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Intro: Drug-resistant tuberculosis (DR-TB) has been declared to be a major contributor to antimicrobial resistance worldwide and remains a global public health concern. The genetic basis of antibiotic resistance in clinical DR Mycobactetium tuberculosis isolates has been widely studied and is predominantly attributed to mutations in specific genes. However, the role of some specific mutations in these genes has not yet been fully elucidated. This study aimed to characterize the mutations associated with resistance to first- and second-line anti-TB drugs classified in Group 3: Uncertain significance in the WHO catalogue and to investigate their relation with the phenotypic resistance profile. Methods: We performed whole genome sequencing of 50 strains of Mycobacterium tuberculosis phenotypically resistant to at least one anti-TB drug. All mutations in genes associated with resistance to first- and second-line anti-TB drugs were called and compared with the catalogue of mutations published by WHO. Findings: Variable sensitivities and specificities for genotype-phenotype correlation of resistance predictions ranging from 15% (pyrazinamide) to 92.7% (isoniazid) and 92.3% (izoniazid) to 100% (streptomycin) were obtained. Resistance conferring mutation was found in 22/50 (40%) isolates. Genotypic resistance to streptomycin was confirmed only in 11/30 phenotypically resistant isolates. For 6/30 isolates without a known mutation, we characterized a unique variants in the gidB gene (V77A; V202A; L35P; A119D; a-60c; c11-t) with uncertain significance in STM resistance. In 3 phenotypic PZA-monoresistant isolates we detected the mutation with uncertain significance in pncA (G162R) and kefB (A107V). All these mutations were present in the genome of phenotypically resistant isolates. Conclusion: In this study we characterized several mutations with uncertain significance in resistance to first- and second-line anti-TB drugs. Comparison of the phenotypic and genotypic resistance profile may contribute in the reclassification of some of these mutations with into the group of mutations associated with resistance.

Aims: Better prediction of outcome after total hip arthroplasty (THA) is warranted. Systemic inflammation and central neuroinflammation are possibly involved in progression of osteoarthritis and pain. We explored whether inflammatory biomarkers in blood and cerebrospinal fluid (CSF) were associated with clinical outcome, and baseline pain or disability, 12 months after THA. Methods: A total of 50 patients from the Danish Pain Research Biobank (DANPAIN-Biobank) between January and June 2018 were included. Postoperative outcome was assessed as change in Oxford Hip Score (OHS) from baseline to 12 months after THA, pain was assessed on a numerical rating scale, and disability using the Pain Disability Index. Multiple regression models for each clinical outcome were included for biomarkers in blood and CSF, respectively, including age, sex, BMI, and Kellgren-Lawrence score. Results: Change in OHS was associated with blood concentrations of tumour necrosis factor (TNF), interleukin-8 (IL-8), interleukin-6 receptor (IL-6R), glycoprotein 130 (gp130), and IL-1β (R2 = 0.28, p = 0.006), but not with CSF biomarkers. Baseline pain was associated with blood concentrations of lymphotoxin alpha (LTα), TNFR1, TNFR2, and IL-6R (R2 = 0.37, p < 0.001) and CSF concentrations of TNFR1, TNFR2, IL-6, IL-6R, and IL-1Ra (R2 = 0.40, p = 0.001). Baseline disability was associated with blood concentrations of TNF, LTα, IL-8, IL-6, and IL-1α (R2 = 0.53, p < 0.001) and CSF concentrations of gp130, TNF, and IL-1β (R2 = 0.26, p = 0.002). Thus, preoperative systemic low-grade inflammation predicted 12-month postoperative outcome after THA, and was associated with preoperative pain and disability. Conclusion: This study highlights the importance of systemic inflammation in osteoarthritis, and presents a possible path for better patient selection for THA in the future. Preoperative central neuroinflammation was associated with preoperative pain and disability, but not change in OHS after THA. Cite this article: Bone Joint Res 2024;13(12):741–749.

Objective: Graduate students are more likely to experience mental illness than their peers in the general population. One potential source of support for personal issues and/or mental illness is a graduate student's faculty advisor. Although the relationship between faculty advisors and graduate students can positively influence the success and overall well-being of graduate students, graduate students may be reluctant to disclose mental health issues to their advisors. This study explores graduate students' perspectives on factors that influence their decision to disclose, or not to disclose, personal mental health information to their faculty advisor. Participants: The participants for this study were 28 graduate students from three universities in the southern United States. Methods: Four semi-structured focus groups were conducted over Zoom. Results: Thematic analysis of a series of focus groups with graduate students identified several consistent themes related to this disclosure decision-making process. Conclusions: Results have implications for mental health literacy and interpersonal communication interventions for those charged with mentoring graduate students.

