Copy number variation (CNV) is a form of genetic variation in addition to single nucleotide polymorphisms. The significance of CNV in the manifestation of a number of diseases is only recently receiving considerable attention. We genotyped 163 dengue patients from Peninsular Malaysia for genes possibly linked to dengue infection using quantitative real-time PCR. Here, we report a serendipitous discovery of a novel rare CNV of the ABCF1 gene among the dengue patients. Among these patients, two had a gain of 1 copy (CN = 3) and one had lost 1 copy (CN = 1), indicating that a rare CNV of the ABCF1 gene was detected among dengue patients from Peninsular Malaysia. Although the gene is suspected to regulate inflammatory responses and pathogen-induced cytokine storm, its relevance to dengue requires further investigation.
MeSH terms: Dengue/genetics*; Dengue/pathology; Genotype; Humans; Malaysia; Genetic Variation; ATP-Binding Cassette Transporters/genetics*; Genetic Predisposition to Disease; DNA Copy Number Variations*
This paper reports the utilization of ZnO nanorod arrays (NRAs) doped with various concentrations of Ga (0, 0.5, 1, 2, and 3 at %) as electron acceptors in organic solar cells. The donor, poly(3-hexylthiophene) (P3HT), was spin coated onto Ga-doped ZnO NRAs that were grown on fluorine-doped tin oxide (FTO) substrates, followed by the deposition of a Ag electrode by a magnetron sputtering method. Adjusting the Ga precursor concentration allowed for the control of the structural and optical properties of ZnO NRAs. The short circuit current density increased with increasing Ga concentration from 0 to 1 at %, mainly because of improved exciton dissociation and increased charge extraction. Meanwhile, the reduced charge recombination and lower hole leakage current led to an increase in the open circuit voltage with Ga concentrations up to 1 at %. The device with the optimum Ga concentration of 1 at % exhibited power conversion efficiency nearly three times higher compared to the device without Ga doping. This finding suggests that the incorporation of Ga can be a simple and effective approach to improve the photovoltaic performance of organic solar cells.
Familial hypercholesterolemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected, and current treatment is often suboptimal. To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment, and management of FH in adults and children and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of noncholesterol risk factors, and the safe and effective use of low-density lipoprotein-lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed. This international guidance acknowledges evidence gaps but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be used to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.
MeSH terms: Adult; Anticholesteremic Agents/administration & dosage; Child; Cost-Benefit Analysis; Genetic Testing; Humans; Hyperlipoproteinemia Type II/metabolism; Hyperlipoproteinemia Type II/pathology*; Hyperlipoproteinemia Type II/therapy*; Lipoproteins, LDL/metabolism*; Cholesterol, LDL/metabolism*; Risk Factors; Guidelines as Topic
Doripenem is approved in the Asia-Pacific (APAC) region for treating nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP), complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs). Clinical usage of doripenem (500mg intravenously, infused over 1h or 4h every 8h for 5-14 days) in APAC was evaluated in a prospective, open-label, non-comparative, multicentre study of inpatients (≥18 years) with NP, VAP, cIAI or cUTI. A total of 216 [intention-to-treat (ITT)] patients received doripenem: 53 NP (24.5%); 77 VAP (35.6%); 67 cIAI (31.0%); and 19 cUTI (8.8%). Doripenem MIC90 values for Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae were 32, 32, 0.094 and 0.64μg/mL, respectively. Doripenem was used most commonly as monotherapy (86.6%) and as second-line therapy (62.0%). The clinical cure rate in clinically evaluable patients was 86.7% at the end of therapy (EOT) and 87.1% at test of cure (TOC) (7-14 days after EOT). In the ITT population, overall clinical cure rates were 66.2% at EOT and 56.5% at TOC. The median duration of hospital stay, intensive care unit (ICU) stay and mechanical ventilation was 20, 12 and 10 days, respectively. Of 146 discharged patients, 7 were re-admitted within 28 days of EOT; 1 VAP patient was re-admitted to the ICU. The all-cause mortality rate was 22.7% (49/216). The most common treatment-related adverse events were diarrhoea (1.4%) and vomiting (1.4%). Doripenem is a viable option for treating APAC patients with NP, VAP, cIAI or cUTI. [ClinicalTrials.gov: NCT 00986102].
