Parasitic diseases of the central nervous system: lessons for clinicians and policy makers

Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, diagnosis, therapeutic strategies and recent milestones, and aspects related to prevention and control

A hazard model of the probability of medical school dropout in the United Kingdom

From individual level longitudinal data for two entire cohorts of medical students in UK universities, we use multilevel models to analyse the probability that an individual student will drop out of medical school. We find that academic preparedness—both in terms of previous subjects studied and levels of attainment therein—is the major influence on withdrawal by medical students. Additionally, males and more mature students are more likely to withdraw than females or younger students respectively. We find evidence that the factors influencing the decision to transfer course differ from those affecting the decision to drop out for other reasons

Stratified care vs stepped care for depression : a cluster randomized clinical trial

Importance: Depression is a major cause of disability worldwide. Although empirically supported treatments are available, there is scarce evidence on how to effectively personalize psychological treatment selection. Objective: To compare the clinical effectiveness and cost-effectiveness of 2 treatment selection strategies: stepped care and stratified care. Design, Setting, and Participants: This multisite, cluster randomized clinical trial recruited participants from the English National Health Service from July 5, 2018, to February 1, 2019. Thirty clinicians working across 4 psychological therapy services were randomly assigned to provide stratified (n = 15) or stepped (n = 15) care. In stepped care, patients sequentially access low-intensity guided self-help followed by high-intensity psychotherapy. In stratified care, patients are matched with either low- or high-intensity treatments at initial assessment. Data were analyzed from May 18, 2020, to October 13, 2021, using intention-to-treat principles. Interventions: All clinicians used the same interview schedule to conduct initial assessments with patients seeking psychological treatment for common mental disorders, but those in the stratified care group received a personalized treatment recommendation for each patient generated by a machine learning algorithm. Eligible patients received either stratified or stepped care (ie, treatment as usual). Main Outcomes and Measures: The preregistered outcome was posttreatment reliable and clinically significant improvement (RCSI) of depression symptoms (measured using the 9-item Patient Health Questionnaire). The RCSI outcome was compared between groups using logistic regression adjusted for baseline severity. Cost-effectiveness analyses compared incremental costs and health outcomes of the 2 treatment pathways. Results: A total of 951 patients were included (618 women among 950 with data available [65.1%]; mean [SD] age, 38.27 [14.53] years). The proportion of cases of RCSI was significantly higher in the stratified care arm compared with the stepped care arm (264 of 505 [52.3%] vs 134 of 297 [45.1%]; odds ratio, 1.40 [95% CI, 1.04-1.87]; P = .03). Stratified care was associated with a higher mean additional cost per patient (£104.5 [95% CI, £67.5-£141.6] [$139.83 (95$90.32-$189.48)]; P < .001) because more patients accessed high-intensity treatments (332 of 583 [56.9%] vs 107 of 368 [29.1%]; χ2 = 70.51; P < .001), but this additional cost resulted in an approximately 7% increase in the probability of RCSI. Conclusions and Relevance: In this cluster randomized clinical trial of adults with common mental disorders, stratified care was efficacious and cost-effective for the treatment of depression symptoms compared with stepped care. Stratified care can improve depression treatment outcomes at a modest additional cost. Trial Registration: isrctn.org Identifier: ISRCTN1110618

Cultural Orientations of sport managers

Various interpretations of sport management are cultural constructs underpinned by core assumptions and values held by members of professional communities. Sport managers world wide share common problems, but differ in how they resolve them. These universal differences emerge from the relationships they form with other people, and their attitude to time, activities and the natural environment. This paper examines the role of sport managers’ cultural orientations in the interpretation and practice of sport management. Using a multiple dimension model (Hampden-Turner and Trompenaars, 2000) it sketches the cultural profiles of fifteen sport managers from seven countries. A combination of methods was employed including questionnaires, interviews and participant observation. It is contended that the culture of sport management concerns a social process by which managers get involved in reconciling seven fundamental cultural dilemmas in order to perform tasks and achieve certain ends. Thus, a knowledge of the cultural meaning of sport management in a particular country would equip sport managers with a valuable tool in managing both the cultural diversity of their own work forces and in developing appropriate cross-cultural skills needed for running international events, marketing campaigns, sponsorship deals and joint ventures

Mapping medical careers: Questionnaire assessment of career preferences in medical school applicants and final-year students

