAseq analysis revealed substantial heterogeneity within the chicken splenic XCR1 + cDC population. Immature MHC class II (MHCII) LOW XCR1 + cDCs expressed a range of viral resistance genes. Maturation to MHCII HIGH XCR1 + cDCs was associated with reduced expression of anti-viral gene expression and increased expression of genes related to antigen presentation via the MHCII and cross-presentation pathways. To visualise and transiently ablate chicken XCR1 + cDCs in situ , we generated XCR1 -iCaspase9-RFP chickens using a CRISPR-Cas9 knockin transgenesis approach to precisely edit the XCR1 locus, replacing the XCR1 coding region with genes for a fluorescent protein (TagRFP), and inducible Caspase 9. After inducible ablation, the chicken spleen is initially repopulated by immature CD1.1 + XCR1 + cDCs. XCR1 + cDCs are abundant in the splenic red pulp, in close association with CD8 + T-cells. Knockout of XCR1 prevented this clustering of cDCs with CD8 + T-cells. Taken together these data indicate a conserved role for chicken and mammalian XCR1 + cDCs in driving CD8 + T-cells responses., 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 © 2023 Wu, Shih, Macdonald, Meunier, Hogan, Chintoan-Uta, Gilhooley, Hu, Beltran, Henderson, Sang, Stevens, McGrew and Balic.)

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Bacterial adhesion is the first step in the formation of surface biofilms. The number of bacteria that bind to a surface from the solution depends on how many bacteria can reach the surface (bacterial transport) and the strength of interactions between bacterial adhesins and surface receptors (adhesivity). By using microfluidic channels and video microscopy as well as computational simulations, we investigated how the interplay between bacterial transport and adhesivity affects the number of the common human pathogen Escherichia coli that bind to heterogeneous surfaces with different receptor densities. We determined that gravitational sedimentation causes bacteria to concentrate at the lower surface over time as fluid moves over a non-adhesive region, so bacteria preferentially adhere to adhesive regions on the lower, inflow-proximal areas that are downstream of non-adhesive regions within the entered compartments. Also, initial bacterial attachment to an adhesive region of a heterogeneous lower surface may be inhibited by shear due to mass transport effects alone rather than shear forces per se, because higher shear washes out the sedimented bacteria. We also provide a conceptual framework and theory that predict the impact of sedimentation on adhesion between and within adhesive regions in flow, where bacteria would likely bind both in vitro and in vivo, and how to normalize the bacterial binding level under experimental set-ups based on the flow compartment configuration.

A 13-year-old female spayed border collie cross presented for pericardial effusion, arrhythmia, and a suspected cardiac mass. Echocardiogram revealed severe thickening and hypokinesis of the interventricular septum with a heterogenous, cavitated myocardium, concerning for neoplasia. Electrocardiogram revealed predominantly accelerated idioventricular rhythm with frequent periods of nonsustained ventricular tachycardia. Occasional prolonged PR intervals terminating in an aberrantly conducted QRS complex were present. These beats were postulated to represent either first-degree atrioventricular block with aberrant QRS conduction or atrioventricular dissociation. Cytology of the pericardial effusion revealed atypical, suspected neoplastic, mast cells. The patient was euthanized, and postmortem examination confirmed full-thickness infiltration of the interventricular septum by a mast cell tumor, with metastasis to the tracheobronchial lymph node and spleen. Given the anatomic location of the mass, the observed atrioventricular nodal conduction delay may represent neoplastic infiltration of the atrioventricular node. Neoplastic infiltration of the ventricle was suspected to cause the accelerated idioventricular rhythm and ventricular tachycardia. To the authors' knowledge, this is the first reported case of a primary cardiac mast cell tumor causing arrhythmia and pericardial effusion in a dog., Competing Interests: Conflict of Interest Statement The authors do not have any conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We describe 33 cases of myxoid pseudotumor involving the renal sinus from 31 patients. Patients included 21 men and 10 women, ages 30 to 95 years. Twenty-seven cases (82%) had an associated malignancy, including urothelial carcinoma of the renal pelvis (22 cases), clear cell renal cell carcinoma (3 cases), urothelial carcinoma of the bladder (1 case), and poorly differentiated carcinoma of uncertain lineage (1 case). The remaining 6 (18%) had no associated malignancy and included 3 nephrectomies for ureteral stricture, 2 ureteropelvic junction repairs, and 1 resection of a "periureteral mass" (subsequently shown to be myxoid pseudotumor). Myxoid pseudotumor was identified by preoperative computed tomography imaging in 2 patients (6%) and identified by the gross dissector in 9 cases (27%). The mean size was 14 mm (range: 5 to 38 mm). All cases had an admixture of adipocytes, myxoid stromal matrix, variable collagenization, and a hypocellular population of bland spindled and stellate stromal cells. No multilobated atypical stromal cells were present. Clinical follow-up was available for 28 patients (90%), ranging from 1 to 132 months (mean: 24.6 mo). No patients had adverse events related to the myxoid pseudotumor. Myxoid pseudotumor of the renal sinus is often associated with a variety of adjacent neoplastic and non-neoplastic conditions and may present as a mass lesion detectable by imaging and/or gross inspection. Awareness of this benign process is important to avoid confusion with a neoplasm, especially liposarcoma., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Group A Streptococcus is a common cause of pharyngitis, scarlet fever, glomerulonephritis, and various skin infections. However, there have only been a few reports of Group A Streptococcus (GAS) associated with infective endocarditis. We present a case of a 31-year-old male who presented to the hospital with a few days of weakness and myalgias after recently receiving treatment with azithromycin for GAS pharyngitis as an outpatient. The patient was admitted to the intensive care unit in septic shock from Group A beta-hemolytic Streptococcus bacteremia and acute hypoxic respiratory failure. He was found to have new severe aortic insufficiency from infective endocarditis. He underwent urgent partial aortic valve annuloplasty reconstruction and incision and drainage of root abscess with intraoperative cultures growing gram positive cocci consistent with GAS. The majority of cases of infective endocarditis are caused by Staphylococcus aureus , virdians group Streptococci and Streptococcus gallolyticus , while Streptococcus pneumoniae and Streptococcus pyogenes have the lowest prevalence of infective endocarditis. Penicillin remains the first line treatment for GAS pharyngitis. However, in cases of severe penicillin allergy, macrolides should be avoided given the increasing rate of macrolide resistance GAS strains. This case emphasizes the importance of using beta-lactams as first line therapy for GAS pharyngitis to avoid harmful complications and infection recurrence., Competing Interests: All authors declare no conflicting interests., (© 2023 The Authors.)

