AGTR1 variant rs2638355 is associated with increased salt sensitivity of blood pressure: a female-specific effect in individuals from the HyperPath cohort.

OBJECTIVE: Salt-sensitive hypertension (SSH) affects approximately half of the hypertensive population, increasing the risk of vascular complications. The underlying pathophysiological mechanisms of SSH remain complex and need to be fully elucidated. Our prior research has identified genetic factors contributing to the salt sensitivity of blood pressure (SSBP), particularly involving genes regulating volume and blood pressure. We also observed enhanced peripheral vascular response to angiotensin II in humans with salt-sensitive hypertension. Given the pivotal role of the angiotensin II receptor type-1 (AT1R or AGTR1) in blood pressure and intravascular volume regulation, we hypothesized a genetic association between AGTR1 and SSBP. METHODS: Our study involved 240 individuals of European ancestry from the HyperPATH cohort, examined under restricted and high dietary salt conditions. We employed a tagging single nucleotide variant approach to genotype participants at AGTR1. RESULTS: Our regression model revealed a significant association between the rs2638355 (A/G) variant and salt-sensitive systolic blood pressure (SS-SBP), and rs2638355 increased AGTR1 gene expression. Notably, carriers of the risk-allele of the noncoding regulatory variant rs2638355 exhibited higher systolic blood pressure under high salt diet conditions than nonrisk allele individuals. A sex-stratified analysis showed this salt-driven effect on systolic blood pressure was significant only in females, underscoring the role of dietary salt in modulating genetic effects in this group. Furthermore, a restricted salt diet in these individuals diminished blood pressure and negated the blood pressure phenotype-genotype association. CONCLUSION: Overall, our findings could aid in pinpointing individuals with salt-sensitive blood pressure among hypertensive patients, especially considering dietary and sex-specific factors.

Donor-recipient age- or sex-mismatched osteochondral allografts do not adversely affect cumulative graft survival rates after transplantation in the knee.

BACKGROUND: Osteochondral allograft transplantation (OCAT) can be performed without the need for blood-type matching or anti-rejection medications. However, other donor-recipient mismatch variables could influence outcomes. Therefore, it is critical to examine the impacts of sex and age mismatching on functional OCA survival. METHODS: Prospectively collected data for patients undergoing primary knee OCAT enrolled in a lifelong outcomes registry were analyzed for functional OCA survival based on sex- and age-matched and -mismatched cohorts. Treatment failure was defined as the need for OCAT revision surgery or knee arthroplasty. RESULTS: 162 donor-recipient pairs were analyzed; 57 (35.2%) were sex-mismatched and 89 (54.9%) were age-mismatched. Sex-mismatched OCATs were not associated with a significantly different cumulative graft survival rate when compared to sex-matched OCATs (78.9% vs 75.2% p = 0.324). Age-mismatched OCATs were not associated with a significantly different cumulative graft survival rate when compared to age-matched OCATs (71.6% vs 81.5% p = 0.398). When adjusting for sex, BMI, concomitant procedures, and surgery type, age-mismatched and sex-mismatched OCATs were not significantly associated with higher likelihood for treatment failure. CONCLUSION: By analyzing functional graft survival rates for donor-recipient sex- or age-mismatched OCAs following primary OCAT, the results of the present study support current donor-recipient matching protocols for OCA transplantation in the knee. Based on current evidence, donor-recipient blood-type, sex-, and age-matching are not required for safe and effective primary OCAT in the knee. However, further studies are imperative for defining modifiable variables that further optimize safety and outcomes while maximizing donor tissue quality, availability, access, and use.

Enrollment in a Behavioral Health Program Positively Impacts 2-Year Cumulative Survival Rates in Osteochondral Allograft Transplant Patients.

