Associations between ALDH Genetic Variants, Alcohol Consumption, and the Risk of Nasopharyngeal Carcinoma in an East Asian Population.

Nasopharyngeal carcinoma (NPC) and alcohol flush syndrome are thought to be strongly influenced by genetic factors and are highly prevalent amongst East Asians. Diminished activity of aldehyde dehydrogenase (ALDH), a major enzyme in the alcohol-metabolizing pathway, causes the flushing syndrome associated with alcoholic consumption. The genetic effect of ALDH isoforms on NPC is unknown. We therefore investigated the association between the genetic polymorphisms of all 19 ALDH isoforms and NPC among 458 patients with NPC and 1672 age- and gender-matched healthy controls in Taiwan. Single-nucleotide polymorphisms (SNPs) located between the 40,000 base pairs upstream and downstream of the 19 ALDH isoform coding regions were collected from two genome-wise association studies conducted in Taiwan and from the Taiwan Biobank. Thirteen SNPs located on ALDH4A1, ALDH18A1, ALDH3B2, ALDH1L2, ALDH1A2, and ALDH2 Glu487Lys (rs671) were associated with NPC susceptibility. Stratification by alcohol status revealed a cumulative risk effect for NPC amongst drinkers and non-drinkers, with odds ratios of 4.89 (95% confidence interval 2.15-11.08) and 3.57 (1.97-6.47), respectively. A synergistic effect was observed between SNPs and alcohol. This study is the first to report associations between genetic variants in 19 ALDH isoforms, their interaction with alcohol consumption and NPC in an East Asian population.

Therapeutic inertia in proteinuria management among type 2 diabetes (T2DM) patients in primary care settings: prevalence and associated risk factors.

BACKGROUND: Therapeutic inertia (TI), defined as physicians' failure to increase therapy when treatment goals are unmet, is an impediment to chronic disease management. This study aimed to identify the prevalence of TI in proteinuria management among T2DM patients managed in primary care settings and to explore possible associating factors. METHODS: This was a cross-sectional study. T2DM patients with proteinuria (either microalbuminuria or macroalbuminuria) and had been followed up in 7 public primary care clinics of the Hospital Authority of Hong Kong from 1 Jan, 2014 to 31 Dec, 2015 were included. The prevalence of TI in proteinuria management and its association with patients' demographic and clinical parameters and the working profile of the attending doctors were explored. Student's t test and analysis of variance were used for analyzing continuous variables and Chi square test was used for categorical data. Multivariate stepwise logistic regression was used to determine the association between TI and the significant variables from patients' and doctors' characteristics. RESULTS: Among the 22,644 T2DM patients identified in the case register, 5163 (26.4%) patients were found to have proteinuria. Among the sampled 385 T2DM patients with proteinuria, TI was identified in 155 cases, with a prevalence rate of 40.3%. Male doctor, doctor with longer duration of clinical practice and have never received any form of Family Medicine training were found to have a higher TI. Patients with microalbuminuria range and lower systolic and diastolic blood pressure (BP) were also found to have higher TI. Logistic regression study revealed that patients' systolic BP level and microalbuminuria range of proteinuria were negatively associated with the presence of TI, whereas doctor's year of clinical practice being over 20 years and patients being treated with submaximal dose of medication were positively associated with the presence of TI. CONCLUSIONS: TI is commonly present in proteinuria management among T2DM patients, with a prevalence of 40.3% in primary care. Systolic BP and microalbuminuria range of urine ACR were negatively associated with the presence of TI, whereas submaximal ACEI/ARB dose and doctors practicing over 20 years were positively associated with the presence of TI. Further studies exploring the strategies to combat TI are needed to improve the clinical outcome of T2DM patients.

Nanotopography as Artificial Microenvironment for Accurate Visualization of Metastasis Development via Simulation of ECM Dynamics.

Metastatic progression is mediated by complex interactions between deregulated extracellular matrix (ECM) and cancer cells and remains a major challenge in cancer management. To investigate the role of ECM dynamics in promoting metastasis development, we developed an artificial microenvironment (AME) platform comprised of nanodot arrays of increasing diameter. Cells cultured on the platform showed increasing signs of mesenchymal-like cell transition as AME diameter increased, suggesting accurate simulation of ECM-mediated gene regulation. Gene expression was analyzed to determine genes significant to transition, which were then used to select appropriate small molecule drugs for time course treatments. Our results suggest that the platform can identify critical target genes as well as possible drug candidates. Overall, the AME platform allows for the study of intricate ECM-induced gene expression trends across metastasis development that would otherwise be difficult to visualize in vivo and may open new avenues toward successful personalized cancer management.

