Hong Kong Chinese school children with elevated urine melamine levels: A prospective follow up study

<p>Abstract</p> <p>Background</p> <p>In 2008, the outbreak of kidney stones in children fed by melamine-tainted milk products in Mainland China has caused major public concern of food safety. We identified Hong Kong school children with elevated urine melamine level from a community-based school survey in 2007-08 and reviewed their clinical status in 2009.</p> <p>Methods</p> <p>In 2007-08, 2119 school children participated in a primary and secondary school survey in Hong Kong using a cluster sampling method. Urine aliquots from 502 subjects were assayed for melamine level. High urine melamine level was defined as urine melamine/creatinine ratio >7.1 μg/mmol. Subjects with high urine melamine level were invited for clinical evaluation in 2009 including urinalysis and ultrasound imaging of the urinary system.</p> <p>Results</p> <p>The age range of this subcohort was 6 - 20 years with 67% girls (335 female and 167 male subjects). The spot urine melamine/creatinine ratio of the 502 urine aliquots ranged from undetectable to 1467 μg/mmol (median 0.8 μg/mmol). Of these, 213 subjects had undetectable level (42%). We invited 47 (9%) subjects with high urine melamine level for re-evaluation and one subject declined. The median duration of follow-up was 23.5 months (interquartile range: 19.8 - 30.6 months). None of the 46 subjects (28% boys, mean age 13.9 ± 2.9 years) had any abnormality detected on ultrasound study of the urinary system. All subjects had stable renal function with a median urine albumin-creatinine ratio of 0.70 mg/mmol (interquartile range: 0.00 - 2.55 mg/mmol).</p> <p>Conclusions</p> <p>Hong Kong Chinese school children with high urine melamine levels appeared to have benign clinical course in the short term although a long term follow-up study is advisable in those with persistently high urine melamine level.</p

What is the potential for bisexual men in China to act as a bridge of HIV transmission to the female population? Behavioural evidence from a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>HIV prevalence among men who have sex with men (MSM) in China has rapidly increased in recent years. It is suggested that MSM could be a potential bridge of HIV transmission to the general female population. We investigated the bisexual behaviour of MSM in China through systematic review and meta-analysis.</p> <p>Methods</p> <p>We conducted a systematic review and meta-analyses on published peer-reviewed Chinese and English literature during 2001-2010 according to the PRISMA guidelines. Marital status and sexual behavioural indicators of MSM were presented graphically using forest plots. The pooled effect rates with 95% confidence intervals were also calculated. Meta-regression analyses were performed to examine the factors associated with high heterogeneities across the studies.</p> <p>Results</p> <p>Forty-three eligible articles (11 in English and 32 in Chinese) were identified. Our results showed that 17.0% (95% CI: 15.1-19.1%) of MSM in China are currently married to a woman and 26.3% (95% CI: 23.6-29.1%) of MSM had female sexual partners in the last six months. The pooled estimates for condom use rate between MSM and female sex partners was 41.4% (95% CI: 35.5-47.5%) at the last sex act; and 25.6% (95% CI: 23.0-28.4%) in the last six months. The consistent condom use rates with regular, non-commercial, casual and commercial female sex partners in the last six months were 23.3% (95% CI: 11.25-42.1%), 39.0% (95% CI: 28.8-50.3%) and 55.8% (95% CI: 41.4-69.4%), respectively.</p> <p>Conclusions</p> <p>A substantial proportion of Chinese MSM is currently married or had sexual relations with a female in the past six months. In addition, low condom usage was common between married MSM and their wives, hence posing a higher risk of transmitting HIV. Harm-reduction programs targeting married MSM and their female partners are necessary to curb the further spread of HIV infection to the general female population.</p

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

VILIP-1 Downregulation in Non-Small Cell Lung Carcinomas: Mechanisms and Prediction of Survival

