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Background: Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is a glycoprotein that has been approved by the FDA for the treatment of neutropenia and leukemia in combination with chemotherapies. Recombinant hGM-CSF is produced industrially using the baker's yeast, Saccharomyces cerevisiae, by large-scale fermentation. The methylotrophic yeast, Pichia pastoris, has emerged as an alternative host cell system due to its shorter and less immunogenic glycosylation pattern together with higher cell density growth and higher secreted protein yield than S. cerevisiae. In this study, we compared the pipeline from gene to recombinant protein in these two yeasts., Results: Codon optimization in silico for both yeast species showed no difference in frequent codon usage. However, rhGM-CSF expressed from S. cerevisiae BY4742 showed a significant discrepancy in molecular weight from those of P. pastoris X33. Analysis showed purified rhGM-CSF species with molecular weights ranging from 30 to more than 60 kDa. Fed-batch fermentation over 72 h showed that rhGM-CSF was more highly secreted from P. pastoris than S. cerevisiae (285 and 64 mg total secreted protein/L, respectively). Ion exchange chromatography gave higher purity and recovery than hydrophobic interaction chromatography. Purified rhGM-CSF from P. pastoris was 327 times more potent than rhGM-CSF from S. cerevisiae in terms of proliferative stimulating capacity on the hGM-CSF-dependent cell line, TF-1., Conclusion: Our data support a view that the methylotrophic yeast P. pastoris is an effective recombinant host for heterologous rhGM-CSF production.

Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic 12 C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length [Formula: see text] to calculate the lineal energy was introduced as an alternative to the mean chord length [Formula: see text] because it was found that adopting Cauchy's formula for the [Formula: see text] was not appropriate for the radiation field typical of HIT as it is very directional. [Formula: see text] can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident 12 C ion beam can be adopted as [Formula: see text]. The tissue equivalence conversion method and [Formula: see text] were adopted to determine the RBE 10 , calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE 10 along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of the determination of [Formula: see text].

Background: This study investigated the prevalence of and risk factors for oral human papillomavirus (HPV) infection with multiple genotypes in the United States., Methods: Data were from the nationally representative 2009-2012 National Health and Nutrition Examination Survey. This analysis comprised 9257 participants for whom data on oral HPV (37 genotypes) and associated risk factors were available., Results: The weighted prevalence of multitype (2-6 types) oral HPV infection was 1.5% (2.5% for men, 0.4% for women) in the whole sample and 19.7% (22.0% for men, 12.1% for women) in those who had any type of oral HPV positivity. Most multitype oral HPV cases (83.8%) harbored one or more oncogenic types. In the adjusted multinominal logistic regression model, being male (relative risk ratio [RRR] = 3.69; 95% confidence interval [CI], 1.57-8.65), being a current cigarette smoker (RRR = 2.57; 95% CI, 1.23-5.36), and having a new sex partner in the past year (RRR = 2.10; 95% CI, 1.03-4.28) were associated with an increased risk of multitype oral HPV infection over single-type HPV infection., Conclusions: Men, smokers, and those who had new sexual partners were at a significantly higher risk for multitype oral HPV infection.

We investigate options for grouping templates for the purpose of template identification and extraction from electronic medical records. We sampled a corpus of 1000 documents originating from Veterans Health Administration (VA) electronic medical record. We grouped documents through hashing and binning tokens (Hashed) as well as by the top 5% of tokens identified as important through the term frequency inverse document frequency metric (TF-IDF). We then compared the approaches on the number of groups with 3 or more and the resulting longest common subsequences (LCSs) common to all documents in the group. We found that the Hashed method had a higher success rate for finding LCSs, and longer LCSs than the TF-IDF method, however the TF-IDF approach found more groups than the Hashed and subsequently more long sequences, however the average length of LCSs were lower. In conclusion, each algorithm appears to have areas where it appears to be superior.

There is need for cataloging signs and symptoms, but not all are documented in structured data. The text from clinical records are an additional source of signs and symptoms. We describe a Natural Language Processing (NLP) technique to identify symptoms from text. Using a human-annotated reference corpus from VA electronic medical notes we trained and tested an NLP pipeline to identify and categorize symptoms. The technique includes a model created from an automatic machine learning model selection tool. Tested on a hold-out set, its precision at the mention level was 0.80, recall 0.74 and an overall f-score of 0.80. The tool was scaled-up to process a large corpus of 964,105 patient records.

Potato virus Y (PVY) is a serious threat to potato production due to effects on tuber yield and quality, in particular, due to induction of potato tuber necrotic ringspot disease (PTNRD), typically associated with recombinant strains of PVY. These recombinant strains have been spreading in the United States for the past several years, although the reasons for this continuing spread remained unclear. To document and assess this spread between 2011 and 2015, strain composition of PVY isolates circulating in the Columbia Basin potato production area was determined from hundreds of seed lots of various cultivars. The proportion of nonrecombinant PVY O isolates circulating in Columbia Basin potato dropped ninefold during this period, from 63% of all PVY-positive plants in 2011 to less than 7% in 2015. This drop in PVY O was concomitant with the rise of the recombinant PVY N-Wi strain incidence, from less than 27% of all PVY-positive plants in 2011 to 53% in 2015. The proportion of the PVY NTN recombinant strain, associated with PTNRD symptoms in susceptible cultivars, increased from 7% in 2011 to approximately 24% in 2015. To further address the shift in strain abundance, screenhouse experiments were conducted and revealed that three of the four most popular potato cultivars grown in the Columbia Basin exhibited strain-specific resistance against PVY O . Reduced levels of systemic movement of PVY O in such cultivars would favor spread of recombinant strains in the field. The negative selection against the nonrecombinant PVY O strain is likely caused by the presence of the Ny tbr gene identified in potato cultivars in laboratory experiments. Presence of strain-specific resistance genes in potato cultivars may represent the driving force changing PVY strain composition to predominantly recombinant strains in potato production areas.

Objective: This study aimed to investigate factors that inhibit and facilitate discussion about alcohol between general practitioners (GPs) and patients., Design: Data analysis from a cross-sectional survey., Setting and Participants: 894 GP delegates of a national health seminar series held in five capital cities of Australia in 2014., Main Outcome Measures: Likelihood of routine alcohol enquiry; self-assessed confidence in assessing and managing alcohol issues in primary healthcare., Results: Most GPs (87%) reported that they were likely to routinely ask patients about their alcohol consumption and had sufficient skills to manage alcohol issues (74%). Potential barriers to enquiring about alcohol included perceptions that patients are not always honest about alcohol intake (84%) and communication difficulties (44%). 'I usually ask about alcohol' was ranked by 36% as the number one presentation likely to prompt alcohol discussion. Altered liver function test results followed by suspected clinical depression were most frequently ranked in the top three presentations. Suspicious or frequent injuries, frequent requests for sickness certificates and long-term unemployment were ranked in the top three presentations by 20% or less. Confidence in managing alcohol issues independently predicted likelihood to 'routinely ask' about alcohol consumption. Lack of time emerged as the single most important barrier to routinely asking about alcohol. Lack of time was predicted by perceptions of competing health issues in patients, fear of eliciting negative responses and lower confidence in ability to manage alcohol-related issues., Conclusions: Improving GPs' confidence and ability to identify, assess and manage at-risk drinking through relevant education may facilitate greater uptake of alcohol-related enquiries in general practice settings. Routine establishment of brief alcohol assessments might improve confidence in managing alcohol issues, reduce the time burden in risk assessment, decrease potential stigma associated with raising alcohol issues and reduce the potential for negative responses from patients., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