Background: Despite multiple studies suggesting that low 25(OH)D-vitamin levels are associated with worse outcomes in critically ill individuals, attempts to mitigate the outcomes by fixed dose enteral supplementation unguided by baseline or target blood levels have been unsuccessful. Since a single measurement of 25(OH)D may not optimally reflect an individual's vitamin D status, we studied the plasma concentration of different vitamin D metabolites and their recovery during and following resolution of acute critical illness., Methods: A prospective observational study including patients 18 years and older admitted to a mixed medical-surgical ICU in Reykjavik, Iceland, located at a high-northern altitude (64° N). Vitamin D metabolites were measured at three timepoints; On admission (S1), 3-5 days following admission (S2) and after recovery from acute illness (median 178 days) (S3). Concentrations of total 25(OH)D-vitamin, cholecalciferol (D 3 ), total 24,25(OH)D-vitamin, vitamin D binding protein (VDBP) were measured with LC-tandem mass spectrometry (LC-MS/MS) and free 25-(OH)D was measured with enzyme-linked immunosorbent assay., Results: Most individuals were vitamin D deficient when assessed during critical illness, with 25(OH)D-vitamin levels under 30 ng/ml for 37/40 individuals at timepoint S1 and 34/38 at S2. After recovery, 18/30 patients were deficient at S3. Levels of all vitamin D metabolites measured were low during critical illness but rose substantially following resolution of acute illness. No strong correlation was found between markers of acute illness severity or duration and resolution of vitamin D metabolites in the interval between acute illness and recovery., Conclusions: In critically ill patients, levels of multiple vitamin D metabolites are low but substantial recovery occurs following resolution of acute illness. It is unclear whether a single metabolite is sufficient to assess vitamin D status of critically ill patients and guide potential supplementation., (© 2022 Acta Anaesthesiologica Scandinavica Foundation.)