Spatial distribution of sorption and desorption process of 14C-radiolabelled hexazinone and tebuthiuron in tropical soil.

The understanding of the interaction between soil physicochemical attributes and herbicide behavior is fundamental for optimizing the efficient use of PRE-emergence herbicides in a more sustainable approach. However, it is still a poorly studied area within precision agriculture. Thus, the objective of this research was to evaluate the correlation of soil physicochemical attributes with the sorption and desorption processes of hexazinone and tebuthiuron to support application maps considering the field level variability. Soil samples from an agricultural area had their physicochemical attributes analyzed and were submitted to sorption and desorption studies of 14C-tebuthiuron and 14C-hexazinone using the batch equilibrium method. The values of sorption and desorption apparent coefficients (Kd), sorption and desorption percentage and bioavailability were correlated with soil attributes by Pearson's correlation. The Kd values of tebuthiuron and hexazinone sorption ranged from 1.2 to 2.9 mL g-1 and 0.4-0.6 mL g-1, respectively. For desorption of tebuthiuron and hexazinone, Kd values ranged from 3.4 to 4.4 mL g-1 and 2.6-3.0 mL g-1, respectively. A positive correlation among clay content, soil organic matter (OM), and tebuthiuron and hexazinone sorption Kd values were found. Both herbicides had variable retention according to geographic position in the area. The recommendation of application of PRE herbicides, such as tebuthiuron and hexazinone, observing the physicochemical attributes of the soil is an alternative to increase efficiency in weed control and decrease the risk of environmental contamination.

Prothymosin α activates type I collagen to develop a fibrotic placenta in gestational diabetes.

High-risk pregnancies, such as pregnancies with gestational diabetes mellitus (GDM), are becoming more common and as such, have become important public health issues worldwide. GDM increases the risks of macrosomia, premature infants, and preeclampsia. Although placental dysfunction, including fibrosis is associated with the development of GDM, factors that link these observations remain unknown. Prothymosin α (ProTα) is expressed in the placenta and is involved in cell proliferation and immunomodulation. It also plays an important role in insulin resistance and fibrosis. However, the role of ProTα in GDM is still unclear. In the present study, we found that fibrosis-related protein expressions, such as type I collagen (Col-1) were significantly increased in the placentae of ProTα transgenic mice. With elevated fibrosis-related protein expressions, placental weights significantly increased in GDM group. In addition, placental and circulating ProTα levels were significantly higher in patients with GDM (n=39), compared with the healthy group (n=102), and were positively correlated with Col-1 expression. Mice with streptozotocin (STZ)-induced GDM had increased ProTα, fasting blood glucose, Col-1, and placental weight, whereas plasma insulin levels were decreased. ProTα overexpression enhanced nuclear factor κB (NFκB) activation to increase fibrosis-related protein expressions in 3A-Sub-E trophoblasts, while treatment with an NFκB inhibitor reversed the effect of ProTα on fibrosis-related protein expressions. We further investigated whether ProTα is regulated by hyperglycemia-induced reactive oxygen species (ROS). In conclusion, ProTα increases the amount of placental connective tissue and thus contributes to the pathogenesis of placental fibrosis in GDM. Therefore, ProTα may be a novel therapeutic target for GDM.

A Cross-Diagnostic Investigation of the Differential Impact of Discrimination on Clinical and Personal Recovery.