ABSTRACT Mycobacterium abscessus is an emerging opportunistic pathogen affecting patients with chronic lung diseases, primarily cystic fibrosis (CF), or those under immunosuppression. Hence, investigations into the epidemiology and transmission of M. abscessus and accurate antibiotic susceptibility data are essential for the effective treatment of infections caused by this pathogen. This retrospective nationwide study included all clinical M. abscessus isolates (n = 59) from 29 patients diagnosed in the Czech Republic and Slovakia between 2018 and 2023. Whole genome sequencing (WGS) was performed to identify clusters and classify isolates into predominant circulating clones (DCC). Subspecies identification of unique isolates showed subspecies abscessus as the most prevalent (69.0%). The results of drug-susceptibility testing showed that 65.5% of all isolates were resistant to at least three antibiotics tested. CF patients under 24 years of age were the most at-risk group for M. abscessus infection. WGS identified seven clusters (including two cross-border) comprising CF and non-CF patients with a total clustering rate of 48.3%. One cluster involved patients infected with subspecies massiliense strains differing by 0 single nucleotide polymorphisms hospitalized in the same center. Furthermore, we identified representatives of all major DCCs. This study revealed predominant Mycobacterium abscessus complex clones circulating in the Czech Republic and Slovakia. The results show the high discriminatory power of WGS in the molecular epidemiology of M. abscessus and provide supporting evidence of direct or indirect cross-transmission of subspecies massiliense among both CF and non-CF patients.IMPORTANCEThis study highlights the importance of understanding Mycobacterium abscessus transmission because it poses a growing threat to vulnerable populations, especially young cystic fibrosis patients. Investigating how it spreads and which antibiotics work best is crucial for effective treatment. This research used whole genome sequencing to track M. abscessus and found evidence of potential transmission between patients, including across borders. The findings suggest that dominant strains are circulating and some patients may be infected through direct or indirect contact. This knowledge can inform infection control and treatment strategies.

Aims: The aim of this study was to describe the pattern of revision indications for unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) and any change to this pattern for UKA patients over the last 20 years, and to investigate potential associations to changes in surgical practice over time. Methods: All primary knee arthroplasty surgeries performed due to primary osteoarthritis and their revisions reported to the Danish Knee Arthroplasty Register from 1997 to 2017 were included. Complex surgeries were excluded. The data was linked to the National Patient Register and the Civil Registration System for comorbidity, mortality, and emigration status. TKAs were propensity score matched 4:1 to UKAs. Revision risks were compared using competing risk Cox proportional hazard regression with a shared γ frailty component. Results: Aseptic loosening (loosening) was the most common revision indication for both UKA (26.7%) and TKA (29.5%). Pain and disease progression accounted for 54.6% of the remaining UKA revisions. Infections and instability accounted for 56.1% of the remaining TKA revision. The incidence of revision due to loosening or pain decreased over the last decade, being the second and third least common indications in 2017. There was a decrease associated with fixation method for pain (hazard ratio (HR) 0.40; 95% confidence interval (CI) 0.17 to 0.94) and loosening (HR 0.29; 95% CI 0.10 to 0.81) for cementless compared to cemented, and units UKA usage for pain (HR 0.67, 95% CI 0.50 to 0.91), and loosening (HR 0.51; 95% CI 0.37 to 0.70) for high usage. Conclusion: The overall revision patterns for UKA and TKA for the last 20 years are comparable to previous published patterns. We found large changes to UKA revision patterns in the last decade, and with the current surgical practice, revision due to pain or loosening are significantly less likely. Cite this article: Bone Jt Open 2023;4(12):923–931.

