Urbanicity, posttraumatic stress disorder, and effect modification by socioeconomic position: A nested case-control study of the Korean National Health Insurance Database.

BACKGROUND: We aimed to estimate the association between urbanicity and the onset of posttraumatic stress disorder (PTSD) and to investigate heterogeneity therein according to age and socioeconomic position (SEP). METHODS: We analyzed administrative data from the Korean National Health Insurance Database for patients with PTSD from 2004 to 2018 (N = 109,230) and for a 1:4 sample of age-, sex-, and enrollment year-matched controls. Information on eligibility, SEP (proxied by insurance premium), place of residence, diagnosis, and medical claims was obtained. Urbanicity of administrative districts was assessed using data from the Korean Statistical Information Service, 2005-2018. We estimated hazard ratios (HRs) from baseline and time-dependent models. Subgroup analyses and polynomial splines were used to investigate heterogeneity by age and SEP. RESULTS: Urbanicity was associated with an increased risk of PTSD (per 10%p increase, HR = 1.056, 95% CI 1.050-1.061). A positive association was estimated among patients aged 0-29 years (HR = 1.115, CI 1.106-1.124), while negative associations were estimated among patients aged 30-64 years (HR = 0.990, CI 0.987-0.994) and 65 years or older (HR = 0.992, CI 0.979-1.014). The estimated associations with urbanicity were more prominent at the extremes of SEP, but only among younger participants. CONCLUSION: Urban residence was associated with an increased risk of PTSD diagnosis. The estimated association was larger among younger individuals (but not among middle-aged and older individuals). Among younger individuals, the estimated association was larger at both extremes of SEP.

Can natural language processing models extract and classify instances of interpersonal violence in mental healthcare electronic records: an applied evaluative study.

OBJECTIVE: This paper evaluates the application of a natural language processing (NLP) model for extracting clinical text referring to interpersonal violence using electronic health records (EHRs) from a large mental healthcare provider. DESIGN: A multidisciplinary team iteratively developed guidelines for annotating clinical text referring to violence. Keywords were used to generate a dataset which was annotated (ie, classified as affirmed, negated or irrelevant) for: presence of violence, patient status (ie, as perpetrator, witness and/or victim of violence) and violence type (domestic, physical and/or sexual). An NLP approach using a pretrained transformer model, BioBERT (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining) was fine-tuned on the annotated dataset and evaluated using 10-fold cross-validation. SETTING: We used the Clinical Records Interactive Search (CRIS) database, comprising over 500 000 de-identified EHRs of patients within the South London and Maudsley NHS Foundation Trust, a specialist mental healthcare provider serving an urban catchment area. PARTICIPANTS: Searches of CRIS were carried out based on 17 predefined keywords. Randomly selected text fragments were taken from the results for each keyword, amounting to 3771 text fragments from the records of 2832 patients. OUTCOME MEASURES: We estimated precision, recall and F1 score for each NLP model. We examined sociodemographic and clinical variables in patients giving rise to the text data, and frequencies for each annotated violence characteristic. RESULTS: Binary classification models were developed for six labels (violence presence, perpetrator, victim, domestic, physical and sexual). Among annotations affirmed for the presence of any violence, 78% (1724) referred to physical violence, 61% (1350) referred to patients as perpetrator and 33% (731) to domestic violence. NLP models' precision ranged from 89% (perpetrator) to 98% (sexual); recall ranged from 89% (victim, perpetrator) to 97% (sexual). CONCLUSIONS: State of the art NLP models can extract and classify clinical text on violence from EHRs at acceptable levels of scale, efficiency and accuracy.

Views and experiences of traditional and Western medicine practitioners on potential collaboration in the care of people living with mental illness in Malawi.

