DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis.

Bacillus anthracis is the causative agent of anthrax. This Gram-positive bacterium poses a substantial risk to human health due to high mortality rates and the potential for malicious use as a bioterror weapon. To survive within the vertebrate host, B. anthracis relies on two-component system (TCS) signaling to sense host-induced stresses and respond to alterations in the environment through changes in target gene expression. HitRS and HssRS are cross-regulating TCSs in B. anthracis that respond to cell envelope disruptions and high heme levels, respectively. In this study, an unbiased and targeted genetic selection was designed to identify gene products that are involved in HitRS and HssRS signaling. This selection led to the identification of inactivating mutations within dnaJ and clpX that disrupt HitRS- and HssRS-dependent gene expression. DnaJ and ClpX are the substrate-binding subunits of the DnaJK protein chaperone and ClpXP protease, respectively. DnaJ regulates the levels of HitR and HitS to facilitate signal transduction, while ClpX specifically regulates HitS levels. Together, these results reveal that the protein homeostasis regulators, DnaJ and ClpX, function to maintain B. anthracis signal transduction activities through TCS regulation.

Directed evolution reveals the mechanism of HitRS signaling transduction in Bacillus anthracis.

Two component systems (TCSs) are a primary mechanism of signal sensing and response in bacteria. Systematic characterization of an entire TCS could provide a mechanistic understanding of these important signal transduction systems. Here, genetic selections were employed to dissect the molecular basis of signal transduction by the HitRS system that detects cell envelope stress in the pathogen Bacillus anthracis. Numerous point mutations were isolated within HitRS, 17 of which were in a 50-residue HAMP domain. Mutational analysis revealed the importance of hydrophobic interactions within the HAMP domain and highlighted its essentiality in TCS signaling. In addition, these data defined residues critical for activities intrinsic to HitRS, uncovered specific interactions among individual domains and between the two signaling proteins, and revealed that phosphotransfer is the rate-limiting step for signal transduction. Furthermore, this study establishes the use of unbiased genetic selections to study TCS signaling and provides a comprehensive mechanistic understanding of an entire TCS.

Effect of Low-Intensity vs Standard-Intensity Warfarin Prophylaxis on Venous Thromboembolism or Death Among Patients Undergoing Hip or Knee Arthroplasty: A Randomized Clinical Trial.

Importance: The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. Objective: To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. Design, Setting, and Participants: The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. Main Outcomes and Measures: The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Results: Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%). Conclusions and Relevance: Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01006733.

Safety and Efficacy of New Anticoagulants for the Prevention of Venous Thromboembolism After Hip and Knee Arthroplasty: A Meta-Analysis.

BACKGROUND: Venous thromboembolism (VTE) is a common and potentially fatal complication of arthroplasty. METHODS: We reviewed randomized trials to determine which anticoagulant has the best safety and efficacy in hip and knee arthroplasty patients. We searched PubMed, MEDLINE, and EMBASE through January 2016. RESULTS: Compared to enoxaparin (most commonly dosed 40 mg once daily), the relative risk (RR) of VTE was lowest for edoxaban 30 mg once daily (0.49; 95% confidence interval [CI], 0.32-0.75), fondaparinux 2.5 mg once daily (0.53; 95% CI, 0.45-0.63), and rivaroxaban 10 mg once daily (0.55; 95% CI, 0.46-0.66), and highest for dabigatran 150 mg once daily (1.19; 95% CI; 0.98-1.44). The RR of major/clinically relevant bleeding was lowest for apixaban 2.5 mg twice daily (0.84; 95% CI; 0.70-0.99) and highest for rivaroxaban (1.27; 95% CI, 1.01-1.59) and fondaparinux (1.64; 95% CI, 0.24-11.35). Fondaparinux was the only agent that was more effective than enoxaparin 30 mg twice daily (VTE RR = 0.58; 95% CI, 0.43-0.76). CONCLUSION: With the possible exception of apixaban, newer anticoagulants that lower the risk of postoperative VTE increase bleeding.

