Impact of Lifetime Alcohol Use on Liver Fibrosis in a Population of HIV-Infected Patients With and Without Hepatitis C Coinfection

BACKGROUND: The effect of alcohol on liver disease in HIV infection has not been well characterized. METHODS: We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, "FIB-4," which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index ("APRI"), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg). RESULTS: Subjects (n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus (HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm(3) . Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis (FIB-4 <1.45) (adjusted odds ratio [AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis (FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection. CONCLUSIONS: In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population.

Characterization of a stem cell population in lung cancer A549 cells

We isolated a stem cell subpopulation from human lung cancer A549 cells using FACS/Hoechst 33342. This side population (SP), which comprised 24% of the total cell population, totally disappeared after treatment with the selective ABCG 2 inhibitor fumitremorgin C. In a repopulation study, isolated SP and non-SP cells were each able to generate a heterogeneous population of SP and non-SP cells, but this repopulation occurred more rapidly in SP cells than non-SP. An MTT assay and cell cycle distribution analysis reveal a similar profile between SP and non-SP groups. However, in the presence of doxorubicin (DOX) and methotrexate (MTX), SP cells showed significantly lower Annexin V staining when compared to non-SP cells. Taken together, these results demonstrate that SP cells have an active regeneration capacity and high anti-apoptotic activity compared with non-SP cells. Furthermore, our GeneChip data revealed a heightened mRNA expression of ABCG2 and ABCC2 in SP cells. Overall these data explain why the SP of A549 has a unique ability to resist DOX and MTX treatments. Therefore, we suggest that the expression of the ABCG2 transporter plays an important role in the multidrug resistance phenotype of A549 SP cells.

What do case-control studies estimate? Survey of methods and assumptions in published case-control research

To evaluate strategies used to select cases and controls and how reported odds ratios are interpreted, the authors examined 150 case-control studies published in leading general medicine, epidemiology, and clinical specialist journals from 2001 to 2007. Most of the studies (125/150; 83%) were based on incident cases; among these, the source population was mostly dynamic (102/125; 82%). A minority (23/125; 18%) sampled from a fixed cohort. Among studies with incident cases, 105 (84%) could interpret the odds ratio as a rate ratio. Fifty-seven (46% of 125) required the source population to be stable for such interpretation, while the remaining 48 (38% of 125) did not need any assumptions because of matching on time or concurrent sampling. Another 17 (14% of 125) studies with incident cases could interpret the odds ratio as a risk ratio, with 16 of them requiring the rare disease assumption for this interpretation. The rare disease assumption was discussed in 4 studies but was not relevant to any of them. No investigators mentioned the need for a stable population. The authors conclude that in current case-control research, a stable exposure distribution is much more frequently needed to interpret odds ratios than the rare disease assumption. At present, investigators conducting case-control studies rarely discuss what their odds ratios estimate.

Metabolic syndrome and alanine aminotransferase: a global perspective from the NAVIGATOR screening population

Non-alcoholic fatty liver disease (NAFLD) is associated with features of the metabolic syndrome (MetS) and may be an expression of the syndrome within the liver. Using screening data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study (n = 42 149), we examined whether alanine aminotransferase (ALT), a biomarker for NAFLD, clustered with features of MetS and whether the clusters differed across global geographic regions.

Research Partnerships for Addressing Global Challenges: Opening Speech

Humankind today is challenged by numerous threats brought about by global change. Climate has been and is being modified by human activities, which calls for mitigation and adaptation measures at an unprecedented scale. Natural resources have been degraded by human development by means of land cover and land use changes, for which protective and restoration measures have to be taken by land users and governments in most countries of the North and South. Low levels of economic development and insufficient policies in most developing countries have led to widespread poverty, which affects nearly half of the world’s population and directly threatens almost one billion people. Finally, uncontrolled economic growth has increased disparities between and within populations and has led to widespread environmental problems in many nations. Generating and sharing knowledge is a key to addressing such global challenges. Knowledge can be used to develop the best solutions and to avoid or repair threats. Research partnerships have proven to be suitable means to bridge the divides and disparities between knowledge societies and developing countries, thereby reducing gaps. Research partnerships are tools for further capacity development and thereby lead to societal empowerment. Institutional settings allowing for research partnerships are needed both in the North and the South, so that the different networks can work together in a long-term enabling environment.

Cell population, viability, and some key immunomodulatory molecules in different milk somatic cell samples in dairy cows

Immune cells in the milk are most important in combating pathogens that invade the mammary gland. This study investigated the immune competence and viability of somatic milk cells that are already resident in milk and udders free of infection. Cells were studied in freshly removed milk to simulate conditions in the udder. Effects of incubation, cell preparation, and immunological stimulation with 0.5 mug/ml lipopolysaccharide (LPS) from Escherichia coli were analysed. Viability and differential counts of milk cells between high and low somatic cell count (SCC) quarters, and cisternal and alveolar milk with and without LPS stimulation were compared. Incubation and preparation of cells caused a cell loss which further increased with time independently of SCC and milk fraction. The viability of these cells was stable until 3 h post incubation and decreased until 6 h. Cell populations differed between both investigations, but did not change during the course of the experiment. mRNA expression of immune and apoptosis factors of the cells, measured by qPCR, did not change substantially: mRNA expression of caspase 3, Toll like receptor 4, and GM-CSF did not change, whereas the expression of the death receptor Fas/APO-1 (CD95), lactoferrin and lysozyme was decreased at 6 h. Cyclooxygenase-2 and TNF-alpha mRNA expression were decreased after 6 h of LPS treatment. In comparison with other studies in vivo or in vitro (in cell culture), in this study where cells are studied ex vivo (removed from the udder but kept in their natural environment, the milk) resident milk cells seem to be more vulnerable, less viable, less able to respond to stimulation, and thus less immune competent compared with cells that have freshly migrated from blood into milk after pathogen stimulation. The cell viability and differential cell count differed between high- and low-SCC milk and between cisternal and alveolar milk depending on the individual cow. In conclusion, the results support the view that for a most effective defence against invading pathogens the mammary gland is reliant on the recruitment of fresh immune cells from the blood.

