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Limited research has examined the early neuropsychological and neurobiological changes associated with comorbid affective disorders and alcohol dependence.
Objectives & Aims
To investigate the cognitive and volumetric changes in individuals diagnosed with affective disorders with or without comorbid alcohol dependence.
Young adults (n = 21) who were undergoing medically-managed inpatient alcohol detoxification with comorbid affective disorders were neuropsychologically assessed 4-weeks following hospital discharge, and additionally underwent MRI brain scans during admission and 4-weeks following discharge. An affective disorders-only group (n = 21) with an equal distribution of anxiety and mood disorders was recruited through a youth mental health clinic.
Compared to affective disorders only (M = 31.8 ± 4.4 years old), individuals with affective disorders and alcohol dependence (M = 33.9 ± 6.3 years old; M = 21.1 ± 9.2 standard drinks/day) exhibited worse sustained attention and visual memory functioning. There was a highly significant association between drinking levels since detoxification and total brain volume change, such that resumption of heavy drinking attenuated brain volume gains associated with short-term abstinence (r = -0.87, p < 0.001).
In young adults with affective disorders, comorbid alcohol dependence is associated with more pronounced cognitive dysfunction, suggesting that these deficits are most relevant for cognitive remediation interventions. Crucially, abstinence or reduced drinking was associated with brain volume gains, whereas resumption of heavy drinking was associated with brain volume reductions, suggesting that medically-managed alcohol detoxification may, at least, partially reverse the neurobiological changes associated with prolonged alcohol dependence in young adults.
The mental health of youth is continually changing and requires reliable monitoring to ensure that adequate social and economic resources are allocated. This study assessed trends in mental health among Canadian youth, 12–24 years old. Specifically, we examined the prevalence of poor/fair perceived mental health, diagnosis of mood and anxiety disorders, suicidality, perceived stress and sleep problems, substance use, and mental health consultations.
Data were collected from eight cycles of the annual Canadian Community Health Survey (2011–2018). Prevalence of mental health outcomes was calculated from each survey, and meta-regression was used to assess trends over time. In the absence of a significant trend over time, the eight cycles were pooled together using meta-analysis techniques to gain precision. Trends in prevalence were assessed for the overall sample of youth (12–24 years) and separately for male and female adolescents (12–18 years) and young adults (19–24 years).
The prevalence of poor/fair perceived mental health, diagnosed mood and anxiety disorders, and past-year mental health consultations increased from 2011 to 2018, most strongly among young adult females. Past-year suicidality increased among young adult females but did not change for other age and sex groups. Notably, the prevalence of binge drinking decreased by 2.4% per year for young adult males, 1.0% for young adult females and 0.7% per year for adolescent males, while staying relatively stable for adolescent females. Prevalence of cannabis use declined among adolescents before legalisation (2011–2017); however, this trend did not persist in 2018. Instead, the 2018 prevalence was 5.6% higher than the 2017 prevalence (16.3 v. 10.7%). The combined prevalence of other illicit drug use was stable at 4.6%; however, cocaine use and hallucinogens increased by approximately 0.2% per year.
Our findings highlight a growing need for youth mental health services, as indicated by a rise in the prevalence of diagnosed mood and anxiety disorders and past-year mental health consultations. The reason for these observed increases is less apparent – it may represent a true rise in the prevalence of mental illness, or be an artefact of change in diagnostic practices, mental health literacy or diminishing stigma. Nonetheless, the findings indicate a need for the health care system to respond to the rising demand for mental health services among youth.
Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.
Cognitive behavioral therapy (CBT) is an effective treatment for many patients suffering from major depressive disorder (MDD), but predictors of treatment outcome are lacking, and little is known about its neural mechanisms. We recently identified longitudinal changes in neural correlates of conscious emotion regulation that scaled with clinical responses to CBT for MDD, using a negative autobiographical memory-based task.
We now examine the neural correlates of emotional reactivity and emotion regulation during viewing of emotionally salient images as predictors of treatment outcome with CBT for MDD, and the relationship between longitudinal change in functional magnetic resonance imaging (fMRI) responses and clinical outcomes. Thirty-two participants with current MDD underwent baseline MRI scanning followed by 14 sessions of CBT. The fMRI task measured emotional reactivity and emotion regulation on separate trials using standardized images from the International Affective Pictures System. Twenty-one participants completed post-treatment scanning. Last observation carried forward was used to estimate clinical outcome for non-completers.
Pre-treatment emotional reactivity Blood Oxygen Level-Dependent (BOLD) signal within hippocampus including CA1 predicted worse treatment outcome. In contrast, better treatment outcome was associated with increased down-regulation of BOLD activity during emotion regulation from time 1 to time 2 in precuneus, occipital cortex, and middle frontal gyrus.
