Cohort profile: biological pathways of risk and resilience in Syrian refugee children (BIOPATH)

The BIOPATH cohort was established to explore the interplay of psychosocial and biological factors in the development of resilience and mental health problems in Syrian refugee children. Based in Lebanon, a middle-income country significantly impacted by the refugee crisis, it is the first such cohort of refugees in the Middle East. Families were recruited from informal tented settlements in the Beqaa region using purposive cluster sampling. At baseline (October 2017–January 2018), N = 3188 individuals participated [n = 1594 child–caregiver dyads; child gender, 52.6% female; mean (SD) age = 11.44 (2.44) years, range = 6–19]. Re-participation rate at 1-year follow-up was 62.8%. Individual interviews were conducted with children and primary caregivers and biological samples collected from children. Measures include: (1) children’s well-being and mental health problems (using tools validated against clinical interviews in a subsample of the cohort); (2) psychosocial risk and protective factors at the level of the individual (e.g. coping strategies), family (e.g. parent–child relationship), community (e.g. collective efficacy), and wider context (e.g. services); (3) saliva samples for genetic and epigenetic (methylation) analyses; (4) hair samples to measure cortisol, dehydroepiandrosterone (DHEA) and testosterone. This cohort profile provides details about sampling and recruitment, data collection and measures, demographic data, attrition and potential bias, key findings on resilience and mental health problems in children and strengths and limitations of the cohort. Researchers interested in accessing data should contact Professor Michael Pluess at Queen Mary University of London, UK (e-mail: m.pluess@qmul.ac.uk).

     

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials

Lanthanides are a series of critical elements widely used in multiple industries, such as optoelectronics and healthcare. Although initially considered to be of low toxicity, concerns have emerged during the last few decades over their impact on human health. The toxicological profile of these metals, however, has been incompletely characterized, with most studies to date solely focusing on one or two elements within the group. In the current study, we assessed potential toxicity mechanisms in the lanthanide series using a functional toxicogenomics approach in baker’s yeast, which shares many cellular pathways and functions with humans. We screened the homozygous deletion pool of 4,291 Saccharomyces cerevisiae strains with the lanthanides and identified both common and unique functional effects of these metals. Three very different trends were observed within the lanthanide series, where deletions of certain proteins on membranes and organelles had no effect on the cellular response to early lanthanides while inducing yeast sensitivity and resistance to middle and late lanthanides, respectively. Vesicle-mediated transport (primarily endocytosis) was highlighted by both gene ontology and pathway enrichment analyses as one of the main functions disturbed by the majority of the metals. Protein–protein network analysis indicated that yeast response to lanthanides relied on proteins that participate in regulatory paths used for calcium (and other biologically relevant cations), and lanthanide toxicity included disruption of biosynthetic pathways by enzyme inhibition. Last, multiple genes and proteins identified in the network analysis have human orthologs, suggesting that those may also be targeted by lanthanides in humans.

