MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Incidental lymphadenopathy in renal transplantation.

INTRODUCTION: Iliac lymphadenectomy is performed to provide anastomotic access during the vascular implantation procedure in renal transplantation. Iliac lymph nodes (LNs) are often enlarged, but there are no standardised guidelines for the management of incidentally enlarged LNs during transplantation. We aimed to evaluate histological findings of LNs sent for examination at our unit. METHODS: Patients were evaluated in two distinct date cycles. In the first cycle, lymphadenectomy and histological assessment were performed at the discretion of the transplanting surgeon. In the second cycle, all incidentally enlarged LNs were sent for histological assessment, regardless of size. RESULTS: In the first cycle (n = 76), 11 patients (14.47%) had incidentally enlarged iliac LNs on lymphadenectomy and histology showed only reactive changes. In the second cycle (n = 165), eight patients (4.85%) had incidentally enlarged LNs on lymphadenectomy. One patient was found to have mature B cell chronic lymphocytic leukaemia. The patient was referred to haematology and a "watch and wait" approach was taken, with the patient still alive at last follow-up (511 days post-transplantation). DISCUSSION: There are currently no published guidelines on the management of incidentally enlarged iliac LNs during transplantation. Current literature suggests that clinically significant lymphadenopathy needs to be investigated in all patients. Based on our centre's experience of a 5.26% (1 in 19) positive pathological LN sampling, we recommend that all incidental LNs with suspicious features and/or that are greater than 10mm in diameter should be considered for histological, microbiological and molecular assessment as appropriate.

Causal relationships between breast cancer risk factors based on mammographic features.

BACKGROUND: Mammogram risk scores based on texture and density defined by different brightness thresholds are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. We aimed to investigate causal relationships between these intercorrelated mammogram risk scores to determine their relevance to breast cancer aetiology. METHODS: We used digitised mammograms for 371 monozygotic twin pairs, aged 40-70 years without a prior diagnosis of breast cancer at the time of mammography, from the Australian Mammographic Density Twins and Sisters Study. We generated normalised, age-adjusted, and standardised risk scores based on textures using the Cirrus algorithm and on three spatially independent dense areas defined by increasing brightness threshold: light areas, bright areas, and brightest areas. Causal inference was made using the Inference about Causation from Examination of FAmilial CONfounding (ICE FALCON) method. RESULTS: The mammogram risk scores were correlated within twin pairs and with each other (r = 0.22-0.81; all P < 0.005). We estimated that 28-92% of the associations between the risk scores could be attributed to causal relationships between the scores, with the rest attributed to familial confounders shared by the scores. There was consistent evidence for positive causal effects: of Cirrus, light areas, and bright areas on the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively); and of light areas and bright areas on Cirrus (accounting for 37% and 28%, respectively). CONCLUSIONS: In a mammogram, the lighter (less dense) areas have a causal effect on the brightest (highly dense) areas, including through a causal pathway via textural features. These causal relationships help us gain insight into the relative aetiological importance of different mammographic features in breast cancer. For example our findings are consistent with the brightest areas being more aetiologically important than lighter areas for screen-detected breast cancer; conversely, light areas being more aetiologically important for interval breast cancer. Additionally, specific textural features capture aetiologically independent breast cancer risk information from dense areas. These findings highlight the utility of ICE FALCON and family data in decomposing the associations between intercorrelated disease biomarkers into distinct biological pathways.

Perception of learners on the effectiveness and suitability of MyDispense: a virtual pharmacy simulation and its integration in the clinical pharmacy module in Viet Nam.