CBT may modulate the neural circuitry of emotion regulation. The neural correlates of emotional reactivity may be more strongly predictive of CBT outcome. The finding that treatment outcome was predicted by BOLD signal in CA1 may suggest overgeneralized memory as a negative prognostic factor in CBT outcome.
Le code de la santé publique et notamment l’arrêté du 11 janvier 2007, relatif aux
limites et références de qualité des eaux brutes et des eaux destinées à la consommation
humaine, fixe quatre indicateurs de la qualité radiologique des eaux du robinet
globale, l’activité β globale, l’activité du tritium et la dose totale
indicative), ainsi que des valeurs guides et des références de qualité. Les chroniques
issues de la surveillance des eaux filtrées du Rhône aval montrent que, si la
radioactivité d’origine naturelle demeure bien évidemment constante au cours du temps, les
niveaux de contamination radioactive d’origine artificielle ont fortement diminué à partir
du début des années 90, de 10 à 100 fois suivant les radionucléides. Les données
soulignent également qu’aucune des limites d’activités α globale, β globale et en tritium n’a
été dépassée dans l’eau filtrée du Rhône aval au cours de l’ère industrielle nucléaire.
Les doses totales indicatives (DTI) calculées à partir des prélèvements d’eau filtrée du
Rhône aval (canal Philippe Lamour – Réseau hydraulique régional propriété de la région
Languedoc Roussillon géré par BRL), de l’Orb et de l’Hérault effectués en 2011 sont très
inférieures à la valeur de référence de 100 μSv/an. La contribution à la DTI des radionucléides
artificiels détectés dans ces hydrosystèmes est en outre négligeable (<0,01 %).
Une étude radioécologique a été menée sur les canaux rhodaniens du réseau hydraulique régional propriété de la région Languedoc Roussillon, gérés par BRL. Ces canaux transfèrent de l’eau du fleuve Rhône vers les territoires des départements du Gard et de l’Hérault à des fins d’irrigation et de production d’eau potable. Nos résultats montrent que les caractéristiques hydrauliques intrinsèques des canaux de transport d’eau influent sur la distribution solide/solution des éléments traces en transit et par conséquent sur leur transfert vers les milieux récepteurs. Si les concentrations en phase dissoute (eau filtrée) sont conservées, les concentrations en phase particulaire (matières en suspension et sédiments) sont significativement modifiées au cours du transit. Outre la ségrégation granulométrique des particules entre l’amont et l’aval du système, ces résultats sont très probablement liés à la production biologique autochtone (phyto et zooplancton). Ces résultats originaux soulignent le caractère atypique des canaux de transport d’eau quant au transfert des éléments potentiellement contaminants.
We investigated norovirus (NoV) concentrations and genotypes in oyster and faecal samples associated with two separate oyster-related outbreaks of gastroenteritis in Ireland. Quantitative analysis was performed using real-time quantitative reverse transcription polymerase chain reaction and phylogenetic analysis was conducted to establish the NoV genotypes present. For both outbreaks, the NoV concentration in oysters was >1000 genome copies/g digestive tissue and multiple genotypes were identified. In faecal samples, GII.13 was the only genotype detected for outbreak 1, whereas multiple genotypes were detected in outbreak 2 following the application of cloning procedures. While various genotypes were identified in oyster samples, not all were successful in causing infection in consumers. In outbreak 2 NoV GII.1 was identified in all four faecal samples analysed and NoV GII concentrations in faecal samples were >108 copies/g. This study demonstrates that a range of NoV genotypes can be present in highly contaminated oysters responsible for gastroenteritis outbreaks.
The carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into mitochondria to provide substrates for β-oxidation. We performed an analysis including three coding SNP in the muscle isoform of the CPT1b gene (rs3213445, rs2269383 and rs470117) and one coding SNP in the CPT2 gene (rs1799821) to find associations with traits of the metabolic syndrome (MetS). Male participants (n 755) from the Metabolic Intervention Cohort Kiel were genotyped and phenotyped for features of the MetS. Participants underwent a glucose tolerance test and a postprandial assessment of metabolic variables after a standardised mixed meal. Carriers of the rare CPT1b 66V (rs3213445) allele had significantly higher γ-glutamyl transpeptidase (GGT), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) activities (P< 0·0001, P= 0·03 and P= 0·048, respectively) and a higher fatty liver index (FLI, P= 0·026). Fasting and postprandial TAG (P= 0·007 and P= 0·009, respectively) and fasting glucose (P= 0·012) were significantly higher in 66V-allele carriers. The insulin sensitivity index determined after a glucose load was lower in those subjects (P= 0·005). Total cholesterol (P= 0·051) and LDL-cholesterol (P= 0·062) tended to be higher in 66V-allele carriers when compared with I66I homozygotes. Homozygosity of the rare K531E allele presented with lower GGT and GOT activities (P= 0·011 and P= 0·027, respectively). E531E homozygotes tended to have lower GPT and FLI (P= 0·078 and P= 0·052, respectively). CPT2 V368I (rs1799821) genotypic groups did not differ in the investigated anthropometric and metabolic parameters. The present results confirm the association of CPT1b coding polymorphisms with the MetS, with a deleterious effect of the CPT1b I66V and a protective impact of the CPT1b K531E SNP, whereas haplotype analysis indicates a relevance of the E531K polymorphism only.
