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Previous research in US populations has found associations between disaster-related variables, psychological variables, and post-disaster increases in smoking and alcohol use. To date, no research has examined this association in an international population of disaster exposed individuals. Data used in this study were drawn from a larger study involving a two-wave assessment of a disaster-affected sample of Vietnamese citizens ( N = 798). Interviews were conducted to assess the effects of mental health variables and typhoon related variables on reported increases in alcohol use and cigarette smoking. Results indicate that post-disaster increases in smoking were associated with post-disaster diagnosis of generalized anxiety disorder. Post-disaster increases in alcohol use were associated with posttraumatic stress disorder and panic disorder. None of the typhoon-characteristics were significantly associated with increases in substance use. Implications for mental health providers and future research directions are discussed. [ABSTRACT FROM AUTHOR]

Ectonucleotide pyrophosphate phosphodiesterase type II (ENPP2), also known as Autotaxin (ATX), is an enzyme present in blood circulation that converts lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA). While LPA has been demonstrated to play diverse roles in skeletal myogenesis, mainly through in vitro studies, the role of ENPP2 in skeletal myogenesis has not been determined. We previously found that Enpp2 is induced by a positive WNT/β-Catenin signaling regulator, R-spondin2 (RSPO2), in C2C12 myoblast cells. As RSPO2 promotes myogenic differentiation via the WNT/β-Catenin signaling pathway, we hypothesized that ENPP2 may act as a key mediator for the crosstalk between WNT and LPA signaling during myogenic differentiation. Herein, we found that ENPP2 function is essential for myogenic differentiation in C2C12 cells. Pharmacological ENPP2 inhibitors or RNAi-mediated Enpp2 gene knockdown severely impaired the myogenic differentiation, including the cell fusion process, whereas administration of the recombinant ENPP2 protein enhanced myogenic differentiation. Consistent with the in vitro results, mice lacking the Enpp2 gene showed a disrupted muscle regeneration after acute muscle injury. The size of newly regenerated myofibers in Enpp2 mutant muscle was significantly reduced compared with wild-type regenerated muscle. Modified expression patterns of myogenic markers in Enpp2 mutant muscle further emphasized the impaired muscle regeneration process. Finally, we convincingly demonstrate that the Enpp2 gene is a direct transcriptional target for WNT/β-Catenin signaling. Functional TCF/LEF1 binding sites within the upstream region of Enpp2 gene were identified by chromatin immunoprecipitation using anti-β-Catenin antibodies and reporter assay. Our study reveals that ENPP2 is regulated by WNT/β-Catenin signaling and plays a key positive role in myogenic differentiation. [ABSTRACT FROM AUTHOR]

