Factors affecting loneliness among left-behind children.

BACKGROUND: In Vietnam, research on the impact of parental migration on left-behind children (LBC) has discussed various dimensions of the subject such as subjective well-being, emotional states, social skills, self-esteem and nutrition of LBC. However, there are still gaps in studies on loneliness among LBC in Vietnam. The study aims to explore the status of loneliness in LBC, including associated protective and risk factors, to make suggestions on preventive measures against LBC's loneliness. PARTICIPANTS AND PROCEDURE: The conveniently selected sample includes 439 LBC in 4 Vietnamese provinces: Thai Nguyen, Bac Ninh, Thai Binh and Nghe An. The mean age is 12.73 (SD = 1.68). Female children account for 47.80%. The Children's Loneliness Scale was employed in the study. RESULTS: The total loneliness score of LBC is 28.62 (SD = 9.40), 95% CI: 27.75-29.48. Perceived social support from friends, caregivers and resilience factors of affect control (RAC), family support (RFS) and help-seeking (RHS) are protective factors for loneliness of LBC, with regression coefficient of -.27, -.18, -.11, -.11 and -.09 respectively. CONCLUSIONS: Perceived social support from friends, care-giving attachment and resilience factors of RAC, RFS, and RHS are protective factors for LBC against loneliness. Parents, teachers and guardians are encouraged to have a close connection with LBC, provide adequate care giving; and create a supportive environment for LBC in pursuing healthy peer relationships and train/improve children's skills to strengthen their resilience.

Endogenous Protein-Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex.

NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein-protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics. The current study investigated protein-protein interactions specific to the wild-type and the most prevalent NPC1 mutation (NPC1I1061T) while filtering out any protein interactor identified in the Npc1-/- mouse model. Additionally, the results were matched across the two species to map the parallel interactome of wild-type and mutant NPC1I1061T. Most of the identified wild-type NPC1 interactors were related to cytoskeleton organization, synaptic vesicle activity, and translation. We found many putative NPC1 interactors not previously reported, including two SCAR/WAVE complex proteins that regulate ARP 2/3 complex actin nucleation and multiple membrane proteins important for neuronal activity at synapse. Moreover, we identified proteins important in trafficking specific to wild-type and mutant NPC1I1061T. Together, the findings are essential for a comprehensive understanding of NPC1 biological functions in addition to its classical role in sterol efflux.

Comparative Hippocampal Proteome and Phosphoproteome in a Niemann-Pick, Type C1 Mouse Model Reveal Insights into Disease Mechanisms.

Niemann-Pick disease, type C (NPC) is a neurodegenerative, lysosomal storage disorder in individuals carrying two mutated copies of either the NPC1 or NPC2 gene. Consequently, impaired cholesterol recycling and an array of downstream events occur. Interestingly, in NPC, the hippocampus displays lysosomal lipid storage but does not succumb to progressive neurodegeneration as significantly as other brain regions. Since defining the neurodegeneration mechanisms in this disease is still an active area of research, we use mass spectrometry to analyze the overall proteome and phosphorylation pattern changes in the hippocampal region of a murine model of NPC. Using 3 week old mice representing an early disease time point, we observed changes in the expression of 47 proteins, many of which are consistent with the previous literature. New to this study, changes in members of the SNARE complex, including STX7, VTI1B, and VAMP7, were identified. Furthermore, we identified that phosphorylation of T286 on CaMKIIα and S1303 on NR2B increased in mutant animals, even at the late stage of the disease. These phosphosites are crucial to learning and memory and can trigger neuronal death by altering protein-protein interactions.

Discovery of a Small-Molecule Modulator of the Autophagy-Lysosome Pathway That Targets Lamin A/C and LAMP1, Induces Autophagic Flux, and Affects Lysosome Positioning in Neurons.

Autophagy is a major catabolic degradation and recycling process that maintains homeostasis in cells and is especially important in postmitotic neurons. We implemented a high-content phenotypic assay to discover small molecules that promote autophagic flux and completed target identification and validation studies to identify protein targets that modulate the autophagy pathway and promote neuronal health and survival. Efficient syntheses of the prioritized compounds were developed to readily access analogues of the initial hits, enabling initial structure-activity relationship studies to improve potency and preparation of a biotin-tagged pulldown probe that retains activity. This probe facilitated target identification and validation studies through pulldown and competition experiments using both an unbiased proteomics approach and western blotting to reveal Lamin A/C and LAMP1 as the protein targets of compound RH1115. Evaluation of RH1115 in neurons revealed that this compound induces changes to LAMP1 vesicle properties and alters lysosome positioning. Dysfunction of the autophagy-lysosome pathway has been implicated in a variety of neurodegenerative diseases, including Alzheimer's disease, highlighting the value of new strategies for therapeutic modulation and the importance of small-molecule probes to facilitate the study of autophagy regulation in cultured neurons and in vivo.