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the workforce planning of health-care services. However, there is little theoretical understanding of how different medical specialities are perceived or how choices are made, despite there being much work in general on this topic in occupational psychology, which is influenced by Holland's RIASEC (Realistic-Investigative-Artistic-Social-Enterprising-Conventional) typology of careers, and Gottfredson's model of circumscription and compromise. In this study, we use three large-scale cohorts of medical students to produce maps of medical careers. METHODS: Information on between 24 and 28 specialities was collected in three UK cohorts of medical students (1981, 1986 and 1991 entry), in applicants (1981 and 1986 cohorts, N = 1135 and 2032) or entrants (1991 cohort, N = 2973) and in final-year students (N = 330, 376, and 1437). Mapping used Individual Differences Scaling (INDSCAL) on sub-groups broken down by age and sex. The method was validated in a population sample using a full range of careers, and demonstrating that the RIASEC structure could be extracted. RESULTS: Medical specialities in each cohort, at application and in the final-year, were well represented by a two-dimensional space. The representations showed a close similarity to Holland's RIASEC typology, with the main orthogonal dimensions appearing similar to Prediger's derived orthogonal dimensions of 'Things-People' and 'Data-Ideas'. CONCLUSIONS: There are close parallels between Holland's general typology of careers, and the structure we have found in medical careers. Medical specialities typical of Holland's six RIASEC categories are Surgery (Realistic), Hospital Medicine (Investigative), Psychiatry (Artistic), Public Health (Social), Administrative Medicine (Enterprising), and Laboratory Medicine (Conventional). The homology between medical careers and RIASEC may mean that the map can be used as the basis for understanding career choice, and for providing career counselling

Human cytomegalovirus gene UL76 induces IL-8 expression through activation of the DNA damage response.

Human cytomegalovirus (HCMV), a β-herpesvirus, has evolved many strategies to subvert both innate and adaptive host immunity in order to ensure its survival and propagation within the host. Induction of IL-8 is particularly important during HCMV infection as neutrophils, primarily attracted by IL-8, play a key role in virus dissemination. Moreover, IL-8 has a positive effect in the replication of HCMV. This work has identified an HCMV gene (UL76), with the relevant property of inducing IL-8 expression at both transcriptional and protein levels. Up-regulation of IL-8 by UL76 results from activation of the NF-kB pathway as inhibition of both IKK-β activity or degradation of Ikβα abolishes the IL-8 induction and, concomitantly, expression of UL76 is associated with the translocation of p65 to the nucleus where it binds to the IL-8 promoter. Furthermore, the UL76-mediated induction of IL-8 requires ATM and is correlated with the phosphorylation of NEMO on serine 85, indicating that UL76 activates NF-kB pathway by the DNA Damage response, similar to the impact of genotoxic drugs. More importantly, a UL76 deletion mutant virus was significantly less efficient in stimulating IL-8 production than the wild type virus. In addition, there was a significant reduction of IL-8 secretion when ATM -/- cells were infected with wild type HCMV, thus, indicating that ATM is also involved in the induction of IL-8 by HCMV. In conclusion, we demonstrate that expression of UL76 gene induces IL-8 expression as a result of the DNA damage response and that both UL76 and ATM have a role in the mechanism of IL-8 induction during HCMV infection. Hence, this work characterizes a new role of the activation of DNA Damage response in the context of host-pathogen interactions

A novel TLR3 inhibitor encoded by African swine fever virus (ASFV)

African swine fever virus (ASFV) encodes proteins that manipulate important host antiviral mechanisms. Bioinformatic analysis of the ASFV genome revealed ORF I329L, a gene without any previous functional characterization as a possible inhibitor of TLR signaling. We demonstrate that ORF I329L encodes a highly glycosylated protein expressed in the cell membrane and on its surface. I329L also inhibited dsRNA-stimulated activation of NFκB and IRF3, two key players in innate immunity. Consistent with this, expression of I329L protein also inhibited the activation of interferon-β and CCL5. Finally, overexpression of TRIF reversed I329L-mediated inhibition of both NFκB and IRF3 activation. Our results suggest that TRIF, a key MyD88-independent adaptor molecule, is a possible target of this viral host modulation gene. The demonstration of an ASFV host evasion molecule inhibiting TLR responses is consistent with the ability of this virus to infect vertebrate and invertebrate hosts, both of which deploy innate immunity controlled by conserved TLR systems