Capacitance of biological membranes is determined by the properties of the lipid portion of the membrane as well as the morphological features of a cell. In neurons, membrane capacitance is a determining factor of synaptic integration, action potential propagation speed, and firing frequency due to its direct effect on the membrane time constant. Besides slow changes associated with increased morphological complexity during postnatal maturation, neuronal membrane capacitance is considered a stable, non-regulated, and constant magnitude. Here we report that, in two excitatory neuronal cell types, pyramidal cells of the mouse primary visual cortex and granule cells of the hippocampus, the membrane capacitance significantly changes between the start and the end of a daily light-dark cycle. The changes are large, nearly 2-fold in magnitude in pyramidal cells, but are not observed in cortical parvalbumin-expressing inhibitory interneurons. Consistent with daily capacitance fluctuations, the time window for synaptic integration also changes in pyramidal cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Tyrosine kinase inhibitors (TKIs) are currently the standard therapy for patients with non-small cell lung cancer (NSCLC) bearing mutations in epidermal growth factor receptor (EGFR). Unfortunately, drug-acquired resistance is inevitable due to the emergence of new mutations in EGFR. Moreover, the TKI treatment is associated with severe toxicities due to the unspecific inhibition of wild-type (WT) EGFR. Thus, treatment that is customised to an individual's genetic alterations in EGFR may offer greater therapeutic benefits for patients with NSCLC., Methods: In this study, we demonstrate a new therapeutic strategy utilising customised antisense oligonucleotides (ASOs) to selectively target activating mutations in the EGFR gene in an individualised manner that can overcome drug-resistant mutations. We use extracellular vesicles (EVs) as a vehicle to deliver ASOs to NSCLC cells., Findings: Specifically guided by the mutational profile identified in NSCLC patients, we have successfully developed ASOs that selectively inhibit point mutations in the EGFR gene, including L858R and T790M, while sparing the WT EGFR. Delivery of the EGFR-targeting ASOs by EVs significantly reduced tumour growth in xenograft models of EGFR-L858R/T790M-driven NSCLC. Importantly, we have also shown that EGFR-targeting ASOs exhibit more potent anti-cancer effect than TKIs in NSCLC with EGFR mutations, effectively suppressing a patient-derived TKI-resistant NSCLC tumour., Interpretation: Overall, by harnessing the specificity and efficacy of ASOs, we present an effective and adaptable therapeutic platform for NSCLC treatment., Funding: This study was funded by Singapore's Ministry of Health (NMRC/OFIRG/MOH-000643-00, OFIRG21nov-0068, NMRC/OFLCG/002-2018, OFYIRG22jul-0034), National Research Foundation (NRF-NRFI08-2022, NRF-CRP22-2019-0003, NRF-CRP23-2019-0004), A∗STAR, and Ministry of Education., Competing Interests: Declaration of interests M.T.N.L is a cofounder and advisor of Carmine Therapeutics, which develops gene therapy, and has a patent relating to Vesicle-Based Compositions and Uses Thereof. Carmine Therapeutics provides a proprietary transfection reagent required for loading of ASOs into EVs used in this study. C.D.P has a patent relating to Vesicle-Based Compositions and Uses Thereof. M.K.J has received consulting fees from Jotbody HK Ltd and patent royalties from Carmine Therapeutics. He also has two pending patents filed with NUS ILO and NTUITIVE pertaining to EVs. B.C.G has a patent relating to Modulation of Signal Transducer and Activator of Transcription 3 (STAT3) Expression. D.S.W.T has received grants from ACM Biolabs, Amgen, Astra Zeneca, Bayer and Pfizer, consulting fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, DKSH, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche and Takeda, honoraria from Amgen, Bayer, Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda, BeiGene, Regeneron and Zymeworks. He has also obtained support for travel from Bayer, Merck, Pfizer, Regeneron and Zymeworks. Other authors declare no competing financial interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Body core temperature (T c ) monitoring is crucial for minimizing heat injury risk. However, validated strategies are invasive and expensive. Although promising, aural canal temperature (T ac ) is susceptible to environmental influences. This study investigated whether incorporation of external auricle temperature (T ea ) into an ear-based T c algorithm enhances its accuracy during multiple heat stress conditions. Twenty males (mean ± SD; age = 25 ± 3 years, BMI = 21.7 ± 1.8, body fat = 12 ± 3%, maximal aerobic capacity (VO 2max ) = 64 ± 7 ml/kg/min) donned an ear-based wearable and performed a passive heating (PAH), running (RUN) and brisk walking trial (WALK). PAH comprised of immersion in hot water (42.0 ± 0.3 °C). RUN (70 ± 3%VO 2max ) and WALK (50 ± 10%VO 2max ) were conducted in an environmental chamber (T db  = 30.0 ± 0.2 °C, RH = 71 ± 2%). Several T c models, developed using T ac , T ea and heart rate, were validated against gastrointestinal temperature. Inclusion of T ea as a model input improved the accuracy of the ear-based T c algorithm. Our best performing model (T rf3 ) displayed good group prediction errors (mean bias error = - 0.02 ± 0.26 °C) but exhibited individual prediction errors (percentage target attainment ± 0.40 °C = 88%) that marginally exceeded our validity criterion. Therefore, T rf3 demonstrates potential utility for group-based T c monitoring, with additional refinement needed to extend its applicability to personalized heat strain monitoring., (© 2024. The Author(s).)