Comparative genomics of Nocardia seriolae reveals recent importation and subsequent widespread dissemination in mariculture farms in the South Central Coast region, Vietnam.

Between 2010 and 2015, nocardiosis outbreaks caused by Nocardia seriolae affected many permit farms throughout Vietnam, causing mass fish mortalities. To understand the biology, origin and epidemiology of these outbreaks, 20 N. seriolae strains collected from farms in four provinces in the South Central Coast region of Vietnam, along with two Taiwanese strains, were analysed using genetics and genomics. PFGE identified a single cluster amongst all Vietnamese strains that was distinct from the Taiwanese strains. Like the PFGE findings, phylogenomic and SNP genotyping analyses revealed that all Vietnamese N. seriolae strains belonged to a single, unique clade. Strains fell into two subclades that differed by 103 SNPs, with almost no diversity within clades (0-5 SNPs). There was no association between geographical origin and subclade placement, suggesting frequent N. seriolae transmission between Vietnamese mariculture facilities during the outbreaks. The Vietnamese strains shared a common ancestor with strains from Japan and China, with the closest strain, UTF1 from Japan, differing by just 220 SNPs from the Vietnamese ancestral node. Draft Vietnamese genomes range from 7.55 to 7.96 Mbp in size, have an average G+C content of 68.2 % and encode 7 602-7958 predicted genes. Several putative virulence factors were identified, including genes associated with host cell adhesion, invasion, intracellular survival, antibiotic and toxic compound resistance, and haemolysin biosynthesis. Our findings provide important new insights into the epidemiology and pathogenicity of N. seriolae and will aid future vaccine development and disease management strategies, with the ultimate goal of nocardiosis-free aquaculture.

Characterization of the Cerebrospinal Fluid Proteome in Patients with Fragile X-Associated Tremor/Ataxia Syndrome.

Fragile X-associated tremor/ataxia syndrome (FXTAS), first described in 2001, is a neurodegenerative and movement disorder, caused by a premutation in the fragile X mental retardation 1 (FMR1) gene. To date, the biological mechanisms causing this condition are still not well understood, as not all premutation carriers develop FXTAS. To further understand this syndrome, we quantitatively compared the cerebrospinal fluid (CSF) proteome of FXTAS patients with age-matched controls using mass spectrometry. We identified 415 proteins of which 97 were altered in FXTAS patients. These proteins suggest changes in acute phase response signaling, liver X receptor/ retinoid X receptor (LXR/RXR) activation, and farnesoid X receptor (FXR)/RXR activation, which are the main pathways found to be affected. Additionally, we detected changes in many other proteins including amyloid-like protein 2, contactin-1, afamin, cell adhesion molecule 4, NPC intracellular cholesterol transporter 2, and cathepsin B, that had been previously noted to hold important roles in other movement disorders. Specific to RXR pathways, several apolipoproteins (APOA1, APOA2, APOA4, APOC2, and APOD) showed significant changes in the CSF of FXTAS patients. Lastly, CSF parameters were analyzed to investigate abnormalities in blood brain barrier function. Correlations were observed between patient albumin quotient values, a measure of permeability, and CGG repeat length as well as FXTAS rating scale scores.

Mass spectrometry-based lipid analysis and imaging.

Mass spectrometry imaging (MSI) is a powerful tool for in situ mapping of analytes across a sample. With growing interest in lipid biochemistry, the ability to perform such mapping without antibodies has opened many opportunities for MSI and lipid analysis. Herein, we discuss the basics of MSI with particular emphasis on MALDI mass spectrometry and lipid analysis. A discussion of critical advancements as well as protocol details are provided to the reader. In addition, strategies for improving the detection of lipids, as well as applications in biomedical research, are presented.

PPARα and PPARγ Signaling Is Enhanced in the Brain of the Naked Mole-Rat, a Mammal that Shows Intrinsic Neuroprotection from Oxygen Deprivation.

Naked mole-rats (NMRs) are a long-lived animal that do not develop age-related diseases including neurodegeneration and cancer. Additionally, NMRs have a profound ability to consume reactive oxygen species (ROS) and survive long periods of oxygen deprivation. Here, we evaluated the unique proteome across selected brain regions of NMRs at different ages. Compared to mice, we observed numerous differentially expressed proteins related to altered mitochondrial function in all brain regions, suggesting that the mitochondria in NMRs may have adapted to compensate for energy demands associated with living in a harsh, underground environment. Keeping in mind that ROS can induce polyunsaturated fatty acid peroxidation under periods of neuronal stress, we investigated docosahexaenoic acid (DHA) and arachidonic acid (AA) peroxidation under oxygen-deprived conditions and observed that NMRs undergo DHA and AA peroxidation to a far less extent compared to mice. Further, our proteomic analysis also suggested enhanced peroxisome proliferator-activated receptor (PPAR)-retinoid X receptor (RXR) activation in NMRs via the PPARα-RXR and PPARγ-RXR complexes. Correspondingly, we present several lines of evidence supporting PPAR activation, including increased eicosapetenoic and omega-3 docosapentaenoic acid, as well as an upregulation of fatty acid-binding protein 3 and 4, known transporters of omega-3 fatty acids and PPAR activators. These results suggest enhanced PPARα and PPARγ signaling as a potential, innate neuroprotective mechanism in NMRs.

Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging.

Despite being a critical molecule in the brain, mass spectrometry imaging (MSI) of cholesterol has been under-reported compared to other lipids due to the difficulty in ionizing the sterol molecule. In the present work, we have employed an on-tissue enzyme-assisted derivatization strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific structures of the mouse brain, in a model of Niemann-Pick type C1 disease, and during brain development. MSI revealed that in the adult mouse, cholesterol is the highest in the pons and medulla and how its distribution changes during development. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. Our study demonstrates the potential of MSI to the study of sterols in neuroscience.

Exposure to sexually explicit Internet material among adolescents: a study in Vietnam.

BACKGROUND: With the influence of Confucian culture, sex is often considered a taboo subject in Vietnam. This study aimed to examine the prevalence of exposure to sexually explicit Internet material (SEIM) among adolescents in Vietnam, as well as the factors affecting exposure to SEIM. PARTICIPANTS AND PROCEDURE: The sample consisted of 886 Vietnamese adolescents (58.10% female) aged 15 to 18 years (M = 16.72, SD = 0.72). The survey was adapted from the study of Van Ouytsel, Ponnet and Walrave to assess the frequency of exposure to SEIM. Several measurement scales of factors affecting exposure to SEIM among adolescents were used including the Perceived Realism of SEIM, the Sexual Sensation Seeking Scale, the Family Cohesion and the Parental Monitoring Scale. RESULTS: The overall prevalence of exposure to SEIM was 84.10%, with a gender difference: 89.80% in males and 80.00% in females. The prevalence of passive exposure to SEIM was 58.30%, higher than 41.70% for active exposure. Perceived realism of SEIM, sexual sensation seeking and Internet usage time for entertainment are factors affecting frequencies of exposure to SEIM among adolescents, with ß coefficient values of .29, .18 and .16 respectively. CONCLUSIONS: The majority of children in this study reported SEIM exposure. Parents, schools and other stakeholders should pay attention to sex education for children early on, diversifying forms and subjects of sex education. The content of sex education should emphasize the responsibility in the decisions made by children related to sex.

Investigating Phosphorylation Patterns of the Ion Channel TRPM7 Using Multiple Extraction and Enrichment Techniques Reveals New Phosphosites.

The study of membrane proteins, and in particular ion channels, is crucial to understanding cellular function. Mass spectrometry-based approaches including bottom-up strategies to study membrane proteins have been successful yet still can remain challenging. In this study, we sought to evaluate the phosphorylation patterns of the ion channel TRPM7 which is involved in a range of critical physiological functions. To overcome extraction obstacles associated with analyzing membrane proteins, we incorporated the use of 5% SDS solubilization coupled with SCAD and S-Trap digestion methods to eliminate detergent interference in downstream LC-MS/MS analysis. We found that the SCAD method was more efficient, yielding 84% of the overall identified proteins; however, the variability was greater than the S-Trap method. Using both methods together with TiO2 and Fe-NTA phospho-enrichment protocols, we successfully observed the phosphorylation pattern of TRPM7 in a transfected cell line. An average of 22 ± 6% of the TRPM7 amino acid sequence was observed. In addition to several previously reported phosphorylation sites, we identified six new phosphosites (S5, S233, S554, S824, T1265, and S1401), providing new targets for further functional analyses of TRPM7.

Quantitative, Label-Free Proteomics in the Symptomatic Niemann-Pick, Type C1 Mouse Model Using Standard Flow Liquid Chromatography and Thermal Focusing Electrospray Ionization.

Niemann-Pick disease, type C1 (NPC1) is a fatal, autosomal recessive, neurodegenerative disorder caused by mutations in the NPC1 gene. As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. This abnormal accumulation results in a cascade of pathophysiological events including progressive, cerebellar neurodegeneration, among others. While significant progress has been made to better understand NPC1, the downstream effects of cholesterol storage and the major mechanisms that drive neurodegeneration remain unclear. In the current study, a) the use of a commercial, highly efficient standard flow-ESI platform for protein biomarker identification is implemented and b) protein biomarkers are identified and evaluated at a terminal time point in the NPC1 null mouse model. In this study, alterations are observed in proteins related to fatty acid homeostasis, calcium binding and regulation, lysosomal regulation, and inositol biosynthesis and metabolism, as well as signaling by Rho family GTPases. New observations from this study include altered expression of Pcp2 and Limp2 in Npc1 mutant mice relative to control, with Pcp2 exhibiting multiple isoforms and specific to the cerebella. This study provides valuable insight into pathways altered in the late-stage pathophysiology of NPC1.