Background and Objectives: Spinal muscular atrophy (SMA) was added to the Recommended Uniform Screening Panel in July 2018 largely on the basis of the availability and efficacy of newly approved disease-modifying therapies. New York State (NYS) started universal newborn screening for SMA in October 2018. The authors report the findings from the first 3 years of screening., Methods: Statewide neonatal screening was conducted using DNA extracted from dried blood spots using a real-time quantitative PCR assay. Retrospective follow-up data were collected from 9 referral centers across the state on 34 infants., Results: In the first 3 years since statewide implementation, nearly 650,000 infants have been screened for SMA. Thirty-four babies screened positive and were referred to a neuromuscular specialty care center. The incidence remains lower than previously predicted. The majority (94%), including all infants with 2-3 copies of survival motor neuron ( SMN) 2, have received treatment. Among treated infants, the overwhelming majority (94%; 30/32) have received gene replacement. All infants in this cohort with 3 copies of SMN2 are clinically asymptomatic posttreatment based on early clinical follow-up data. Infants with 2 copies of SMN2 are more variable in their outcomes. Electrodiagnostic outcomes data obtained from a subgroup of patients (n = 11) demonstrated either improvement or no change in compound muscle action potential (CMAP) amplitude at last clinical follow-up compared with pretreatment baseline. Most infants were treated before 6 weeks of age (median = 34.5 days of life; range 11-180 days). Delays and barriers to treatment identified by treating clinicians followed 2 broad themes: medical and nonmedical. Medical delays most commonly reported were the presence of AAV9 antibodies and elevated troponin I levels. Nonmedical barriers included delays in obtaining insurance and insurance policies regarding specific treatment modalities., Discussion: The findings from the NYS cohort of newborn screen-identified infants are consistent with other reports of improved outcomes from early diagnosis and treatment. Additional biomarkers of motor neuron health including EMG can potentially be helpful in detecting preclinical decline., (© 2022 American Academy of Neurology.)

This paper provides insights into how 17 community-based organizations (CBOs) recruited, trained, and retained educators in pregnancy prevention program implementations for underserved adolescents in different areas of the United States. The paper also highlights problems and potential solutions associated with these practices. The study adopted a qualitative descriptive framework. We conducted 41 interviews with leaders and educators of CBOs and conducted qualitative content analysis of the interview data integrating deductive and inductive coding approaches. We found that a commonly emphasized recruitment and selection challenge was finding qualified candidates for short-term project-based employment. Interviewees highlighted limitations of curriculum training in preparing novice educators for program implementation and shared their strategies to overcome these limitations. Post-onboarding professional development opportunities were available for long-term educators, but not for short-term project-based educators. Educators reported receiving sufficient support from their organizations and coworkers to perform their jobs and maintain their well-being. Although none of the educators desired to leave their roles, they shared potential reasons for turnover, such as project-based employment and a desire to explore different career paths. We align the study findings with best practices proposed in the adolescent health education and human resources literatures and present a set of recommendations. Researchers interested in adolescent pregnancy prevention program implementation and organizations that plan to implement programs can benefit from the findings and recommendations presented in this article., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Balca Alaybek reports financial support was provided by Health and Human Services, Office of the Assistant Secretary for Health., (© 2022 The MITRE Corporation.)

Microbiology courses are often designed as either a lecture class with a laboratory component or a seminar-style class. Each type of course provides students with unique learning opportunities. Lab courses allow students to perform simple experiments that relate to fundamental concepts taught in the corresponding lectures, while seminar courses challenge students to read and discuss primary literature. Microbiology courses offering a combination of seminar-style discussions and laboratory procedures are rare. Our goal in the "Microbial Diversity and Pathogenesis" undergraduate course is to integrate experiences of a seminar class with those of a discovery-driven lab course, thereby strengthening students' learning experiences through diversified didactic approaches. In the first half of the course, students read and discuss published peer-reviewed articles that cover major topics in both basic and applied microbiology, including antibiotic resistance, pathogenesis, and biotechnology applications. Complementing this primary literature, students perform microbiology experiments related to the topics covered in the readings. The assigned readings, discussions, and experiments provide a foundation in the second half of the course for inquiry-based exploratory research using student-designed transposon screens and selections. The course culminates in each student drafting a hypothesis-driven research proposal based on their literature review, their learned experimental techniques, and the preliminary data generated as a class. Through such first-hand experimental experience, students gain fundamental lab skills that are applicable beyond the realm of microbiology, such as sterile technique and learning how to support conclusions with scientific evidence. We observed a tremendous synergy between the seminar and lab aspects of our course. This unique didactic experience allows students to understand and connect primary literature to their experiments, while the discovery-driven aspect of this approach fosters active engagement of students with scientific research., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Egan et al.)

Beryllium has been considered a potential alternative to magnesium as a p-type dopant in GaN, but attempts to produce conductive p-GaN:Be have not been successful. Photoluminescence studies have repeatedly shown Be to have an acceptor level shallower than that of Mg, but deep Be defects and other compensating defects render most GaN:Be materials n-type or semi-insulating at best. Previous reports use molecular beam epitaxy or ion implantation to dope GaN with Be, almost exclusively. Due to the high toxicity of Be organometallics, reports of GaN:Be by metal-organic chemical vapor deposition (MOCVD) have been largely absent. Here, we report a systematic study of growth of GaN:Be by MOCVD. All doped samples show the established UV band and yellow luminescence signature of GaN:Be, and growth conditions resulting in high-quality GaN with stable Be incorporation were established. Our results show that the MOCVD growth technique allows for Be incorporation pathways that have not been possible with previous growth methodologies and is highly promising in achieving p-type conductivity in GaN:Be., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

