Developmental Profiles of Mucosal Immunity in Pre-school Children

This study investigated the effect of attending pre-school on mucosal immunity. Children 3.5 to 5 years of age who attended pre-school were observed for a 10 month period. Demographic information was collected on previous childcare experiences, the home environment and clinical information relating to the child and the family. A daily illness log was kept for each child. A multivariate longitudinal analysis of the relation between immunoglobulins in saliva and age, gender, childcare experience, pre-school exposure, number of siblings, environmental tobacco smoke (ETS), atopy and hospitalisation was conducted. There was a positive association of higher IgA levels with the winter season and with children being older than 4 years (P < .001), having attended childcare prior to commencing pre-school (P < .05), and having been exposed to ETS at home (P < .05). Lower IgA levels were associated with being atopic (P < .05). Higher IgG levels were associated with exposure to ETS (P < .001), while lower levels were associated to having atopy. Higher IgM levels were associated with previous childcare experience (P < .01) whilst having been hospitalised was associated with having low salivary IgM levels (P < .01). Lagged analyses demonstrated that immunological parameters were affected by the number of respiratory infections in the preceding 2 months

Developmental Profiles of Mucosal Immunity in Pre-school Children

This study investigated the effect of attending pre-school on mucosal immunity. Children 3.5 to 5 years of age who attended pre-school were observed for a 10 month period. Demographic information was collected on previous childcare experiences, the home environment and clinical information relating to the child and the family. A daily illness log was kept for each child. A multivariate longitudinal analysis of the relation between immunoglobulins in saliva and age, gender, childcare experience, pre-school exposure, number of siblings, environmental tobacco smoke (ETS), atopy and hospitalisation was conducted. There was a positive association of higher IgA levels with the winter season and with children being older than 4 years (P < .001), having attended childcare prior to commencing pre-school (P < .05), and having been exposed to ETS at home (P < .05). Lower IgA levels were associated with being atopic (P < .05). Higher IgG levels were associated with exposure to ETS (P < .001), while lower levels were associated to having atopy. Higher IgM levels were associated with previous childcare experience (P < .01) whilst having been hospitalised was associated with having low salivary IgM levels (P < .01). Lagged analyses demonstrated that immunological parameters were affected by the number of respiratory infections in the preceding 2 months

What is the impact of intellectual property rules on access to medicines? A systematic review

BACKGROUND: It is widely accepted that intellectual property legal requirements such as patents and data exclusivity can affect access to medicines, but to date there has not been a comprehensive review of the empirical evidence on this topic. The World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires Member States to implement minimum standards of intellectual property protection including patents for pharmaceutical products, but also contains ‘flexibilities’ designed to address barriers to access to medicines. National intellectual property laws can also include TRIPS-plus rules that go beyond what is required by TRIPS. We aimed to systematically review literature that measures the impact of intellectual property rules on access to medicines, whether implemented as a result of TRIPS, TRIPS-plus provisions in other trade agreements, or unilateral policy decisions. METHODS: We searched Proquest, SCOPUS, Web of Science, PubMed, JSTOR, Westlaw and Lexis Nexis. Peer reviewed articles, government reports and other grey literature were included. Articles were eligible for inclusion if they were quantitative, in English, included a measure of cost, price, availability of or access to medicines, were about intellectual property or data exclusivity rules and published between January 1995 and October 2020. Ninety-one studies met our inclusion criteria. We systematically reviewed the studies’ findings and evaluated their quality using a modified quality assessment template. RESULTS AND CONCLUSION: Five broad overarching themes and 11 subthemes were identified based on the articles’ foci. They were: trade agreements (divided into EU FTAs and those that include the USA); use of TRIPS flexibilities (divided into compulsory licencing and parallel importation); patent expiry/generic entry/generic pathway (divided into comparative studies and single country studies); patent policies (also divided into comparative studies and single country studies) and TRIPS-plus rules (divided into data exclusivity, patent term extensions and secondary patenting). Most studies focused not on specific trade agreements, but on TRIPS-plus provisions, which can also be found within some trade agreements. The main finding of this review is that the stronger pharmaceutical monopolies created by TRIPs-plus intellectual property rules are generally associated with increased drug prices, delayed availability and increased costs to consumers and governments. There is evidence that TRIPS flexibilities can facilitate access to medicines although their use is limited to date. There were few studies that included resource poor settings, signalling a need for greater research in such settings where the impact on access to medicines is likely to be more damaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12992-022-00826-4

Risk factors associated with acute respiratory illnesses in athletes : a systematic review by a subgroup of the IOC consensus on 'acute respiratory illness in the athlete'