Abstract Aneurysm hemodynamics is known for its crucial role in the natural history of abdominal aortic aneurysms (AAA). However, there is a lack of well-developed quantitative assessments for disturbed aneurysmal flow. Therefore, we aimed to develop innovative metrics for quantifying disturbed aneurysm hemodynamics and evaluate their effectiveness in predicting the growth status of AAAs, specifically distinguishing between fast-growing and slowly-growing aneurysms. The growth status of aneurysms was classified as fast (≥ 5 mm/year) or slow (

Abstract DLCO/NO, the combined single‐breath measurement of the diffusing capacity to carbon monoxide (DLCO) and nitric oxide (DLNO) measured either during exercise or in the resting supine position may be a useful physiological measure of alveolar–capillary reserve. In the present study, we investigated the between‐day test–retest reliability of DLCO/NO‐based metrics. Twenty healthy volunteers (10 males, 10 females; mean age 25 (SD 2) years) were randomized to repeated DLCO/NO measurements during upright rest followed by either exercise (n = 11) or resting in the supine position (n = 9). The measurements were repeated within 7 days. The smallest real difference (SRD), defined as the 95% confidence limit of the standard error of measurement (SEM), the coefficient of variance (CV), and intraclass correlation coefficients were used to assess test–retest reliability. SRD for DLNO was higher during upright rest (5.4 (95% CI: 4.1, 7.5) mmol/(min kPa)) than during exercise (2.7 (95% CI: 2.0, 3.9) mmol/(min kPa)) and in the supine position (3.0 (95% CI: 2.1, 4.8) mmol/(min kPa)). SRD for DLCOc was similar between conditions. CV values for DLNO were slightly lower than for DLCOc both during exercise (1.5 (95% CI: 1.2, 1.7) vs. 3.8 (95% CI: 3.2, 4.3)%) and in the supine position (2.2 (95% CI: 1.8, 2.5) vs. 4.8 (95% CI: 3.8, 5.4)%). DLNO increased by 12.3 (95% CI: 11.1, 13.4) and DLCOc by 3.3 (95% CI: 2.9, 3.7) mmol/(min kPa) from upright rest to exercise. The DLCO/NO technique provides reliable indices of alveolar–capillary reserve, both during exercise and in the supine position.

Roads impact a disproportionately larger area than the land area that they occupy, often called the road effect zone. This effect extends to wildlife populations. Impacts on federally listed species include habitat loss and fragmentation, road mortality, the barrier effect, and the habituation effect. Per the Endangered Species Act, these impacts must be assessed before roadway impacts occur. This publication provides an overview of the potential impacts to 29 of Florida’s threatened and endangered animal species from roads. Potential mitigation options include road configuration, signage, speed limits, habitat protection, improved technology, wildlife fencing, and wildlife crossing structures. The goal is to educate transportation engineers and planners to allow for sustainable transportation infrastructure growth while protecting, conserving, and ultimately recovering Florida’s threatened and endangered species.

Bisphenol A (BPA) is a high production volume (HPV) chemical used to make polycarbonate (PC) plastics and epoxy resins. Due to its potential adverse health effects, BPA has been restricted or banned in some products and thus many alternatives to BPA have been introduced into the market. Most of these alternatives such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol M (BPM), have similar chemical structures to BPA and termed as BPA analogues (BPAAs). In this study, a method was developed for the simultaneous determination of 16 BPAAs in indoor dust by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The method was sensitive, with method detection limits (MDLs) ranging from 0.001 μg/g to 0.017 μg/g. The method demonstrated good recoveries (>80%) for the majority of the target compounds and was applied to the analysis of dust samples collected from 2007 to 2010 in 13 cities across Canada under the Canadian House Dust Study (CHDS). Samples were collected using two different techniques: household vacuum dust samples collected from household vacuum bags (HD); fresh vacuum dust (FD) samples collected by a trained technician from dry floor surfaces. In addition to BPA with 100% detection in 119 HD samples, BPS, BPF, and BPM were detected with high detection frequencies (>75%) with median (range) concentrations of 0.242 (

Introduction Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity.Methods and analysis Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components.Ethics and dissemination The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study’s findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders.PROSPERO registration number CRD42020177408.

Our indoor microbiome consists of a wide range of microbial taxa. Whilst many of these microbes are benign, some are beneficial, some harmful, yet our knowledge of the spatial heterogeneity of bacterial assemblages in our residential environment remains limited. To investigate the existence of a common core house dust bacterial microbiome we selected household vacuum dusts, collected through a citizen science approach, from homes across two bioclimatic regions (UK, Oceanic/Maritime and Greece, Mediterranean). Following the extraction of DNA from each dust sample, we targeted the bacterial 16S rRNA gene using Illumina NextSeq sequencing. PERMANOVA analysis of the microbial communities at family level grouped samples within their distinct bioclimatic region and SIMPER analysis at genus level identified the statistically significant taxa responsible for driving diversity between these groups. A “common to all” core house dust microbiome consisted of Acinetobacter, Massalia, Rubellimicrobium, Sphingomonas and Staphylococcus; genera typically associated with human occupancy and common environmental sources. Additionally, a “unique location specific” microbiome was identified, reflective of the bioclimatic region. The Greek dusts indicated a lower average diversity than the UK house dusts, with a high abundance of Rhizobiaceae in the Greek samples. Our study highlights citizen science as a powerful approach to access the indoor residential environment, at scale, and establishes the existence of a “core” house dust microbiome independent of bioclimatic region.

