A Cambrian spiny stem mollusk and the deep homology of lophotrochozoan scleritomes.

Mollusks encompass enormous disparity, including familiar clams and snails alongside less familiar aculiferans (chitons and vermiform aplacophorans) with complex multicomponent skeletons. Paleozoic fossils trace crown mollusks to forms exhibiting a combination of biomineralized shells and sclerites (e.g., scales, spines, and spicules). We describe a shell-less, Cambrian stem mollusk, Shishania aculeata gen. et sp. nov., with conical, hollow chitinous sclerites and a smooth girdle, broad foot, and mantle cavity. The sclerites have a microstructure of narrow canals consistent with the impressions of chaetal microvilli found in annelids and brachiopods. Shishania sclerites provide a morphological stepping stone between typical chaetae (chitinous bristles) and the external organic part of aculiferan sclerites that encloses a mineralized body. This discovery reinforces a common origin of lophotrochozoan chaetae and the biomineralized aculiferan sclerites, suggesting that the mollusk ancestor was densely covered with hollow chitinous chaetae.

Immune checkpoints and pancreatic beta cell dysfunction in HIV.

We explored the impact of immune dysregulation on pancreatic beta cell injury in HIV patients. Analyzing 105 participant samples, we observed lower IL-21 levels and elevated immune checkpoint levels (e.g. PD-1, CD27+, CD40+) in untreated HIV patients. Notably, soluble TIM-3 correlated positively with improved beta cell function and inversely with beta cell stress, suggesting its potential role in beta cell protection in untreated HIV.

Endogenously produced itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophages.

A wide variety of electrophilic derivatives of itaconate, the Kreb's cycle-derived metabolite, are immunomodulatory, yet these derivatives have overlapping and sometimes contradictory activities. Therefore, we generated a genetic system to interrogate the immunomodulatory functions of endogenously produced itaconate in human macrophages. Endogenous itaconate is driven by multiple innate signals restraining inflammatory cytokine production. Endogenous itaconate directly targets cysteine 13 in IRAK4 (disrupting IRAK4 autophosphorylation and activation), drives the degradation of nuclear factor κB, and modulates global ubiquitination patterns. As a result, cells unable to make itaconate overproduce inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1ß in response to these innate activators. In contrast, the production of interferon (IFN)ß, downstream of LPS, requires the production of itaconate. These data demonstrate that itaconate is a critical arbiter of inflammatory cytokine production downstream of multiple innate signaling pathways, laying the groundwork for the development of itaconate mimetics for the treatment of autoimmunity.

Annelid methylomes reveal ancestral developmental and aging-associated epigenetic erosion across Bilateria.

BACKGROUND: DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as "mosaic". Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla. RESULTS: Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis. CONCLUSIONS: Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.

The relations of difficulties in emotion regulation and distress intolerance with cannabis problems: The role of protective behavioral strategies underutilization.

INTRODUCTION: Difficulties with emotion regulation and distress tolerance are related to more cannabis problems, yet little research has identified why this is the case. Cannabis-related protective behavioral strategies (PBS; behaviors used to mitigate cannabis related problems) are related to less cannabis consumption and related problems. Potentially, these individuals may use cannabis to alleviate the distress and/or in an attempt to regulate their emotions. Thus, the present study aimed to examine the mediational role of PBS on the relations of emotion dysregulation and distress intolerance with cannabis problems. METHODS: Undergraduate students who endorsed past-month cannabis use (N = 339, Mage = 19.33, SDage = 1.37; 77.9 % female) at a southern United States university completed a survey online via Qualtrics. RESULTS: More emotion dysregulation and less distress tolerance predicted less PBS use and more cannabis problems, but not cannabis use frequency. After statistically controlling for sex, the relation of each transdiagnostic factor with cannabis problems occurred indirectly via the relations of less PBS use and greater cannabis use frequency CONCLUSIONS: The present study supports previous claims that emotion dysregulation and distress intolerance are related to more cannabis problems. Additionally, results suggest that individuals with high levels of these problems underutilize PBS which, in turn, is associated with more frequent cannabis use and use-related problems. Clinical implications are discussed.

Altered Corticobrainstem Connectivity during Spontaneous Fluctuations in Pain Intensity in Painful Trigeminal Neuropathy.

Chronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging signal covariations between the midbrain periaqueductal gray (PAG) matter, rostral ventromedial medulla (RVM), and spinal trigeminal nucleus are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN). Since this brainstem circuit is modulated by higher brain input, we sought to determine which cortical sites might be influencing this brainstem network during spontaneous fluctuations in pain intensity. Over 12 min, we recorded the ongoing pain intensity in 24 PTN participants and classified them as fluctuating (n = 13) or stable (n = 11). Using a PAG seed, we identified connections between the PAG and emotional-affective sites such as the hippocampal and posterior cingulate cortices, the sensory-discriminative posterior insula, and cognitive-affective sites such as the dorsolateral prefrontal (dlPFC) and subgenual anterior cingulate cortices that were altered dependent on spontaneous high and low pain intensity. Additionally, sliding-window functional connectivity analysis revealed that the dlPFC-PAG connection anticorrelated with perceived pain intensity over the entire 12 min period. These findings reveal cortical systems underlying moment-to-moment changes in perceived pain in PTN, which likely cause dysregulation in the brainstem circuits previously identified, and consequently alter the appraisal of pain across time.

A case study using spectroscopy and computational modelling for Co speciation in a deep eutectic solvent.

Cobalt has a vital role in the manufacturing of reliable and sustainable clean energy technologies. However, the forecasted supply deficit for cobalt is likely to reach values of 150 kT by 2030. Therefore, it is paramount to consider end-of-life devices as secondary resources for cobalt. Electrorecovery of cobalt from leached solutions has attracted attention due to the sustainability of the recovery process over solvent extraction followed by chemical precipitation. Recently, we reported Co electrorecovery from two different cobalt sources (CoCl2·6H2O and CoSO4·7H2O) using ethylene glycol : choline chloride (EG : ChCl) in a 4.5 : 1 molar ratio, leading to higher purity and easier electrodeposition when sulfate was present as an additive. Here, Co2+ speciation is reported for the two EG : ChCl systems depending on the cobalt source using several spectroscopic techniques (e.g. NMR, EPR, FTIR) in combination with molecular dynamics simulations. Monodentate coordination of SO42- to Co2+, forming the tetrahedral [CoCl3(SO4)]3- was observed as the dominant structure in the system containing CoSO4·7H2O, whereas the system comprising CoCl2·6H2O shows a homoleptic tetrahedral [CoCl4]2- as the dominant structure. This resulted in knowledge being gained regarding Co2+ speciation and the correlation with electrochemistry will contribute to the science required for designing safe electrolytes for efficient electrorecovery.

Antidepressant and antipsychotic prescribing in patients with type 2 diabetes in Scotland: A time-trend analysis from 2004 to 2021.

AIMS: Prescribing of antidepressant and antipsychotic drugs in general populations has increased in the United Kingdom, but prescribing trends in people with type 2 diabetes (T2D) have not previously been investigated. The aim of this study was to describe time trends in annual prevalence of antidepressant and antipsychotic drug prescribing in adult patients with T2D. METHODS: We conducted repeated annual cross-sectional analysesof a population-based diabetes registry with 99% coverage, derived from primary and secondary care data in Scotland, from 2004 to 2021. For each cross-sectional calendar year time period, we calculated the prevalence of antidepressant and antipsychotic drug prescribing, overall and by sociodemographic characteristics and drug subtype. RESULTS: The number of patients with a T2D diagnosis in Scotland increased from 161 915 in 2004 to 309 288 in 2021. Prevalence of antidepressant and antipsychotic prescribing in patients with T2D increased markedly between 2004 and 2021 (from 20.0 per 100 person-years to 33.3 per 100 person-years and from 2.8 per 100 person-years to 4.7 per 100 person-years, respectively). We observed this pattern for all drug subtypes except for first-generation antipsychotics, prescribing of which remained largely stable. The degree of increase, as well as the overall prevalence of prescribing, differed by age, sex, socioeconomic status and subtype of drug class. CONCLUSIONS: There has been a marked increase in the prevalence of antidepressant and antipsychotic prescribing in patients with T2D in Scotland. Further research should identify the reasons for this increase, including indication for use and the extent to which this reflects increases in incident prescribing rather than increased duration.

Efficiency and Mechanism of Catalytic Siloxane Exchange in Vitrimer Polymers: Modeling and Density Functional Theory Investigations.