Older adults are among the most vulnerable to adverse cognitive effects of psychotropic medications and, therefore, the personalization of psychotropic treatment based on adverse drug reactions in this demographic is of great importance. We examined changes on neuropsychological tests of attention attributable to selective serotonin reuptake inhibitor (SSRI) treatment in anxious older adults. We also examined whether variation in serotonin receptor genes was associated with reduced attentional performance with SSRIs. We examined change from pre- to post-treatment in two attention measures – digit span and coding – in 133 adults aged ⩾60 yr with generalized anxiety disorder in a 12-wk trial of escitalopram vs. placebo. We also examined attentional change in relation to genetic variability in four central serotonin receptors: the serotonin transporter and serotonin 1A, 2A and 1B receptors. Digit span scores were significantly lowered in patients receiving escitalopram relative to placebo, indicating reduced attentional performance attributable to the SSRI. Individuals with high-transcription variants in the receptors 5-HTR2A rs6311 and 5-HTR1B rs11568817 had greater reductions in attention with SSRI treatment compared to placebo. We conclude that SSRIs reduce attention in older adults, particularly in those with high-expression genetic variants at the serotonin 2A and 1B receptors. Analysing neuropsychological changes with SSRIs in relation to genetic variation in the serotonin system may be a useful strategy for detecting subgroups of older adults who are more susceptible to side-effects of SSRIs. These results, if confirmed, could lead to the personalization of SSRI use to reduce adverse neurocognitive effects.
To determine the extent age, sex and co-infection affect morbidity in people infected with hepatitis C virus (HCV), we performed a population-based study linking HCV notifications in New South Wales, Australia with their hospital (July 2000 to June 2006), hepatitis B virus (HBV) and HIV notification, and death records. Poisson models were used to calculate hospitalization rate ratios (RRs) for all-cause, illicit drug and liver-related admissions. Co-infection RRs were used to estimate attributable risk (AR). The 86 501 people notified with HCV contributed 422 761 person-years of observation; 0·8% had HIV, 3·7% HBV, and 0·04% had both. RRs for males were equal to or lower than for females in younger ages, but higher in older ages (P for interaction ⩽0·013). HBV/HIV co-infection resulted in ARs of over 70% for liver disease and 30–60% otherwise. However, at the cohort level the impact was minimal (population ARs 1·3–8·7%). Our findings highlight the importance and success of public health measures, such as needle and syringe exchange programmes, which have helped to minimize the prevalence of co-infection in Australia. The findings also suggest that the age of study participants needs to be considered whenever the burden of HCV-related morbidity is reported by sex. The results are likely to be representative of patterns in hospital-related morbidity for the entire HCV-infected population in Australia and the ARs generalizable to other developed countries.
Mucosal dendritic cells are at the heart of decision-making processes that dictate immune reactivity to intestinal microbes. They ensure tolerance to commensal bacteria and a vigorous immune response to pathogens. It has recently been demonstrated that the former involves a limited migration of bacterially loaded dendritic cells from the Peyer's patches to the mesenteric lymph nodes. During lactation, cells from gut-associated lymphoid tissue travel to the breast via the lymphatics and peripheral blood. Here, we show that human peripheral blood mononuclear cells and breast milk cells contain bacteria and their genetic material during lactation. Furthermore, we show an increased bacterial translocation from the mouse gut during pregnancy and lactation and the presence of bacterially loaded dendritic cells in lactating breast tissue. Our observations show bacterial translocation as a unique physiological event, which is increased during pregnancy and lactation. They suggest endogenous transport of intestinally derived bacterial components within dendritic cells destined for the lactating mammary gland. They also suggest neonatal immune imprinting by milk cells containing commensal-associated molecular patterns.
