Sustained submaximal isometric wrist flexion and wrist extension contractions uniquely impair maximal voluntary contraction force in the antagonist wrist action.

When fatigued, the wrist extensors, which are the primary wrist stabilizers, impair distal upper limb motor performance in a surprisingly similar way as when fatiguing the wrist flexors. It is possible that the wrist extensors are so active as antagonists that they develop an equal degree of fatigue during wrist flexion contractions, making it difficult to truly isolate their impact on performance. Thus, the purpose of this study was to examine how wrist flexion/extension forces are impaired following either agonist or antagonist sustained submaximal wrist contractions. 13 male participants attended four laboratory sessions. In these sessions, fatigue was induced via a sustained submaximal isometric contraction of either wrist flexion or extension. These contractions were held for up to 10 min at 20% of the participant's baseline maximal voluntary contraction (MVC) force. Throughout the sustained contraction, intermittent agonist (matching the sustained contraction) or antagonist (opposing the sustained contraction) MVCs were performed. Unsurprisingly, agonist MVC forces decreased significantly more than antagonist (Agonist: 58.5%, Antagonist: 86.5% of MVC, P < 0.001). However, while there were no differences in antagonist wrist extension and flexion MVC decreases (Wrist Flexion: 87.5%, Wrist Extension: 85.5%, P = 0.41), wrist extension MVCs did decrease significantly more than wrist flexion MVCs when forces were expressed relative to the agonist (P = 0.036). These findings partially support the hypothesis that the wrist extensors may be more susceptible to developing fatigue when functioning as antagonists than the wrist flexors. This work will help equip future research into the motor control of the upper limb and the prevention of forearm-related musculoskeletal disorders.

Colonization, spread and persistence of Salmonella (Typhimurium, Infantis and Reading) in internal organs of broilers.

Transfer of Salmonella to internal organs of broilers over a 35 d grow-out period was evaluated. A total of 360 one-day old chicks were placed in 18 floor pens of 3 groups with 6 replicate pens each. On d 0, broilers were orally challenged with a cocktail of Salmonella (equal population of marked serovars; nalidixic acid-resistant S. Typhimurium, rifampicin-resistant S. Infantis, and kanamycin-resistant S. Reading) to have 3 groups: L (low; ∼2 log CFU/bird); M (medium; ∼5 log CFU/bird); and H (High; ∼8 log CFU/bird). On d 2, 7 and 35, 4 birds/pen were euthanized and ceca, liver, and spleen samples were collected aseptically. Gizzard samples (4/pen) were collected on d 35. The concentration of Salmonella in liver and spleen were transformed to binary outcomes (positive and negative) and fitted in glm function of R using cecal Salmonella concentrations (log CFU/g) and inoculation doses (L, M, and H) as inputs. On d 2, H group showed greater (P ≤ 0.05) cecal colonization of all 3 serovars compared to L and M groups. However, M group showed greater (P ≤ 0.05) colonization of all 3 serovars in the liver and spleen compared to L group. Salmonella colonization increased linearly in the ceca and quadratically in the liver and spleen with increasing challenge dose (P ≤ 0.05). On d 35, L group had greater (P ≤ 0.05) S. Infantis colonization in the ceca and liver compared to M and H groups (P ≤ 0.05). Moreover, within each group on d 35, the concentration of S. Reading was greater than those of S. Typhimurium and S. Infantis for all 3 doses in the ceca and high dose in the liver and gizzard (P ≤ 0.05). Salmonella colonization diminished in the ceca, liver, and spleen during grow-out from d 0 to d 35 (P ≤ 0.05). On d 35, birds challenged with different doses of Salmonella cocktail showed a similar total Salmonella spp. population in the ceca (ca. 3.14 log CFU/g), liver (ca. 0.54 log CFU/g), spleen (ca. 0.31 log CFU/g), and gizzard (ca. 0.42 log CFU/g). Estimates from the fitted logistic model showed that one log CFU/g increase in cecal Salmonella concentration will result in an increase in relative risk of liver and spleen being Salmonella-positive by 4.02 and 3.40 times (P ≤ 0.01), respectively. Broilers from H or M group had a lower risk (28 and 23%) of being Salmonella-positive in the liver compared to the L group when the cecal Salmonella concentration is the same (P ≤ 0.05). Oral challenge of broilers with Salmonella spp. with various doses resulted in linear or quadratic increases in Salmonella colonization in the internal organs during early age and these populations decreased during grow-out (d 35). This research can provide guidance on practices to effectively mitigate the risk of Salmonella from chicken parts and enhance public health.

Regional centromere configuration in the fungal pathogens of the Pneumocystis genus.

