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Frontal bone fractures are amongst the most common facial fractures and surgical management, which has traditionally involved access via a coronal flap, can result in unsightly scarring, alopecia, paraesthesia, facial nerve weakness and temporal hollowing. Alternative approaches include use of endoscopically-assisted surgery, often through the eyebrow, which minimises the risk of unsightly scarring but may also sacrifice access in the process. In this technical note, we discuss a surgical technique for open reduction and internal fixation of fractures of the bone overlying the frontal sinus and supra-orbital rim, which the authors have not found in the literature, which involves the making of a "zig-zag" incision through the eyebrow in a trichophytic manner which reduces the risk of unsightly scarring whilst simultaneously allowing for sufficient surgical access to the fracture site., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Pannexin 1 (PANX1) is upregulated in many cancers, where its activity and signalling promote tumorigenic properties. Here, we report a novel ∼25 kDa isoform of human PANX1 (hPANX1-25K) which lacks the N-terminus and was detected in several human cancer cell lines including melanoma, osteosarcoma, breast cancer and glioblastoma multiforme. This isoform was increased upon hPANX1 CRISPR/Cas9 deletion targeting the first exon near M1, suggesting a potential alternative translation initiation (ATI) site. hPANX1-25K was confirmed to be a hPANX1 isoform via mass spectrometry, can be N-linked glycosylated at N254, and can interact with both β-catenin and full length hPANX1. A double deletion of hPANX1 and hPANX1-25K reduces cell growth and viability in cancer cells. hPANX1-25K is prevalent throughout melanoma progression, and its levels are increased in squamous cell carcinoma cells and patient-derived tumours, compared to keratinocytes and normal skin, indicating that it may be differentially regulated in normal and cancer cells.

In this study, we explored the intricate relationship between Pannexin 1 (PANX1) and the Hippo signaling pathway effector, Yes-associated protein (YAP). Analysis of The Cancer Genome Atlas (TCGA) data revealed a significant positive correlation between PANX1 mRNA and core Hippo components, YAP, TAZ, and Hippo scaffold, IQGAP1, in invasive cutaneous melanoma and breast carcinoma. Furthermore, we demonstrated that PANX1 expression is upregulated in invasive melanoma cell lines and is associated with increased YAP protein levels. Notably, our investigations uncovered a previously unrecognized interaction between endogenous PANX1 and the Hippo scaffold protein IQGAP1 in melanoma cells. Moreover, our findings revealed that IQGAP1 exhibits differential expression in melanoma cells and plays a regulatory role in cellular morphology. Functional studies involving PANX1 knockdown provided compelling evidence that PANX1 modulates YAP protein levels and its co-transcriptional activity in both melanoma and breast carcinoma cells. Importantly, our study showcases the potential therapeutic relevance of targeting PANX1, as pharmacological inhibition of PANX1 using selective FDA-approved inhibitors or PANX1 knockdown reduced YAP abundance in melanoma cells. Furthermore, our Clariom ™ S analysis unveiled key genes implicated in cell proliferation, such as neuroglin1 (NRG1), β-galactoside binding protein, galectin-3 (LGALS3), that are affected in PANX1-deficient cells. In summary, our investigation delves into the intricate interplay between PANX1 and YAP in the context of invasive melanoma, offering valuable insights into potential therapeutic strategies for effective treatment., Competing Interests: Conflict of Interest Statement The authors declare no conflict of interest with this manuscript.

Objective: This case series explored the integration of smartwatches in a community mental health service to support severe mental illness (SMI) management and intervention. We examined whether biometric data provided by smartwatches could help to predict relapse and inform treatment decisions., Method: Four Australian SMI outpatients of mixed diagnoses (age range = 19-24) were selected from a prior study. Clinicians accessed patients' biometric data (activity, sleep, heart rate, and electrodermal activity) through smartwatches., Results: Changes in circadian rhythm and electrodermal activity preceded hospitalization in two cases. Additionally, smartwatch data was effectively used to guide targeted interventions, improving patient treatment outcomes., Conclusion: Integrating smartwatches in community mental health services offers promise as adjunct tools for SMI management. However, ethical considerations on data privacy and technology reliance require further evaluation. Additionally, as this is a small case series, randomized controlled trials with larger sample sizes are required to provide evidence for generalisability of results., (© 2024 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Maturity Onset Diabetes of the Young (MODY) is a young-onset, monogenic form of diabetes without needing insulin treatment. Diagnostic testing is expensive. To aid decisions on who to test, we aimed to develop a MODY probability calculator for paediatric cases at the time of diabetes diagnosis, when the existing "MODY calculator" cannot be used. Firth logistic regression models were developed on data from 3541 paediatric patients from the Swedish 'Better Diabetes Diagnosis' (BDD) population study (n = 46 (1.3%) MODY (HNF1A, HNF4A, GCK)). Model performance was compared to using islet autoantibody testing. HbA1c, parent with diabetes, and absence of polyuria were significant independent predictors of MODY. The model showed excellent discrimination (c-statistic = 0.963) and calibrated well (Brier score = 0.01). MODY probability > 1.3% (ie. above background prevalence) had similar performance to being negative for all 3 antibodies (positive predictive value (PPV) = 10% v 11% respectively i.e. ~ 1 in 10 positive test rate). Probability > 1.3% and negative for 3 islet autoantibodies narrowed down to 4% of the cohort, and detected 96% of MODY cases (PPV = 31%). This MODY calculator for paediatric patients at time of diabetes diagnosis will help target genetic testing to those most likely to benefit, to get the right diagnosis., (© 2024. The Author(s).)

Objectives: To offer a comprehensive overview of the critical elements contributing to the achievements of oncology navigation, address challenges in standardized implementation, and examine recent advancements influencing the acknowledgment and reimbursement of navigation services. Lastly, the AONN+ 35 evidence-based navigation metrics will be shared, emphasizing the five core metrics that should be utilized by all navigation models in all settings., Methods: Employed in this review involves synthesizing information from established oncology organizations, documenting the development of navigator professional standards of practice and navigation metrics that measure patient experience, clinical outcomes, and return on investment, and analyzing outcomes from national studies and collaborations to present a summary of advancements in oncology navigation., Results: The key components vital for ensuring the enduring success of programs encompass the core competencies of navigators, adherence to standards of navigation practice set by the Professional Oncology Navigation Taskforce, and the establishment of well-defined metrics specific to oncology navigation., Conclusions: Despite these advancements, challenges persist in implementing and recognizing the newly defined standards and metrics. Effective solutions involve aligning navigation programs with leadership, integrating standards into daily practice, defining navigator roles, measuring navigation program outcomes through defined metrics, and leveraging certifications. Standardized measurement and practice are imperative for national policy development and reimbursement models, aligning with the Cancer Moonshot's goal of high-quality, patient-centered, and cost-effective cancer care., Implications for Nursing Practice: To contribute to standardizing measurement and practice in oncology navigation for national policy development and reimbursement models., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brenda Nevidjon reports a relationship with Oncology Nursing Society that includes: employment. Tricia Strusowski MS, RN reports writing assistance was provided by Oncology Nursing Society. Tricia Strusowski reports a relationship with Oncology Nursing Society that includes: non-financial support. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Connexins are channel-forming proteins that function to facilitate gap junctional intercellular communication. Here, we use dual cell voltage clamp and dye transfer studies to corroborate past findings showing that Cx31.1 (encoded by GJB5) is defective in gap junction channel formation, illustrating that Cx31.1 alone does not form functional gap junction channels in connexin-deficient mammalian cells. Rather Cx31.1 transiently localizes to the secretory pathway with a subpopulation reaching the cell surface, which is rarely seen in puncta reminiscent of gap junctions. Intracellular retained Cx31.1 was subject to degradation as Cx31.1 accumulated in the presence of proteasomal inhibition, had a faster turnover when Cx43 was present and ultimately reached lysosomes. Although intracellularly retained Cx31.1 was found to interact with Cx43, this interaction did not rescue its delivery to the cell surface. Conversely, the co-expression of Cx31 dramatically rescued the assembly of Cx31.1 into gap junctions where gap junction-mediated dye transfer was enhanced. Collectively, our results indicate that the localization and functional status of Cx31.1 is altered through selective interplay with co-expressed connexins, perhaps suggesting Cx31.1 is a key regulator of intercellular signaling in keratinocytes., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