The very few studies that have examined the association between vaginal douching and genital human papillomavirus (HPV) infection have found contrary results. We investigated the associations between douching and numbers of HPV genotypes infecting 1271 participants aged 20-49 years in the 2003-2004 US National Health and Nutrition Examination Survey. After controlling for relevant covariates, douching in the past 6 months was significantly associated with infection by higher numbers of all genital HPV types (relative risk ratio, 1.26; 95% confidence interval, 1.03-1.54) and HPV high-risk types (1.40; 1.09-1.80)., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: The association of waterpipe tobacco (WPT) smoking with gastric cancer (GC) risk was suggested., Methods: A hospital-based case-control study was conducted to examine the association of WPT with GC risk among Vietnamese men, in Hanoi city, during the period of 2003-2011. Newly-diagnosed GC cases (n = 454) and control patients (n = 628) were matched by age (+/- 5 years) and the year of hospitalization. Information on smoking and alcohol drinking habits and diet including salty food intake and fruits/vegetables consumption were obtained by the interview. Maximum likelihood estimates of odds ratios (ORs) and corresponding 95% confidence intervals (Cis) were obtained using conditional logistic regression models., Results: The group with the highest consumption of citrus fruits showed a significantly low GC risk (OR = 0.6, 95%CI = 0.4-0.8, P for trend = 0.002). However, there was no association of raw vegetable consumption with GC risk. Referring to never smokers, GC risk was significantly higher in current WPT smokers (OR = 1.8, 95%CI = 1.3-2.4), and it was more evident in exclusively WPT smokers (OR = 2.7, 95%CI = 1.2-6.5). GC risk tended to be higher with daily frequency and longer duration of WPT smoking but these trends were not statistically significant (P for trend: 0.144 and 0.154, respectively). GC risk of those who started smoking WPT before the age of 25 was also significantly high (OR = 3.7, 95%CI = 1.2-11.3). Neither cigarette smoking nor alcohol drinking was related to GC risk., Conclusion: The present findings revealed that WPT smoking was positively associated with GC risk in Vietnamese men., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Substantial amounts of clinically significant information are contained only within the narrative of the clinical notes in electronic medical records. The v3NLP Framework is a set of "best-of-breed" functionalities developed to transform this information into structured data for use in quality improvement, research, population health surveillance, and decision support., Background: MetaMap, cTAKES and similar well-known natural language processing (NLP) tools do not have sufficient scalability out of the box. The v3NLP Framework evolved out of the necessity to scale-up these tools up and provide a framework to customize and tune techniques that fit a variety of tasks, including document classification, tuned concept extraction for specific conditions, patient classification, and information retrieval., Innovation: Beyond scalability, several v3NLP Framework-developed projects have been efficacy tested and benchmarked. While v3NLP Framework includes annotators, pipelines and applications, its functionalities enable developers to create novel annotators and to place annotators into pipelines and scaled applications., Discussion: The v3NLP Framework has been successfully utilized in many projects including general concept extraction, risk factors for homelessness among veterans, and identification of mentions of the presence of an indwelling urinary catheter. Projects as diverse as predicting colonization with methicillin-resistant Staphylococcus aureus and extracting references to military sexual trauma are being built using v3NLP Framework components., Conclusion: The v3NLP Framework is a set of functionalities and components that provide Java developers with the ability to create novel annotators and to place those annotators into pipelines and applications to extract concepts from clinical text. There are scale-up and scale-out functionalities to process large numbers of records.

Intravaginal practices (IVPs) are associated with several adverse health outcomes, including HIV infection. However, few studies have examined this topic in Asian cultures, particularly in female sex workers (FSWs). This theory-based qualitative study aimed to describe the IVPs and to identify salient determinants of these practices in FSWs in Phnom Penh, Cambodia. We conducted in-depth interviews using open-ended questions with 30 FSWs in July-August 2014. We analyzed data using thematic content analysis, with thematic codes based on the constructs of the theory of planned behavior. The results showed that the most common IVP was a combination of intravaginal washing and wiping, to which we refer as intravaginal cleansing. There was a clear and close connection between IVP and sex work. Perceived benefits of intravaginal cleansing were numerous, while the perceived risks were few. As a result, the attitude toward intravaginal cleansing was favorable. A common misperception of benefit was that intravaginal cleansing could prevent sexually transmitted infections. Local physicians considerably influenced the subjective norm related to IVP. Intention to quit IVPs was suboptimal. In conclusion, the psychological factors associated with IVPs in FSWs were somewhat different from those in the general population of Cambodian women and women in other countries. Behavioral beliefs, attitude, and subjective norms appeared salient and important factors in IVPs. Interventions aimed at reducing IVPs should target these constructs as well as the sex-work-associated economic motives. Local physicians may be an agent to change IVP and an effective channel to deliver interventions.

Objective: To report atypical MRI patterns associated with POLR3A and POLR3B mutations., Methods: This was a multicenter retrospective study to collect neuroradiologic, clinical, and molecular data of patients with mutations in POLR3A and POLR3B without the classic MRI phenotype, i.e., diffuse hypomyelination associated with relative T2 hypointensity of the ventrolateral thalamus, globus pallidus, optic radiation, corticospinal tract at the level of the internal capsule, and dentate nucleus, cerebellar atrophy, and thinning of the corpus callosum., Results: Eight patients were identified: 6 carried mutations in POLR3A and 2 in POLR3B. We identified 2 novel MRI patterns: 4 participants presented a selective involvement of the corticospinal tracts, specifically at the level of the posterior limbs of the internal capsules; 4 patients presented moderate to severe cerebellar atrophy. Incomplete hypomyelination was observed in 5 participants., Conclusion: Diffuse hypomyelination is not an obligatory feature of POLR3-related disorders. Two distinct patterns, selective involvement of the corticospinal tracts and cerebellar atrophy, are added to the MRI presentation of POLR3-related disorders., (© 2016 American Academy of Neurology.)

Background: Effective control of sexually transmitted infections (STIs) depends on affected patients notifying their sexual partners, and partners following through with screening and treatment. Our study assessed high-risk-STI women's confidence in STI-diagnosis-related communications with their primary male partners in Ho Chi Minh City, Vietnam, and determined associated characteristics of the women and their partners., Methods: We employed convenience and snowball sampling in a clinic-based setting to recruit 126 women from August to October 2013. All data were obtained from women's self-report., Results: The proportions of participants who were "slightly confident" or "very confident" that they could disclose their STI positivity to partners, ask partners to have an STI examination or treatment, and give partners bacterial-STI medications were 70.3%, 62.1%, and 69.0%, respectively. The proportions who perceived that their partners would be "very likely" to have an STI examination and to take STI medications were 16.2% and 38.8%, respectively. Significantly lower self-efficacy was observed in women who had a lower education level, who had ever traded sex, or whose primary partners were not husbands or fiancés., Conclusions: Our results suggest potential for piloting STI-partner-targeted interventions. To be effective, these programs should improve women's self-efficacy and primary partners' cooperation with screening and treatment.