OBJECTIVE : To review risk factors associated with acute respiratory illness (ARill) in athletes, including non-infectious ARill and suspected or confirmed acute respiratory infections (ARinf). DESIGN : Systematic review. DATA SOURCES : Electronic databases: PubMed-Medline, EbscoHost and Web of Science. ELIGIBILITY CRITERIA : Original research articles published between January 1990 and July 2020 in English were searched for prospective and retrospective full text studies that reported quantitative data on risk factors associated with ARill/ARinf in athletes, at any level of performance (elite/non-elite), aged 15–65 years. RESULTS : 48 studies (n=19 390 athletes) were included in the study. Risk factors associated with ARill/ARinf were: increased training monotony, endurance training programmes, lack of tapering, training during winter or at altitude, international travel and vitamin D deficits. Low tear-(SIgA) and salivary-(IgA) were immune biomarkers associated with ARill/ARinf. CONCLUSIONS : Modifiable training and environmental risk factors could be considered by sports coaches and athletes to reduce the risk of ARill/ARinf. Clinicians working with athletes can consider assessing and treating specific nutritional deficiencies such as vitamin D. More research regarding the role and clinical application of measuring immune biomarkers in athletes at high risk of ARill/ARinf is warranted.http://bjsm.bmj.comhj2023Sports Medicin

Incidence of acute respiratory illnesses in athletes: a systematic review and meta-analysis by a subgroup of the IOC consensus on 'acute respiratory illness in the athlete'

OBJECTIVE : To determine the incidence of acute respiratory illness (ARill) in athletes and by method of diagnosis, anatomical classification, ages, levels of performance and seasons. DESIGN : Systematic review and meta-analysis. DATA SOURCES : Electronic databases: PubMed-Medline, EbscoHost and Web of Science. ELIGIBILITY CRITERIA : Original research articles published between January 1990 and July 2020 in English reporting the incidence of ARill in athletes, at any level of performance (elite/non-elite), aged 15–65 years. RESULTS : Across all 124 studies (n=1 28 360 athletes), the incidence of ARill, estimated by dividing the number of cases by the total number of athlete days, was 4.7 (95% CI 3.9 to 5.7) per 1000 athlete days. In studies reporting acute respiratory infections (ARinf; suspected and confirmed) the incidence was 4.9 (95% CI 4.0 to 6.0), which was similar in studies reporting undiagnosed ARill (3.7; 95% CI 2.1 to 6.7). Incidences of 5.9 (95% CI 4.8 to 7.2) and 2.8 (95% CI 1.8 to 4.5) were found for studies reporting upper ARinf and general ARinf (upper or lower), respectively. The incidence of ARinf was similar across the different methods to diagnose ARinf. A higher incidence of ARinf was found in non-elite (8.7; 95% CI 6.1 to 12.5) vs elite athletes (4.2; 95% CI 3.3 to 5.3). SUMMARY/CONCLUSIONS : These findings suggest: (1) the incidence of ARill equates to approximately 4.7 per athlete per year; (2) the incidence of upper ARinf was significantly higher than general (upper/lower) ARinf; (3) elite athletes have a lower incidence of ARinf than non-elite athletes; (4) if pathogen identification is not available, physicians can confidently use validated questionnaires and checklists to screen athletes for suspected ARinf. For future studies, we recommend that a clear diagnosis of ARill is reported. PROSPERO registration number CRD42020160472.https://bjsm.bmj.comhj2023Sports Medicin

Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia

Mucosal immune responses and risk of respiratory illness in elite athletes

Revue de synthèse : la fonction des muqueuses dans le système immunitaire. Physiologie de la glande salivaire et rôle des immunoglobulines. Effet de l'intensité, du volume, de la durée de l'effort et de l'entraînement sur les paramètres immunitaires muqueux. Analyse des concentrations d'IgA et d'IgM dans la salive, en rapport avec un risque accru d'infection virale des voies aériennes supérieures chez l'athlète de haut niveau

Respiratory inflammation and infections in high-performance athletes

Upper respiratory illness is the most common reason for non-injury-related presentation to a sports medicine clinic, accounting for 35-65% of illness presentations. Recurrent or persistent respiratory illness can have a negative impact on health and performance of athletes undertaking high levels of strenuous exercise. The cause of upper respiratory symptoms (URS) in athletes can be uncertain but the majority of cases are related to common respiratory viruses, viral reactivation, allergic responses to aeroallergens and exercise-related trauma to the integrity of respiratory epithelial membranes. Bacterial respiratory infections are uncommon in athletes. Undiagnosed or inappropriately treated asthma and/or allergy are common findings in clinical assessments of elite athletes experiencing recurrent URS. High-performance athletes with recurrent episodes of URS should undergo a thorough clinical assessment to exclude underlying treatable conditions of respiratory inflammation. Identifying athletes at risk of recurrent URS is important in order to prescribe preventative clinical, training and lifestyle strategies. Monitoring secretion rates and falling concentrations of salivary IgA can identify athletes at risk of URS. Therapeutic interventions are limited by the uncertainty of the underlying cause of inflammation. Topical anti-inflammatory sprays can be beneficial for some athletes. Dietary supplementation with bovine colostrum, probiotics and selected antioxidants can reduce the incidence or severity of URS in some athletes. Preliminary studies on athletes prone to URS indicate a genetic predisposition to a pro-inflammatory response and a dysregulated anti-inflammatory cytokine response to intense exercise as a possible mechanism of respiratory inflammation. This review focuses on respiratory infections and inflammation in elite/professional athletes