Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models:A Cross-sectional Study in Rural Guangxi

Objective This study aimed to investigate the potential relationship between urinary metals copper(Cu),arsenic(As),strontium(Sr),barium(Ba),iron(Fe),lead(Pb)and manganese(Mn)and grip strength.Methods We used linear regression models,quantile g-computation and Bayesian kernel machine regression(BKMR)to assess the relationship between metals and grip strength.Results In the multimetal linear regression,Cu(β=−2.119),As(β=−1.318),Sr(β=−2.480),Ba(β=0.781),Fe(β=1.130)and Mn(β=−0.404)were significantly correlated with grip strength(P<0.05).The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was−1.007(95%confidence interval:−1.362,−0.652;P<0.001)when each quartile of the mixture of the seven metals was increased.Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength,with Cu,As and Sr being negatively associated with grip strength levels.In the total population,potential interactions were observed between As and Mn and between Cu and Mn(P_(interactions) of 0.003 and 0.018,respectively).Conclusion In summary,this study suggests that combined exposure to metal mixtures is negatively associated with grip strength.Cu,Sr and As were negatively correlated with grip strength levels,and there were potential interactions between As and Mn and between Cu and Mn.

Determination of HCH and DDT in soils following Wenchuan 5.12 Violent Earthquake in China

A large number of disinfectants and insecticides were used on a large scale after the Wenchuan 5.12 Violent Earthquake. The disinfectants and insecticides, including HCH (hexachlorocyclohexane) and DDT (dichlorodiphenyltrichoroethane) as representative OCPs, could lead to serious environmental problems. In order to disclose the residues of HCH and DDT in soils following the Wenchuan 5.12 Violent Earthquake, surface soils in Dujiangyan City and Beichuan County were sampled in 2009. The samples were analyzed by GC/MS after pre- treatment by ultrasonic solvent extraction. It has been found that the concentra-tions of γ-HCH, β-HCH and 4,4'-DDT in soils of Beichuan County were 94–102.4, 14.1–36.1 and 2.9–4.3 times high their concentrations in those of the Wolong Nature Reserve, and the concentrations in soils of Dujiangyan City were 52.4–61.6, 8.8 –45.3 and 5.4–6.2 times high their concentrations in soils of the Wolong Nature Reserve, respectively. According to the isomers of HCHs and metabolites of DDTs, it could be concluded that these areas may have additional inputs of lindane and 4,4'-DDT.

Assessment of circulating levels of microRNA-326,microRNA-424,and microRNA-511 as biomarkers for hepatocellular carcinoma in Egyptians

BACKGROUND Hepatocellular carcinoma(HCC)is the fifth most common cancer.Differential expression of microRNAs(miRNAs)-326,miRNA-424,and miRNA-511 has been associated with the diagnosis and prognosis of HCC in different populations.However,limited information is available regarding their expression in Egyptian HCC patients.AIM To assess the role of circulating miRNAs-326,miRNA-424,and miRNA-511 in Egyptian HCC patients.METHODS This prospective observational study included 70 HCC patients and 25 healthy controls.The circulating levels of these three miRNAs were evaluated by real-time PCR.Receiver operating characteristic curve analysis was used to test the diagnostic accuracy of micro RNA expression levels.RESULTS All miRNAs were differentially expressed in HCC patients;miRNAs326 and miRNA-424 were upregulated,while miRNA-511 was downregulated.Both miRNA-326 and miRNA-424 showed sensitivity and specificity of 97%,71.4%,and 52%,60%,respectively,to differentiate HCC from controls.Moreover,miRNA-326 was associated with survival and could differentiate between Child grades(A vs B);miRNA-424 significantly differentiated early vs intermediate stages of HCC;while miRNA-511 was significantly correlated with response to modified Response Evaluation Criteria in Solid Tumors(m RECIST).CONCLUSION We conclude that miRNA-326,miRNA-424,and miRNA-511 have diagnostic and prognostic roles in Egyptian patients with hepatitis C virus-related HCC and should be considered for better disease management.