Introduction: Collaboration between traditional and biomedical medicine can lead to holistic care and improved health outcomes for people with mental illnesses. The current study aimed to explore the views and experiences of traditional and western medicine practitioners on potential collaboration in the care of people living with mental illness in Blantyre, Malawi. Method: A phenomenological qualitative research design was used. Data were collected using both one-on-one in-depth interviews (IDIs) and focus group discussions (FGDs). Participants were traditional healers and western medicine practitioners in Blantyre, Malawi. We conducted 10 in-depth interviews with traditional healers, 4 focus group discussions (2 for traditional healers and 2 for western medicine practitioners) and 6 key informant interviews with leaders of the two groups. The sample was determined based on data saturation. Thematic analysis was used to analyse the data. We used a combination of deductive and inductive coding. Results: Five broad themes were identified from the data: experiences with collaboration, views on collaboration, models of collaboration, barriers to collaboration, and factors that can facilitate collaboration. participants had no experience of formal collaboration between traditional healers and western healthcare workers in the management of mental illness. However, some reported experience of successful collaborations in other health areas such as safe motherhood, tuberculosis and HIV/AIDS. Many participants showed a positive attitude toward collaboration and were in support of it. Barriers to collaboration included negative attitudes and a lack of resources. Factors that can facilitate collaboration were dialogue, training and respect. Referral and training were the preferred forms of collaboration. Conclusion: With proper structures and respectful dialogue, a collaboration between traditional and western medicine practitioners is possible in Blantyre, Malawi.

Evaluation of Bivalirudin As an Alternative to Heparin for Systemic Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: Heparin is the universal anticoagulant for patients receiving extracorporeal membrane oxygenation support. However, heparin has many disadvantages, especially in young children, who develop heparin resistance. Recently our center has used bivalirudin, a direct thrombin inhibitor, for systemic anticoagulation in pediatric extracorporeal life support. Bivalirudin binds directly to thrombin with no need for antithrombin III and it inhibits both circulating and clot-bound thrombin. In this study, we sought to evaluate our experience with bivalirudin in pediatric extracorporeal life support. DESIGN: Retrospective chart review study of patients receiving extracorporeal membrane oxygenation support between October 2014 and May 2018. SETTING: Tertiary, academic PICU. PATIENTS: Sixteen patients receiving heparin and 16 patients receiving bivalirudin on extracorporeal life support were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients in the bivalirudin group had a median age of 31 months versus 59 months in the heparin group (p = 0.41). Recovery and extracorporeal membrane oxygenation decannulation were similar in both groups (56% in the heparin group and 62% in the bivalirudin group; p = 0.62). Time to reach goal therapeutic anticoagulation level was shorter in the bivalirudin group (11 vs 29 hr; p = 0.01). Bleeding events were fewer in the bivalirudin group, and there was no difference in the rate of thrombotic events between the two groups. Comprehensive cost analysis that includes anticoagulant, laboratories, and antithrombin III cost, showed that heparin anticoagulation therapy total cost was significantly higher than bivalirudin (1,184 dollars per day in heparin group vs 494 dollars per day in bivalirudin group; p = 0.03). Bivalirudin dose required to maintain target anticoagulation will increase over time, and this is associated with an increase in creatinine clearance and an increase in fibrinogen serum levels. CONCLUSIONS: This study showed that the use of bivalirudin in pediatric extracorporeal membrane oxygenation support is feasible, safe, reliable, and cost-effective in comparison to heparin. Further prospective randomized clinical trials are necessary to confirm our observations.

Perinatal mental health around the world: priorities for research and service development in Africa.

Africa is a diverse and changing continent with a rapidly growing population, and the mental health of mothers is a key health priority. Recent studies have shown that: perinatal common mental disorders (depression and anxiety) are at least as prevalent in Africa as in high-income and other low- and middle-income regions; key risk factors include intimate partner violence, food insecurity and physical illness; and poor maternal mental health is associated with impairment of infant health and development. Psychological interventions can be integrated into routine maternal and child healthcare in the African context, although the optimal model and intensity of intervention remain unclear and are likely to vary across settings. Future priorities include: extension of research to include neglected psychiatric conditions; large-scale mixed-method studies of the causes and consequences of perinatal common mental disorders; scaling up of locally appropriate evidence-based interventions, including prevention; and advocacy for the right of all women in Africa to safe holistic maternity care.

