A Multicentre Molecular Analysis of Hepatitis B and Blood-Borne Virus Coinfections in Viet Nam

Hepatitis B (HBV) infection is endemic in Viet Nam, with up to 8.4 million individuals estimated to be chronically infected. We describe results of a large, multicentre seroepidemiological and molecular study of the prevalence of HBV infection and blood-borne viral coinfections in Viet Nam. Individuals with varying risk factors for infection (n = 8654) were recruited from five centres; Ha Noi, Hai Phong, Da Nang, Khanh Hoa and Can Tho. A mean prevalence rate of 10.7% was observed and levels of HBsAg were significantly higher in injecting drug users (IDUs) (17.4%, n = 174/1000) and dialysis patients (14.3%, n = 82/575) than in lower-risk groups (9.4%; p<0.001). Coinfection with HIV was seen in 28% of HBV-infected IDUs (n = 49/174) and 15.2% of commercial sex workers (CSWs; n = 15/99). HCV infection was present in 89.8% of the HBV-HIV coinfected IDUs (n = 44/49) and 40% of HBV-HIV coinfected CSWs (n = 16/40). Anti-HDV was detected in 10.7% (n = 34/318) of HBsAg positive individuals. Phylogenetic analysis of HBV S gene (n = 187) showed a predominance of genotype B4 (82.6%); genotypes C1 (14.6%), B2 (2.7%) and C5 (0.5%) were also identified. The precore mutation G1896A was identified in 35% of all specimens, and was more frequently observed in genotype B (41%) than genotype C (3%; p<0.0001). In the immunodominant ‘a’ region of the surface gene, point mutations were identified in 31% (n = 58/187) of sequences, and 2.2% (n = 4/187) and 5.3% (n = 10/187) specimens contained the major vaccine escape mutations G145A/R and P120L/Q/S/T, respectively. 368 HBsAg positive individuals were genotyped for the IL28B SNP rs12979860 and no significant association between the IL28B SNP and clearance of HBsAg, HBV viral load or HBeAg was observed. This study confirms the high prevalence of HBV infection in Viet Nam and also highlights the significant levels of blood-borne virus coinfections, which have important implications for hepatitis-related morbidity and development of effective management strategies

Amamentação ao seio, amamentação com leite de vaca e o diabetes mellitus tipo 1: examinando as evidências Breast- feeding, bottle- feeding and the type 1 diabetes mellitus: examining the evidences

A etiologia do diabetes mellitus tipo 1 (DM1) envolve tanto herança genética como a exposição a fatores ambientais. Evidências de estudos epidemiológicos e experimentais sugerem que a dieta pode ser importante na etiopatogenia dessa doença. Em 1984, Borch-Johnsen e col. sugeriram, com base nos resultados de um estudo caso-controle, que o leite materno seria um fator de proteção para o DM1; esse efeito se daria devido às propriedades anti-infecciosas desse tipo de leite, ou pelo fato de que a amamentação ao seio evitaria que as crianças pudessem ser precocemente expostas a outros agentes etiológicos contidos nos substitutos do leite materno. Esses mesmos achados foram poste-riormente encontrados em diversos estudos, mas o papel do leite materno no aparecimento do DM1 ainda permanece controverso. Em 1992, Karjalainen e col., ao compararem os soros de indivíduos com e sem DM1, observaram, entre os diabéticos, altas concentrações de anticorpos anti-albumina bovina. Os autores postularam a hipótese de que a albumina bovina poderia atuar como desencadeadora do processo destrutivo das células ß do pâncreas e, conseqüentemente, do diabetes. Resultados conflitantes foram observados nas publicações que se sucederam a essa. Neste artigo, resumem-se e discutem-se os achados de diferentes pesquisadores que investigaram a importância desses fatores dietéticos para o aparecimento do DM1.<br>The aetiology of type 1 diabetes mellitus (DM1) includes genetic heritage and environmental exposure. Evidence from animal and epidemiological studies suggests that some diet components may play a role in the aetiology of DM1. In 1984, Borch-Johnsen et al. suggested, based on a case-control study, that breast-feeding was a protective factor for DM1, probably due its anti-infectious properties or because breast-feeding delays exposure to other etiologic agents in the diet. Afterwards, the same results were found in several studies but the role of breast milk in the development of DM1, is still subject to controversy. In 1992, Karjalainen et al., compared the blood serum of subjects with and without DM1 and they observed a higher concentration of anti-bovine albumin antibodies among diabetic subjects. The authors suggested that bovine albumin could act as a trigger of the destructive process of the pancreas and, in this way, lead to diabetes; discordant results have been observed in the literature since then. In this paper, we summarise and discuss the results found in different studies on dietary factors and DM1

Achieving the optimal power of patent rights

This article examines how policy instruments governing the grant and enforcement of patent rights affect the ex ante incentive to invest in inventive activity. In order to encourage investment into the creation of an asset, capitalism extends to firms and individuals the right to appropriate the returns from owning that asset. Preventing theft, and accordingly, the expropriation of one's profits, hinges on being able to define the asset. For tangible assets, this mechanism is certain since the boundaries around what are (and are not) part of the asset can be precisely articulated and title to the ownership is mostly complete. However, this is not the case for intangible assets such as intellectual property because the boundary between a new asset and existing ones is often ambiguous when expressed in written form. From a welfare perspective, granting patent rights gives rise to a further issue. Unlike property rights over tangible assets, patents create deadweight social losses by temporarily blocking imitation and preventing others from using a non-rivalrous resource. These deadweight losses arise because the patent system operates by creating a distortion (a monopoly right) to correct a distortion. Given the existence of legislation enshrining patent owners' rights, the power of a patent is determined in two stages: first, acquiring the title to the right (patent granting) and, second, getting competitors to accede to the right by modifying their behavior (patent enforcement). These two stages occur over a continuum of administrative, legal and quasi-legal activities including drafting the patent application, examining (and opposing) the application at the patent office, and enforcing the patent

Onto better TRAILs for cancer treatment

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. By cross-linking TRAIL-Receptor (TRAIL-R) 1 or TRAIL-R2, also known as death receptors 4 and 5 (DR4 and DR5), TRAIL has the capability to induce apoptosis in a wide variety of tumor cells while sparing vital normal cells. The discovery of this unique property among TNF superfamily members laid the foundation for testing the clinical potential of TRAIL-R-targeting therapies in the cancer clinic. To date, two of these therapeutic strategies have been tested clinically: (i) recombinant human TRAIL and (ii) antibodies directed against TRAIL-R1 or TRAIL-R2. Unfortunately, however, these TRAIL-R agonists have basically failed as most human tumors are resistant to apoptosis induction by them. It recently emerged that this is largely due to the poor agonistic activity of these agents. Consequently, novel TRAIL-R-targeting agents with increased bioactivity are currently being developed with the aim of rendering TRAIL-based therapies more active. This review summarizes these second-generation novel formulations of TRAIL and other TRAIL-R agonists, which exhibit enhanced cytotoxic capacity toward cancer cells, thereby providing the potential of being more effective when applied clinically than first-generation TRAIL-R agonists

Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3–58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5–56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5·43 mmol/L (IQR 4·32–6·72) among patients not taking lipid-lowering medications and 4·23 mmol/L (3·20–5·66) among those taking them. Among patients taking lipid-lowering medications, 2·7% had LDL cholesterol lower than 1·8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin–kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1·8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p<0·001). Interpretation Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron