Quantitation of pretreatment serum interferon-γ-inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response

Polymorphisms of the IL28B gene are highly associated with sustained virological response (SVR) in patients with chronic hepatitis C treated with peginterferon and ribavirin. Quantitation of interferon-γ-inducible protein-10 (IP-10) may also differentiate antiviral response. We evaluated IP-10 levels in pretreatment serum from 115 nonresponders and 157 sustained responders in the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C cohort, including African American (AA) and Caucasian American (CA) patients. Mean IP-10 was lower in sustained responders compared with nonresponders (437 ± 31 vs 704 ± 44 pg/mL, P < 0.001), both in AA and CA patients. The positive predictive value of low IP-10 levels (<600 pg/mL) for SVR was 69%, whereas the negative predictive value of high IP-10 levels (>600 pg/mL) was 67%. We assessed the combination of pretreatment IP-10 levels with IL28B genotype as predictors of treatment response. The IL28B polymorphism rs12979860 was tested in 210 participants. The CC, CT, and TT genotypes were found in 30%, 49%, and 21% of patients, respectively, with corresponding SVR rates of 87%, 50%, and 39% (P < 0.0001). Serum IP-10 levels within the IL28B genotype groups provided additional information regarding the likelihood of SVR (P < 0.0001). CT carriers with low IP-10 had 64% SVR versus 24% with high IP-10. Similarly, a higher SVR rate was identified for TT and CC carriers with low versus high IP-10 (TT, 48% versus 20%; CC, 89% versus 79%). IL28B genotype and baseline IP-10 levels were additive but independent when predicting SVR in both AA and CA patients. CONCLUSION: When IL28B genotype is combined with pretreatment serum IP-10 measurement, the predictive value for discrimination between SVR and nonresponse is significantly improved, especially in non-CC genotypes. This relationship warrants further investigation to elucidate the mechanisms of antiviral response and prospective validation.     

Impact of barrier precautions and antibiotic consumption on the incidence rate of acquired cases of infection or colonization with Acinetobacter baumannii: a 10-year multi-department study

Following a previous investigation, this ecological study assessed the impact of barrier precautions and various factors on the annual incidence rate of acquired Acinetobacter baumannii cases in each of the 32 departments of the University Hospital of Besan?on from 2000 to 2009. Ultimately, our study confirms the effectiveness of barrier precautions in addition to standard precautions for controlling A baumannii within our hospital departments. In comparison with the previous research, it emphasizes the significant role of fluoroquinolones in the emergence and the spread of this microorganism.     

Language lateralization in left-handed patients with schizophrenia

We evaluated hemispheric lateralization of language production in non-right-handed (NRH) patients with schizophrenia compared with matched right-handed (RH) patients, NRH control, and RH control subjects. First, the ability to generate verbs during overt training trials was checked in 78 subjects. They were then evaluated with functional magnetic resonance imaging (fMRI) while performing a covert verb generation task. No significant interactions between illness and handedness and no illness effect were observed in functional asymmetry. There was significantly less leftward asymmetry of the inferior frontal, precentral, and supramarginal gyri as well as the intra-parietal sulcus in non-right-handers compared to right-handers taking into account the task performances. Our findings suggested that decreased lateralization for language production was more closely related to handedness than to schizophrenia.     

From prenatal HIV testing of the mother to prevention of sexual HIV transmission within the couple

The first step in preventing mother-to-child HIV transmission (PMTCT) programmes is offering HIV counselling and testing to pregnant women. In developing countries where HIV testing remains rare, it represents a unique opportunity for many women to learn their HIV status. This prenatal HIV testing is not only the entry point to prevention of mother-to-child HIV transmission, but also an occasion for women to sensitize their male partner to sexual risks. Here we explore if these women, HIV-tested as mothers, apply the prevention recommendations they also receive as women.In the Ditrame Plus PMTCT program in Abidjan, Côte d'Ivoire, two cohorts of women (475 HIV-infected women and 400 HIV-negative women) were followed up two years after the pregnancy when they were offered prenatal HIV testing. In each cohort, we compared the proportion of women who communicated with their regular partner on sexual risks, prior to and after prenatal HIV testing. We analysed socio-demographic factors related to this communication. We measured two potential conjugal outcomes of women HIV testing: the level of condom use at sex resumption after delivery and the risk of union break-up.Prenatal HIV testing increased conjugal communication regarding sexual risks, whatever the woman's serostatus. This communication was less frequent for women in a polygamous union or not residing with their partner. Around 30% of women systematically used condoms at sex resumption. Among HIV infected ones, conjugal talk on sexual risks was related to improved condom use. After HIV testing, more HIV-infected women separated from their partners than HIV-uninfected women, despite very few negative reactions from the notified partners.In conclusion, offering prenatal HIV counselling and testing is an efficient tool for sensitizing women and their partners to HIV prevention. But sexual prevention in a conjugal context remains difficult and need to be specifically addressed.     