Nanoparticles (NPs) hold great potential as therapeutics, particularly in the realm of drug delivery. They are effective at functional cargo delivery and offer a great degree of amenability that can be used to offset toxic side effects or to target drugs to specific regions in the body. However, there are many challenges associated with the development of NP-based drug formulations that hamper their successful clinical translation. Arguably, the most significant barrier in the way of efficacious NP-based drug delivery systems is the tedious and time-consuming nature of NP formulation-a process that needs to account for downstream effects, such as the onset of potential toxicity or immunogenicity, in vivo biodistribution and overall pharmacokinetic profiles, all while maintaining desirable therapeutic outcomes. Computational and AI-based approaches have shown promise in alleviating some of these restrictions. Via predictive modeling and deep learning, in silico approaches have shown the ability to accurately model NP-membrane interactions and cellular uptake based on minimal data, such as the physicochemical characteristics of a given NP. More importantly, machine learning allows computational models to predict how specific changes could be made to the physicochemical characteristics of a NP to improve functional aspects, such as drug retention or endocytosis. On a larger scale, they are also able to predict the in vivo pharmacokinetics of NP-encapsulated drugs, predicting aspects such as circulatory half-life, toxicity, and biodistribution. However, the convergence of nanomedicine and computational approaches is still in its infancy and limited in its applicability. The interactions between NPs, the encapsulated drug and the body form an intricate network of interactions that cannot be modeled with absolute certainty. Despite this, rapid advancements in the area promise to deliver increasingly powerful tools capable of accelerating the development of advanced nanoscale therapeutics. Here, we describe computational approaches that have been utilized in the field of nanomedicine, focusing on approaches for NP design and engineering., Competing Interests: ML was scientific co-founders and advisors of Carmine Therapeutics. MP was employed by Jotbody (HK) Pte Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jayasinghe, Lee, Tran, Tan, Chew, Yeo, Loh, Pirisinu and Le.)

Phytoremediation and advanced oxidation processes are among the most promising techniques for removing organic pollutants from soils. A field trial was performed for six months to evaluate the effect of nano-Fe 3 O 4 on the degradation of organochlorine pesticide residues including Lindane, p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (DDE), and p,p'-dichlorodiphenyldichloroethane (DDD) in pesticide-contaminated soils in the presence of vetiver in Bac Giang province, Vietnam. Vetiver was planted in three zones with different nano-Fe 3 O 4 concentrations. Soil samples from each zone were periodically collected to determine the remaining concentrations of selected organochlorine pesticides via gas chromatography-electron capture detector. Results indicated that the total DDT concentrations in the examined soil were 1.9-13 times higher than the permissible threshold level (10 µg g -1 ) established by the national technical regulation on pesticide residues in soil. The (p,p'-DDE + p,p'-DDD)/p,p'-DDT ratios ranged from 13.5 to 114, indicating the absence of recent inputs of technical DDTs at the study area. DDT dechlorination mainly occurred under aerobic pathways to form DDE. Furthermore, DDE degradation in soil was adequately described by the pseudo-first-order kinetics model (R 2  > 0.892). In the presence of vetiver, the rate constants of DDE degradation were 0.264, 0.350, and 0.434 month -1 with 0, 25, and 100 mg kg -1 of added nano-Fe 3 O 4 , respectively, indicating that the degradation of DDE correlated positively with Fe 3 O 4 concentration in the soil. Additionally, the presence of vetiver and nano-Fe 3 O 4 in the soil increased DDT removal rates, which might be linked to the involvement of Fenton/Fenton-like reactions.

Aging often impairs cognitive functions associated with the medial temporal lobe (MTL). Anatomical studies identified the layer II pyramidal cells of the lateral entorhinal cortex (LEC) as one of the most vulnerable elements within the MTL. These cells provide a major excitatory input to the dentate gyrus hippocampal subfield through synapses onto granule cells and onto local inhibitory interneurons, and a fraction of these contacts are lost in aged individuals with impaired learning. Using optogenetics, we evaluated the functional status of the remaining inputs in an outbred rat model of aging that distinguishes between learning-impaired and learning-unimpaired individuals. We found that aging affects the presynaptic and postsynaptic strength of the LEC inputs onto granule cells. However, the magnitude of these changes was similar in impaired and unimpaired rats. In contrast, the recruitment of inhibition by LEC activation was selectively reduced in the aged impaired subjects. These findings are consistent with the notion that the preservation of an adequate balance of excitation and inhibition is crucial to maintaining proficient memory performance during aging., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Twelve B1 cluster mycobacteriophages were isolated from soil samples collected in Philadelphia, PA, USA, using Mycobacterium smegmatis mc 2 155 as a host, and were sequenced. The genome sequences range in size from 66,887 bp to 68,953 bp in length and have between 99 and 105 putative protein-coding genes.