VILIP-1, a member of the neuronal Ca++ sensor protein family, acts as a tumor suppressor gene in an experimental animal model by inhibiting cell proliferation, adhesion and invasiveness of squamous cell carcinoma cells. Western Blot analysis of human tumor cells showed that VILIP-1 expression was undetectable in several types of human tumor cells, including 11 out of 12 non-small cell lung carcinoma (NSCLC) cell lines. The down-regulation of VILIP-1 was due to loss of VILIP-1 mRNA transcripts. Rearrangements, large gene deletions or mutations were not found. Hypermethylation of the VILIP-1 promoter played an important role in gene silencing. In most VILIP-1-silent cells the VILIP-1 promoter was methylated. In vitro methylation of the VILIP-1 promoter reduced its activity in a promoter-reporter assay. Transcriptional activity of endogenous VILIP-1 promoter was recovered by treatment with 5′-aza-2′-deoxycytidine (5′-Aza-dC). Trichostatin A (TSA), a histone deacetylase inhibitor, potently induced VILIP-1 expression, indicating that histone deacetylation is an additional mechanism of VILIP-1 silencing. TSA increased histone H3 and H4 acetylation in the region of the VILIP-1 promoter. Furthermore, statistical analysis of expression and promoter methylation (n = 150 primary NSCLC samples) showed a significant relationship between promoter methylation and protein expression downregulation as well as between survival and decreased or absent VILIP-1 expression in lung cancer tissues (p<0.0001). VILIP-1 expression is silenced by promoter hypermethylation and histone deacetylation in aggressive NSCLC cell lines and primary tumors and its clinical evaluation could have a role as a predictor of short-term survival in lung cancer patients

The Probable Cell of Origin of NF1- and PDGF-Driven Glioblastomas

Primary glioblastomas are subdivided into several molecular subtypes. There is an ongoing debate over the cell of origin for these tumor types where some suggest a progenitor while others argue for a stem cell origin. Even within the same molecular subgroup, and using lineage tracing in mouse models, different groups have reached different conclusions. We addressed this problem from a combined mathematical modeling and experimental standpoint. We designed a novel mathematical framework to identify the most likely cells of origin of two glioma subtypes. Our mathematical model of the unperturbed in vivo system predicts that if a genetic event contributing to tumor initiation imparts symmetric self-renewing cell division (such as PDGF overexpression), then the cell of origin is a transit amplifier. Otherwise, the initiating mutations arise in stem cells. The mathematical framework was validated with the RCAS/tv-a system of somatic gene transfer in mice. We demonstrated that PDGF-induced gliomas can be derived from GFAP-expressing cells of the subventricular zone or the cortex (reactive astrocytes), thus validating the predictions of our mathematical model. This interdisciplinary approach allowed us to determine the likelihood that individual cell types serve as the cells of origin of gliomas in an unperturbed system

Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours

The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormone-responsive phenotype of breast cancer. Microarray analyses have revealed that forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) are expressed in close association with ERalpha, both encoding for transcription factors with a potential involvement in the ERalpha-mediated action in breast cancer. The purpose of this study was to explore if the expression of FOXA1 and GATA-3 may provide an opportunity to stratify subsets of patients that could have better outcome, among the ERalpha-negative/poor prognosis breast cancer group.The present study was supported by a research grant (SFRH/BD/15316/ 2005 to AA) financed by the Portuguese Science and Technology Foundation (FCT). The authors thank Prof. Raquel Seruca ( coordinator from the Cancer Genetics group at IPATIMUP) for scientific assistance, Dr Jose Luis Costa (postdoctorate at IPATIMUP) for critically reading the manuscript before submission, and Dr Nuno Marcos ( PhD student at IPATIMUP) for artwork assistance

Strain-Specific Differences in the Genetic Control of Two Closely Related Mycobacteria