Do we really know the cause of death of the very old? Comparison between official mortality statistics and cohort study classification

Causes of death of 625 subjects who died during the 4-year follow-up of a large population-based elderly cohort (Three-City study) were independently classified by the study adjudication committee and the national mortality register. The former used all available data about the cause of death (hospital records, medical data obtained from family physicians or specialists, and proxy interviews) and the latter used internationally standardized recommendations for processing death certificate data. Comparison showed a moderate overall agreement for underlying cause of death between the study adjudication committee and the national register (kappa = 0.51). Differences were found especially for cardiovascular diseases (20.6% of deaths from the study committee vs. 32.5% from the national register) and ill-defined causes of death (22.7 vs. 4%). The proportion of disagreement increased in participants dying at age >85 compared to those dying at age ≤70 (adjusted odds ratio = 2.46, 95% confidence interval = 1.10–5.49). It was also higher when the study committee used hospital record data for defining cause of death, compared to adjudication based on data obtained from proxy (adjusted odds ratio = 1.85, 95% CI = 1.09–3.14). These findings raise questions about the validity of national mortality registers in very old persons. Disease-specific causes of death, especially vascular diseases, could be overestimated in this age group.     

Functional deficit in the medial prefrontal cortex during a language comprehension task in patients with schizophrenia

OBJECTIVE: We and others have observed that patients with schizophrenia commonly presented a reduced left recruitment in language semantic brain regions. However, most studies include patients with leftward and rightward lateralizations for language. We investigated whether a cohort comprised purely of patients with typical lateralization (leftward) presented a reduced left recruitment in semantic regions during a language comprehension task. The goal was to reduce the inter-subject variability and thus improve the resolution for studying functional abnormalities in the language network. METHODS: Twenty-three patients with schizophrenia (DSM-IV) were matched with healthy subjects in age, sex, level of education and handedness. All patients exhibited leftward lateralization for language. Functional MRI was performed as subjects listened to a story comprising characters and social interactions. Functional MRI signal variations were analyzed individually and compared among groups. RESULTS: Although no differences were observed in the recruitment of the semantic language network, patients with schizophrenia presented significantly lower signal variations compared to controls in the medial part of the left superior frontal gyrus (MF1) (x=-6, y=58, z=20; Z(score)=5.6; p<0.001 uncorrected). This region corresponded to the Theory of Mind (ToM) network. Only 5 of the 23 patients (21.7%) and 21 of the 23 (91.3%) control subjects demonstrated a positive signal variation in this area. CONCLUSIONS: A left functional deficit was observed in a core region of the ToM network in patients with schizophrenia and typical lateralizations for language. This functional defect could represent a neural basis for impaired social interaction and communication in patients with schizophrenia.     

Plasma carotenoids and onset of dysglycemia in an elderly population: results of the Epidemiology of Vascular Ageing Study

OBJECTIVE—The hypothesis of carotenoid having a preventive role in diabetes is suggested by their antioxidant properties. In this report, we investigated the relationship between baseline total plasma carotenoid levels and 9-year onset of dysglycemia (impaired fasting glucose or type 2 diabetes) in a healthy elderly population.RESEARCH DESIGN AND METHODS—The Epidemiology of Vascular Ageing Study is a 9-year longitudinal study including 1,389 volunteers aged 59–71 years. Fasting plasma glucose was measured at baseline and at 2, 4, and 9 years after inclusion. The relationship between plasma carotenoid at baseline and incidence of dysglycemia was determined by Cox proportional hazards regression analysis adjusting for potential confounders.RESULTS—At 9 years, 127 incident cases of dysglycemia had occurred. Risk of dysglycemia was significantly lower in participants with plasma carotenoid in the highest quartile (Q4) compared with participants in the lowest quartile (Q1) (Q4 vs. Q1: relative risk 0.26 [95% CI 0.14–0.49], P < 10⁻⁴; Q3 vs. Q1: 0.55 [0.34–0.89], P = 0.01; and Q2 vs. Q1: 0.82 [0.51–1.31], P = 0.40). After controlling for sociodemographic variables, lifestyle habits, cardiovascular disease, blood pressure, BMI, and lipid profile, risk of dysglycemia remained significantly lower in participants in the highest quartile of total plasma carotenoid compared with participants in the lowest quartile (Q4 vs. Q1: 0.42 [0.22–0.82], P = 0.01; Q3 vs. Q1: 0.69 [0.41–1.15], P = 0.16; and Q2 vs. Q1: 0.80 [0.48–1.32], P = 0.38).CONCLUSIONS—This study prospectively confirms that plasma carotenoid levels have an independent relationship to onset of dysglycemia.Carotenoids are natural pigments synthesized by plants and microorganisms but not by animals or by humans. These pigments are found in food, especially in fruits and vegetables. It is highly suggested that they play a protective role in chronic diseases (1) or cancers. Even if the biological mechanisms for such a protection are currently unclear (2), their protective effects could come from their antioxidant properties (3).Several cross-sectional (4–6) and case-control (7–9) studies have shown an inverse relationship between serum carotenes and type 2 diabetes status. A longitudinal study (10) on dietary intake of antioxidants found a significant relationship between β-cryptoxanthin intake and reduced risk of type 2 diabetes; however, the association between serum carotenoid and diabetes was called into question by the results of two other longitudinal studies (11,12) and one randomized double-blind trial (13).To investigate if carotenoids could have a role in diabetes incidence in the elderly, possibly through their antioxidant capacity, we explored the relationships between total plasma carotenoid levels at baseline and 9-year occurrence of type 2 diabetes or impaired fasting glucose (IFG) in a healthy elderly population.