A quantitative analysis of complexity of human pathogen-specific CD4 T cell responses in healthy M. tuberculosis infected South Africans

Author Summary: Human pathogen-specific immune responses are tremendously complex and the techniques to study them ever expanding. There is an urgent need for a quantitative analysis and better understanding of pathogen-specific immune responses. Mycobacterium tuberculosis (Mtb) is one of the leading causes of mortality due to an infectious agent worldwide. Here, we were able to quantify the Mtb-specific response in healthy individuals with Mtb infection from South Africa. The response is highly diverse and 66 epitopes are required to capture 80% of the total reactivity. Our study also show that the majority of the identified epitopes are restricted by multiple HLA alleles. Thus, technical advances are required to capture and characterize the complete pathogen-specific response. This study demonstrates further that the approach combining identified epitopes into "megapools" allows capturing a large fraction of the total reactivity. This suggests that this technique is generally applicable to the characterization of immunity to other complex pathogens. Together, our data provide for the first time a quantitative analysis of the complex pathogen-specific T cell response and provide a new understanding of human infections in a natural infection setting

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Power of cognition

ating disorders (EDs) are characterized by marked cognitive distortions and maladaptive schemas. Cognitive models of EDs highlight the direct impact of cognitive dysfunctions on eating-related disturbances, insofar as specific cognitive contents such as thoughts about diet rules and food or loss of control may trigger disturbed eating behavior. Moreover, early maladaptive schemas that reflect perfectionist standards and relate to achievement and performance seem to be associated with disturbed eating, e.g., via their impact on situation-specific appraisals. However, so far, no study has investigated these assumptions. Hence, the present study sought to demonstrate whether and how cognitive content exerts an impact on eating behavior in daily life, and whether maladaptive core schemas impact the occurrence of binge eating via dysfunctional ED cognitions in eating-related contexts. $\it {N}$ = 29 females with bulimia nervosa (BN), $\it {n}$ = 31 females with binge eating disorder (BED) and $\it {n}$ = 30 female controls without EDs (NC) participated in the study. All participants received a handheld computer for a 48-h period to capture antecedents of disturbed eating behavior in daily life. Event-sampling (meals, binge eating, purging, stressful situations) and signal-sampling (five times a day) methods were applied. EMA included a short questionnaire to assess dysfunctional cognitions and level of craving and to capture information about situational contexts. Early maladaptive schemas were assessed using a short version of the Young Schema Questionnaire at baseline. The main results showed specific patterns of dysfunctional eating-related cognitions for BED and BN. Binge eating was predicted by thoughts about loss of control (positively) and dietary restraint (negatively). For meal situations, no significant differences between the two ED groups emerged. All three domains exerted indirect effects on craving via thoughts about "$\textit {eating/loss of control}$", whereas neither a direct nor an indirect effect emerged regarding thoughts about "$\textit {dietary restraint}$". These results fit well with previous studies and support cognitive models of EDs; schema therapeutic approaches may be a valuable contribution to enhance treatment of EDs. Further studies should explore whether the findings from emerging adulthood can be generalized to younger age groups

Enhanced nitric oxide (NO) and decreased ADMA synthesis in pediatric ADHD and selective potentiation of NO synthesis by methylphenidate

Attention deficit hyperactivity disorder (ADHD) is a common pediatric psychiatric disorder, frequently treated with methylphenidate (MPH). Recently, MPH’s cardiovascular safety has been questioned by observational studies describing an increased cardiovascular risk in adults and blood pressure alterations in children. We considered members of the L-arginine (Arg)/nitric oxide (NO) pathway as possible early cardiovascular risk factors in pediatric ADHD children. They include the NO metabolites, nitrite and nitrate, the NO precursor Arg, and asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor and a cardiovascular risk factor in adults. We conducted a prospective clinical trial with 42 ADHD children (aged 6–16 years) with ($\it n$ = 19) and without ($\it n$ = 23) MPH treatment. Age-matched children without ADHD ($\it n$ = 43) served as controls. All plasma and urine metabolites were determined by gas chromatography-mass spectrometry. We observed higher plasma nitrite and lower plasma ADMA concentrations in the ADHD children. MPH-treated ADHD children had higher plasma nitrite concentrations than MPH-untreated ADHD children. As NOS activity is basally inhibited by ADMA, MPH treatment seems to have decreased the inhibitory potency of ADMA. Percentiles of systolic blood pressure were higher in MPH-treated ADHD children. The underlying mechanisms and their implications in the MPH therapy of pediatric ADHD with MPH remain to be elucidated in larger cohorts