BACKGROUND: My Dispense is a virtual pharmacy simulation developed for students to train and practice dispensing skills in a safe environment that causes no harm to patients. This study was aimed to investigate learners' perspectives on the effectiveness of MyDispense and its suitability to integrate into the clinical pharmacy module in Viet Nam. METHODS: A mixed method approach was undertaken. Fourth- and fifth-year pharmacy students at University of Medicine and Pharmacy at Ho Chi Minh city and community pharmacists were invited to complete a survey questionnaire and to participate in semi-structured interviews. RESULTS: A total of 92/99 participants agreed to take part, of which 75% of participants were students and 65.2% were female. About three-quarters of the participants agreed or strongly agreed that MyDispense improved their dispensing skills, such as patient counselling (70.6%) and collecting patient infomation (85.9%). The majority of the participants (84.8%) considered that MyDispense was suitable to integrate into the clinical pharmacy module. Qualitative analysis from the interviews highlighted the advantages of MyDispense, comprising high interactivity with users, safe environment for practicing medication dispensing, and diversity of common marketed medications. In addition, certain barriers of this programme were also reported, including the complicated process, inconsistent quality of product images, and mixed English-Vietnamese languages. CONCLUSIONS: From learner's perspectives, MyDispense was an effective tool to enhance dispensing skills and was suitable to integrated into the clinical pharmacy module in Viet Nam.

Clinical evaluation of hysterectomy for the treatment of invasive mole in Southern Vietnam.

OBJECTIVE: This study aimed to determine the rate of salvage chemotherapy and review associated factors in invasive mole patients treated by primary or delayed hysterectomy. PATIENTS AND METHODS: This study was carried out at the Tu Du Hospital, where a total of 189 patients were diagnosed with invasive mole based on histologic examination by hysterectomy between 01/2016 to 12/2020. We used the life table method to estimate the cumulative rate. We applied the Cox proportional hazard model to determine the factors associated with the need for salvage chemotherapy. RESULTS: At 12-month follow-up, 47 patients had required salvage chemotherapy. The incidence was 24.87% (95% CI: 18.88-31.66). Applying the multivariate model, prophylactic chemotherapy (HR = 2.75, 95% Cl: 1.20-6.30) and two weeks postoperative hCG value greater than 1,900 mIU/mL (HR = 4.30, 95% Cl: 2.08-8.87) increased the risk of requiring salvage chemotherapy. Postoperative chemotherapy decreased the risk of requiring salvage chemotherapy (HR = 0.43, 95% Cl: 0.22-0.83). CONCLUSIONS: Hysterectomy can be considered safe and effective in treating invasive mole patients. Although patients were treated by hysterectomy, 24.87% of patients needed salvage chemotherapy to achieve remission. This study affirms the malignant nature of invasive mole, a subtype of gestational trophoblastic neoplasia (GTN). It is not purely a local invasion of molar villi. Postoperative chemotherapy plays an essential role in reducing the risk of requiring salvage chemotherapy.

A robotic approach to clamshell augmentation enterocystoplasty.

Augmentation cystoplasty (AC) is a well-established surgical option for the management of overactive bladder where conservative management has failed. We describe the case of a man in his 50s with chronic bladder dysfunction secondary to refractory detrusor overactivity and small capacity bladder. His lower urinary tract symptoms (LUTS) of urinary frequency and nocturia persisted despite pharmacological therapy and peripheral neural modulation; hence, he underwent surgical intervention for management of his bladder dysfunction. A robot-assisted clamshell enterocystoplasty was performed with a successful outcome. His LUTS have improved significantly post surgery. This case highlights modern advances in minimally invasive and robotic surgical techniques in the management of functional urological conditions. It also further demonstrates that the robotic approach is a viable option for AC, an operation traditionally performed as open surgery.

Genetic Aspects of Mammographic Density Measures Associated with Breast Cancer Risk.

Cumulus, Altocumulus, and Cirrocumulus are measures of mammographic density defined at increasing pixel brightness thresholds, which, when converted to mammogram risk scores (MRSs), predict breast cancer risk. Twin and family studies suggest substantial variance in the MRSs could be explained by genetic factors. For 2559 women aged 30 to 80 years (mean 54 years), we measured the MRSs from digitized film mammograms and estimated the associations of the MRSs with a 313-SNP breast cancer polygenic risk score (PRS) and 202 individual SNPs associated with breast cancer risk. The PRS was weakly positively correlated (correlation coefficients ranged 0.05−0.08; all p < 0.04) with all the MRSs except the Cumulus-white MRS based on the "white but not bright area" (correlation coefficient = 0.04; p = 0.06). After adjusting for its association with the Altocumulus MRS, the PRS was not associated with the Cumulus MRS. There were MRS associations (Bonferroni-adjusted p < 0.04) with one SNP in the ATXN1 gene and nominally with some ESR1 SNPs. Less than 1% of the variance of the MRSs is explained by the genetic markers currently known to be associated with breast cancer risk. Discovering the genetic determinants of the bright, not white, regions of the mammogram could reveal substantial new genetic causes of breast cancer.