From the inception of the Special Warfare Training Wing in fiscal year 2019 through 2021, 753 male, enlisted candidates attempted at least 1 Assessment and Selection and did not self-eliminate (i.e., quit). Candidates were on average 23 years of age. During candidates' first attempt, 356 (47.3%) individuals experienced a musculoskeletal (MSK) injury. Among the injuries, the most frequent type was nonspecific (n=334/356; 93.8%), and the most common anatomic region of injury was the lower extremity (n=255/356; 71.6%). When included in a multivariable model, older age, slower run times on initial fitness tests, and prior nonspecific injury were associated with both any injury and specifically lower extremity MSK injury.

The visual system uses ON and OFF pathways to signal luminance increments and decrements. Increasing evidence suggests that ON and OFF pathways have different signaling properties and serve specialized visual functions. However, it is still unclear the contribution of ON and OFF pathways to visual behavior. Therefore, we examined the effects on optomotor response and the retinal dopamine system in nob mice with ON pathway dysfunction and Vsx1 -/- mice with partial OFF pathway dysfunction. Spatial frequency and contrast sensitivity thresholds were determined, and values were compared to age-matched wild-type controls. Retinas were collected immediately after visual testing to measure levels of dopamine and its metabolite, DOPAC. At 4 weeks of age, we found that nob mice had significantly reduced spatial frequency (19%) and contrast sensitivity (60%) thresholds compared to wild-type mice. Vsx1 -/- mice also exhibited reductions in optomotor responses (3% in spatial frequency; 18% in contrast sensitivity) at 4 weeks, although these changes were significantly smaller than those found in nob mice. Furthermore, nob mice had significantly lower DOPAC levels (53%) and dopamine turnover (41%) compared to controls while Vsx1 -/- mice displayed a transient increase in DOPAC levels at 4 weeks of age (55%). Our results show that dysfunction of ON pathways leads to reductions in contrast sensitivity, spatial frequency threshold, and retinal dopamine turnover whereas partial loss of the OFF pathway has minimal effect. We conclude that ON pathways play a critical role in visual reflexes and retinal dopamine signaling, highlighting a potential association for future investigations., (Published by Elsevier Ltd.)

The Southern Ocean surrounding Antarctica is a region that is key to a range of climatic and oceanographic processes with worldwide effects, and is characterised by high biological productivity and biodiversity. Since 2013, the International Bathymetric Chart of the Southern Ocean (IBCSO) has represented the most comprehensive compilation of bathymetry for the Southern Ocean south of 60°S. Recently, the IBCSO Project has combined its efforts with the Nippon Foundation - GEBCO Seabed 2030 Project supporting the goal of mapping the world's oceans by 2030. New datasets initiated a second version of IBCSO (IBCSO v2). This version extends to 50°S (covering approximately 2.4 times the area of seafloor of the previous version) including the gateways of the Antarctic Circumpolar Current and the Antarctic circumpolar frontal systems. Due to increased (multibeam) data coverage, IBCSO v2 significantly improves the overall representation of the Southern Ocean seafloor and resolves many submarine landforms in more detail. This makes IBCSO v2 the most authoritative seafloor map of the area south of 50°S., (© 2022. The Author(s).)

The global prevalence of myopia, or nearsightedness, has increased at an alarming rate over the last few decades. An eye is myopic if incoming light focuses prior to reaching the retinal photoreceptors, which indicates a mismatch in its shape and optical power. This mismatch commonly results from excessive axial elongation. Important drivers of the myopia epidemic include environmental factors, genetic factors, and their interactions, e.g., genetic factors influencing the effects of environmental factors. One factor often hypothesized to be a driver of the myopia epidemic is environmental light, which has changed drastically and rapidly on a global scale. In support of this, it is well established that eye size is regulated by a homeostatic process that incorporates visual cues (emmetropization). This process allows the eye to detect and minimize refractive errors quite accurately and locally over time by modulating the rate of elongation of the eye via remodeling its outermost coat, the sclera. Critically, emmetropization is not dependent on post-retinal processing. Thus, visual cues appear to influence axial elongation through a retina-to-sclera, or retinoscleral, signaling cascade, capable of transmitting information from the innermost layer of the eye to the outermost layer. Despite significant global research interest, the specifics of retinoscleral signaling pathways remain elusive. While a few pharmacological treatments have proven to be effective in slowing axial elongation (most notably topical atropine), the mechanisms behind these treatments are still not fully understood. Additionally, several retinal neuromodulators, neurotransmitters, and other small molecules have been found to influence axial length and/or refractive error or be influenced by myopigenic cues, yet little progress has been made explaining how the signal that originates in the retina crosses the highly vascular choroid to affect the sclera. Here, we compile and synthesize the evidence surrounding three of the major candidate pathways receiving significant research attention - dopamine, retinoic acid, and adenosine. All three candidates have both correlational and causal evidence backing their involvement in axial elongation and have been implicated by multiple independent research groups across diverse species. Two hypothesized mechanisms are presented for how a retina-originating signal crosses the choroid - via 1) all-trans retinoic acid or 2) choroidal blood flow influencing scleral oxygenation. Evidence of crosstalk between the pathways is discussed in the context of these two mechanisms., (Published by Elsevier Ltd.)

