Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

The Role of the Family Doctor in HIV Medicine

The outlook of people living with HIV (PLHIV) has changed for the better. With the discovery of effective drugs HIV is more like a chronic disease. The family doctor has several roles in HIV medicine: find, test, treat, and retain. Find - at risk individuals, and reduce their HIV risks. Test – to diagnosis those with acute HIV infection, to identify the asymptomatic patients, and to identify those with AIDS defining illnesses. Treat - participate in shared care management with HIV specialists. Retain – retain wellbeing of PLHIV - monitor for complications, provide patient education to help them minimise complications. Routine testing for HIV infection is now the practice. For treatment, A combination ART regimen consisting of two NRTIs + one active drug from one of the classes: NNRT, PI, INSTI, or a CCRS antagonist. Retaining the wellbeing of PLHIV requires monitoring for complications, and providing patient education to help them minimise complications.

Histopathological classification and location of consecutively operated meningiomas at a single institution in China from 2001 to 2010 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Meningioma is one of the most common primary tumors of the central nervous system, but there are not many detailed studies on the sex, age, subtypes and locations of large series. This study was a retrospective analysis of the characteristics of meningioma cases consecutively operated on at a single institution in China from 2001 to 2010.</p><p><b>METHODS</b>This study investigated the demographic background of 7084 meningioma cases, and the subtypes and locations of the tumors. Sex and age distributions were analyzed, and the pathological subtypes were classified according to the World Health Organization (WHO) classification. The location of the meningiomas was also categorized.</p><p><b>RESULTS</b>The female:male ratio of the 7084 cases was 2.34:1. The mean age was 51.4 years (range, 11 months-86 years). The mean age of cases of WHO grade I meningioma was significantly older than that of grade II or III meningiomas (P < 0.001, Fisher's Least Significant Digit test). There was a significantly higher female:male ratio in WHO grade I meningiomas than in grade II or grade III meningiomas (2.57, 1.03 and 0.76, respectively; P < 0.001, χ(2) test). Meningothelial (n = 2061) and fibrous meningiomas (n = 3556) were the most common subtypes, comprising 79.3% of all meningiomas. All meningioma cases were classified into 23 locations in this study, with the cerebral convexity the most common site (38.33%, n = 2722). Cases with uncommon locations such as extra-cranial and sylvian fissure meningiomas were also present in this series.</p><p><b>CONCLUSIONS</b>Female predominance was found for benign meningiomas, while malignant subtypes showed male predominance. The mean age of patients with WHO grade I meningiomas was older than that of patients with higher-grade tumors. Meningothelial and fibrous meningiomas were the most common subtypes. The cerebral convexity was the most common meningioma location.</p>

Risk factors and time-trends of cytomegalovirus (CMV), syphilis, toxoplasmosis and viral hepatitis infection and seroprevalence in human immunodeficiency virus (HIV) infected patients

<p><b>INTRODUCTION</b>Chronic bacterial, viral and parasitic infections contribute to the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. This study investigated risk factors and time-trends of the seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly diagnosed HIV individuals in Singapore.</p><p><b>MATERIALS AND METHODS</b>This was a cross-sectional study. A random sample of 50% of HIV infected patients who visited the Communicable Disease Centre (CDC), Singapore for first-time care from January 2006 to December 2011 were analysed.</p><p><b>RESULTS</b>Among the 793 study subjects, 93.4% were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was 41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm³. The prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%; hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C, 73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was significantly more common among men who have sex with men (MSM) (multivariate OR: 2.53, 95% CI, 1.31 to 4.90, P = 0.006).</p><p><b>CONCLUSION</b>This study described the baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore, and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates compared to the general population may have important consequences for disease progression, response to antiretroviral treatment and long-term general health.</p>

Causes of death in hospitalised HIV-infected patients at a National Referral Centre in Singapore: a retrospective review from 2008 to 2010