Path analyses of risk factors for linear growth faltering in four prospective cohorts of young children in Ghana, Malawi and Burkina Faso.

Stunting prevalence is an indicator of a country's progress towards United Nations' Sustainable Development Goal 2, which is to end hunger and achieve improved nutrition. Accelerating progress towards reducing stunting requires a deeper understanding of the factors that contribute to linear growth faltering. We conducted path analyses of factors associated with 18-month length-for-age z-score (LAZ) in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements Project in Ghana (n=1039), Malawi (n=684 and 1504) and Burkina Faso (n=2619). In two cohorts, women were enrolled during pregnancy. In two other cohorts, infants were enrolled at 6 or 9 months. We examined the association of 42 indicators of environmental, maternal, caregiving and child factors with 18-month LAZ. Using structural equation modelling, we examined direct and indirect associations through hypothesised mediators in each cohort. Out of 42 indicators, 2 were associated with 18-month LAZ in three or four cohorts: maternal height and body mass index (BMI). Six factors were associated with 18-month LAZ in two cohorts: length for gestational age z-score (LGAZ) at birth, pregnancy duration, improved household water, child dietary diversity, diarrhoea incidence and 6-month or 9-month haemoglobin concentration. Direct associations were more prevalent than indirect associations, but 30%-62% of the associations of maternal height and BMI with 18-month LAZ were mediated by LGAZ at birth. Factors that were not associated with LAZ were maternal iron status, illness and inflammation during pregnancy, maternal stress and depression, exclusive breast feeding during 6 months post partum, feeding frequency and child fever, malaria and acute respiratory infections. These findings may help in identifying interventions to accelerate progress towards reducing stunting; however, much of the variance in linear growth status remained unaccounted for by these 42 individual-level factors, suggesting that community-level changes may be needed to achieve substantial progress.

Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis in the cerebellum. The lack of beneficial therapeutic behavioral effects and potentially detrimental skeletal effects of EGCG found in Ts65Dn mice emphasize the importance of identifying dosages of EGCG that reliably improve DS phenotypes and linking those effects to actions of EGCG (or EGCG-containing supplements) in specific targets in brain and bone.

Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso.

BACKGROUND: Previous reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD. METHODS: We conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana (n = 1,023), Malawi (n = 675 and 1,385), and Burkina Faso (n = 1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9 months. In multiple linear regression and structural equation models (SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD. RESULTS: Out of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6 months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts. CONCLUSIONS: Key elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status.

Microstructural characteristics and gastro-small intestinal digestion in vitro of potato starch: Effects of refrigerated storage and reheating in microwave.

The objective of our study was to evaluate paste clarity, retrogradation (syneresis %), thermal characteristics and kinetics of glucose release during in vitro gastro-small intestinal digestion of freshly cooked and refrigerated potato starch. Freshly cooked starch pastes had a paste clarity of 71%, which decreased to 35.4% whereas syneresis (%) increased after 7days of refrigerated storage. The X-ray and thermal characteristics of native, retrograded and microwave reheated starch samples differed significantly from each other. For the freshly cooked starch pastes, ∼88% starch hydrolysis was observed at the end (150min) of digestion under simulated gastro-small intestinal conditions that decreased to ∼70% for the 7day stored pastes. The hydrolysis (%) of refrigerated pastes increased to 86% and 92% after one and two cycles of microwave reheating, respectively. These results contribute to the understanding of starch retrogradation in relation to starch digestion.

The impact of maternal diet fortification with lipid-based nutrient supplements on postpartum depression in rural Malawi: a randomised-controlled trial.