Physicians' adherence to acute coronary syndrome prescribing guidelines in Vietnamese hospital practice: a cross-sectional study.

OBJECTIVES: To determine the extent of physicians' adherence to prescribing guidelines for acute coronary syndrome in Vietnamese hospitals. METHODS: Retrospective cross-sectional study of medical records of all patients with ACS admitted to two public hospitals in Ho Chi Minh City, Vietnam, from January to December 2013. Percentages of eligible patients receiving guideline-recommended medications were determined. Factors associated with non-adherence were identified using multivariate logistic regression. RESULTS: Overall, 711 medical records were reviewed and 284 patients fulfilled inclusion criteria (mean age 64 years; 69.4% male). Of those patients eligible for treatment, aspirin was prescribed for 97.9% at arrival and 96.3% at discharge; dual antiplatelet therapy was prescribed for 92.3% at arrival and 91.7% at discharge; loading doses were prescribed for 79.5% (aspirin) and 55.8% (clopidogrel); beta blockers were prescribed for 58.7% at arrival and 76.7% at discharge; angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were prescribed for 89.1% at arrival or discharge; and statins were prescribed for 94.1% at arrival and 90.7% at discharge. Patients undergoing an invasive procedure were more likely to receive guideline-recommended medications at discharge: dual antiplatelet therapy (OR 3.77; 95% CI 1.23-11.52), beta blocker (OR 3.95; 95% CI 1.86-8.40) and ACEI/ARB (OR 4.01; 95% CI 1.30-12.41). Ninety of the excluded patients were discharged without completing treatment. CONCLUSIONS: In general, physicians closely adhered to ACS prescribing guidelines in Vietnamese hospital practice. Prescribing of beta blockers and clopidogrel loading doses was probably suboptimal. Why patients do not complete treatment needs to be investigated.

Novel application of a spatial frequency domain imaging system to determine signature spectral differences between infected and noninfected burn wounds.

Complications of infection can increase burn-related morbidity and mortality. Early detection of burn wound infection could lead to more precise and effective treatment, reducing systemic complications and the need for long-term, broad-spectrum intravenous antibiotics. Quantitative cultures from biopsies are the accepted standard to determine infection. However, this methodology can take days to yield results and is invasive. This investigation focuses on the use of noninvasive imaging to determine the infection status of burn wounds in a controlled in vivo model. Full-thickness burn wounds were created on the dorsum of adult male rats (n = 6). Twenty-four hours after burn wound creation, wounds in the "Infected" group were inoculated with a vehicle containing 1 × 10(8) colony forming unit Staphylococcus aureus. "Control" group animals received vehicle alone. Subsequently, the wounds were imaged daily for a total of 10 days and the differences of skin optical properties were assessed using spatial frequency domain imaging at 16 different wavelengths from 500 to 700 nm. Regions of interest on the resulting images were selected and averaged at each time point. Statistically significant differences in average absorption and reduced scattering coefficients (µ(a) and µ(s)') at 620 and 700 nm were observed between the two groups (P < .05). Differential optical properties were most evident by day 4 and persisted throughout the time course. Differential signature changes in optical properties are evident in infected burn wounds. This novel application of spatial frequency domain imaging may prove to be a valuable adjunct to burn wound assessment. Further work will be aimed at determining dose-response relationships and prokaryotic species differences.

Three-dimensional phantoms for curvature correction in spatial frequency domain imaging.

The sensitivity to surface profile of non-contact optical imaging, such as spatial frequency domain imaging, may lead to incorrect measurements of optical properties and consequently erroneous extrapolation of physiological parameters of interest. Previous correction methods have focused on calibration-based, model-based, and computation-based approached. We propose an experimental method to correct the effect of surface profile on spectral images. Three-dimensional (3D) phantoms were built with acrylonitrile butadiene styrene (ABS) plastic using an accurate 3D imaging and an emergent 3D printing technique. In this study, our method was utilized for the correction of optical properties (absorption coefficient µ(a) and reduced scattering coefficient µ(s)') of objects obtained with a spatial frequency domain imaging system. The correction method was verified on three objects with simple to complex shapes. Incorrect optical properties due to surface with minimum 4 mm variation in height and 80 degree in slope were detected and improved, particularly for the absorption coefficients. The 3D phantom-based correction method is applicable for a wide range of purposes. The advantages and drawbacks of the 3D phantom-based correction methods are discussed in details.