Search

The high rate of antibiotic resistance constitutes a global threat to the continuous use of these drugs, because of increasing treatment failures. The aim of this study was to survey antibiotic prescription practices of veterinarians and the possible contribution to antimicrobial resistance (AMR) and antimicrobial stewardship (AMS) in Nigeria during the COVID era. This was a cross-sectional study that used a 33-question survey questionnaire administered to registered veterinarians in Nigeria. The study was both online survey and hard copy administered during the annual meeting of the veterinarians from July to October 2021. Descriptive statistics, bivariate analysis using Chi-square test were also done to analyze the results, while a two-tailed P-value of0.05 at 95% confidence level was considered statistically significant. IBM SPSS Version 26 was used to analyze the data. A total of 172 respondents completed the online and hard copy questionnaire. Majority of the respondents engaged majorly in mixed veterinary practice (72.1%). A total of 53.5% were aware of the country's policy concerning antibiotic prescription, while majority (64.5%) do not do culture and sensitivity before antibiotic prescription. Majority (34.3%) felt that the risk of potential adverse drug reaction could affect their decision when choosing to prescribe an antibiotic to the owner. Majority (51.2%) felt that some antibiotics were over prescribed, while 26.7% opined that all antibiotics were appropriately prescribed. To improve antibiotic use and practice amongst veterinarians in Nigeria, dependence on laboratory services for antibiotic prescription, enforcement of national guidelines and monitoring of antibiotic prescription amongst the veterinarians is essential to curb over-prescription and strengthen antimicrobial stewardship.

The introduction of anaesthesia on 16 October 1846 brought about tremendous changes in the discipline of surgery. We sought to determine whether the concept of painless surgery was accepted by practitioners and patients, and whether this led to an increase in frequency and variety of surgical operations performed. To study these changes, we analysed surgical records from Massachusetts General Hospital, Boston, Massachusetts (MGH) in the months surrounding the discovery of ether anaesthesia. Surgical records from MGH between 25 February 1846 and 14 March 1847 were examined, and the variables studied included number of operations, type of operations, patient demographics, complications and analgesics used, as well as comments made by surgeons. Immediately following the introduction of anaesthesia, MGH experienced a sizeable increase in the volume of surgical operations. This included a doubling in the percentage of female patients undergoing surgery. Orthopaedic procedures and amputations both increased in frequency, as did the number of surgeons operating. Several records indicated the presence of postoperative wound infection. Operations were still performed without anaesthesia. Following the introduction of ether anaesthesia in 1846, surgical volume increased, and more women underwent surgery. This suggests early acceptance of anaesthesia by patients and the medical profession. In an era prior to the introduction of antiseptic and aseptic techniques it is not surprising that wound infections were observed in several patients. We provide a glimpse of anaesthesia and surgery during the first few months after the first public demonstration of anaesthesia at MGH.

The COVID-19 pandemic is a traumatic stressor resulting in anxiety, depression, post-traumatic stress, and burnout among healthcare workers. We describe an intervention to support the health workforce and summarize results from its 40-week implementation in a large, tri-state health system during the COVID-19 pandemic.We conducted 121 virtual and interactive Stress and Resilience Town Halls attended by 3555 healthcare workers. Town hall participants generated 1627 stressors and resilience strategies that we coded and analyzed using rigorous qualitative methods (Kappa = 0.85).We identify six types of stressors and eight types of resilience strategies reported by healthcare workers, how these changed over time, and how town halls were responsive to emerging health workforce needs. We show that town halls dedicated to groups working together yielded 84% higher mean attendance and more sharing of stressors and resilience strategies than those offered generally across the health system, and that specific stressors and strategies are reported consistently while others vary markedly over time.The virtual and interactive Stress and Resilience Town Hall is an accessible, scalable, and sustainable intervention to build mutual support, wellness, and resilience among healthcare workers and within hospitals and health systems responding to emerging crises, pandemics, and disasters.

Background The Kids Intracranial Injury Decision Support tool for Traumatic Brain Injury (KIIDS-TBI) tool is a validated risk prediction model for managing children with mild traumatic brain injuries (mTBI) and intracranial injuries. Electronic clinical decision support (CDS) may facilitate the clinical implementation of this evidence-based guidance. Objective Our objective was to evaluate the acceptability and usability of an electronic CDS tool for managing children with mTBI and intracranial injuries. Methods Emergency medicine and neurosurgery physicians (10 each) from 10 hospitals in the United States were recruited to participate in usability testing of a novel CDS prototype in a simulated electronic health record environment. Testing included a think-aloud protocol, an acceptability and usability survey, and a semi-structured interview. The prototype was updated twice during testing to reflect user feedback. Usability problems recorded in the videos were categorized using content analysis. Interview transcripts were analyzed using thematic analysis. Results Among the 20 participants, most worked at teaching hospitals (80%), freestanding children's hospitals (95%), and level-1 trauma centers (75%). During the two prototype updates, problems with clarity of terminology and navigating through the CDS interface were identified and corrected. Corresponding to these changes, the number of usability problems decreased from 35 in phase 1 to 8 in phase 3 and the number of mistakes made decreased from 18 (phase 1) to 2 (phase 3). Through the survey, participants found the tool easy to use (90%), useful for determining a patient's level of care (95%), and likely to improve resource use (90%) and patient safety (79%). Interview themes related to the CDS's ability to support evidence-based decision-making and improve clinical workflow proposed implementation strategies and potential pitfalls. Conclusion After iterative evaluation and refinement, the KIIDS-TBI CDS tool was found to be highly usable and useful for aiding the management of children with mTBI and intracranial injuries.

Price transparency is an increasingly popular solution for high healthcare expenditures in the United States, but little is known about its potential to facilitate patient price shopping. Our objective was to analyze interhospital and interpayer price variability in spine surgery and spine imaging using newly public payer-specific negotiated charges (PNCs). We selected a subset of billing codes for spine surgery and spine imaging at 12 hospitals within a Saint Louis metropolitan area healthcare system. We then compared PNCs for these procedures and tested for significant differences in interhospital and interinsurer IQR using the Mann-Whitney U Test. We found significantly greater IQRs of PNCs as a factor of the insurance plan than as a factor of the hospital for cervical spinal fusions (interinsurer IQR $8256; interhospital IQR $533; P.0001), noncervical spinal fusions (interinsurer IQR $28 423; interhospital IQR $5512; P.001), computed tomographies of the lower spine (interinsurer IQR $595; interhospital IQR $113; P.0001), and MRIs lower spinal canal (interinsurer IQR $1010; interhospital IQR $158; P.0001). There was no significant difference between the interinsurer IQR and the interhospital IQR for lower spine x-rays (interinsurer IQR $107; interhospital IQR $67; P = .0543). Despite some between-hospital heterogeneity, we show significantly higher price variability between insurers than between hospitals. Our single system analysis limits our ability to generalize, but our results suggest that savings depend more on hospital and provider negotiations than patient price shopping, given the difficulty of switching insurers.