A New Method for Non-Invasive Estimation of Human Muscle Fiber Type Composition

Background: It has been established that excellence in sports with short and long exercise duration requires a high proportion of fast-twitch (FT) or type-II fibers and slow-twitch (ST) or type-I fibers, respectively. Until today, the muscle biopsy method is still accepted as gold standard to measure muscle fiber type composition. Because of its invasive nature and high sampling variance, it would be useful to develop a non-invasive alternative.status: publishe

Neoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Protein

Virus host evasion genes are ready-made tools for gene manipulation and therapy. In this work we have assessed the impact in vivo of the evasion gene A238L of the African Swine Fever Virus, a gene which inhibits transcription mediated by both NF-κB and NFAT. The A238L gene has been selectively expressed in mouse T lymphocytes using tissue specific promoter, enhancer and locus control region sequences for CD2. The resulting two independently derived transgenic mice expressed the transgene and developed a metastasic, angiogenic and transplantable CD4+CD8+CD69– lymphoma. The CD4+CD8+CD69– cells also grew vigorously in vitro. The absence of CD69 from the tumour cells suggests that they were derived from T cells at a stage prior to positive selection. In contrast, transgenic mice similarly expressing a mutant A238L, solely inhibiting transcription mediated by NF-κB, were indistinguishable from wild type mice. Expression of Rag1, Rag2, TCRβ-V8.2, CD25, FoxP3, Bcl3, Bcl2 l14, Myc, IL-2, NFAT1 and Itk, by purified CD4+CD8+CD69– thymocytes from A238L transgenic mice was consistent with the phenotype. Similarly evaluated expression profiles of CD4+CD8+ CD69– thymocytes from the mutant A238L transgenic mice were comparable to those of wild type mice. These features, together with the demonstration of (mono-)oligoclonality, suggest a transgene-NFAT-dependent transformation yielding a lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas

Efficacy of high-intensity, low-volume interval training compared to continuous aerobic training on insulin resistance, skeletal muscle structure and function in adults with metabolic syndrome: study protocol for a randomized controlled clinical trial (Intraining-MET)

ABSTRACT: Evidence of the efficacy of high-intensity, low-volume interval training (HIIT-low volume) in treating insulin resistance (IR) in patients with metabolic disorders is contradictory. In addition, it is unknown whether this effect is mediated through muscle endocrine function, which in turn depends on muscle mass and fiber type composition. Our aims were to assess the efficacy of HIIT-low volume compared to continuous aerobic exercise (CAE) in treating IR in adults with metabolic syndrome (MS) and to establish whether musclin, apelin, muscle mass and muscle composition are mediators of the effect. Methods: This is a controlled, randomized, clinical trial using the minimization method, with blinding of those who will evaluate the outcomes and two parallel groups for the purpose of showing superiority. Sixty patients with MS and IR with ages between 40 and 60 years will be included. A clinical evaluation will be carried out, along with laboratory tests to evaluate IR (homeostatic model assessment (HOMA)), muscle endocrine function (serum levels of musclin and apelin), thigh muscle mass (by dual energy x-ray absorptiometry (DXA) and thigh muscle composition (by carnosine measurement with proton magnetic resonance spectroscopy (H–MRS)), before and after 12 weeks of a treadmill exercise program three times a week. Participants assigned to the intervention (n = 30) will receive HIIT-low volume in 22-min sessions that will include six intervals at a load of 90% of maximum oxygen consumption (VO2 max) for 1 min followed by 2 min at 50% of VO2 max. The control group (n = 30) will receive CAE at an intensity of 60% of VO2 max for 36 min. A theoretical model based on structural equations will be proposed to estimate the total, direct and indirect effects of training on IR and the proportion explained by the mediators. Discussion: Compared with CAE, HIIT-low volume can be effective and efficient at improving physical capacity and decreasing cardiovascular risk factors, such as IR, in patients with metabolic disorders. Studies that evaluate mediating variables of the effect of HIIT-low volume on IR, such as endocrine function and skeletal muscle structure, are necessary to understand the role of skeletal muscle in the pathophysiology of MS and their regulation by exercise. Trial registration: NCT03087721. High-intensity Interval, Low Volume Training in Metabolic Syndrome (Intraining-MET). Registered on 22 March 2017, retrospectively registered