Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer's disease

Epidemiological and pathogenetic evidences suggest a strong association between vascular risk factors and sporadic Alzheimer's disease (sAD). In agreement with the vascular hypothesis of AD, the role of various candidate genes for atherosclerosis has been investigated, leading to conflicting results. In order to clarify the significance of angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism in a group of patients with sAD, we conducted a case-control study including 149 cases and 149 age and sex matched controls. All subjects were genotyped for ACE and Apolipoprotein E (APOE). There were no significant differences in ACE genotype or allele frequencies between cases and controls, even after stratification for APOE4 carrier status. Our data suggest that the ACE I/D polymorphism is not associated to genetic susceptibility in sAD patients.     

TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations

The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β‐tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron‐specific expression pattern. A recurrent heterozygous mutation, c.1228G > A; p.E410K, in TUBB3 gene is responsible of a rare disorder clinically characterized by congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability and a wide range of neurological and endocrine abnormalities. Other mutations have been described spanning the entire gene and genotype–phenotype correlations have been proposed. We report on a 3‐year‐old boy in whom clinical exome sequencing allowed to identify a de novo TUBB3 E410K mutation as the molecular cause underlying a complex phenotype characterized by a severe bilateral palpebral ptosis refractory to eye surgery, psychomotor delay, absent speech, hypogonadism, celiac disease, and cyclic vomiting. Brain MRI revealed thinning of the corpus callosum with no evidence of malformation cortical dysplasia. We reviewed available records of patients with TUBB3 E410K mutation and compared their phenotype with the clinical outcome of patients with other mutations in TUBB3 gene. The present study confirms that TUBB3 E410K results in a clinically recognizable phenotype, unassociated to the distinct cortical dysplasia caused by other mutations in the same gene. Early molecular characterization of TUBB3 E410K syndrome is critical for targeted genetic counseling and prompt prospective care in term of neurological, ophthalmological, endocrine, and gastrointestinal follow‐up.     

Dissociation of conditioned locomotion and Fos induction in response to stimuli formerly paired with cocaine

A discrete stimulus (flashing light) was paired with cocaine (20 mg/kg) to induce conditioned locomotion. To identify brain regions activated during this response, Fos was measured with immunohistochemistry. Although paired subjects displayed robust conditioned locomotion, Fos was not increased in any limbic brain regions analyzed. In contrast, pairing of cocaine with generalized contextual cues (whole room) produced conditioned locomotion and Fos activation in the prelimbic portion of prefrontal cortex and the nucleus accumbens core. These results suggest that the pattern of neuronal activation during cocaine-conditioned activity differs depending on whether a discrete or contextual stimulus is used as a conditioned stimulus. The possibility that expectancy and frustrative nonreward contribute to Fos expression in rats conditioned to contextual cues is discussed.     

Production of IL-12, IL-23 and IL-27p28 by bone marrow-derived conventional dendritic cells rather than macrophages after LPS/TLR4-dependent induction by Salmonella Enteritidis

Induction of the interleukin-12 (IL-12) cytokine family comprising IL-12, IL-23, IL-27, and IL-12p40 by intracellular pathogens is required for orchestration of cell-mediated immune responses. Macrophages (MΦ) have been shown to be a source of IL-12 following TLR4-dependent activation by Salmonella (S.). In this study another antigen-presenting cell type, the conventional dendritic cell (cDC), was analyzed and its cytokine responses compared with those of MΦ. We generated bone marrow-derived conventional dendritic cells (BMDC) and macrophages (BMMΦ) by incubating murine bone marrow cells with supernatants containing granulocyte/macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF), respectively. Stimulation of BMDC and BMMΦ with S. enterica serovar Enteritidis (SE) or LPS resulted in the release of IL-12 and IL-23 by BMDC but not by BMMΦ. Furthermore, BMDC secreted approx. 20-fold more IL-12p40 and IL-27p28 than BMMΦ. However, BMDC and BMMΦ produced similar levels of IL-10. Using BMDC originating from wild-type (wt), TLR2^def and TLR4^def mice, we show that in BMDC the induction of IL-12, IL-23, and IL-27p28 by SE is dependent on TLR4, whereas low-level production of p40 is also mediated by pattern recognition receptors (PRR) other than TLR4. Interestingly, LPS- and SE-provoked responses of BMDC were remarkably similar indicating that LPS is the primary danger molecule of SE. Taken together, our results point to cDC rather than MΦ as the major producers of the IL-12 family members during in vitro infection with SE. The mechanisms of recognition of SE, however, appear to be the same for cDC and MΦ     

