Household cleaning products and the risk of allergic dermatitis: a prospective cohort study with primary-school children.

BACKGROUND: Household cleaning products are widely used by the public, but limited data have been obtained on whether their use induces allergic dermatitis in children. OBJECTIVE: This study investigated the association between exposure to household cleaning products and allergic dermatitis in primary-school children. METHODS: A prospective cohort study of Hong Kong primary-school children was conducted between 2012 and 2014. A baseline survey was administered to 1812 students who did not have allergic dermatitis. Information on respiratory symptoms, exposure to household chemical cleaning products and other topics was collected using a self-administered questionnaire. A cumulative chemical burden (CCB) score was calculated for each student by summing the duration of exposure to 14 chemical cleaning products. Principal component analysis was used to identify patterns in the use of these cleaning products. Logistic regression was performed to calculate relative risk (RR) with 95% confidence intervals (CIs) after adjusting for potential confounders. RESULTS: Eighty-nine (4.9%) of the students surveyed had dermatitis during the follow-up. However, exposure to individual chemical cleaning products was not found to be associated with the children's allergic dermatitis (all P > 0.05). In contrast to those in the lowest tertile, neither CCB scores in the middle tertile (RR: 1.16, 95% CI: 0.67 to 2.00) nor those in the highest tertile (RR: 1.24, 95% CI: 0.73 to 2.14) were significantly associated with the risk of allergic dermatitis. The adjusted RR for every 5-unit increment in CCB score was 1.01 (95% CI: 0.98 to 1.03). Four patterns of cleaning-product use were derived, but none were found to be associated with the risk of dermatitis (all P > 0.05). CONCLUSION: The use of household chemical cleaning products is not associated with the risk of dermatitis in primary-school children.

Hyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns.

Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency. A human embryonic stem cell line (VAL3) was used as the cell model for studying the effects of hyperglycemia upon differentiation into definitive endoderm (DE), an early stage of the pancreatic lineage. Hyperglycemic conditions significantly down-regulated the expression levels of DE markers SOX17, FOXA2, CXCR4 and EOMES during differentiation. This was associated with retention of the repressive histone methylation mark H3K27me3 on their promoters under hyperglycemic conditions. The disruption of histone methylation patterns was observed as early as the mesendoderm stage, with Wnt/ß-catenin signaling being suppressed during hyperglycemia. Treatment with Wnt/ß-catenin signaling activator CHIR-99021 restored the expression levels and chromatin methylation status of DE markers, even in a hyperglycemic environment. The disruption of DE development was also found in mouse embryos at day 7.5 post coitum from diabetic mothers. Furthermore, disruption of DE differentiation in VAL3 cells led to subsequent impairment in pancreatic progenitor formation. Thus, early exposure to hyperglycemic conditions hinders DE development with a possible relationship to the later impairment of pancreas specification.

Chaperones and intimate physical examinations: what do male and female patients want?

INTRODUCTION: Many studies of patients' perception of a medical chaperone have focused on female patients; that of male patients are less well studied. Moreover, previous studies were largely based on patient populations in English-speaking countries. Therefore, this study was conducted to investigate the perception and attitude of male and female Chinese patients to the presence of a chaperone during an intimate physical examination. METHODS: A cross-sectional guided questionnaire survey was conducted on a convenient sample of 150 patients at a public teaching hospital in Hong Kong. RESULTS: Over 90% of the participants considered the presence of a chaperone appropriate during intimate physical examination, and 84% felt that doctors, irrespective of gender, should always request the presence of a chaperone. The most commonly cited reasons included the availability of an objective account should any legal issue arise, protection against sexual harassment, and to provide psychological support. This contrasted with the experience of those who had previously undergone an intimate physical examination of whom only 72.6% of women and 35.7% of men had reportedly been chaperoned. Among female participants, 75.0% preferred to be chaperoned during an intimate physical examination by a male doctor, and 28.6% would still prefer to be chaperoned when being examined by a female doctor. Among male participants, over 50% indicated no specific preference but a substantial minority reported a preference for chaperoned examination (21.2% for male doctor and 25.8% for female doctor). CONCLUSIONS: Patients in Hong Kong have a high degree of acceptance and expectations about the role of a medical chaperone. Both female and male patients prefer such practice regardless of physician gender. Doctors are strongly encouraged to discuss the issue openly with their patients before they conduct any intimate physical examination.

Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis.

PURPOSE: Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health-related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. METHODS: English- and Chinese-speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. RESULTS: Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well-being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. CONCLUSION: Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships.

