Immune profile at HIV infection diagnosis: Evolution in the French Alps area over the last 20 years

ObjectivesHealth of HIV-infected people relies on early antiretroviral therapy, i.e. early diagnosis. We aimed to determine whether the characteristics at HIV diagnosis in two French medical centres changed over the last 20 years.Patients and methodsAll individuals diagnosed with HIV infection in Grenoble University Hospital (N = 814) and Annecy Hospital (N = 246) between 1997 and 2015 were included. We collected age, country of birth, mode of transmission, CD4 T cell count, CD4/CD8 ratio, and HIV viral load.ResultsAmong the 1060 patients (mean age 37.4 ± 11 years, 70.2% of men), 42.5% were men having sex with men (MSM); 65.2% were born in France, and 24.4% were born in Africa. Mean CD4 T cell count at diagnosis was 396 ± 288/mm³ and was stable over the study period when considering all patients; when considering the MSM group, a significant increase over time was observed, with a mean increase of 7.3 CD4/mm³ per year (P < 0.001). A higher CD4 count at diagnosis was observed after 2005 (400 ± 289 vs 468 ± 271/mm³, P = 0.005). The proportion of MSM patients with a CD4 count < 200/mm³ at diagnosis was lower after 2005 (14.7% after 2005 and 25.6% before, P = 0.028) This was not observed in heterosexual patients (born in Africa or not).ConclusionIn the MSM population, CD4 count at diagnosis is higher after 2005, suggesting that screening campaigns have become more efficient. This was not observed in other populations, who should be better targeted in future strategies.     

Impact of polymorphisms in the HCP5 and HLA-C,and ZNRD1 genes on HIV viral load

AIMSSingle nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL < 51 copies/ml and on CD4⁺ T-cell recovery after initiation of combination antiretroviral therapy (cART).Material and methodsWe genotyped the rs2395029 (A > C), rs9264942 (T > C), and rs3869068 (C > T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study — a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0–18 months after diagnosis and on CD4⁺ T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL < 51 copies/ml. All models were assuming additive genetic effects.ResultsThe rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660–79,433], A/C: 33,884 [19,498–58,884], P = 0.002; rs9264942: TT: 81,283 [67,608–97,724], T/C: 63,096 [54,954–75,858], CC: 38,905 [25,119–58,884], P < 0.0001; rs3869068, CC: 72,444 [63,096–83,176], C/T: 45,709 [33,113–64,565], TT: 58,884 [20,417–169,824], P = 0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL < 51 copies/ml: (HR [95% confidence interval], 1.67 [1.09–1.72], P = 0.008; 1.16 [1.06–1.28], P = 0.002; 1.30 [1.08–1.53], P = 0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4⁺ T-cell recovery during cART.ConclusionsThe minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL < 51 copies/ml during cART even after adjustment for VL before cART.     

Self-assessment of immediate post-vaccination pain after two different MMR vaccines administered as a second dose in 4- to 6-year-old children

The aim of this study was to compare self-reported immediate post-vaccination pain and safety of Priorix^® versus RORVax^® in 4- to 6-year-old children receiving their second dose of MMR vaccine, using the Faces Pain Scale-Revised (FPS-R), a validated self-report pain scale recommended by the French National Accreditation Agency and Health Evaluation.A total of 620 children from 28 French pediatricians completed all study procedures. Immediate post-vaccination pain was reported by 17.8% of the subjects in Priorix^® group (N = 309) and by 44.7% of the subjects in RORVax^® group (N = 311) [OR = 3.7; P < 0.001]. Parents’ pain scores correlated significantly with children's scores. The reduction of immediate pain incidence in Priorix^® group persisted over the 4 post-vaccination days.This study, using a validated self-assessment pain scale, confirmed previous data showing a significantly lower incidence of immediate post-vaccination pain with Priorix^® as compared to RORVax^®.     

Polymorphisms in the oligoadenylate synthetase gene cluster and its association with clinical outcomes of dengue virus infection

