High prevalence of hepatitis C virus type 5 in central France evidenced by a prospective study from 1996 to 2002

From 1996 to 2002, hepatitis C virus (HCV) typing was prospectively performed for 1,281 unselected HCV-infected and viremic patients, irrespective of their clinical status. Eighty-three patients (6.5%) were coinfected with human immunodeficiency virus (HIV) and HCV. A total of 1,195 strains were identified by a serotype screening (Murex HCV Serotyping 1-6 assay) and/or genotyping (Inno-LiPA HCV II) test. The distribution of HCV types showed an unusually high rate of type 5 (14.2%) that was stable over time and was the third most frequent type, after type 1 (59.1%) and type 3 (15.1%). HCV type 5 was more frequent in patients who were older than 50 (P = 10(-6)), but its frequency did not differ significantly by gender (P = 0.21). Serotyping was performed for 1,160 strains but failed for 30.2% of them. The efficiency depended on HIV status (for HCV-HIV-coinfected patients, half of the strains were untypeable) and HCV type. Genotyping was performed for 428 samples, with an overall efficiency of 99.3%. It failed in three cases, which were subsequently identified as HCV type 2. Serotyping and genotyping results for 39 patients showed discrepancies between the two methods for 4 patients, who had HCV type 2, type 6, or mixed infections. Thus, HCV type 5 may also be encountered frequently in Western countries. Its apparent confinement to a restricted area raises the question of how it emerged and underscores the need for further studies of HCV type prevalence, routes of transmission, pathogenicity, and responses to treatment.     

Fatal cerebral phaeohyphomycosis due to Curvularia lunata in an immunocompetent patient

Curvularia infections in humans are relatively uncommon despite the ubiquitous presence of this soil-dwelling dematiaceous fungus in the environment. Originally thought to be solely a pathogen of plants, Curvularia has been described as a pathogen of humans and animals in the last half-century, causing respiratory tract, cutaneous, and corneal infections. Only three previous cases of central nervous system involvement by Curvularia have been documented in the medical literature. We report a fatal case of cerebral Curvularia infection in which there was no known history of immunocompromise or prior respiratory tract or sinus infection in the patient.     

Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt–mTOR–S6K1 pathway and insulin sensitivity

The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LC n –3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LC n –3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LC n –3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 μmol kg⁻¹ h⁻¹ ( P = 0.006). The study further showed that in the fed steady-state, chronic adaptation to LC n –3PUFA induces greater activation ( P < 0.05) of the Akt–mTOR–S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 μmol kg⁻¹ h⁻¹ ( P = 0.04) and oxidative metabolism was decreased ( P = 0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism.     

Prevalence, geographical distribution and genealogical investigations of mutation 188 of lipoprotein lipase gene in the French Canadian population of Québec

Familial lipoprotein lipase deficiency (FLD) is of particular interest to the French Canadian population of Québec since the largest concentration of homozygotes and carriers of this genetic disease in the world resides in this area. We have previously described a missense mutation (M-188) in the lipoprotein lipase (LPL) gene which was present in FLD patients belonging to different ancestries, including a number of French Canadians (Monsalve MV et al. J Clin Invest 1990: 86: 728-734). In the present report, we show that this mutation, although found in largest absolute numbers among French Canadians as compared to other groups in the world, accounts for only a small proportion (24%) of all the LPL mutant alleles in this population. The M-188 occurs either in the homozygote state or as a compound heterozygote with another LPL mutation. Analysis of geographic distribution indicates that the M-188 is more prevalent in western Québec, with the highest carrier rate in the Mauricie region. Genealogical reconstruction leads to the recognition of four founders for M-188, all emigrants from France to Québec in the 17th century.     

Educational benefits of diversity in medical school: a survey of students.

PURPOSE: Many U.S. medical schools have abandoned affirmative action, limiting the recruitment and reducing the admission of underrepresented minority (URM) students even though research supports the premise that the public benefits from an increase in URM physicians and that URM physicians are likely to serve minority, poor, and Medicaid populations. Faculty and students commonly assume they benefit from peer cultural exchange, and the published evidence for the past two decades supports this notion. This research examined the students' perceptions of the educational merits of a diverse student body by surveying medical students at two schools. METHOD: In 2000, medical students from all four years at Harvard Medical School and the University of California, San Francisco, School of Medicine were enrolled in a telephone survey about the relevance of racial diversity (among students) in their medical education. Students responded to the interviewer's questions on a five-point Likert-type scale. RESULTS: Of the 55% of students who could be located, 97% responded to the survey. Students reported having little intercultural contact during their formative years but significantly more interactions during higher education years, especially in medical school. Students reported contacts with diverse peers greatly enhanced their educational experience. They strongly supported strengthening or maintaining current affirmative action policies in admissions. The responses and demography of the Harvard and UCSF students did not differ significantly, nor did they differ for majority students and URM students-all groups overwhelmingly thought that racial and ethnic diversity among their peers enhanced their education. CONCLUSIONS: Diversity in the student body enhanced the educational experiences of students in two U.S. medical schools.     