Familial Aspects of Mammographic Density Measures Associated with Breast Cancer Risk.

Cumulus, Cumulus-percent, Altocumulus, Cirrocumulus, and Cumulus-white are mammogram risk scores (MRSs) for breast cancer based on mammographic density defined in effect by different levels of pixel brightness and adjusted for age and body mass index. We measured these MRS from digitized film mammograms for 593 monozygotic (MZ) and 326 dizygotic (DZ) female twin pairs and 1592 of their sisters. We estimated the correlations in relatives (r) and the proportion of variance due to genetic factors (heritability) using the software FISHER and predicted the familial risk ratio (FRR) associated with each MRS. The ρ estimates ranged from: 0.41 to 0.60 (standard error [SE] 0.02) for MZ pairs, 0.16 to 0.26 (SE 0.05) for DZ pairs, and 0.19 to 0.29 (SE 0.02) for sister pairs (including pairs of a twin and her non-twin sister), respectively. Heritability estimates were 39% to 69% under the classic twin model and 36% to 56% when allowing for shared non-genetic factors specific to MZ pairs. The FRRs were 1.08 to 1.17. These MRSs are substantially familial, due mostly to genetic factors that explain one-quarter to one-half as much of the familial aggregation of breast cancer that is explained by the current best polygenic risk score.

Novel mammogram-based measures improve breast cancer risk prediction beyond an established mammographic density measure.

Mammograms contain information that predicts breast cancer risk. We developed two novel mammogram-based breast cancer risk measures based on image brightness (Cirrocumulus) and texture (Cirrus). Their risk prediction when fitted together, and with an established measure of conventional mammographic density (Cumulus), is not known. We used three studies consisting of: 168 interval cases and 498 matched controls; 422 screen-detected cases and 1197 matched controls; and 354 younger-diagnosis cases and 944 controls frequency-matched for age at mammogram. We conducted conditional and unconditional logistic regression analyses of individually- and frequency-matched studies, respectively. We estimated measure-specific risk gradients as the change in odds per standard deviation of controls after adjusting for age and body mass index (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). For interval, screen-detected and younger-diagnosis cancer risks, the best fitting models (OPERAs [95% confidence intervals]) involved: Cumulus (1.81 [1.41-2.31]) and Cirrus (1.72 [1.38-2.14]); Cirrus (1.49 [1.32-1.67]) and Cirrocumulus (1.16 [1.03 to 1.31]); and Cirrus (1.70 [1.48 to 1.94]) and Cirrocumulus (1.46 [1.27-1.68]), respectively. The AUCs were: 0.73 [0.68-0.77], 0.63 [0.60-0.66], and 0.72 [0.69-0.75], respectively. Combined, our new mammogram-based measures have twice the risk gradient for screen-detected and younger-diagnosis breast cancer (P ≤ 10-12 ), have at least the same discriminatory power as the current polygenic risk score, and are more correlated with causal factors than conventional mammographic density. Discovering more information about breast cancer risk from mammograms could help enable risk-based personalised breast screening.

Incidence of Infection of Enterovirus 71 and Coxsackieviruses A6 and A16 among Household Contacts of Index Cases in Dong Thap Province, Southern Vietnam.