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

Importance: Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. Objective: To determine whether genotype-guided dosing improves the safety of warfarin initiation. Design, Setting, and Patients: The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. Main Outcomes and Measures: The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Results: Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51-0.99), 33 vs 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54-1.34), and there were no deaths. Conclusions and Relevance: Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Further research is needed to determine the cost-effectiveness of personalized warfarin dosing. Trial Registration: clinicaltrials.gov Identifier: NCT01006733.

Evaluating compliance with the 2013 best practice guidelines for preventing surgical site infection in high-risk pediatric spine surgery.

PURPOSE: Best Practice Guidelines (BPGs) were published one decade ago to decrease surgical site infection (SSI) in pediatric spinal deformity. Successful implementation has not been established. This study evaluated surgeon compliance with items on the BPG. We hypothesized that BPG authors and surgeons with more experience, higher caseload, and awareness of the BPG would have higher compliance. METHODS: We queried North American and European surgeons, authors and non-authors, and members of various spine study groups on adherence to BPGs using an anonymous survey. Mean compliance scores (MCSs) were developed by correlating Likert responses with MCSs ("None of the time" = no compliance = MCS 0, "Sometimes" = weak to moderate = MCS 1, "Most of the time" = high = MCS 2, "All the time" = perfect = MCS 3). RESULTS: Of the 142 respondents, 73.7% reported high or perfect compliance. Average compliance scores for all guidelines was 2.2 ± 0.4. There were significantly different compliance scores between North American and European surgeons (2.3 vs 1.8, p < 0.001), authors and non-authors (2.5 vs. 2.2, p = 0.023), and surgeons with and without knowledge of the BPGs (2.3 vs. 1.8, p < 0.001). There was a weak correlation between BPG awareness and compliance (r = 0.34, p < 0.001) and no correlation between years in practice (r = 0.0, p = 0.37) or yearly caseload (r = 0.2, p = 0.78) with compliance. CONCLUSIONS: Compliance among our cohort of surgeons surveyed was high. North American surgeons, authors of the BPGs and those aware of the guidelines had increased compliance. Participation in a spine study group, years in practice, and yearly caseload were not associated with compliance. LEVEL OF EVIDENCE: Level V-expert opinion.

Evaluating compliance with the best practice guidelines for wrong-level surgery prevention in high-risk pediatric spine surgery.

PURPOSE: In 2018, Best Practice Guidelines (BPGs) were published for preventing wrong-level surgery in pediatric spinal deformity, but successful implementation has not been established. The purpose of this study was to evaluate BPG compliance 5 years after publication. We hypothesized higher compliance among BPG authors and among surgeons with more experience, higher caseload, and awareness of the BPGs. METHODS: We queried North American and European surgeons, authors and nonauthors, and members of pediatric spinal study groups on adherence to BPGs using an anonymous survey consisting of 18 Likert scale questions. Respondents provided years in practice, yearly caseload, and guideline awareness. Mean compliance scores (MCS) were developed by correlating Likert responses with MCS scores ("None of the time" = no compliance = MCS 0, "Sometimes" = weak to moderate = MCS 1, "Most of the time" = high = MCS 2, and "All the time" = perfect = MCS 3). RESULTS: Of the 134 respondents, 81.5% reported high or perfect compliance. Average MCS for all guidelines was 2.4 ± 0.4. North American and European surgeons showed no compliance differences (2.4 vs. 2.3, p = 0.07). Authors and nonauthors showed significantly different compliance scores (2.8 vs 2.4, p < 0.001), as did surgeons with and without knowledge of the BPGs (2.5 vs 2.2, p < 0.001). BPG awareness and compliance showed a moderate positive correlation (r = 0.48, p < 0.001), with non-significant associations between compliance and both years in practice (r = 0.41, p = 0.64) and yearly caseload (r = 0.02, p = 0.87). CONCLUSION: Surgeons reported high or perfect compliance 81.5% of the time with BPGs for preventing wrong-level surgery. Authorship and BPG awareness showed increased compliance. Location, study group membership, years in practice, and yearly caseload did not affect compliance. LEVEL OF EVIDENCE: Level V-expert opinion.

Ultrasound Shear Wave Elastography Quantitatively Assesses Tension Changes of Supraspinous/Interspinous Ligament Complex Under Varied Loads.