The successful implementation of prevention programs for mother-to-child human immunodeficiency virus (HIV) transmission has dramatically reduced the prevalence of infants infected with HIV while increasing that of HIV-exposed uninfected (HEU) children. Neuropsychological assessments indicate that HEU children may exhibit differences in neurodevelopment compared to unexposed children (HUU). Pathological mechanisms leading to such neurodevelopmental delays are not clear. In this observational birth cohort study we explored the integrity of regional white matter microstructure in HEU infants, shortly after birth. Microstructural changes in white matter associated with prenatal HIV exposure were evaluated in HEU infants (n = 15) and matched controls (n = 22) using diffusion tensor imaging and tract-based spatial statistics. Additionally, diffusion values were extracted and compared for white matter tracts of interest, and associations with clinical outcomes from the Dubowitz neonatal neurobehavioral tool were investigated. Higher fractional anisotropy in the middle cerebellar peduncles of HEU compared to HUU neonates was found after correction for age and gender. Scores on the Dubowitz abnormal neurological signs subscale were positively correlated with FA (r = 0.58, P = 0.038) in the left uncinate fasciculus in HEU infants. This is the first study to present data suggesting that prenatal HIV exposure without infection is associated with altered white matter microstructural integrity in the neonatal period. Longitudinal studies of HEU infants as their brains mature are necessary to understand further the significance of prenatal HIV and antiretroviral treatment exposure on white matter integrity and neurodevelopmental outcomes., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To develop a method to exploit the UMLS Metathesaurus for extracting and categorizing concepts found in clinical text representing signs and symptoms to anatomically related organ systems. The overarching goal is to classify patient reported symptoms to organ systems for population health and epidemiological analyses., Materials and Methods: Using the concepts' semantic types and the inter-concept relationships as guidance, a selective portion of the concepts within the UMLS Metathesaurus was traversed starting from the concepts representing the highest level organ systems. The traversed concepts were chosen, filtered, and reviewed to obtain the concepts representing clinical signs and symptoms by blocking deviations, pruning superfluous concepts, and manual review. The mapping process was applied to signs and symptoms annotated in a corpus of 750 clinical notes., Results: The mapping process yielded a total of 91,000 UMLS concepts (with approximately 300,000 descriptions) possibly representing physical and mental signs and symptoms that were extracted and categorized to the anatomically related organ systems. Of 1864 distinct descriptions of signs and symptoms found in the 750 document corpus, 1635 of these (88%) were successfully mapped to the set of concepts extracted from the UMLS. Of 668 unique concepts mapped, 603 (90%) were correctly categorized to their organ systems., Conclusion: We present a process that facilitates mapping of signs and symptoms to their organ systems. By providing a smaller set of UMLS concepts to use for comparing and matching patient records, this method has the potential to increase efficiency of information extraction pipelines., (Published by Elsevier Inc.)

"Identifying and labeling" (annotating) sections improves the effectiveness of extracting information stored in the free text of clinical documents. OBSecAn, an automated ontology-based section annotator, was developed to identify and label sections of semi-structured clinical documents from the Department of Veterans Affairs (VA). In the first step, the algorithm reads and parses the document to obtain and store information regarding sections into a structure that supports the hierarchy of sections. The second stage detects and makes correction to errors in the parsed structure. The third stage produces the section annotation output using the final parsed tree. In this study, we present the OBSecAn method and its scale to a million document corpus and evaluate its performance in identifying family history sections. We identify high yield sections for this use case from note titles such as primary care and demonstrate a median rate of 99% in correctly identifying a family history section.

Unlabelled: Background Evidence regarding whether male partners' characteristics can influence women's likelihood of getting sexually transmissible infections (STIs) is insufficient and inconsistent. Our study examined associations between women's perception of primary male partners' demographic and behavioural characteristics and women's history of bacterial STI diagnoses among 126 women at risk for STIs in Ho Chi Minh City, Vietnam., Methods: All variables were obtained by women's self-report. Due to the excess zeroes of the number of bacterial STI diagnoses for women, we used Zero-Inflated Poisson regression to examine associations of interest., Results: Among women who had one lifetime male partner (n=49), the partner's number of female sexual partners [prevalence ratio (PR)=4.63, 95%CI=1.44-14.88] and number of STI diagnoses (PR=27.32, 95%CI=1.56-477.70) were associated with the woman's number of bacterial STI diagnoses, after adjusting for women's education level. For women who had >1 lifetime male partner (n=77), a greater number of women's bacterial STI diagnoses was also associated with their partners' STI history (PR=9.12, 95% CI=2.44-34.11)., Conclusions: An increased risk for STIs in women was associated with both individual characteristics and their primary male partner's behavioural risk factors. Therefore, primary male partners' risk factors should be included in STI risk assessments, treatment and interventions for women.

This study aims to develop a reproducible rat model for post-traumatic bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our previous studies using dental extraction as an inducing factor, only 30%-60% of zoledronate-treated animals fulfilled the definition of clinical BRONJ. We modified the zoledronate regimen and introduced repeated surgical extraction to illicit quantifiable BRONJ in all animals. Eighty retired-breeder female Sprague-Dawley rats were divided between the treatment (i.v. zoledronate; 80 μg/kg/week for 13 weeks) and control (saline) groups. On week 13, the left mandibular first molar was surgically extracted, followed by the second molar a week later. Animals were euthanized at 1-week, 2-weeks, and 8-weeks following extraction. The occurrence and severity of BRONJ were scored in each animal based on gross and MicroCT analysis. Parameters of bone formation and osteoclast functions at the extraction site were compared between groups. All zoledronate-treated animals developed a severe case of BRONJ that fulfilled the clinical definition of the condition in humans. Osteoclast attachment continued to be defective eight weeks after stopping the treatment. There were no signs of kidney or liver toxicity. Our data confirmed that repeated surgical extraction (major trauma) by itself consistently precipitated massive bone necrosis in ZA-treated animals, eliminating the need to induce pre-existing infection or comorbidity. These results will be the basis for further studies examining the in-vivo pathogenesis and prevention of BRONJ.

A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.

Objectives: This study aimed to examine the relationships among self-reported oral health, oral hygiene practices, and oral human papillomavirus (HPV) infection in women at risk for sexually transmitted infections (STIs) in Ho Chi Minh City, Vietnam., Study Design: Convenience and referral sampling methods were used in a clinic-based setting to recruit 126 women aged 18-45 years between August and October 2013. Behavioral factors were self-reported. Oral-rinse samples were tested for HPV DNA of 2 low-risk and 13 high-risk genotypes., Results: A higher unadjusted prevalence of oral HPV infection was associated with poorer self-rated overall oral health (P = .001), reported oral lesions or problems in the past year (P = .001), and reported a tooth loss not because of injury (P = .001). Higher unadjusted prevalence of oral HPV infection was also associated with two measures of oral hygiene: lower frequencies of toothbrushing per day (P = .047) and gargling without toothbrushing (P = .037). After adjusting for other factors in multivariable logistic regression models, poorer self-rated overall oral health remained statistically associated with oral HPV infection (P = .042); yet the frequency of tooth-brushing per day did not (P = .704)., Conclusion: Results corroborate the association between self-reported poor oral health and oral HPV infection. The effect of oral hygiene on oral HPV infection remains inconclusive., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Influenza A/H1N1pdm09 virus was first detected in Vietnam on May 31, 2009, and continues to circulate in Vietnam as a seasonal influenza virus. This study has monitored genotypic and phenotypic changes in this group of viruses during 2010-2013 period., Design and Setting: We sequenced hemagglutinin (HA) and neuraminidase (NA) genes from representative influenza A/H1N1pdm09 and compared with vaccine strain A/California/07/09 and other contemporary isolates from neighboring countries. Hemagglutination inhibition (HI) and neuraminidase inhibition (NAI) assays also were performed on these isolates., Sample: Representative influenza A/H1N1pdm09 isolates (n = 61) from ILI and SARI surveillances in northern Vietnam between 2010 and 2013., Main Outcome Measures and Results: The HA and NA phylogenies revealed six and seven groups, respectively. Five isolates (8·2%) had substitutions G155E and N156K in the HA, which were associated with reduced HI titers by antiserum raised against the vaccine virus A/California/07/2009. One isolate from 2011 and one isolate from 2013 had a predicted H275Y substitution in the neuraminidase molecule, which was associated with reduced susceptibility to oseltamivir in a NAI assay. We also identified a D222N change in the HA of a virus isolated from a fatal case in 2013., Conclusions: Significant genotypic and phenotypic changes in A/ H1N1pdm09 influenza viruses were detected by the National Influenza Surveillance System (NISS) in Vietnam between 2010 and 2013 highlighting the value of this system to Vietnam and to the region. Sustained NISS and continued virological monitoring of seasonal influenza viruses are required for vaccine policy development in Vietnam. 3., (© 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