In vitro studies with recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1): production and activity of an AMA1 vaccine and generation of a multiallelic response

Apical membrane antigen 1 (AMA1) is regarded as a leading malaria blood-stage vaccine candidate. While the overall structure of AMA1 is conserved in Plasmodium spp., numerous AMA1 allelic variants of P. falciparum have been described. The effect of AMA1 allelic diversity on the ability of a recombinant AMA1 vaccine to protect against human infection by different P. falciparum strains is unknown. We characterize two allelic forms of AMA1 that were both produced in Pichia pastoris at a sufficient economy of scale to be usable for clinical vaccine studies. Both proteins were used to immunize rabbits, singly and in combination, in order to evaluate their immunogenicity and the ability of elicited antibodies to block the growth of different P. falciparum clones. Both antigens, when used alone, elicited high homologous anti-AMA1 titers, with reduced strain cross-reactivity. Similarly, sera from rabbits immunized with a single antigen were capable of blocking the growth of homologous parasite strains at levels theoretically sufficient to clear parasite infections. However, heterologous inhibition was significantly reduced, providing experimental evidence that AMA1 allelic diversity is a result of immune pressure. Encouragingly, rabbits immunized with a combination of both antigens exhibited titers and levels of parasite inhibition as good as those of the single-antigen-immunized rabbits for each of the homologous parasite lines, and consequently exhibited a broadening of allelic diversity coverage.     

Human herpesvirus 8 infection among various population groups in southern Israel

OBJECTIVE: To compare the prevalence of antibodies to human herpesvirus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus among Israeli and Ethiopian subjects. METHODS: Serum samples were obtained from 98 Israeli Jewish students aged 18-30 years, 100 HIV-1-seronegative Ethiopian immigrants to Israel of the same age, and 100 HIV-1-seronegative Ethiopian children 1-12 years old upon their arrival in southern Israel. Plasma samples were obtained from 3 hospitalized patients with multicentric Castleman disease (MCD) as positive controls. All serum samples were tested for antibodies to both latent and lytic antigens. Antibodies to the lytic antigens and the latency-associated nuclear antigen (LANA) of HHV-8 were detected by enzyme linked immunosorbent assay and by immunofluorescence assay. HHV-8 DNA from serum or plasma samples was detected by polymerase chain reaction analysis. RESULTS: Antibodies to HHV-8 LANA were detected in 2.9% of the Israeli subjects aged 18-30 years and in 26% of the Ethiopian subjects from both age groups tested. Antibodies to the lytic antigens were detected in all 3 MCD patients, in 4% of the Ethiopian children, and in 2% of the 18- to 30-year-old Ethiopians. No antibodies to the lytic antigens were detected in the Israeli students. HHV-8 DNA was detected in all 3 MCD patients and in 2 of 4 of the Ethiopian children positive for the lytic antigens. CONCLUSIONS: HHV-8 is highly prevalent in Ethiopian immigrants to Israel as compared with Israeli students. Antibodies to HHV-8 in Ethiopia are acquired before puberty. The results of this study indicate the association of HHV-8 with MCD, as has been documented by many other researchers.     

Comparison of Digene hybrid capture 2 and conventional culture for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in cervical specimens

Digene's Hybrid Capture 2 (HC2) CT/GC, CT-ID, and GC-ID DNA tests were evaluated by comparison to traditional culture methods for detecting Chlamydia trachomatis and Neisseria gonorrhoeae infections in 669 cervical specimens from high-risk female populations attending two sexually transmitted disease clinics. For detection of either or both infections, the HC2 CT/GC test algorithm had 93.8% sensitivity and 95.9% specificity compared to those of culture. After resolution of discrepant results by direct fluorescent-antibody (DFA) staining or PCR assay, the relative sensitivity and specificity of the HC2 CT/GC test algorithm increased to 94.8 and 99.8%, while the values for culture were 83.6% (McNemar's P value, 0.0062) and 100%, respectively. For detection of the individual pathogens, the relative sensitivities for the HC2 CT-ID and GC-ID tests were 97.2 and 92.2% and the specificities were greater than 99% compared to culture adjucated by DFA staining and PCR. Test performance varied at the two clinics: the HC2 CT/GC algorithm, CT-ID, and GC-ID tests had significantly higher sensitivities (McNemar's P value, <0.05) than that of culture for the population at one clinic as well as for the combined populations. At the other clinic, the HC2 tests performed as well as culture.