Early clinical and laboratory risk factors of intensive care unit requirement during 2004–2008 dengue epidemics in Singapore: a matched case–control study

Background: Dengue infection can result in severe clinical manifestations requiring intensive care. Effective triage is critical for early clinical management to reduce morbidity and mortality. However, there is limited knowledge on early risk factors of intensive care unit (ICU) requirement. This study aims to identify early clinical and laboratory risk factors of ICU requirement at first presentation in hospital and 24 hours prior to ICU requirement. Method: A retrospective 1:4 matched case–control study was performed with 27 dengue patients who required ICU, and 108 dengue patients who did not require ICU from year 2004–2008, matched by year of dengue presentation. Univariate and multivariate conditional logistic regression were performed. Optimal predictive models were generated with statistically significant risk factors identified using stepwise forward and backward elimination method. Results: ICU dengue patients were significantly older (P=0.003) and had diabetes (P=0.031), compared with non-ICU dengue patients. There were seven deaths among ICU patients at median seven days post fever. At first presentation, the WHO 2009 classification of dengue severity was significantly associated (P<0.001) with ICU, but not the WHO 1997 classification. Early clinical risk factors at presentation associated with ICU requirement were hematocrit change ≥20% concurrent with platelet <50 K [95% confidence-interval (CI)=2.46-30.53], hypoproteinemia (95% CI=1.09-19.74), hypotension (95% CI=1.83-31.79) and severe organ involvement (95% CI=3.30-331). Early laboratory risk factors at presentation were neutrophil proportion (95% CI=1.04-1.17), serum urea (95% CI=1.02-1.56) and alanine aminotransferase level (95% CI=1.001-1.06). This predictive model has sensitivity and specificity up to 88%. Early laboratory risk factors at 24 hours prior to ICU were lymphocyte (95% CI=1.03-1.38) and monocyte proportions (95% CI=1.02-1.78), pulse rate (95% CI=1.002-1.14) and blood pressure (95% CI=0.92-0.996). This predictive model has sensitivity and specificity up to 88.9% and 78%, respectively. Conclusions: This is the first matched case–control study, to our best knowledge, that identified early clinical and laboratory risk factors of ICU requirement during hospitalization. These factors suggested differential pathophysiological background of dengue patients as early as first presentation prior to ICU requirement, which may reflect the pathogenesis of dengue severity. These risk models may facilitate clinicians in triage of patients, after validating in larger independent studies.Published versio

Mitochondrial Apoptosis and FAK Signaling Disruption by a Novel Histone Deacetylase Inhibitor, HTPB, in Antitumor and Antimetastatic Mouse Models

BACKGROUND: Compound targeting histone deacetylase (HDAC) represents a new era in molecular cancer therapeutics. However, effective HDAC inhibitors for the treatment of solid tumors remain to be developed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we propose a novel HDAC inhibitor, N-Hydroxy-4-(4-phenylbutyryl-amino) benzamide (HTPB), as a potential chemotherapeutic drug for solid tumors. The HDAC inhibition of HTPB was confirmed using HDAC activity assay. The antiproliferative and anti-migratory mechanisms of HTPB were investigated by cell proliferation, flow cytometry, DNA ladder, caspase activity, Rho activity, F-actin polymerization, and gelatin-zymography for matrix metalloproteinases (MMPs). Mice with tumor xenograft and experimental metastasis model were used to evaluate effects on tumor growth and metastasis. Our results indicated that HTPB was a pan-HDAC inhibitor in suppressing cell viability specifically of lung cancer cells but not of the normal lung cells. Upon HTPB treatment, cell cycle arrest was induced and subsequently led to mitochondria-mediated apoptosis. HTPB disrupted F-actin dynamics via downregulating RhoA activity. Moreover, HTPB inhibited activity of MMP2 and MMP9, reduced integrin-β1/focal adhesion complex formation and decreased pericellular poly-fibronectin assemblies. Finally, intraperitoneal injection or oral administration of HTPB efficiently inhibited A549 xenograft tumor growth in vivo without side effects. HTPB delayed lung metastasis of 4T1 mouse breast cancer cells. Acetylation of histone and non-histone proteins, induction of apoptotic-related proteins and de-phosphorylation of focal adhesion kinase were confirmed in treated mice. CONCLUSIONS/SIGNIFICANCE: These results suggested that intrinsic apoptotic pathway may involve in anti-tumor growth effects of HTPB in lung cancer cells. HTPB significantly suppresses tumor metastasis partly through inhibition of integrin-β1/FAK/MMP/RhoA/F-actin pathways. We have provided convincing preclinical evidence that HTPB is a potent HDAC targeted inhibitor and is thus a promising candidate for lung cancer chemotherapy