Emerging evidence suggests that patients' behavioral health may influence outcomes after osteochondral allograft transplantation (OCAT). A comprehensive behavioral health program (BHP) including preoperative screening and education, and postoperative counseling and support, led by a health behavior psychologist was implemented for patients considering OCAT. We hypothesized that patients undergoing knee OCAT and enrolled in the BHP would have a significantly higher 2-year graft survival rate than those not enrolled. Prospectively collected data for patients undergoing knee OCAT enrolled in the lifelong outcomes registry were analyzed. Based on the timing of implementation of a comprehensive BHP to provide preoperative screening and education followed by postoperative counseling and support, BHP and no-BHP cohorts were compared. Treatment failure was defined as the need for either OCAT revision surgery or knee arthroplasty. The Kaplan-Meier method using log-rank tests compared cumulative survival rates. Multivariable Cox regression analysis was used to determine the effects of confounding variables on the influence of BHP enrollment on graft survival. A total of 301 patients were analyzed (no-BHP = 220 and BHP = 81). At 2-year follow-up, a significantly lower cumulative graft survival rate was observed for patients not enrolled in the BHP (68.2 vs. 91.4%; p = 0.00347). Adjusting for sex, age, body mass index, tobacco use, tibiofemoral bipolar OCAT type surgery, and nonadherence, patients not enrolled in the BHP were 2.8 times more likely to experience OCAT treatment failure by 2 years after primary OCAT compared with patients in the BHP (95% confidence interval, 1.02-4.98; p = 0.01). A comprehensive BHP contributes to significant improvements in 2-year graft survival rates following OCAT in the knee. Preoperative mental and behavioral health screening and support for shared decision-making regarding treatment options, in conjunction with patient and caregiver education and assistance through integrated health care team engagement, are beneficial to patients pursuing complex joint preservation surgeries. Level of evidence is 2, prospective cohort study.

Heterogeneity in the surgical approach to recurrent abdominal wall hernias: an opportunity for quality improvement.

BACKGROUND: Despite being a challenging and morbid clinical problem, operative approaches to recurrent abdominal wall hernia repairs receive little attention. Given this, we performed a retrospective study to evaluate surgical techniques of recurrent abdominal wall hernias requiring reoperation. METHODS: Adult patients from the Michigan Surgical Quality Collaborative Core Optimization Hernia Registry (MSQC-COHR) were included in this study. All elective ventral hernia operations performed between January 1, 2020, and March 31, 2023, were included. Descriptive analyses via t-tests and Fisher exact tests were conducted to evaluate sociodemographic, operative, and hernia-specific attributes associated with primary and recurrent hernia repairs. RESULTS: We identified 8587 patients who underwent elective abdominal wall hernia repair. Of these, 7887 (91.8%) underwent primary repair, and 700 (8.2%) underwent recurrent repair. Patients who underwent recurrent hernia repair were older (mean age 57.9 years vs. 54.1 years, p < 0.001), more often female (53.8% vs. 41.9%, p < 0.001), and had higher BMI (34.0 vs. 32.6, p < 0.001). Patients with recurrent hernias were more likely to have comorbid conditions including hypertension (p < 0.001), diabetes (p < 0.005), COPD (p < 0.01), and BMI > 40 (p < 0.05). Recurrent hernia repairs were more likely to have any 30-day complication (6.4% versus 1.9%, p < 0.001), including higher rates of all surgical site infections. There was no difference in 30-day readmission rates. CONCLUSION: Considerable variation persists in operative management of recurrent abdominal wall hernias. Importantly, not all recurrent hernias were managed with mesh, which may precipitate additional recurrences and further morbidity. Understanding outcomes for these varied approaches to recurrent hernia repairs is critical to optimize management of this complex clinical problem and prevent future episodes of recurrence.

The digital revolution in veterinary pathology.

For the past two centuries, the use of traditional light microscopy to examine tissues to make diagnoses has remained relatively unchanged. While the fundamental concept of tissue slide analysis has stayed the same, our interaction with the microscope is undergoing significant changes. Digital pathology (DP) has gained momentum in veterinary science and is on the verge of becoming a vital tool in diagnostics, research and education. Many diagnostic laboratories have incorporated DP as a critical part of their workflows. Innovations in DP and whole slide image technology have made telediagnosis (the process of transmitting digital clinical data using telecommunication networks for distant diagnosis) more accessible, leading to improved patient care through streamlining of workflows and greater accessibility of second opinions. The integration of machine learning and artificial intelligence and human-in-the-loop protocols for DP workflows will further the development of computer-aided diagnosis and prognostic tools. Despite its present weaknesses, DP will progressively aid veterinary clinicians and pathologists in delivering more accurate and reliable diagnoses. Consistent incorporation of DP frontline advancements into routine veterinary diagnostic pipelines will assist in improving current tools and help prepare pathologists for the progression of digitalization in the field.

FDG-PET/MRI in the presurgical evaluation of pediatric epilepsy.