Developing multifunctional nanostructures that promote bone repair while fighting infection is highly desirable in bone regenerative therapies. Previous efforts have focused on achieving one property or another by altering the chemical makeup of nanostructures or using growth factors or antibiotics. We present nanostructures with several simultaneous functional attributes including positive effects of strontium on bone formation and prevention of osteoclast differentiation along with incorporation of antimicrobial peptides (AMP) to prevent infection. To form these multifunctional nanostructures, mesoporous calcium silicate (CaMSN) was modified with high levels of strontium. For this, CaMSNs were either partially substituted (20 wt% Ca) or completely replaced with strontium (Sr) to form Sr-CaMSN or SrMSN. The mesoporous nature of these bioactive silicate nanostructures rendered a configuration for substantial AMP loading as well as their effective delivery. The physico-chemical and structural characterization of synthesized MSNs confirmed the mesoporous nature of the synthesized MSNs and their total surface area, pore size, pore volume and SBF-mediated bioactivity remained unaltered with the incorporation of Sr. However, biological evaluation confirmed that synthesized SrMSN upregulated osteogenic differentiation of mesenchymal stromal cells and significantly downregulated osteoclast differentiation. Also, the AMP-loaded MSNs prevented formation and growth of methicillin resistant Staphylococcus aureus (MRSA) biofilms. Thus, high Sr-containing AMP-loaded SrMSNs may combat MRSA-associated infection while promoting bone regeneration. The controlled availability of therapeutic Sr and AMP release as SrMSN degrade enables its potential application in bone tissue regeneration., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Blood-based Alzheimer's disease (AD) biomarkers show promise, but pre-analytical protocol differences may pose problems. We examined seven AD blood biomarkers (amyloid beta [ A β ] 42 , A β 40 , phosphorylated tau [ p - ta u 181 , total tau [t-tau], neurofilament light chain [NfL], A β 42 40 , and p - ta u 181 A β 42 ) in three collection tube types (ethylenediaminetetraacetic acid [EDTA] plasma, heparin plasma, serum)., Methods: Plasma and serum were obtained from cerebrospinal fluid or amyloid positron emission tomography-positive and -negative participants (N = 38) in the Wisconsin Registry for Alzheimer's Prevention. We modeled AD biomarker values observed in EDTA plasma versus heparin plasma and serum, and assessed correspondence with brain amyloidosis., Results: Results suggested bias due to tube type, but crosswalks are possible for some analytes, with excellent model fit for NfL ( R 2 = 0.94), adequate for amyloid ( R 2 = 0.40-0.69), and weaker for t-tau ( R 2 = 0.04-0.42) and p - ta u 181 ( R 2 = 0.22-0.29). Brain amyloidosis differentiated several measures, especially EDTA plasma pTa u 181 A β 42 ( d = 1.29)., Discussion: AD biomarker concentrations vary by tube type. However, correlations for some biomarkers support harmonization across types, suggesting cautious optimism for use in banked blood., Competing Interests: SCJ serves on an advisory board for Roche Diagnostics. KB has served as a consultant, on advisory boards, or on data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, all unrelated to the present study. HZ has served on scientific advisory boards for Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, and CogRx; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, and Biogen; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). BB has received precursors and tracers from Avid Radiopharmaceuticals. CEG is a member of the Executive Board for the Alzheimer's and Dementia Alliance of Wisconsin, and receives support from the Alzheimer's Association for travel to AAIC, for which she is on the Scientific Program Committee. GK is a full‐time employee of Roche Diagnostics GmbH. IS is a full‐time employee and shareholder of Roche Diagnostics International Ltd. Authors KH, CE, OO, TB, CVH, RK, LH, and EMJ have no disclosures., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Objectives: The objective of this study was to verify the safety of policosanol supplementation for domestic cats. The effects of raw and encapsulated policosanol were compared with positive (L-carnitine) and negative (no supplementation) controls on outcomes of complete blood count, serum biochemistry, energy expenditure, respiratory quotient and physical activity in healthy young adult cats., Methods: The study was a replicated 4 × 4 complete Latin square design. Eight cats (four castrated males, four spayed females; mean age 3.0 ± 1.0 years; mean weight 4.36 ± 1.08 kg; mean body condition score 5.4 ± 1.4) were blocked by sex and body weight then randomized to treatment groups: raw policosanol (10 mg/kg body weight), encapsulated policosanol (50 mg/kg body weight), L-carnitine (200 mg/kg body weight) or no supplementation. Treatments were supplemented to a basal diet for 28 days with a 1-week washout between periods. Food was distributed equally between two offerings to ensure complete supplement consumption (first offering) and measure consumption time (second offering). Blood collection (lipid profile, complete blood count, serum biochemistry) and indirect calorimetry (energy expenditure, respiratory quotient) were conducted at days 0, 14 and 28 of each period. Activity monitors were worn 7 days prior to indirect calorimetry and blood collection. Data were analyzed using a repeated measures mixed model (SAS, v.9.4)., Results: Food intake and body weight were similar among treatments. There was no effect of treatment on lipid profile, serum biochemistry, activity, energy expenditure or respiratory quotient ( P >0.05); however, time to consume a second meal was greatest in cats fed raw policosanol ( P <0.05)., Conclusions and Relevance: These data suggest that policosanol is safe for feline consumption. Further studies with cats demonstrating cardiometabolic risk factors are warranted to confirm whether policosanol therapy is an efficacious treatment for hyperlipidemia and obesity.

