Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004). CONCLUSIONS: Serum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information.     

Dengue Fever among Renal Transplant Recipients: A Series of 10 Cases in a Tropical Country

Few studies have focused on Rift Valley fever virus (RVFV) transmission in less arid, transitional landscapes surrounding known high-risk regions. The objective of this study was to identify evidence of RVFV exposure in Bodhei Village in a forested area at the edge of the RVFV-epidemic Garissa region. In a household cluster-based survey conducted between epidemics in early 2006, 211 participants were enrolled. Overall seroprevalence for anti-RVFV was high (18%) and comparable with rates in the more arid, dense brush regions farther north. Seroprevalence of adults was 28%, whereas that of children was significantly lower (3%; P < 0.001); the youngest positive child was age 3 years. Males were more likely to be seropositive than females (25% versus 11%; P < 0.01), and animal husbandry activities (birthing, sheltering, and butchering) were strongly associated with seropositivity. The results confirm that significant RVFV transmission occurs outside of recognized high-risk areas and independent of known epidemic periods.     

Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study

BACKGROUND: Natural immunity to Streptococcus pneumoniae is thought to be induced by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies of carriage of and immune responses to S. pneumoniae have been conducted using sophisticated immunological laboratory techniques. METHODS: We enrolled 121 families with young children into this study. Nasopharyngeal (NP) swabs were collected monthly for 10 months from all family members and were cultured in a standard fashion. Cultured S. pneumoniae isolates were serotyped. At the beginning (month 0) and end (month 10) of the study, venous blood was collected from family members >18 years old. Serotype-specific antipolysaccharide immunoglobulin G (IgG) and functional antibody and antibodies to pneumolysin, pneumococcal surface protein A (PspA), and pneumococcal surface antigen A (PsaA) were measured in paired serum samples. RESULTS: Levels of anticapsular IgG increased significantly after carriage of serotypes 9V, 14, 18C, 19F, and 23F by an individual or family member. For serotype 14, a higher level of anticapsular IgG at the beginning of the study was associated with reduced odds of carriage (P = .006). There was a small (approximately 20%) but significant increase in titers of antibodies to PsaA and pneumolysin but no change in titers of antibody to PspA. CONCLUSIONS: Adults respond to NP carriage by mounting anticapsular and weak antiprotein antibody responses, and naturally induced anticapsular IgG can prevent carriage.     

Evaluation of Pyrosequencing for Detecting Extensively Drug-Resistant Mycobacterium tuberculosis among Clinical Isolates from Four High-Burden Countries

Reliable molecular diagnostics, which detect specific mutations associated with drug resistance, are promising technologies for the rapid identification and monitoring of drug resistance in Mycobacterium tuberculosis isolates. Pyrosequencing (PSQ) has the ability to detect mutations associated with first- and second-line anti-tuberculosis (TB) drugs, with the additional advantage of being rapidly adaptable for the identification of new mutations. The aim of this project was to evaluate the performance of PSQ in predicting phenotypic drug resistance in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) clinical isolates from India, South Africa, Moldova, and the Philippines. A total of 187 archived isolates were run through a PSQ assay in order to identify M. tuberculosis (via the IS6110 marker), and to detect mutations associated with M/XDR-TB within small stretches of nucleotides in selected loci. The molecular targets included katG, the inhA promoter and the ahpC-oxyR intergenic region for isoniazid (INH) resistance; the rpoB core region for rifampin (RIF) resistance; gyrA for fluoroquinolone (FQ) resistance; and rrs for amikacin (AMK), capreomycin (CAP), and kanamycin (KAN) resistance. PSQ data were compared to phenotypic mycobacterial growth indicator tube (MGIT) 960 drug susceptibility testing results for performance analysis. The PSQ assay illustrated good sensitivity for the detection of resistance to INH (94%), RIF (96%), FQ (93%), AMK (84%), CAP (88%), and KAN (68%). The specificities of the assay were 96% for INH, 100% for RIF, FQ, AMK, and KAN, and 97% for CAP. PSQ is a highly efficient diagnostic tool that reveals specific nucleotide changes associated with resistance to the first- and second-line anti-TB drug medications. This methodology has the potential to be linked to mutation-specific clinical interpretation algorithms for rapid treatment decisions.     