In the current paper, we aim to expand the dialogue about applying psychological flexibility processes to moral injury-related spiritual suffering using Acceptance and Commitment Therapy (ACT). Psychological flexibility is the process of practicing present moment awareness and openness to experiences of emotions and thoughts, while also choosing to engage in actions that are consistent with one's values. This open, aware, and engaged approach to life fits well with spiritual endeavors. We provide a framework and a case example illustrating how spiritual care providers and Chaplains can use psychological flexibility processes to target spiritual suffering in the context of moral injury.

Background The impact of telemedicine on ambulatory care quality is a key question for policymakers as they navigate payment reform for remote care. Objective To evaluate whether utilizing telemedicine in the first 9 months of the COVID-19 pandemic impacted performance on a diabetes quality of care measure for patients at a large academic medical center. We hypothesized care quality would reduce less among telemedicine users. Design Quasi-experimental design using binomial logistic regression. Covariates included age, gender, race, ethnicity, type of insurance, hierarchical condition category score, primary language at the individual level, and zip code–level income. Participants All adult patients younger than 75 years of age diagnosed with type 2 diabetes mellitus (N = 16,588) as of 3/19/2020 at a single academic health center. Interventions Completion of one or more telemedicine encounters with an institutional primary care physician or endocrinologist between 3/19/2020 and 12/19/2020. Main Measures The components met in a five-item composite measure of diabetes quality of care, as of patients’ last clinical encounter. Items were (1) systolic blood pressure less than 140 mmHg, (2) hemoglobin A1c less than 8.0%, (3) using a statin and (4) aspirin, and (5) tobacco non-use. Key Results From the pre- to post-period, the probability of meeting any given component of the composite measure for patients only utilizing in-person care was 21% lower (OR, 95% CI 0.79; 0.76, 0.81) and for the telemedicine users 2% lower (OR 0.98; 0.85, 1.13). There was an increased likelihood of meeting any given component among telemedicine users compared to in-person care alone (OR 1.25; 1.08, 1.44). Conclusions Patients with diabetes utilizing telemedicine performed similarly on a composite measure of diabetes care quality compared to before the pandemic. Those not utilizing telemedicine had reductions. Telemedicine use maintained quality of care for patients with diabetes during the first 9 months of the COVID-19 pandemic.

Although blood DNA methylation (DNAm) profiles are reported to be associated with breast cancer incidence, they have not been widely used in breast cancer risk assessment. Among a breast cancer case–cohort of 2774 women (1551 cases) in the Sister Study, we used candidate CpGs and DNAm estimators of physiologic characteristics to derive a methylation‐based breast cancer risk score, mBCRS. Overall, 19 CpGs and five DNAm estimators were selected using elastic net regularization to comprise mBCRS. In a test set, higher mBCRS was positively associated with breast cancer incidence, showing similar strength to the polygenic risk score (PRS) based on 313 single nucleotide polymorphisms (313 SNPs). Area under the curve for breast cancer prediction was 0.60 for self‐reported risk factors (RFs), 0.63 for PRS, and 0.63 for mBCRS. Adding mBCRS to PRS and RFs improved breast cancer prediction from 0.66 to 0.71. mBCRS findings were replicated in a nested case–control study within the EPIC‐Italy cohort. These results suggest that mBCRS, a risk score derived using blood DNAm, can be used to enhance breast cancer prediction., Blood samples were collected between 2003 and 2009 from a prospective cohort of 50 844 cancer‐free women. Among a case–cohort subsample (2774 women; 1551 incident breast cancers) selected in 2014, DNA methylation was profiled using HumanMethylation450 BeadChips. Elastic net regularization derived a methylation‐based breast cancer risk score (mBCRS). In a validation sample, mBCRS values were higher among cases and improved breast cancer prediction.

This study aimed to test the efficacy of self-monitoring and feedback (SM+FB) versus SM without FB (SM) in a behavioral weight-loss intervention at 6 months.This was a randomized clinical trial. Eligibility criteria included the following: ≥18 years of age, BMI ≥ 27 and ≤43, smartphone user, and ability to engage in moderate physical activity. All participants received a 90-minute 1:1 counseling session, a Fitbit Charge 2, and a digital scale for SM. SM+FB participants were provided access to a customized smartphone application that provided three daily FB messages. The primary outcome was percentage of weight change from 0 to 6 months.The sample (N = 502) was 45 (SD 14.4) years old, BMI was 33.7 (SD 4.00) kg/mThere was no significant between-group difference in weight loss at 6 months.

BACKGROUND CONTEXT There is growing interest among payers in profiling hospital value and quality-of-care, including both the cost and safety of common surgeries, such as lumbar fusion. Nonetheless, there is sparse evidence describing the statistical reliability of such measures when applied to lumbar fusion for spondylolisthesis. PURPOSE To evaluate the reliability of 90-day inpatient hospital costs, overall complications, and rates of serious complications for profiling hospital performance in lumbar fusion surgery for spondylolisthesis. STUDY DESIGN/SETTING Data for this analysis came from State Inpatient Databases from nine states made available through the Healthcare Cost and Utilization Project. PATIENT SAMPLE Patients undergoing elective lumbar spine fusion for spondylolisthesis from 2010 to 2017 in participating states. OUTCOME MEASURES Statistical reliability, defined as the ability to distinguish true performance differences across hospitals relative to statistical noise. Reliability was assessed separately for 90-day inpatient costs (standardized across years to 2019 dollars), overall complications, and serious complication rates. METHODS Statistical reliability was measured as the amount of variation between hospitals relative to the total amount of variation for each measure. Total variation includes both between-hospital variation (“signal”) and within-hospital variation (“statistical noise”). Thus, reliability equals signal over (signal plus noise) and ranges from 0 to 1. To adjust for differences in patient-level risk and procedural characteristics, hierarchical linear and logistic regression models were created for the cost and complication outcomes. Random hospital intercepts were used to assess between-hospital variation. We evaluated the reliability of each measure by study year and examined the number of hospitals meeting different thresholds of reliability by year. RESULTS We included a total of 66,571 elective lumbar fusion surgeries for spondylolisthesis performed at 244 hospitals during the study period. The mean 90-day hospital cost was $30,827 (2019 dollars). 12.0% of patients experienced a complication within 90 days of surgery, including 7.8% who had a serious complication. The median reliability of 90-day cost ranged from 0.97to 0.99 across study years, and there was a narrow distribution of reliability values. By comparison, the median reliability for the overall complication metric ranged from 0.22 to 0.44, and the reliability of the serious complication measure ranged from 0.30 to 0.49 across the study years. At least 96% of hospitals had high (> 0.7) reliability for cost in any year, whereas only 0-9% and 0-11% of hospitals reached this cutoff for the overall and serious complication rate in any year, respectively. By comparison, 10%–69% of hospitals per year achieved a more moderate threshold of 0.4 reliability for overall complications, compared to 21%–80% of hospitals who achieved this lower reliability threshold for serious complications. CONCLUSIONS 90-day inpatient costs are highly reliable for assessing variation across hospitals, whereas overall and serious complications are only moderately reliable for profiling performance. These results support the viability of emerging bundled payment programs that assume true differences in costs of care exist across hospitals.