Objective: To replicate a previously defined behavioral procedure to acclimate adult cats to temporary restriction in indirect calorimetry chambers and measure energy expenditure and respiratory quotient changes during acclimation., Animals: 8 healthy adult cats (4 spayed females, and 4 neutered males; mean ± SEM age, 2.5 ± 1.5 years; mean body weight, 4.8 ± 1.8 kg)., Procedures: Cats underwent a 13-week incremental acclimation procedure whereby cats were acclimated to the chambers in their home environment (weeks 1 to 3), to the study room (weeks 4 to 6), and to increasing lengths of restriction within their home environment (weeks 7 to 8) and the chambers (weeks 9 to 13). Cat stress score, respiratory rate, fearfulness (assessed with a novel object test), energy expenditure, and respiratory quotient were measured. Data were analyzed by use of a repeated-measures mixed model., Results: Stress, based on cat stress scores, fearfulness, and respiration, peaked at weeks 4, 9, and 10 but returned to baseline levels by week 11. Energy expenditure and respiratory quotient peaked at weeks 10 and 11, respectively, but were reduced significantly by weeks 11 and 13, respectively. All cats returned to baseline by the end of the study and were deemed fully acclimated., Clinical Relevance: Changes in perceived stress level, energy expenditure, and respiratory quotient at various stages of the acclimation procedure suggest that stress should be considered a significant variable in energy balance measurements when indirect calorimetry is used in cats. An incremental acclimation procedure should therefore be used to prepare cats for the temporary space restriction necessary for indirect calorimetry studies.

Competing Interests: Conflicts of Interest: The authors disclose no conflicts.

The role of maternal investment in avian offspring has considerable life history implications on production traits and therefore potential for the poultry industry. A first generation (G 1 ) of Japanese quail (Coturnix japonica) were bred from a 2 × 2 factorial design. Parents were fed either a control or methyl-enhanced (HiBET) diet, and their eggs were treated with a vehicle or corticosterone injection during day 5 of incubation. A subset of G 1 birds were subjected to an open field trial (OFT) and capture-restraint stress protocol. Significant effects of HiBET diet were found on parental egg and liver weights, G 1 hatch, liver and female reproductive tract weights, egg productivity, latency to leave the OFT central zone, male baseline 11-dehydrocorticosterone, and female androstenedione plasma concentrations. In ovo treatment significantly affected latency to return to the OFT, male baseline testosterone and androstenedione, and change in androstenedione plasma concentration. Diet by treatment interactions were significant for G 1 liver weight and male baseline plasma concentrations of corticosterone. These novel findings suggest significant positive effects on reproduction, growth, precociousness, and hypothalamic-pituitary-adrenal axis function from enhanced methyl diets, and are important in understanding how in ovo stressors (representing maternal stress), affect the first offspring generation., (© 2021. The Author(s).)