In Drosophila, only one cell in a multicellular female germline cyst is specified as an oocyte and a similar process occurs in mammals. The symmetry-breaking cue for oocyte selection is provided by the fusome, a tubular structure connecting all cells in the cyst. The Drosophila spectraplakin Shot localises to the fusome and translates its asymmetry into a polarised microtubule network that is essential for oocyte specification, but how Shot recognises the fusome is unclear. Here, we demonstrate that the actin-binding domain (ABD) of Shot is necessary and sufficient to localise Shot to the fusome and mediates Shot function in oocyte specification together with the microtubule-binding domains. The calponin homology domain 1 of the Shot ABD recognises fusomal F-actin and requires calponin homology domain 2 to distinguish it from other forms of F-actin in the cyst. By contrast, the ABDs of utrophin, Fimbrin, Filamin, Lifeact and F-tractin do not recognise fusomal F-actin. We therefore propose that Shot propagates fusome asymmetry by recognising a specific conformational state of F-actin on the fusome., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

In this work we present an oblique plane microscope designed to work seamlessly with a commercially available microscope base. To support all the functionality offered by the microscope base, where the position of the objective lens is not fixed, we adopted a two-mirror scanning geometry that can compensate for changes to the position of the objective lens during routine microscope operation. We showed that within a ± 1 mm displacement range of the 100X, 1.35 NA objective lens away from its designed position, the PSF size increased by <3% and <11% in the lateral and axial dimensions, respectively, while the error in magnification was <0.5% within volumes extending ± 10 µm about the focal plane. Compared to the more traditional scan-lens/galvo-mirror combination, the two-mirror scanning geometry offers higher light efficiency and a more compact footprint, which could be beneficial to all OPM designs regardless of the use of a commercial base or not., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Background and Purpose: Symptomatic arrhythmia is common following radiotherapy for non-small cell lung cancer (NSCLC), frequently resulting in morbidity and hospitalization. Modern treatment planning technology theoretically allows sparing of cardiac substructures. Atrial fibrillation (AF) comprises the majority of post-radiotherapy arrhythmias, but efforts to prevent this cardiotoxicity have been limited as the causative cardiac substructure is not known. In this study we investigated if incidental radiation dose to the pulmonary veins (PVs) is associated with AF., Material and Methods: A single-centre study of patients completing contemporary (chemo)radiation for NSCLC, with modern planning techniques. Oncology, cardiology and death records were examined, and AF events were verified by a cardiologist. Cardiac substructures were contoured on planning scans for retrospective dose analysis., Results: In 420 eligible patients with NSCLC treated with intensity-modulated (70%) or 3D-conformal (30%) radiotherapy with a median OS of 21.8 months (IQR 10.8-35.1), there were 26 cases of new AF (6%). All cases were grade 3 except two cases of grade 4. Dose metrics for both the left (V55) and right (V10) PVs were associated with the incidence of new AF. Metrics remained statistically significant after accounting for the competing risk of death and cardiovascular covariables for both the left (HR 1.02, 95%CI 1.00-1.03, p = 0.005) and right (HR 1.01 (95%CI 1.00-1.02, p = 0.033) PVs., Conclusion: Radiation dose to the PVs during treatment of NSCLC was associated with the onset of AF. Actively sparing the PVs during treatment planning could reduce the incidence of AF during follow-up, and screening for AF may be warranted for select cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The influx of Forcibly Displaced Myanmar Nationals (FDMNs) has left the Southwest coastal district of Cox's Bazar with one of the greatest contemporary humanitarian crises, stressing the existing water, sanitation, and hygiene (WASH) resources and services. This study aimed to assess the existing capacity of local institutions involved in delivering WASH services and identify relevant recommendations for intervention strategies., Methods: We used a qualitative approach, including interviews and capacity assessment workshops with institutions engaged in WASH service delivery. We conducted five key informant interviews (KII) with sub-district level officials of the Department of Public Health Engineering (DPHE), Directorate General of Health Services (DGHS), Directorate of Primary Education (DPE) and Bangladesh Rural Advancement Committee (BRAC) to have a general idea of WASH service mechanisms. Seven capacity assessment workshops were organized with the relevant district and sub-district level stakeholders from August 2019 to September 2019. These workshops followed three key areas: i) knowledge of policy, organizational strategy, guidelines, and framework; ii) institutional arrangements for service delivery such as planning, implementation, coordination, monitoring, and reporting; and iii) availability and management of human, financial and infrastructural resources. Data were categorized using thematic content analysis., Results: The majority of stakeholders lacked awareness of national WASH policies. Furthermore, the top-down planning approaches resulted in activities that were not context-specific, and lack of coordination between multiple institutions compromised the optimal WASH service delivery at the local level. Shortage of human resources in delivering sustainable WASH services, inadequate supervision, and inadequate evaluation of activities also required further improvement, as identified by WASH stakeholders., Conclusion: Research evidence suggests that decision-makers, donors, and development partners should consider learning from the WASH implementers and stakeholders about their existing capacity, gaps, and opportunities before planning for any WASH intervention in any particular area., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rahman 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.)

Aims: Cardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events. The purpose of this study was to assess the association of heart base radiation dose with overall survival and the risk of cardiac events with individual heart base contours., Materials and Methods: Patients treated between 2015 and 2020 were reviewed for baseline patient, tumour and cardiac details and both cancer and cardiac outcomes as part of the NI-HEART study. Three cardiologists verified cardiac events including atrial fibrillation, heart failure and acute coronary syndrome. Cardiac substructure delineations were completed using a validated deep learning-based autosegmentation tool and a composite cardiac base structure was generated. Cox and Fine-Gray regressions were undertaken for the risk of death and cardiac events., Results: Of 478 eligible patients, most received 55 Gy/20 fractions (96%) without chemotherapy (58%), planned with intensity-modulated radiotherapy (71%). Pre-existing cardiovascular morbidity was common (78% two or more risk factors, 46% one or more established disease). The median follow-up was 21.1 months. Dichotomised at the median, a higher heart base Dmax was associated with poorer survival on Kaplan-Meier analysis (20.2 months versus 28.3 months; hazard ratio 1.40, 95% confidence interval 1.14-1.75, P = 0.0017) and statistical significance was retained in multivariate analyses. Furthermore, heart base Dmax was associated with pooled cardiac events in a multivariate analysis (hazard ratio 1.75, 95% confidence interval 1.03-2.97, P = 0.04)., Conclusions: Heart base Dmax was associated with the rate of death and cardiac events after adjusting for patient, tumour and cardiovascular factors in the NI-HEART study. This validates the findings from previous unsupervised analytical approaches. The heart base could be considered as a potential sub-organ at risk towards reducing radiation cardiotoxicity., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Worldwide colonic cancer is the third most common cancer with up to 30% of cases presenting with large bowel obstruction. Self-expanding metal stents (SEMS) have been used as a bridge to surgery (BTS) in the treatment of this malignant obstruction. We review the outcomes of SEMS as a BTS across two high volume colorectal units., Methodology: A retrospective analysis of patients undergoing colonic stenting as a bridge to surgery was performed; outcomes were compared to previously published figures on emergency colonic resections. Inclusion criteria were adults (>18 years of age) undergoing colonic stenting for colonic obstruction with a view to elective resection. Patients undergoing stenting for palliation of symptoms were excluded., Results: 39 patients were identified across both trusts over a ten-year period. 90 day mortality following BTS was found to be 3.6% and there was an 82.1% (32/39) technical success rate. 46.4% proceeded to an elective resection which was started laparoscopically. Permanent stoma rate was observed at 14.3% for elective surgery., Conclusion: Stenting for relief of acute malignant obstruction as a bridge to surgery is a viable option in select patients. Further research is required to determine oncological safety and rate of local recurrences., (Copyright © 2024 Ulster Medical Society.)

