Viral cysteine proteinases

Summary Dozens of novel cysteine proteinases have been identified in positive single-stranded RNA viruses and, for the first time, in large double-stranded DNA viruses. The majority of these proteins are distantly related to papain or chymotrypsin and may be direct descendants of primordial proteolytic enzymes. Virus genome synthesis and expression, virion formation, virion entry into the host cell, as well as cellular architecture and functioning can be under the control of viral cysteine proteinases during infection. RNA virus proteinases mediate their liberation from giant multidomain precursors in which they tend to occupy conserved positions. These proteinases possess a narrow substrate specificity, can cleave in cis and in trans, and may also have additional, nonproteolytic functions. The mechanisms of catalysis, substrate recognition and RNA binding were highlighted by the recent analysis of the three-dimensional structure of the chymotrypsin-like cysteine proteinases of two RNA viruses.     

cDNA probes for the diagnosis of bovine torovirus (Breda virus) infection.

A genomic cDNA library of RNA from Breda virus (BRV), a bovine torovirus, was prepared. The nucleotide sequence of the 3' end of the genome was found to be highly conserved (93% identical) between BRV and Berne virus, the torovirus prototype. Cross-hybridization experiments were performed to select Berne virus cDNA clones for use as probes in a dot hybridization assay; the objective was to detect heterologous torovirus RNA in fecal material. A rapid RNA extraction method was employed to make the test applicable for routine diagnosis. Samples from calves after experimental and natural infection with BRV were assayed to establish the sensitivity and specificity of the test and to compare the test with the enzyme-linked immunosorbent assay (ELISA) for antigen detection. For this purpose, 53 samples from seven infected calves were tested with both methods. In the ELISA, BRV was detected in six fecal samples from three inoculated calves. By use of the hybridization test, 16 samples from seven calves reacted positively. With one exception, only postinoculation samples were found positive in hybridization. No signal was seen in feces from uninoculated calves or from calves infected with rotavirus or coronavirus.     

Contribution of Alcohol and Nicotine Dependence to the Prevalence of Depressed Mood in Different Ethnic Groups in The Netherlands: The HELIUS Study

Abstract

Objective: Ethnic minorities report different levels of drinking and smoking and higher rates of depression compared to native populations. In this study we aimed to investigate in six ethnic groups whether tobacco and alcohol use were associated with depressive symptoms, which are more prevalent in ethnic minorities.

Methods: Cross-sectional data from the multi-ethnic Healthy Life in an Urban Setting (HELIUS) study sample (N?=?22,471) was used, comprising 4,580 native Dutch participants which were compared with participants from five ethnic minority groups (3,259 South Asian Surinamese, 4,292 African Surinamese, 2,262 Ghanaian, 3,891 Turkish, and 4,187 Moroccan).

Results: Alcohol misuse was positively associated with depressed mood in all ethnic groups except for the Dutch and the Ghanaians. Nicotine dependence was positively associated with depressed mood in all ethnic groups except for the Ghanaian group.

Conclusions: Alcohol misuse and nicotine dependence were significantly associated with depressed mood in most but not all ethnic groups and especially in men. However, across all groups the contribution of alcohol misuse and nicotine dependence to depressed mood was small. Prospective multi-ethnic studies should confirm whether the relations are causal and elucidate their direction.     

Clinical Worsening During Long-Term Follow-Up in Inoperable Chronic Thromboembolic Pulmonary Hypertension

Background  

Pulmonary endarterectomy is the treatment of choice in chronic thromboembolic pulmonary hypertension (CTEPH). Modern pulmonary vasoactive medication (like endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclins) is used in patients with an inoperable disease and improved prognosis. We evaluate mortality and time to clinical worsening (TtCW) in inoperable CTEPH patients during long-term follow-up.     

Hereditary hemorrhagic telangiectasia: How accurate are the clinical criteria?

The clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) is based on the Curaçao criteria. Three out of four criteria are required for a definite clinical diagnosis HHT, two criteria are considered “possible” HHT, and 0 or 1 criterion makes the diagnosis unlikely. However, these consensus diagnostic criteria have not been validated. We report on the diagnostic accuracy of the clinical criteria. A total of 450 consecutive persons ≥16 years of age were screened for HHT between May 2004 and September 2009, including a chest CT to screen for pulmonary arteriovenous malformations (AVMs). We selected 263 first‐degree relatives of disease‐causing mutation carriers who underwent mutation analysis. Genetic test results were considered the gold standard. The family mutation was present in 186 patients (mean age 42.9 ± 14.6 yr; 54.8% female). A clinical diagnosis was definite, “possible”, and unlikely in 168 (90.3%), 17 (9.1%), and 1 (0.5%) patient, respectively. In 77 persons the family mutation was absent (mean age 37.1 ± 12.3 yr, 59.7% female). In this group a clinical diagnosis was definite, possible, and unlikely in 0, 35 (45.5%), and 42 (54.5%) persons, respectively. The positive predictive value of a definite clinical diagnosis was 100% (95% CI 97.8–100), the negative predictive value of an unlikely diagnosis 97.7% (95% CI 87.9–99.6). Of 52 patients with “possible” HHT, 17 (32.7%) displayed an HHT‐causing mutation. The Curaçao clinical criteria have a good diagnostic performance. Genetic testing is particularly helpful in patients with a “possible” clinical diagnosis HHT. © 2013 Wiley Periodicals, Inc.     

Ethnic disparities in the association of impaired fasting glucose with the 10-year cumulative incidence of type 2 diabetes

Aims

Evidence of ethnic disparities in the conversion of prediabetes to type 2 diabetes is scarce. We studied the association of impaired fasting glucose (IFG) and fasting plasma glucose (FPG) with the 10-year cumulative incidence of type 2 diabetes in three ethnic groups.

Methods

We analyzed data for 90 South-Asian Surinamese, 190 African-Surinamese, and 176 ethnic Dutch that were collected in the periods 2001–2003 and 2011–2012. We excluded those with type 2 diabetes or missing FPG data. We defined baseline IFG as FPG of 5.7–6.9 mmol/L. We defined type 2 diabetes at follow-up as FPG ≥ 7.0 mmol/L, HbA1c ≥ 48 mmol/mol (6.5%), or self-reported type 2 diabetes.

Results

10-Year cumulative incidences of type 2 diabetes were: South-Asian Surinamese, 18.9%; African-Surinamese, 13.7%; ethnic Dutch, 4.5% (p < 0.05). The adjusted association of baseline IFG and FPG with the 10-year cumulative incidence of type 2 diabetes was stronger for South-Asian Surinamese than for African-Surinamese and ethnic Dutch. The IFG (compared to normoglycaemia) ORs were 11.1 [3.0–40.8] for South-Asian Surinamese, 5.1 [2.0–13.3] for African-Surinamese, and 2.2 [0.5–10.1] for ethnic Dutch.

Conclusions

The 10-year cumulative incidence of type 2 diabetes was higher and associations with baseline IFG and FPG were stronger among South-Asian Surinamese and African-Surinamese than among ethnic Dutch. Our findings confirm the high risk of type 2 diabetes in South-Asians and suggest more rapid conversion in populations of South-Asian origin and (to a lesser extent) African origin than European origin.