Of late, siloxane-containing vitrimers have gained significant interest due to their fast dynamic characteristics over a reasonable temperature range (180-220 °C), making them well-suited for diverse applications. The exchange reaction pathway in the siloxane vitrimers is accountable for the covalent adaptive network, with the reaction's effectiveness being regulated by either organic or organometallic catalysts. However, directly studying the exchange reaction pathway in the bulk phase using experimental approaches is challenging because of the intricate and interconnected structure of these vitrimers. Here, we perform comprehensive density functional theory (DFT) and experimental investigations to discover the detailed catalytic efficacy of siloxane exchange and provide direction for the reaction process using a 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) catalyst. The calculated transition barrier energy and catalytic efficiency of hexamethyldisiloxane and dihydroxy-dimethylsilane exchange derived from the nudged elastic band with transition-state calculations strongly agree with the experimental findings. In addition, Fukui indices, along with partial charges, are employed to evaluate the nucleophilic and electrophilic behaviors of silanol and siloxane molecules. Our analysis revealed that by utilizing the Fukui indices of both the acid and the base, we can make an approximate estimation of the respective kinetics of the SN2 process in the siloxane exchange reaction mechanism. These findings establish a foundation for comprehending a crucial aspect of the exchange mechanism in siloxane vitrimer systems and could aid in the development of novel catalysts.

PROTOCOL: Behavioral, information and monetary interventions to reduce energy consumption in households: A "living" systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows: Our proposed systematic review and meta-analysis will integrate the evidence available from all sources to answer the following questions: (1) to what extent can information, behavioral and monetary interventions reduce energy consumption of households in residential buildings? (average treatment effect of interventions) (2) what is the relative effectiveness of interventions? (account for heterogeneity in treatment effects across and within studies) (3) how effective are combinations of different interventions?

DNA methylation enables recurrent endogenization of giant viruses in an animal relative.

5-Methylcytosine (5mC) is a widespread silencing mechanism that controls genomic parasites. In eukaryotes, 5mC has gained complex roles in gene regulation beyond parasite control, yet 5mC has also been lost in many lineages. The causes for 5mC retention and its genomic consequences are still poorly understood. Here, we show that the protist closely related to animals Amoebidium appalachense features both transposon and gene body methylation, a pattern reminiscent of invertebrates and plants. Unexpectedly, hypermethylated genomic regions in Amoebidium derive from viral insertions, including hundreds of endogenized giant viruses, contributing 14% of the proteome. Using a combination of inhibitors and genomic assays, we demonstrate that 5mC silences these giant virus insertions. Moreover, alternative Amoebidium isolates show polymorphic giant virus insertions, highlighting a dynamic process of infection, endogenization, and purging. Our results indicate that 5mC is critical for the controlled coexistence of newly acquired viral DNA into eukaryotic genomes, making Amoebidium a unique model to understand the hybrid origins of eukaryotic DNA.

Brain gray matter changes in children at risk for sudden unexpected death in epilepsy.

BACKGROUND: Potential failing adult brain sites, stratified by risk, mediating Sudden Unexpected Death in Epilepsy (SUDEP) have been described, but are unknown in children. METHODS: We examined regional brain volumes using T1-weighted MRI images in 21 children with epilepsy at high SUDEP risk and 62 healthy children, together with SUDEP risk scores, calculated from focal seizure frequency. Gray matter tissue type was partitioned, maps normalized, smoothed, and compared between groups (SPM12; ANCOVA; covariates, age, sex, and BMI). Partial correlations between regional volumes and seizure frequency were examined (SPM12, covariates, age, sex, and BMI); 67% were at high risk for SUDEP. RESULTS: The cerebellar cortex, hippocampus, amygdala, putamen, cingulate, thalamus, and para-hippocampal gyrus showed increased gray matter volumes in epilepsy, and decreased volumes in the posterior thalamus, lingual gyrus, and temporal cortices. The cingulate, insula, and putamen showed significant positive relationships with focal seizure frequency indices using whole-brain voxel-by-voxel partial correlations. Tissue volume changes in selected sites differed in direction from adults; particularly, cerebellar sites, key for hypotensive recovery, increased rather than adult declines. CONCLUSION: The volume increases may represent expansion by inflammatory or other processes that, with sustained repetitive seizure discharge, lead to tissue volume declines described earlier in adults. IMPACT: Children with epilepsy, who are at risk for Sudden Unexplained Death, show changes in brain volume that often differ in direction of change from adults at risk for SUDEP. Sites of volume change play significant roles in mediating breathing and blood pressure, and include areas that serve recovery from prolonged apnea and marked loss of blood pressure. The extent of volume changes correlated with focal seizure frequency. Although the underlying processes contributing to regional volume changes remain speculative, regions of tissue swelling in pediatric brain areas may represent transitory conditions that later lead to tissue loss in the adult condition.