Objectives: To evaluate the clinical features of first branchial cleft anomalies (BCAs) and their relationship to pre-operative imaging, pathologic data, and post-operative surveillance outcomes. Additional aims were to assess the validity of the Work classification and describe features of recurrent cysts., Methods: Records for 56 children (34 females, 22 males; age at surgery of 5.6 ± 4.4 years) collected over a 12-year period (2009-2021) were reviewed. Imaging and pathologic slides were re-reviewed in a blinded fashion by experts in those respective areas. Parents were contacted via telephone to obtain extended follow-up. An alternate classification method based on the presence (type II) or absence (type I) of parotid involvement is provided., Results: Only 55% of first BCAs could be successfully classified using Work's method. First BCAs within the parotid were more likely to present with recurrent infections, involve scarred tissue planes and lymphadenopathy, and demonstrate enlarged lymphoid follicles on pathology. The overall recurrence rate was 16%, and recurrence was 5.3 times more likely when external auditory canal cartilage was not resected. Preoperative imaging was useful for predicting the extent of surgery required and the presence of scarred tissue planes., Conclusion: First BCAs within the parotid gland involve more difficult and extensive surgical resection and the potential for morbidity related to facial nerve dissection. Appropriately aggressive surgical resection, which may include the resection of involved ear cartilage, is necessary to prevent morbidity related to recurrence., Level of Evidence: 4 Laryngoscope, 134:459-465, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

The Asian community - the second largest non-European ethnic community in New Zealand - plays an important role in combatting the COVID-19 pandemic, evidenced by their active advocation for border control and mass masking. Despite the long history of racial discrimination against the Asian population, the Asian community has experienced certain degrees of racial discrimination associated with the stigmatisation as the cause of the COVID-19 outbreak in New Zealand. Based on data from a quantitative online survey with 402 valid responses within the Asian communities across New Zealand and the in-depth interviews with 19 Asian people in Auckland, New Zealand, this paper will illustrate Asian people's experience of racial discrimination and stigmatisation during the pandemic in the country. The survey shows that since the outbreak of COVID-19, under a quarter of the participants reported experiencing discrimination, and a third reported knowing an immediate contact who had experienced discrimination. However, when looking beyond their immediate social circle, an even higher proportion reported noticing racism and stigmatisation through the traditional or social media due to COVID-19. Major variations of the degree of racial discrimination experienced are determined by three demographic variables: ethnicity, age, and region. The in-depth interviews largely echoed the survey findings and highlighted a strong correlation between the perceived racial discrimination among the local Asian community and the stigmatisation associated with COVID-19. These findings are important for improving the way we manage future pandemics and other disasters within the context of the UN Sendai Framework for Disaster Risk Reduction., (© 2022. The Author(s).)

Reconstructions of coupled carbon, oxygen, and sulfur cycles rely heavily on sedimentary pyrite sulfur isotope compositions (δ 34 S pyr ). With a model of sediment diagenesis, paired with global datasets of sedimentary parameters, we show that the wide range of δ 34 S pyr (~100 per mil) in modern marine sediments arises from geographic patterns in the relative rates of diffusion, burial, and microbial reduction of sulfate. By contrast, the microbial sulfur isotope fractionation remains large and relatively uniform. Over Earth history, the effect of increasing seawater sulfate and oxygen concentrations on sulfate and sulfide transport and reaction may explain the corresponding increase observed in the δ 34 S offset between sulfate and pyrite. More subtle variations may be related to changes in depositional environments associated with sea level fluctuations and supercontinent cycles.

Species ecology and life history patterns are often reflected in animal morphology. Blue whales are globally distributed, with distinct populations that feed in different productive coastal regions worldwide. Thus, they provide an opportunity to investigate how regional ecosystem characteristics may drive morphological differences within a species. Here, we compare physical and biological oceanography of three different blue whale foraging grounds: (1) Monterey Bay, California, USA; (2) the South Taranaki Bight (STB), Aotearoa New Zealand; and (3) the Corcovado Gulf, Chile. Additionally, we compare the morphology of blue whales from these regions using unoccupied aircraft imagery. Monterey Bay and the Corcovado Gulf are seasonally productive and support the migratory life history strategy of the Eastern North Pacific (ENP) and Chilean blue whale populations, respectively. In contrast, the New Zealand blue whale population remains in the less productive STB year-round. All three populations were indistinguishable in total body length. However, New Zealand blue whales were in significantly higher body condition despite lower regional productivity, potentially attributable to their non-migratory strategy that facilitates lower risk of spatiotemporal misalignment with more consistently available foraging opportunities. Alternatively, the migratory strategy of the ENP and Chilean populations may be successful when their presence on the foraging grounds temporally aligns with abundant prey availability. We document differences in skull and fluke morphology between populations, which may relate to different feeding behaviors adapted to region-specific prey and habitat characteristics. These morphological features may represent a trade-off between maneuverability for prey capture and efficient long-distance migration. As oceanographic patterns shift relative to long-term means under climate change, these blue whale populations may show different vulnerabilities due to differences in migratory phenology and feeding behavior between regions. Spanish abstract La ecología y patrones de historia de vida de las especies a menudo se reflejan en la morfología animal. Las ballenas azules están distribuidas globalmente, con poblaciones separadas que se alimentan en diferentes regiones costeras productivas de todo el mundo. Por lo tanto, brindan la oportunidad de investigar cómo las características regionales de los ecosistemas pueden impulsar diferencias morfológicas dentro de una especie. Aquí, comparamos la oceanografía física y biológica de tres zonas de alimentación diferentes de la ballena azul: (1) Bahía de Monterey, California, EE. UU., (2) Bahía del sur de Taranaki (BST), Nueva Zelanda, y (3) Golfo de Corcovado, Chile. Adicionalmente, comparamos la morfología de las ballenas azules de estas regiones utilizando imágenes de aeronaves no tripuladas. La Bahía de Monterey y el Golfo de Corcovado son estacionalmente productivos y apoyan la estrategia migratoria de la historia de vida de las poblaciones de ballena azul chilena y del Pacífico Norte Oriental (PNO), respectivamente. Por el contrario, la población de ballena azul de Nueva Zelanda permanece en la menos productiva BST durante todo el año. Las tres poblaciones eran indistinguibles en cuanto a la longitud corporal total. Sin embargo, las ballenas azules de Nueva Zelanda tenían una condición corporal significativamente mayor a pesar de una menor productividad regional, potencialmente atribuible a su estrategia no migratoria que facilita un menor riesgo de desalineación espaciotemporal con oportunidades de alimentación disponibles de manera más consistente. Alternativamente, la estrategia migratoria de las poblaciones de ballenas PNO y chilena puede tener éxito cuando su presencia en las zonas de alimentación se alinea temporalmente con la abundante disponibilidad de presas. Documentamos diferencias en la morfología del cráneo y la aleta caudal entre poblaciones, que pueden estar relacionadas con diferentes comportamientos de alimentación adaptados a las características de hábitat y presas específicas para cada región. Estas características morfológicas pueden representar una compensación entre la maniobrabilidad para la captura de presas y una migración eficiente a larga distancia. A medida que los patrones oceanográficos cambian en términos de mediano a largo plazo debido al cambio climático, estas poblaciones de ballenas azules pueden mostrar diferentes vulnerabilidades debido a diferencias en la fenología migratoria y el comportamiento de alimentación entre regiones., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