Clinical significance of skin rash in dengue fever:A focus on discomfort,complications,and disease outcome

Objective:To assess whether the cutaneous features in patients with dengue fever are associated with abnormal blood biochemistry,complications,and poor disease outcome.Methods:Forty five patients with dengue fever were identified at a medical center in Kaohsiung,Taiwan,from September to November 2014.All cases were exclusively caused by type 1 dengue virus.Patients were classified into two groups,based on the presence or absence of skin rash,and their rash was subclassified into maculopapular,morbilliform,and petechial types.Clinical symptoms,laboratory data,disease outcome,and complications were compared between the two groups.Results:Thirty two patients with dengue fever developed skin rash(SP group,n=32) while the rest of 13 did not(SN group,n=13).The patient numbers in the maculopapular,morbilliform,and petechial group were 4,21,and 7,respectively.The SP group was younger(P=0.001),experienced more pruritus(P=0.008) and more swollen palms/soles(P=0.015) than the SN group.However,the SN group had greater genital mucosa involvement(P=0.008),higher platelet transfusion rate(P=0.003),and lower hemoglobin and hematocrit levels(P=0.030) than the SP group.Patients with morbilliform lesions had a higher incidence of palm/sole swelling,less genital mucosal involvement,and a lower platelet transfusion rate than did patients with maculopapular or petechial lesions.Conclusions:Cutaneous manifestations provide an important clue to dengue fever.In patients with dengue fever,those with skin rash tend to have itching and swelling of the palms/soles,however,those without skin rash tend to have more complications and poor disease outcomes.

Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice

Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress(PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead(Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling. Bone parameters were evaluated using microCT, histomorphometry, and strength determination in 8-month-old male mouse offspring subjected to PS on gestational days 16 and 17, lifetime Pb exposure(100 p.p.m. Pb in drinking water), or to both. Pb reduced trabecular bone mass and, when combined with PS, Pb unmasked an exaggerated decrement in bone mass and tensile strength. Next, to characterize a mechanism of glucocorticoid effect on bone, prednisolone was implanted subcutaneously(controlled-release pellet, 5 mg·kg^(-1) per day) in 5-month-old mice that decreased osteoblastic activity and increased sclerostin and leptin levels. Furthermore, the synthetic glucocorticoid dexamethasone alters the anabolic Wnt signaling pathway. The Wnt pathway inhibitor sclerostin has several glucocorticoid response elements, and dexamethasone administration to osteoblastic cells induces sclerostin expression. Dexamethasone treatment of isolated bone marrow cells decreased bone nodule formation, whereas removal of sclerostin protected against this decrement in mineralization.Collectively, these findings suggest that bone loss associated with steroid-induced osteoporosis is a consequence of sclerostin-mediated restriction of Wnt signaling, which may mechanistically facilitate glucocorticoid toxicity in bone.

Quality of Life in Egyptian Children with Cancer

Background and Objectives: Cancer treatments leading to increased survival rates are reported to participate in the creation of debilitating physical and psychosocial deficits for cancer survivors. Measures of health-related quality of life (HRQOL) are designed to tap such consequences of cancer treatment together with the impact of the disease itself. Methods: Parents of 67 included patients aged 8 - 12 years, were asked to complete the parent proxy report of PedsQLTM 3.0 Cancer Module (Arabic version), as well as a separate sheet for socio-demographic data. Results: The ratio of Males to females was 1.8:1 among study patients with a median age of 8 years at diagnosis. Hematological malignancies represented 70.1% of the sample, with the highest proportion for ALL (52.2%). Total QOL showed to be relatively low with mean value of 62.29 for the whole group. Subscales with least scores were for;worry (44.11), perceived physical appearance (50.6), and procedural anxiety (55.34). On the other hand, the best score was 75.98 for communication, followed by 72.63 for cognitive problems. The impacts of some medical and socio-demographic variables on QOL and its subscales were elicited in our results. Conclusion: Increased treatment intensity, long duration of hospital admission, higher frequency of hospital visits, female sex, younger age at diagnosis, and large family size were all associated with a poorer total QOL and/or its subscales among Egyptian pediatric cancer patients.

