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The protein kinases IKKε and TBK1 are activated in liver and fat in mouse models of obesity. We have previously demonstrated that treatment with the IKKε/TBK1 inhibitor amlexanox produces weight loss and relieves insulin resistance in obese animals and patients. While amlexanox treatment caused a transient reduction in food intake, long-term weight loss was attributable to increased energy expenditure via FGF21-dependent beiging of white adipose tissue (WAT). Amlexanox increased FGF21 synthesis and secretion in several tissues. Interestingly, although hepatic secretion determined circulating levels, it was dispensable for regulating energy expenditure. In contrast, adipocyte-secreted FGF21 may have acted as an autocrine factor that led to adipose tissue browning and weight loss in obese mice. Moreover, increased energy expenditure was an important determinant of improved insulin sensitivity by amlexanox. Conversely, the immediate reductions in fasting blood glucose observed with acute amlexanox treatment were mediated by the suppression of hepatic glucose production via activation of STAT3 by adipocyte-secreted IL-6. These findings demonstrate that amlexanox improved metabolic health via FGF21 action in adipocytes to increase energy expenditure via WAT beiging and that adipocyte-derived IL-6 has an endocrine role in decreasing gluconeogenesis via hepatic STAT3 activation, thereby producing a coordinated improvement in metabolic parameters.

As an innovative propulsion technique, combustion mechanism of laser-augmented chemical propulsion has still to be ascertained. Benefiting from high nitrogen content and thermal stability, 5-aminotetrazole is a suitable ingredient for LACP. Under a flowing nitrogen environment, two kinds of unique burning surfaces were observed to occur for 5-ATZ, used as a single reacting propellant ingredient with the addition of carbon, under laser ablation. Both surfaces are hollow structures and differ by the possible presence of edges. Using micro computed tomography, the 3D perspective structures of both surfaces were revealed. Resorting to various characterization methods, a unified formation mechanism for both surfaces is proposed. This mechanism specifically applies to laser ablation, but could be crucial to common burning mechanisms in LACP.

Abstract We report the findings from a randomized, parallel study designed to evaluate nicotine pharmacokinetics (PK) following 10 min of ad libitum use of electronic nicotine delivery system (ENDS) in four flavor variants. Subjects were randomized an investigational product (IP) and blood samples were collected for PK assessments during a test session. Primary endpoints were baseline-adjusted values of maximum plasma nicotine concentration (Cmax) and area under the nicotine concentration-vs-time curve up to 60 min (AUCnic0–60). Baseline-adjusted mean Cmax ranged from 6.53 to 8.21 ng/mL, and mean AUCnic0–60 ranged from 206.87 to 263.52 ng min/mL for all ENDS IPs. Results of geometric mean Cmax and AUCnic0–60 values were within 95% confidence intervals (CI) among the ENDS IP flavor variants tested.

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety of recreational SARM users. On 10 November 2022 PubMed, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies that reported safety data of SARMs. A multi-tiered screening approach was utilized, and any study or case report of generally healthy individuals exposed to any SARM was included. Thirty-three studies were included in the review with 15 case reports or case series and 18 clinical trials (total patients N = 2136 patients, exposed to SARM N = 1447). There were case reports of drug-induced liver injury (DILI) (N = 15), Achilles tendon rupture (N = 1), rhabdomyolysis (N = 1), and mild reversible liver enzyme elevation (N = 1). Elevated alanine aminotransferase (ALT) was commonly reported in clinical trials in patients exposed to SARM (mean 7.1% across trials). Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI.

Colleges and universities should serve as inclusive environments positioned to provide a strong education to all students. However, bias and discrimination mar the college atmosphere for many. Simultaneously, there is a paucity of research that examines student views of diversity and inclusion in both higher education and sport management. Employing mixed methods, this research examined the perceptions of diversity and inclusion among undergraduate students in sport management programs. Data demonstrate that student perceptions differ across measures of sex, race/ethnicity, upbringing, internship experiences, and transfer status. Findings suggest implications for embedding diversity and inclusion topics within sport management curricula to develop competencies crucial to students' educational success and future in the sport industry.

This article reports research that identified and analyzed assessment for learning strategies employed by six Canadian music educators to support and develop student creativity. Findings include descriptions of creativity-nurturing practices organized into four categories: (a) developing assessment criteria; (b) encouraging creative processes; (c) optimizing the classroom context; and (d) activating self-assessment. Results include detailed descriptions of strategies that educators can employ to leverage formative assessment to nurture student creativity within and beyond music education contexts.