Hyperactivity within the hippocampal formation, frequently observed in aged individuals, is thought to be a potential contributing mechanism to the memory decline often associated with aging. Consequently, we evaluated the postsynaptic strength of excitatory and inhibitory synapses in the granule cells of the dentate gyrus and CA1 pyramidal cells of a rat model of aging, in which each individual was behaviorally characterized as aged impaired (AI) or aged unimpaired (AU, with performance comparable to young (Y) individuals). In hippocampal slices of these 3 aged groups (Y, AI, AU), we found that compared to the young, the miniature excitatory and inhibitory currents (mEPSCs and mIPSCs) were larger in amplitude in the granule cells of the AU group and smaller in the AI group. In contrast, in CA1 cells, neither the mEPSCs nor the mIPSCs were affected by age, whereas the extrasynaptic conductance responsible for tonic inhibition was selectively enhanced in CA1 cells of AU individuals. Tonic inhibition conductance was not affected by age in the granule cells. These results support the notion that upregulation of synaptic inhibition could be a necessary condition for the maintenance of performance during aging. These findings also underscore the notions that successful aging requires adaptive upregulation, not merely the preservation of youthful functionality, and that age effects are not homogeneous across hippocampal subfields., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Models of firing rate homeostasis such as synaptic scaling and the sliding synaptic plasticity modification threshold predict that decreasing neuronal activity (for example, by sensory deprivation) will enhance synaptic function. Manipulations of cortical activity during two forms of visual deprivation, dark exposure (DE) and binocular lid suture, revealed that, contrary to expectations, spontaneous firing in conjunction with loss of visual input is necessary to lower the threshold for Hebbian plasticity and increase miniature excitatory postsynaptic current (mEPSC) amplitude. Blocking activation of GluN2B receptors, which are upregulated by DE, also prevented the increase in mEPSC amplitude, suggesting that DE potentiates mEPSCs primarily through a Hebbian mechanism, not through synaptic scaling. Nevertheless, NMDA-receptor-independent changes in mEPSC amplitude consistent with synaptic scaling could be induced by extreme reductions of activity. Therefore, two distinct mechanisms operate within different ranges of neuronal activity to homeostatically regulate synaptic strength.

Purpose: The aim of this study is to investigate the mechanisms of interactions between TGF-β and Wnt/β-catenin pathways that induce and regulate EMT and promote breast cancer cells to become resistant to treatment., Methods: The effect of TGF-β on Wnt/β-catenin signaling pathway was examined by using a human Wnt/β-catenin-regulated cDNA plate array and western blot analysis. The interaction of Twist at promoter of Wnt3 was examined by chromatin immunoprecipitation (ChIP) assay. Secreted Wnt3 level was determined by ELISA assay., Results: HER2-overexpressing breast cancer cells treated with TGF-β have a reduced response to trastuzumab and exhibited EMT-like phenotype. The TGF-β-induced EMT in HER2-cells was concordant with upregulation of Wnt3 and β-catenin pathways. The TGF-β-induced induction of Wnt3 during EMT was found to be Smad3-dependent. ChIP analysis identified occupancy of Twist at promoter region of Wnt3. Knock-down of Twist by shRNA confirmed the significance of Twist in response to TGF-β regulating Wnt3 during EMT. Subsequently, TGF-β-induced matrix metalloproteinases, MMP1, MMP7, MMP9, MMP26, Vascular endothelial growth factors (VEGF), and activation of Wnt/β-catenin signaling were repressed by the shRNA treatment. TGF-βR1 ALK5 kinase inhibitor, A83-01 can effectively prevent the TGF-β-induced Twist and Wnt3. Co-treating A83-01 and trastuzumab inhibited TGF-β-induced cell invasion significantly in both trastuzumab responsive and resistant cells., Conclusions: Our data demonstrated an important interdependence between TGF-β and Wnt/β-catenin pathways inducing EMT in HER2-overexpressing breast cancer cells. Twist served as a linkage between the two pathways during TGF-β-induced EMT. A83-01 could inhibit the TGF-β-initiated pathway interactions and enhance HER2-cells response to trastuzumab treatment.