OBJECTIVE: Although the negative association between discrimination and recovery has been established, only a few studies have attempted to investigate the underlying mechanism of how perceived discrimination dampens both clinical and personal recovery among people with psychiatric disorders. This study aimed to examine the mediating roles of self-stigma and mental health service engagement in the relationship between perceived discrimination and recovery. METHODS: A total of 374 people (half men and half women; mean±SD age=43.47±12.76) living in Hong Kong and in recovery with a primary diagnosis of a psychotic disorder, mood disorder, or substance use disorder responded to a cross-sectional questionnaire on discrimination, self-stigma, mental health service adherence, recovery orientation of services, clinical recovery, and personal recovery. Multisample structural equation modeling was conducted to examine whether the hypothesized model for perceived discrimination and recovery produced results that could be generalized across people with various psychiatric diagnoses. RESULTS: Findings indicated that respondents perceived discrimination from the general public and from health care professionals, which was positively associated with self-stigmatization and service disengagement and was negatively associated with clinical and personal recovery across three different types of psychiatric disorder. CONCLUSIONS: This study showed that the influence of perceived discrimination on recovery was universal and could be generalized across people with different psychiatric diagnoses. Multipronged stigma reduction interventions targeting the general public, health care professionals, and people in recovery, along with policies that avert discrimination and uphold human rights in health care settings and beyond, should be implemented.

Different mechanisms of risperidone result in improved interpersonal trust, social engagement and cooperative behavior in patients with schizophrenia compared to trifluoperazine.

AIM: Atypical antipsychotic treatment (e.g. risperidone) has been found to improve social functioning more than standard antipsychotic treatment. However, it is unclear which specific social behaviors are implicated in this improvement. The current study employed an interactive puzzle game to examine how social behaviors contribute to the improvement of social functioning by comparing patients receiving risperidone with those receiving trifluoperazine. METHODS: Scores on the Positive and Negative Syndrome Scale, executive functioning, and social functioning were obtained from 24 patients with schizophrenia receiving either risperidone (n = 12) or trifluoperazine (n = 12), before their social behavior was measured in the interactive Tangrams Game. Immediately after the Tangrams Game, participants filled in two questionnaires measuring their interpersonal trust and rejection toward their game partner. RESULTS: Patients receiving risperidone showed more social engagement, cooperative behavior and interpersonal trust toward their game partners than those receiving trifluoperazine. Additional multivariate analysis of variance revealed that lower affiliative behavior was a function of positive symptoms; interpersonal trust had an impact on social engagement but executive functioning did not explain lower interpersonal trust or social disengagement. CONCLUSION: Improvement of social competence by risperidone might be related to the enhancement of both social behaviors and interpersonal trust as well as better symptom resolution.

Ketamine users have high rates of psychosis and/or depression.

Ketamine has been linked to psychosis and used in the treatment of depression. However, no study has examined the prevalence of psychotic and depressive disorders in dependent ketamine users. This study aimed to examine the frequency of various psychopathologies among a series of patients seeking treatment for ketamine use in Hong Kong, China. The case records of 129 patients with a history of ketamine use receiving treatment at three substance use clinics between January 2008 and August 2012 were retrieved for data collection. Patients' demographic data, patterns of substance misuse, and comorbid psychiatric diagnoses were recorded and entered into analyses. The mean age of onset and length of ketamine use were 17.7 ± 4.4 and 8.7 ± 5.7 years, respectively. All patients were dependent on ketamine at the time of data collection. Multiple substance misuse was common. Eighty-four of the 129 (65.1%) patients were found to have comorbid psychiatric disorders, most commonly substance-induced psychotic disorder (31.8%) followed by depressive disorder (27.9%). Psychosis and/or depression were common in ketamine-dependent patients referred to a psychiatric substance use clinic. The findings provide evidence of an association between chronic ketamine use and the presence of psychosis and/or depression. The results raise the issue of safety when using ketamine in the long-term treatment of depression.

Are sexes affected differently by ketamine? An exploratory study in ketamine users.

One hundred primary ketamine users and 100 controls were recruited in Hong Kong between December 2009 and December 2011. Cognitive assessment included general intelligence, working, verbal, and visual memory, and executive functions. A Univariate General Linear Model was used to compare cognitive performance between the male and female ketamine users and controls. The female users appeared to have a higher risk of visual memory impairment than their male counterparts. Further studies are warranted to clarify the mechanism of the sex-specific effect of ketamine on cognitive functions.