Prevalence of obstructive sleep apnea in patients with mucopolysaccharidosis types I,II, and VI in a reference center

Purpose

Mucopolysaccharidosis (MPS) encompasses a group of rare lysosomal storage disorders that are associated with the accumulation of glycosaminoglycans in organs and tissues. Respiratory disorders occur in all MPS types. In these patients, the prevalence of obstructive sleep apnea syndrome (OSAS), which may confer additional morbidity, remains overlooked, and the results of the few existing studies are controversial. The present study aimed to characterize the prevalence of OSAS in patients with MPS types I, II, and VI in a reference center.

Methods

Forty-five patients with MPS (I, n?=?17; II, n?=?16; and VI; n?=?12) in the Centro de Referência em Erros Inatos do Metabolismo, who underwent full-night polysomnography, were enrolled in a retrospective study. Demographic data and clinical history were collected from medical records of the first medical consultation.

Results

The prevalence of OSAS in patients with MPS was 69.8 %. MPS type I patients seemed to be more susceptible to OSA-induced hypoxemia, as indicated by reduced mean SpO₂ levels during both NREM and rapid eye movement sleep as well as during SpO₂ nadir.

Conclusions

Patients with MPS displayed a high prevalence of OSAS, often with moderate to high severity. Together, our results reinforce the need for OSAS screening in all patients with MPS.     

A systematic review of cancer GWAS and candidate gene meta-analyses reveals limited overlap but similar effect sizes

Candidate gene and genome-wide association studies (GWAS) represent two complementary approaches to uncovering genetic contributions to common diseases. We systematically reviewed the contributions of these approaches to our knowledge of genetic associations with cancer risk by analyzing the data in the Cancer Genome-wide Association and Meta Analyses database (Cancer GAMAdb). The database catalogs studies published since January 1, 2000, by study and cancer type. In all, we found that meta-analyses and pooled analyses of candidate genes reported 349 statistically significant associations and GWAS reported 269, for a total of 577 unique associations. Only 41 (7.1%) associations were reported in both candidate gene meta-analyses and GWAS, usually with similar effect sizes. When considering only noteworthy associations (defined as those with false-positive report probabilities ≤0.2) and accounting for indirect overlap, we found 202 associations, with 27 of those appearing in both meta-analyses and GWAS. Our findings suggest that meta-analyses of well-conducted candidate gene studies may continue to add to our understanding of the genetic associations in the post-GWAS era.     

Fasciola hepatica IN BOVINES IN BRAZIL: DATA AVAILABILITY AND SPATIAL DISTRIBUTION

Fasciolosis is a disease of importance for both veterinary and public health. For the first time, georeferenced prevalence data of Fasciola hepatica in bovines were collected and mapped for the Brazilian territory and data availability was discussed. Bovine fasciolosis in Brazil is monitored on a Federal, State and Municipal level, and to improve monitoring it is essential to combine the data collected on these three levels into one dataset. Data were collected for 1032 municipalities where livers were condemned by the Federal Inspection Service (MAPA/SIF) because of the presence of F. hepatica. The information was distributed over 11 states: Espírito Santo, Goiás, Minas Gerais, Mato Grosso do Sul, Mato Grosso, Pará, Paraná, Rio de Janeiro, Rio Grande do Sul, Santa Catarina and São Paulo. The highest prevalence of fasciolosis was observed in the southern states, with disease clusters along the coast of Paraná and Santa Catarina and in Rio Grande do Sul. Also, temporal variation of the prevalence was observed. The observed prevalence and the kriged prevalence maps presented in this paper can assist both animal and human health workers in estimating the risk of infection in their state or municipality.