Baculoviruses are recognized as viral workhorses of biotechnology, being used for production of vaccines, complex recombinant proteins, gene delivery vectors' and safe biological pesticides. Improving production yields and understanding the interactions of the virus and its host cell are important aspects of ensuring baculovirus-based processes are commercially competitive. This study aims at potential optimization of host cells used in in vitro virus production by systemically investigating changes in host gene expression in response to virus replication and transcription inside host cells. The study focuses on in vitro interactions of the Helicoverpa armigera virus with Helicoverpa zea insect cells. We used 22 genome-wide microarrays to simultaneously measure both virus and host genes in infected cells in multiple batch suspension cultures, representing high- and low-producing infection conditions. Among 661 differentially expressed genes, we identified a core set of 59 host genes consistently overexpressed post infection, with strong overrepresentation of genes involved in retrotransposition, protein processing in the endoplasmic reticulum, and ubiquitin-mediated proteolysis. Applying a whole genome correlation network analysis to link gene expression to productivity, we revealed 18 key genes significantly associated to virus yield. In addition, this study is among the first to perform a genome-wide expression study for a major baculovirus group II strain, the H. armigera virus, extending current understanding of baculovirus-insect interactions, which mainly focuses on group I viruses.

The phenomenon of the reduction in the cell-specific yield with increasing infection cell density (ICD), the cell density effect, is one of the main hurdles for improving virus yields in vitro. In the current study, the reduction in cell-specific yields (viral DNA [vDNA], polyhedrin mRNA and occlusion body [OB]) with increasing ICD for Helicoverpa armigera nucleopolyhedrovirus (HearNPV)-infected HzAM1 (Helicoverpa zea) insect cells has been investigated. HzAM1 cells were propagated in Sf900™ III serum-free medium and synchronously infected with wild-type HearNPV at various ICDs of 0.5-5 × 10(6) cells/mL at an MOI of 5 PFU/cell. Infection was conducted either in the original medium or in fresh medium. As found previously for Sf9 and High Five cells, there were negative correlations between the three key virus infection indicators (vDNA, mRNA and OB) and the peak cell density (PCD). Generally, the yield decline with increasing PCD was most pronounced for OB, followed by mRNA, and was more moderate for vDNA. The decline was significantly reduced, but not totally arrested, when fresh medium was used. There were also strong correlations between OB and mRNA, mRNA and vDNA, and OB and vDNA levels. These results suggest that the reduction in baculovirus yield (OB) at high PCDs is associated with limitations during the upstream processes of replication and transcription together with limitations during protein translation. Furthermore, the peak protein productivity per unit of cell volume in the HzAM1/HearNPV system was shown to be higher than that of the Sf9/rAcMNPV system, but lower than that of the High Five/rAcMNPV system.

An important factor that may affect the severity and time of onset of Alzheimer's disease (AD) is chronic stress. Epidemiological studies report that chronically stressed individuals are at an increased risk for developing AD. The purpose of this study was to reveal whether chronic psychosocial stress could hasten the appearance of AD symptoms including changes in basal levels of cognition-related signaling molecules in subjects who are at risk for the disease. We investigated the effect of chronic psychosocial stress on basal levels of memory-related signaling molecules in area CA1 of subclinical rat model of AD. The subclinical symptomless rat model of AD was induced by osmotic pump continuous intracerebroventricular (ICV) infusion of 160 pmol/day Aβ1-42 for 14 days. Rats were chronically stressed using the psychosocial stress intruder model. Western blot analysis of basal protein levels of important signaling molecules in hippocampal area CA1 showed no significant difference between the subclinical AD rat model and control rat. Following six weeks of psychosocial stress, molecular analysis showed that subclinical animals subjected to stress have significantly reduced basal levels of p-CaMKII and decreased p-CaMKII/t-CaMKII ratio as well as decreased basal levels of p-CREB, total CREB, and BDNF. The present results suggest that these changes in basal levels of signaling molecules may be responsible for impaired learning, memory, and LTP in this rat model, which support the proposition that chronic stress may accelerate the emergence of AD in susceptible individuals.