Objectives. The vagal nerve exerts an essential pathway in controlling the cholinergic anti-inflammatory reflex. Thus, the study is aimed at investigating the acute effect of a noninvasive transcutaneous vagus nerve stimulation on clinical disease activity and systemic levels of inflammation in patients with psoriatic arthritis or ankylosing spondylitis. Methods. Twenty patients with psoriatic arthritis (PsA) and 20 patients with ankylosing spondylitis (AS) were included and stimulated bilaterally with a handheld vagal nerve stimulator for 120 seconds 3 times a day for 5 consecutive days. All patients were in remission. Cardiac vagal tone, clinical scores, CRP, and cytokine levels were assessed. Results. In PsA and AS, decreased heart rate was observed, confirming compliance. Furthermore, in PsA, a clear reduction of clinical disease activity associated with a 20% reduction in CRP was shown. In AS, a reduction in interferon-γ, interleukin- (IL-) 8, and 10 was shown. No side effects were described. Conclusion. This open-label study provides support for an anti-inflammatory effect of transcutaneous vagus nerve stimulation in patients with psoriatic arthritis and ankylosing spondylitis. The modulated immune response and reduced disease activity and CRP-levels raise the fascinating possibility of using neuromodulation as an add-on to existing pharmacological treatments.

Severe traumatic brain injury (TBI) is a leading cause of death and disability worldwide, especially in low- and middle-income countries, and in austere, rural, and remote settings. The purpose of this Perspective is to challenge the notion that accurate and actionable diagnosis of the most severe brain injuries should be limited to physicians and other highly-trained specialists located at hospitals. Further, we aim to demonstrate that the great opportunity to improve severe TBI care is in the prehospital setting. Here, we discuss potential applications of prehospital diagnostics, including ultrasound and near-infrared spectroscopy (NIRS) for detection of life-threatening subdural and epidural hemorrhage, as well as monitoring of cerebral hemodynamics following severe TBI. Ultrasound-based methods for assessment of cerebrovascular hemodynamics, vasospasm, and intracranial pressure have substantial promise, but have been mainly used in hospital settings; substantial development will be required for prehospital optimization. Compared to ultrasound, NIRS is better suited to assess certain aspects of intracranial pathology and has a smaller form factor. Thus, NIRS is potentially closer to becoming a reliable method for non-invasive intracranial assessment and cerebral monitoring in the prehospital setting. While one current continuous wave NIRS-based device has been FDA-approved for detection of subdural and epidural hemorrhage, NIRS methods using frequency domain technology have greater potential to improve diagnosis and monitoring in the prehospital setting. In addition to better technology, advances in large animal models, provider training, and implementation science represent opportunities to accelerate progress in prehospital care for severe TBI in austere, rural, and remote areas.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is becoming a standardized adjunct in the management of non-compressible hemorrhage. Ultrasound (US)-guided femoral access has been taught as the best practice for femoral artery cannulation. However, there is a lack of evidence to support its use in patients in extremis with severe hemorrhage. We hypothesize that no differences in outcome will exist between US-guided and to blind percutaneous or cutdown access methods. Methods: This was an international, multicenter retrospective review of all patients managed with REBOA from the ABOTrauma Registry and the AORTA database. REBOA characteristics and outcomes were compared among puncture access methods. Significance was set at P < 0.05. Results: The cohort included 523 patients, primarily male (74%), blunt injured (77%), with median age 40 (27–58), and an Injury Severity Score of 34 (25–45). Percutaneous using external landmarks/palpation was the most common femoral puncture method (53%) used followed by US-guided (27.9%). There was no significant difference in overall complication rates (37.4% vs 34.9%; P = 0.615) or mortality (47.8% vs 50.3%; P = 0.599) between percutaneous and US-guided methods; however, access by cutdown was significantly associated with emergency department (ED) mortality (P = 0.004), 24 hour mortality (P = 0.002), and in-hospital mortality (P = 0.007). Conclusions: In patients with severe hemorrhage in need of REBOA placement, the percutaneous approach using anatomic landmarks and palpation, when compared with US-guided femoral access, was used more frequently without an increase in complications, access attempts, or mortality.