Membrane-mediated interactions

Interactions mediated by the cell membrane between inclusions, such as membrane proteins or antimicrobial peptides, play important roles in their biological activity. They also constitute a fascinating challenge for physicists, since they test the boundaries of our understanding of self-assembled lipid membranes, which are remarkable examples of two-dimensional complex fluids. Inclusions can couple to various degrees of freedom of the membrane, resulting in different types of interactions. In this chapter, we review the membrane-mediated interactions that arise from direct constraints imposed by inclusions on the shape of the membrane. These effects are generic and do not depend on specific chemical interactions. Hence, they can be studied using coarse-grained soft matter descriptions. We deal with long-range membrane-mediated interactions due to the constraints imposed by inclusions on membrane curvature and on its fluctuations. We also discuss the shorter-range interactions that arise from the constraints on membrane thickness imposed by inclusions presenting a hydrophobic mismatch with the membrane.Comment: 38 pages, 10 figures, pre-submission version. In: Bassereau P., Sens P. (eds) Physics of Biological Membranes. Springer, Cha

A cross-site comparing study on child behavior and emotional problems in Hong Kong and Chengdu

Objective: To compare the behavior and emotional problems of children in Hong Kong and in Chengdu, and to investigate the effects of socio-cultural factors on assessments. Methods: A total of 2673 Hong Kong children and 858 Chengdu Children aged 6-18 years old were randomly sampled. Their parents completed Achenbach’s Child Behavior Checklist (CBCL). Results: Most of the subscale scores were significantly higher in Hong Kong samples than those in Chengdu samples. The differences in the subscales of anxious/depressed, attention problems and externalizing were very significant between two sites measured by the effect sizes. Conclusions: The results suggest that there may be difference in the prevalence of children psychopathology in these two cities. However, the possibility of differences in parental awareness, attitudes and reporting bias in the children’s psychopathology cannot be excluded. 目的 :比較香港和成都市少年兒童的行為和情緒問題 ,探討社會文化因素對評定結果的影響。方法 :使用Achenbach兒童行為量表 (Achenbach’sChildBehaviorChecklist,CBCL)對香港 2 6 73名、成都市 85 8名 6— 18歲樣本進行評定。結果 :發現CBCL多數綜合征評分香港地區高于成都。作用強度分析可見兩地的焦慮抑郁、注意缺陷和外向性因子的差異特別明顯。結論 :可能香港少年兒童的心理問題出現率高于成都市 ,但也不能排除兩地父母對兒童心理問題的認識理解、態度以及評定偏差有所不同造成兩地評定結果的差

A systematic review of the methodology of sonographic assessment of upper limb activities-associated carpal tunnel syndrome

202207 bcwwVersion of RecordOthersPolyU HTI Internal Funding; Shenzhen Basic Research Funding; Science and Technology Innovation Commission of Shenzhen MunicipalityPublishe

Preparation and characterisation of poly(vinyl) alcohol (PVA)/starch (ST)/halloysite nanotube (HNT) nanocomposite films as renewable materials

Poly(vinyl) alcohol (PVA)/starch (ST) films (weight ratio: 80/20) were prepared using a solution casting method, in the presence of 30 wt% glycerol (GL) as a plasticiser. Halloysite nanotubes (HNTs) were used as relatively new clay nanofillers to PVA/ST/GL blends for more economical material packaging. HNTs at filler loadings of 0.25, 0.5, 1, 3 and 5 wt% were incorporated to enhance mechanical and thermal properties of resulting PVA/ST/HNT nanocomposites. The tensile strength of such nanocomposites was found to be improved by 20 and 3.4%, respectively, with the inclusion of 0.25 and 0.5 wt% HNTs as opposed to those of PVA/ST/GL blends. However, a decreasing strength trend was observed beyond the HNT loading of 0.5 wt% due to HNT agglomeration, as evidenced by relevant micrographs via scanning electron microscopy (SEM). However, Young’s modulus was enhanced by 148% with the addition of 1 wt% HNTs when compared with PVA/ST/GL blends. X-ray diffraction (XRD) analysis is indicative of slightly intercalated nanocomposite structures formed at low HNT loadings of 0.25–1 wt%. In general, the incorporation of HNTs improved the thermal stability of PVA/ST/GL blends by increasing melting and decomposition temperatures along with the reduction in weight loss