BACKGROUND: Although interspinous and supraspinous ligaments of the lumbar spine are thought to contribute to spinal stability, little is known about their dynamic biomechanics. We demonstrate that shear wave elastography (SWE) offers a novel technique to noninvasively and quantitatively evaluate posterior spinous ligament complex functional loading and stiffness in different physiologic positions. METHODS: We performed SWE and measured the length of the interspinous/supraspinous ligament complex in cadaveric torsos (N = 5), isolated ligaments (N = 10), and healthy volunteers (N = 9) to obtain length and shear wave velocity measurements. For cadavers and volunteers, SWE was utilized in 2 lumbar positions: lumbar spine flexion and extension. In addition, SWE was performed on isolated ligaments undergoing uniaxial tension to correlate shear wave velocities with experienced load. RESULTS: Average shear wave velocity in cadaveric supraspinous/interspinous ligament complexes increased for lumbar levels (23%-43%) and most thoracic levels (0%-50%). This corresponded to an average increase in interspinous distance from extension to flexion for the lumbar spine (19%-63%) and thoracic spine (3%-8%). Volunteer spines also demonstrated an average increase in shear wave velocity from extension to flexion for both the lumbar spine (195% at L2-L3 to 200% at L4-L5) and thoracic spine (31% at T10-T11). There was an average increase in interspinous distance from extension to flexion for the lumbar spine (93% at L2-L3 to 127% at L4-L5) and thoracic spine (11% at T10-T11). In isolated ligaments, there was a positive correlation between applied tensile load and average shear wave velocity. CONCLUSION: This study creates a foundation to apply SWE as a noninvasive tool for assessing the mechanical stiffness of posterior ligamentous structures and has potential applications in augmenting or evaluating these ligaments in patients with spine pathology. CLINICAL RELEVANCE: The interspinous and supraspinous ligaments are critical soft tissue supports of the posterior lumbar spine. Disruption of these structures is thought to have a negative impact on spinal stability in trauma and spine deformities.

Clinical spine care partnerships between high-income countries and low-and-middle-income countries: A scoping review.

BACKGROUND: Clinical collaboration between spine professionals in high-income countries (HICs) and low-and-middle-income countries (LMICs) may provide improvements in the accessibility, efficacy, and safety of global spine care. Currently, the scope and effectiveness of these collaborations remain unclear. In this review, we describe the literature on the current state of these partnerships to provide a framework for exploring future best practices. METHODS: PubMed, Embase, and Cochrane Library were queried for articles on spine-based clinical partnerships between HICs and LMICs published between 2000 and March 10, 2023. This search yielded 1528 total publications. After systematic screening, nineteen articles were included in the final review. RESULTS: All published partnerships involved direct clinical care and 13/19 included clinical training of local providers. Most of the published collaborations reviewed involved one of four major global outreach organizations with the majority of sites in Africa. Participants were primarily physicians and physicians-in-training. Only 5/19 studies reported needs assessments prior to starting their partnerships. Articles were split on evaluative focus, with some only evaluating clinical outcomes and some evaluating the nature of the partnership itself. CONCLUSIONS: Published studies on spine-focused clinical partnerships between HICs and LMICs remain scarce. Those that are published often do not report needs assessments and formal metrics to evaluate the efficacy of such partnerships. Toward improving the quality of spine care globally, we recommend an increase in the quality and quantity of published studies involving clinical collaborations between HICs and LICs, with careful attention to reporting early needs assessments and evaluation strategies.

Living with a C2-Sacrum Spinal Fusion: Surgical Outcomes and Quality of Life in Patients Fused from C2 to the Sacrum.