His-tagged proteins can undergo N-terminal acylation as an undesired side-reaction. Here, the authors utilize this to develop a method for highly selective acylation and further modification of peptides and proteins using an optimized His sequence and 4-methoxyphenyl esters as acyl donors.

Mercury (Hg) is one of the top ten chemicals of concern for public health, according to the World Health Organization. This study investigates Hg concentrations in house dust collected from urban single family homes, to better understand typical indoor residential exposures. Using direct solid sample analysis, total Hg and carbon (TC) were determined in the n = 995). A small subset (9.0 mg/kg). A comparison of Hg concentrations in fresh dust and household vacuum dust collected from the same homes indicated no significant difference in the two sampling methods. Total carbon concentrations displayed a median/geomean of 29.3/28.5% (n = 1011). A significant correlation between total Hg and TC in house dust (p < 0.00001) reflects the association between Hg and organic carbon previously observed in soil and sediments. The results of this study indicate a 10-fold enrichment in house dust compared with the average background concentrations reported for soil and sediments (0.07 mg/kg). The observed enrichment is attributable to Hg emissions from indoor sources and/or Hg carried home from occupational sources.

Road dust is an important source of resuspended particulate matter (PM) but information is lacking on the chemical composition of the ultrafine particle fraction (UFP; 10). The UFP fraction accounted for about 2% of the total mass of resuspended PM10 (range 0.23–8.36%). Elemental analysis using ICP-MS and ICP-OES revealed a marked enrichment in Cd, Cr, Zn and V concentration in UFP compared to the dust box material (nano to dust box ratio ≥ 2). UFP from arterial roads contained two times more Cd, Zn and V and nine times more Cr than UFP from local roads. The highest median concentration of Zn was observed for the municipal expressway, attributed to greater volumes of traffic, including light to heavy duty vehicles, and higher speeds. The observed elevated concentrations of transition metals in UFP are a human health concern, given their potential to cause oxidative stress in lung cells.

Lipid-soluble micronutrients may be beneficial to non-alcoholic fatty liver disease due to their important roles in metabolism and maintaining tissue functions. Utilizing 2017–2018 National Health and Nutrition Examination Survey, this study examined the potential overall and race/ethnicity-specific (black, Hispanic and white) associations of dietary lipid-soluble micronutrients (α-tocopherol, retinol, vitamin D, β-carotene and total carotenoids) with hepatic steatosis. The analysis included 4376 adults (1037 blacks, 981 Hispanics, 1549 whites) aged ≥20 years who completed the transient elastography examination with dietary data available. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regressions. The age-adjusted prevalence of steatosis was 20.9% for blacks, 34.0% for Hispanics and 28.7% for whites. Overall, dietary α-tocopherol was inversely associated with steatosis (highest vs. lowest quartile: OR = 0.51, 95%CI = 0.35–0.74, Ptrend = 0.0003). The associations remained significant among blacks (highest vs. lowest tertile: OR = 0.45, 95%CI = 0.26–0.77, Ptrend = 0.002) and whites (highest vs. lowest tertile: OR = 0.56, 95%CI = 0.33–0.94, Ptrend = 0.02). Higher α-tocopherol intake was associated with lower odds of steatosis among all (Ptrend = 0.016) and black participants (Ptrend = 0.003) classified as never/rare/occasional alcohol drinkers. There was a trend suggesting higher β-carotene intake with lower odds of steatosis (Ptrend = 0.01). Our results suggest potential protective effects of dietary vitamin E as α-tocopherol on steatosis particularly among blacks.

A fluidized bed aerosol generator was connected to a 13-stage cascade impactor (nanoMOUDI) for the size fractionation of urban dust (10 (thoracic) fraction of road dust sampled from expressways, arterial roads and local roads in Toronto, Canada. The fine particle fractions (10 (by weight). Elemental analysis using ICP-MS and ICP-OES revealed an overall trend of element enrichment in the p < 0.05) for Zn when using Gamble solution, and for seven out of the 14 target elements when using ammonium citrate. These results show the importance of characterizing the fine fraction of road dust.