The diagnosis values of whole blood IFN-γrelease assay on pulmonary tuberculosis and extra-pulmonary tuberculosis / 预防医学

Objective To evaluate the diagnosis values of whole blood IFN-γ release assay on pulmonary tuberculosis ( TB)and extra-pulmonary tuberculosis. Methods One hundred and eighty five patients with tuberculosis( including 119 pulmonary TB and 66 extra-pulmonary TB),139 patients with other respiratory diseases and 100 healthy people were enrolled. Mycobacterium tuberculosis infection testing was conducted with methods of IFN -γ release assay,sputum bacterial culture and sputum smear,respectively. Results of pathogen culture and/or clinical diagnosis were used as the golden standard to evaluate the sensitivity and specificity of these three methods. Results Compared with the results of clinical diagnosis,the sensitivity and specificity of IFN-γ release assays was 93. 51% and 84. 52%,respectively. There was no significant difference in sensitivity between pulmonary diagnosis( 90. 76%) and extra - pulmonary diagnosis (98. 49%)(P>0. 05). The sensitivity of sputum smear was 11. 76% in patients with pulmonary and 3. 03% in patients with extra - pulmonary. And the sensitivity of sputum bacterial culture in these two patient groups was 24. 37% and 3. 03%,respectively. Sensitivity of the IFN-γ release assay was higher than that of sputum culture and sputum smear (P<0. 05). The results of pathogen culture showed that 33 of 424 samples were positive,in which 2 were mycobacterium abscessus positive and 31 were mycobacterium tuberculosis positive. Compared with the results of pathogen culture,the sensitivity of IFN-γrelease assay was 90. 32%(95%CI:75. 10% -96. 65%). Conclusion IFN-γrelease assay is a fast,sensitive and convenient method to detect pulmonary and extra pulmonary tuberculosis. It is worthy to be applied to clinical practice.

Intercalated disc-associated protein, mXin-alpha, influences surface expression of ITO currents in ventricular myocytes.

Mouse Xin-alpha (mXin-alpha) encodes a Xin repeat-containing, actin-binding protein localized to the intercalated disc (ICD). Ablation of mXin-alpha progressively leads to disrupted ICD structure, cardiac hypertrophy and cardiomyopathy with conduction defects during adulthood. Such conduction defects could be due to ICD structural defects and/or cell electrophysiological property changes. Here, we showed that despite the normal ICD structure, juvenile mXina-null cardiomyocytes (from 3~4-week-old mice) exhibited a significant reduction in the transient outward K+ current (ITO), similar to adult mutant cells. Juvenile but not adult mutant cardiomyocytes also had a significant reduction in the delayed rectifier K+ current. In contrast, the mutant adult ventricular myocytes had a significant reduction in the inward rectifier K+ current (IK1) on hyperpolarization. These together could account for the prolongation of action potential duration (APD) and the ease of developing early afterdepolarization observed in juvenile mXin-alpha-null cells. Interestingly, juvenile mXin-alpha-null cardiomyocytes had a notable decrease in the amplitude of intracellular Ca2+ transient and no change in the L-type Ca2+ current, suggesting that the prolonged APD did not promote an increase in intracellular Ca2+ for cardiac hypertrophy. Juvenile mXin-alpha-null ventricles had reduced levels of membrane-associated Kv channel interacting protein 2, an auxiliary subunit of ITO, and filamin, an actin cross-linking protein. We further showed that mXin-alpha interacted with both proteins, providing a novel mechanism for ITO surface expression.

Multi-component quantitative method of Chinese herbal additives based on fingerprint / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a full-quantified fingerprint method for analyzing Chinese herbal additives by HPLC.</p><p><b>METHOD</b>A HPLC in combination with PDA detector was applied with a phenomenex luna C18 (4.6 mm x 250 mm, 5 microm) column by gradient elution using acetonitrile-0.1% formic acid solution as the mobile phase. The flow rate was 1 mL x min(-1) and the detection wavelength was set at full spectrum scan.</p><p><b>RESULT</b>According to the selected chromatographic conditions, the full-quantified fingerprint of the Chinese herbal additive has good precision, reproducibility, stability and recovery.</p><p><b>CONCLUSION</b>The HPLC method developed for simultaneous determination of seven compounds is simple and valid. It can be used for quality evaluation and quality control of Chinese herbal additive and its processing products.</p>

Essential roles of an intercalated disc protein, mXinbeta, in postnatal heart growth and survival.