Background High-cost high-need patients are typically defined by risk or cost thresholds which aggregate clinically diverse subgroups into a single ‘high-need high-cost’ designation. Programs have had limited success in reducing utilization or improving quality of care for high-cost high-need Medicaid patients, which may be due to the underlying clinical heterogeneity of patients meeting high-cost high-need designations. Methods Our objective was to segment a population of high-cost high-need Medicaid patients (N = 676,161) eligible for a national complex case management program between January 2012 and May 2015 to disaggregate clinically diverse subgroups. Patients were eligible if they were in the top 5 % of annual spending among UnitedHealthcare Medicaid beneficiaries. We used k-means cluster analysis, identified clusters using an information-theoretic approach, and named clusters using the patients’ pattern of acute and chronic conditions. We assessed one-year overall and preventable hospitalizations, overall and preventable emergency department (ED) visits, and cluster stability. Results Six clusters were identified which varied by utilization and stability. The characteristic condition patterns were: 1) pregnancy complications, 2) behavioral health, 3) relatively few conditions, 4) cardio-metabolic disease, and complex illness with relatively 5) low or 6) high resource use. The patients varied by cluster by average ED visits (2.3–11.3), hospitalizations (0.3–2.0), and cluster stability (32–91%). Conclusions We concluded that disaggregating subgroups of high-cost high-need patients in a large multi-state Medicaid sample identified clinically distinct clusters of patients who may have unique clinical needs. Segmenting previously identified high-cost high-need populations thus may be a necessary strategy to improve the effectiveness of complex case management programs in Medicaid.

Background: The development and consequences of hypertension involve multiple biological systems that may include changes in immune profiles. Whether hypertension is related to peripheral immune cell composition has not been examined in large human cohorts. Methods: We estimated circulating proportions of 12 leukocyte subsets from the lymphoid and myeloid lineages by deconvolving cell-type-specific DNA methylation data from 4124 women. Hypertension status at baseline was defined by current use of antihypertensive medication and blood pressure measurements while new incident cases were identified during follow-up via annual health questionnaires. Results: Among hypertension-free women at baseline, higher B cell and lower naïve CD4+ helper T cell proportions were associated with subsequent increased hazard of hypertension incidence (B cells; adjusted HR: 1.17 [95% CI: 1.02–1.35]; P =0.03; naïve CD4+ T cell, adjusted HR: 0.88 [95% CI: 0.78–0.99]; P =0.04). Blood pressure measurements at baseline were similarly positively associated with B cells and inversely associated with naïve CD4+ helper T cells. Compared to normotensive women, women with hypertension had higher circulating proportions of neutrophils (adjusted odds ratio: 1.18 [95% CI: 1.07–1.31]; P =0.001) and lower proportions of CD4+ helper T cells (adjusted odds ratio: 0.90 [95% CI: 0.81–1.00] P =0.05), natural killers (adjusted odds ratio: 0.82 [95% CI: 0.74–0.91]; P P =0.01). Conclusions: These observations suggest that shifts in lymphocyte subsets occur before hypertension development, followed by later changes to neutrophils and additional lymphocytes.

Metabolic syndrome (MetS) refers to the clustering of risk factors for cardiovascular disease and diabetes, including central adiposity, hypertension, dyslipidemia, and hyperglycemia. During the past 20 years, there have been parallel and epidemic increases in MetS and impaired sleep. This article describes evidence on the association between MetS and short sleep duration, circadian misalignment, insomnia, and sleep apnea. Potential mechanisms where impaired sleep desynchronizes and worsens metabolic control and interventions to improve sleep and potentially improve MetS are presented.

Ethnobiology as a discipline has evolved increasingly to embrace theory-inspired and hypothesis-driven approaches to study why and how local people choose plants and animals they interact with and use for their livelihood. However, testing complex hypotheses or a network of ethnobiological hypotheses is challenging, particularly for data sets with non-independent observations due to species phylogenetic relatedness or socio-relational links between participants. Further, to account fully for the dynamics of local ecological knowledge, it is important to include the spatially explicit distribution of knowledge, changes in knowledge, and knowledge transmission and use. To promote the use of advanced statistical modelling approaches that address these limitations, we synthesize methodological advances for hypothesis-driven research in ethnobiology while highlighting the need for more figures than tables and more tables than text in ethnobiological literature. We present the ethnobiological motivations for conducting generalized linear mixed-effect modelling, structural equation modelling, phylogenetic generalized least squares, social network analysis, species distribution modelling, and predictive modelling. For each element of the proposed ethnobiologists quantitative toolbox, we present practical applications along with scripts for a widespread implementation. Because these statistical modelling approaches are rarely taught in most ethnobiological programs but are essential for careers in academia or industry, it is critical to promote workshops and short courses focused on these advanced methods. By embracing these quantitative modelling techniques without sacrificing qualitative approaches which provide essential context, ethnobiology will progress further towards an expansive interaction with other disciplines.

Epigenetic age acceleration is considered a measure of biological aging based on genome-wide patterns of DNA methylation. Although age acceleration has been associated with the incidence of diseases and death, less is known about how it is related to lifestyle behaviors. Among 2316 women, we evaluate associations between self-reported alcohol consumption and various metrics of epigenetic age acceleration. Recent average alcohol consumption was defined as the mean number of drinks consumed per week within the past year; lifetime average consumption was estimated as the mean number of drinks per year drinking. Whole-blood genome-wide DNA methylation was measured with HumanMethylation450 BeadChips and used to assess 4 epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) and their corresponding metrics of epigenetic age acceleration (Hannum AgeAccel, Horvath AgeAccel, PhenoAgeAccel, and GrimAgeAccel). Although alcohol consumption showed little association with most age acceleration metrics, both lifetime and recent average consumption measures were positively associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β = 0.30 years, 95% confidence interval [CI]: 0.11, 0.48, p = .002; recent, per additional 5 drinks/week: β = 0.19 years, 95% CI: 0.01, 0.37, p = .04). In a mutually adjusted model, only average lifetime alcohol consumption remained associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β = 0.27 years, 95% CI: 0.04, 0.50, p = .02; recent, per 5 additional drinks/week: β = 0.05 years, 95% CI: −0.16, 0.26, p = .64). Although alcohol use does not appear to be strongly associated with biological age measured by most epigenetic clocks, lifetime average consumption is associated with higher biological age assessed by the GrimAge epigenetic clock.