Understanding the role of cannabis use on cigarette dependence severity among individuals with e-cigarette and combustible tobacco dual use.

BACKGROUND AND OBJECTIVES: The use of both electronic and combustible cigarettes is related to greater rates of cannabis use. Further, cannabis use is associated with worse combustible smoking-related outcomes, yet little research has identified mechanisms underlying such relations. It may be that negative-affect-related transdiagnostic factors such as emotion dysregulation, anxiety sensitivity, and/or distress intolerance play a mechanistic role in the cannabis-tobacco interrelations. METHODS: The current study tested this hypothesis among 400 adults who endorsed dual use, 33% of whom endorsed current (past 3 months) cannabis use. We conducted analyses of variance and indirect effects model using the PROCESS v4.1 macro in SPSS version 29. RESULTS: Results indicated that participants who use cannabis reported greater difficulty with emotion regulation, anxiety sensitivity, and cigarette dependence severity. Cannabis use was related to cigarette dependence severity indirectly via difficulty with emotion regulation and anxiety sensitivity. DISCUSSION AND CONCLUSIONS: These results indicate that specific transdiagnostic negative-affect-related factors of difficulty with emotion regulation and anxiety sensitivity are associated with cannabis use among adults who smoke combustible and electronic cigarettes. SCIENTIFIC SIGNIFICANCE: Given that these transdiagnostic factors are malleable, these findings suggest targeting and engaging such mechanisms may offer novel behavioral change strategies for this high-risk population.

Pulmonary artery catheter use and in-hospital outcomes in cardiac surgery: a systematic review and meta-analysis.

OBJECTIVES: To determine the association of intraoperative pulmonary artery catheter (PAC) use with in-hospital outcomes in cardiac surgical patients. METHODS: MEDLINE, Embase, and Cochrane Library (Wiley) databases were screened for studies that compared cardiac surgical patients receiving intraoperative PAC with controls and reporting in-hospital mortality. Secondary outcomes included intensive care unit length of stay, cost of hospitalization, fluid volume administered, intubation time, inotropes use, acute kidney injury (AKI), stroke, myocardial infarction (MI), and infections. RESULTS: Seven studies (25 853 patients, 88.6% undergoing coronary artery bypass graft surgery) were included. In-hospital mortality was significantly increased with PAC use [odds ratio (OR) 1.57; 95% confidence interval (CI) 1.12-2.20, P = 0.04]; PAC use was also associated with greater intraoperative inotrope use (OR 2.61; 95% CI 1.54-4.41) and costs [standardized mean difference (SMD) = 0.20; 95% CI 0.16-0.23], longer intensive care unit stay (SMD = 0.29; 95% CI 0.25-0.33), and longer intubation time (SMD = 0.44; 95% CI 0.12-0.76). CONCLUSIONS: PAC use is associated with significantly increased odds of in-hospital mortality, but the amount and quality of the available evidence is limited. Prospective randomized trials testing the effect of PAC on the outcomes of cardiac surgical patients are urgently needed.

Tuning Surface Adhesion Using Grayscale Electron-beam Lithography.

Surface texturing of manufactured products tailors their properties, such as friction, adhesion, biocompatibility, or fluid interactions. However, advancements in this area are largely the result of trial-and-effort testing and generally lack a science-guided framework for determining the surface topography that will optimize performance. The present investigation explores grayscale electron-beam lithography as a means to create multiscale surface patterns to control surface performance. Here, we created and characterized a set of surface textures on a silicon wafer; the textures were superpositions of sine waves of varying wavelengths and amplitudes. First, the multiscale topography of the patterned surface was characterized, using profilometry and atomic force microscopy, to understand its fidelity to the designed-in pattern. The results of this analysis demonstrated how grayscale lithography accurately controlled the lateral size of features but was less precise on the vertical height of the surface, and also introduced inherent roughness below the scale of patterning. Second, a micromechanical tester was used to characterize the adhesion of the surfaces with large-scale polished silicon spheres. The results showed that adhesion could be tailored, with significant contribution from all of the designed-in length scales of topography. The strength of adhesion did not correlate with conventional roughness parameters but could be accurately modeled using simple numerical integration. Taken together, this investigation demonstrates the promise and challenges of grayscale e-beam lithography with multiscale patterns as a method for the tailoring of surface performance.