The immunology of human babesiosis is poorly investigated. We present a comprehensive investigation of a 75-year-old man with B-cell deficiency who experienced 3 episodes of babesiosis over a 6-year period. Slowly evolving clinical immunity was observed, as evidenced by milder clinical symptoms and lower peak parasite burden after each subsequent babesiosis episode. The patient exhibited several striking immunologic findings. First, the patient had exceptionally high Babesia microti -specific antibodies despite very few circulating B cells, which predominantly coexpressed CD27 (memory marker) and CD95 (death receptor). Second, we demonstrated the presence of long-lasting NK cells and expansion of T memory stem cells. Third, levels of the IP-10 cytokine directly correlated with parasite burden. These results raise fundamental questions on the priming, maintenance, and location of a B-cell population that produces high antibody levels in the face of severe B-cell deficiency. Our results should invoke interest among researchers to study the immunology and pathogenesis of human babesiosis., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Following a severe acquired brain injury, individuals often have low return to work rates. The Vocational Intervention Program (VIP), a partnership of Brain Injury Rehabilitation Program community rehabilitation centres with external vocational rehabilitation providers in New South Wales, Australia, was developed to facilitate a return to competitive employment for working-age people., Objectives: To evaluate the efficacy of the VIP partnership model, this intervention was compared to outcomes from a health-based brain injury vocational rehabilitation centre (H-VR) or community brain injury rehabilitation centres ("treatment as usual"; TAU)., Methods: A 3-arm non-randomized controlled trial was conducted among the 12 adult rehabilitation centres of the NSW Brain Injury Rehabilitation Program. The VIP arm was delivered by 6 community rehabilitation centres in partnership with 3 external private Vocational Rehabilitation providers. The H-VR arm was delivered by 1 health-based vocational rehabilitation centre and the 5 remaining centres delivered TAU. Competitive employment status ("Yes"/"No") and clinician ratings of disability and participation were collected pre- and post-intervention, and at 3-month follow-up. Multilevel models were conducted to investigate change over time by treatment arm., Results: In total, 148 individuals with severe brain injury were included in the trial: n = 75 (VIP), n = 33 (H-VR) and n = 40 (TAU). Sixty-five people (of 108, 60%) completed the VR intervention. A significant arm-by-time interaction was found, with higher return to work rates from pre- to post-intervention in VIP and H-VR arms compared to TAU (P = 0.0002). Significant arm-by-time interactions also indicated improved work-related participation and independent living skills from pre- to post-intervention in VIP and H-VR compared to the TAU arm (P < 0.05). These improvements were maintained at 3-month follow-up., Conclusions: The VIP improved return to competitive employment at comparable rates to the specialist H-VR. Larger-scale adoption of the VIP model could provide significant improvements in vocational rehabilition sevices to support people in their return to work following severe brain injury., Anzctr Trial Registry Number: ACTRN12622000769785., Competing Interests: Declaration of Competing Interest The salaries of authors GS, DJ, and IC are supported in part by the NSW icare Lifetime Care and Support Scheme. Authors PM, TG, and MD declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The concept of food and nutrition policy has broadened from simply being an aspect of health policy, to policy interventions from across a wide range of sectors, but still with potentially important impact on nutritional outcomes. This wider and more complex conceptualisation involves policy with multiple objectives and stakeholder influences. Thus, it becomes particularly important to understand the dynamics of these policy processes, including policy design and implementation. To add to this literature, we apply the Kaleidoscope Model for understanding policy change in developing country contexts to the case-study of an agricultural input subsidy (AIS) programme in Malawi, the Farm Input Subsidy Programme (FISP), exploring the dynamics of the FISP policy process including nutritional impact. Over a three-month period between 2017 and 2019 we conducted in-depth interviews with key stakeholders at national and district levels, and focus groups with people from rural districts in Malawi. We also undertook a review of literature relating to the political economy of the FISP. We analysed the data thematically, as per the domains of the Kaleidoscope Model. The analysis across the FISP policy process including policy design and implementation highlights how stakeholders' ideas, interests and influence have shaped the evolution of FISP policy including constraints to policy improvement-and the nutritional impacts of this. This approach extends the literature on the tensions, contradictions and challenges in food and nutrition policy by examining the reasons that these occur in Malawi with the FISP. We also add to the political science and policy analysis literature on policy implementation, extending the concept of veto players to include those targeted by the policy. The findings are important for consideration by policymakers and other stakeholders seeking to address malnutrition in rural, food-insecure populations in Malawi and other low-income settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Walls 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.)

Extreme heat negatively impacts cognition, learning, and task performance. With increasing global temperatures, workers may therefore be at increased risk of work-related injuries and illness. This study estimates the effects of temperature on worker health using records spanning 1985-2020 from an Australian mandatory insurance scheme. High temperatures are found to cause significantly more claims, particularly among manual workers in outdoor-based industries. These adverse effects have not diminished across time, with the largest effect observed for the 2015-2020 period, indicating increasing vulnerability to heat. Within occupations, the workers most adversely affected by heat are female, older-aged and higher-earning. Finally, results from firm-level panel analyses show that the percentage increase in claims on hot days is largest at "safer" firms., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To identify variables that are associated with poor compliance to thyroid hormone replacement therapy in children after total thyroidectomy., Method: A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 1/2014 and 9/2021. Postoperative poor compliance was characterized by at least three separate measurements of high TSH levels not associated with radioactive iodine treatment., Results: There were 100 patients, ages 3-20 years old who met inclusion criteria; 44 patients underwent thyroidectomy for cancer diagnosis, and 56 for Graves' disease. The mean follow-up time was 36.5 months (range 3.0-95.6 months). Overall, 42 patients (42%) were found to have at least three measurements of high TSH during follow-up, and 29 patients (29%) were diagnosed with clinical hypothyroidism. Sex, race, income, insurance type, and benign versus malignant etiology for thyroidectomy were not associated with adherence to therapy. Multivariate regression analysis identified patients with Graves' disease and hyperthyroidism at the time of surgery and Hispanic ethnicity to be associated with postoperative clinical hypothyroidism (OR 9.38, 95% CI 2.16-49.2, p = 0.004 and OR 6.15, 95% CI 1.21-36.0, p = 0.033, respectively)., Conclusions: Preoperative hyperthyroidism in patients with Graves' disease and Hispanic ethnicity were predictors of postoperative TSH abnormalities. Preoperative counseling for patients and their families on the implications of total thyroidectomy and the need for life-long medications postoperatively is necessary. Efforts should be made to evaluate and improve adherence to therapy pre-and postoperatively in patients with Graves' disease., Level of Evidence: 4 Laryngoscope, 133:2402-2406, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Motor skill assessment is part of the fetal alcohol spectrum disorder (FASD) multidisciplinary assessment. Some clinicians opt to exclude assessment of the subcomponents of visual-motor integration (visual perception and motor coordination), on the assumption that challenges will be revealed based on the assessment of visual-motor integration. The objective is to describe the visual-motor integration, visual perception, and fine motor coordination pattern of abilities in children with confirmed prenatal alcohol exposure being assessed for fetal alcohol spectrum disorder., Methods: This cross-sectional study included 91 children (65 males; mean age: 10 years, 6 months SD = 2 years, 10 months) undergoing assessment for FASD. Friedman and Wilcoxon statistics were used to compare mean visual-motor integration, visual perception, and fine motor coordination percentiles from the Beery-Buktenica Developmental Test of Visual-Motor Integration, Sixth Edition (Beery-6)., Results: Children being assessed for FASD (n = 91) had the highest normative scores in visual perception, followed by visual-motor integration and fine motor coordination (mean percentiles (SD): 35.9 (24.9), 20.6 (18.3), and 13.8 (15.5), respectively) (χ 2 distribution = 46.909, p ≤ 0.001)., Conclusion: Children being assessed for FASD experience more challenges with fine motor coordination compared with visual-motor integration and visual perception tasks. This pattern differs from the pattern established for the general population in which tasks that require visual-motor integration are more challenging than tasks that isolate visual perception and fine motor coordination. These results suggest that fine motor coordination should be included in FASD diagnostic assessments and considered as an area for intervention., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Machine learning methods have emerged as objective tools to evaluate operative performance in urological procedures. Our objectives were to establish machine learning-based methods for predicting surgeon caseload for nerve-sparing robot-assisted radical prostatectomy using our validated hydrogel-based simulation platform and identify potential metrics of surgical expertise., Methods: Video, robotic kinematics, and force sensor data were collected from 35 board-certified urologists at the 2022 AUA conference. Video was annotated for surgical gestures. Objective performance indicators were derived from robotic system kinematic data. Force metrics were calculated from hydrogel model integrated sensors. Data were fitted to 3 supervised machine learning models-logistic regression, support vector machine, and k-nearest neighbors-which were used to predict procedure-specific learning curve proficiency. Recursive feature elimination was used to optimize the best performing model., Results: Logistic regression predicted caseload with the highest AUC score for 5/7 possible data combinations (force, 64%; objective performance indicators + gestures, 94%; objective performance indicators + force, 90%; gestures + force, 93%; objective performance indicators + gestures + force, 94%). Support vector machine predicted the highest AUC score for objective performance indicators (82%) and gestures (94%). Logistic regression with recursive feature elimination was the most effective model reaching 96% AUC in predicting case-specific experience. Most contributory features were identified across all model types., Conclusions: We have created a machine learning-based algorithm utilizing a novel combination of objective performance indicators, gesture analysis, and integrated force metrics to predict surgical experience, capable of discriminating between surgeons with low or high robot-assisted radical prostatectomy caseload with 96% AUC in a standardized, simulation-based environment.