STUDY DESIGN Retrospective analysis of administrative billing data. OBJECTIVE To evaluate the extent to which a metric of serious complications determined from administrative data can reliably profile hospital performance in spine fusion surgery. SUMMARY OF BACKGROUND DATA While payers are increasingly focused on implementing pay-for-performance measures, quality metrics must reliably reflect true differences in performance among the hospitals profiled. METHODS We used State Inpatient Databases from nine states to characterize serious complications after elective cervical and thoracolumbar fusion. Hierarchical logistic regression was used to risk-adjust differences in case mix, along with variability from low case volumes. The reliability of this risk-stratified complication rate (RSCR) was assessed as the variation between hospitals that was not due to chance alone, calculated separately by fusion type and year. Finally, we estimated the proportion of hospitals that had sufficient case volumes to obtain reliable (>0.7) complication estimates. RESULTS From 2010 to 2017 we identified 154,078 cervical and 213,133 thoracolumbar fusion surgeries. 4.2% of cervical fusion patients had a serious complication, and the median RSCR increased from 4.2% in 2010 to 5.5% in 2017. The reliability of the RSCR for cervical fusion was poor and varied substantially by year (range 0.04-0.28). Overall, 7.7% of thoracolumbar fusion patients experienced a serious complication, and the RSCR varied from 6.8% to 8.0% during the study period. Although still modest, the RSCR reliability was higher for thoracolumbar fusion (range 0.16-0.43). Depending on the study year, 0% to 4.5% of hospitals had sufficient cervical fusion case volume to report reliable (>0.7) estimates, whereas 15% to 36% of hospitals reached this threshold for thoracolumbar fusion. CONCLUSION A metric of serious complications was unreliable for benchmarking cervical fusion outcomes and only modestly reliable for thoracolumbar fusion. When assessed using administrative datasets, these measures appear inappropriate for high-stakes applications, such as public reporting or pay-for-performance.Level of Evidence: 3.

BackgroundInappropriate use of antimicrobial agents in animal production has led to the development of antimicrobial resistance (AMR) in foodborne pathogens. Transmission of AMR foodborne pathogens from reservoirs, particularly chickens to the human population does occur. Recently, we reported that occupational exposure was a risk factor for multidrug-resistant (MDR)Escherichia coli (E. coli)among poultry-workers. Here we determined the prevalence and genetic relatedness among MDRE. coliisolated from poultry-workers, chickens, and poultry environments in Abuja, Nigeria. This study was conducted to address the gaps identified by the Nigerian AMR situation analysis.MethodsWe conducted a cross-sectional study among poultry-workers, chickens, and poultry farm/live bird market (LBM) environments. The isolates were tested phenotypically for their antimicrobial susceptibility profiles, genotypically characterized using whole-genome sequencing (WGS) and in silico multilocus sequence types (MLST). We conducted a phylogenetic single nucleotide polymorphism (SNPs) analysis to determine relatedness and clonality among the isolates.ResultsA total of 115 (26.8%) out of 429 samples were positive forE. coli.Of these, 110 isolates were viable for phenotypic and genotypic characterization. The selection comprised 47 (42.7%) isolates from poultry-workers, 36 (32.7%) from chickens, and 27 (24.5%) from poultry-farm or LBM environments. Overall, 101 (91.8%) of the isolates were MDR conferring resistance to at least three drug classes.High frequency of resistance was observed for tetracycline (n = 102; 92.7%), trimethoprim/sulfamethoxazole (n = 93; 84.5%), streptomycin (n = 87; 79.1%) and ampicillin (n = 88; 80%). Two plasmid-mediated colistin genes—mcr-1.1harboured on IncX4 plasmids were detected in environmental isolates. The most prevalent sequence types (ST) were ST-155 (n = 8), ST-48 (n = 8) and ST-10 (n = 6). Two isolates of human and environmental sources with a SNPs difference of 6161 originating from the same farm shared a novel ST. The isolates had similar AMR genes and plasmid replicons.ConclusionMDRE.coliisolates were prevalent amongst poultry-workers, poultry, and the poultry farm/LBM environment. The emergence of MDRE. coliwith novel ST in two isolates may be plasmid-mediated. Competent authorities should enforce AMR regulations to ensure prudent use of antimicrobials to limit the risk of transmission along the food chain.

Citrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor and a regulator of fatty acid synthesis1-3. Thus, the rate of fatty acid synthesis correlates directly with the cytosolic concentration of citrate4,5. Liver cells import citrate through the sodium-dependent citrate transporter NaCT (encoded by SLC13A5) and, as a consequence, this protein is a potential target for anti-obesity drugs. Here, to understand the structural basis of its inhibition mechanism, we determined cryo-electron microscopy structures of human NaCT in complexes with citrate or a small-molecule inhibitor. These structures reveal how the inhibitor-which binds to the same site as citrate-arrests the transport cycle of NaCT. The NaCT-inhibitor structure also explains why the compound selectively inhibits NaCT over two homologous human dicarboxylate transporters, and suggests ways to further improve the affinity and selectivity. Finally, the NaCT structures provide a framework for understanding how various mutations abolish the transport activity of NaCT in the brain and thereby cause epilepsy associated with mutations in SLC13A5 in newborns (which is known as SLC13A5-epilepsy)6-8.

Background Prior research on the relationship between sleep and attempted weight loss failed to recognize the multidimensional nature of sleep. We examined the relationship between a composite measure of sleep health and change in weight and body composition among adults in a weight loss intervention. Methods Adults (N = 125) with overweight or obesity (50.3 ± 10.6 years, 91% female, 81% white) participated in a 12-month behavioral weight loss intervention, with assessments of sleep, weight, fat mass, and fat-free mass at baseline, 6 months, and 12 months. Six sleep dimensions (regularity, satisfaction, alertness, timing, efficiency, and duration) were categorized as "good" or "poor" using questionnaires and actigraphy. A composite score was calculated by summing the number of "good" dimensions. Obstructive sleep apnea (OSA) was assessed in a subsample (n = 117), using the apnea-hypopnea index (AHI) to determine OSA severity. Linear mixed modeling was used to examine the relationships between sleep health and outcomes of percent weight, fat mass, or fat-free mass change during the subsequent 6-month interval, adjusting for age, sex, bed partner, and race; an additional model adjusted for AHI. Results Mean baseline and 6-month sleep health was 4.5 ± 1.1 and 4.5 ± 1.2, respectively. Mean weight, fat mass, and fat-free mass changes from 0 to 6 months were -9.3 ± 6.1%, -16.9 ± 13.5%, and -3.4 ± 3.4%, respectively, and 0.4 ± 4.8%, -0.3 ± 10.3%, and 0.7 ± 4.1% from 6 to 12 months. Better sleep health was associated with greater subsequent weight loss (P = 0.016) and fat loss (P = 0.006), but not fat-free mass loss (P = 0.232). Following AHI adjustment, the association between sleep health and weight loss was attenuated (P = 0.102) but remained significant with fat loss (P = 0.040). Regularity, satisfaction, timing, and efficiency were each associated with weight and/or fat loss (P ≤ 0.041). Conclusions Better sleep health was associated with greater weight and fat loss, with associations attenuated after accounting for OSA severity. Future studies should explore whether improving sleep health, OSA, or the combination improves weight loss.