POLR3-related (or 4H) leukodystrophy is an autosomal recessive disorder caused by mutations in POLR3A or POLR3B and is characterized by neurological and non-neurological features. In a small proportion of patients, no mutation in either gene or only one mutation is found. Analysis of the POLR3B cDNA revealed a large deletion of exons 21-22 in one case and of exons 26-27 in another case. These are the first reports of long deletions causing POLR3-related leukodystrophy, suggesting that deletions and duplications in POLR3A or POLR3B should be investigated in patients with a compatible phenotype, especially if one pathogenic variant has been identified.

Objective: This study aims to ascertain frequency of mutations in POLR3A or POLR3B, which are associated with 4H leukodystrophy, in a cohort of patients with unclassified hypomyelination., Methods and Results: In a cohort of 22 patients with the magnetic resonance imaging (MRI) diagnosis of unclassified hypomyelination and without typical clinical signs, we evaluated clinical and MRI features. Developmental delay or intellectual disability, ataxia, and spasticity were frequent symptoms. POLR3A and POLR3B were sequenced. A compound heterozygote mutation in POLR3B was found in only one patient. Additional investigations allowed a definitive diagnosis in 10 patients., Conclusion: Mutations in POLR3A or POLR3B are rare in patients with unclassified hypomyelination, and alternative diagnoses should be considered first., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: In general, fusion of recombinant genes to strong inducible promoters allowing intracellular expression in Bacillus subtilis is a two-step process. The ligation products are transformed into Escherichia coli, followed by identification of the correct plasmid, and this plasmid is subsequently transformed into B. subtilis. This raises the problem that basal level of expression of the recombinant gene could be harmful for E. coli cells. Based on the Pgrac promoter, we optimized the UP element, the -35, 15, -10 and the +1 region to enhance the promoter activity in B. subtilis after induction. However, detailed investigations for a promoter to develop expression vectors that allows high protein production levels in B. subtilis and a relatively low basal expression levels in E. coli has not been studied yet., Results: We screened the previously constructed library of E. coli - B. subtilis shuttle vectors for high level expression in B. subtilis and low basal level in E. coli. Promoter Pgrac100 turned out to meet these criteria, in which ß-galactosidase expression level of Pgrac100-bgaB is about 9.2 times higher than Pgrac01-bgaB in B. subtilis and the ratio of those in induced B. subtilis over un-induced E. coli from Pgrac100-bgaB is 1.3 times higher than Pgrac01-bgaB. Similarly, GFP expression level of Pgrac100-gfp is about 27 times higher than that of Pgrac01-gfp and the ratio from Pgrac100-gfp is 35.5 times higher than Pgrac01-gfp. This promoter was used as a basis for the construction of three novel vectors, pHT253 (His-tag-MCS), pHT254 (MCS-His-tag) and pHT255 (MCS-Strep-tag). Expression of the reporter proteins BgaB and GFP using these expression vectors in B. subtilis at a low IPTG concentration were measured and the fusion proteins could be purified easily in a single step by using Strep-Tactin or IMAC-Ni columns., Conclusions: This paper describes the construction and analysis of an IPTG-inducible expression vector termed Pgrac100 for the high level production of intracellular recombinant proteins in B. subtilis and a relatively low basal expression level in E. coli. Based on this vector, the derivative vectors, Pgrac100-His-tag-MCS, Pgrac100-MCS-His-tag and Pgrac100-MCS-Strep-tag have been constructed.

Several studies indicate that douching has few benefits but numerous adverse health outcomes, including increased risk for sexually transmitted infections and HIV. No published study explores douching practices among Cambodian female sex workers. This report provides preliminary data about the prevalence and frequency of douching among female sex workers in Phnom Penh, Cambodia. Survey data were obtained from 81 female sex workers who were taken into custody due to engagement in commercial sex from March to June 2011. Results showed that 91% of participants douched. The mean numbers of times douched before sex and after sex per 10 sex episodes were 4.43 (SD = 3.87) and 4.63 (SD = 3.94), respectively. Half of the participants thought that douching could help to prevent sexually transmitted infections including HIV; 24% were unsure about this. Usually, douching after sex was associated with ever obtaining an HIV test (p = .012) and was marginally associated (although not statistically significant) with a higher average number of clients per week (p =. 063) and consistent condom use with clients (p = .053). This suggests that these practices may be related to individual perceptions of sexually transmitted infections/HIV risk or susceptibility. Given the commonness of douching and related misperceptions among Cambodian female sex workers, future studies and interventions are needed to prevent adverse health problems., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

This study used ecological momentary assessment data from adult daily smokers attempting to quit smoking to assess relations between exposure to contextual risk factors and cessation failure, latency to a first smoking lapse, or progression from lapse to relapse (smoking 7 days in a row). Participants were adult, daily smokers enrolled in a randomized controlled clinical trial of bupropion SR and individual counseling who were followed to 1 year postquit. Participants reported exposure to high-risk contexts and behaviors, including being where cigarettes were available or smoking was permitted, being around others smoking in prospective, real-time assessment for 2 weeks pre- and 4 weeks postquit. Results showed that greater exposure to contextual risk factors during the prequit did not predict cessation failure. However, Cox regression survival analyses revealed that spending a greater proportion of time where cigarettes were easily available following at least 1 day of abstinence predicted shorter latency to a first lapse, even after controlling for baseline risk factors such as gender, nicotine dependence, depressive symptoms, and living with a smoker. Greater cigarette availability following a lapse was not associated with progression from lapse to relapse with or without baseline risk factors in the model. This suggests that postquit environmental risk factors, such as cigarette availability, increase lapse risk, and stable risk factors, such as living with smokers and higher baseline carbon monoxide level or depressive symptoms, remain potent predictors of progression to relapse. Real-time contextual risk assessments postquit predict lapse above and beyond stable, baseline risk factors. (PsycINFO Database Record, ((c) 2015 APA, all rights reserved).)