Erythrocytes require glucose-6-phosphate dehydrogenase (G6PD) to generate NADPH and protect themselves against hemolytic anemia induced by oxidative stress. Peroxiredoxin 2 (Prx2) is a major antioxidant enzyme that requires NADPH to recycle its oxidized (disulfide-bonded) form. Our aims were to determine whether Prx2 is more highly oxidized in G6PD-deficient erythrocytes and whether these cells are able to recycle oxidized Prx2 after oxidant challenge. Blood was obtained from 61 Malaysian neonates with G6PD deficiency (average 33% normal activity) and 86 controls. Prx2 redox state was analyzed by Western blotting under nonreducing conditions. Prx2 in freshly isolated blood was predominantly reduced in both groups, but the median level of oxidation was significantly higher (8 vs 3%) and the range greater for the G6PD-deficient population. When treated with reagent H2O2, the G6PD-deficient erythrocytes were severely compromised in their ability to recycle oxidized Prx2, with only 27 or 4% reduction after 1 h treatment with 0.1 or 1 mM H2O2 respectively, compared with >97% reduction in control erythrocytes. The accumulation of oxidized Prx2 in oxidatively stressed erythrocytes with common G6PD variants suggests that impaired antioxidant activity of Prx2 could contribute to the hemolysis and other complications associated with the condition.-Cheah, F.-C., Peskin, A. V., Wong, F.-L., Ithnin, A., Othman, A., Winterbourn, C. C. Increased basal oxidation of peroxiredoxin 2 and limited peroxiredoxin recycling in glucose-6-phosphate dehydrogenase deficient erythrocytes from newborn infants.
BACKGROUND: Recent studies reported a high prevalence of small intestinal bacterial overgrowth (SIBO) in Parkinson's disease (PD), and a possible association with gastrointestinal symptoms and worse motor function. We aimed to study the prevalence and the potential impact of SIBO on gastrointestinal symptoms, motor function, and quality of life in a large cohort of PD patients.
METHODS: 103 Consecutive PD patients were assessed using the lactulose-hydrogen breath test; questionnaires of gastrointestinal symptoms and quality of life (PDQ-39); the Unified PD Rating Scale (UPDRS) including "on"-medication Part III (motor severity) score; and objective and quantitative measures of bradykinesia (Purdue Pegboard and timed test of gait). Patients and evaluating investigators were blind to SIBO status.
RESULTS: 25.3% of PD patients were SIBO-positive. SIBO-positive patients had a shorter mean duration of PD (5.2 ± 4.1 vs. 8.1 ± 5.5 years, P = 0.007). After adjusting for disease duration, SIBO was significantly associated with lower constipation and tenesmus severity scores, but worse scores across a range of "on"-medication motor assessments (accounting for 4.2-9.0% of the variance in motor scores). There was no association between SIBO and motor fluctuations or PDQ-39 Summary Index scores.
CONCLUSIONS: This is the largest study to date on SIBO in PD. SIBO was detected in one quarter of patients, including patients recently diagnosed with the disease. SIBO was not associated with worse gastrointestinal symptoms, but independently predicted worse motor function. Properly designed treatment trials are needed to confirm a causal link between SIBO and worse motor function in PD.
KEYWORDS: Gastrointestinal dysfunction; Parkinson's disease/Parkinsonism; Small intestinal bacterial overgrowth
Many biological research areas such as drug design require gene regulatory networks to provide clear insight and understanding of the cellular process in living cells. This is because interactions among the genes and their products play an important role in many molecular processes. A gene regulatory network can act as a blueprint for the researchers to observe the relationships among genes. Due to its importance, several computational approaches have been proposed to infer gene regulatory networks from gene expression data. In this review, six inference approaches are discussed: Boolean network, probabilistic Boolean network, ordinary differential equation, neural network, Bayesian network, and dynamic Bayesian network. These approaches are discussed in terms of introduction, methodology and recent applications of these approaches in gene regulatory network construction. These approaches are also compared in the discussion section. Furthermore, the strengths and weaknesses of these computational approaches are described.
The [Co(Me(2)Salen)(PBu(3))(OH(2))]BF4 and [Co(Me(2)Salen)(PPh(3))(Solv)]BF(4), complexes were synthesized and characterized by FT-IR, UV-Vis, (1)H NMR spectroscopy and elemental analysis techniques. The coordination geometry of [Co(Me(2)Salen)(PPh(3))(H(2)O)]BF(4) was determined by X-ray crystallography. It has been found that the complex is containing [Co(Me(2)Salen)(PPh(3))(H(2)O)]BF(4) and [Co(Me(2)Salen)(PPh(3))(EtOH)]BF(4) hexacoordinate species in the solid state. Cobalt atom exhibits a distorted octahedral geometry and the Me(2)Salen ligand has the N2O2 coordinated environment in the equatorial plane. The [Co(Me(2)Salen)(PPh(3))(H(2)O)]BF(4) complex shows a dimeric structure via hydrogen bonding between the phenolate oxygen and hydrogens of coordinated H2O molecule. These complexes were incorporated into Montmorillonite-K10 nanoclay. The modified clays were identified by FT-IR, XRD, EDX, TGA/DTA, SEM and TEM techniques. According to the XRD results of the new nanohybrid materials, the Schiff base complexes are intercalated in the interlayer spaces of the clay. SEM and TEM micrographs show that the resulting hybrid nanomaterials have layer structures. Also, TGA/DTG results show that the intercalation reaction was taken place successfully.