Tenofovir-based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir.

Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore, our aim was to compare the effectiveness of two alternate therapies--tenofovir (TDF) monotherapy and combination therapy of ETV+TDF--in CHB patients with ETV partial virological response. We conducted a retrospective study of 68 patients who had partial virological response to ETV, defined as having detectable HBV DNA following at least 12 months of ETV, and were switched to TDF monotherapy (n = 25) or ETV+TDF (n = 43). Patients were seen in seven US liver/community-based clinics and started on ETV between 2005 and 2009. The majority of patients were male; the vast majority were Asian and had positive hepatitis B e antigen (HBeAg). Patients in both groups had similar pretreatment characteristics. Complete viral suppression (CVS) rates with TDF monotherapy and ETV+TDF were similar after 6 months (71% vs 83%, P = 0.23) and 12 months (86% vs 84%, P = 0.85), and there was no statistically significant difference in CVS rates even when only patients with higher HBV DNA levels at switch (>1000 IU/mL) were evaluated. Multivariate analysis indicated that ETV+TDF was not an independent predictor of CVS compared to TDF monotherapy (OR = 1.19, P = 0.63). In conclusion, TDF monotherapy and ETV+TDF are comparable in achieving CVS in CHB patients with partial virological response to ETV. Long-term alternate therapy with one pill (TDF monotherapy) vs two pills (ETV+TDF) could lead to lower nonadherence rates and better treatment outcomes.

Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits.

Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism.

CCHCR1 interacts with EDC4, suggesting its localization in P-bodies.

Coiled-coil alpha-helical rod protein 1 (CCHCR1) is suggested as a candidate biomarker for psoriasis for more than a decade but its function remains poorly understood because of the inconsistent findings in the literature. CCHCR1 protein is suggested to be localized in the cytoplasm, nucleus, mitochondria, or centrosome and to regulate various cellular functions, including steroidogenesis, proliferation, differentiation, and cytoskeleton organization. In this study, we attempted to find a consensus between these findings by identifying the interaction partners of CCHCR1 using co-immunoprecipiation with a stable cell line expressing EGFP-tagged CCHCR1. Out of more than 100 co-immunoprecipitants identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), the enhancer of mRNA-decapping protein 4 (EDC4), which is a processing body (P-body) component, was particularly found to be the major interacting partner of CCHCR1. Confocal imaging confirmed the localization of CCHCR1 in P-bodies and its N-terminus is required for this subcellular localization, suggesting that CCHCR1 is a novel P-body component. As P-bodies are the site for mRNA metabolism, our findings provide a molecular basis for the function of CCHCR1, any disruption of which may affect the transcriptome of the cell, and causing abnormal cell functions.

Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated colitis in Cnlp(-/-) mice.

Cathelicidin is a pleiotropic host defense peptide secreted by epithelial and immune cells. Whether endogenous cathelicidin is protective against ulcerative colitis, however, is unclear. Here we sought to delineate the role of endogenous murine cathelicidin (mCRAMP) and the therapeutic efficacy of intrarectal administration of mCRAMP-encoding plasmid in ulcerative colitis using dextran sulfate sodium (DSS)-challenged cathelicidin-knockout (Cnlp(-/-)) mice as a model. Cnlp(-/-) mice had more severe symptoms and mucosal disruption than the wild-type mice in response to DSS challenge. The tissue levels of interleukin-1ß and tumor necrosis factor-α, myeloperoxidase activity and the number of apoptotic cells were increased in the colon of DSS-challenged Cnlp(-/-) mice. Moreover, mucus secretion and mucin gene expression were impaired in Cnlp(-/-) mice. All these abnormalities were reversed by the intrarectal administration of mCRAMP or mCRAMP-encoding plasmid. Taken together, endogenous cathelicidin may protect against ulcerative colitis through modulation of inflammation and mucus secretion.

Cathelicidin protects against Helicobacter pylori colonization and the associated gastritis in mice.

Cathelicidin, an antimicrobial peptide of the innate immune system, has been shown to modulate microbial growth, wound healing and inflammation. However, whether cathelicidin controls Helicobacter pylori infection in vivo remains unexplored. This study sought to elucidate the role of endogenous and exogenous mouse cathelicidin (CRAMP) in the protection against H. pylori infection and the associated gastritis in mice. Results showed that genetic ablation of CRAMP in mice significantly increased the susceptibility of H. pylori colonization and the associated gastritis as compared with the wild-type control. Furthermore, replenishment with exogenous CRAMP, delivered via a bioengineered CRAMP-secreting strain of Lactococcus lactis, reduced H. pylori density in the stomach as well as the associated inflammatory cell infiltration and cytokine production. Collectively, these findings indicate that cathelicidin protects against H. pylori infection and its associated gastritis in vivo. Our study also demonstrates the feasibility of using the transformed food-grade bacteria to deliver cathelicidin, which may have potential clinical applications in the treatment of H. pylori infection in humans.

Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins.

BACKGROUND: Childhood adverse experiences are known to induce persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. However, the mechanisms by which these experiences shape the neuroendocrine response to stress remain unclear. Method We tested whether bullying victimization influenced serotonin transporter gene (SERT) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994-1995 cohort of families with twins. RESULTS: Bullied twins had higher SERT DNA methylation at the age of 10 years compared with their non-bullied MZ co-twins. This group difference cannot be attributed to the children's genetic makeup or their shared familial environments because of the study design. Bullied twins also showed increasing methylation levels between the age of 5 years, prior to bullying victimization, and the age of 10 years whereas no such increase was detected in non-bullied twins across time. Moreover, children with higher SERT methylation levels had blunted cortisol responses to stress. CONCLUSIONS: Our study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific cytosine-phosphate-guanine (CpG) site in the SERT promoter and HPA functioning and suggests that these two systems may be functionally associated.

Preclinical predictors of anticancer drug efficacy: critical assessment with emphasis on whether nanomolar potency should be required of candidate agents.

In the current paradigm of anticancer drug development, candidate compounds are evaluated by testing their in vitro potency against molecular targets relevant to carcinogenesis, their effect on cultured cancer cells, and their ability to inhibit cancer growth in animal models. We discuss the key assumptions inherent in these approaches. In recent years, great emphasis has been placed on selecting for development compounds with nanomolar in vitro potency, expecting that they will be efficacious and safer based on the assumption that they can be used at lower doses ("the nanomolar rule"). However, this rule ignores critical parameters affecting efficacy and toxicity such as physiochemical and absorption, distribution, metabolism and excretion properties, off-target effects, and multitargeting activities. Thus, uncritical application of the nanomolar rule may reject efficacious compounds or select ineffective or toxic compounds. We present examples of efficacious chemotherapeutic (alkylating agents, hormonal agents, antimetabolites, thalidomide, and valproic acid) and chemopreventive (aspirin and sulindac) agents having millimolar potency and compounds with nanomolar potency (cyclooxygenase-2 inhibitors) that, nevertheless, failed or proved to be unsafe. The effect of candidate drugs on animal models of cancer is a better predictor of human drug efficacy; particularly useful are tumor xenografts. Given the cost of failure at clinical stages, it is imperative to keep in mind the limitations of the nanomolar rule and use relevant in vivo models early in drug discovery to prioritize candidates. Although in vivo models will continue having a major role in cancer drug development, more robust approaches that combine high predictive ability with simplicity and low cost should be developed.

Little-Parks oscillations in an insulator.

We present the results of a magnetoresistance study of the disorder-induced superconductor-insulator transition in an amorphous indium-oxide thin film patterned by a nanoscale periodic array of holes. We observed Little-Parks-like oscillations over our entire range of disorder spanning the transition. The period of oscillations was unchanged and corresponded to the superconducting flux quantum in the superconducting as well as in the insulating phases. Our results provide direct evidence for electron pairing in the insulator bordering with superconductivity.

A systematic review of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds.

BACKGROUND: Stromal vascular fraction (SVF), derived enzymatically or mechanically from adipose tissue, contains a heterogenous population of cells and stroma, including multipotent stem cells. The regenerative capacity of SVF may potentially be adapted for a broad range of clinical applications, including the healing of acute cutaneous wounds. OBJECTIVE: To evaluate the available literature on the efficacy and safety of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds in humans. METHODS: A systematic review of the literature utilizing MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify published clinical trials of autologous adipose-derived SVF or similar ADSC-containing derivatives for patients with acute cutaneous wounds. This was supplemented by searches for ongoing clinical trials through ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. RESULTS: 872 records were initially retrieved. Application of inclusion and exclusion criteria yielded 10 relevant studies: two completed non-randomized controlled trials and eight ongoing clinical trials. Both completed studies reported a statistically significant benefit in percentage re-epithelialization and time to healing for the SVF treatment arms. Safety information for SVF was not provided. Ongoing clinical trials were assessing outcomes such as safety, patient and observer reported scar appearance, wound healing rate, and wound epithelization. CONCLUSION: In the context of substantial limitations in the quantity and quality of available evidence, the existing literature suggests that SVF may be a useful treatment for acute cutaneous wounds in humans. More clinical trials with improved outcome measures and safety assessment are needed.