Background: Concurrent infection with multiple types of Human Papillomavirus (HPV) is associated with an increased risk of cervical cancer; yet, little is known about risk factors for concurrent HPV infection in Vietnam. This study investigated the prevalence of and risk factors for high-risk-type HPV and multi-type HPV infections among women in Ho Chi Minh City, Vietnam., Methods: Data were collected from a population-based survey of 1,550 women (mean age = 42.4; SD = 9.5), using a multi-stage sampling process. Socio-demographic and behavioral variables were obtained by self-report. HPV genotypes in cervical specimens were identified using PCR protocols., Results: The prevalence of any high-risk HPV infection was 9.0%, and of multi-type HPV infection was 1.9%. In the HPV+ subsample, the percentage of high-risk HPV was 84% and of multi-type HPV was 20%. All multi-type HPV infections were high-risk-type. Lifetime smoking and older age of first sex were significantly associated with any high-risk and multi-type HPV infections. Regular condom use was inversely associated with high-risk and multi-type HPV infection., Conclusions: Risk factors for high-risk and multi-type HPV infections were similar. Further research and intervention are needed to reduce HPV infections in order to prevent HPV-related cancers.

Measuring the quality of food consumed by individuals or groups in the U.S. is essential to informed public health surveillance efforts and sound nutrition policymaking. For example, the Healthy Eating Index-2010 (HEI) is an ideal metric to assess the food quality of households, but the traditional methods of collecting the data required to calculate the HEI are expensive and burdensome. We evaluated an alternative source: rather than measuring the quality of the foods consumers eat, we want to estimate the quality of the foods consumers buy. To accomplish that we need a way of estimating the HEI based solely on the count of food items. We developed an estimation model of the HEI, using an augmented set of the What We Eat In America (WWEIA) food categories. Then we mapped ~92,000 grocery food items to it. The model uses an inverse Cumulative Distribution Function sampling technique. Here we describe the model and report reliability metrics based on NHANES data from 2003-2010.

Aicardi-Goutières syndrome (AGS) is a rare genetic disorder with inflammatory immune-mediated pathogenesis. Disease onset is most commonly marked by recurrent fevers, irritability, and developmental regression in the 1st year of life. A stable phase characterized by severe spastic quadriparesis and cognitive deficit follows. Brain calcifications, leukoencephalopathy, and cerebral atrophy are the radiological hallmarks of AGS and often show progression over time. We present an atypical patient with late-onset AGS characterized by spastic paraparesis and a leukoencephalopathy that markedly improved during follow-up, demonstrating a nonprogressive disease course and the exceptional amelioration of the white matter abnormalities., (Georg Thieme Verlag KG Stuttgart · New York.)

Cytotoxic chemotherapeutic drugs, especially when used in combination, are widely employed to treat a variety of cancers in patients but often lead to serious symptoms that negatively affect physical functioning and quality of life. There is compelling evidence that implicates cytotoxic chemotherapy-induced inflammation in the etiology of these symptoms. Because IL-1β plays a central role as an initiator cytokine in immune responses, we compared doxorubicin, a drug known to induce IL-1β production, with ten other commonly prescribed chemotherapeutic drugs in their ability to lead to processing and secretion of IL-1β by primary mouse macrophages. Seven of them (melphalan, cisplatin, vincristine, etoposide, paclitaxel, methotrexate, and cytarabine) caused the production of IL-1β in cells pretreated with lipopolysaccharide. When delivered in combination with doxorubicin, one of the drugs, vincristine, was also capable of synergistically activating the NLRP3-dependent inflammasome and increasing expression of IL-1β, IL-6, and CXCL1. The absence of TNF-α and IL-1 signaling caused a partial reduction in the production of mature IL-1β. Three small-molecule inhibitors known to suppress activity of kinases situated upstream of mitogen-activated kinases (MAPKs) inhibited the expression of IL-1β, IL-6, and CXCL1 when doxorubicin and vincristine were used singly or together, so specific kinase inhibitors may be useful in reducing inflammation in patients receiving chemotherapy.

Circular ion-implanted silicon detector of α-particles with a large, 5-cm(2), sensitive area has been developed. An advantage of the detector is that the detector surface is easily cleanable with chemicals. The hardened surface of the detector shows no signs of deterioration of the spectroscopic and electrical characteristics upon repeated cleaning. The energy resolution along the diameters of the detector was (1.0±0.1)% for the 5.486-MeV α-particles. Detailed tests of the charge collection efficiency and uniformity of the detector entrance window were also performed with a 5.5-MeV He(2+) microbeam., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Main Conclusion: The apple MdMYB9 gene encodes a positive regulator of proanthocyanidin synthesis that activates anthocyanidin reductase promoters from apple and poplar via interaction with basic helix-loop-helix proteins. The regulation of proanthocyanidins (PAs, condensed tannins) is of great importance in food plants due to the many benefits of PAs in the human diet. Two candidate flavonoid MYB regulators, MdMYB9 and MdMYB11, were cloned from apple (Malus × domestica) based on their similarity to known MYB PA regulators. Transcript accumulation of both MdMYB9 and MdMYB11 was induced by high light and wounding, similar to the poplar (Populus spp) PA regulator PtMYB134. In transient activation assays with various basic helix-loop-helix (bHLH) co-regulators, MdMYB9 activated apple and poplar anthocyanidin reductase (ANR) promoters, while MdMYB11 showed no activity. Potential transcription factor binding elements were found within several ANR promoters, and the importance of the bHLH binding site (E-box) on ANR promoter activation was demonstrated via mutational analysis. The ability of MdMYB9 and PtMYB134 to reciprocally activate ANR promoters from both apple and poplar and to partner with heterologous bHLH co-factors from these plants confirms the high degree of conservation of PA regulatory complexes across species. The similarity in apple and poplar PA regulation suggests that regulatory genes from poplar could be effectively employed for metabolic engineering of the PA pathway in apple.

Background: Despite evidence supporting the importance of breastfeeding to child health, breastfeeding practices remain suboptimal in Vietnam. There is currently little evidence on the importance of breastfeeding in the prevention of morbidity during infancy in Vietnam. In order to provide country specific data for policy makers to support breastfeeding friendly policies and programs, analysis was undertaken on a cross-sectional dataset to investigate the association between breastfeeding practices and prevalence of diarrhea and acute respiratory infection (ARI) among infants aged 0-5 months., Methods: Data on socio-demographic characteristics, infant feeding practices and prevalence of diarrhea and ARI were obtained from 6,068 mother-child dyads in 11 provinces of Vietnam in 2011. Multivariate logistic regression was used to examine the associations between breastfeeding practices and child illnesses., Results: On average, the prevalence of diarrhea and ARI among infants 0-5 months was 5.3% and 24.5%, respectively. Though half of all infants were breastfed within one hour of birth, 73.3% were given prelacteal foods in the first three days after birth. Only 20.2% of children 0-5 months old were exclusively breastfed, while 32.4% were predominantly breastfed and 47.4% partially breastfed. After adjusting for confounders, early initiation of breastfeeding was associated with lower prevalence of diarrhea [adjusted odds ratio (AOR) = 0.74 (95% CI 0.58, 0.93)], while prelacteal feeding was associated with higher prevalence [AOR = 1.53 (95% CI 1.15, 2.03)]. Compared to infants who were exclusively breastfed, infants who were predominantly [AOR = 1.52 (95% CI 1.05, 2.21)] or partially breastfed [AOR = 1.55 (95% CI 1.07, 2.24)] were more likely to have diarrhea. Prelacteal feeding [AOR = 1.16 (95% CI 1.01, 1.33)] and partial breastfeeding [AOR relative to exclusive breastfeeding = 1.24 (95% CI 1.03, 1.48)] were associated with higher prevalence of ARI. While the protective effects of exclusive breastfeeding against diarrhea declined with child age, this effect for ARI appears to have remained constant., Conclusions: Early initiation and exclusive breastfeeding protects against diarrhea and ARI. Results confirm that interventions to improve early and exclusive breastfeeding would contribute to improving child health and nutrition in Vietnam.

