Smoking and Sleep Disorders

Snoring and sleep apnea-hypopnea syndrome (SAHS) are two disorders of considerable relevance due to their high prevalence in the general population and their notable morbidity and mortality, particularly in association with their harmful effects on the cardiovascular system. As well as sex, age, weight, craniofacial malformations, alcohol consumption, and use of hypnotic drugs, it has been suggested that smoking may be a risk factor for developing sleep-disordered breathing. While there is solid evidence for the independent association between snoring and smoking in both children and adults, it is still unclear whether smoking constitutes an independent risk factor for developing SAHS, despite the many studies carried out to assess this link. This is probably because the association, if it exists, is very weak.     

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

BACKGROUND: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD. METHODS: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education. RESULTS: In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency). CONCLUSIONS: Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.     

Diurnal rhythms of leptin and ghrelin in the systemic circulation and in the gastric mucosa are related to food intake in rats

We investigated diurnal changes in leptin and ghrelin levels in the stomach and in the systemic circulation and their relation to food intake rhythms in Wistar rats housed at 22 °C with a 12-h light/dark cycle and free access to food and water. Animals were sacrificed every 3 h over a 24-h period. Leptin and ghrelin levels in serum and in the gastric mucosa were analysed by immunoassay. Leptin mRNA levels were determined in the gastric mucosa by RT-PCR and in different adipose tissue depots (epididymal, retroperitoneal and mesenteric) by Northern blot. Ghrelin mRNA levels were determined by Northern blot. Gastric and serum leptin levels displayed similar diurnal rhythms, rising during the dark phase and decreasing gradually during the light phase. Leptin expression in the different adipose tissue depots correlated positively with circulating leptin levels (P<0.05), although there were some depot-associated differences. Leptin mRNA levels in the mesenteric depot correlated positively with food intake (P<0.05). In blood, ghrelin levels rose sharply just before the onset of the dark phase and dropped suddenly just after. In the stomach, ghrelin levels were high during the fasting period of light and low during the night, and correlated inversely with food intake, gastric contents and serum leptin levels (P<0.05). Leptin and ghrelin in the stomach and in the systemic circulation thus show diurnal variations that are influenced by food intake rhythms. The results agree with a role for ghrelin as a stimulant of meal initiation.     

C3 promotes clearance of Klebsiella pneumoniae by A549 epithelial cells

The airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense.     

Evaluation of an educational module on dengue and Aedes aegypti for schoolchildren in Honduras]

OBJECTIVE: To evaluate the effectiveness of a special course on environmental health and dengue, given to primary school students and intended to promote behavioral changes in the mothers of those students that would lead to the safe handling of water, adequate disposal of trash, and control of household breeding sites of Aedes aegypti, the mosquito vector for dengue. METHODS: In the period from April to November 2002 a community field trial was carried out that included four public schools in the city of Comayaguela, Honduras. Two of the schools formed the intervention group, and the two others made up the comparison or control group. The data collection activities before and after the intervention included knowledge tests for the schoolchildren and the teachers; surveys of the knowledge, attitudes, and practices of the students' mothers; entomological surveys (systematic checking in order to find water containers, to search for mosquito larvae) in the homes of the schoolchildren; in-depth interviews with the students' mothers; observation in the classrooms; and postintervention focus group with the teachers. RESULTS: During the intervention period the largest epidemic of classical dengue ever in the history of Tegucigalpa, the capital of Honduras, occurred. That event prompted the Secretariat of Health to undertake large-scale control activities. In the two intervention schools there was a significant increase in the students' knowledge of the following three variables: dengue caused by a virus, life cycle of the vector, and reduction of breeding sites, which is the most effective measure for controlling the vector (P < 0.0001 for all those increases in knowledge). There were also significant increases in the knowledge of the same variables among the teachers in the intervention schools: dengue caused by a virus (P = 0.03), life cycle of the vector (P = 0.01), and reduction of breeding sites (P = 0.004). Reducing the number of breeding sites as being the best measure for controlling Aedes aegypti was the knowledge variable that showed the greatest change among the mothers in the intervention group (P = 0.02). The values for two of the entomological indices (the House index and the Breteau index) were better in the intervention group than in the control group, but the difference was not statistically significant. However, there was a statistically significant difference in the Breteau index values between the two control group schools and the one intervention school where the education course was implemented more adequately than in the other intervention school. CONCLUSIONS: The application of educational interventions directed to schoolchildren, as a part of a comprehensive plan for controlling Aedes aegypti, is an effective way to raise the awareness of teachers and parents with respect to the problem of dengue, and it also helps in encouraging family members to be involved in reducing breeding sites in the home. In moving to control the dengue vector, this strategy should take into consideration the involvement not only of families but also of civic and public institutions in the community. Given our results, it appears that this approach of using a special course for schoolchildren can constitute a fundamental pillar in the strategy for integrated dengue control.     

The Impact of Schools on Juvenile Substance Initiation and Use

We use data from the two rounds of the NLSY97 and the corresponding QED data to examine the effectiveness of school endowments and curricula in targeting juvenile use of tobacco, alcohol, and marijuana. Our results support the notion that schools matter in reducing juvenile involvement in substance use. Higher discretionary dollars per pupil are linked to reduced rates of juvenile initiation and repetitive use rates of cigarettes and marijuana. Additionally, school curricula, as indicated by the implementation of year round classes and some innovative and after-school programs--such as gifted and talented, attendance monitoring, homework hotline, international baccalaureate, extended-day, and mentoring, programs, affect both juvenile initiation to tobacco and alcohol use and juvenile repetitive use of tobacco and alcohol. In particular, we find that juvenile initiation to cigarette use is approximately between 2 percentage points and 3 percentage points lower among youths attending schools with gifted and talented and international baccalaureate programs. In addition, juvenile repetitive cigarette use is approximately 54%, 52%, and 48% lower among youths attending schools offering year round classes, international baccalaureate, and twenty-first century programs, respectively. Finally, juvenile initiation to alcohol use and juvenile repetitive use of alcohol are approximately 3% and 20% lower, respectively, among youths in schools offering gifted and talented programs. In sum, while these programs are not implemented to address substance use problems among the student body, we find that the implementation of these programs is often accompanied by a reduction in juvenile initiation and repetitive substance use.     

The challenges of androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling.     

Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.