This paper reports on a study of student peer mentorship in the context of nursing education in a higher education program in Canada. The study used an embodied hermeneutic phenomenological methodology to investigate student peer mentors' perceptions of teaching during peer mentorship. The data were collected over one calendar year (2019) and involved analysis of 10 participants' interview data and their 'body maps,' produced in response to guided questions. Through the data analysis a core theme of 'commitment to mentee growth' was identified, along with seven interrelated themes: sharing responsibility for learning, moderating stress, mediating power relations, navigating unknown processes, valuing creative approaches, offering generous acceptance, and facilitating confidence. Student peer mentorship has the potential to contribute to health professions education in a number of unique ways including through embodied attunement, trusting intersubjective relations, and dialogic education. This study is innovative in its purposeful design and aim to investigate both cognitive and embodied perceptions of student peer mentors. The findings point to the promise of student peer mentorship for advancing health sciences education. Implications for peer mentorship program development in health professions education are discussed.

Communities of color have been disproportionately impacted by the coronavirus disease (COVID-19) pandemic, exposing the influence of decades of policies that have under-resourced and marginalized these communities. The history of segregation and inadequate funding in education has been exacerbated by the pandemic, compounding the educational inequities already present in the United States. The intersection of this inequity alongside immigration policies over the past years have led the undocumented student population to be adversely impacted. The lack of access to health care and social safety net programs, fear of deportation, and an over reliance on technology for schooling leaves a large segment of students vulnerable for adverse academic, emotional, and social outcomes. This paper will trace the historical path of educational segregation, immigration policies, and how these led to the disproportionate impact of COVID-19 on undocumented students. It will discuss interventions for undocumented students within an antioppressive ecological framework and the ethical responsibilities that school-based mental health professionals have to support undocumented students to fulfill their highest potential, manage the emotional toll of the pandemic, and advocate for change in immigration and educational policies.

This study employed a quantitative research design to investigate Chinese teachers' conceptions of classroom assessment and perceived skills. A total of 746 teachers were recruited through professional teaching groups. Results showed that a higher percentage of Chinese teachers selected contemporary assessment approaches to classroom assessment (e.g., assessment for learning) than more traditional approaches (e.g., assessment of learning). Chinese teachers also reported high levels of confidence in items that addressed aspects of assessment theory. Significant differences in approaches to classroom assessment were found across (a) age groups, (b) educational qualifications, and (c) between full-time classroom teachers and classroom teachers that held additional positions (e.g., school administrator, leader, head). Implications for educational policy-makers and practitioners in light of enhancing teacher assessment literacy are discussed.

Muscle fascicles are shorter and stiffer than normal in spastic Cerebral Palsy (CP). Increasing fascicle length (FL) has been attempted in CP, the outcomes of which have been unsatisfactory. In healthy muscles, FL can be increased using eccentric exercise at high velocities (ECC). Three conditions are possibly met during such ECC: muscle micro-damage, positive fascicle strain, and momentary muscle deactivation during lengthening. Participants with and without CP underwent a single bout of passive stretching at (appropriately) high velocities using isokinetic dynamometry, during which we examined muscle and fascicle behaviour. Vastus lateralis (VL) FL change was measured using ultrasonography and showed positive fascicle strain. Measures of muscle creatine kinase were used to establish whether micro-damage occurred in response to stretching, but the results did not confirm damage in either group. Vastus medialis (VM) and biceps femoris muscle activity were measured using electromyography in those with CP. Results supported momentary spastic muscle deactivation during lengthening: all participants experienced at least one epoch (60 ms) of increased activation followed by activation inhibition/deactivation of the VM during knee flexion. We argue that high-velocity passive stretching in CP provides a movement context which mimics ECC and could be used to increase spastic FL with training.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

A gratidão pode ser entendida como orientação para vida e capacidade de perceber e apreciar o positivo no mundo. O presente estudo objetivou mapear quantos e quais instrumentos estão disponíveis para mensuração da gratidão, as circunstâncias da avaliação e população predominante. Esta revisão sistemática localizou artigos em quatro bases de dados, resultando em um total de 36 artigos. Destes, foram encontradas 16 escalas originais e o restante indicado como adaptações e validações. Os principais resultados demonstram a disparidade numérica da percepção de gratidão entre gêneros e em relação à faixa etária avaliada. GQ-6 e GRAT são as escalas usadas com mais frequência, tendo maior variedade de contextos e públicos de aplicação. As medidas utilizadas para avaliação da consistência demonstraram, na maioria dos estudos, fidedignidade concisas. Conclui-se trazendo a necessidade de maior acesso a medidas de gratidão validadas, além do avanço na discussão referente à saúde mental