The phenomenon of the cell density effect is not readily explained by an obvious nutrient limitation, and a recent study has suggested that for recombinant Autographa californica multiple nucleopolyhedrovirus (rAcMNPV)-infected Sf9 cells, a drop in messenger RNA (mRNA) levels may be sufficient to explain the cell density effect for this system. The current study aims to investigate the response in cell-specific yields (viral DNA (vDNA), LacZ mRNA and β-galactosidase (β-Gal) protein) with increasing infection cell density (ICD) for rAcMNPV-infected Hi5 cells, where the rAcMNPV expresses the β-Gal gene under control of the polyhedral promoter. Hi5 cells in suspension culture of Express Five® medium were synchronously infected with a rAcMNPV at multiple ICDs between 0.5 and 6 × 10(6) cells/mL and a multiplicity of infection of 10 plaque-forming units (PFU)/cell either in the original or fresh medium conditions. There were negative correlations between the three key virus infection indicators (vDNA, mRNA and β-Gal) and the peak cell density (PCD). However, unlike infected Sf9 cells, the yield decline started at the lowest PCD investigated (0.6 × 10(6) cells/mL). Generally, the yield decline with increasing PCD was most pronounced for β-Gal followed by mRNA and was more moderate for vDNA. The decline was significantly reduced but not totally arrested when fresh medium replacement was used. The results suggest that the reduction in recombinant protein-specific yields at high PCDs is associated with limitations during the up-stream processes of replication and transcription rather than entirely caused by limitations during translation. In addition, low production rates at late infection stages of moderate to high ICDs are a probable cause of the cell density effect.

The CA1 and dentate gyrus regions of the hippocampus are physically and functionally closely related but they react differently to insults. This study examined the effect of chronic psychosocial stress on the dentate gyrus of an at-risk (preclinical) rat model of Alzheimer's disease (subAβ rats). Chronic psychosocial stress was produced using a rat intruder model. The at-risk rat model of Alzheimer's disease was created by osmotic pump infusion of sub-pathological dose of Aβ (160 pmol Aβ1-42/day i.c.v) for 14 days. Electrophysiological methods were used to evoke and record early and late phase LTP in the dentate gyrus of anesthetized rats, and immunoblotting was used to measure levels of memory-related signaling molecules in the same region. Electrophysiological and molecular tests in the dentate gyrus showed that subAβ rats or stressed rats were not different from control rats. However, when the subAβ rats were chronically stressed, the combined treatments severely suppressed early phase LTP without affecting the late phase LTP of dentate gyrus. Additionally, in the chronically stressed subAβ rats the expected elevation of levels of phosphorylated CaMKII did not materialize after expression of early phase LTP suggesting impaired phosphorylation, which may explain the severely blocked early phase LTP., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: There are significant gaps in the literature on the prevalence of mental health problems and associated needs in Vietnam. A thorough understanding of culture-specific expressions of psychiatric distress is vital for the identification of the mental health needs of a community, and more research on the development and evaluation of culturally-sensitive mental health assessments is warranted. This study aims to evaluate the psychometric properties of the World Health Organization 20-item Self-Reporting Questionnaire (SRQ-20) in an epidemiologic study of Vietnamese adults., Methods: A latent variable modeling approach investigated the underlying factor structure of the SRQ-20 items. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted on SRQ-20 item-level data gathered from 4980 participants., Results: Based on scree plots and EFA results, two latent structures were deemed plausible and were subsequently subjected to further modeling. A bi-factor model (BFM) and a correlated three-factor model solution (Negative Affect, Somatic Complaints, and Hopelessness) provided reasonable fits. The BFM specifies a single dominant General Distress factor (all SRQ-20 items) with orthogonal group factors for the subsets of items: Negative Affect (9 items), Somatic Complaints (8 items), and Hopelessness (3 items). This model fit the data as well or better than the three-factor model. Results also showed differences in endorsement rates of SRQ-20 items among males and females., Conclusions: Study results provide an evaluation of the psychometric properties of a commonly used screening tool and offer insight into the presentation of mental distress in a representative sample of Vietnamese adults., (Published by Elsevier Inc.)