STUDY DESIGN: Single center, retrospective cohort study. OBJECTIVES: Little is known about the surgical outcomes and quality of life in patients with C2-sacrum posterior spinal fusion (PSF). Though it is thought to be a "final" construct, it remains unknown how patients fare postoperatively. We sought to evaluate the surgical outcomes and quality of life of patients after C2-sacrum PSF. METHODS: Consecutive patients undergoing C2-Sacrum PSF from 2015-2020 by 4 surgeons at a single institution were included. The study time period for each patient began after their index operation that led to the C2-sacrum fusion. Dates of surgery, complications, reoperations, patient reported outcomes (PROs) including EuroQol 5 Dimensions (EQ-5D), Oswestry Disability Index (ODI), Scoliosis Research Society (SRS) questionnaires, and activities of daily living (ADL) questions were collected and analyzed. Descriptive statistics, paired t-tests, student t-tests, and linear regression were used. RESULTS: Of the 23 patients who underwent C2-sacrum PSF, 6 patients (26%) required a total of 10 reoperations after a mean of 1.5 years (range 0-4 years) after C2-sacrum PSF. Five reoperations were for mechanical failure; 3 for wound complications/infection; and 2 for instrumentation and spinous process prominence. PROs were collected on 18 patients with mean follow-up of 2.4 years (range .5-4.5) after their C2-sacrum PSF. At 6-months, both SRS-22 and ODI scores improved significantly after C2-sacrum PSF (SRS: 57.5 to 76.3, P = .0014; ODI: 47.0 to 31.7, P = .013). Similarly, at a mean 2.4 years postoperatively, mean ODI improved significantly (47.0 to 30.4, P = .0032). Six patients (33%) had minimal symptoms (ODI <20). The median postoperative EQ-5D score was .74 (range .19 to 1.0), which compares favorably to patients with hip/knee osteoarthritis (EQ-5D .63) and diabetes mellitus (DM) (EQ-5D .69) and hypertension (HTN). In terms of activities of daily living (ADL), 10 patients (56%) exercised regularly-a mean 4.5 days/week. 11 (61%) could do light aerobic activity (e.g. stationary bike). 10 (55%) were able to play with children/grandchildren as desired. Eight patients (44%) hiked, and 2 (11%) drove independently. 11 (61%) could tolerate short air-travel comfortably. Of the 17 patients who could toilet and perform basic hygiene preoperatively, 16 (94%) were able to do so postoperatively. CONCLUSION: Though C2-sacrum PSF is thought to be a "final" construct, approximately 1 in 4 patients require subsequent operations. However, C2-sacrum PSF patients had a significant improvement in SRS and ODI scores by 6 months postop. Over 60% of patients were regularly performing light aerobic activity 2 years after their C2-sacrum PSF. EQ-5D suggests that this population fares better than those with degenerative hip/knee arthritis and similarly to those with common chronic conditions like DM and HTN.

Association Between In-Home Treatment and Engagement in Psychosocial Services Among Medicaid-Enrolled Youth.

OBJECTIVE: Prior studies have identified low rates of engagement in mental health (MH) services in clinic settings among children enrolled in Medicaid. Yet, little is known about whether the delivery of in-home MH treatment (in which the clinician travels to the child's home) improves engagement for this population. This study examines the association between the delivery of in-home psychosocial treatment and engagement in services among Medicaid-enrolled youth. METHOD: We used 2010 to 2014 Georgia Medicaid claims data to identify 53,508 children and adolescents (aged 5-17 years) with a MH diagnosis that initiated new psychosocial treatment. We estimated regression models controlling for covariates to examine the relationship of the receipt of any in-home psychosocial treatment in the home setting with 3 outcome measures of engagement: receipt of at least 4 psychosocial visits during the first 12 weeks; total number of psychosocial visits during the first 12 weeks; and total duration of service use. RESULTS: Those who received any in-home psychosocial treatment (compared to those who did not) had 4.3 times the odds (odds ratio = 4.3, 95% CI = 4.0, 4.7) of receiving at least 4 visits during the first 12 weeks, had 4.5 (95% CI = 4.3, 4.7) more predicted visits during the first 12 weeks, and had a longer treatment episode duration (mean rate ratio = 1.54, 95% CI = 1.48,1.59). CONCLUSION: Although many Medicaid-enrolled youth do not receive a sufficient number of MH services to achieve positive outcomes, our findings suggest that providing in-home psychosocial treatment can improve service engagement and potentially help address this challenge.

An RNA-binding protein acts as a major post-transcriptional modulator in Bacillus anthracis.

HitRS is a two-component system that responds to cell envelope damage in the human pathogen Bacillus anthracis. Here we identify an RNA-binding protein, KrrA, that regulates HitRS function by modulating the stability of the hitRS mRNA. In addition to hitRS, KrrA binds to over 70 RNAs and, directly or indirectly, affects the expression of over 150 genes involved in multiple processes, including genetic competence, sporulation, RNA turnover, DNA repair, transport, and cellular metabolism. KrrA does not exhibit detectable nuclease activity in vitro, and thus the mechanism by which it modulates mRNA stability remains unclear.