Prospective cohort study.The aim was to assess the association between diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) measures and cervical spondylotic myelopathy (CSM) clinical assessments at baseline and two-year follow-up.Despite advancements in diffusion-weighted imaging, few studies have examined associations between diffusion magnetic resonance imaging (MRI) markers and CSM-specific clinical domains at baseline and long-term follow-up.A single-center prospective cohort study enrolled 50 CSM patients who underwent surgical decompression and 20 controls from 2018 to 2020. At initial evaluation, all patients underwent diffusion-weighted MRI acquisition, followed by DTI and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. To improve estimations of intra-axonal anisotropic diffusion, DBSI measures intra-/extra-axonal fraction and intra-axonal axial diffusivity. DBSI also evaluates extra-axonal isotropic diffusion by restricted and nonrestricted fraction. Clinical assessments were performed at baseline and two-year follow-up and included the modified Japanese Orthopedic Association (mJOA); 36-Item Short Form Survey physical component summary (SF-36 PCS); SF-36 mental component summary; neck disability index; myelopathy disability index; and disability of the arm, shoulder, and hand. Pearson correlation coefficients were computed to compare associations between DTI/DBSI and clinical measures. A False Discovery Rate correction was applied for multiple comparisons testing.At baseline presentation, of 36 correlations analyzed between DTI metrics and CSM clinical measures, only DTI fractional anisotropy showed a positive correlation with SF-36 PCS ( r =0.36, P =0.02). In comparison, there were 30/81 (37%) significant correlations among DBSI and clinical measures. Increased DBSI axial diffusivity, intra-axonal axial diffusivity, intra-axonal fraction, restricted fraction, and extra-axonal anisotropic fraction were associated with worse clinical presentation (decreased mJOA; SF-36 PCS/mental component summary; and increased neck disability index; myelopathy disability index; disability of the arm, shoulder, and hand). At latest follow-up, increased preoperative DBSI intra-axonal axial diffusivity and extra-axonal anisotropic fraction were significantly correlated with improved mJOA.This findings demonstrate that DBSI measures may reflect baseline disease burden and long-term prognosis of CSM as compared with DTI. With further validation, DBSI may serve as a noninvasive biomarker following decompressive surgery.3.

Purpose We propose a fast, patient-specific workflow for on-line specific absorption rate (SAR) supervision. An individualized electromagnetic model is created while the subject is on the table, followed by rapid SAR estimates for that individual. Our goal is an improved correspondence between the patient and model, reducing reliance on general anatomical body models. Methods A 3D fat-water 3T acquisition (~2 minutes) is automatically segmented using a computer vision algorithm (~1 minute) into what we found to be the most important electromagnetic tissue classes: air, bone, fat, and soft tissues. We then compute the individual's EM field exposure and global and local SAR matrices using a fast electromagnetic integral equation solver. We assess the approach in 10 volunteers and compare to the SAR seen in a standard generic body model (Duke). Results The on-the-table workflow averaged 7'44″. Simulation of the simplified Duke models confirmed that only air, bone, fat, and soft tissue classes are needed to estimate global and local SAR with an error of 6.7% and 2.7%, respectively, compared to the full model. In contrast, our volunteers showed a 16.0% and 20.3% population variability in global and local SAR, respectively, which was mostly underestimated by the Duke model. Conclusion Timely construction and deployment of a patient-specific model is computationally feasible. The benefit of resolving the population heterogeneity compared favorably to the modest modeling error incurred. This suggests that individualized SAR estimates can improve electromagnetic safety in MRI and possibly reduce conservative safety margins that account for patient-model mismatch, especially in non-standard patients.

Importance: Predicting nasal soft tissue envelope (STE) thickness is an important component of the preoperative evaluation for rhinoplasty that presently lacks validated tools. Objective: Assess for patient facial features and factors that can help predict nasal STE thickness. Design, Setting, and Participants: Retrospective review and prospective assessment conducted at an academic tertiary referral center. This study included 190 adult patients and four expert raters. The patients had high-resolution maxillofacial CT scans and standardized facial photographs on file and did not have a history of nasal fracture, septal perforation, rhinoplasty, or other surgery or medical conditions altering nasal form. Main Outcomes and Measures: Assess each face for features that could help predict nasal STE thickness: sebaceous quality of skin, visibility of nasal tip cartilages, presence of freckles, presence of telangiectasias, Fitzpatrick skin type, patient age, sex, and body mass index (BMI). Measure actual nasal STE thickness using high-resolution CT scans. Analyze which facial features and patient factors help predict nasal STE thickness. Results: Pearson correlations were calculated between actual nasal STE thickness and patient facial features and factors. These showed that more sebaceous skin, telangiectasias, higher Fitzpatrick skin type, male sex, and higher BMI were associated with a thicker nasal STE. Increased visibility of nasal tip cartilages, freckles, lower Fitzpatrick skin type, female sex, and lower BMI were associated with a thinner nasal STE. Conclusions and Relevance: There are patient facial features and factors that can help surgeons predict nasal STE thickness before rhinoplasty. An accurate prediction of nasal STE thickness can improve preoperative planning for rhinoplasty, allowing implementation of pre-, intra-, and post-operative treatments to optimize the nasal STE, which may ultimately improve patient outcomes and satisfaction.

OBJECTIVE To evaluate differences in standardized scores and surgical confidence in the completion of a standardized total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (TLH-BSO) among obstetrician-gynecologists (ob-gyns) with different levels of training, and to assess a TLH-BSO model for validity. METHODS We conducted a prospective cohort study of 68 participants within four categories of ob-gyns: 1) graduating or recently graduated residents (n=18), 2) minimally invasive gynecologic surgery graduating or recently graduated fellows (n=16), 3) specialists in general obstetrics and gynecology (n=15), and 4) fellowship-trained minimally invasive gynecologic surgery subspecialists (n=19) who completed a TLH-BSO simulation. Participants completed presimulation questionnaires assessing laparoscopic confidence. Participants performed a video-recorded TLH-BSO and contained specimen removal on a standardized 250-g biological model in a simulated operating room and completed a postsimulation questionnaire. RESULTS Randomized videos were scored by blinded experts using the validated OSATS (Objective Structured Assessment of Technical Skills). The surgery was divided into five standardized segments: 1) adnexa, 2) dissection and pedicles, 3) colpotomy, 4) cuff closure, and 5) tissue extraction. Minimally invasive gynecologic surgery subspecialists averaging 8.9 years in practice scored highest in all categories (overall median score 91%, P

Resistance to first- and second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and development and progression of central nervous system metastases remain significant issues in the treatment of ALK-positive non-small-cell lung cancer. Lorlatinib is a novel third-generation ALK TKI that is able to penetrate the blood-brain barrier and has broad-spectrum potency against most known resistance mutations that can develop during treatment with crizotinib and second-generation ALK TKIs. The safety profile of lorlatinib is distinct from those of other ALK TKIs. Adverse events are typically mild to moderate in severity, seldom result in permanent discontinuations, and are generally manageable through lorlatinib dose modifications and/or standard medical therapy. This article provides guidance to advanced practice providers (e.g., nurses, nurse practitioners, physician assistants) and oncology pharmacists for the clinical management of key lorlatinib-emergent adverse reactions (i.e., hyperlipidemias, central nervous system effects, bodyweight increase, edema, and peripheral neuropathy). As lorlatinib is both a substrate and inducer of the CYP3A enzyme system and is contraindicated with strong CYP3A inducers, relevant drug-drug interactions are also highlighted.