Metabolomics refer to the global analysis of small molecule metabolites in a biological system, and can be a powerful tool to elucidate and optimize cellular processes, particularly when integrated into a systems biology framework. Determining the endometabolome in cultured animal cells is especially challenging, due to the conflicting demands for rapid quenching of metabolism and retention of membrane integrity, while cells are separated from the complex medium. The challenge is magnified in virus infected cells due to increased membrane fragility. This paper describes an effective methodology for quantitative intracellular metabolite analysis of the baculovirus-insect cell expression system, an important platform for the production of heterologous proteins and baculovirus-based biopesticides. These two applications were represented by Spodoptera frugiperda (Sf9) and Helicoverpa zea (HzAM1) cells infected with recombinant Autographa californica and wild-type Helicoverpa armigera nucleopolyhedroviruses (AcMNPV and HaSNPV), respectively. Specifically, an ice-cold quenching solution comprising 1.1% w/v NaCl and 0.2% w/v Pluronic® F-68 (NaCl+P) was found to be efficacious in preserving cell viability and minimizing cell leakage during quenching and centrifugation-based washing procedures (prior to extraction using cold 50% v/v acetonitrile). Good recoveries of intracellular adenosine triphosphate, total adenosine phosphates and amino acids were obtained after just one wash step, for both uninfected and infected insect cells. The ability to implement wash steps is critical, as insect cell media are metabolites-rich, while infected insect cells are much more fragile than their uninfected counterparts. Hence, a promising methodology has been developed to facilitate endometabolomic analysis of insect cell-baculovirus systems for bioprocess optimization., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by increased deposition of beta-amyloid (Aβ) peptides and progressive cholinergic dysfunction in regions of the brain involved in learning and memory processing. In AD, progressive accumulation of Aβ peptide impairs nicotinic acetylcholine receptor (nAChR) function by an unknown mechanism believed to involve α(7)- and α(4)β(2)-nAChR blockade. The three approaches of the current study evaluated the effects of chronic nicotine treatment in the prevention of Aβ-induced impairment of learning and short-term memory. Rat AD model was induced by 14-day i.c.v. osmotic pump infusion of a 1:1 mixture of 300 pmol/day Aβ(1-40)/Aβ(1-42) or Aβ(40-1) (inactive peptide, control). The effect of nicotine (2 mg/(kg day)) on Aβ-induced spatial learning and memory impairments was assessed by evaluation of performance in the radial arm water maze (RAWM), in vivo electrophysiological recordings of early-phase long-term potentiation (E-LTP) in urethane-anesthetized rats, and immunoblot analysis to determine changes in the levels of beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), Aβ and memory-related proteins. The results indicate that 6 weeks of nicotine treatment reduced the levels of Aβ(1-40) and BACE1 peptides in hippocampal area CA1 and prevented Aβ-induced impairment of learning and short-term memory. Chronic nicotine also prevented the Aβ-induced inhibition of basal synaptic transmission and LTP in hippocampal area CA1. Furthermore, chronic nicotine treatment prevented the Aβ-induced reduction of α(7)- and α(4)-nAChR. These effects of nicotine may be due, at least in part, to upregulation of brain derived neurotropic factor (BDNF)., (Copyright © 2009 Elsevier Inc. All rights reserved.)

In 2006, typhoon Xangsane disrupted a large-scale multi-agency mental health study of 4,982 individuals in the DaNang province of Vietnam. Following this disaster, 795 of the original 4,982 participants were randomly assigned to be re-interviewed by either a medical doctor or a lay interviewer using structured clinical interviews to determine prevalence of lifetime and post-typhoon post-traumatic stress disorder (PTSD), major depressive disorder (MDD), panic disorder (PD), and generalized anxiety disorder (GAD) according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (APA, 1994). The aim of the present study was to determine if prevalence of disorders differed by interviewer type. Bivariate analyses and multivariable analyses, as well as internal reliability estimates, all indicated no significant differences between the medical doctor interviewers versus the lay interviewers. This held for both lifetime prevalence as well as post-typhoon prevalence of disorders. This study has implications for epidemiologic studies, as it indicates that with adequate training, the use of lay interviewers may be a valid means of data collection.