RATIONALE: The Xin repeat-containing proteins mXinalpha and mXinbeta localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinalpha directly interacts with beta-catenin, p120-catenin, and actin filaments. Ablation of mXinalpha results in adult late-onset cardiomyopathy with conduction defects. An upregulation of the mXinbeta in mXinalpha-deficient hearts suggests a partial compensation. OBJECTIVE: The essential roles of mXinbeta in cardiac development and intercalated disc maturation were investigated. METHODS AND RESULTS: Ablation of mXinbeta led to abnormal heart shape, ventricular septal defects, severe growth retardation, and postnatal lethality with no upregulation of the mXinalpha. Postnatal upregulation of mXinbeta in wild-type hearts, as well as altered apoptosis and proliferation in mXinbeta-null hearts, suggests that mXinbeta is required for postnatal heart remodeling. The mXinbeta-null hearts exhibited a misorganized myocardium as detected by histological and electron microscopic studies and an impaired diastolic function, as suggested by echocardiography and a delay in switching off the slow skeletal troponin I. Loss of mXinbeta resulted in the failure of forming mature intercalated discs and the mislocalization of mXinalpha and N-cadherin. The mXinbeta-null hearts showed upregulation of active Stat3 (signal transducer and activator of transcription 3) and downregulation of the activities of Rac1, insulin-like growth factor 1 receptor, protein kinase B, and extracellular signal-regulated kinases 1 and 2. CONCLUSIONS: These findings identify not only an essential role of mXinbeta in the intercalated disc maturation but also mechanisms of mXinbeta modulating N-cadherin-mediated adhesion signaling and its crosstalk signaling for postnatal heart growth and animal survival.

Adaptive AOA-aided TOA self-positioning for mobile wireless sensor networks.

Location-awareness is crucial and becoming increasingly important to many applications in wireless sensor networks. This paper presents a network-based positioning system and outlines recent work in which we have developed an efficient principled approach to localize a mobile sensor using time of arrival (TOA) and angle of arrival (AOA) information employing multiple seeds in the line-of-sight scenario. By receiving the periodic broadcasts from the seeds, the mobile target sensors can obtain adequate observations and localize themselves automatically. The proposed positioning scheme performs location estimation in three phases: (I) AOA-aided TOA measurement, (II) Geometrical positioning with particle filter, and (III) Adaptive fuzzy control. Based on the distance measurements and the initial position estimate, adaptive fuzzy control scheme is applied to solve the localization adjustment problem. The simulations show that the proposed approach provides adaptive flexibility and robust improvement in position estimation.

Cooperative anchor-free position estimation for hierarchical wireless sensor networks.

This paper proposes a distributed algorithm for establishing connectivity and location estimation in cluster-based wireless sensor networks. The algorithm exploits the information flow while coping with distributed signal processing and the requirements of network scalability. Once the estimation procedure and communication protocol are performed, sensor clusters can be merged to establish a single global coordinate system without GPS sensors using only distance information. In order to adjust the sensor positions, the refinement schemes and cooperative fusion approaches are applied to reduce the estimation error and improve the measurement accuracy. This paper outlines the technical foundations of the localization techniques and presents the tradeoffs in algorithm design. The feasibility of the proposed schemes is shown to be effective under certain assumptions and the analysis is supported by simulation and numerical studies.

Clinical research about heating infusion for premature infants to promote their restoration of physiological function / 中国实用护理杂志

Objective In order to know the effect of heating infusion for premature infants to pro-mote their restoration of physiological function. Methods Divided 160 premature infants who need infu-sion into the experimental group and the control group randomly, there were 80 cases in each group. Normal temperature infusion was used in the control group, while heating infusion was used in the experimental group, compared the body temperature, pluse, respiration, blood pressure, oxygen saturation and the blood ghcose between the two groups. Results There were significant difference about the indexes which had mentioned above between the two groups. Conclusions Heating infusion can effective promote the reha-bilitation of physiological function of premature infants.

Maternal acceptance of human papillomavirus vaccine in Malaysia.

Acceptability rates of human papillomavirus (HPV) vaccination by 362 Malaysian mothers were 65.7% and 55.8% for daughters and sons, respectively. Younger mothers, and those who knew someone with cancer, were more willing to vaccinate their daughters. If the vaccine was routine and cost free, acceptability rate was 97.8%.

Intestinal tuberculosis mimicking fistulizing Crohn's disease.

A patient is reported with intestinal tuberculosis that mimicked fistulizing Crohn's disease endoscopically. He had complete resolution of symptoms after a full course of antituberculosis therapy. Gastroenterologists and general physicians should aware of the possibility of intestinal tuberculosis in areas with a high prevalence of tuberculosis infection.