Background The use of eye-tracking technology in plastic surgery has gained popularity over the past decade due to its ability to assess observers’ visual preferences in an objective manner. Objectives The goal of this study was to provide a comprehensive review of eye-tracking studies in plastic and reconstructive surgery, which can aid in the design and conduct of high-quality eye-tracking studies. Methods Through application of Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines, a comprehensive search of articles published on eye-tracking across several databases was conducted from January 1946 to January 2019. Inclusion criteria included studies evaluating the use of eye-tracking technology in the field of plastic and reconstructive surgery. The resulting publications were screened by 2 independent reviewers. Results A total of 595 articles were identified, 23 of which met our inclusion criteria. The most common application of eye-tracking was to assess individuals with cleft lip/palate (9 studies). All 19 studies that evaluated fixation patterns among conditions vs controls reported significant differences between the 2 groups. Five out of 7 studies assessing visual data between preoperative and postoperative patients identified significant differences between the preoperative and postoperative groups, whereas 2 studies did not. Nine studies examined the relation between severity indices, attractiveness scores, or personality ratings and gaze patterns. Correlation was found in 7 out of the 9 studies. Conclusions This systematic review demonstrates the utility of eye-tracking technology as a quantifiable objective assessment and emerging research tool for evaluating outcomes in several domains of plastic and reconstructive surgery.

Background Osteoarthritis (OA) is a clinical problem affecting an estimated 27 million adults in the United States, with the only clear treatment options being pain management. Cycling is an integral component of exercise for individuals with knee osteoarthritis, while the joint reaction forces during cycling remain unknown. Methods Thirteen subjects with medial compartment knee osteoarthritis and eleven healthy subjects performed a cycling protocol with a neutral pedal and four pedal modifications. Six hundred muscle-actuated inverse-dynamic simulations (24 subjects, 5 trials in each of 5 conditions) were performed to estimate joint reaction force differences between conditions. Findings Subjects with knee osteoarthritis had many significant changes among them was a reduction in knee adduction-abduction moment by 45% (5° lateral wedge), 77% (10° lateral wedge), 54% (5° toe-in) and 58% (10° toe-in). Conversely the healthy subjects had no significant changes in the knee adduction-abduction moment for the lateral wedge conditions and the 5° toe-in but did decrease by 18% for the 10° toe-in condition. When comparing the cohorts across the different pedal conditions, the data showed many significant differences among the groups. Interpretation This study showed that while cycling in different pedal modifications, the knee osteoarthritis subjects had more beneficial changes in their knee adduction-abduction moment compared to the healthy subjects with the lateral-wedge modification resulting in the greatest impact on the subjects with knee osteoarthritis. Both groups had greater contact forces at the hip and ankle across pedal modifications compared to neutral. For the knee, subjects with osteoarthritis mostly decreased their knee contact forces but the healthy subjects mostly increased these forces with all pedal modifications.

Objective: In this paper, we introduce global Maxwell tomography (GMT), a novel volumetric technique that estimates electric conductivity and permittivity by solving an inverse scattering problem based on magnetic resonance measurements. Methods: GMT relies on a fast volume integral equation solver, MARIE, for the forward path, and a novel regularization method, match regularization, designed specifically for electrical property estimation from noisy measurements. We performed simulations with three different tissue-mimicking numerical phantoms of different complexity, using synthetic transmit sensitivity maps with realistic noise levels as the measurements. We performed an experiment at 7 T using an eight-channel coil and a uniform phantom. Results: We showed that GMT could estimate relative permittivity and conductivity from noisy magnetic resonance measurements with an average error as low as 0.3% and 0.2%, respectively, over the entire volume of the numerical phantom. Voxel resolution did not affect GMT performance and is currently limited only by the memory of the graphics processing unit. In the experiment, GMT could estimate electrical properties within 5% of the values measured with a dielectric probe. Conclusion: This work demonstrated the feasibility of GMT with match regularization, suggesting that it could be effective for accurate in vivo electrical property estimation. GMT does not rely on any symmetry assumption for the electromagnetic field, and can be generalized to estimate also the spin magnetization, at the expense of increased computational complexity. Significance: GMT could provide insight into the distribution of electromagnetic fields inside the body, which represents one of the key ongoing challenges for various diagnostic and therapeutic applications., National Science Foundation (U.S.) (Grant 1453675), National Institutes of Health (U.S.) (Grants R01 EB024536, P41 EB017183)

Objectives To determine the prevalence and factors associated with post-discharge prophylactic antibiotic use after spinal fusion and whether use was associated with decreased risk of surgical site infection (SSI). Methods Persons aged 10–64 years undergoing spinal fusion between 1 January 2010 and 30 June 2015 were identified in the MarketScan Commercial Database. Complicated patients and those coded for infection from 30 days before to 2 days after the surgical admission were excluded. Outpatient oral antibiotics were identified within 2 days of surgical discharge. SSI was defined using ICD-9-CM diagnosis codes within 90 days of surgery. Generalized linear models were used to determine factors associated with post-discharge prophylactic antibiotic use and with SSI. Results The cohort included 156 446 fusion procedures, with post-discharge prophylactic antibiotics used in 9223 (5.9%) surgeries. SSIs occurred after 2557 (1.6%) procedures. Factors significantly associated with post-discharge prophylactic antibiotics included history of lymphoma, diabetes, 3–7 versus 1–2 vertebral levels fused, and non-infectious postoperative complications. In multivariable analysis, post-discharge prophylactic antibiotic use was not associated with SSI risk after spinal fusion (relative risk 0.98; 95% CI 0.84–1.14). Conclusions Post-discharge prophylactic oral antibiotics after spinal fusion were used more commonly in patients with major medical comorbidities, more complex surgeries and those with postoperative complications during the surgical admission. After adjusting for surgical complexity and infection risk factors, post-discharge prophylactic antibiotic use was not associated with decreased SSI risk. These results suggest that prolonged prophylactic antibiotic use should be avoided after spine surgery, given the lack of benefit and potential for harm.