Since their discovery, lanthanides have presented both difficulty and opportunity for researchers. As a series, these elements behave rather similarly: most of them form +3 ions in aqueous solution (1), prefer highly electronegative anionic ligands (2), and form insoluble hydroxide precipitates at neutral pH if not otherwise complexed (3). Although the chemical similarities between these elements made their initial isolation and characterization a significant challenge, they now have unique applications in industry and medicine. Several lanthanides have become critical materials for many clean and sustainable energy technologies that will drive the future of our societies and are used, for example, in the production of batteries, magnets, motors, and other electronic components (4); low-concentration mixtures of lanthanides are used in Chinese agriculture to increase body weight gain among livestock (5, 6); lanthanum carbonate (sold under the commercial name of Fosrenol) is a noncalcium phosphate binder used to control hyperphosphataemia (7); and gadolinium is employed in diagnostic medicine, as an essential component of MRI contrast agents (8, 9).The growing use of lanthanides has increased the potential for human exposure to large concentrations of these metals, requiring more detailed investigations into their toxicological properties. For instance, administration of gadolinium-based contrast agents has been associated with the development of nephrogenic systemic fibrosis in patients with compromised renal function (10–12). Moreover, accumulation of gadolinium in the brains of patients who received repeated doses of gadolinium-based contrast agents has also been reported (13). Despite the current ubiquity of lanthanides, their toxicological profile has been incompletely characterized because until recently they were considered to be of low toxicological concern (14, 15). Previous toxicity studies primarily focused on lanthanum or cerium (and, to a lesser extent, neodymium and gadolinium), with the notion that these metals were representative of the series (14, 16–18). However, to our knowledge, no comprehensive mechanistic assay has been conducted to evaluate metal toxicity across the series, and little is known about what toxicological mechanisms may be shared by the different lanthanides.Saccharomyces cerevisiae is one of the best-characterized model organisms (19, 20), and there are many tools available for analyzing its genomic data (21–23). For example, yeast functional toxicogenomic screening is a powerful tool for investigating cellular mechanisms of cytotoxicity (24, 25). This method makes use of the yeast deletion libraries generated by the Yeast Deletion Project (26), a consortium of researchers across the United States and Canada, to establish relationships between genes and chemical exposures. Researchers used heterozygous and homozygous deletion pools of barcoded yeast strains to derive mechanistic toxicological information about a wide array of chemicals, pharmaceuticals, metals, and biological compounds (27, 28). As eukaryotes, yeast and humans share many cellular pathways and functions, and many components of cell biology identified in S. cerevisiae have homologs in human biology (29–31). Consequently, functional toxicogenomic screening offers unique opportunities to evaluate the mechanisms of cytotoxicity and general biological activity across the lanthanide series in yeast and explore potentially conserved mechanisms in humans.Here, we identify fundamental cellular functions disrupted by lanthanides using functional toxicogenomics in S. cerevisiae. The metals studied had distinct behaviors: early lanthanides showed limited unique functional effects, while middle and late lanthanides had prominent and distinct ones. Although the functional effects of each lanthanide were different and suggested some very efficient element discrimination by endogenous molecules, we observed a few common trends. In particular, vesicle-mediated transport (primarily endocytosis) was perturbed by the majority of the lanthanides tested. Moreover, protein–protein network analysis suggested that lanthanides mimic calcium ions, interacting with calcium-binding proteins and disrupting processes regulated by this cation. Finally, several of the highly interconnected proteins targeted by multiple lanthanides in the network analysis are conserved in humans, suggesting their roles in the origin of the human health issues associated with lanthanide exposure and opening many directions for the determination of mechanisms associated with toxicity.     

Inter-Organizational Collaboration in the Implementation of Evidence-based Practices Among Public Agencies Serving Abused and Neglected Youth

This study examined the role of inter-organizational collaboration in implementing new evidence-based practices for addressing problem behaviors in at-risk youth. Semi-structured interviews were conducted with 38 systems leaders of probation, mental health, and child welfare departments of 12 California counties participating in a large randomized controlled trial to scale-up the use of Multidimensional Treatment Foster Care. Three sets of collaboration characteristics were identified: (1) characteristics of collaboration process, (2) characteristics of the external environment, and (3) characteristics of participating organizations and individuals. Inter-organizational collaboration enables an exchange of information and advice and a pooling of resources individual agencies may require for successful implementation.     

Heart failure disease management: impact on hospital care,length of stay,and reimbursement

Congestive heart failure (CHF) is a major medical problem with significant hospital costs. The authors developed an inpatient disease management program for CHF in a community hospital setting to determine if it is possible to: 1) increase implementation of Agency for Health Care Policy and Research criteria for CHF; 2) improve the quality of patient care, while lowering length of stay and treatment cost for CHF; and 3) maintain nursing staff satisfaction. The program encompassed a clinical pathway incorporating Agency for Health Care Policy and Research criteria for CHF, CHF education, and patient educational materials. When compared to "unmanaged" patients (n=197) not participating in the algorithm due to physician choice, "managed" patients (n=396) had significantly increased documentation of left ventricular dysfunction and of angiotensin-converting enzyme inhibitor use. In contrast to unmanaged patients, managed patients had a significantly lower length of stay (3.9+/-2.2 vs. 6.1+/-2.8 days; p<0.0001) with a significant reduction in cost per patient ($4404+/-$1989 vs. $6828+/-$3347; p<0.0001). These changes were sustained in follow-up over 1 year and were associated with an improvement in nursing staff education and nursing care. Thus, a disease management program for CHF can be successfully implemented in a general community hospital setting, achieving improved compliance with Agency for Health Care Policy and Research treatment criteria and enhancing patient care, while reducing length of stay and cost.     