Perinatal depression is highly prevalent in low-and-middle-income countries and has been linked to poor child health. Suboptimal maternal nutrition may be a risk factor for perinatal depression. In this randomised-controlled trial conducted in rural Malawi, we set out to test the hypothesis that women taking a fatty acid-rich lipid-based nutrient supplement (LNS) would have fewer depressive symptoms postpartum than those taking iron-folate (IFA) or multiple-micronutrient (MMN) capsules. Women were recruited from antenatal clinics and randomised to receive LNS or MMN during pregnancy and for 6 months postpartum, or IFA during pregnancy only. Maternal depressive symptoms were measured using validated translations of the Self Reporting Questionnaire (SRQ) and Edinburgh Postnatal Depression Scale (EPDS), antenatally (SRQ only) and at 6 months postpartum (SRQ and EPDS). Analysis was by modified intention to treat. One thousand three hundred and ninety one women were randomised (LNS = 462, MMN = 466, IFA = 463). The groups were similar across a range of baseline variables. At 6 months postpartum, 1078 (77.5%) had SRQ completed; mean (SD) scores were LNS 1.76(2.73), MMN 1.92(2.75), IFA 1.71(2.66), P = 0.541. One thousand and fifty seven (76.0%) had EPDS completed; mean (SD) scores were LNS 5.77(5.53), MMN 5.43(4.97), IFA 5.52(5.18), P = 0.676. There were no statistically significant differences between the groups on SRQ or EPDS scores (continuous or dichotomised) in unadjusted or adjusted models. In conclusion, fortification of maternal diet with LNS compared with MMN or IFA did not reduce postnatal depressive symptoms in this study.

Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study.

OBJECTIVE: To investigate whether cannabis use is associated with increased risk of relapse, as indexed by number of hospital admissions, and whether antipsychotic treatment failure, as indexed by number of unique antipsychotics prescribed, may mediate this effect in a large data set of patients with first episode psychosis (FEP). DESIGN: Observational study with exploratory mediation analysis. SETTING: Anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust. PARTICIPANTS: 2026 people presenting to early intervention services with FEP. EXPOSURE: Cannabis use at presentation, identified using natural language processing. MAIN OUTCOME MEASURES: admission to psychiatric hospital and clozapine prescription up to 5 years following presentation. MEDIATOR: Number of unique antipsychotics prescribed. RESULTS: Cannabis use was present in 46.3% of the sample at first presentation and was particularly common in patients who were 16-25, male and single. It was associated with increased frequency of hospital admission (incidence rate ratio 1.50, 95% CI 1.25 to 1.80), increased likelihood of compulsory admission (OR 1.55, 1.16 to 2.08) and greater number of days spent in hospital (ß coefficient 35.1 days, 12.1 to 58.1). The number of unique antipsychotics prescribed, mediated increased frequency of hospital admission (natural indirect effect 1.09, 95% CI 1.01 to 1.18; total effect 1.50, 1.21 to 1.87), increased likelihood of compulsory admission (natural indirect effect (NIE) 1.27, 1.03 to 1.58; total effect (TE) 1.76, 0.81 to 3.84) and greater number of days spent in hospital (NIE 17.9, 2.4 to 33.4; TE 34.8, 11.6 to 58.1). CONCLUSIONS: Cannabis use in patients with FEP was associated with an increased likelihood of hospital admission. This was linked to the prescription of several different antipsychotic drugs, indicating clinical judgement of antipsychotic treatment failure. Together, this suggests that cannabis use might be associated with worse clinical outcomes in psychosis by contributing towards failure of antipsychotic treatment.

Association of asthma and anxiety: A nationwide population-based study in Taiwan.