Decreased Strength, Complication Rate and Higher Satisfaction in Conservative Treatment of Partial Distal Biceps Tendon Rupture Compared to Surgical Treatment: A Systematic Review.

Background: Treatment modalities for partial distal biceps tendon (DBT) ruptures include conservative management (immobilization, medication, and physical therapy) or surgery. Selecting treatment modality can present a challenge to both patient and provider. Hypothesis: It was hypothesized that patients undergoing surgical treatment for partial DBT rupture would have higher complications but better overall strength, range of motion (ROM), and patient satisfaction. Study Design: Systematic Review. Methods: A systematic review was performed in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane, Embase, and Medline databases were searched for studies published through May 2023. Studies were included if they examined patients with a partial DBT rupture who underwent treatment. Exclusion criteria were non-human studies, studies not in English, reviews, technical notes, letters to the editor, surgical technique papers, and studies reported in a prior review. Results: 13 studies consisting of 290 patients with a partial DBT tear were included in this review. 75% of the patients were male and the ages ranged from 23 - 75 years. The follow up for the patients ranged from 1 - 94 months. 55 patients underwent conservative treatment versus 256 patients underwent surgical treatment. Outcomes examined by the studies included pain, strength, range of motion (ROM), complications, patient reported outcomes (PROs), return to activity, and patient satisfaction. Conclusion: Treatment for partial DBT tear via surgery or conservative treatment both produce good clinical outcomes. There are similar outcomes between treatment options for pain and ROM. Conservative treatment had some poorer outcomes in terms of strength after treatment. Surgical treatment had more complications and a few patients with decreased satisfaction. Overall, both are viable treatment options, requiring a physician and patient discussion regarding the pros and cons of both options as a part of a shared decision-making process that incorporates patient priorities.

Remote work transition amidst COVID-19: Impacts on presenteeism, absenteeism, and worker well-being-A scoping review.

BACKGROUND: The COVID-19 pandemic has accelerated the transition to remote work, leading to increased attention on presenteeism and absenteeism among remote workers. Understanding the implications of these phenomena on worker health and productivity is crucial for optimizing remote work arrangements and developing policies to improve employee well-being. OBJECTIVES: This scoping review aims to examine the occurrence of presenteeism and absenteeism among remote workers during the COVID-19 pandemic and the interrelated physical and mental health issues during these periods. METHODS: PsycINFO, Medline, Embase, CINAHL, Eric, Business Source Premier, SCOPUS, and sociological abstracts were searched resulting in 1792 articles. Articles were included if the population of interest was 18+ (i.e., working age), engaged in full or part-time work, and the employees shifted from in-person to remote work due to the COVID-19 pandemic. All study designs, geographical areas, and papers written post-onset of the COVID-19 pandemic were included; however, systematic reviews were excluded. Data was charted into Microsoft Excel by 2 independent reviewers. RESULTS: The literature search identified 10 studies (i.e., seven cross-sectional studies, two qualitative studies, and one observational study). Five major overarching themes were identified specifically (1) telework and mental health (2) telework and physical health (3) worker benefits (4) gender dynamics and (5) difficulty navigating the teleworking environment. While remote work offers flexibility in terms of saved commute time and flexible work schedules, it also exacerbates challenges related to presenteeism, absenteeism, and work-life balance. These challenges include experiencing psychological distress, depression, anxiety, stress, sleep deprivation, musculoskeletal pain, difficulties concentrating at work for both women and working parents, struggles disconnecting after hours, and the inability to delineate between the work and home environment. DISCUSSION: The findings suggest that remote work during the COVID-19 pandemic has both positive and negative implications for worker well-being and productivity. However, future research needs to incorporate the potential effects of telework frequency (full time vs. part time) on employee productivity and its role on presenteeism and absenteeism, to gain a more comprehensive understanding on remote work difficulties. Addressing these challenges requires proactive interventions and support mechanisms to promote worker health and productivity in remote settings.