Although it is generally accepted that Abeta contributes to the pathogenesis of Alzheimer's disease (AD), other factors that impact the severity and time of onset of the disease are not well known. Aside from genetic factors, environmental factors such as stress may also play a critical role in the manifestation of AD. The present study examined the effect of chronic psychosocial stress in an at-risk, subthreshold Abeta (subAbeta) rat model of AD by three approaches: learning and memory tests in the radial arm water maze, electrophysiological recordings of long-term potentiation (LTP) in anesthetized rats, and immunoblot analysis of learning- and memory-related signaling molecules. Chronic psychosocial stress was induced using a rat intruder model. The subAbeta rat model of AD was induced by continuous i.c.v. infusion of 160 pmol/day Abeta(1-42) via a 14-day osmotic pump. Behavioral tests and electrophysiological recordings showed that subAbeta rats were not significantly different from control rats. However, chronically stressed subAbeta rats showed more significant impairment of cognitive functions and early-phase LTP (E-LTP) than that caused by stress alone. Molecular analysis of essential signaling molecules after induction of E-LTP revealed an increase in the levels of p-CaMKII in control as well as subAbeta infused rats, but not in stressed or stressed at-risk rats. In addition, compared to unstimulated control, the levels of both total CaMKII and calcineurin were increased in all stimulated animals groups after HFS. These findings suggest that the stress-induced alterations may accelerate the impairment of cognition and synaptic plasticity in individuals "at-risk" for AD., (2010 Elsevier Inc. All rights reserved.)

In 2006, typhoon Xangsane struck Vietnam and disrupted a large-scale mental health needs analysis in the Da Nang province of Vietnam. Recruitment of new participants was halted, and the design of study was altered to that of a pre-/post-event investigation in which 798 of the original 4,982 participants were re-interviewed. This produced the first pre-post disaster epidemiological study. Specifically, risk and protective factors were evaluated with respect to probable mental health "caseness" on the bases of the World Health Organization Short Response Questionnaire (SRQ-20) 7/8 cutoff (i.e., scores of 8 or more). Caseness prevalence was 20.7% pre-disaster and 27.1% post-disaster. Specific risk factors associated with mental health caseness included poor health, extreme peri-disaster fear, and experienced injury. Religious affiliation appeared to be a protective factor. In contrast to US samples, gender was not predictive of outcome.

Mullerian inhibiting substance (MIS), a member of the TGFbeta superfamily, causes regression of the Mullerian duct in male embryos. The presence of MIS type II and type I receptors in tissues and cell lines derived from the prostate suggests that prostate is a likely target for MIS. In this report, we demonstrate that MIS inhibits androgen-stimulated growth of LNCaP cells and decreases their survival in androgen-deprived medium by preventing cell cycle progression and inducing apoptosis. Expression of dominant-negative Smad1 reversed the ability of MIS to decrease LNCaP cell survival in androgen-deprived medium but not androgen-stimulated growth, whereas abrogation of nuclear factor-kappaB (NFkappaB) activation ablated the suppressive effects of MIS on both androgen-stimulated growth and androgen-independent survival. The effect of MIS on androgen-induced growth was not due to changes in androgen receptor expression. However, MIS suppressed androgen-stimulated transcription of prostate-specific antigen; ablation of NFkappaB activation reversed MIS-mediated suppression of prostate-specific antigen. These observations suggest that MIS regulates androgen-induced gene expression and growth in prostate cancer cells through a NFkappaB-dependent but Smad1-independent mechanism. Thus, MIS, in addition to potentially regulating prostate growth indirectly by suppressing testicular testosterone synthesis, may also be a direct regulator of androgen-induced gene expression and growth in the prostate at the cellular level.