ObjectiveTo determine the prevalence of genital infections (GIs), including sexual transmitted STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and opportunistic pathogens that generally do not cause STIs, non-classic STI: Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma hominis, in women with high-risk oncogenic human papillomavirus (hr-HPV) infection and their association with cervical lesions.MethodsA cross-sectional study was carried out including 231 hr-HPV positive women. Of these, 46 has histologically confirmed cervical intraepithelial neoplasia 3 (CIN3) or more (including CIN3 and cervical cancer lesions-CIN3+). GIs were detected by multiplex real time PCR. Odds ratios (OR) were estimated to explore possible associations between GIs and the presence or absence of CIN3+ lesions. Additionally, we examined associations between sociodemographic, sexual, and clinical characteristics and the presence of GIs.ResultsIn total, there were 174/231 cases of GIs corresponding to an overall prevalence of 75.3% (95%CI: 69.4-80.4), being non-classic STIs the most common (72.3%) compared to STIs (12.6%). The most prevalent non-classic STI and STI were U. parvum (49.8%) and C. trachomatis (7.4%), respectively. The odds of presenting GIs were 3 times higher in women under 46 years compared to older counterparts (OR: 3.32, 95%CI: 1.74-6.16), and in women with a normal Pap smear with inflammation compared to those without inflammation (OR: 3.31, 95%CI: 1.15-9.77). GIs were equally present in women with and without CIN3+ lesions.ConclusionWe observed an association of GIs with inflammation in the Pap smear, but no association with CIN3+, as some of them are very common and likely part of the normal vaginal flora, suggesting that such infections do not appear to be cofactors in cervical carcinogenesis, although larger prospective studies are needed.

Mental illness in media can shape viewer’s beliefs about mental health, help-seeking, and empathic behaviors. The current study sought to investigate how mental health and substance use is depicted in popular media targeted for youth. The visual-verbal video analysis (VVVA) framework was applied to the HBO American drama television series Euphoria to understand how mental illness, substance use, and mental health service use is portrayed, and how characters respond to mental health scenes. Euphoria follows a group of high school students as they navigate adolescence, mental illness and substance use. The VVVA provides a framework for social science and medical researchers to qualitatively analyze multimodal information (e.g., text, cinematography, music and sounds, body language and facial expressions) of visual content. This commentary will briefly describe the VVVA framework, provide an overview of how the framework was applied and adapted to analyze a scene in the television series Euphoria , note similarities and differences to the original VVVA framework, and benefits and drawbacks. The VVVA framework was flexible and effective in coding various elements (e.g., body language, camera angles) in a scene in Euphoria.

Migrants and refugees face elevated risks for mental health problems but have limited access to services. This study compared two strategies for training and supervising nonspecialists to deliver a scalable psychological intervention, Group Problem Management Plus (gPM+), in northern Colombia. Adult women who reported elevated psychological distress and functional impairment were randomized to receive gPM+ delivered by nonspecialists who received training and supervision by: 1) a psychologist (specialized technical support); or 2) a nonspecialist who had been trained as a trainer/supervisor (nonspecialized technical support). We examined effectiveness and implementation outcomes using a mixed-methods approach. Thirteen nonspecialists were trained as gPM+ facilitators and three were trained-as-trainers. We enrolled 128 women to participate in gPM+ across the two conditions. Intervention attendance was higher in the specialized technical support condition. The nonspecialized technical support condition demonstrated higher fidelity to gPM+ and lower cost of implementation. Other indicators of effectiveness, adoption and implementation were comparable between the two implementation strategies. These results suggest it is feasible to implement mental health interventions, like gPM+, using lower-resource, community-embedded task sharing models, while maintaining safety and fidelity. Further evidence from fully powered trials is needed to make definitive conclusions about the relative cost of these implementation strategies.

Este artículo aborda la promoción económica y territorial en Tierra del Fuego, Antártida e Islas del Atlántico Sur como un medio para profundizar la soberanía argentina en Malvinas y el Atlántico Sur. Se examinan las tensiones entre las inversiones extranjeras y las críticas internas al régimen de promoción económica. Además, se analiza el estudio de FUNDAR, que propone una reconversión productiva en la región, destacando la eficiencia de la industria fueguina y su contribución al ahorro de divisas. Sin embargo, se critica la falta de consideración de la ocupación británica en Malvinas y se cuestiona la interpretación centralista del impacto fiscal del régimen.

Abstract La Fossa Caldera at Vulcano (Italy) has been showing signs of unrest since September 2021. To investigate this phenomenon, we conducted an analysis of geodetic and seismological data from July to December 2021. In particular, we analyzed Multi Temporal Interferometric Synthetic Aperture Radar and Global Navigation Satellite System data, showing a pronounced elliptical uplift signal, which we elaborated using analytical source modeling. Additionally, seismic data were used to identify seismicity associated with hydrothermal system activity and assess its temporal evolution. The results indicate that the observed deformation is consistent with the expansion of the hydrothermal system within the La Fossa Caldera. These findings align with the analysis of seismic data, revealing signals indicative of hydrothermal activity, such as Very Long Period events. The results suggest that the ongoing phenomenon since 2021 represents a hydrothermal unrest, similar to the one observed during the late 1970s to early 1990s.