What Radiographic and Clinical Factors Ultimately Necessitate a C2-Sacrum Instrumented Posterior Spinal Fusion?

OBJECTIVE: /Hypothesis: Patients undergoing C2-sacrum PSF have unique medical histories and multiple prior operations over an extended period. DESIGN: Single center, retrospective cohort. METHODS: Consecutive C2-sacrum PSF patients operated on by 4 surgeons at a single-center from 2015-2020 were reviewed. Demographics, comorbidities, indications, surgical history, and radiographic parameters were collected. RESULTS: 23 patients underwent C2-sacrum PSF. 13 (57%) were male, and 21 (91.3%) were adults. Mean age at time of first spine surgery was 44 years (range 5-71) and 53 years (range 14-72) at the time of C2-sacrum PSF. Six patients (26%) had osteoporosis, and 6 patients (26%) had neurologic comorbidities-including Parkinson's disease (4), cerebral palsy (1), and Brown Sequard syndrome (1). Four (17%) had connective tissue disease. Two patients underwent C2-sacrum PSF as an index procedure: (1) 67M with myelomatous fractures and 124° of cervicothoracic kyphosis; (2) 28F with severe Marfan syndrome with 140° thoracic scoliosis and 130° thoracic kyphosis. The remaining 21 (91%) underwent C2-sacrum PSF as a revision following prior spinal surgeries on average, 4 previous surgeries (range 1-13) over 10.5 years (range .3-37.4). Indications for the remaining 21 C2-sacrum PSF revision procedures included 17 (81%) for kyphosis (5 of whom also had significant coronal deformity), 1 (5%) for only coronal malalignment, 2 (10%) for instrumentation failure, and 1 (5%) for myelopathy. CONCLUSIONS: 91% (21/23) of patients requiring C2-sacrum PSF were treated as revisions of prior fusions, with a mean of 4 prior surgeries over 10 years. Over 80% of these patients underwent C2-sacrum PSF to address kyphosis. 26% had neurologic conditions, and 26% had osteoporosis.

Neuroscience, Empathy, and Violent Crime in an Incarcerated Population: A Narrative Review.

Empathy is a fundamental construct that allows individuals to perceive and understand the cognitive and emotional state of others. Empathy is not only a psychological and sociological concept; it also heavily impacts our daily lives by affecting our decisions and actions. Empathy is connected to and involves specific parts of the brain which, if damaged or of reduced volume, can lead to actions that are morally unjust, aggressive, or simply denoting a lack of understanding and sensitivity. The literature affirms that the low level of empathy, guilt, embarrassment, and moral reasoning displayed by violent and psychopathic criminals is strongly associated with empathy-linked brain regions that are smaller in size or less developed. The aim of this review is to show empirical data over the last 5 years on the connection between empathy and neuroscience among violent and psychopathic offenders, reflecting on future research on the topic.

Radiology podcasting as a model for asynchronous remote learning in the COVID-19 era.

RATIONALE AND OBJECTIVES: We aimed to create an open access online radiology podcast to educate listeners at any time, from anywhere. To meet learner needs and improve the likelihood of successful implementation and utilization, we assessed radiology trainee attitudes and experiences of podcasts. MATERIALS AND METHODS: We developed an educational podcast, From the Viewbox, focused on evergreen themes and practical approaches to radiology. Content categories included Diagnostic Approach, Specific Imaging Diagnoses, Noninterpretive Skills, and Special Topics. We released and promoted episodes on multiple digital platforms. Radiology trainees were surveyed and data were analyzed to assess listener preferences and usage trends. RESULTS: Only 19% of our trainees had previously listened to a radiology podcast, yet 81% expressed interest in listening routinely. After initial release, 86% of trainees listened to the podcast and 62% listened routinely. Episodes gained the most plays immediately following release but retained and continued to attract more listeners. The most popular episode discussing COVID-19 diagnosis and imaging, emphasized the importance of selecting high yield content to match listener needs. Most trainees felt the podcast had "very high" or "high" value in educational value, accessibility, and time efficiency. CONCLUSIONS: From the Viewbox offers efficient and accessible audio-only learning modules that can be used independently or effectively paired with traditional resources to decrease barriers in radiology education and enhance learner productivity. Podcasting is an underutilized asynchronous remote learning tool that can help overcome current challenges of social distancing, and more importantly address the diverse preferences and needs of our learners.