BACKGROUND: Few studies have investigated the bidirectional relationship between asthma and anxiety; we sought to investigate asthma and anxiety in a large national sample. METHODS: Cases were identified from Taiwan's National Health Insurance Research Database with a new primary diagnosis of asthma (ICD-9:493) aged more than 15 years between 2000 and 2007. Case status required the presence of any inpatient diagnosis of asthma and/or at least one year diagnosis of asthma in outpatient service. These 22,797 cases were compared to 22,797 sex-, age-, residence- and insurance premium-matched controls and both groups were followed until the end of 2008 for instances of anxiety, defined as ICD-9 codes 300.0, 300.01, 300.02, 300.2, 300.21, 300.23, 300.3. Competing risk adjusted Cox regression analyses were applied, adjusting for sex, age, residence, insurance premium, prednisone use, Charlson comorbidity index, cardiovascular disease, diabetes, depression disorder, and hospital admission days for any disorder. The effect of asthma on the risk of panic disorder and the effect of anxiety disorder on the risk of later asthma were also examined as competing risk adjusted Cox regression analyses RESULTS: Of the 45,594 subjects, 2792 were ascertained as having anxiety during a mean (SD) follow-up period of 5.3 (2.5) years. Asthma, females, older age, rural residence, depression disorder, and prednisone use were independent risks on anxiety in the fully adjusted model. Anxiety, older age, rural residence, and prednisone use were independent risks on asthma in the fully adjusted model. LIMITATIONS: The severity of asthma and anxiety disorder, the duration of prednisone treatment and adherence, stressful life events, smoking, family history and relationship were not evaluated. CONCLUSIONS: Bidirectional relationship between asthma and anxiety disorder was confirmed in this population, in dependent of a number of potential confounding factors.

Cannabis use and treatment resistance in first episode psychosis: a natural language processing study.

BACKGROUND: Cannabis is frequently used among individuals with first episode psychosis and is associated with poor clinical outcomes. However, little is known about the effect of cannabis use on the response to antipsychotic medications and how use could affect outcomes. Using natural language processing on clinical data from a large electronic case register, we sought to investigate whether resistance to antipsychotic treatment mediated poor clinical outcomes associated with cannabis use. METHODS: Data were obtained from 2026 people with first episode psychosis in south London, UK. Cannabis use documented in free text clinical records was identified with natural language processing. Data for age, sex, ethnicity, marital status, psychotic disorder diagnosis, subsequent hospital admission, and number of unique antipsychotic medications prescribed were obtained using the Clinical Record Interactive Search instrument. The association of these variables with cannabis use was analysed with multivariable regression and mediation analysis. FINDINGS: 939 people (46·3%) with first episode psychosis were using cannabis at first presentation. Cannabis use was most strongly associated with being 16-25 years old, male, and single, and was also associated with an increase in number of hospital admissions (incidence rate ratio 1·50, 95% CI 1·25-1·80), compulsory hospital admission (odds ratio 1·55, 1·16-2·08), and number of days spent in hospital (ß coefficient 35·1 days, 12·1-58·1) over 5 years' follow-up. An increase in number of unique antipsychotic medications mediated an increase in number of hospital admissions (natural indirect effect 1·11, 1·04-1·17; total effect 1·41, 1·22-1·64), compulsory hospital admission (1·27, 1·10-1·45; 1·71, 1·05-2·78), and number of days spent in hospital (16·1, 6·7-25·5; 19·9, 2·5-37·3). INTERPRETATION: We showed that a substantial number of people with first episode psychosis used cannabis and that its use was associated with increased likelihood of hospital admission and number of days spent in hospital. These associations were partly mediated by an increase in number of unique antipsychotic medications prescribed. These findings suggest that cannabis might reduce response to conventional antipsychotic treatment and highlight the importance of strategies to reduce its use. FUNDING: National Institute for Health Research, UK Medical Research Council.

Zinc and Vitamin Supplementation in an Under-5 Indigenous Population of Guatemala: Influence of Lay Health Promoters in Decreasing Incidence of Diarrhea.

BACKGROUND: Malnutrition is an urgent problem in the developing world, especially for children under 5 years of age. The article describes the utilization of a standard of practice designed to prevent illness in a malnourished, under-5 indigenous population and reinforced by weekly basic health messages taught by lay community health promoters. METHOD: The two villages were chosen for observation after administration of the standard of care among the Maya-Kíché, the most numerous Mayan group in Guatemala. The standard of practice, 20 mg of daily oral zinc, was administered for 10 days in the home and followed by daily vitamin supplementation that continued throughout the 3 months of the project. All patients received four monthly clinic visits, with one of the village groups receiving weekly health promoter visits. RESULTS: Data evaluated after the quality improvement project showed significant differences in adherence to the zinc regimen (χ(2) = 3.677, p ≤ .05) as well as lower rates of diarrheal illnesses (χ(2) = 5.850, p ≤ .05), with both of these improved in the health promoter group. DISCUSSION: This study suggests that the training and implementation of para-health professionals from the lay community in response to specific health care needs could be considered a best practice in developing countries. IMPLICATIONS: Public health professionals are key to health promoter training and direction, and their importance in the global setting cannot be understated.

