The aim of this study was to investigate the immunological responses and the association between variation in exercise load and self-reported occurrence of upper respiratory illness (URI) symptoms in ...young basketball athletes.
The sample was composed of twelve young male athletes aged 12.7 ± 0.6 years, with a height of 170 ± 10 cm, body mass of 57.6 ± 12.6 kg, and fat-free mass of 18.7 ± 5.9%. Daily training and occurrences of URI symptoms were recorded. Blood samples were collected at baseline (M1) and after 8 weeks (M2) of the preparatory period of periodization training to measure total and differential leukocyte counts, serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α).
There was a significant decrease in monocytes at M2 compared to M1 (P = 0.004). There were no significant alterations in total leukocytes (P = 0.07), neutrophils (P = 0.07), or lymphocytes (P = 0.09). No significant changes in plasma concentrations of TNF-α (P = 0.30) or IL-6 (P = 0.90) were found. The weekly load from week 6 was higher when compared with weeks 1, 2, 4, and 8 (P < 0.05), and week 8 was the lowest when compared with week 5 (P < 0.05). Self-reported URI incidences were highest at weeks 1 and 2.
Variations in weekly training load during the preparatory period were not correlated with changes in self-reported occurrence of URI incidences, suggesting that young athletes may have an attenuated response to exercise-induced perturbations to the immune system.
Although most Latin American and the Caribbean (LAC) countries made important progress in maternal and child health indicators from the 1990s up to 2010, little is known about such progress in the ...last decade. This study aims at documenting progress for each country as a whole, and to assess how within-country socioeconomic inequalities are evolving over time.
We identified LAC countries for which a national survey was available between 2011-2015 and a second comparable survey in 2018-2020. These included Argentina, Costa Rica, Cuba, the Dominican Republic, Guyana, Honduras, Peru, and Suriname. The 16 surveys included in the analysis collected nationally representative data on 221,989 women and 152,983 children using multistage sampling. Twelve health-related outcomes were studied, seven of which related to intervention coverage: the composite coverage index, demand for family planning satisfied with modern methods, antenatal care (four or more visits and eight or more visits), skilled attendant at birth, postnatal care for the mother and full immunization coverage. Five additional impact indicators were also investigated: stunting prevalence among under-five children, tobacco use by women, adolescent fertility rate, and under-five and neonatal mortality rates. For each of these indicators, average annual relative change rates were calculated between the baseline and endline national level estimates, and changes in socioeconomic inequalities over time were assessed using the slope index of inequality.
Progress over time and the magnitude of inequalities varied according to country and indicator. For countries and indicators where baseline levels were high, as Argentina, Costa Rica and Cuba, progress was slow and inequalities small for most indicators. Countries that still have room for improvements, such as Guyana, Honduras, Peru and Suriname, showed faster progress for some but not all indicators, although also had wider inequalities. Among the countries studied, Peru was the top performer in terms of increasing coverage and reducing inequalities over time, followed by Honduras. Declines in family planning and immunization coverage were observed in some countries, and the widest inequalities were present for adolescent fertility and antenatal care coverage with eight or more visits.
Although LAC countries are well placed in terms of current levels of health indicators compared to most low- and middle-income countries, important inequalities remain, and reversals are being observed in some areas. More targeted efforts and actions are needed in order to leave no one behind. Monitoring progress with an equity lens is essential, but this will require further investment in conducting surveys routinely.
Microglia have fundamental roles in health and disease; however, effects of age, sex, and genetic factors on human microglia have not been fully explored. We applied bulk and single‐cell approaches ...to comprehensively characterize human microglia transcriptomes and their associations with age, sex, and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single‐cell microglia transcriptomes. We discovered microglial co‐expression network modules associated with age, sex, and APOE‐ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single‐cell transcriptomes revealed significant overlap between age‐associated module genes and both pro‐inflammatory and disease‐associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2, and BIN1. Meta‐analyses with published bulk and single‐cell microglial datasets further supported our findings. Thus, these data represent a well‐characterized human microglial transcriptome resource and highlight age, sex, and APOE‐related microglial immunometabolism perturbations with potential relevance in neurodegeneration.