Transoral robotic surgery (TORS) in children is in its infancy, and indications have been primarily limited to lingual tonsillar hypertrophy and superficial mucosal lesions. However, the relatively avascular channel of the midline posterior tongue, vallecula, and posterior hyoid space provides a safe plane of dissection for deep lesions of the tongue and access to structures in the anterior neck. As robotic surgeons gain experience, application of this technology will continue to grow. The method is retrospective case series. We present seven patients who had either a primary (n = 3) or recurrent (n = 4) lingual thyroglossal duct cyst (TGDC) and underwent TORS excision. Four of the seven patients also underwent transoral resection of the central portion of the hyoid bone, while three had central hyoid resection during prior surgery. Two minor complications occurred with no evidence of lesion recurrence after mean follow-up of 19.7 mo. The midline avascular channel of the tongue allows for relatively bloodless surgical access to pathologies of the midline base of tongue and anterior neck. Lingual thyroglossal duct cysts can safely be removed via a TORS approach with evidence of limited recurrence. Robotic technology can provide safe and effective surgical alternatives for children with a variety of pathologies, and we aim to promote the widespread adoption of TORS in pediatric head and neck surgery by sharing our knowledge and clinical experience. Further study and publication are needed to establish safety and efficacy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The channel-forming glycoprotein PANX3 functions in cutaneous wound healing and keratinocyte differentiation, but its role in maintaining skin homeostasis through aging is not yet understood. We found that PANX3 is absent in newborn skin but becomes upregulated with age. We characterized the skin of global Panx3-knockout (KO) mice and found that KO dorsal skin showed sex differences at different ages but generally had reduced dermal and hypodermal areas compared with age-matched controls. Transcriptomic analysis of the KO epidermis revealed reduced E-cadherin stabilization and Wnt signaling compared with that of wild-type, consistent with the inability of primary KO keratinocytes to adhere in culture and diminished epidermal barrier function in KO mice. We also observed increased inflammatory signaling in the KO epidermis and a higher incidence of dermatitis in aged KO mice compared with that in wild-type controls. These findings suggest that during skin aging, PANX3 is critical in the maintenance of dorsal skin architecture, keratinocyte cell-cell and cell-matrix adhesion, and inflammatory skin responses., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies to date have yielded inconclusive results as to whether maternal medical history during pregnancy, and a child's early-life medical history contribute to the development of childhood brain tumours (CBTs). This study examined associations between maternal and childhood medical history and the risk of CBTs., Methods: The Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) examined children 0-15 years of age with newly diagnosed CBTs from 1997 to 2003. Multivariable logistic regression analysis determined associations for prenatal medications and childhood medical history, adjusted for child's demographics, and maternal education. Analyses were stratified by histology. A latency period analysis was conducted using 12- and 24-month lead times., Results: Maternal intake of immunosuppressants during the prenatal period was significantly associated with glial tumours (OR 2.73, 95% CI 1.17-6.39). Childhood intake of anti-epileptics was significantly associated with CBTs overall, after accounting for 12-month (OR 8.51, 95% CI 3.35-21.63) and 24-month (OR 6.04, 95% CI 2.06-17.70) lead time before diagnosis. No associations for other medications were found., Conclusions: This study underscores the need to examine potential carcinogenic effects of the medication classes highlighted and of the indication of medication use. Despite possible reverse causality, increased CBT surveillance for children with epilepsy might be warranted., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Providing intravenous (IV) fluids to a patient with signs or symptoms of hypoperfusion is common. However, evaluating the IV fluid 'dose-response' curve of the heart is elusive. Two patients were studied in the emergency department with a wireless, wearable Doppler ultrasound system. Change in the common carotid arterial and internal jugular Doppler spectrograms were simultaneously obtained as surrogates of left ventricular stroke volume (SV) and central venous pressure (CVP), respectively. Both patients initially had low CVP jugular venous Doppler spectrograms. With preload augmentation, only one patient had arterial Doppler measures indicative of significant SV augmentation (i.e., 'fluid responsive'). The other patient manifested diminishing arterial response, suggesting depressed SV (i.e., 'fluid unresponsive') with evidence of ventricular asynchrony. In this short communication, we describe how a wireless, wearable Doppler ultrasound simultaneously tracks surrogates of cardiac preload and output within a 'Doppler Starling curve' framework; implications for IV fluid dosing are discussed., (© 2023. The Author(s).)

Background: Controversy persists regarding the optimal treatment for large abdominal aortic aneurysm (AAA), highlighted by the publication of the National Institute for Health and Care Excellence (NICE) guideline (NG156) on March 2020. The pendulum of opinion swings once more from endovascular to open surgical treatment. We report our experience over the last 15 years in treating consecutive AAA by open surgery., Methods: A retrospective review of a prospectively collected vascular database of all patients undergoing infra-renal open abdominal aortic aneurysm repair (OR) repair from 2004 to 2019 at the largest aneurysm centre in the United Kingdom. OR for elective and emergency (ruptured and symptomatic) outcomes included early morbidity and 30-day mortality, and long-term survival., Results: 1017 patients underwent OR between 2004-2019, on application of our inclusion-criteria 994 patients formed our cohort for analysis (81.2% male) with a mean age 73.6 ± 7.8 years treated by OR for AAA. In that group 672 were elective and 308 were emergency (for ruptured or symptomatic). Overall 30 day mortality was 11.3%, elective 30 day mortality was 2.5%, and emergency 30 day mortality was 29.9%. 30 day re-intervention rate was 9.5%, (elective 7.0%, emergency 15.9%). Survival at 1000 days for elective repair was 72 v 46.7% for emergency and at 2000 days was 43.4% for elective v 25% for emergency., Conclusion: Our data confirm that open surgery for AAA can be performed in large volume centres quite safely. Elective and Emergency surgery does affect early 30 day mortality but does not influence long-term outcome.

BACKGROUND: Vitamin K antagonists are the only oral anticoagulants approved to prevent valve thrombosis and valve-related thromboembolism in patients with mechanical heart valves. Whether patients with an On-X mechanical aortic valve can be safely anticoagulated with apixaban is unknown. METHODS: Patients with an On-X aortic valve implanted at least 3 months before enrollment were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalized ratio 2.0 to 3.0). The primary efficacy end point was the composite of valve thrombosis or valve-related thromboembolism with coprimary analyses comparing apixaban with warfarin for noninferiority and comparing the apixaban event rate with an objective performance criterion (OPC). RESULTS: The trial was stopped after 863 participants were enrolled owing to an excess of thromboembolic events in the apixaban group. Most (94%) participants took aspirin. A total of 26 primary end-point events occurred, 20 (in 16 participants) in the apixaban group (4.2%/patient-year; 95% confidence interval [CI], 2.3 to 6.0) and 6 (in 6 participants) in the warfarin group (1.3%/patient-year; 95% CI, 0.3 to 2.3). The difference in primary end-point rates between the apixaban and warfarin groups was 2.9 (95% CI, 0.8 to 5.0); noninferiority and OPC success criteria were not met. Major bleeding rates were 3.6%/patient-year with apixaban and 4.5%/patient-year with warfarin. CONCLUSIONS: Apixaban did not demonstrate noninferiority to warfarin and is less effective than warfarin for the prevention of valve thrombosis or thromboembolism in patients with an On-X mechanical aortic valve. (Funded by Artivion; ClinicalTrials.gov number, NCT04142658.)