BACKGROUND: Scarce information exists about immunity to hand, foot, and mouth disease (HFMD) among household contacts of index cases in Vietnam and what that means for reducing ongoing HFMD transmission in the community. METHODS: We analyzed neutralizing antibodies (NT) and the incidence of enterovirus (EVs) infection among household contacts of index cases in a province where HFMD remains endemic. Throat swab and 2 mL blood samples from household contacts were collected at enrollment, during and after 2 weeks follow-up. RESULTS: The incidence of EV-A71 infection among household contacts was 40/84 (47.6%, 95% Cl: 36.9-58.3%), compared with 106/336 (31.5%, 95% Cl: 26.6-36.5%) for CV-A6 and 36/107 (33.6%, 95% Cl: 24.7-42.6%) for CV-A16. The incidence of CV-A6 infection was fairly constant across ages; in contrast, CV-A71 and CV-A16 had some variation across ages. At baseline, higher geometric mean titer (GMT) of EV-A71, CV-A6, and CV-A16 antibody titers was found for 25-34-year groups (range 216.3 to 305.0) compared to the other age groups. There was a statistically significant difference in GMT values of CV-A6 and CV-A16 between those who had an infection or did not have infection among households with an index case of these serotypes. CONCLUSIONS: Our results indicated that adults were becoming infected with HFMD and could be contributing to the transmission. There is, therefore, a need for considering the household setting as an additional target for intervention programs for HFMD.

Add-on effect of clarithromycin to oral steroids as post- operative therapy for chronic rhinosinusitis with nasal polyps: a randomised controlled trial.

BACKGROUND: Evidence is lacking regarding the efficacy of macrolides and oral corticosteroids in chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS). Therefore, we examined the benefits of adding clarithromycin to oral pred- nisolone as post-ESS medical therapy in patients with CRSwNP. METHODS: In this randomised, double-blind, placebo-controlled trial, patients were enrolled and allocated to three study groups receiving different post-ESS medical therapies: group A (placebo for 14 weeks), group B (oral prednisolone [15 mg twice daily] for 2 weeks, followed by placebo for 12 weeks), and group C (oral prednisolone [15 mg twice daily] for 2 weeks, followed by clari- thromycin [500 mg daily] for 12 weeks). All enrolled patients received the perioperative care following a routine protocol, which included oral amoxicillin/clavulanate, and intranasal corticosteroid spray. The baseline and post-operative visual analogue scale (VAS) scores, Sino-nasal Outcome Test (SNOT-22) scores, and Lund-Kennedy endoscopy scores (LKES) were determined as the primary outcomes. RESULTS: One hundred twenty-six patients who received ESS for bilateral CRSwNP were randomised into group A (n=43), B (n=42), or C (n=41). Compared to groups A and B, group C showed greater VAS and SNOT-22 score improvement at 12 weeks after ESS. Group C showed significantly better LKES than did groups A and B at 8, 12, and 24 weeks after ESS. On stratifying the LKES results according to the presence/absence of tissue eosinophilia, greater add-on effects of clarithromycin were observed in the patient subgroup without tissue eosinophilia. CONCLUSIONS: Adding low-dose clarithromycin to oral corticosteroids as post-ESS therapy was well tolerated and showed benefi- cial subjective and objective outcomes in patients with CRSwNP, especially those without tissue eosinophilia.

Spontaneous reduction of low-potential silver(I) dithiosulfate complex in bioelectrochemical systems for recovery of silver and simultaneous electricity production.

Waste fixer solutions generated from photographic processing are silver-rich effluents, in which silver exists in the form of a dithiosulfate complex ([Ag(S2O3)2]3-), a stable and water-soluble chemical compound. This study investigated the electrochemical reduction of [Ag(S2O3)2]3- at different initial concentrations for silver recovery, combined with electricity production in a two-chamber bio-electrochemical system using a cation exchange membrane as the separator. During the biological oxidation of acetate to produce electrons in the anode chamber, [Ag(S2O3)2]3- was reduced spontaneously by acting as an electron acceptor in the cathode chamber, despite its low standard redox potential ([Ag(S2O3)2]3-/Ag0, E 0 = 0.016 V). After 48 h in each batch of operation, a Ag recovery efficiency of 81.7-95.2%, with a columbic efficiency of 12.9-21.4% and a maximum power density of 1500-2647 mW/m3, were obtained with an initial [Ag(S2O3)2]3- concentration of 10-20 mM, respectively. When the initial [Ag(S2O3)2]3- concentration increased to 30 mM, cell voltage production did not improve significantly, and a small decrease in Ag recovery efficiency to 93.2% was found. After 61 days of operation, the cathode surface was covered by different-sized silver clusters under SEM observation. The results were confirmed by EDX and XRD characterization, in which metallic silver with high purity was detected. SEM-EDX-XRD characterization of the membrane and the measurements in the control reactor confirmed that there was no diffusion of negatively charged [Ag(S2O3)2]3- complex through the membrane. Thus, this study showed a successful recovery of Ag from the low-potential [Ag(S2O3)2]3- complex without energy consumption, secondary waste generation, and loss of Ag.