Quercetin has been described as having a wide range of beneficial effects in humans, ranging from anti-carcinogenic properties to reducing the risk of CVD. Nevertheless, underlying molecular mechanisms have been mostly investigated in vitro. Here, we tested whether a daily supplementation of quercetin leads to reproducible changes in human monocyte gene expression profiles. In study I, quercetin in varying dosages was given to healthy subjects for 2 weeks. RNA from monocytes isolated at the beginning and end of the study from subjects receiving 150 mg quercetin per d was subjected to transcriptome-wide microarray analysis. In study II, a double-blind cross-over study, twenty subjects exhibiting a ‘cardiovascular risk phenotype’ received 150 mg quercetin or placebo daily for 6 weeks each and served as the verification group. Microarray analysis revealed a number of differentially expressed genes. The most significantly represented functional groups were those of the immune system, nucleic acid metabolism, apoptosis and O-glycan biosynthesis. Twenty-four genes were chosen for technical replication and independent verification by quantitative real-time PCR. When comparing placebo and quercetin treatment, four genes showed significantly different expression changes (C1GALT1, O-glycan biosynthesis; GM2A, glycolipid catabolism; HDGF, cell proliferation; SERPINB9, apoptosis). However, these were minimal in respect to magnitude of fold change. In conclusion, although microarray analysis revealed extensive effects of quercetin on gene expression, the employment of a placebo-controlled study design showed no comparable results for twenty-four verification targets. This emphasises the need for stringent designs in nutritional intervention studies with the aim to identify relevant changes in gene expression.
Canadian cases and outbreaks of illness caused by Listeria monocytogenes between 1995 and 2004 were assessed. Isolates (722 total) were characterized by serotyping, and pulsed-field gel electrophoresis (PFGE) was performed to provide a means of detecting case clusters. Rates of listeriosis remained fairly consistent during the period of study, and patient characteristics were similar to those seen in studies of other populations. Most isolates were obtained from blood and cerebrospinal fluid, although during some outbreak investigations isolates were also obtained from stools. Serotype 1/2a predominated in isolates from patients in Canada, followed by serotypes 4b and 1/2b. Outbreaks caused by L. monocytogenes that occurred during the period of study were caused by isolates with serotypes 1/2a and 4b. A retrospective analysis of PFGE data uncovered several clusters that might have represented undetected outbreaks, suggesting that comprehensive prospective PFGE analysis coupled with prompt epidemiological investigations might lead to improved outbreak detection and control.
Genotyping was used to analyse Pseudomonas aeruginosa isolates from sink drains and 15 intubated patients as part of a 3-month prospective study of strain transmission in a medical-surgical intensive care unit. Ninety percent of all washbasin drains were persistently contaminated with several P. aeruginosa genotypes. In 60% (9/15) of the patients, P. aeruginosa colonization or infection was hospital-acquired: P. aeruginosa strains isolated from these patients were present in hospital sinks or in other patients before their admission. Since all patients were immobile, personnel were the probable route of transmission of P. aeruginosa in the hospital. The mechanism of strain transmission from sinks to hands during hand washing was investigated in a children's hospital. When P. aeruginosa was present at densities of > 105/c.f.u. per ml in sink drains, hand washing resulted in hand contamination with P. aeruginosa via aerosol generation in the majority of experiments or P. aeruginosa was detected using an air sampler above the washing basin. High P. aeruginosa cfu were present at 4.30 h in the eight sinks (5.4 × 105−7.0 × 1010 c.f.u./ml), whereas at 13.00 h P. aeruginosa c.f.u. were significantly lower (3.1 × 102−8.0 × 105 c.f.u. / ml). These data reveal that the danger of bacterial contamination of hands during hand washing is highest in the morning. The identified transmission routes demand more effective hygienic measures in hospital settings particularly concerning personnel hands and sink drains.
Plusieurs laboratoires et centres techniques ont
commencé à travailler sur la possibilité de réaliser des
composés multimatériaux via la Métallurgie des Poudres. Dans un
tel cas, ce procédé permet d'éviter le problème de
l'assemblage et d'obtenir une production aux cotes. Les compressions
dynamique (CGV) et conventionnelle sont deux voies possibles qui pourront
être comparées grâce à une presse de laboratoire
instrumentée pour l'analyse des phénomènes. Pour certaines
poudres, la CGV permet d'améliorer les propriétés à vert et
de modifier favorablement les conditions de frittage. La compression est
suivie d'un frittage conventionnel. Différents types de poudres (poudres
métalliques, poudres dures mais également des poudres
céramiques) sont utilisés dans ce projet permettant ainsi de
proposer de nombreuses applications. Cette présentation montre les
premiers résultats obtenus par le groupe de recherche.