In patients with drug-resistant epilepsy, difficulties in identifying the epileptogenic zone are well known to correlate with poorer clinical outcomes post-surgery. The integration of PET and MRI in the presurgical assessment of pediatric patients likely improves diagnostic precision by confirming or widening treatment targets. PET and MRI together offer superior insights compared to either modality alone. For instance, PET highlights abnormal glucose metabolism, while MRI precisely localizes structural anomalies, providing a comprehensive understanding of the epileptogenic zone. Furthermore, both methodologies, whether utilized through simultaneous PET/MRI scanning or the co-registration of separately acquired PET and MRI data, present unique advantages, having complementary roles in lesional and non-lesional cases. Simultaneous FDG-PET/MRI provides precise co-registration of functional (PET) and structural (MR) imaging in a convenient one-stop-shop approach, which minimizes sedation time and reduces radiation exposure in children. Commercially available fusion software that allows retrospective co-registration of separately acquired PET and MRI images is a commonly used alternative. This review provides an overview and illustrative cases that highlight the role of combining 18F-FDG-PET and MRI imaging and shares the authors' decade-long experience utilizing simultaneous PET/MRI in the presurgical evaluation of pediatric epilepsy.

A program for real-time surveillance of SARS-CoV-2 genetics.

The COVID-19 pandemic brought forth an urgent need for widespread genomic surveillance for rapid detection and monitoring of emerging SARS-CoV-2 variants. It necessitated design, development, and deployment of a nationwide infrastructure designed for sequestration, consolidation, and characterization of patient samples that disseminates de-identified information to public authorities in tight turnaround times. Here, we describe our development of such an infrastructure, which sequenced 594,832 high coverage SARS-CoV-2 genomes from isolates we collected in the United States (U.S.) from March 13th 2020 to July 3rd 2023. Our sequencing protocol ('Virseq') utilizes wet and dry lab procedures to generate mutation-resistant sequencing of the entire SARS-CoV-2 genome, capturing all major lineages. We also characterize 379 clinically relevant SARS-CoV-2 multi-strain co-infections and ensure robust detection of emerging lineages via simulation. The modular infrastructure, sequencing, and analysis capabilities we describe support the U.S. Centers for Disease Control and Prevention national surveillance program and serve as a model for rapid response to emerging pandemics at a national scale.

'If It Was Easy Somebody Would Have Fixed It': An Exploration of Loneliness and Social Isolation Amongst People Who Frequently Call Ambulance Services.

INTRODUCTION: The aim of the study was to explore social isolation and loneliness in those who frequently contacted the ambulance service, what factors contributed to this and how unmet needs could be addressed. METHODS: Semi-structured interviews with staff from the ambulance service and service users who were identified as frequently contacting the ambulance service. Service users also completed the UCLA loneliness scale and personal community maps. Data were analysed thematically before triangulation with the UCLA loneliness scale and personal community maps. RESULTS: The final analysis was drawn from 15 staff and seven service user participants. The relationship between social isolation and loneliness and contacting the ambulance service was a contributing, but not the driving, factor in contacting the ambulance service. For service users, we identified three key themes: (1) impact on activities of daily living and loneliness and/or isolation as a result of a health condition; (2) accessing appropriate health and social care services to meet needs; (3) the link between social isolation and/or loneliness and contact with the ambulance service. The analysis of staff data also highlighted three key themes: (1) social isolation and/or loneliness in their role; (2) access to other appropriate health and social care services; (3) the impact of austerity and Covid-19 on social isolation and/or loneliness. CONCLUSIONS: Our research emphasises the complex nature of social isolation and loneliness, including the cyclic nature of poor health and social isolation and loneliness, and how this contributes to contact with the ambulance service. PATIENT OR PUBLIC CONTRIBUTION: The advisory group for the study was supported by a public and patient representative who contributed to the design of the study documentation, data analysis and authorship.

Development of the individual participant data integrity tool for assessing the integrity of randomised trials using individual participant data.