Exploring professional identity in rehabilitation professions: a scoping review

Advances in Health Sciences Education - Professional identity is believed to foster self-confidence and resilience in health care professionals. While literature exists describing professional...     

Determinants of attrition in a pediatric healthy lifestyle intervention: The CIRCUIT program experience

IntroductionAttrition in pediatric weight management programs is notoriously high. Greater understanding of its determinants is needed to inform retention strategies. We identified determinants of attrition in CIRCUIT, a healthy lifestyle intervention program for youth at risk of cardiovascular disease.MethodsA one-arm intervention study of children aged 4-18 years who initiated the CIRCUIT program in the first five years of its existence (N = 403). We defined attrition as attending the baseline visit but ceasing attendance prior to the 1-year follow-up. Potential determinants of dropout included the child’s age, sex, ethnicity, body mass index (BMI) z-score, family socio-demographic characteristics, and estimated driving time to the program, all measured at baseline. Associations were estimated bivariately, using chi-squared- and t-tests, and simultaneously in a multivariable logistic regression model.ResultsOf the 403 participants who started the program, 198 (49%) dropped out within 12 months of enrollment. Youth who dropped out were older (mean age 12.8y vs. 11.3y; p < 0.01), were less likely to live with both parents (62% vs. 71%; p = 0.05), and to have mothers who had completed high school (79% vs. 88%; p = 0.01). No group differences were observed for sex, ethnicity, baseline BMI z-score, fathers’ education, or driving time to the program. In multivariate models, only older age at initiation of the intervention (OR: 1.2; CI: 1.1,1.3) and lower maternal education (OR: 2.0; CI: 1.0,3.8) were associated with dropout.ConclusionImproved tailoring of interventions to older pediatric participants and to families of lower maternal education may help reduce attrition in CIRCUIT and similar lifestyle intervention programs.     

Social Inequalities in Changes in Diet in Adolescents during Confinement Due to COVID-19 in Spain: The DESKcohort Project

Adolescence is a critical period in the consolidation of healthy lifestyles that can last into adulthood. To analyze changes in food consumption and eating behaviors in high-school adolescents during the first confinement, a cross-sectional study was conducted at the end of confinement in Spain. Changes in the frequency or quantity of consumption of different types of food and food-related behaviors were analyzed. Socioeconomic and health-related variables were also considered. To determine whether dietary changes were related to socioeconomic position (SEP), Poisson regression models with robust variance were estimated. Overall, there were some changes towards a healthier diet such as an increase in fruit consumption (38.9%) and a decrease in the consumption of soft drinks (49.8%), sweets and pastries (39.3%), and convenience foods (49.2%). Some changes, however, were related to less healthy behaviors, such as a more irregular pattern of meal distribution (39.9%) or an increase in snacking between meals (56.4%). Changes towards less healthy eating were also related to students’ SEP. The risk of worsening the diet was found to be 21% higher in adolescents from a more disadvantaged SEP. Future public policies could be adapted to avoid increasing nutritional and health inequalities.     

Highly Pathogenic Avian Influenza A(H5N8) Virus Spread by Short- and Long-Range Transmission,France, 2016–17

We detected 3 genotypes of highly pathogenic avian influenza A(H5N8) virus in France during winter 2016–17. Genotype A viruses caused dramatic economic losses in the domestic duck farm industry in southwestern France. Our phylogenetic analysis suggests that genotype A viruses formed 5 distinct geographic clusters in southwestern France. In some clusters, local secondary transmission might have been started by a single introduction. The intensity of the viral spread seems to correspond to the density of duck holdings in each production area. To avoid the introduction of disease into an unaffected area, it is crucial that authorities limit the movements of potentially infected birds.