<p><b>INTRODUCTION</b>Highly active antiretroviral therapy (HAART) has improved outcomes for individuals infected with human immunodeficiency virus (HIV). This study describes the causes of death in hospitalised HIV-positive patients from 2008 to 2010 in Tan Tock Seng Hospital, the national referral centre for HIV management in Singapore.</p><p><b>MATERIALS AND METHODS</b>Data were retrospectively collected from HIV-positive patients who died in Tan Tock Seng Hospital from January 2008 to December 2010.</p><p><b>RESULTS</b>Sixty-seven deaths occurred in the study period. A majority of patients died of non-acquired immune deficiency syndrome (AIDS)-defining illnesses (54.7%). The median CD4 count was 39.5 (range, 20.0 to 97.0), and 7 patients had HIV viral loads of <200 copies/mL. There were 27 deaths due to opportunistic infections, 27 due to non AIDS-defining infections, 4 due to non AIDS-associated malignancies. This study also describes 3 deaths due to cardiovascular events, and 1 due to hepatic failure. Patients who had virologic suppression were more likely to die from non AIDS-defining causes.</p><p><b>CONCLUSION</b>Causes of death in HIV-positive patients have changed in the HAART era. More research is required to further understand and address barriers to testing and treatment to further improve outcomes in HIV/AIDS.</p>

Older age at initial presentation to human immunodeficiency virus (HIV) care and treatment at the Communicable Disease Centre (CDC) in Singapore, 2006 to 2011

<p><b>INTRODUCTION</b>The incidence of newly diagnosed older patients diagnosed with human immunodeficiency virus (HIV) has increased worldwide in recent years. In this study, we compared the demographics and clinical presentation of younger and older patients in our HIV sentinel cohort.</p><p><b>MATERIALS AND METHODS</b>Among all HIV patients presenting to the Communicable Disease Centre (CDC), Singapore from 2006 to 2011, 793 were randomly included in our cohort, representing about 50% of the patients seen during that period. We collected demographic, clinical, laboratory, and outcome data from patient records to compare younger (<50 years old) and older (≥50 years old) HIV patients.</p><p><b>RESULTS</b>Older patients comprised 27.1% of our HIV cohort and presented with lower median CD4 T cell counts (65 cells/mm³, interquartile range [IQR]: 27 to 214 cells/mm³) compared to younger patients (250 cells/mm³, IQR: 74 to 400 cells/mm³; P <0.001). The median time from HIV diagnosis to initiation of antiretroviral therapy (ART) differed significantly for both age groups as well (49 days for patients <50 years old, IQR: 18 to 294 days; versus 35 days for patients ≥50 years old, IQR: 14 to 102 days; P = 0.008). More of our younger patients were single (72.2%) or homosexual (44.1%), in contrast to older patients, of whom 48.8% were married and 84.7% were heterosexual.</p><p><b>CONCLUSION</b>Upon comparison of our younger and older patients, we identified distinct differences in risk transmission and clinical presentation. Increased awareness of older patients at risk of HIV may improve time to diagnosis among this age group.</p>

Healthcare workers and HIV health issues

Should healthcare workers (HCWs) be routinely tested for HIV? The authors reviewed the literature on the risk and incidence of HIV transmission from HCW to patients and offer recommendations for HIV testing in HCWs in Singapore. Management of HCWs who are tested seropositive for HIV infection is also discussed in this paper.

Cluster of Staphylococcus aureus and dengue co-infection in Singapore

<p><b>INTRODUCTION</b>Singapore saw a resurgence of dengue infections in 2005. Concurrent bacterial co-infections in dengue is rare.</p><p><b>CLINICAL PICTURE</b>We report a cluster of serious methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia or severe soft tissue infection in 5 epidemiologically linked construction workers presenting with dengue and non-resolving fever.</p><p><b>TREATMENT</b>Surgical intervention was indicated in 4 of the 5 patients despite appropriate antistaphylococcal therapy.</p><p><b>OUTCOME</b>All but 1 patient were eventually discharged. Clonality and Panton-Valentine leucocidin genes were not demonstrated. Epidemiological investigations suggested that occupational contact dermatitis could have predisposed the patients to this opportunistic co-infection.</p><p><b>CONCLUSION</b>Clinicians need to be vigilant to unusual manifestations of dengue which may signal a concomitant aetiology.</p>