Brain metastases are the most common central nervous system malignancy, and the leading cause of cancer-related deaths. Non-small cell lung carcinomas (NSCLC) comprise the most common cell of origin. Immunotherapy, particularly checkpoint inhibitors, has emerged as the standard of care for many patients with advanced lung cancer. Pannexin1 (PANX1) is a transmembrane glycoprotein that forms large-pore channels and has been reported to promote cancer metastasis. However, the roles of PANX1 in lung cancer brain metastases and tumor immune microenvironment have not been characterized. 42 patient-matched formalin-fixed paraffin-embedded tissue samples from lung carcinomas and the subsequent brain metastases were constructed into three tissue microarrays (TMAs). PANX1 and markers of tumor-infiltrating immune cells (CD3, CD4, CD8, CD68, and TMEM119) were assessed using immunohistochemistry and digital image analysis. The expression of PANX1 was significantly higher in brain metastases than in their paired primary lung carcinoma. The high levels of PANX1 in lung carcinoma cells in the brain inversely correlated with infiltration of peripheral blood-derived macrophages. Our findings highlight the role of PANX1 in the progression of metastatic NSCLC, and the potential therapeutic approach of targeting PANX1 enhances the efficacy of immune checkpoint inhibitors in brain metastasis.

Objectives: To investigate long-term outcomes, imaging, and pathologic findings in pediatric patients who underwent superficial parotidectomy for recalcitrant juvenile recurrent parotitis (JRP)., Methods: Records for 20 children (23 parotidectomies; 9 females, 11 males; age at surgery of 8.6 ± 3.7 years) collected over a 10-year period (2012-2021) were reviewed. Parents were contacted via telephone to obtain extended follow-up. A simplified scoring system was used to assess imaging findings and an additional pathologic review was conducted to further clarify the underlying disease process., Results: All but one patient experienced resolution of their recurrent symptoms after superficial parotidectomy. Three of the patients studied required surgery on the contralateral side, and this could be predicted based on their imaging at the time of the initial surgery. Pathologic findings included ductal fibrosis, metaplasia, and dilatation as well as parenchymal atrophy and fatty deposition. There were no major surgical complications, however, the incidence of Frey's syndrome in this sample was 43.5% of surgical sites., Conclusion: For patients with frequent recalcitrant symptoms or significant quality of life impairment related to JRP, superficial parotidectomy represents a potential treatment option with the noted reduction in symptom burden following surgery. Further longitudinal studies are needed., Level of Evidence: 4 Laryngoscope, 133:1495-1500, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Aim: Asians are the second largest and fastest growing non-European population in New Zealand but are under-researched in terms of their COVID-19 pandemic response. The paper aims to illustrates Asians' risk perceptions and knowledge of COVID-19, and self-protection practices to avoid infection and prevent community transmission., Subject and Methods: An online survey was used to collect data and received 402 valid responses. Data analyses included: 1) a descriptive analysis by using Chi -square tests and a Kruskal-Wallis rank sum tests to explore associations between responses and the four demographic variables (i.e. age, gender, country of origin/ethnicity, and region); and 2) a correlation analysis between different survey objectives., Results: The descriptive analysis of the survey found that while ethnicity (within the Asian category) was the most influential variable that resulted in varying responses to many questions, gender and age were other two important variables in influencing the answering patterns. The correlation analysis found a positive correlation between the perceived 'dangerousness' of COVID-19 and respondents' overall compliance behaviour to New Zealand authorities' recommendations to prevent spread of COVID-19., Conclusion: The majority of the respondents provided correct answers to the questions about the vulnerable populations, symptoms, asymptomatic transmission and potential sequelae of COVID-19; however, their understanding of the availability of a cure for, and the incubation period of COVID-19 was not consistent with the official information. The research also found that the higher perceived dangerousness of COVID-19, the better compliance to self-protection practices among the surveyed population., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial conflict of interests to disclose. Submission declaration and verification: The work has not published previously and submitted to any other journal., (© The Author(s) 2023.)

Introduction: the global rise in antibiotic resistance (ABR), coupled with a dry pipeline for the discovery of new antibiotics requires the conservation of currently available antibiotics. Antimicrobial stewardship (AMS) interventions are being implemented to optimize antibiotic use including the use of antibiotic prescription charts. This study reviewed the use of antibiotics before and after the introduction of an antibiotic prescription chart in a paediatric medical ward of an academic tertiary hospital in Johannesburg., Methods: a cross-sectional retrospective review of patient records was conducted for patients admitted to a paediatric medical ward of an academic tertiary hospital over two study periods; before and after the introduction of an antibiotic prescription chart. Data were captured on a Microsoft® Excel (2010) spreadsheet and analyzed using Stata/IC 15.1 (StataCorp, USA)., Results: antibiotic use decreased significantly by 7.04% following the introduction of the antibiotic prescription chart (p=0.027). Fields often left unfilled on the antibiotic prescription chart include age (100%), a record of renal function (GFR/CrCl) (97.46%), time of antibiotic prescribing (83.62%) and a record of culture and sensitivity results (80.17%)., Conclusion: the findings of this study show an improvement in antibiotic use, the frequency of culture and sensitivity testing and documentation of relevant parameters after the introduction of the antibiotic prescription chart. The use of an antibiotic prescription chart is a practical way to achieve optimal antibiotic use and to encourage proper detailing of the clinical components necessary for antibiotic selection in a hospital setting in a developing country., Competing Interests: The authors declare no competing interests., (Copyright: Habibat Dolapo Salau et al.)

Purpose: This correlational study compared dichotic listening among children with significant hearing loss to typically developing children and children clinically assessed for auditory processing disorder., Method: Recorded versions of two dichotic tests were delivered under earphones or in the sound field for children using amplification. Individual ear scores and interaural asymmetry were compared to normative data. Matched deficit patterns from both tests were identified, ranked for severity of deficit, and compared across groups. Relationships between dichotic scores and factors related to amplification were investigated in the children with hearing loss., Results: Dichotic scores were significantly poorer among children with hearing loss without the large interaural asymmetries seen in children assessed clinically for auditory processing problems. Device type and age of implantation had no effect on scores; non-dominant ear scores on the digits test were significantly correlated to age of device use in the left ear and duration of device use in the right ear. Non-dominant ear scores with digits were also significantly correlated with bilateral word recognition., Conclusions: Poor dichotic perception in children with significant hearing losses may be related to the use of recorded test materials, immature skills in attention and working memory, or other factors that contribute to development of vocabulary and language. These weaknesses may interfere with successful mainstream educational placement in these children. Assessment of dichotic performance in this population could lead to deficit-specific interventions that may improve outcomes and enhance educational opportunities for children with hearing loss., (Copyright © 2023. Published by Elsevier B.V.)