Interval breast cancer risk associations with breast density, family history and breast tissue aging.

Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case-control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first-degree family history by questionnaire, measured body mass index (BMI) and calculated age-adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age-adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69-0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts-an increased risk of developing an interval breast cancer.

Left dorsolateral prefrontal cortex supports context-dependent prioritisation of off-task thought.

When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when 'on-task' under demanding conditions and 'off-task' in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC.

Endoscopic submucosal dissection with a novel high viscosity injection solution (LiftUp) in an ex vivo model: a prospective randomized study.

Introduction Endoscopic submucosal dissection (ESD) is increasingly being used in the western world. Submucosal injectates are an essential tool for the ESD procedure. In this study, we evaluated a novel copolymer injectate (LiftUp, Ovesco, Tübingen Germany) in an established ESD model (EASIE-R) in comparison to existing submucosal injectables. Materials and methods We conducted a prospective, randomized ex vivo study performing ESD with three injectates: LiftUp, hydroxyethyl starch (HAES 6 %) and normal saline solution (NaCl 0.9 %). A total of 60 artificial lesions, each 3 × 3 cm in size, were resected in an ex vivo porcine model, utilizing one of the three studied injectates (n = 20 ESDs per injectate). Study parameters were: en bloc resection rate, perforation rate, lifting property, time of injection, injectate volume, general ESD procedure time, and overall procedure time. Results All 60 lesions were successfully resected using the standard ESD technique. LiftUp had no procedure related perforations, one perforation occurred in the HAES group, and two perforations in the NaCl group ( P  > 0.05). Furthermore, adequate lifting was achieved in 16/20 (80 %) using LiftUp, 6/20 (30 %) in the HAES group and 6/20 (30 %) in the NaCl group ( P  < 0.0002). En bloc resection was achieved in 19 (95 %) with LiftUp, in 20 (100 %) with HAES, and in 16 (80 %) with NaCl. General ESD procedure time and overall procedure time were not different among the three groups. Conclusion LiftUp appears to be a safe alternative to established fluids for ESD. It had a significantly improved lifting effect and required significantly less injected volume compared to well-established lifting solutions.

Absorptive and Secretory Transport of Selected Artemisinin Derivatives Across Caco-2 Cell Monolayers.

BACKGROUND: Malaria continues to be a major health concern and affects more than 200 million people a year. Drugs currently used for treatment of malaria are increasingly rendered ineffectual by the ongoing emergence of parasite resistance. For any new drugs, however, knowledge of their membrane permeability is an essential pre-requisite for eventual use. Treatment failure and emergence of resistance can occur as a result of reduced availability of the drug at the desired site of action. Cellbased permeability assays such as Caco-2 cell monolayers serve as a model for predicting drug absorption and efflux, and provide an estimate of drug bioavailability. OBJECTIVE: Here we have studied the bi-directional transport of new anti-malarial compounds, artemisone and artemiside, as well as reference compounds, namely the known anti-malarial drug artemether, and caffeine and atenolol. METHODS: The Caco-2 cell monolayer model was used to assess the membrane permeation properties of these compounds, and to identify if they are subject to P-gp associated efflux, in the presence and absence of verapamil. The effect of piperine on the transport of the compounds that were identified to be P-gp substrates was also assessed. Samples withdrawn from the acceptor chambers at pre-determined time intervals were analysed by means of high-performance liquid chromatography (HPLC). RESULTS: Transport results in terms of the absorptive direction revealed that artemisone and artemether had low absorption rates relative to the reference compounds. It was further demonstrated that artemisone is slightly effluxed, and although both artemether and artemiside were susceptible to P-gp mediated efflux, it appears that other efflux proteins may also be involved. CONCLUSION: The low permeability of anti-malarial drugs must be borne in mind during development of effective dosage regimens of new drugs.

Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial.

Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received l-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications. The pre-defined primary outcome was change in plasma methylfolate at 12 weeks. Secondary outcomes included change in symptoms (Positive and Negative Syndrome Scale (PANSS), Scale for Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia), cognition (Measurement and Treatment Research to Improve Cognition in Schizophrenia composite) and three complementary magnetic resonance imaging measures (working memory-related activation, resting connectivity, cortical thickness). Primary, mixed model, intent-to-treat analyses covaried for six genetic variants in the folate pathway previously associated with symptom severity and/or response to folate supplementation. Analyses were repeated without covariates to evaluate dependence on genotype. Compared with placebo, l-methylfolate increased plasma methylfolate levels (d=1.00, P=0.0009) and improved PANSS Total (d=0.61, P=0.03) as well as PANSS Negative and General Psychopathology subscales. Although PANSS Total and General Psychopathology changes were influenced by genotype, significant PANSS Negative changes occurred regardless of genotype. No treatment differences were seen in other symptom rating scales or cognitive composite scores. Patients receiving l-methylfolate exhibited convergent changes in ventromedial prefrontal physiology, including increased task-induced deactivation, altered limbic connectivity and increased cortical thickness. In conclusion, l-methylfolate supplementation was associated with salutary physiological changes and selective symptomatic improvement in this study of schizophrenia patients, warranting larger clinical trials. ClinicalTrials.gov, NCT01091506.

Dietary tofu intake and long-term risk of death from stroke in a general population.

BACKGROUND & AIM: Although dietary soy intake is linked with health benefits, a relation with stroke has not been established. The present study examined the association between the intake of tofu, the richest source of dietary soy, with stroke mortality in a general population cohort of Japanese men and women. METHODS: Data comprise 9244 Japanese enrolled in the National Nutrition Survey of Japan in 1980. Participants were free of cardiovascular disease and followed for 24 years. Dietary intake was estimated from 3-day weighed food records. Multivariable Cox regression models were used to estimate hazard ratios across levels of tofu intake. RESULTS: During follow-up, there were 417 deaths due to stroke (88 cerebral hemorrhage [CH], 245 cerebral infarction [CI], and 84 of other subtypes). Among all men, and in women aged 65 years or more, tofu intake was unrelated to each form of stroke. For young women (<65 years of age), a significantly lower risk of CH in the top versus bottom quartile of tofu intake was observed (Multivariable-adjusted HR = 0.26, 95% CI: 0.08-0.85). CONCLUSIONS: In this large prospective study with long follow-up of Japanese men and women, consumption of tofu was unrelated to the risk of stroke except for CH in women <65 years of age. Whether the association in younger women is real or due to chance alone warrants further study.

A spatial and temporal analysis of paediatric central nervous system infections from 2005 to 2015 in Ho Chi Minh City, Vietnam.

Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.

Bio-electrochemical reactors using AMI-7001S and CMI-7000S membranes as separators for silver recovery and power generation.

Bioelectrochemical reactors using AMI-7001S and CMI-7000S membranes were investigated for silver recovery and power generation. High silver removal (83.73-92.50%) and columbic efficiency (11.50-19.89%) were obtained in CMI-based reactor after 24h, although, some diffusion of Ag+ ions was observed. In contrast, substrate loss was found in AMI-based reactor, which caused low overall performance. At an initial Ag+ concentration 2000mg/L, a maximum power density of 5396mW/m3 and 3385mW/m3 were obtained in CMI and AMI-based reactor, respectively. Under SEM analysis, different morphologies of metallic silver deposits were detected on the cathode surfaces, and was confirmed by EDX and XRD technique. High diversity of anodic microbial communities were also found, in which Firmulates, Proteobacteria, and Bateroidetes were dominant phyla. Geobacter sp. and other exoelectrogens could be detected while no Shewanella-like sequences were retrieved. The study suggests that CMI-7000S showed better performance when compared to AMI-7001S at the same operational conditions.