Centromeres are constricted chromosomal regions that are essential for cell division. In eukaryotes, centromeres display a remarkable architectural and genetic diversity. The basis of centromere-accelerated evolution remains elusive. Here, we focused on Pneumocystis species, a group of mammalian-specific fungal pathogens that form a sister taxon with that of the Schizosaccharomyces pombe, an important genetic model for centromere biology research. Methods allowing reliable continuous culture of Pneumocystis species do not currently exist, precluding genetic manipulation. CENP-A, a variant of histone H3, is the epigenetic marker that defines centromeres in most eukaryotes. Using heterologous complementation, we show that the Pneumocystis CENP-A ortholog is functionally equivalent to CENP-ACnp1 of S. pombe. Using organisms from a short-term in vitro culture or infected animal models and chromatin immunoprecipitation (ChIP)-Seq, we identified CENP-A bound regions in two Pneumocystis species that diverged ~35 million years ago. Each species has a unique short regional centromere (<10 kb) flanked by heterochromatin in 16-17 monocentric chromosomes. They span active genes and lack conserved DNA sequence motifs and repeats. These features suggest an epigenetic specification of centromere function. Analysis of centromeric DNA across multiple Pneumocystis species suggests a vertical transmission at least 100 million years ago. The common ancestry of Pneumocystis and S. pombe centromeres is untraceable at the DNA level, but the overall architectural similarity could be the result of functional constraint for successful chromosomal segregation.IMPORTANCEPneumocystis species offer a suitable genetic system to study centromere evolution in pathogens because of their phylogenetic proximity with the non-pathogenic yeast S. pombe, a popular model for cell biology. We used this system to explore how centromeres have evolved after the divergence of the two clades ~ 460 million years ago. To address this question, we established a protocol combining short-term culture and ChIP-Seq to characterize centromeres in multiple Pneumocystis species. We show that Pneumocystis have short epigenetic centromeres that function differently from those in S. pombe.

Hospitalisation and mortality among privately insured individuals with COVID-19 in the United States: The role of intellectual disabilities and Neurogenetic disorders.

BACKGROUND: Individuals with intellectual disabilities (IDs) and neurogenetic conditions (IDNDs) are at greater risk for comorbidities that may increase adverse outcomes for this population when they have coronavirus disease 2019 (COVID-19). The study aims are to examine the population-level odds of hospitalisation and mortality of privately insured individuals with COVID-19 with and without IDNDs IDs, controlling for sociodemographics and comorbid health conditions. METHODS: This is a retrospective, cross-sectional study of 1174 individuals with IDs and neurogenetic conditions within a population of 752 237 de-identified, privately insured, US patients diagnosed with COVID-19 between February 2020 and September 2020. Odds of hospitalisation and mortality among COVID-19 patients with IDNDs adjusted for demographic characteristics, Health Resources and Services Administration region, states with Affordable Care Act and number of comorbid health conditions were analysed. RESULTS: Patients with IDNDs overall had higher rates of COVID-19 hospitalisation than those without IDNDs (35.01% vs. 12.65%, P < .0001) and had higher rates of COVID-19 mortality than those without IDNDs (4.94% vs. .88%, P < .0001). Adjusting for sociodemographic factors only, the odds of being hospitalised for COVID-19 associated with IDNDs was 4.05 [95% confidence interval (CI) 3.56-4.61]. Adjusting for sociodemographic factors and comorbidity count, the odds of hospitalisation for COVID-19 associated with IDNDs was 1.42 (95% CI 1.25-1.61). The odds of mortality from COVID-19 for individuals with IDNDs adjusted for sociodemographic factors only was 4.65 (95% CI 3.47-6.24). The odds of mortality from COVID-19 for patients with IDNDs adjusted for sociodemographic factors and comorbidity count was 2.70 (95% CI 2.03-3.60). A major finding of the study was that even when considering the different demographic structure and generally higher disease burden of patients with IDNDs, having a IDND was an independent risk factor for increased hospitalisation and mortality compared with patients without IDNDs. CONCLUSIONS: Individuals with IDNDs had significantly higher odds of hospitalisation and mortality after adjusting for sociodemographics. Results remained significant with a slight attenuation after adjusting for sociodemographics and comorbidities. Adjustments for comorbidity count demonstrated a dose-response increase in odds of both hospitalisation and mortality, illustrating the cumulative effect of health concerns on COVID-19 outcomes. Together, findings highlight that individuals with IDNDs experience vulnerability for negative COVID-19 health outcomes with implications for access to comprehensive healthcare.

Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE. CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Mental health impacts of climate change and extreme weather events on mothers.

Background: The perinatal period is a time of increased vulnerability for perinatal mood and anxiety disorders (PMADs). Emotional trauma is a risk factor for PMAD development and is common among survivors of extreme weather events (EWEs), which are becoming more frequent and intense as the climate crisis progresses. EWE-related stress and anxiety have not been extensively studied in the perinatal population. However, the limited available data suggest a negative impact of EWE exposure on perinatal mental health, warranting further investigation and investment.Objective: To address this knowledge gap, we interviewed new Australian mothers to understand how EWEs affect the mental health of the perinatal population.Method: Australian mothers (18 years of age or older) with a baby under 12 months of age were recruited to participate in a single virtual focus group session (seven group sessions were run in total) and complete an anonymous survey. Participants were asked questions regarding their concerns about extreme weather and its impact, as well as their general maternal functioning. Maternal functioning, depression, and climate distress were measured via the survey.Results: The study sample comprised 31 Australian mothers (Mage = 31.74, SD = 4.86), predominantly located in Queensland. Findings from the focus groups suggested six key themes; however, of focus to this study are three themes related to maternal mental health: health and well-being, helplessness and avoidant coping, and resilience and adaptation. Predominant subthemes focused on trauma resulting from EWE exposure, economic and heat concerns, social isolation, hopelessness about the future, and feelings of resilience.Conclusions: The evidence linking adverse perinatal mental health outcomes with climate change and EWEs highlights the urgent need for interventions in this context to protect perinatal mental health and well-being. By acknowledging the traumatic impact of these experiences on mothers, this study supports advocacy for policies that specifically address this issue.