The global and national response to the COVID-19 pandemic has been inadequate due to a collective lack of preparation and a shortage of available tools for responding to a large-scale pandemic. By applying lessons learned to create better preventative methods and speedier interventions, the harm of a future pandemic may be dramatically reduced. One potential measure is the widespread use of contact tracing apps. While such apps were designed to combat the COVID-19 pandemic, the time scale in which these apps were deployed proved a significant barrier to efficacy. Many companies and governments sprinted to deploy contact tracing apps that were not properly vetted for performance, privacy, or security issues. The hasty development of incomplete contact tracing apps undermined public trust and negatively influenced perceptions of app efficacy. As a result, many of these apps had poor voluntary public uptake, which greatly decreased the apps' efficacy. Now, with lessons learned from this pandemic, groups can better design and test apps in preparation for the future. In this viewpoint, we outline common strategies employed for contact tracing apps, detail the successes and shortcomings of several prominent apps, and describe lessons learned that may be used to shape effective contact tracing apps for the present and future. Future app designers can keep these lessons in mind to create a version that is suitable for their local culture, especially with regard to local attitudes toward privacy-utility tradeoffs during public health crises., (©Katie Hogan, Briana Macedo, Venkata Macha, Arko Barman, Xiaoqian Jiang. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 19.07.2021.)

Ruxolitinib is a JAK2/JAK1 inhibitor that blocks the inflammatory JAK-STAT signaling pathway. Ruxolitinib has been demonstrated to be effective in the treatment of steroid-resistant acute graft-versus-host disease (GVHD). Ruxolitinib's effect on inflammatory cells of hematopoietic origin is known. However, its effect on nonhematopoietic cell types with immune-modulating and antigen-presenting cell competency plausibly involved in pathogenesis of GVHD has not been explored. Mesenchymal stromal cells (MSCs) are CD45 - nonhematopoietic cells of the bone marrow with immune modulatory functions in vivo. MSCs' immunobiology largely depends on their responsiveness to IFNγ. We aimed to define the effect of ruxolitinib on the immunobiology of MSCs that are modulated by IFNγ. Human bone marrow derived MSCs, peripheral blood mononuclear cells (PBMCs), and primary bone marrow aspirates were analyzed for their sensitivity to ruxolitinib-mediated blocking of IFNγ-induced STAT-1 phosphorylation and downstream effector molecules, utilizing Western blot, flow cytometry, secretome analysis, and phosflow techniques. IFNγ-induced cytostatic effects on MSCs are reversed by ruxolitinib. Ruxolitinib inhibits IFNγ and secretome of activated peripheral PBMC-induced STAT-1 phosphorylation on human bone marrow derived MSCs. In addition, ruxolitinib inhibits IFNγ-induced pro-GVHD pathways on MSCs, which includes HLAABC(MHCI), HLADR(MHCII), CX3CL1, and CCL2. IFNγ-induced immunosuppressive molecules IDO and PDL-1 were also inhibited by ruxolitinib on MSCs. Comparative analysis with PBMCs has demonstrated that MSCs are as equal as to HLADR + PBMC populations in responding to ruxolitinib-mediated inhibition of IFNγ-induced STAT-1 phosphorylation. Ex vivo analysis of human marrow aspirates has demonstrated that ruxolitinib blocks IFNγ-induced STAT-1 phosphorylation in CD45 +/- HLADR +/- populations at different levels, which is depending on their sensitivity to IFNγ responsiveness. These results inform the hypothesis that ruxolitinib's immune-modulatory effects in vivo may pharmacologically involve marrow and tissue-resident MSCs. Ruxolitinib affects the immunobiology of MSCs equivalent to professional HLADR + antigen presenting cells, which collectively mitigate GVHD., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Thwaites Glacier is the most rapidly changing outlet of the West Antarctic Ice Sheet and adds large uncertainty to 21st century sea-level rise predictions. Here, we present the first direct observations of ocean temperature, salinity, and oxygen beneath Thwaites Ice Shelf front, collected by an autonomous underwater vehicle. On the basis of these data, pathways and modification of water flowing into the cavity are identified. Deep water underneath the central ice shelf derives from a previously underestimated eastern branch of warm water entering the cavity from Pine Island Bay. Inflow of warm and outflow of melt-enriched waters are identified in two seafloor troughs to the north. Spatial property gradients highlight a previously unknown convergence zone in one trough, where different water masses meet and mix. Our observations show warm water impinging from all sides on pinning points critical to ice-shelf stability, a scenario that may lead to unpinning and retreat., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The results from this study demonstrate the potential of an AlGaN/GaN high electron mobility transistor sensor for the detection of reactive and transient biological molecules such as hydrogen peroxide. A boronate-based fluorescent probe was used with this device to detect the presence of micromolar levels of hydrogen peroxide typically associated with intracellular processes. The real-time electrical response of the high electron mobility transistor sensor showed a gradual decrease in the two-dimensional electron gas current as the reaction proceeded over time. A corresponding increase in the emission intensity was measured from the fluorescent probe with the progression of the reaction. The fluorescence from the boronate probe was used as an indicator to confirm the detection of hydrogen peroxide. These results demonstrate the dynamic measurement capability of AlGaN/GaN high electron mobility transistor sensors in monitoring real-time reactions of reactive oxygen species such as hydrogen peroxide.