Controlling inplane orientation of a monolayer colloidal crystal by meniscus pinning.

We demonstrate the usage of meniscus pinning by surface relief boundaries to control in-plane orientation of monolayer colloidal crystals without the interruption of grain disorientation. By optimizing the pinning boundary and withdrawal speed, a well controlled linear meniscus contact line offers unidirectional growth of a colloidal crystal-densely packed crystal direction ⟨11⟩ and ⟨10⟩ parallel to linear edge-giving rise to a single domain crystal with only twins and vacancies present as residual defects. The pinning effect works by eliminating the wavy contact line induced by fingering instability which is commonly found in liquid wetting film. It is found that surfactants and colloidal particles play significant roles to enhance edge pinning, increasing the distance traveled by receding bulk meniscus (during substrate withdrawal) before liquid depinning or rupturing.

In-situ monitoring of the thermal desorption of alkanethiols with surface plasmon resonance spectroscopy (SPRS).

Thermal desorption investigations on self-assembled monolayers (SAMs) had previously been carried out using techniques such as thermal desorption spectroscopy (TDS), scanning tunneling microscopy (STM) and X-ray photo-electron spectroscopy (XPS). In this paper, the thermal dissociation of alkanethiols (CnH(2n + 1)SH) at various chain lengths (n= 6, 12, 18) on sputtered gold layers was monitored in-situ using the Kretschmann surface plasmon resonance configuration on a spectroscopic ellipsometer. We found that the longest alkanethiol (C18) exhibits the greatest thermal stability, manifested by the least amount of angular shift, during heating, in the resonant spectral features. Predictions of desorption temperatures from SPRS for the longer chain thiols are in good agreement with XPS measurements.

Sensitivity enhancement in grating coupled surface plasmon resonance by azimuthal control.

We present a method for improving the sensing capability of grating coupled surface plasmon resonance (GCSPR) sensors. The grating is rotated azimuthally (phi) until the excitation of double surface plasmon polaritions (SPPs) by a single wavelength is possible. Close to this condition, further tuning of the incident wavelength will merge the double SPPs into a multi-SPP resonance which is angularly broad but spectrally sharp. This is the condition where the momentum vector of the propagating SPP is perpendicular to the incident light momentum. We demonstrate this sensitivity enhancement on a Au grating surface using a dodecanethiol (C12) self-assembled monolayer (SAM). Using this method, a shift in resonance angle as large as 3 degrees can be observed. The simulated sensitivity of this method shows that a sensitivity up to 800 degrees /RIU is achievable, which is one order of magnitude greater than that in a conventional fixed grating (phi = 0 degrees ) as well as the prism-coupled Kretschmann configuration.

Post-implantation Deformation of Titanium Rod and Cobalt Chrome Rod in Adolescent Idiopathic Scoliosis.

Introduction: Post-implantation rod deformation is anticipated in scoliosis surgery but the difference in rod deformation between titanium and cobalt chrome rod has not been elucidated. This study aims to compare the difference in rod deformation between two groups. Materials and Methods: Twenty-one adolescent idiopathic scoliosis (AIS) patients were recruited from a single center. The over-contoured concave rods were traced prior to insertion. Post-operative sagittal rod shape was determined from lateral radiographs. Rod deformation was determined using maximal rod deflection and angle of the tangents to rod end points. The differences between pre- and post-operative rod contour were analysed statistically. Rod deformation and thoracic kyphosis between two types of implants were analysed. Results: Both rods exhibited significant change of rod angle and deflection post-operatively. Curvature of the titanium rod and cobalt chrome rod decreased from 60.5° to 37°, and 51° to 28° respectively. Deflection of titanium rod and cobalt chrome rod reduced from 28mm to 23.5mm and 30mm to 17mm respectively. There was no significant difference between titanium and cobalt chrome groups with regard to rod angle (p=0.173) and deflection (p=0.654). Thoracic kyphosis was increased from 20° to 26° in titanium group but a reduction from 25° to 23° was noticed in cobalt chrome group, but these findings were not statistically significant. Conclusion: There was no statistical difference in rod deformation between the two groups. Thus, the use of titanium rod in correction of sagittal profile is not inferior in outcome compared with cobalt chrome but with lower cost.