Background: Patients with pure native aortic regurgitation (AR) have been excluded from transcatheter aortic valve replacement (TAVR) trials. We sought to examine midterm outcomes with TAVR in AR compared with surgical AVR (SAVR) in a contemporary cohort., Methods: Medicare beneficiaries who underwent elective TAVR or SAVR for pure AR from 2016 to 2019 were identified. Patients with concomitant aortic stenosis and who underwent a valve-in-valve intervention or concomitant mitral valve or ascending aorta operation were excluded. The primary outcome was all-cause mortality in the longest follow-up. Secondary outcomes included stroke, endocarditis, and redo AVR. Overlap propensity score weighting was used to adjust for confounders., Results: During the study period, 11,027 patients with pure AR underwent elective AVR (TAVR, n = 1147; SAVR, n = 9880). SAVR patients were younger, with fewer comorbidities and less frailty compared with TAVR patients. TAVR was associated with adjusted 30-day mortality comparable to SAVR. After a median follow-up of 31 months (interquartile range, 18-44 months), TAVR was associated with higher adjusted risk of death (hazard ratio [HR], 1.41; 95% CI, 1.03-1.93; P = .02) and need for redo-AVR (HR, 2.13; 95% CI, 1.05-4.34; P = .03) compared with SAVR. The risk of stroke (HR, 1.65; 95% CI, 0.95-2.87; P = .07) and endocarditis (HR, 2.60; 95% CI, 0.92-7.36; P = .07) was numerically higher with TAVR., Conclusions: In Medicare patients with pure native AR, TAVR with the current commercially available transcatheter valves has comparable short-term outcomes. Although long-term outcomes were inferior to SAVR, the possibility of residual confounding, biasing long-term outcomes, given older and frailer TAVR patients, cannot be excluded., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The implications of left ventricular remodeling and dysfunction before and after aortic valve replacement (AVR) for mixed aortic valve disease (MAVD) are not well understood. This study aims to evaluate the impact of AVR on left ventricular (LV) systolic function in MAVD, and determine the prognostic value of postoperative LV global longitudinal strain (LV-GLS) and LV ejection fraction (LVEF)., Methods: We retrospectively assessed 489 consecutive patients with MAVD (defined as at least moderate aortic stenosis and at least moderate aortic regurgitation) and baseline LVEF ≥50%, who underwent AVR between February 2003 and August 2018. All patients had baseline echocardiography, whereas 192 patients underwent postoperative echocardiography between 3 and 18 months after AVR. The primary endpoint was all-cause mortality., Results: Mean age was 65 ± 15 years, and 65% were male. AVR in MAVD patients has a neutral effect on LV systolic function quantitated by LVEF and LV-GLS. During a median follow-up period of 5.8 years, 65 patients (34%) of 192 patients with follow-up echocardiography died. The patients with postoperative LVEF ≥50% had better survival than those with postoperative LVEF <50% (P < .001). Furthermore, among patients with postoperative LVEF ≥50%, mortality differed between patients with postoperative LV-GLS worse than -15% and those with postoperative LV-GLS better than -15% (P < .001)., Conclusions: In patients with MAVD who underwent AVR, the mean postoperative LV-GLS and LVEF remain at a similar value to baseline. However, worse postoperative LV-GLS and LVEF were both independently associated with higher mortality in this population., (© 2023 Wiley Periodicals LLC.)

In Maryland, residential service agencies deliver Medicaid Home and Community-Based Services (HCBS) to older adults with disabilities through direct care workers (e.g., personal care aides). Leveraging survey data from residential service agency administrators, linked to interRAI Home Care assessments for 1144 participants, we describe agency characteristics, and participant and family caregiver experiences by participant dementia status. Most (61.7%) participants experienced low social engagement, and roughly 10.0% experienced a hospitalization or emergency room visit within 90 days. Few (14.4%) participants were served by agencies requiring dementia-specific direct care worker training, and most were served by agencies offering supplemental services, or in which direct care workers helped with health information technology (81.2% and 72.8%, respectively). Few caregivers reported negative care experiences. Participants with dementia and those served by agencies with training and support more often reported negative care experiences. Findings lay the foundation for future longitudinal and embedded interventions within Medicaid HCBS.

The detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA in wastewater can be used as an indicator of the presence of SARS-CoV-2 infection in specific catchment areas. We conducted a hospital-based study to explore wastewater management in healthcare facilities and analyzed SARS-CoV-2 RNA in the hospital wastewater in Dhaka city during the Coronavirus disease (COVID-19) outbreak between September 2020-January 2021. We selected three COVID-hospitals, two non-COVID-hospitals, and one non-COVID-hospital with COVID wards, conducted spot-checks of the sanitation systems (i.e., toilets, drainage, and septic-tank), and collected 90 untreated wastewater effluent samples (68 from COVID and 22 from non-COVID hospitals). E. coli was detected using a membrane filtration technique and reported as colony forming unit (CFU). SARS-CoV-2 RNA was detected using the iTaq Universal Probes One-Step kit for RT-qPCR amplification of the SARS-CoV-2 ORF1ab and N gene targets and quantified for SARS-CoV-2 genome equivalent copies (GEC) per mL of sample. None of the six hospitals had a primary wastewater treatment facility; two COVID hospitals had functional septic tanks, and the rest of the hospitals had either broken onsite systems or no containment of wastewater. Overall, 100 % of wastewater samples were positive with a high concentration of E. coli (mean = 7.0 log 10 CFU/100 mL). Overall, 67 % (60/90) samples were positive for SARS-CoV-2. The highest SARS-CoV-2 concentrations (median: 141 GEC/mL; range: 13-18,214) were detected in wastewater from COVID-hospitals, and in non-COVID-hospitals, the median SARS-CoV-2 concentration was 108 GEC/mL (range: 30-1829). Our results indicate that high concentrations of E. coli and SARS-CoV-2 were discharged through the hospital wastewater (both COVID and non-COVID) without treatment into the ambient water bodies. Although there is no evidence for transmission of SARS-CoV-2 via wastewater, this study highlights the significant risk posed by wastewater from health care facilities in Dhaka for the many other diseases that are spread via faecal oral route. Hospitals in low-income settings could function as sentinel sites to monitor outbreaks through wastewater-based epidemiological surveillance systems. Hospitals should aim to adopt the appropriate wastewater treatment technologies to reduce the discharge of pathogens into the environment and mitigate environmental exposures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The Enterobacterales are a group of Gram-negative bacteria frequently exhibiting extended antimicrobial resistance (AMR) and involved in the transmission of resistance genes to other bacterial species present in the same environment. Due to their impact on human health and the paucity of new antibiotics, the World Health Organization (WHO) categorized carbapenem resistant and ESBL-producing as critical. Enterobacterales are ubiquitous and the role of the environment in the transmission of AMR organisms or antimicrobial resistance genes (ARGs) must be examined in tackling AMR in both humans and animals under the one health approach. Animal manure is recognized as an important source of AMR bacteria entering the environment, in which resistant genes can accumulate., Methods: To gain a better understanding of the dissemination of third generation cephalosporin and fluoroquinolone resistance genes between isolates in the environment, we applied whole genome sequencing (WGS) to Enterobacterales (79 E. coli , 1 Enterobacter cloacae , 1 Klebsiella pneumoniae , and 1 Citrobacter gillenii ) isolated from farm effluents in Ireland before ( n  = 72) and after ( n  = 10) treatment by integrated constructed wetlands (ICWs). DNA was extracted using the MagNA Pure 96 system (Roche Diagnostics, Rotkreuz, Switzerland) followed by WGS on a MiSeq platform (Illumina, Eindhoven, Netherlands) using v3 chemistry as 300-cycle paired-end runs. AMR genes and point mutations were identified and compared to the phenotypic results for better understanding of the mechanisms of resistance and resistance transmission., Results: A wide variety of cephalosporin and fluoroquinolone resistance genes (mobile genetic elements (MGEs) and chromosomal mutations) were identified among isolates that mostly explained the phenotypic AMR patterns. A total of 31 plasmid replicon types were identified among the 82 isolates, with a subset of them ( n  = 24), identified in E. coli isolates. Five plasmid replicons were confined to the Enterobacter cloacae isolate and two were confined to the Klebsiella pneumoniae isolate. Virulence genes associated with functions including stress, survival, regulation, iron uptake secretion systems, invasion, adherence and toxin production were identified., Conclusion: Our study showed that antimicrobial resistant organisms (AROs) can persist even following wastewater treatment and could transmit AMR of clinical relevance to the environment and ultimately pose a risk to human or animal health., 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 Prendergast, Slowey, Burgess, Murphy, Johnston, Morris, O’ Doherty, Moriarty and Gutierrez.)

Little is known about digital health interventions used to support treatment for pregnant and early parenting women (PEPW) with substance use disorders (SUD)., Methods: Guided by the Arksey and O'Malley's Scoping Review Framework, empirical studies were identified within the CINAHL, PsycInfo, PubMed, and ProQuest databases using subject headings and free-text keywords. Studies were selected based on a priori inclusion/exclusion criteria, and data extraction and descriptive analysis were performed., Results: A total of 27 original studies and 30 articles were included. Varying study designs were used, including several feasibility and acceptability studies. However, efficacious findings on abstinence and other clinically important outcomes were reported in several studies. Most studies focused on digital interventions for pregnant women (89.7%), suggesting a dearth of research on how digital technologies may support early parenting women with SUD. No studies included PEPW family members or involved PEPW women in the intervention design., Conclusions: The science of digital interventions to support treatment for PEPW is in an early stage, but feasibility and efficacy results are promising. Future research should explore community-based participatory partnerships with PEPW to develop or tailor digital interventions and include family or external support systems to engage in the intervention alongside PEPW.