Basic symptoms in the general population and in psychotic and non-psychotic psychiatric adolescents

Cognitive-perceptive 'basic symptoms' are used complementary to ultra-high-risk criteria in order to predict onset of psychosis in the pre-psychotic phase. The aim was to investigate the prevalence of a broad selection of 'basic symptoms' in a representative general adolescent population sample (GPS; N=96) and to compare it with adolescents first admitted for early onset psychosis (EOP; N=87) or non-psychotic psychiatric disorders (NP; N=137).

Life partnerships in childhood cancer survivors, their siblings, and the general population

Background: Life partnerships other than marriage are rarely studied in childhood cancer survivors (CCS). We aimed (1) to describe life partnership and marriage in CCS and compare them to life partnerships in siblings and the general population; and (2) to identify socio-demographic and cancer-related factors associated with life partnership and marriage. Methods: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to all CCS (aged 20–40 years) registered in the Swiss Childhood Cancer Registry (SCCR), aged <16 years at diagnosis, who had survived ≥5 years. The proportion with life partner or married was compared between CSS and siblings and participants in the Swiss Health Survey (SHS). Multivariable logistic regression was used to identify factors associated with life partnership or marriage. Results: We included 1,096 CCS of the SCCSS, 500 siblings and 5,593 participants of the SHS. Fewer CCS (47%) than siblings (61%, P < 0.001) had life partners, and fewer CCS were married (16%) than among the SHS population (26%, P > 0.001). Older (OR = 1.14, P < 0.001) and female CCS (OR = 1.85, <0.001) were more likely to have life partners. CCS who had undergone radiotherapy, bone marrow transplants (global PTreatment = 0.018) or who had a CNS diagnosis (global PDiagnosis < 0.001) were less likely to have life partners. Conclusion: CCS are less likely to have life partners than their peers. Most CCS with a life partner were not married. Future research should focus on the effect of these disparities on the quality of life of CCS.

Background pathology of the ovary in a laboratory population of zebrafish Danio rerio

Adult zebrafish Danio rerio originating from one stock used as control animals in a toxicological study were examined histopathologically for the occurrence of spontaneous lesions in the gonads. While no histopathological changes were seen in the testes, the ovaries showed lesions consisting mainly of acute granulomatous inflammation with increased atresia and the presence of egg debris in the ovarian parenchyma and in the oviduct. Since infectious agents could not be detected and the fish were not exposed to toxicants, we consider these lesions as spontaneous alterations of the ovaries.

Researcher allegiance in psychotherapy outcome research: an overview of reviews

Researcher allegiance (RA) is widely discussed as a risk of bias in psychotherapy outcome research. The relevance attached to RA bias is related to meta-analyses demonstrating an association of RA with treatment effects. However, recent meta-analyses have yielded mixed results. To provide more clarity on the magnitude and robustness of the RA-outcome association this article reports on a meta-meta-analysis summarizing all available meta-analytic estimates of the RA-outcome association. Random-effects methods were used. Primary study overlap was controlled. Thirty meta-analyses were included. The mean RA-outcome association was r=.262 (p=.002, I(2)=28.98%), corresponding to a moderate effect size. The RA-outcome association was robust across several moderating variables including characteristics of treatment, population, and the type of RA assessment. Allegiance towards the RA bias hypothesis moderated the RA-outcome association. The findings of this meta-meta-analysis suggest that the RA-outcome association is substantial and robust. Implications for psychotherapy outcome research are discussed.

Health literacy among young adults: a short survey tool for public health and health promotion research

Health literacy (HL) is context-specific. In public health and health promotion, HL in the private realm refers to individuals' knowledge and skills to prevent disease and to promote health in everyday life. However, there is a scarcity of measurement tools explicitly geared to private realm contexts. Our aim was to develop and test a short survey tool that captures different dimensions of HL in the context of family and friends. We used cross-sectional data from the Swiss Federal Surveys of Adolescents from 2010 to 2011, comprising 7983 males and 366 females between 18 and 25 years. HL was assessed through a set of eight items (self-reports). We used principal component analysis to explore the underlying factor structure among these items in the male sample and confirmatory factor analysis to verify the factor structure in the female sample. The results showed that the tested item set represented dimensions of functional, interactive and critical HL. Two sub-dimensions, understanding versus finding health-relevant information, denoted functional HL. Interactive and critical HL were each represented with two items. A sum score based on all eight items (Cronbach's α: 0.64) showed expected positive associations with own and parental education among males and females (p < 0.05). The short item set appears to be a feasible measurement tool to assess HL in the private realm. Its broader application in survey studies may help to improve our understanding of how this form of HL is distributed in the general population.