Excitotoxicity and disruption of Ca(2+) homeostasis have been implicated in amyotrophic lateral sclerosis (ALS) and limiting Ca(2+) entry is protective in models of ALS caused by mutation of SOD1. Lomerizine, an antagonist of L- and T-type voltage-gated calcium channels and transient receptor potential channel 5 transient receptor potential channels, is well tolerated clinically, making it a potential therapeutic candidate. Lomerizine reduced glutamate excitotoxicity in cultured motor neurons by reducing the accumulation of cytoplasmic Ca(2+) and protected motor neurons against multiple measures of mutant SOD1 toxicity: Ca(2+) overload, impaired mitochondrial trafficking, mitochondrial fragmentation, formation of mutant SOD1 inclusions, and loss of viability. To assess the utility of lomerizine in other forms of ALS, calcium homeostasis was evaluated in culture models of disease because of mutations in the RNA-binding proteins transactive response DNA-binding protein 43 (TDP-43) and Fused in Sarcoma (FUS). Calcium did not play the same role in the toxicity of these mutant proteins as with mutant SOD1 and lomerizine failed to prevent cytoplasmic accumulation of mutant TDP-43, a hallmark of its pathology. These experiments point to differences in the pathogenic pathways between types of ALS and show the utility of primary culture models in comparing those mechanisms and effectiveness of therapeutic strategies., (© 2014 International Society for Neurochemistry.)

We report a case of mild cavitating leukoencephalopathy associated with a homozygous c.755A > G (p.Asp252Gly) NDUFS1 mutation in a 7-year old boy. Biochemical analysis confirmed an isolated reduction in complex I activity. Magnetic resonance imaging of the brain showed a diffuse cystic leukoencephalopathy with the involvement of the corpus callosum and sparing of the gray matter. The clinical course was marked by an acute presentation of neurological deficits at 24 months followed by recurrent episodes of mild neurological deterioration, subsequent remissions, and prolonged periods of stability. This is one of the mildest known clinical presentations of complex I deficiency secondary to mutations in NDUFS1, expanding the clinical spectrum and natural history of this disorder. Consideration of clinical variability needs to be taken into account in patient management and family counseling.

Introduction: The term Janus particles was used to describe particles that are the combination of two distinct sides with differences in chemical nature and/or polarity on each face. Due to the exponential growth of interest on multifunctional nanotechnologies, such anisotropic nanoparticles are promising tools in the field of drug delivery., Areas Covered: The main preparation processes and the materials used have been described first. Then a specific focus has been done on therapeutic and/or diagnostic applications of Janus particles., Expert Opinion: Janus particles are demonstrated as interesting objects with advanced properties that combine features and functionalities of different materials in one single unit. Due to their dual structure, Janus particles are promising candidates for a variety of high-quality applications dealing with drug delivery purposes. Still, the main challenges for the future lie in the development of the preparation of shape-controlled and nano-sized particles with large-scale production processes and approved pharmaceutical excipients.

The purpose of this study was to investigate the effect of chronic treatment with prazosin, a selective α1-adrenoceptor antagonist, on the development of hypertension in fructose-fed rats (FFR). High-fructose feeding and treatment with prazosin (1 mg/kg/day via drinking water) were initiated simultaneously in male Wistar rats. Systolic blood pressure, fasted plasma parameters, insulin sensitivity, plasma norepinephrine (NE), uric acid, and angiotensin II (Ang II) were determined following 9 weeks of treatment. FFR exhibited insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension, as well as elevations in plasma NE and Ang II levels. Treatment with prazosin prevented the rise in blood pressure without affecting insulin levels, insulin sensitivity, uric acid, or Ang II levels, while normalizing plasma NE levels in FFR. These data suggest that over-activation of the sympathetic nervous system, specifically α1-adrenoceptors, contributes to the development of fructose-induced hypertension, however, this over-activation does not appear to an initial, precipitating event in FFR.

Thin, ultra-flexible devices that can be manufactured in a process that covers a large area will be essential to realizing low-cost, wearable electronic applications including foldable displays and medical sensors. The printing technology will be instrumental in fabricating these novel electronic devices and circuits; however, attaining fully printed devices on ultra-flexible films in large areas has typically been a challenge. Here we report on fully printed organic thin-film transistor devices and circuits fabricated on 1-μm-thick parylene-C films with high field-effect mobility (1.0 cm(2) V(-1) s(-1)) and fast operating speeds (about 1 ms) at low operating voltages. The devices were extremely light (2 g m(-2)) and exhibited excellent mechanical stability. The devices remained operational even under 50% compressive strain without significant changes in their performance. These results represent significant progress in the fabrication of fully printed organic thin-film transistor devices and circuits for use in unobtrusive electronic applications such as wearable sensors.

Objective: We assessed associations of maternal common mental disorders (CMD) with undernutrition and two common illnesses in children aged 0-5 years., Design: Cross-sectional survey. Maternal CMD was measured using the WHO Self-Reporting Questionnaire-20. Child undernutrition was defined as stunting, underweight or wasting. Child illnesses included diarrhoea and acute respiratory infections (ARI). Multivariate logistic regression was used to test these associations adjusting for confounders at child, maternal and household levels., Setting: Bangladesh, Vietnam and Ethiopia., Subjects: Mothers with children aged 0-5 years from 4400 households in Bangladesh, 4029 households in Vietnam and 3000 households in Ethiopia., Results: The prevalence of maternal CMD was high, ranging from 31 % in Vietnam to 49 % in Bangladesh. Child undernutrition was more prevalent in Bangladesh and Ethiopia than in Vietnam. Symptoms of ARI and diarrhoea were also prevalent. In multivariate analysis, maternal CMD was associated with child stunting in Bangladesh (OR = 1·21; 95 % CI 1·03, 1·41) and with child underweight in Vietnam (OR = 1·27; 95 % CI 1·01, 1·61); no association was found with wasting. Maternal CMD was strongly associated with diarrhoea and ARI in all three countries., Conclusions: Maternal CMD, which affected nearly half of women in Bangladesh and one-third in Vietnam, was an important determinant of child stunting and underweight, respectively. No such association was found in Ethiopia, although CMD affected 39 % of women. Maternal CMD was strongly associated with childhood illnesses in all three countries. Interventions to support maternal mental health are important for women's own well-being and could make important contributions to improving child health and nutrition.

We have recently developed a general liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using a stable isotope-labeled (SIL) monoclonal antibody (mAb) as an internal standard (IS) for single-analyte quantification of mAb (Li et al. Anal Chem 84(3):1267-1273, 2012). The method offers an advantage over ligand binding assay in reducing the time and resources needed for bioanalytical support in preclinical stages of drug development. In this paper, we report another marked increase in assay efficiency for multi-analyte bioanalysis using unique surrogate peptides for each analyte and the strategic choice of the SIL-IS peptide. The method was qualified for the simultaneous determinations of four mAbs in rat plasma and applied to samples from discrete- and cassette-dosed rats. The pharmacokinetic parameters of the four mAbs of cassette dosing were comparable to those of discrete dosing and of enzyme-linked immunosorbent assay results. Although there may be limitations and special considerations for cassette-dosing of biologics, these results demonstrate the robust performance of the multi-analyte LC-MS/MS method allowing cassette-dosing that would ultimately reduce animal use and improve efficiency.

