Induction of cellular immune response and anti-Salmonella enterica serovar typhi bactericidal antibodies in healthy volunteers by immunization with a vaccine candidate against typhoid fever

Typhoid fever remains a serious public health problem. We have developed a vaccine from Salmonella enterica serovar typhi (S. typhi) outer-membrane proteins (OMPs) known as porins. A single subcutaneous dose of 10 microg of porins induced a five-fold (P = 0.05) seroconversion index consisting of IgM and IgG at 7 and 15 days after vaccination as well as the production of IgG1 and IgG2 isotypes. The porins-based vaccine induced a two-fold increase (P = 0.05) in bactericidal titres in volunteers, whom also developed a T-cell response characterized by the production of interferon-gamma (INF-gamma). Side effects after vaccination were mild and transient. The data showed that our S. typhi porins-based candidate vaccine is safe and immunogenic in healthy humans.     

Long‐term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle‐aged Ts65Dn mice,a model of Down syndrome

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age‐related cholinergic degeneration, and increased brain expression of β‐amyloid precursor protein (AβPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long‐term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AβPP and β‐amyloid levels of TS mice. Melatonin was administered for 5 months to 5‐ to 6‐month‐old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)‐positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AβPP or β‐amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age‐related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age‐related progression of cognitive deterioration found in DS.     

The Effectiveness of Lifestyle Interventions to Reduce Cardiovascular Risk in Patients with Severe Mental Disorders: Meta-Analysis of Intervention Studies

Patients with severe mental illness have higher prevalences of cardiovascular risk factors (CRF). The objective is to determine whether interventions to modify lifestyles in these patients reduce anthropometric and analytical parameters related to CRF in comparison to routine clinical practice. Systematic review of controlled clinical trials with lifestyle intervention in Medline, Cochrane Library, Embase, PsycINFO and CINALH. Change in body mass index, waist circumference, cholesterol, triglycerides and blood sugar. Meta-analyses were performed using random effects models to estimate the weighted mean difference. Heterogeneity was determined using i² statistical and subgroups analyses. 26 studies were selected. Lifestyle interventions decrease anthropometric and analytical parameters at 3 months follow up. At 6 and 12 months, the differences between the intervention and control groups were maintained, although with less precision. More studies with larger samples and long-term follow-up are needed.     

Within a Hospital Setting

A psychoanalyst may function as an enlivening object, to awaken the growth of relatedness in patients whose curtailed object relations confine them to primitive forms of engagement. The model is informed by the insights of the child psychoanalytic psychotherapist Anne Alvarez in her treatment of disturbed youth. The idea of the analyst in an enlivening role is viewed within a contemporary context of expanded perspectives on the analyst's role and evolving notions of therapeutic action.     

Genetic and Epigenetic Determinants of Low Dysferlin Expression in Monocytes

Dysferlinopathies are autosomal recessive inherited muscular dystrophies caused by mutations in the gene DYSF. Dysferlin is primarily expressed in skeletal muscle, cardiac muscle, and peripheral blood monocytes. Expression in skeletal muscle and monocytes strongly correlates in healthy and disease states. We evaluated the efficiency of the monocyte assay to detect carriers and to determine the carrier frequency of dysferlinopathies in the general population. We enrolled 149 healthy volunteers and collected peripheral blood samples for protein analysis. While 18 of these individuals with protein levels in the range of 40%–64% were predicted to be carriers by the monocyte assay, subsequent DYSF sequencing analysis in 14 of 18 detected missense variants in only four. Analysis of DNA methylation patterns at the DYSF locus showed no changes in methylation levels at CpG islands and shores between samples. Our results suggest that: (1) dysferlin expression can also be regulated by factors outside of the dysferlin gene, but not related to DNA methylation; (2) carrier frequency and therefore the number of affected individuals could be higher than previously estimated; and (3) although reliable for evaluating dysferlinopathies, the monocyte assay cannot be used to determine the carrier status; for this, a molecular analysis of DYSF must be performed.