Research Participants' Attitudes towards Receiving Information on Genetic Susceptibility to Arsenic Toxicity in Rural Bangladesh.

BACKGROUND: In human genetics research, it has become common practice for researchers to consider returning genetic information to participants who wish to receive it. Research participants in lower-resource settings may have barriers or competing interests that reduce the benefit or relevance of such information. Thus, the decision to return genetic information in these settings may involve special considerations of participants' interests and preferences. In this project, our goal was to assess Bangladeshi research participants' attitudes towards receiving information regarding genetic susceptibility to the effects of consuming arsenic-contaminated drinking water, a serious environmental health concern in Bangladesh and other countries. METHODS: We administered a short questionnaire to 200 individuals participating in the Health Effects of Arsenic Longitudinal Study. Associations between survey responses and participant characteristics were estimated using logistic regression. RESULTS: Overall, 100% of our participants were interested in receiving information regarding their genetic susceptibility to arsenic toxicities, and 91% indicated that being at increased genetic risk would motivate them to make efforts to reduce their exposure. Lower levels of education showed evidence of association with less concern regarding the health effects of arsenic and lower levels of motivation to reduce exposure in response to genetic information. CONCLUSIONS: Research participants in this low-resource setting appeared interested in receiving information on their genetic susceptibility to arsenic toxicity and motivated to reduce exposure in response to such information. Additional research is needed to understand how best to communicate genetic information in this population and to assess the impact of such information on individuals' behaviors and health.

Dose-response relationship between local anesthetic volume and hemidiaphragmatic paresis following ultrasound-guided supraclavicular brachial plexus blockade.

BACKGROUND: There is no consensus regarding what volume of local anesthetic should be used to achieve successful supraclavicular block while minimizing hemidiaphragmatic paresis (HDP). This study investigated the dose-response relationship between local anesthetic volume and HDP after ultrasound-guided supraclavicular brachial plexus block. METHODS: A dose escalation design was used to define the dose response curve for local anesthetic volume and incidence of HDP in subjects undergoing upper extremity surgery with supraclavicular block as the primary anesthetic. Dosing levels of 5, 10, 15, 20, 25, 30, 35 and 40 mL of local anesthetic were administered in cohorts of three subjects per dose. Diaphragm function was assessed with M-mode ultrasound before and after block. Secondary objectives included assessment of negative inspiratory force (NIF), oxygen saturation, subjective dyspnea and extent of sensory and motor blockade. RESULTS: Twenty-one subjects completed the study. HDP was present at all doses, with an incidence of 33% at 5 mL to 100% at 30-35 mL. There was a significant decrease in NIF (7.5 cmH2O, IQR (22,0); p=0.01) and oxygen saturation on room air (1%, IQR (2,0); p=0.01) 30 min postblock in subjects experiencing HDP but not in those without HDP. There was no increase in dyspnea in subjects with or without HDP. No subject required respiratory intervention. Motor and sensory block improved with increasing dose, and subjects with HDP exhibited denser blocks than those without (p<0.01). CONCLUSIONS: There is no clinically relevant volume of local anesthetic at which HDP can be avoided when performing a supraclavicular block. In our subject population free of respiratory disease, HDP was well tolerated. TRIAL REGISTRATION NUMBER: NCT03138577.

Determinants of telomere length across human tissues.

Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little is known regarding variability in TL in nonblood, disease-relevant tissue types. Here, we characterize variability in TLs from 6391 tissue samples, representing >20 tissue types and 952 individuals from the Genotype-Tissue Expression (GTEx) project. We describe differences across tissue types, positive correlation among tissue types, and associations with age and ancestry. We show that genetic variation affects TL in multiple tissue types and that TL may mediate the effect of age on gene expression. Our results provide the foundational knowledge regarding TL in healthy tissues that is needed to interpret epidemiological studies of TL and human health.