Increasing integrity concerns in medical research have prompted the development of tools to detect untrustworthy studies. Existing tools primarily assess published aggregate data (AD), though scrutiny of individual participant data (IPD) is often required to detect trustworthiness issues. Thus, we developed the IPD Integrity Tool for detecting integrity issues in randomised trials with IPD available. This manuscript describes the development of this tool. We conducted a literature review to collate and map existing integrity items. These were discussed with an expert advisory group; agreed items were included in a standardised tool and automated where possible. We piloted this tool in two IPD meta-analyses (including 116 trials) and conducted preliminary validation checks on 13 datasets with and without known integrity issues. We identified 120 integrity items: 54 could be conducted using AD, 48 required IPD, and 18 were possible with AD, but more comprehensive with IPD. An initial reduced tool was developed through consensus involving 13 advisors, featuring 11 AD items across four domains, and 12 IPD items across eight domains. The tool was iteratively refined throughout piloting and validation. All studies with known integrity issues were accurately identified during validation. The final tool includes seven AD domains with 13 items and eight IPD domains with 18 items. The quality of evidence informing healthcare relies on trustworthy data. We describe the development of a tool to enable researchers, editors, and others to detect integrity issues using IPD. Detailed instructions for its application are published as a complementary manuscript in this issue.

Real-time single-molecule observation of incipient collagen fibrillogenesis and remodeling.

The hierarchic assembly of fibrillar collagen into an extensive and ordered supramolecular protein fibril is critical for extracellular matrix function and tissue mechanics. Despite decades of study, we still know very little about the complex process of fibrillogenesis, particularly at the earliest stages where observation of rapidly forming, nanoscale intermediates challenges the spatial and temporal resolution of most existing microscopy methods. Using video rate scanning atomic force microscopy (VRS-AFM), we can observe details of the first few minutes of collagen fibril formation and growth on a mica surface in solution. A defining feature of fibrillar collagens is a 67-nm periodic banding along the fibril driven by the organized assembly of individual monomers over multiple length scales. VRS-AFM videos show the concurrent growth and maturation of small fibrils from an initial uniform height to structures that display the canonical banding within seconds. Fibrils grow in a primarily unidirectional manner, with frayed ends of the growing tip latching onto adjacent fibrils. We find that, even at extremely early time points, remodeling of growing fibrils proceeds through bird-caging intermediates and propose that these dynamics may provide a pathway to mature hierarchic assembly. VRS-AFM provides a unique glimpse into the early emergence of banding and pathways for remodeling of the supramolecular assembly of collagen during the inception of fibrillogenesis.

Traumatic Brain Injury, Seizures, and Cognitive Impairment Among Older Adults.

Importance: Traumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups. Objective: To investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association. Design, Setting, and Participants: This multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer's Coordination Center. Statistical analysis was performed from February 1 to April 3, 2024. Data were collected from participants from 36 Alzheimer's Disease Research Centers in the US who were 65 years or older at baseline, cognitively normal at baseline (Clinical Dementia Rating of 0 and no impairment based on a presumptive etiologic diagnosis of AD), and had complete information on race and ethnicity, age, sex, educational level, and apolipoprotein E genotype. Exposure: Health history of TBI, seizures, or both conditions. Main Outcomes and Measures: Progression to cognitive impairment measured by a Clinical Dementia Rating greater than 0. Results: Among the cohort of 7180 older adults (median age, 74 years [range, 65-102 years]; 4729 women [65.9%]), 1036 were African American or Black (14.4%), 21 were American Indian or Alaska Native (0.3%), 143 were Asian (2.0%), 332 were Hispanic (4.6%), and 5648 were non-Hispanic White (78.7%); the median educational level was 16.0 years (range, 1.0-29.0 years). After adjustment for selection basis using propensity score weighting, seizure was associated with a 40% higher risk of cognitive impairment (hazard ratio [HR], 1.40; 95% CI, 1.19-1.65), TBI with a 25% higher risk of cognitive impairment (HR, 1.25; 95% CI, 1.17-1.34), and both seizure and TBI were associated with a 57% higher risk (HR, 1.57; 95% CI, 1.23-2.01). The interaction models indicated that Hispanic participants with TBI and seizures had a higher risk of cognitive impairment compared with other racial and ethnic groups. The use of antiseizure medications (HR, 1.23; 95% CI, 0.99-1.53), antidepressants (HR, 1.32; 95% CI, 1.17-1.50), and antipsychotics (HR, 2.15; 95% CI, 1.18-3.89) was associated with a higher risk of cognitive impairment, while anxiolytic, sedative, or hypnotic use (HR, 0.88; 95% CI, 0.83-0.94) was associated with a lower risk. Conclusions and Relevance: This study highlights the importance of addressing TBI and seizures as risk factors for cognitive impairment among older adults. Addressing the broader social determinants of health and bridging the health divide across various racial and ethnic groups are essential for the comprehensive management and prevention of dementia.