Associations between n-3 PUFA concentrations and cognitive function after recovery from late-life depression.

BACKGROUND: Lower concentrations of n-3 PUFAs have been reported to be associated with cognitive impairment and dementia, but also with depression-itself a potential risk factor for cognitive decline. OBJECTIVE: The aims of this study were to investigate associations between n-3 PUFA concentrations in erythrocyte membrane or plasma and cognitive function in an at-risk sample of older people with previous major depression and to explore specificity with respect to cognitive domains. DESIGN: A cross-sectional sample of 132 eligible participants who had recovered from major depression (mean ± SD age: 67.8 ± 6.6 y) were enrolled from outpatient psychiatric services. A series of cognitive tests and a structured questionnaire were administered. Fasting blood samples were collected for n-3 PUFA measurements. RESULTS: Higher EPA and total n-3 PUFA concentrations and a lower ratio of arachidonic acid to EPA in erythrocyte membranes were associated with a higher cognitive composite score: independent of age and sex, but no longer significant after adjustment for education. No associations were found with plasma concentrations of any fatty acid. Considering individual cognitive tests, the strongest and most consistent correlations were found between immediate recall and concentrations of total n-3 PUFAs and α-linolenic acid (ALA) in erythrocytes, which were observed only in participants with recurrent depression. CONCLUSIONS: Total erythrocyte n-3 PUFA concentrations are positively associated with cognitive function, particularly immediate recall, in older people with previous depression. Lower concentrations of n-3 PUFAs or ALA in erythrocyte membranes may be good predictors for cognitive impairment in older people with previous recurrent depression.

Effects of neuropeptide Y and ethanol on arousal and anxiety-like behavior in alcohol-preferring rats.

Neuropeptide Y (NPY) is abundant in the mammalian brain and plays a prominent role in behaviors related to negative affect and alcohol. NPY suppresses anxiety-like behavior and alcohol-drinking behaviors in a wide array of rodent models and also affects changes in these behaviors produced by fearful and stressful stimuli. Rats selectively bred for high alcohol preference (P rats) appear to be particularly sensitive to the behavioral effects of NPY. The dual purpose of the present investigation was to determine the effects of intraventricular NPY on (1) the acoustic startle response (ASR) of P rats in a high-anxiety setting and (2) social interaction behavior of P rats. In experiment 1, P rats were either cycled through periods of long-term ethanol access and abstinence or they remained ethanol naive. Rats were injected with one of four NPY doses and tested for ASR before and after footshock stress. NPY suppressed ASR in all P rats regardless of shock condition or drinking history. In experiment 2, rats received intraventricular infusion of one of four NPY doses and were then injected with either ethanol (0.75 g/kg) or saline and tested for social interaction. NPY increased social interaction in P rats even at doses that suppressed locomotor activity, regardless of ethanol dose. Suppression of anxiety-like and arousal behaviors by NPY in the present study confirm a role for NPY in alcohol-related behaviors in alcohol-preferring P rats.

Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors.

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.

The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study.

A 24-week, randomized, double-blind placebo-controlled study was carried out to test the feasibility of using omega-3 polyunsaturated fatty acids (PUFAs) monotherapy in people with cognitive impairment and to explore its effects on cognitive function and general clinical condition in these participants. Twenty three participants with mild or moderate Alzheimer's disease and twenty three with mild cognitive impairment were randomized to receive omega-3 PUFAs 1.8 g/day or placebo (olive oil). The data of 35 (76%) participants with at least one post-treatment visit was analyzed. There were no severe adverse effects in either group and it suggests that omega-3 PUFAs were well tolerable in this population. The treatment group showed better improvement on the Clinician's Interview-Based Impression of Change Scale (CIBIC-plus) than those in the placebo group over the 24 week follow-up (p=0.008). There was no significant difference in the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) change during follow-up in these two groups. However, the omega-3 fatty acids group showed significant improvement in ADAS-cog compared to the placebo group in participants with mild cognitive impairment (p=0.03), which was not observed in those with Alzheimer's disease. Higher proportions of eicosapentaenoic acid on RBC membranes were also associated with better cognitive outcome (p=0.003). Further studies should be considered with a larger-sample size, diet registration, higher dosages, comparisons between different combinations of PUFAs, and greater homogeneity of participants, especially those with mild Alzheimer's disease and mild cognitive impairment.