To evaluate ocular biometric parameters and darkroom prone provocative test (DPPT) in family members of primary angle closure (PAC) glaucoma (PACG) patients and to establish any correlation between these biometric parameters and the DPPT response.
MeSH terms: Adult; Aged; Aged, 80 and over; Biometry/methods; Dark Adaptation*; Diagnostic Techniques, Ophthalmological*; Family Health; Female; Gonioscopy; Humans; Male; Middle Aged; Risk Factors; Tonometry, Ocular; Glaucoma, Angle-Closure/diagnosis*; Microscopy, Acoustic; Early Diagnosis
Split-skin grafting (SSG) is the gold standard treatment for full-thickness skin defects. For certain patients, however, an extensive skin lesion resulted in inadequacies of the donor site. Tissue engineering offers an alternative approach by using a very small portion of an individual's skin to harvest cells for propagation and biomaterials to support the cells for implantation. The objective of this study was to determine the effectiveness of autologous bilayered tissue-engineered skin (BTES) and single-layer tissue-engineered skin composed of only keratinocytes (SLTES-K) or fibroblasts (SLTES-F) as alternatives for full-thickness wound healing in a sheep model. Full-thickness skin biopsies were harvested from adult sheep. Isolated fibroblasts were cultured using medium Ham's F12: Dulbecco modified Eagle medium supplemented with 10% fetal bovine serum, whereas the keratinocytes were cultured using Define Keratinocytes Serum Free Medium. The BTES, SLTES-K, and SLTES-F were constructed using autologous fibrin as a biomaterial. Eight full-thickness wounds were created on the dorsum of the body of the sheep. On 4 wounds, polyvinyl chloride rings were used as chambers to prevent cell migration at the edge. The wounds were observed at days 7, 14, and 21. After 3 weeks of implantation, the sheep were euthanized and the skins were harvested. The excised tissues were fixed in formalin for histological examination via hematoxylin-eosin, Masson trichrome, and elastin van Gieson staining. The results showed that BTES, SLTES-K, and SLTES-F promote wound healing in nonchambered and chambered wounds, and BTES demonstrated the best healing potential. In conclusion, BTES proved to be an effective tissue-engineered construct that can promote the healing of full-thickness skin lesions. With the support of further clinical trials, this procedure could be an alternative to SSG for patients with partial- and full-thickness burns.
Tropical agriculture is expanding rapidly at the expense of forest, driving a global extinction crisis. How to create agricultural landscapes that minimise the clearance of forest and maximise sustainability is thus a key issue. One possibility is protecting natural forest within or adjacent to crop monocultures to harness important ecosystem services provided by biodiversity spill-over that may facilitate production. Yet this contrasts with the conflicting potential that the retention of forest exports dis-services, such as agricultural pests. We focus on oil palm and obtained yields from 499 plantation parcels spanning a total of ≈23,000 ha of oil palm plantation in Sabah, Malaysian Borneo. We investigate the relationship between the extent and proximity of both contiguous and fragmented dipterocarp forest cover and oil palm yield, controlling for variation in oil palm age and for environmental heterogeneity by incorporating proximity to non-native forestry plantations, other oil palm plantations, and large rivers, elevation and soil type in our models. The extent of forest cover and proximity to dipterocarp forest were not significant predictors of oil palm yield. Similarly, proximity to large rivers and other oil palm plantations, as well as soil type had no significant effect. Instead, lower elevation and closer proximity to forestry plantations had significant positive impacts on oil palm yield. These findings suggest that if dipterocarp forests are exporting ecosystem service benefits or ecosystem dis-services, that the net effect on yield is neutral. There is thus no evidence to support arguments that forest should be retained within or adjacent to oil palm monocultures for the provision of ecosystem services that benefit yield. We urge for more nuanced assessments of the impacts of forest and biodiversity on yields in crop monocultures to better understand their role in sustainable agriculture.
