Alcohol marketing and drunkenness among students in the Philippines: findings from the nationally representative Global School-based Student Health Survey

BACKGROUND: A largely unaddressed issue in lower income countries and the Philippines, in particular, is the role of alcohol marketing and its potential link to early alcohol use among youth. This study examines the associations between exposures to alcohol marketing and Filipino youths’ drinking prevalence and drunkenness. METHODS: Cross-sectional analyses were used to examine the Global School-based Student Health Survey (GSHS) conducted in Philippines (2011). The self-administered questionnaires were completed by students primarily 13 to 16 years of age (N = 5290). Three statistical models were computed to test the associations between alcohol marketing and alcohol use, while controlling for possible confounding factors. RESULTS: Alcohol marketing, specifically through providing free alcohol through a company representative, was associated with drunkenness (AOR: 1.84; 95% CI = 1.06–3.21) among youths after controlling for demographic and psychosocial characteristics, peer environment, and risky behaviors. In addition, seeing alcohol ads in newspapers and magazines (AOR: 1.65, 95% CI = 1.05–2.58) and seeing ads at sports events, concerts or fairs (AOR: 1.50, 95% CI = 1.06–2.12) were significantly associated with increased reports of drunkenness. CONCLUSIONS: There are significant associations between alcohol marketing exposure and increased alcohol use and drunkenness among youth in the Philippines. These findings highlight the need to put policies into effect that restrict alcohol marketing practices as an important prevention strategy for reducing alcohol use and its dire consequences among vulnerable youth

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

Evaluation of emotion processing in HIV-infected patients and correlation with cognitive performance

Background: Facial emotion recognition depends on cortical and subcortical networks. HIV infection of the central nervous system can damage these networks, leading to impaired facial emotion recognition. Methods: We performed a cross-sectional single cohort study consecutively enrolling HIV + subjects during routine outpatient visits. Age, gender and education-matched HIV-negative healthy individuals were also selected. Subjects were submitted to a Facial Emotion Recognition Test, which assesses the ability to recognize six basic emotions (disgust, anger, fear, happiness, surprise, sadness). The score for each emotion and a global score (obtained by summing scores for each emotion) were analyzed. General cognitive status of patients was also assessed. Results: A total of 49 HIV + and 20 HIV−subjects were enrolled. On the Facial Emotion Recognition Test, ANOVA revealed a significantly lower performance of HIV + subjects than healthy controls in recognizing fear. Moreover, fear facial emotion recognition was directly correlated with Immediate Recall of Rey Words. The lower the patients’ neurocognitive performance the less accurate they were in recognizing happiness. AIDS-defining events were negatively related to the correct recognition of happiness. Conclusions: Fear recognition deficit in HIV + patients might be related to the impaired function of neural networks in the frontostriatal system. AIDS events, including non-neurological ones, may have a negative effect on this system. Inclusion of an emotion recognition test in the neuropsychological test battery could help clinicians during the long term management of HIV-infected patients, to better understand the cognitive mechanisms involved in the reduction of emotion recognition ability and the impact of this impairment on daily lif

The Peter Pan paradigm

Genetic and environmental agents that disrupt organogenesis are numerous and well described. Less well established, however, is the role of delay in the developmental processes that yield functionally immature tissues at birth. Evidence is mounting that organs do not continue to develop postnatally in the context of these organogenesis insults, condemning the patient to utilize under-developed tissues for adult processes. These poorly differentiated organs may appear histologically normal at birth but with age may deteriorate revealing progressive or adult-onset pathology. The genetic and molecular underpinning of the proposed paradigm reveals the need for a comprehensive systems biology approach to evaluate the role of maternal-fetal environment on organogenesis

Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli

Gram-negative bacteria, such as Escherichia coli, expel toxic chemicals via tripartite efflux pumps spanning both the inner and outer membranes. The three parts are: 1) a membrane fusion protein connecting 2) a substrate-binding inner membrane transporter to 3) an outer membrane-anchored channel in the periplasmic space. A crystallographic model of this tripartite efflux complex has been unavailable simply because co-crystallization of different components of the system has proven to be extremely difficult. We previously described the crystal structures of both the inner membrane transporter CusA1 and membrane fusion protein CusB2 of the CusCBA efflux system3,4 from E. coli. We here report the co-crystal structure of the CusBA efflux complex, revealing the trimeric CusA efflux pump interacts with six CusB protomers at the upper half of the periplasmic domain. These six CusB molecules form a channel extending contiguously from the top of the pump. The affinity of the CusA and CusB interaction was found to be in the micromolar range. Finally, we predicted a three-dimensional structure of the trimeric CusC outer membrane channel, and develop a model of the tripartite efflux assemblage. This CusC3-CusB6-CusA3 model presents a 750 kDa efflux complex spanning the entire bacterial cell envelope to export Cu(I)/Ag(I) ions

Transcriptomics in Interferon-α-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression

Owing to the unique opportunity to assess individuals before and after they develop depression within a short timeframe, interferon-α (IFN-α) treatment for chronic hepatitis C virus (HCV) infection is an ideal model to identify molecular mechanisms relevant to major depression, especially in the context of enhanced inflammation. Fifty-eight patients were assessed prospectively, at baseline and monthly over 24 weeks of IFN-α treatment. New-onset cases of depression were determined using the Mini International Neuropsychiatric Interview (MINI). Whole-blood transcriptomic analyses were conducted to investigate the following: (1) baseline gene expression differences associated with future development of IFN-α-induced depression, before IFN-α, and (2) longitudinal gene expression changes from baseline to weeks 4 or 24 of IFN-α treatment, separately in those who did and did not develop depression. Transcriptomics data were analyzed using Partek Genomics Suite (1.4-fold, FDR adjusted pless than or equal to0.05) and Ingenuity Pathway Analysis Software. Twenty patients (34%) developed IFN-α-induced depression. At baseline, 73 genes were differentially expressed in patients who later developed depression compared with those who did not. After 4 weeks of IFN-α treatment, 592 genes were modulated in the whole sample, representing primarily IFN-α-responsive genes. Substantially more genes were modulated only in patients who developed depression (n=506, compared with n=70 in patients who did not), with enrichment in inflammation-, neuroplasticity- and oxidative stress-related pathways. A similar picture was observed at week 24. Our data indicate that patients who develop IFN-α-induced depression have an increased biological sensitivity to IFN-α, as shown by larger gene expression changes, and specific signatures both as predictors and as correlates

Predictors of colorectal cancer screening in diverse primary care practices

BACKGROUND: To explain why rates of colorectal cancer (CRC) screening including fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), colonoscopy (CS), and barium enema (BE), are low, this study assessed determinants of CRC screening from medical records. METHODS: Data were abstracted from patients aged ≥64 years selected from each clinician from 30 diverse primary care practices (n = 981). Measurements included the rates of annual FOBT, ever receiving FOBT, ever receiving FS/CS/BE under a combination variable, endoscopy/barium enema (EBE). RESULTS: Over five years, 8% had received annual FOBT, 53% had ever received FOBT and 22% had ever received EBE. Annual FOBT was negatively associated with female gender, odds ratio (OR) = .23; 95% confidence interval = .12–.44 and positively associated with routinely receiving influenza vaccine, OR = 2.55 (1.45–4.47); and more office visits: 3 to <5 visits/year, OR = 2.78 (1.41–5.51), and ≥5 visits/year, OR = 3.35 (1.52-7.42). Ever receiving EBE was negatively associated with age ≥75 years, OR = .66 (.46–.95); being widowed, OR = .59 (.38–.92); and positively associated with more office visits: 3 to <5 visits/year, OR = 1.83 (1.18–2.82) and ≥5 visits/year, OR = 2.01 (1.14–3.55). CONCLUSION: Overall CRC screening rates were low, but were related to the number of primary care office visits. FOBT was related to immunization status, suggesting the possible benefit of linking these preventive services

Alcohol, binge drinking and associated mental health problems in young urban Chileans

OBJECTIVE: To explore the link between alcohol use, binge drinking and mental health problems in a representative sample of adolescent and young adult Chileans. METHODS: Age and sex-adjusted Odds Ratios (OR) for four mental wellbeing measures were estimated with separate conditional logistic regression models for adolescents aged 15-20 years, and young adults aged 21-25 years, using population-based estimates of alcohol use prevalence rates from the Chilean National Health Survey 2010. RESULTS: Sixty five per cent of adolescents and 85% of young adults reported drinking alcohol in the last year and of those 83% per cent of adolescents and 86% of young adults reported binge drinking in the previous month. Adolescents who reported binging alcohol were also more likely, compared to young adults, to report being always or almost always depressed (OR 12.97 [95% CI, 1.86-19.54]) or to feel very anxious in the last month (OR 9.37 [1.77-19.54]). Adolescent females were more likely to report poor life satisfaction in the previous year than adolescent males (OR 8.50 [1.61-15.78]), feel always or almost always depressed (OR 3.41 [1.25-9.58]). Being female was also associated with a self-reported diagnosis of depression for both age groups (adolescents, OR 4.74 [1.49-15.08] and young adults, OR 4.08 [1.65-10.05]). CONCLUSION: Young people in Chile self-report a high prevalence of alcohol use, binge drinking and associated mental health problems. The harms associated with alcohol consumption need to be highlighted through evidence-based prevention programs. Health and education systems need to be strengthened to screen and support young people. Focussing on policy initiatives to limit beverage companies targeting alcohol to young people will also be needed

Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport

Gram-negative bacteria, such as Escherichia coli, frequently utilize tripartite efflux complexes in the resistance-nodulation-cell division (RND) family to expel diverse toxic compounds from the cell.1,2 The efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I) ions.3,4 No prior structural information was available for the heavy-metal efflux (HME) subfamily of the RND efflux pumps. Here we describe the crystal structures of the inner membrane transporter CusA in the absence and presence of bound Cu(I) or Ag(I). These CusA structures provide important new structural information about the HME sub-family of RND efflux pumps. The structures suggest that the metal binding sites, formed by a three-methionine cluster, are located within the cleft region of the periplasmic domain. Intriguingly, this cleft is closed in the apo-CusA form but open in the CusA-Cu(I) and CusA-Ag(I) structures, which directly suggests a plausible pathway for ion export. Binding of Cu(I) and Ag(I) triggers significant conformational changes in both the periplasmic and transmembrane domains. The crystal structure indicates that CusA has, in addition to the three-methionine metal binding site, four methionine pairs - three located in the transmembrane region and one in the periplasmic domain. Genetic analysis and transport assays suggest that CusA is capable of actively picking up metal ions from the cytosol, utilizing these methionine pairs/clusters to bind and export metal ions. These structures suggest a stepwise shuttle mechanism for transport between these sites