Diagnostic accuracy of a 'sarcopenia index' based on serum biomarkers creatinine and cystatin C in 458,702 UK Biobank participants.

BACKGROUND & AIMS: There is an emerging and urgent need to identify biomarkers of sarcopenia. A novel sarcopenia index (SI), based on serum creatinine and cystatin C, has emerged as a potential biomarker for use. The SI can predict clinical outcomes and discriminate between the presence of sarcopenia in a range of chronic and acute conditions. However, the SI has not yet been tested in a large real-world general population dataset. This study aimed to investigate the accuracy of the SI in the identification of sarcopenia in a large prospective general population cohort. METHODS: Data were taken from UK Biobank, a large prospective epidemiological study in the United Kingdom (UK). Serum creatinine and cystatin C values were used to calculate the SI [creatinine (mg/dl)/cystatin C (mg/dl) × 100]. Probable sarcopenia was defined by maximum handgrip strength (HGS). Muscle mass was assessed using bioelectrical impedance analysis. Low muscle mass was defined as an appendicular lean mass (ALM) index below prespecified thresholds. Confirmed sarcopenia was defined as both low HGS and low muscle mass. Pearson correlation coefficients and logistic regression were used to explore the association between various sarcopenia traits (probable sarcopenia, low ALM index, and confirmed sarcopenia) and the SI. The diagnostic value of the SI was investigated using the area under the receiver operating characteristic curve (area under the curve, AUC). RESULTS: 458,702 participants were included in the analysis (46.4% males, mean age, males: 68.7 (±8.2) years; females: 68.2 (±8.0) years)). Probable sarcopenia was observed in 4.5% of males and 6.1% of females; low ALM index in 2.8% of males and 0.7% of females; confirmed sarcopenia in 0.3% of males and 0.1% of females. SI was significantly lower in individuals with confirmed sarcopenia (males: 86.3 ± 16.6 vs. 99.5 ± 15.3, p < .01; females: 73.6 ± 13.7 vs. 84.6 ± 14.0, p < .01). For every 1-unit increase in the SI, the odds of confirmed sarcopenia were reduced by 5% in males (odds ratio (OR): 0.95, p < 0.001) and 7% in females (OR: 0.923, p < 0.001). The AUC showed acceptable discriminative ability of confirmed sarcopenia (males: AUC = 0.731; females: AUC = 0.711). CONCLUSIONS: Using a large real-world dataset of almost half a million people, our study indicated the SI has acceptable diagnostic accuracy when identifying those with sarcopenia and may be a useful biomarker to aid the stratification of those at risk and in need of intervention.

Acute methamphetamine and alcohol usage alters gaze behaviour during driving: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Methamphetamine is frequently co-consumed with alcohol, yet combined effects on visually guided behaviours have not been experimentally assessed. This study examined whether methamphetamine and alcohol-induced changes in gaze behaviour can be accurately detected and indexed during a simulated driving task to establish characteristic patterns relevant to traffic safety. METHODS: In a randomised, placebo-controlled, cross-over study design, the effects of acute oral methamphetamine (0.42 mg/kg) were assessed with and without low doses of alcohol (target 0.04% blood alcohol content) on gaze behaviour during driving. Twenty healthy adults (mean age 29.5 years (SD ± 4.9), 40% female) completed four, 1-h simulated drives with simultaneous eye monitoring using the SensoMotoric Instruments cap-mounted eye tracker over a 4-week experimental paradigm. Gaze entropy measures were used to quantify visual scanning efficiency, expressed as gaze transition entropy and stationary gaze entropy. Fixations, recorded as duration (milliseconds, ms) and rate (count) per minute, were examined in 10-min bins over the duration of the drive. Driving performance was assessed by the standard deviation of lateral position, standard deviation of speed and steering variability. RESULTS: Methamphetamine increased the rate and duration of fixations and produced a less dispersed but more disorganised pattern of gaze during highway driving while preserving performance. Alcohol alone impaired both oculomotor control and driving performance, even when consumed at levels well below the legal limit stipulated in many international jurisdictions. CONCLUSIONS: Methamphetamine-affected drivers display inefficient exploration in a limited visual range during driving. Eye-tracking metrics thus show potential for indexing intoxication due to psychoactive substance usage.