Using bulk and single‐cell approaches, we identified microglial subclusters enriched for different biological functions. Activated microglia were more abundant with aging and lipid localization genes were upregulated. In APOE‐ε4 carriers, homeostatic microglia were reduced along with downregulation of carbohydrate metabolism genes, whereas cholesterol absorption genes were unregulated in macrophages and activated microglia.
We examined structural factors—social, political, economic, and environmental—that increase vulnerability to HIV among indigenous people in the Peruvian Amazon. Indigenous adults belonging to 12 ...different ethnic groups were purposively recruited in four Amazonian river ports and 16 indigenous villages. Qualitative data revealed a complex set of structural factors that give rise to environments of risk where health is constantly challenged. Ferryboats that cross Amazonian rivers are settings where unprotected sex—including transactional sex between passengers and boat crew and commercial sex work—often take place. Population mobility and mixing also occurs in settings like the river docks, mining sites, and other resource extraction camps, where heavy drinking and unprotected sex work are common. Multilevel, combination prevention strategies that integrate empirically based interventions with indigenous knowledge are urgently needed, not only to reduce vulnerability to HIV transmission, but also to eliminate the structural determinants of indigenous people’s health.
Abstract Background Withdrawing life-sustaining therapy because of perceived poor neurological prognosis (WLST-N) is a common cause of hospital death after out-of-hospital cardiac arrest (OHCA). ...Although current guidelines recommend against WLST-N before 72 h (WLST-N < 72), this practice is common and may increase mortality. We sought to quantify these effects. Methods In a secondary analysis of a multicenter OHCA trial, we evaluated survival to hospital discharge and survival with favorable functional status (modified Rankin Score ≤3) in adults alive >1 h after hospital admission. Propensity score modeling the probability of exposure to WLST-N < 72 based on pre-exposure covariates was used to match unexposed subjects with those exposed to WLST-N < 72. We determined the probability of survival and functionally favorable survival in the unexposed matched cohort, fit adjusted logistic regression models to predict outcomes in this group, and then used these models to predict outcomes in the exposed cohort. Combining these findings with current epidemiologic statistics we estimated mortality nationally that is associated with WLST-N < 72. Results Of 16,875 OHCA subjects, 4265 (25%) met inclusion criteria. WLST-N < 72 occurred in one-third of subjects who died in-hospital. Adjusted analyses predicted that exposed subjects would have 26% survival and 16% functionally favorable survival if WLST-N < 72 did not occur. Extrapolated nationally, WLST-N < 72 may be associated with mortality in approximately 2300 Americans each year of whom nearly 1500 (64%) might have had functional recovery. Conclusions After OHCA, death following WLST-N < 72 may be common and is potentially avoidable. Reducing WLST-N < 72 has national public health implications and may afford an opportunity to decrease mortality after OHCA.
Cholecystokinin (CCK) is a brain-gut neuropeptide and hormone previously shown to inhibit alcohol intake in water- or food-deprived rats. The effects of CCK and the phase of lighting cycle on alcohol ...intake in rats were investigated in a comparison of limited access and water-restriction procedures. The limited access procedure (LAP) is a recently developed technique for inducing free-choice alcohol consumption in nondeprived animals. Two groups of 12 male rats each were maintained in either normal or reversed 12:12 L:D lighting cycles and simultaneously given 40 minutes' access to 6% w/v ethanol and water in nonhome cages. After adaptation to this procedure, CCK octapeptide (0.5-16 micrograms/kg) was injected IP prior to access to fluids. During LAP, CCK reduced alcohol intake and increased water intake more potently in the dark phase. These effects of CCK were more reliable when the design was replicated, which suggests the importance of acquired expectancies for the development of CCK's actions. CCK more effectively reduced alcohol intake in LAP, than in a 23.3-h water-deprivation procedure for inducing alcohol intake in a 2-bottle choice test with water. However, CCK was less so effective in LAP, than in the water-deprivation procedure when alcohol was presented alone in a 1-bottle test. The alcohol satiation effect of CCK is independent of prior deprivation and not an artifact of thirst reduction, debilitation, or conditioned aversion, because CCK strongly increased water intake in the limited access procedure, and ethanol preference remained robust after experience with CCK. CCK may operate endogenously as a specific factor in satiation with ethanol.
Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be ...capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.
The purpose of this study was to determine the reliability of eccentric (ECC) and concentric (CON) kinematic and kinetic variables thought to be critical to jump performance during bilateral vertical ...countermovement jump (VCMJ) and horizontal countermovement jump (HCMJ) across children of different maturity status. Forty-two athletic male and female participants between 9 and 16 years of age were divided into 3 maturity groups according to peak height velocity (PHV) offset (Post-PHV, At-PHV, and Pre-PHV) and percent of predicted adult stature. All the participants performed 3 VCMJ and HCMJ trials and the kinematics, and kinetics of these jumps were measured via a force plate over 3 testing sessions. In both jumps, vertical CON mean and peak power and jump height or distance were the most reliable measures across all groups (change in the mean CM = -5.4 to 6.2%; coefficient of variation CV = 2.1-9.4%; Intraclass correlation coefficient ICC = 0.82-0.98), whereas vertical ECC mean power was the only ECC variable with acceptable reliability for both jumps (CM = -0.7 to 10.1%; CV = 5.2-15.6%; ICC = 0.74-0.97). A less mature state was "likely" to "very likely" to reduce the reliability of the HCMJ ECC kinetics and kinematics. These findings suggested that movement variability is associated with the ECC phase of CMJs, especially in Pre-PHV during the HCMJ. Vertical CON mean and peak power and ECC mean power were deemed reliable and appropriate to be used in children as indicators of jump and stretch-shortening cycle performance.
Purpose
Multi-modality therapy has resulted in improved survival for childhood malignancies. The
Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and ...Young Adult Cancers
provide practitioners with exposure- and risk-based recommendations for the surveillance and management of asymptomatic survivors who are at least 2 years from completion of therapy. This review outlines the pathophysiology and risks for oral and dental late effects in pediatric cancer survivors and the rationale for oral and dental screening recommended by the Children’s Oncology Group.
Methods
An English literature search for oral and dental complications of childhood cancer treatment was undertaken via MEDLINE and encompassed January 1975 to January 2013. Proposed guideline content based on the literature review was approved by a multi-disciplinary panel of survivorship experts and scored according to a modified version of the National Comprehensive Cancer Network “Categories of Consensus” system.
Results
The Children’s Oncology Group oral-dental panel selected 85 relevant citations. Childhood cancer therapy may impact tooth development, salivary function, craniofacial development, and temporomandibular joint function placing some childhood cancer survivors at an increased risk for poor oral and dental health. Additionally, head and neck radiation and hematopoietic stem cell transplantation increase the risk of subsequent malignant neoplasms in the oral cavity. Survivors require routine dental care to evaluate for potential side effects and initiate early treatment.
Conclusions
Certain childhood cancer survivors are at an increased risk for poor oral and dental health. Early identification of oral and dental morbidity and early interventions can optimize health and quality of life.
In utero exposure to maternal immune activation (MIA) is an environmental risk factor for neurodevelopmental and neuropsychiatric disorders. Animal models provide an opportunity to identify ...mechanisms driving neuropathology associated with MIA. We performed time-course transcriptional profiling of mouse cortical development following induced MIA via poly(I:C) injection at E12.5. MIA-driven transcriptional changes were validated via protein analysis, and parallel perturbations to cortical neuroanatomy were identified via imaging. MIA-induced acute upregulation of genes associated with hypoxia, immune signaling, and angiogenesis, by 6 hr following exposure. This acute response was followed by changes in proliferation, neuronal and glial specification, and cortical lamination that emerged at E14.5 and peaked at E17.5. Decreased numbers of proliferative cells in germinal zones and alterations in neuronal and glial populations were identified in the MIA-exposed cortex. Overall, paired transcriptomic and neuroanatomical characterization revealed a sequence of perturbations to corticogenesis driven by mid-gestational MIA.