Bovine herpesvirus 1 (BoHV-1), is associated with several clinical syndromes in cattle, among which bovine respiratory disease (BRD) is of particular significance. Despite the importance of the disease, there is a lack of information on the molecular response to infection via experimental challenge with BoHV-1. The objective of this study was to investigate the whole-blood transcriptome of dairy calves experimentally challenged with BoHV-1. A secondary objective was to compare the gene expression results between two separate BRD pathogens using data from a similar challenge study with BRSV. Holstein-Friesian calves (mean age (SD) = 149.2 (23.8) days; mean weight (SD) = 174.6 (21.3) kg) were either administered BoHV-1 inoculate (1 × 10 7 /mL × 8.5 mL) ( n = 12) or were mock challenged with sterile phosphate buffered saline ( n = 6). Clinical signs were recorded daily from day (d) -1 to d 6 (post-challenge), and whole blood was collected in Tempus RNA tubes on d six post-challenge for RNA-sequencing. There were 488 differentially expressed (DE) genes ( p < 0.05, False Discovery rate (FDR) < 0.10, fold change ≥2) between the two treatments. Enriched KEGG pathways ( p < 0.05, FDR <0.05); included Influenza A, Cytokine-cytokine receptor interaction and NOD-like receptor signalling. Significant gene ontology terms ( p < 0.05, FDR <0.05) included defence response to virus and inflammatory response. Genes that are highly DE in key pathways are potential therapeutic targets for the treatment of BoHV-1 infection. A comparison to data from a similar study with BRSV identified both similarities and differences in the immune response to differing BRD pathogens., 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 O’Donoghue, Earley, Johnston, McCabe, Kim, Taylor, Duffy, Lemon, McMenamy, Cosby, Morris and Waters.)

Background: Little data exist on the time spent by emergency department (ED) personnel providing intravenous (IV) fluid to 'responsive' versus 'unresponsive' patients., Methods: A prospective, convenience sample of adult ED patients was studied; patients were enrolled if preload expansion was indicated for any reason. Using a novel, wireless, wearable ultrasound, carotid artery Doppler was obtained before and throughout a preload challenge (PC) prior to each bag of ordered IV fluid. The treating clinician was blinded to the results of the ultrasound. IV fluid was deemed 'effective' or 'ineffective' based on the greatest change in carotid artery corrected flow time (ccFT ∆ ) during the PC. The duration, in minutes, of each bag of IV fluid administered was recorded., Results: 53 patients were recruited and 2 excluded for Doppler artifact. There were 86 total PCs included in the investigation comprising 81.7 L of administered IV fluid. 19,667 carotid Doppler cardiac cycles were analyzed. Using ccFT ∆  ≥  + 7 ms to discriminate 'physiologically effective' from 'ineffective' IV fluid, we observed that 54 PCs (63%) were 'effective', comprising 51.7 L of IV fluid, whereas, 32 (37%) were 'ineffective' comprising 30 L of IV fluid. 29.75 total hours across all 51 patients were spent in the ED providing IV fluids categorized as 'ineffective.', Conclusions: We report the largest-known carotid artery Doppler analysis (i.e., roughly 20,000 cardiac cycles) in ED patients requiring IV fluid expansion. A clinically significant amount of time was spent providing physiologically ineffective IV fluid. This may represent an avenue to improve ED care efficiency., (© 2023. The Author(s).)

Epidermal keratinocytes are enriched with at least nine connexins that are key regulators of epidermal homeostasis. The role of Cx30.3 in keratinocytes and epidermal health became evident when fourteen autosomal dominant mutations in the Cx30.3-encoding GJB4 gene were linked to a rare and incurable skin disorder called erythrokeratodermia variabilis et progressiva (EKVP). While these variants are linked to EKVP, they remain largely uncharacterized hindering therapeutic options. In this study, we characterize the expression and functional status of three EKVP-linked Cx30.3 mutants (G12D, T85P, and F189Y) in tissue-relevant and differentiation-competent rat epidermal keratinocytes. We found that GFP-tagged Cx30.3 mutants were non-functional likely due to their impaired trafficking and primary entrapment within the endoplasmic reticulum (ER). However, all mutants failed to increase BiP/GRP78 levels suggesting they were not inducing an unfolded protein response. FLAG-tagged Cx30.3 mutants were also trafficking impaired yet occasionally exhibited some capacity to assemble into gap junctions. The pathological impact of these mutants may extend beyond their trafficking deficiencies as keratinocytes expressing FLAG-tagged Cx30.3 mutants exhibited increased propidium iodide uptake in the absence of divalent cations. Attempts to rescue the delivery of trafficking impaired GFP-tagged Cx30.3 mutants into gap junctions by chemical chaperone treatment were ineffective. However, co-expression of wild type Cx30.3 greatly enhanced the assembly of Cx30.3 mutants into gap junctions, although endogenous levels of Cx30.3 do not appear to prevent the skin pathology found in patients harboring these autosomal dominant mutations. In addition, a spectrum of connexin isoforms (Cx26, Cx30, and Cx43) exhibited the differential ability to trans-dominantly rescue the assembly of GFP-tagged Cx30.3 mutants into gap junctions suggesting a broad range of connexins found in keratinocytes may favourably interact with Cx30.3 mutants. We conclude that selective upregulation of compatible wild type connexins in keratinocytes may have potential therapeutic value in rescuing epidermal defects invoked by Cx30.3 EKVP-linked mutants., 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 Lucaciu, Figliuzzi, Neumann, Nazarali, Del Sordo, Leighton, Hauser, Shao, Johnston, Bai and Laird.)

Objectives: Describe the prevalence and types of unmet needs among community-dwelling dementia care partners (CPs) and determine associations between unmet needs with protective factors, risk factors and outcomes., Method: A cross-sectional analysis of 638 racially and cognitively diverse community-dwelling persons living with dementia (PLWD) and their CPs participating in a comprehensive in-home assessment of dementia-related needs. Unmet CP needs (19 items, 6 domains) were rated by a clinician using the Johns Hopkins Dementia Care Needs Assessment (JHDCNA). Multivariate linear regression models were used to examine associations between total percent unmet CP needs with demographic, protective and risk factors., Results: Nearly all CPs had at least one unmet need (99.53%), with a mean of 5.7 (±2.6). The most common domains with ≥1 unmet need were memory disorder education, care skills and knowledge of resources (98%), legal issues/concerns (73.8%), CP mental health (44.6%) and access to informal support (42.7%). Adjusted multivariate models suggest the strongest consistent predictive factors relate to informal emotional support, CP physical health, use or difficulty getting formal services/supports (both for CPs and PLWD), and CP time spent with PLWD. Greater levels of unmet needs were associated with worse PLWD outcomes and CP outcomes, after adjusting for demographics., Conclusions: CPs have high rates of diverse, but modifiable unmet needs. Data suggest optimal approaches to dementia care should take a family-centered home-based approach that includes routine CP needs assessment, offer targeted interventions that include both traditional medical supports as well as strategies to increase and leverage informal social networks, and ones that can bridge and coordinate medical with non-medical supports. These findings can be used to inform new approaches to support CPs, improve PLWD and CP outcomes, and target groups most at risk for inequities.

A preload challenge (PC) is a clinical maneuver that, first, increases the cardiac filling (i.e., preload) and, second, calculates the change in cardiac output. Fundamentally, a PC is a bedside approach for testing the Frank-Starling-Sarnoff (i.e., "cardiac function") curve. Normally, this curve has a steep slope such that a small change in the cardiac preload generates a large change in the stroke volume (SV) or cardiac output. However, in various disease states, the slope of this relationship flattens such that increasing the volume into the heart leads to little rise in the SV. In this pathological scenario, additional cardiac preload (e.g., intravenous fluid) is unlikely to be physiologically effective and could lead to harm if organ congestion evolves. Therefore, inferring both the cardiac preload and output is clinically useful as it may guide intravenous (IV) fluid resuscitation. Accordingly, the goal of this protocol is to describe a method for contemporaneously tracking the surrogates of cardiac preload and output using a novel, wireless, wearable ultrasound during a well-validated preload challenge.