The Individual Participant Data Integrity Tool for assessing the integrity of randomised trials.

Increasing concerns about the trustworthiness of research have prompted calls to scrutinise studies' Individual Participant Data (IPD), but guidance on how to do this was lacking. To address this, we developed the IPD Integrity Tool to screen randomised controlled trials (RCTs) for integrity issues. Development of the tool involved a literature review, consultation with an expert advisory group, piloting on two IPD meta-analyses (including 73 trials with IPD), preliminary validation on 13 datasets with and without known integrity issues, and evaluation to inform iterative refinements. The IPD Integrity Tool comprises 31 items (13 study-level, 18 IPD-specific). IPD-specific items are automated where possible, and are grouped into eight domains, including unusual data patterns, baseline characteristics, correlations, date violations, patterns of allocation, internal and external inconsistencies, and plausibility of data. Users rate each item as having either no issues, some/minor issue(s), or many/major issue(s) according to decision rules, and justification for each rating is recorded. Overall, the tool guides decision-making by determining whether a trial has no concerns, some concerns requiring further information, or major concerns warranting exclusion from evidence synthesis or publication. In our preliminary validation checks, the tool accurately identified all five studies with known integrity issues. The IPD Integrity Tool enables users to assess the integrity of RCTs via examination of IPD. The tool may be applied by evidence synthesists, editors and others to determine whether an RCT should be considered sufficiently trustworthy to contribute to the evidence base that informs policy and practice.

Coupled membranes: a mechanism of frequency filtering and transmission in the field cricket ear evidenced by micro-computed tomography, laser Doppler vibrometry and finite element analysis.

Many animals employ a second frequency filter beyond the initial filtering of the eardrum (or tympanal membrane). In the field cricket ear, both the filtering mechanism and the transmission path from the posterior tympanal membrane (PTM) have remained unclear. A mismatch between PTM vibrations and sensilla tuning has prompted speculations of a second filter. PTM coupling to the tracheal branches is suggested to support a transmission pathway. Here, we present three independent lines of evidence converging on the same conclusion: the existence of a series of linked membranes with distinct resonant frequencies serving both filtering and transmission functions. Micro-computed tomography (µ-CT) highlighted the 'dividing membrane (DivM)', separating the tracheal branches and connected to the PTM via the dorsal membrane of the posterior tracheal branch (DM-PTB). Thickness analysis showed the DivM to share significant thinness similarity with the PTM. Laser Doppler vibrometry indicated the first of two PTM vibrational peaks, at 6 and 14 kHz, originates not from the PTM but from the coupled DM-PTB. This result was corroborated by µ-CT-based finite element analysis. These findings clarify further the biophysical source of neuroethological pathways in what is an important model of behavioural neuroscience. Tuned microscale coupled membranes may also hold biomimetic relevance.

Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks' Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis.

Importance: Resuscitation with lower fractional inspired oxygen (FiO2) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear. Objective: To evaluate the relative effectiveness of initial FiO2 on reducing mortality, severe morbidities, and oxygen saturations (SpO2) in preterm infants born at less than 32 weeks' gestation using network meta-analysis (NMA) of individual participant data (IPD). Data Sources: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023. Study Selection: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks' gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO2. Data Extraction and Synthesis: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates. Main Outcomes and Measures: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO2 at 5 minutes. Results: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO2 was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO2 (OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO2 had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive. Conclusions and Relevance: High initial FiO2 (≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks' gestation compared to low initial FiO2 (low certainty). High initial FiO2 is possibly associated with reduced mortality compared to intermediate initial FiO2 (very low certainty) but more evidence is required.

A statistical primer on classical period-finding techniques in astronomy.