The extra consideration of navigating climatic events with children represented a complicating factor in addition to the demands of motherhood.Heat presented as a serious concern for participants, often as part of maintaining the balance between protecting their children's health and well-being and preserving their own mental health.Mothers simultaneously were disengaged from climate-related discussion or action and expressed feelings of helplessness in the face of the magnitude of climate change.

Results of the Brazilian Osteosarcoma treatment group studies III and IV: prognostic factors and impact on survival

To evaluate the impact of chemotherapy and surgery on the outcome of osteosarcoma (OS) of the extremities and to identify prognostic factors in Brazilian patients. A total of 225 patients with metastatic and nonmetastatic OS of the extremities were enrolled and assessed in two consecutive studies designed and implemented by the Brazilian Osteosarcoma Treatment Group. The 5-year survival and event-free survival rates for the 209 assessable patients were 50.1% and 39%, respectively; for the 178 patients with nonmetastatic disease at diagnosis, the rates were 60.5% and 45.5%, respectively. The multivariate analysis showed that the following variables were associated with a shorter survival: metastases at diagnosis (P < .001), necrosis grades 1 and 2 (P = .046), and tumor size (P = .0071). The overall 5- and 10-year survival rates were lower than the rates reported in North American and European trials. A pattern of advanced disease at diagnosis was often present, with a high proportion of patients having metastases (20.8%) and large tumor size (42.9%). However, these features were not necessarily associated with longer duration of prediagnostic symptoms. These findings were considered in the strategic planning of the current Brazilian cooperative study, with the aim of improving survival and quality of life of a large number of patients with OS.

Niveles de lípidos y de presión arterial en población mapuche de la Región de la Araucanía, en Chile / Blood pressure and serum lipid levels in Chilean aboriginal populations (Mapuche) living in the Chilean region of Araucania

Background: Chilean aboriginal populations (Mapuche) predominantly live in the region of Araucanía, in the southern part of the country. Their cardiovascular risk factors have not been systematically assessed. Aim: To study the prevalence of cardiovascular risk factors in the Mapuche population. Subjects and methods: Blood pressure, weight, height, dietary habits, fasting serum total cholesterol, HDL cholesterol and triglycerides were measured in 1.948 adults living in 28 Mapuche communities. Results: Thirteen percent of males and 16 percent of females had high blood pressure. Body mass index was 25.5 kg/m2 in males and 28.1 kg/m2 in females. Forty five percent of women and 24 percent of men were classified as obese. Mean serum total cholesterol was 186.7ñ9.6 mg/dl, HDL cholesterol was 58.7ñ30.7 mg/dl, total cholesterol/HDL cholesterol was 3.4ñ2 and triglycerides were 155.2ñ91.2 mg/dl. Twenty eight percent of males and 9.6 percent of females smoked. Conclusions: Mapuche individuals have higher levels of HDL cholesterol, a better total cholesterol/HDL cholesterol ratio and lower frequency of smoking than non aboriginal Chileans subjects

Magnesio, calcio y fósforo séricos en neonatos de alto riesgo y controles / Serum magnesium, calcium and phosphorus in normal and high risk neonates

Las convulsiones son un problema neonatal frecuente y grave. Las principales determinaciones sugeridas para investigar su origen tiene relaión por ejemplo con la medición de los niveles de glucosa, magnesio, calcio, etc. Se estudiaron a 32 recién nacidos de alto riesgo y en un grupo control, formado por 30 neonatos sanos, los niveles de magnesio, calcio y fósforo por las metódicas de Calmagite-dye y o-Cresolftaleína-Complexona y Molibdato-Vanadato, respectivamente. Los valores en controles fueron 2,55 ñ 0,28 mg/dl para magnesio; 8,21 ñ 1,20 mg/dl para calcio y 5,96 ñ 1,18 mg/dl para fósforo y en el grupo de riesgo fueron: 2,39 ñ 0,41 mg/dl; 8,21 ñ 1,32 mg/dl y 5,87ñ 1,14 mg/dl. El grupo de riesgo evidenció valores más bajos para magnesio con una mayor dispersión, siendo esto significativo para la prueba de F con un p<0,05. También se observaron niveles levemente más altos de calcio en este grupo, con mayor dispersión de valores pero, no siendo significativas estas diferencias. Los valores de fósforo en ambos grupos fueron muy similares. Se concluye que solamente el magnesio podría ser un indicador sensible ante la presencia de convulsiones, aunque deberían estudiarse estos parámetros conjuntamente con los niveles de glicemia