A Novel Method to Detect a New Biopolymer Material—Poly-?-Glutamic Acid / 中国生物工程杂志

A turbid solution was formed through the reaction between ?-PGA and cetylpyridinium chloride(CPC) and the turibidity was measured by using ultraviolet-visible spectroscopy at 680nm.The linearity between the concentration of ?-PGA and its absorbance,the stability,repeatability and recovery of the method were studied.Through the reaction of ?-PGA with CPC,a homogeneous turbid solution was formed.The turbid solution was stable in 3h under proper pH value and ion strength,the absorbance of the solution at 680nm had a good linear relationshi Pwith the concentration of ?-PGA in the range 12.5~50?g/ml(R2=0.9939).The recovery was within the range of 86%~99.75%(n=5).The relative standard division of the method for determining ?-PGA at the concentrations of 5,10 and 40?g/ml were 0.14%,0.23%和0.025% repeatability.The turbidmetric method has advantages of convenience,simplicity and good repeatability and can be used to control the quality of ?-PGA and its products.

Diagnosis and treatment of dysembryoplastic neuroepithelial tumor / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the diagnosis and treatment of dysembryoplastic neuroepithelial tumor (DNT).</p><p><b>METHODS</b>From November 2001 to February 2005, 18 patients were admitted. The data of the 18 patients were reviewed.</p><p><b>RESULT</b>Epilepsy was the main complaint. There was no mass effect on MRI. Multinodular and specific glioneuronal element was typical in pathological examination, seizure could be controlled by operation.</p><p><b>CONCLUSIONS</b>DNT is benign tumor which could be treated by surgery, total removal of tumor and using intraoperative electrocorticography could improve the result of operation.</p>

Diagnosis of intracranial malignant melanoma / 中华外科杂志

<p><b>OBJECTIVE</b>To analyse the diagnosis points of intracranial malignant melanoma.</p><p><b>METHODS</b>There were ten patients with intracranial malignant melanoma (but without clear extracranial primary lesion), whose epidemiology, clinical symptom, physical sign and imaging data were analysed.</p><p><b>RESULTS</b>Most of patients were young men, The Clinical symptom or physical sign are similar to brain tumor or cerebral hemorrhage, but the course was shot, two cases of among having skin melanotic nevus. As for most of cases, CT were high density, MRI T1WI showed high signal and T2WI low signal, which often had hemorrhage. Histological examination showed all cases were malignant melanoma. Preoperative misdiagnosis was up to eight cases (80%).</p><p><b>CONCLUSIONS</b>For preoperative accurate diagnosis, this disease's epidemiology, clinical symptom, extracranial physical sign and imaging data points could be synthetical analysed.</p>

An allelotype study of primary and corresponding recurrent glioblastoma multiforme / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate molecular genetic alterations associated with primary and corresponding recurrent glioblastoma multiforme(GBM) and to identify which chromosomal regions of the whole genome may be involved in the recurrence of primary GBM.</p><p><b>METHODS</b>A high-resolution allelotyping study of one patient's primary GBM and corresponding recurrent GBM was performed by PCR-based loss of heterozygosity(LOH) analysis with the use of 382 fluorescent dye-labeled polymorphic microsatellite markers covering all 22 autosomes. The mean genetic distance between two flanking markers is 10 cM.</p><p><b>RESULTS</b>LOH at locus D9S157 on 9p21 and at loci D10S537, D10S185, D10S192, D10S597, D10S587, D10S217 on 10q21.3-26.3 was observed in the primary GBM. As for corresponding recurrent tumor, LOH was observed not only in expanded regions on 9p21 and 10q21.3-26.3 but also on multiple other chromosomal arms, including 1q, 7p,7q, 21q, 20p, 20q, 10p, 19p, 19q.</p><p><b>CONCLUSION</b>Chromosome 9p and 10q may be involved in the development of this GBM. Although histopathological diagnoses of the primary and corresponding recurrent tumor are identical, the recurrence of GBM is characterized by an increased involvement of molecular genetic abnormalities and may be accompanied by inactivation of more tumor suppressor genes.</p>