BACKGROUND: Cancer of the nasal vestibule is a rare type of malignancy dominated by squamous cell carcinoma (SCC), and with poor survival. The treatment is either radiotherapy, surgery or a combination of both. Previous studies have shown a 5-year disease-specific survival of 74% and overall survival (OS) of 50%.Our objective was to describe the consecutive cohort of patients diagnosed with SCC of the nasal vestibule in Denmark from 2008 until 2018 and evaluate prognostic factors and treatment outcome using locoregional failure (LRF), disease-specific mortality (DSM), and OS as endpoints.METHODS: All patients diagnosed with SCC of the nasal vestibule from 2008 until 2018 were identified in the nationwide clinical database, DAHANCA and were followed for LRF and death (DSM and OS) until March 2021. OS was analysed using Kaplan-Meier estimator, and cumulative incidence of LRF and DSM were analysed using the Aalen-Johansen estimator. Analysis of prognostic factors was performed using Cox proportional hazard models.RESULTS: A total of 162 patients were identified. The median age was 71 years and 54% were male. Disease stage at the time of diagnosis were stage I (70%), II (17%), III (2%) and IV (11%). Curatively intended treatment was performed in 146 patients (90%), of which treatment failure occurred in 42 patients (29%). Most failures occurred at the primary tumour site (64%). Cancer Patient Pathways recommended time to treatment was fulfilled in 71% of patients. The 5-year OS and DSM in patients treated with curative intent were 65% and 11%, respectively. Stage was a significant independent prognostic factor. No difference in LRF, DSM or OS were shown between the applied treatments.CONCLUSIONS: Stage is the main independent prognostic factor, and failure most commonly appear at the primary tumour site.

BACKGROUND: C. difficile spores are frequently isolated from hospital and non-healthcare settings but a worldwide analysis has not been done. The study objectives were to assess C. difficile spore contamination in the hospital and non-healthcare environments across a variety of countries. METHODS: Field studies assessed hospital vs. non-healthcare C. difficile spore contamination in hospitals, non-healthcare buildings, outdoor environments, and shoes. Swabs were cultured anaerobically for C. difficile and typed using PCR-fluorescent ribotyping. C. difficile contamination by swabbing area and geographic locations were compared FINDINGS: A total of 7,857 unique samples were collected primarily from the USA (89%) in addition to 9 other countries. The global prevalence of C difficile from environmental samples was 25.3% and did not differ between countries. In USA based studies, C. difficile contamination rates were similar for healthcare buildings (23.2%), non-healthcare buildings (23.4%), and outdoor spaces (24.7%). Floor samples had significantly higher (p

Metabolic syndrome (MetS) and obstructive sleep apnea (OSA) are associated with increased risk of cardiometabolic disease. The co-occurrence of OSA with MetS is common, but there are limited data on how OSA risk exacerbates the metabolic impairments present in MetS. The purpose of this analysis was to examine in a representative sample of participants in the National Health and Nutrition Examination Survey 2015-2018 cohorts (1) the association of modifiable cardiometabolic risk factors with OSA risk and MetS severity and (2) the influence of OSA risk and lifestyle behaviors on MetS severity.Metabolic syndrome severity was assessed using MetS Z score, whereas the risk of OSA was measured via multivariable apnea prediction index. Data analyses were conducted using the sample weights provided by the National Health and Nutrition Examination Survey.The sample (N = 11 288) included adults (20 years old) who were overweight (mean body mass index, 29.6 ± 0.2 kg/m 2 ), representative by race (36.9% non-White) and gender (51.9% female). Overall, 19.3% of the sample had elevated MetS severity (MetS Z score ≥ 1), and 38.4% were at a high risk of OSA (multivariable apnea prediction score of ≥0.50). High OSA risk was associated with having elevated MetS severity (odds ratio [OR], 4.94; 95% confidence interval [CI], 3.68-6.65). Obstructive sleep apnea risk predicted increased MetS severity (adjusted: B = 0.06, SE = 0.02, P = .013). Physical activity provided the highest protection from increased MetS severity (OR, 0.52; 95% CI, 0.39-0.70) and OSA risk (OR, 0.59; 95% CI, 0.53-0.66).Our findings suggest that increased OSA risk exacerbates MetS severity and that greater physical activity may mitigate the risk.

Defective gastrointestinal barrier function and, in turn, microbial translocation have been identified as significant contributors to persistent inflammation in antiretroviral (ARV)-treated people living with HIV. Metabolic supplementation of short-chain fatty acids (SCFAs), generally produced by the commensal microbiome, may improve these outcomes. Butyrate is a SCFA that is essential for the development and maintenance of intestinal immunity and has a known role in supporting epithelial integrity. Herein we assessed whether supplementation with the dietary supplement sodium butyrate would improve immune reconstitution and reduce inflammation in ARV-treated, simian immunodeficiency virus (SIV)-infected rhesus macaques. We demonstrate that butyrate supplementation does not significantly improve immune reconstitution, with no differences observed in systemic CD4+ T-cell frequencies, T-cell functionality or immune activation, microbial translocation, or transcriptional regulation. Our findings demonstrate that oral administration of sodium butyrate is insufficient to reduce persistent inflammation and microbial translocation in ARV-treated, SIV-infected macaques, suggesting that this therapeutic may not reduce co-morbidities and co-mortalities in treated people living with HIV.

The vaginal microbiome composition in humans is categorized based upon the degree to which one of four species of Lactobacillus is dominant (Lactobacillus crispatus, community state type I [CST I], Lactobacillus gasseri, CST II, Lactobacillus iners, CST III, and Lactobacillus jensenii, CST V). Women with a vaginal microbiome not dominated by one of the four Lactobacillus species tend to have a more diverse microbiome, CST IV. CSTs I, II, III, and V are common in North America and Europe and are associated with lower incidences of some pathogens, such as human immunodeficiency virus (HIV), human papillomavirus (HPV), and Gardnerella vaginalis. As a result, therapeutic interventions to change the composition of the vaginal microbiomes are under development. However, Homo sapiens is the only mammalian species which has high frequencies of Lactobacillus-dominated vaginal microbiomes. Here, we treated female nonhuman primates (NHPs) with regimens of metronidazole and high levels of L. crispatus to determine how well these animals could be colonized with L. crispatus, how this influenced the immunological milieu, and how Lactobacillus treatment influenced or was influenced by the endogenous vaginal microbiome. We find that NHPs can transiently be colonized with L. crispatus, that beta diversity and not the number of doses of L. crispatus or pretreatment with metronidazole predicts subsequent L. crispatus colonization, that L. crispatus does not alter the local immunological milieu, and that the vaginal microbiome composition was resilient, normalizing by 4 weeks after our manipulations. Overall, this study suggests these animals are not amenable to long-term L. crispatus colonization. IMPORTANCE NHPs have proven to be invaluable animal models for the study of many human infectious diseases. The use of NHPs to study the effect of the microbiome on disease transmission and susceptibility is limited due to differences between the native microbiomes of humans and NHPs. In particular, Lactobacillus dominance of the vaginal microbiome is unique to humans and remains an important risk factor in reproductive health. By assessing the extent to which NHPs can be colonized with exogenously applied L. crispatus to resemble a human vaginal microbiome and examining the effects on the vaginal microenvironment, we highlight the utility of NHPs in analysis of vaginal microbiome manipulations in the context of human disease.