N^ω-Nitro-N^ω’-Substituted Guanidines: A Simple Class of Nitric Oxide Synthase Inhibitors

A series of Nω-nitro-Nω’-substituted guanidines has been prepared as potential inhibitors of the human Nitric Oxide Synthase (NOS) isoforms. The reported utility of amino-guanidine and nitroarginine in iNOS inhibition points to a potential similar utility for analogs of nitro-guanidine. The compound library was tested against the three isoforms of Nitric Oxide Synthase (eNOS, iNOS and nNOS). Several candidates showed excellent activity and good selectivity for nNOS. One particular compound even demonstrated good selectivity for iNOS. The potential usefulness of such selective inhibitors is discussed.

Semen analysis from an epidemiologic perspective

The fifth edition of the World Health Organization （WHO） manual for semen analysis includes for the first time reference values for human semen characteristics. This paper considers whether such values will help to resolve the intensely debated data indicating temporal and geographical shifts in sperm counts and hypotheses that anthropogenic activities that result in the release of chemicals into the environment are detrimental to male reproductive health. The reasons that these reference values will not fulfil these purposes are also explained. Although established reference values for semen characteristics are of limited value in analytical epidemiologic research, the WHO guidelines are of utmost importance for supporting the development of appropriate research protocols. Moreover, in spite of its limitations, semen analysis is still a useful research tool in epidemiological research, and no superior alternatives are on the horizon.

Clinical characteristics of patients with congenital long QT syndrome and bigenic mutations

Background Congenital long QT syndrome （LQTS） is an ion channelopathy associated with genetic mutations. It is well known that most LQTS patients （91%） have a single mutation. The purpose of this study was to investigate the clinical characteristics of congenital LQTS patients with bigenic mutations in Taiwan, China. Methods Congenital LQTS patients were recruited consecutively at Taiwan University Hospital in Taiwan from 2003 to 2009. The diagnosis of LQTS was defined by an LQTS Schwartz score greater than 4. Mutation screening in KCNQ1, KCNH2, KCNE1, and SCN5A was performed using direct sequencing. Results Three of 16 LQTS patients （18.7%） were identified with bigenic mutations. One patient had missense mutations in KCNQ1 and KCNH2, the second in KCNQ1 and KCNE1, and the third in KCNH2 and SCN5A. The mean age at onset of LQTS for patients with bigenic mutations was （17±3） years, and all of these patients were female. Two of them experienced seizure and one presented with syncope, although one of them had a family history of syncope. The mean QTc interval was （515＋17） ms, similar to those with single mutation or SNPs （（536~74） ms, P=-0.63）. Compared to those LQTS patients with single mutation or SNPs, a significantly higher percentage of LQTS patients with bigenic mutations presented with seizure and were younger at onset of the first index event （P=0.03 and 0.001, respectively）, but lower percentage of them presented with sudden cardiac death （P=0.03）. Conclusions Although the percentage of bigenic mutations in LQTS is less than 10% in Caucasian populations, we identified 3 of 16 LQTS patients （18.7%, 95% confidence interval： 0.04-0.46） with bigenic mutations in Taiwan. However, the sevedtv of their clinical presentations was not hioher than those patients with sinele mutation or SNPs.

从流行病学观点论精液分析

在《世界卫生组织人类精液分析实验室技术手册》(简称手册)第5版中,首次增加了人类精液特征的参考值范围。现阐述提供这些数据是否有助于平息就某些问题引发的广泛争议,如时间地点不同,精液计数差异明显;能否证实某些假设,如人类活动向环境中排放的化学物质损害男性生殖健康等。也解释了这些参考值并不能解决上述问题的原因。虽然既定的精液特征参考值对流行病学研究的价值有限,但世界卫生组织(WHO)手册对建立合适的研究方案极具价值。尽管精液分析有局限性,但仍然是流行病学研究的有用工具,而且至今尚无其他更好的方法能取而代之。