Evolving anatomic and electrophysiologic considerations associated with Fontan conversion.

The principles of Fontan conversion with arrhythmia surgery are to restore the cardiac anatomy by converting the original atriopulmonary connection to a total cavopulmonary artery extracardiac connection and treat the underlying atrial arrhythmias. Successful outcomes of this procedure are dependent on a thorough understanding of several factors: the patient's fundamental diagnosis of single-ventricle anatomy, the resultant cardiac configuration from the original atriopulmonary Fontan connection, right atrial dilatation that leads to atrial flutter or fibrillation, and associated congenital cardiac anomalies. The purpose of this article is to present some of the more challenging anatomic and electrophysiologic problems we have encountered with Fontan conversion and arrhythmia surgery and the innovative solutions we have used to treat them. The cases reviewed herein include: takedown of a Bjork-Fontan modification, right ventricular hypertension and tricuspid regurgitation after atriopulmonary Fontan for pulmonary atresia and intact ventricular septum, takedown of atrioventricular valve isolation patch for right-sided maze procedure, resultant hemodynamic considerations leading to intraoperative pulmonary vein stenosis after Fontan conversion, unwanted inferior vena cava retraction during the extracardiac connection, right atrial cannulation in the presence of a right atrial clot, distended left superior vena cava causing left pulmonary vein stenosis, dropped atrial septum, and the modified right-sided maze procedure for various single-ventricle pathology. Since 1994 we have performed Fontan conversion with arrhythmia surgery on 109 patients with a 0.9% mortality rate. We attribute our program's success in no small measure to the strong collaborative efforts of the cardiothoracic surgery and cardiology teams.

Angiotensin receptor blockade with candesartan attenuates atherosclerosis, plaque disruption, and macrophage accumulation within the plaque in a rabbit model.

BACKGROUND: Little is known about whether direct angiotensin receptor blockade can reduce atherosclerosis and plaque disruption. This study evaluated the effect of angiotensin receptor blockade on both the development of atherosclerosis and the disruption of plaque in a modified Constantinides animal model. METHODS AND RESULTS: Twenty-eight New Zealand White rabbits underwent aortic balloon injury followed by a 1% cholesterol diet for 8 weeks. Thirteen rabbits received candesartan at 0.5 mg x kg(-1) x d(-1) beginning 2 days before aortic balloon injury and continued for the total 8 weeks of the cholesterol diet. The rabbits were then pharmacologically triggered and humanely killed, and their aortas were analyzed. The degree of atherosclerosis was determined by intima-media ratio of the infrarenal portion of the aorta. The frequency of intra-aortic thrombosis, a measure of plaque disruption, and the percentages of macrophage area and collagen-staining area of the plaque were determined. Candesartan-treated rabbits had less atherosclerosis (intima-media infrarenal aorta ratio of 1.18+/-0.08 versus 1.57+/-0.08 [mean+/-SEM] for the placebo group, P<0.001); fewer thrombi (3 of 13 versus 11 of 15; P<0.05); lower percentage area of macrophages to total plaque (18.8+/-2.7% versus 27+/-2.5%, P<0.05); and higher collagen to total plaque area (45+/-3% versus 35+/-2%, P<0.01). CONCLUSIONS: These results demonstrate that angiotensin receptor blockade attenuates the degree of atherosclerosis and reduces both plaque disruption and macrophage accumulation while increasing collagen deposition in the aortas of this animal model.