Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise

We evaluated the effects of chronic oral supplementation with l-glutamine and l-alanine in their free form or as the dipeptide l-alanyl-l-glutamine (DIP) on muscle damage, inflammation and cytoprotection, in rats submitted to progressive resistance exercise (RE). Wistar rats (n 8/group) were submitted to 8-week RE, which consisted of climbing a ladder with progressive loads. In the final 21 d before euthanasia, supplements were delivered in a 4 % solution in drinking water. Glutamine, creatine kinase (CK), lactate dehydrogenase (LDH), TNF-α, specific IL (IL-1β, IL-6 and IL-10) and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated in plasma. The concentrations of glutamine, TNF-α, IL-6 and IL-10, as well as NF-κB activation, were determined in extensor digitorum longus (EDL) skeletal muscle. HSP70 level was assayed in EDL and peripheral blood mononuclear cells (PBMC). RE reduced glutamine concentration in plasma and EDL (P<0·05 v. sedentary group). However, l-glutamine supplements (l-alanine plus l-glutamine (GLN+ALA) and DIP groups) restored glutamine levels in plasma (by 40 and 58 %, respectively) and muscle (by 93 and 105 %, respectively). GLN+ALA and DIP groups also exhibited increased level of HSP70 in EDL and PBMC, consistent with the reduction of NF-κB p65 activation and cytokines in EDL. Muscle protection was also indicated by attenuation in plasma levels of CK, LDH, TNF-α and IL-1β, as well as an increase in IL-6, IL-10 and MCP-1. Our study demonstrates that chronic oral l-glutamine treatment (given with l-alanine or as dipeptide) following progressive RE induces cyprotective effects mediated by HSP70-associated responses to muscle damage and inflammation

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018

BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000–2018

Background: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA

Peer tutoring in a medical school: perceptions of tutors and tutees

BACKGROUND: Peer tutoring has been described as “people from similar social groupings who are not professional teachers helping each other to learn and learning themselves by teaching”. Peer tutoring is well accepted as a source of support in many medical curricula, where participation and learning involve a process of socialisation. Peer tutoring can ease the transition of the junior students from the university class environment to the hospital workplace. In this paper, we apply the Experienced Based Learning (ExBL) model to explore medical students’ perceptions of their experience of taking part in a newly established peer tutoring program at a hospital based clinical school. METHODS: In 2014, all students at Sydney Medical School – Central, located at Royal Prince Alfred Hospital were invited to voluntarily participate in the peer tutoring program. Year 3 students (n = 46) were invited to act as tutors for Year 1 students (n = 50), and Year 4 students (n = 60) were invited to act as tutors for Year 2 students (n = 51). Similarly, the ‘tutees’ were invited to take part on a voluntary basis. Students were invited to attend focus groups, which were held at the end of the program. Framework analysis was used to code and categorise data into themes. RESULTS: In total, 108/207 (52 %) students participated in the program. A total of 42/106 (40 %) of Year 3 and 4 students took part as tutors; and of 66/101 (65 %) of Year 1 and 2 students took part as tutees. Five focus groups were held, with 50/108 (46 %) of students voluntarily participating. Senior students (tutors) valued the opportunity to practice and improve their medical knowledge and teaching skills. Junior students (tutees) valued the opportunity for additional practice and patient interaction, within a relaxed, small group learning environment. CONCLUSION: Students perceived the peer tutoring program as affording opportunities not otherwise available within the curriculum. The peer teaching program provided a framework within the medical curriculum for senior students to practice and improve their medical knowledge and teaching skills. Concurrently, junior students were provided with a valuable learning experience that they reported as being qualitatively different to traditional teaching by faculty

Peer tutoring in a medical school: perceptions of tutors and tutees

Background: Peer tutoring has been described as "people from similar social groupings who are not professional teachers helping each other to learn and learning themselves by teaching". Peer tutoring is well accepted as a source of support in many medical curricula, where participation and learning involve a process of socialisation. Peer tutoring can ease the transition of the junior students from the university class environment to the hospital workplace. In this paper, we apply the Experienced Based Learning (ExBL) model to explore medical students' perceptions of their experience of taking part in a newly established peer tutoring program at a hospital based clinical school. Methods: In 2014, all students at Sydney Medical School - Central, located at Royal Prince Alfred Hospital were invited to voluntarily participate in the peer tutoring program. Year 3 students (n = 46) were invited to act as tutors for Year 1 students (n = 50), and Year 4 students (n = 60) were invited to act as tutors for Year 2 students (n = 51). Similarly, the 'tutees' were invited to take part on a voluntary basis. Students were invited to attend focus groups, which were held at the end of the program. Framework analysis was used to code and categorise data into themes. Results: In total, 108/207 (52 %) students participated in the program. A total of 42/106 (40 %) of Year 3 and 4 students took part as tutors; and of 66/101 (65 %) of Year 1 and 2 students took part as tutees. Five focus groups were held, with 50/108 (46 %) of students voluntarily participating. Senior students (tutors) valued the opportunity to practice and improve their medical knowledge and teaching skills. Junior students (tutees) valued the opportunity for additional practice and patient interaction, within a relaxed, small group learning environment. Conclusion: Students perceived the peer tutoring program as affording opportunities not otherwise available within the curriculum. The peer teaching program provided a framework within the medical curriculum for senior students to practice and improve their medical knowledge and teaching skills. Concurrently, junior students were provided with a valuable learning experience that they reported as being qualitatively different to traditional teaching by faculty

Poststreptoccocal uveitis

info:eu-repo/semantics/nonPublishe

Effects of supplementation with L-glutamine and L-alanine in the body composition of rats submitted to resistance exercise

Abstract We investigated the effects of glutamine and alanine supplementation on body composition of rats submitted to resistance exercise. Wistar rats were submitted to eight-week of resistance exercise, which consisted of climbing a ladder with progressive loads (25–100% of body weight). In the last 21 days of training, animals were supplemented with L-glutamine and L-alanine, as a dipeptide or in their free form (DIP, GLN + ALA and ALA groups), or water (SED and CTRL groups). RE attenuated body weight gain and lipid contents of CTRL group (p < 0.05 vs. SED) and DIP supplementation promoted an increase in tibialis muscle weight, as well as in protein content (p < 0.05 vs. CTRL). Taken together, our data indicated that resistance exercise improves body composition and dipeptide potentiated the muscle hypertrophic effect