The aim of our paper is to investigate the properties of the classical phase-dispersion minimization (PDM), analysis of variance (AOV), string-length (SL), and Lomb-Scargle (LS) power statistics from a statistician's perspective. We confirm that when the data are perturbations of a constant function, i.e. under the null hypothesis of no period in the data, a scaled version of the PDM statistic follows a beta distribution, the AOV statistic follows an F distribution, and the LS power follows a chi-squared distribution with two degrees of freedom. However, the SL statistic does not have a closed-form distribution. We further verify these theoretical distributions through simulations and demonstrate that the extreme values of these statistics (over a range of trial periods), often used for period estimation and determination of the false alarm probability (FAP), follow different distributions than those derived for a single period. We emphasize that multiple-testing considerations are needed to correctly derive FAP bounds. Though, in fact, multiple-testing controls are built into the FAP bound for these extreme-value statistics, e.g. the FAP bound derived specifically for the maximum LS power statistic over a range of trial periods. Additionally, we find that all of these methods are robust to heteroscedastic noise aimed to mimic the degradation or miscalibration of an instrument over time. Finally, we examine the ability of these statistics to detect a non-constant periodic function via simulating data that mimics a well-detached binary system, and we find that the AOV statistic has the most power to detect the correct period, which agrees with what has been observed in practice.

Occurrence of a "forever chemical" in the atmosphere above pristine Amazon Forest.

Per- and polyfluoroalkyl substances (PFAS), often referred to as "forever chemicals", are a class of man-made, extremely stable chemicals, which are widely used in industrial and commercial applications. Exposure to some PFAS is now known to be detrimental to human health. By virtue of PFAS long residence times, they are widely detected in the environment, including remote locations such as the Arctics, where the origin of the PFAS is poorly understood. It has been suggested that PFAS may be transported through contaminated waters, leading to accumulation in coastal areas, where they can be aerosolised via sea spray, thereby extending their geographical distribution far beyond their original source regions. The aim of this work is to investigate, for the first time, whether "forever chemicals" could be transported to areas considered to be pristine, far from coastal sites. This study was performed at the Amazonian Tall Tower Observatory (ATTO), a unique remote site situated in the middle of the Amazon rainforest, where a restricted PFAS, perfluorooctanoic acid (PFOA), was observed with concentrations reaching up to 2 pg/m3. A clear trend of increasing concentration with sampling height was observed and air masses from the south over Manaus had the highest concentrations. Atmospheric lifetime estimations, removal mechanisms supported by measurements at two heights (320 and 42 m above the rainforest), and concentration spikes indicated a long-range transport of PFOA to pristine Amazon rainforest. Potential sources, including industrial activities in urban areas, were explored, and historical fire management practices considered. This research presents the first measurements of PFAS in the atmosphere of Amazon rainforest. Remarkably, even in this remote natural environment, appreciable levels of PFAS can be detected. This study provides valuable insights into the long-range transport of the anthropogenic "forever chemical" into a remote natural ecosystem and should raise awareness of potential environmental implications.

Reimagining general surgery resident selection: Collaborative innovation through design thinking.

Introduction: The process by which surgery residency programs select applicants is complex, opaque, and susceptible to bias. Despite attempts by program directors and educational researchers to address these issues, residents have limited ability to affect change within the process at present. Here, we present the results of a design thinking brainstorm to improve resident selection and propose this technique as a framework for surgical residents to creatively solve problems and generate actionable changes. Methods: Members of the Collaboration of Surgical Education Fellows (CoSEF) used the design thinking framework to brainstorm ways to improve the resident selection process. Members participated in one virtual focus group focused on identifying pain points and developing divergent solutions to those pain points. Pain points and solutions were subsequently organized into themes. Finally, members participated in a second virtual focus group to design prototypes to test the proposed solutions. Results: Sixteen CoSEF members participated in one or both focus groups. Participants identified twelve pain points and 57 potential solutions. Pain points and solutions were grouped into the three themes of transparency, fairness, and applicant experience. Members subsequently developed five prototype ideas that could be rapidly developed and tested to improve resident selection. Conclusions: The design thinking framework can help surgical residents come up with creative ideas to improve pain points within surgical training. Furthermore, this framework can supplement existing quantitative and qualitative methods within surgical education research. Future work will be needed to implement the prototypes devised during our sessions and turn them into complete interventions. Key message: In this paper, we demonstrate the results of a resident-led design thinking brainstorm on improving resident selection in which our team identified twelve pain points in resident selection, ideated 57 solutions, and developed five prototypes for further testing. In addition to sharing our results, we believe design thinking can be a useful framework for creative problem solving within surgical education.

Developing and Investigating a Nanovibration Intervention for the Prevention/Reversal of Bone Loss Following Spinal Cord Injury.