We examined condom-use negotiation strategies and condom use among 81 female sex workers (FSWs) in Phnom Penh, Cambodia. Percentages of FSWs who did not negotiate condom use or could not describe a negotiation strategy with native clients, foreign clients, and non-paying partners were 15.0, 29.0 and 67.6 %, respectively. The most common negotiation strategy used was "provision of risk information" for native clients (43.8 %) and non-paying partners (26.5 %), and "direct request" for foreign clients (39.5 %). About half could not describe more than one negotiation strategy. Consistent condom use was high with native clients (98.8 %), yet comparatively lower with foreign clients (86.9 %) and non-paying partners (26.5 %). FSWs who did not negotiate or did not know how to negotiate condom use were less likely to report condom use with non-paying regular partners. Future interventions should enhance condom negotiation strategies between FSWs and all partner types.

Objective: To assess the blood alcohol concentration (BAC; dependent variable) of patients with road traffic injuries (RTIs) presenting at 3 provincial and central hospitals in the Socialist Republic of Viet Nam by age, sex, and road user type (independent variables). This survey formed part of the Viet Nam Road Traffic Injury Prevention Project, funded by Bloomberg Philanthropies., Introduction: RTIs are a leading cause of death and disability in Viet Nam, with 14,690 deaths and 143,940 injuries reported by the Ministry of Health (MOH) in 2010. Research estimates suggest that motorcycle riders and passengers account for 60 percent of fatalities. Alcohol has long been suspected of being a leading cause of road traffic collisions and injuries. However, until now data on this relationship have been limited., Methods: A descriptive cross-sectional study measuring BAC in all consenting patients with RTIs presenting at 3 provincial or central hospitals between July 2009 and September 2010. All results were anonymous and summary information on key variables was sent to MOH and the World Health Organization (WHO) on a monthly basis., Results: Of the 36,418 patients with RTIs presenting to these 3 hospitals between July 2009 and September 2010, BAC analysis was completed on 14,990 patients (41.2%), representing all patients with RTIs 15 years of age and above who consented to anonymous testing. BAC results ranged from 0 to 0.589 g/dL blood, with a mean of 0.0441 g/dL being the average concentration among all tested patients. Of all patients tested, 56.8 percent had no detectable alcohol in their system. Motorcycle riders were most commonly represented in the tested sample (70.7%), with 27.8 percent having a BAC above the legal limit (0.05 g/dL). Car or other vehicle drivers represented 2.7 percent of the sample, with 63.4 percent tested having a BAC above 0 g/dL, the legal limit for these road users., Conclusions: The results of this preliminary study indicate that 29.1 percent of all car drivers and motorcycle riders presenting at hospitals with RTIs exceeded the legal BAC limit for operating a motor vehicle. Though further study is required, this is suggestive that strengthening the enforcement of drink-driving laws is an urgent national road safety priority.

Background: Gender-based violence (GBV) has profound adverse consequences on women's physical, mental, and reproductive health. Although Vietnam has high rates of induced abortion and GBV, literature examining this relationship is lacking., Objective: This study examines the association of GBV with induced abortion among married or partnered women of reproductive age in Thai Nguyen province, Vietnam. In addition, we explore contraceptive use and unintended pregnancy as mediators in the pathway between GBV and induced abortion., Design and Methods: Data were drawn from a cross-sectional survey of 1,281 women aged 18-49 years in four districts of Thai Nguyen province. Bivariate and multivariate logistic regression analyses were applied to examine the associations between lifetime history of GBV, contraceptive use, unintended pregnancy, induced abortion, and repeat abortion, controlling for other covariates., Results: One-third of respondents had undergone induced abortion in their lifetime (33.4%), and 11.5% reported having repeat abortions. The prevalence of any type of GBV was 29.1% (17.0% physical violence, 10.4% sexual violence, and 20.1% emotional violence). History of GBV was associated with induced abortion (OR=1.61, 95% CI: 1.20-2.16) and repeat abortion (OR=2.22, 95% CI: 1.48-3.32). Physical violence was significantly associated with induced abortion, and all three types of violence were associated with repeat abortion. Abused women were more likely than non-abused women to report using contraceptives and having an unintended pregnancy, and these factors were in turn associated with increased risk of induced abortion., Conclusions: GBV is pervasive in Thai Nguyen province and is linked to increased risks of induced abortion and repeat abortion. The findings suggest that a pathway underlying this relationship is increased risk of unintended pregnancy due in part to ineffective use of contraceptives. These findings emphasize the importance of screening and identification of GBV and incorporating women's empowerment in reproductive health and family planning programs.

Introduction: Increasing evidence indicates that gender equity has a significant influence on women's health; yet few culturally specific indicators of gender relations exist which are applicable to health. This study explores dimensions of gender relations perceived by female undergraduate students in southern Vietnamese culture, and qualitatively examines how this perceived gender inequity may influence females' sexual or reproductive health., Methods: Sixty-two female undergraduate students from two universities participated in eight focus group discussions to talk about their perspectives regarding national and local gender equity issues., Results: Although overall gender gaps in the Mekong Delta were perceived to have decreased in comparison to previous times, several specific dimensions of gender relations were emergent in students' discussions. Perceived dimensions of gender relations were comparable to theoretical structures of the Theory of Gender and Power, and to findings from several reports describing the actual inferiority of women. Allocation of housework and social paid work represented salient dimensions of labor. The most salient dimension of power related to women in positions of authority. Salient dimensions of cathexis related to son preference, women's vulnerability to blame or criticism, and double standards or expectations. Findings also suggested that gender inequity potentially influenced women's sexual and reproductive health as regards to health information seeking, gynecological care access, contraceptive use responsibility, and child bearing., Conclusion: Further investigations of the associations between gender relations and different women's sexual and reproductive health outcomes in this region are needed. It may be important to address gender relations as a distal determinant in health interventions in order to promote gender-based equity in sexual and reproductive health.

Chemoresistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). This study demonstrates that the Notch signaling pathway and Notch3 in particular are critical for the regulation of CSCs and tumor resistance to platinum. We show that Notch3 overexpression in tumor cells results in expansion of CSCs and increased platinum chemoresistance. In contrast, γ-secretase inhibitor (GSI), a Notch pathway inhibitor, depletes CSCs and increases tumor sensitivity to platinum. Similarly, a Notch3 siRNA knockdown increases the response to platinum therapy, further demonstrating that modulation of tumor chemosensitivity by GSI is Notch specific. Most importantly, the cisplatin/GSI combination is the only treatment that effectively eliminates both CSCs and the bulk of tumor cells, indicating that a dual combination targeting both populations is needed for tumor eradication. In addition, we found that the cisplatin/GSI combination therapy has a synergistic cytotoxic effect in Notch-dependent tumor cells by enhancing the DNA-damage response, G(2)/M cell-cycle arrest, and apoptosis. Based on these results, we conclude that targeting the Notch pathway could significantly increase tumor sensitivity to platinum therapy. Our study suggests important clinical applications for targeting Notch as part of novel treatment strategies upon diagnosis of ovarian cancer and at recurrence. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increasingly platinum resistant.