Objective: The purpose of this study was to identify cardiac biomarkers of disordered eating as a function of diagnostic subtype as assessed via self-report inventory., Method: Mean heart rate (HR), systolic and diastolic blood pressure, mean R wave amplitude (mV), mean T wave amplitude (mV), QTc interval (sec), Tpeak-Tend interval prolongation (sec), QTc interval prolongation (sec), QRS prolongation (sec), and spectral indicators of cardiac dysfunction (LF/HF spectral ratio, HF spectral power) were assessed via electrocardiography among women with no eating disorder symptoms (n = 32), subclinical eating disorder symptoms (n = 92), anorexia nervosa (n = 7), bulimia nervosa (n = 89), binge eating disorder (BED: n = 20), and other specified feeding and eating disorders (OSFED: n = 19)., Results: MANOVA results showed statistically significant group differences. Follow-up tests revealed significantly decreased mean R wave amplitude among participants with self-indicated clinical (bulimia nervosa, binge eating disorder) and subclinical forms of disordered eating compared to asymptomatic controls., Discussion: Results suggest decreased mean R wave amplitude is a promising cardiac biomarker of disordered eating., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The differential diagnosis of caecal mass is broad and the inclusion of appendiceal pathologies is an important element., Case Report: We report a 37-year-old woman with recurrent right iliac fossa pain. Computed tomography scan revealed a caecal mass suggesting complete inversion or intussusception of the appendix, which was confirmed by pathologic microscopic examination. This case report discusses appendiceal intussusception with emphasis on diagnosis and treatment options., Discussion: Appendiceal intussusception is a rare entity and the complete type typically presents as a polypoid lesion located at the appendiceal orifice in the caecum. It is imperative to include this entity in the differential diagnosis of caecal mass, especially during colonoscopy, as the removal of this polypoid lesion can result in a devastating caecal perforation or haemorrhage.

Trisomy 16 is the most common autosomal trisomy found in spontaneous abortions with mosaic versions seen in survivors. However, surviving children have multiple congenital defects and are at risk of growth and developmental delay. We report an additional case of mosaic trisomy 16 diagnosed by amniocentesis and confirmed after birth. Our patient is the first documented case of living mosaic trisomy 16 with the malformation constellation of lung agenesis, left pulmonary artery agenesis, congenital heart defects, and ipsilateral radial ray and limb abnormalities, expanding the phenotype of this rare condition. Additionally, this individual's unique combination of lung and cardiac defects caused morbidities that were challenging to manage and complicated family counseling as well., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

The effects of feeding frequency on postprandial response of circulating appetite-regulating hormones, insulin, glucose and amino acids, and on physical activity, energy expenditure, and respiratory quotient were studied in healthy adult cats. Two experiments were designed as a 2 x 3 replicated incomplete Latin square design. Eight cats, with an average body weight (BW) of 4.34 kg ± 0.04 and body condition score (BCS) of 5.4 ± 1.4 (9 point scale), were fed isocaloric amounts of a commercial adult maintenance canned cat food either once (0800 h) or four times daily (0800 h, 1130 h, 1500 h, 1830 h). Study 1 consisted of three 21-d periods. On day 14, two fasted and 11 postprandial blood samples were collected over 24 hours to measure plasma concentrations of ghrelin, GLP-1, GIP, leptin, PYY, insulin and amino acids, and whole blood glucose. Physical activity was monitored from day 15 to 21 of each period. In Study 2 indirect calorimetry was performed on the last day of each period. Body weight was measured weekly and feed intake recorded daily in both experiments. No effect of feeding regimen on BW was detected. Cats eating four times daily had lesser plasma concentrations of GIP and GLP-1 (P<0.05) and tended to have lesser plasma PYY concentrations (P<0.1). Plasma leptin and whole blood glucose concentrations did not differ between regimens (P>0.1). Cats fed once daily had a greater postprandial plasma amino acid response, and greater plasma ghrelin and insulin concentrations (P<0.05). Physical activity was greater in cats fed four times (P<0.05), though energy expenditure was similar between treatments at fasting and in postprandial phases. Finally, cats eating one meal had a lower fasting respiratory quotient (P<0.05). Overall, these data indicate that feeding once a day may be a beneficial feeding management strategy for indoor cats to promote satiation and lean body mass., Competing Interests: The authors declare no conflicts of interest. A.V. is the Royal Canin Veterinary Diets Endowed Chair in Canine and Feline Clinical Nutrition at the Ontario Veterinary College. This does not alter our adherence to PLOS ONE policies on sharing data and materials.