The host response to mycobacterial infection depends on host and pathogen genetic factors. Recent studies in human populations suggest a strain specific genetic control of tuberculosis. To test for mycobacterial-strain specific genetic control of susceptibility to infection under highly controlled experimental conditions, we performed a comparative genetic analysis using the A/J- and C57BL/6J-derived recombinant congenic (RC) mouse panel infected with the Russia and Pasteur strains of Mycobacterium bovis Bacille Calmette Guérin (BCG). Bacillary counts in the lung and spleen at weeks 1 and 6 post infection were used as a measure of susceptibility. By performing genome-wide linkage analyses of loci that impact on tissue-specific bacillary burden, we were able to show the importance of correcting for strain background effects in the RC panel. When linkage analysis was adjusted on strain background, we detected a single locus on chromosome 11 that impacted on pulmonary counts of BCG Russia but not Pasteur. The same locus also controlled the splenic counts of BCG Russia but not Pasteur. By contrast, a locus on chromosome 1 which was indistinguishable from Nramp1 impacted on splenic bacillary counts of both BCG Russia and Pasteur. Additionally, dependent upon BCG strain, tissue and time post infection, we detected 9 distinct loci associated with bacillary counts. Hence, the ensemble of genetic loci impacting on BCG infection revealed a highly dynamic picture of genetic control that reflected both the course of infection and the infecting strain. This high degree of adaptation of host genetics to strain-specific pathogenesis is expected to provide a suitable framework for the selection of specific host-mycobacteria combinations during co-evolution of mycobacteria with humans

A Novel and Lethal De Novo LQT-3 Mutation in a Newborn with Distinct Molecular Pharmacology and Therapeutic Response

SCN5A encodes the alpha-subunit (Na(v)1.5) of the principle Na(+) channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS) variant 3 (LQT-3) in adults by disrupting inactivation of the Na(v)1.5 channel. Pharmacological targeting of mutation-altered Na(+) channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS) and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults.Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C) discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na(+) channel blockers flecainide and mexiletine. Our goal was to determine the Na(+) channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na(+) channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C) and a common variant in KCNH2 (K897T). Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na(+) channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically.The results of our study provide further evidence of the grave vulnerability of newborns to Na(+) channel defects and suggest that both genetic background and age are particularly important in developing a mutation-specific therapeutic personalized approach to manage disorders in the young

Diurnal Rhythms Result in Significant Changes in the Cellular Protein Complement in the Cyanobacterium Cyanothece 51142

Cyanothece sp. ATCC 51142 is a diazotrophic cyanobacterium notable for its ability to perform oxygenic photosynthesis and dinitrogen fixation in the same single cell. Previous transcriptional analysis revealed that the existence of these incompatible cellular processes largely depends on tightly synchronized expression programs involving ∼30% of genes in the genome. To expand upon current knowledge, we have utilized sensitive proteomic approaches to examine the impact of diurnal rhythms on the protein complement in Cyanothece 51142. We found that 250 proteins accounting for ∼5% of the predicted ORFs from the Cyanothece 51142 genome and 20% of proteins detected under alternating light/dark conditions exhibited periodic oscillations in their abundances. Our results suggest that altered enzyme activities at different phases during the diurnal cycle can be attributed to changes in the abundance of related proteins and key compounds. The integration of global proteomics and transcriptomic data further revealed that post-transcriptional events are important for temporal regulation of processes such as photosynthesis in Cyanothece 51142. This analysis is the first comprehensive report on global quantitative proteomics in a unicellular diazotrophic cyanobacterium and uncovers novel findings about diurnal rhythms

DNA Fingerprinting of Pearls to Determine Their Origins

We report the first successful extraction of oyster DNA from a pearl and use it to identify the source oyster species for the three major pearl-producing oyster species Pinctada margaritifera, P. maxima and P. radiata. Both mitochondrial and nuclear gene fragments could be PCR-amplified and sequenced. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in the internal transcribed spacer (ITS) region was developed and used to identify 18 pearls of unknown origin. A micro-drilling technique was developed to obtain small amounts of DNA while maintaining the commercial value of the pearls. This DNA fingerprinting method could be used to document the source of historic pearls and will provide more transparency for traders and consumers within the pearl industry