The temperature-dependent development of tomato psyllid (also called potato psyllid), Bactericera cockerelli (Sulc), was studied in the laboratory at seven constant temperatures (8, 10, 15, 20, 23, 27, and 31°C), 50-60% RH, and a photoperiod of 16:8 (L:D) h on leaves of whole potato (Solanum tuberosum L.) and tomato (Solanum lycopersicum L.) plants. Developmental time in days for immature stages and total development (egg to adult) on both host species were inversely proportional to temperature between 8 and 27°C but increased at 31°C. One linear and two nonlinear models were fitted to the data. The lower developmental thresholds, calculated using the linear model for egg, total nymph, and total development (from oviposition to adult emergence) were 7.9, 4.2, and 7.1°C (reared on potato) and 7.2, 5.3, and 7.5°C (reared on tomato), respectively. The thermal constant (K) for total development was 358 (reared on potato), and 368 (reared on tomato) degree-days (DD). Two nonlinear models, Briere and Lactin, fit the data well as measured by goodness-of-fit criteria, the residual sum of square (RSS) and Akaike information criterion (AIC). Temperature threshold parameters for these nonlinear models (T(0), T(opt), and T(max)) were estimated for eggs, total nymphal stages, and total development time (egg to adult). The Briere model is highly recommended for the description of temperature-dependent development of tomato psyllid. Results from this study will provide basic information on the biology of tomato psyllid and have potential for the development of predictive models of the seasonal progress of this invasive pest.

Background: Worldwide, the literature on sexual behaviour has documented associations between gender-based relationship inequality and sexual communication ability and the actual use of condoms or other contraceptives among young women. This study aimed to examine these associations among undergraduate female students in the Mekong Delta of Vietnam., Methods: A cross-sectional survey of 1181 female third-year students from two universities in the Mekong Delta was conducted. Latent variable modelling and logistic regression were employed to examine the hypothesised associations., Results: Among the 72.4% of students who had ever had boyfriends, 44.8% indicated that their boyfriends had asked for sex, 13% had had penile-vaginal sex and 10.3% had had oral sex. For those who had had penile-vaginal sex, 33% did not use any contraceptive method, including condoms, during their first sexual intercourse. The greater a student's perception that women were subordinate to men, the lower her self-efficacy for sexual communication and the lower her actual frequency of discussing safer sex matters and asking her partner to use a condom. Sexual communication self-efficacy was associated with actual contraceptive use (P=0.039) but only marginally with condom use (P=0.092) at first sexual intercourse., Conclusion: Sexual health promotion strategies should address the influence of gender relations on young women's sexual communication self-efficacy and the subsequent impact on actual contraceptive and condom use.

Background: Plant polyphenol oxidases (PPOs) are enzymes that typically use molecular oxygen to oxidize ortho-diphenols to ortho-quinones. These commonly cause browning reactions following tissue damage, and may be important in plant defense. Some PPOs function as hydroxylases or in cross-linking reactions, but in most plants their physiological roles are not known. To better understand the importance of PPOs in the plant kingdom, we surveyed PPO gene families in 25 sequenced genomes from chlorophytes, bryophytes, lycophytes, and flowering plants. The PPO genes were then analyzed in silico for gene structure, phylogenetic relationships, and targeting signals., Results: Many previously uncharacterized PPO genes were uncovered. The moss, Physcomitrella patens, contained 13 PPO genes and Selaginella moellendorffii (spike moss) and Glycine max (soybean) each had 11 genes. Populus trichocarpa (poplar) contained a highly diversified gene family with 11 PPO genes, but several flowering plants had only a single PPO gene. By contrast, no PPO-like sequences were identified in several chlorophyte (green algae) genomes or Arabidopsis (A. lyrata and A. thaliana). We found that many PPOs contained one or two introns often near the 3' terminus. Furthermore, N-terminal amino acid sequence analysis using ChloroP and TargetP 1.1 predicted that several putative PPOs are synthesized via the secretory pathway, a unique finding as most PPOs are predicted to be chloroplast proteins. Phylogenetic reconstruction of these sequences revealed that large PPO gene repertoires in some species are mostly a consequence of independent bursts of gene duplication, while the lineage leading to Arabidopsis must have lost all PPO genes., Conclusion: Our survey identified PPOs in gene families of varying sizes in all land plants except in the genus Arabidopsis. While we found variation in intron numbers and positions, overall PPO gene structure is congruent with the phylogenetic relationships based on primary sequence data. The dynamic nature of this gene family differentiates PPO from other oxidative enzymes, and is consistent with a protein important for a diversity of functions relating to environmental adaptation.

Aim: Intima-media thickness (IMT) is considered a surrogate measurement of atherosclerosis but this is still under debate., Methods: To evaluate the relationship between carotid IMT and atherosclerosis, postmortem specimens of the distal segments of the left common carotid artery (CCA) from 133 Korean men aged from 20 to 78 years were used for histopathology and computer-assisted morphometry. Blood lipids and atherosclerosis-associated collagen and elastin were quantitatively analyzed., Results: Correlation coefficients of IMT were smaller than those of intima thickness but IMT was well associated with age (r= 0.55, p <0.00001), atherosclerosis score (or grade, AS, r= 0.73, p < 0.00001), plaque area (PA, r= 0.72, p <0.00001), total cholesterol (TC, r= 0.69, p <0.00001), low-density lipoprotein cholesterol (LDL-c, r= 0.72, p <0.00001) and triglyceride (TG, r= 0.38, p < 0.001). Coronary artery stenosis (CAS) and coronary calcification were also well associated with age (p <0.00001), IMT (p <0.005) and PA (p <0.00001). When IMT was thicker than 1 mm, the possibility of carotid atherosclerosis accompanied with CAS and coronary calcification, TC, LDL-c and TG was much higher (CAS with coronary calcification,p <0.005; TC, p <0.00001; LDL-c, p < 0.00005; TG, p <0.00001). Collagen tended to increase while elastin tended to decrease as AS increased (p <0.005); collagen increased and elastin decreased (p <0.00001) when comparing plaque to the plaque-free area in the same segment., Conclusion: These results support that the carotid IMT in association with TC, LDL-c and TG can be used as a good surrogate marker of atherosclerosis and predictor of coronary heart disease. Plaque formation may influence significant quantitative changes in collagen and elastin.

Polyphenol oxidases (PPOs) are oxidative enzymes that convert monophenols and o-diphenols to o-quinones using molecular oxygen. The quinone products are highly reactive following tissue damage and can interact with cellular constituents and cause oxidative browning and cross-linking. The induction of PPO in some plants as a result of wounding, herbivore attack, or pathogen infection has implicated them in defense. However, PPO-like enzymes that act as specific hydroxylases, for example in lignan and pigment biosynthesis, have also been discovered. Here, we present the first genome-enabled analysis of a PPO gene family. The Populus trichocarpa genome was found to contain a minimum of nine complete PPO genes, and seven of these were characterized further. The PPO gene family includes both recently duplicated and divergent sequences that are 36-98% identical at the amino acid level. Gene expression profiling in poplar tissues and organs revealed that the PPO genes are all differentially expressed during normal development, but that only a small subset of PPO genes are significantly upregulated by wounding, methyl jasmonate or pathogen infection. Our studies also identified PtrPPO13, a novel PPO gene that is predicted to encode an N-terminal signal peptide. Transient expression of green fluorescent protein fusions demonstrated its localization to the vacuolar lumen. Together, our findings show that the poplar PPO family is diverse and is likely linked to diverse physiological functions.