Endometrial cancer is one of the most frequently diagnosed gynecological cancers worldwide, and its prevalence has increased by more than 50% over the last two decades. Despite the understanding of the major signaling pathways driving the growth and metastasis of endometrial cancer, clinical trials targeting these signals have reported poor outcomes. The heterogeneous nature of endometrial cancer is suspected to be one of the key reasons for the failure of targeted therapies. In this study, we perform a sequential window acquisition of all theoretical fragment ion spectra (SWATH)-based comparative proteomic analysis of 63 tumor biopsies collected from 20 patients and define differences in protein signature in multiple regions of the same tumor. We develop organoids from multiple biopsies collected from the same tumor and show that organoids capture heterogeneity in endometrial cancer growth. Overall, using quantitative proteomics and patient-derived organoids, we define the heterogeneous nature of endometrial cancer within a patient's tumor.

α-Klotho (klotho) is a protein involved in suppressing oxidative stress and inflammation. In animal models, it is reported to underlie numerous aging phenotypes and longevity. Among a nationally representative sample of adults aged 40–79 years in the United States, we investigated whether circulating concentrations of klotho is a marker of mortality risk. Serum klotho was measured by ELISA on 10 069 individuals enrolled in the National Health and Nutrition Examination Survey between 2007 and 2014. Mortality follow-up data based on the National Death Index were available through December 31, 2015. After a mean follow-up of 58 months (range: 1–108), 616 incident deaths occurred. Using survey-weighted Cox regression models adjusted for age, sex, and survey cycle, low serum klotho concentration ( 985 pg/mL, hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.00, 1.71, p = .05). Associations were consistent for mortality caused by heart disease or cancer. Associations of klotho with all-cause mortality did not appear to differ by most participant characteristics. However, we observed effect modification by physical activity, such that low levels of serum klotho were more strongly associated with mortality among individuals who did not meet recommendation-based physical activity guidelines. Our findings suggest that, among the general population of American adults, circulating levels of klotho may serve as a marker of mortality risk.

The COVID-19 pandemic has led to the rapid adoption of telemedicine. Health systems nationwide moved quickly to scale their telemedicine capabilities, and the Centers for Medicare & Medicaid Services (CMS) and other payers expanded reimbursement for telehealth visits.1 While widely lauded as a means to improve value of care, telemedicine may exacerbate disparities in health care access.2 In this study, we describe the increased adoption of telemedicine at a large academic health system since the pandemic and examine our hypothesis that this increase is associated with widening racial, ethnic, and socioeconomic differences in access to care.

ImportanceCervical spinal cord injury (SCI) causes devastating loss of upper extremity function and independence. Nerve transfers are a promising approach to reanimate upper limbs; however, there remains a paucity of high-quality evidence supporting a clinical benefit for patients with tetraplegia.ObjectiveTo evaluate the clinical utility of nerve transfers for reanimation of upper limb function in tetraplegia.Design, Setting, and ParticipantsIn this prospective case series, adults with cervical SCI and upper extremity paralysis whose recovery plateaued were enrolled between September 1, 2015, and January 31, 2019. Data analysis was performed from August 2021 to February 2022.InterventionsNerve transfers to reanimate upper extremity motor function with target reinnervation of elbow extension and hand grasp, pinch, and/or release.Main Outcomes and MeasuresThe primary outcome was motor strength measured by Medical Research Council (MRC) grades 0 to 5. Secondary outcomes included Sollerman Hand Function Test (SHFT); Michigan Hand Outcome Questionnaire (MHQ); Disabilities of Arm, Shoulder, and Hand (DASH); and 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) scores. Outcomes were assessed up to 48 months postoperatively.ResultsTwenty-two patients with tetraplegia (median age, 36 years [range, 18-76 years]; 21 male [95%]) underwent 60 nerve transfers on 35 upper limbs at a median time of 21 months (range, 6-142 months) after SCI. At final follow-up, upper limb motor strength improved significantly: median MRC grades were 3 (IQR, 2.5-4; P = .01) for triceps, with 70% of upper limbs gaining an MRC grade of 3 or higher for elbow extension; 4 (IQR, 2-4; P P Conclusions and RelevanceIn this prospective case series, nerve transfer surgery was associated with improvement of upper limb motor strength and functional independence in patients with tetraplegia. Nerve transfer is a promising intervention feasible in both subacute and chronic SCI.

Background Shift work has been associated with increased risk of age-related morbidity and mortality. Biological age, estimated using DNA methylation (DNAm), may quantify the biological consequences of shift work on the risk of age-related disease. We examined whether prior employment in shift-working occupations was associated with epigenetic age acceleration. Methods In a sample of non-Hispanic White women aged 35–74 (n = 2574), we measured DNAm using the Illumina Infinium Human450 BeadChip and calculated DNAm age using three established epigenetic clocks. Age-acceleration metrics were derived by regressing DNAm age on chronological age and predicting the residuals. Using linear regression, we estimated associations between shift work history and age acceleration. We also conducted an epigenome-wide association study using robust linear-regression models corrected with false discovery rate (FDR) q-values. Results Approximately 7% of women reported any shift work. Higher age acceleration was observed for a 1-year increase in overall [β = 0.11, 95% confidence interval (CI): 0.02–0.21] and night-specific shift work (β = 0.12, 95% CI: 0.03–0.21). The association was strongest for ≥10 years of night shift work (β = 3.16, 95% CI: 1.17–5.15). From the epigenome-wide association study, years of overall and night shift work were associated with DNAm at 66 and 85 CpG sites (FDR Conclusions Shift work was associated with differential CpG site methylation and with differential DNAm patterns, measured by epigenetic age acceleration, consistent with long-term negative health effects.

BACKGROUND: Self-efficacy, or the perceived capability to engage in a behavior, has been shown to play an important role in adhering to weight loss treatment. Given that adherence is extremely important for successful weight loss outcomes and that sleep and self-efficacy are modifiable factors in this relationship, we examined the association between sleep and self-efficacy for adhering to the daily plan. Investigators examined whether various dimensions of sleep were associated with self-efficacy for adhering to the daily recommended lifestyle plan among participants (N=150) in a 12-month weight loss study. METHODS: This study was a secondary analysis of data from a 12-month prospective observational study that included a standard behavioral weight loss intervention. Daily assessments at the beginning of day (BOD) of self-efficacy and the previous night’s sleep were collected in real-time using ecological momentary assessment. RESULTS: The analysis included 44,613 BOD assessments. On average, participants reported sleeping for 6.93±1.28 hours, reported 1.56±3.54 awakenings, and gave low ratings for trouble sleeping (3.11±2.58;0: no trouble; 10: a lot of trouble) and mid-high ratings for sleep quality (6.45±2.09;0: poor; 10: excellent). Participants woke up feeling tired 41.7% of the time. Using linear mixed effects modeling, a better rating in each sleep dimension was associated with higher self-efficacy the following day (all p values