The mantled floral phenotype of oil palm (Elaeis guineensis) affects somatic embryogenesis-derived individuals and is morphologically similar to mutants defective in the B-class MADS-box genes. This somaclonal variation has been previously demonstrated to be associated to a significant deficit in genome-wide DNA methylation. In order to elucidate the possible role of DNA methylation in the transcriptional regulation of EgDEF1, the APETALA3 ortholog of oil palm, we studied this epigenetic mark within the gene in parallel with transcript accumulation in both normal and mantled developing inflorescences. We also examined the methylation and expression of two neighboring retrotransposons that might interfere with EgDEF1 regulation. We show that the EgDEF1 gene is essentially unmethylated and that its methylation pattern does not change with the floral phenotype whereas expression is dramatically different, ruling out a direct implication of DNA methylation in the regulation of this gene. Also, we find that both the gypsy element inserted within an intron of the EgDEF1 gene and the copia element located upstream from the promoter are heavily methylated and show little or no expression. Interestingly, we identify a shorter, alternative transcript produced by EgDEF1 and characterize its accumulation with respect to its full-length counterpart. We demonstrate that, depending on the floral phenotype, the respective proportions of these two transcripts change differently during inflorescence development. We discuss the possible phenotypical consequences of this alternative splicing and the new questions it raises in the search for the molecular mechanisms underlying the mantled phenotype in the oil palm.
The steady boundary layer flow and heat transfer of a nanofluid past a nonlinearly permeable stretching/shrinking sheet is numerically studied. The governing partial differential equations are reduced into a system of ordinary differential equations using a similarity transformation, which are then solved numerically using a shooting method. The local Nusselt number and the local Sherwood number and some samples of velocity, temperature and nanoparticle concentration profiles are graphically presented and discussed. Effects of the suction parameter, thermophoresis parameter, Brownian motion parameter and the stretching/shrinking parameter on the flow, concentration and heat transfer characteristics are thoroughly investigated. Dual solutions are found to exist in a certain range of the stretching/shrinking parameter for both shrinking and stretching cases. Results indicate that suction widens the range of the stretching/shrinking parameter for which the solution exists.
Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple-blind, placebo-controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25-item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p
BACKGROUND: This study assessed the efficacy and safety of the once-daily glucagon-like peptide-1 receptor agonist, lixisenatide, in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin ± sulfonylurea.
METHODS: In this 24-week, double-blind, placebo-controlled, multinational study, patients were randomized to lixisenatide 20 µg once daily or placebo. The primary endpoint was absolute change in glycated haemoglobin (HbA1c ) from baseline to week 24.
RESULTS: A total of 391 patients were randomized. Lixisenatide significantly reduced HbA1c levels compared with placebo (LS mean difference: -0.36%, p = 0.0004). A significantly higher proportion of lixisenatide-treated patients achieved HbA1c targets of <7% (p = 0.003) and ≤6.5% (p = 0.001) versus placebo. Lixisenatide was associated with a statistically significant reduction in 2-h postprandial plasma glucose after a standardized breakfast versus placebo (LS mean difference: -4.28 mmol/L, p
Cerebral tuberculosis is the most severe type of extrapulmonary disease that is in developing countries highly predominant in children. Meningeal tuberculosis is the most common form and usually begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. In comparison with the lung, Mycobacterium tuberculosis induces a very different immune response when infect the central nervous system. Herein, we review several aspects of the pathogenesis and immune response in pulmonary and cerebral tuberculosis in humans and experimental models and discuss the implications of this response in the cerebral infection outcome.
BACKGROUND: Work-family conflict has received increasing attention in recent decades in the area of workplace stressors, which can affect employees' health. However, the dimensionality of the work-family conflict construct among the Malay-speaking population has not been clarified. In order to do so, it is crucial to use an instrument that is appropriate and valid for the Malay-speaking population. As such, the goal of this study was to validate and test the dimensionality of the Malay version of the Work-Family Conflict Questionnaire.
METHODS: The present study conducted exploratory factor analysis, confirmatory factor analysis, discriminant validity, convergent validity, and internal consistency, using Cronbach's alpha, of the work-family conflict construct among 332 working women in Malaysia.
RESULTS: The results supported the existence of four dimensions in the Work-Family Conflict Questionnaire that distinguish between time based and strain-based work-family conflict and family-work conflict. The discriminant validity, convergent validity, and internal consistency of this construct are adequately supported.
CONCLUSION: The findings of this study supported the existence of discriminant and convergent validity, as well as adequate reliability, for the construct. Thus, the Work-Family Conflict Questionnaire is a valid and reliable instrument among Malay-speaking working women.
KEYWORDS: factor analysis; professional-family relation; validity and reliability; working women
MeSH terms: Attention; Goals; Malaysia; Surveys and Questionnaires; Occupational Health; Workplace; Family Conflict