Inside the sausage factory: improving estimates of the effects of health insurance expansion proposals

The fate of a proposal to expand health insurance is influenced by predictions of the proposal's effects on the number of newly insured and the cost of new coverage. Estimates vary widely, for reasons that are often hard to discern and evaluate. This article describes and compares the frameworks and parameters used for insurance modeling. It examines conventions and controversies surrounding a series of modeling parameters: how individuals respond to a change in the price of coverage, the extent of participation in a new plan by those already privately insured, firms' behavior, and the value of public versus private coverage. The article also suggests ways of making models more transparent and proposes "reference case" guidelines for modelers so that consumers can compare modeling results.     

Trombosis del seno venoso cerebral en gestante con síndrome de Job

Cerebral venous sinus thrombosis is uncommon. Pregnancy is a major risk factor for the development of this entity. We report the case of a patient with Job’s syndrome and protein C and S deficiency who developed cerebral venous sinus thrombosis and dural fistula at 36 weeks’ gestation. After heparinization, the treatment of choice, pregnancy termination to eliminate the prothrombotic status and embolization of the dural fistula were required to obtain complete remission of the neurological symptoms.     

Tri-ethnic variations of co-morbid substance and alcohol use disorders in schizophrenia

OBJECTIVES: This study examined the differential prevalence of substance and alcohol use disorders among European Americans, African Americans, and Latinos with schizophrenia (n = 6424) who received public mental health services in San Diego County during fiscal year 2002-2003. METHODS: Data were obtained from the public mental health database used by the San Diego County Mental Health System. Chi-Square analyses and stepwise logistic regression analyses were used to examine differences regarding the prevalence of substance and alcohol use among clients with schizophrenia and schizoaffective disorder, and to analyze the sociodemographic variables associated with this co-morbidity. RESULTS: Significant differences in the prevalence of diagnosed co-morbidity were found across the ethnic groups. Rates of co-morbid diagnosis among African Americans (25%) were significantly higher than those among European Americans (22%) and Latinos (19%). Logistic regression results revealed ethnicity was a significant predictor of co-morbid substance and alcohol use, as was being homeless and male. Among Latinos, language preference was also a significant predictor. Latinos who denoted English as their primary language were 1.7 times more likely to be diagnosed with co-morbid substance or alcohol use disorders than Latinos who denoted Spanish. CONCLUSIONS: Among people with schizophrenia, there were significant differences in prevalence rates and predictors of diagnosed co-morbid substance and alcohol use disorders. Future research is needed to examine the relationship among language preference, level of acculturation, and subsequent diagnosing barriers for Latinos. Among African Americans, the reasons behind increased co-morbidity rates need to be examined, and homelessness should be carefully addressed among all three ethnic groups.     

How much might universal health insurance reduce socioeconomic disparities in health?

A strong association between lower socioeconomic status and worse health has been documented within many countries, but little work has been done to compare the strength of this relationship across countries. We compare the strength of the relationship between income and self-reported health in the US and Canada. We find that being below median income raises the likelihood that a middle-aged person is in poor or fair health by about 15 percentage points in the US, compared with less than 8 percentage points in Canada. We also find that this 7 percentage points stronger relationship between low income and poor health in the US compared with Canada is reduced by about 4 percentage points after age 65, the age at which virtually all US citizens receive basic health insurance through the Medicare programme. Income differences in the probability that an individual lacks a usual source of care are also significantly larger in the US than in Canada before the age of 65, but about the same after age 65. Our results are therefore consistent with the theory that the availability of universal health insurance in the US, or at least some other difference that occurs around the age of 65 in one country but not the other, decreases the difference in the strength of the income-health relationship in the US compared with Canada.     

Extraction of valerenic acids from valerian (Valeriana officinalis L.) rhizomes

Extraction of valerenic acids (valerenic, acetoxyvalerenic and hydroxyvalerenic) from dry ground rhizomes of valerian (Valeriana officinalis L.) was studied. The effect of ethanol concentration in the solvent, extraction temperature and drug particle size on extraction kinetics were investigated and the optimum values of these process parameters were determined for the case of intensively stirred two-phase dispersion. It was found that increased processing temperature favors extraction kinetics, but provokes moderate degradation of valerenic acids.