Osteoporosis disrupts the fine-tuned balance between bone formation and resorption, leading to reductions in bone quantity and quality and ultimately increasing fracture risk. Prevention and treatment of osteoporotic fractures is essential for reductions in mortality, morbidity, and the economic burden, particularly considering the aging global population. Extreme bone loss that mimics time-accelerated osteoporosis develops in the paralyzed limbs following complete spinal cord injury (SCI). In vitro nanoscale vibration (1 kHz, 30 or 90 nm amplitude) has been shown to drive differentiation of mesenchymal stem cells toward osteoblast-like phenotypes, enhancing osteogenesis and inhibiting osteoclastogenesis simultaneously. Here, we develop and characterize a wearable device designed to deliver and monitor continuous nanoamplitude vibration to the hindlimb long bones of rats with complete SCI. We investigate whether a clinically feasible dose of nanovibration (two 2 h/day, 5 days/week for 6 weeks) is effective at reversing the established SCI-induced osteoporosis. Laser interferometry and finite element analysis confirmed transmission of nanovibration into the bone, and microcomputed tomography and serum bone formation and resorption markers assessed effectiveness. The intervention did not reverse SCI-induced osteoporosis. However, serum analysis indicated an elevated concentration of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) in rats receiving 40 nm amplitude nanovibration, suggesting increased synthesis of type 1 collagen, the major organic component of bone. Therefore, enhanced doses of nanovibrational stimulus may yet prove beneficial in attenuating/reversing osteoporosis, particularly in less severe forms of osteoporosis.

Cell-Mediated Immune Responses May Play Roles in Osteochondral Allograft Transplantation Osteointegration Failures.

Prolonged and incomplete osteochondral allograft (OCA) osteointegration is consistently cited as a major mechanism for OCA treatment failure. Subrejection immune responses may play roles in this mode of failure. Preimplantation OCA preparation techniques, including subchondral bone drilling, thorough irrigation, and autogenous bone marrow aspirate concentrate saturation, may dampen immune responses and improve OCA osteointegration. This study sought to further characterize potential immune system contributions to OCA transplantation treatment failures by analyzing donor-recipient ABO and Rh-factor mismatches and histological and immunohistochemical assessments of transplanted OCA tissues recovered from revision surgeries. Using a dedicated registry, OCA transplant recipients with documented treatment failures who met inclusion criteria (n = 33) as well as age-, body mass index-, and joint-matched patients with successful outcomes (n = 70) were analyzed to compare matched cohorts of patients with successful versus failed OCA transplantation outcomes. Tissues recovered from 18 failed OCA transplants and portions of 7 nonimplanted OCA controls were further analyzed to provide contributing evidence for potential immune response mechanisms. For patients analyzed, no statistically significant differences in proportions for treatment success versus failure based on mismatches for ABO type, Rh factor, or both were noted. Further, no statistically significant differences in proportions for histological immune response presence or absence based on mismatches for ABO type, Rh factor, or both were noted. Twelve (67%) of the failed OCA tissues contained lymphocyte aggregations in the subchondral bone, which were comprised of combinations of CD3 + , CD4 + , CD8 + , and CD20+ lymphocytes. The mechanisms of failure for these 12 OCA transplants involved insufficient OCA osteointegration. Results of this study suggest that T- and B-cell-mediated subrejection immune responses may play roles in OCA transplant treatment failures independent of donor-recipient blood type mismatch effects.

How Does Personal Hygiene Influence Indoor Air Quality?

Humans are known to be a continuous and potent indoor source of volatile organic compounds (VOCs). However, little is known about how personal hygiene, in terms of showering frequency, can influence these emissions and their impact on indoor air chemistry involving ozone. In this study, we characterized the VOC composition of the air in a controlled climate chamber (22.5 m3 with an air change rate at 3.2 h-1) occupied by four male volunteers on successive days under ozone-free (∼0 ppb) and ozone-present (37-40 ppb) conditions. The volunteers either showered the evening prior to the experiments or skipped showering for 24 and 48 h. Reduced shower frequency increased human emissions of gas-phase carboxylic acids, possibly originating from skin bacteria. With ozone present, increasing the number of no-shower days enhanced ozone-skin surface reactions, yielding higher levels of oxidation products. Wearing the same clothing over several days reduced the level of compounds generated from clothing-ozone reactions. When skin lotion was applied, the yield of the skin ozonolysis products decreased, while other compounds increased due to ozone reactions with lotion ingredients. These findings help determine the degree to which personal hygiene choices affect the indoor air composition and indoor air exposures.