Oligoadenylate synthetases (OAS) play an important role in the immune response against dengue virus. Single nucleotide polymorphisms (SNPs) in the OAS genes are known to affect OAS activity and are associated with outcome of viral infections. Polymorphisms in the OAS1 (rs1131454 and rs10774671), OAS3 (rs2285932 and rs2072136) and OAS2 (rs15895 and rs1732778) genes were studied using PCR followed by restriction fragment length polymorphism methods in 109 patients hospitalized for dengue (DEN) and 105 healthy controls (HCs) who have no documented evidence of symptomatic dengue. The two locus haplotype of OAS2 G-G was significantly higher in all patient groups [DEN vs. HCs, P = 0.0041, P corrected (Pc) = 0.012, Odds ratio (OR) 1.73 95% CI 1.16–2.59] while the four locus haplotype of OAS3-OAS2 C-G-A-G was significantly lower in all dengue patient groups [DEN vs. HCs, P = 0.0054, Pc = 0.0486, OR 0.09, 95% CI 0.00–0.64] compared to controls. When the six locus haplotypes involving OAS1, OAS3 and OAS2 polymorphisms were analyzed and compared, the frequency of the haplotype A-A-C-A-G-G was significantly higher [P = 0.0267, Pc = 0.486, OR 2.34, 95% CI 1.08–4.91] and the frequency of the haplotype A-A-C-G-G-A was significantly lower in DHF cases [P = 0.014, Pc = 0.252, OR 0.12, 95% CI 0.01–0.85] compared to healthy controls. The results suggest that OAS1-OAS3-OAS2 haplotypes are associated with differential susceptibility to clinical outcomes of dengue infection.     

A 51-item calcium-focused food frequency questionnaire is a reliable tool to assess dietary calcium intake in postmenopausal women

Given the lack in a valid biomarker to assess dietary calcium intake (dCa_i), reproducible estimation of usual dCa_i is crucial for better understanding of its interaction with health outcomes in specific populations. This study tested the hypothesis that a calcium-focused food frequency questionnaire (FFQ) may be used to estimate dCa_i of women ≥50 years residing in a multicultural environment (Montreal, Canada). One hundred and eight women (age, 63.1 ± 7.7 years; 98% postmenopausal) completed the FFQ twice and 4 nonconsecutive 24-hour recalls (24HRs) over 1 month. Medians of dCa_i were compared by Wilcoxon signed rank test. Reproducibility and relative validity of the FFQ were assessed by Spearman correlation (r_s) and Cohen's weighted kappa (κw). Agreement was further assessed by cross-classification by quartiles, Bland-Altman plot, and sensitivity and specificity analyses. The median (interquartile range) dCa_i estimated by the FFQ and 24HRs were 723 (524-1033) mg/d and 854 (666-1068) mg/d, respectively (P < .001). The FFQs had a strong correlation (r_s = 0.72, P < .001) and moderate agreement (κw = 0.55). The FFQ and 24HRs were moderately correlated (r_s = 0.65, P < .001). Cross-classification showed moderate agreement (κw = 0.42), with 85% of the participants classified into identical or contiguous quartiles and 2.8% into extreme opposite quartiles. According to the Bland-Altman plot, the FFQ underestimated dCa_i with a bias of 99 mg/d (95% limits of agreement, −677 to +480 mg/d). Sensitivity and specificity of identifying intakes <1000 mg/d were 90% and 57%, respectively. This FFQ is a useful tool to discriminate dCa_i <600 and ≥1000 mg/d in postmenopausal women and to rank dCa_i in epidemiological studies.     

Occupational exposure to particulate matter from three agricultural crops in California

Agricultural work is a major contributor to California's and the nation's economy and employs a large number of workers. However, agricultural work can have numerous risks, such as exposure to elevated levels of particulate matter (PM) and other airborne pollutants with potential adverse health effects. To determine the magnitude of occupational exposures, PM levels were assessed for 89 workers from three major crops in California; almonds, melons and tomatoes. Personal samples were collected for PM_2.5 and inhalable PM using personal sampling equipment. Geometric mean concentrations from personal exposure for workers in almonds (inhalable PM = 4368 μg/m³, PM_2.5 = 122 μg/m³, N = 5), tomatoes (inhalable PM = 1410 μg/m³, PM_2.5 = 12 μg/m³, N = 33), and melons (inhalable PM = 1118 μg/m³, PM_2.5 = 19 μg/m³, N = 51) showed high PM exposure when working with these three crops. Large exposure differences by crop were more common than by task (i.e. harvesting, packing and weeding) among the three crops studied. This is the largest study of agricultural workers engaged in hand harvesting, a significant employer of farm labor, and relatively high levels of exposure to PM were measured.     

Sex differences in the association between dietary restraint,insulin resistance and obesity

Background & aimsRestrained food consumption may alter metabolic function and contribute to eventual weight gain; however, sex differences in these relationships have not been assessed. The objective of this study was to examine the relationship between restrained eating and insulin resistance and the influence of body mass index and sex on this relationship in a large community sample of both men and women. We hypothesized that restrained eating would be related to insulin resistance and this relationship would be influenced by sex and body mass index.MethodsIn this cross-sectional, observational study, we studied 487 individuals from the community (men N = 222, women N = 265), who ranged from lean (body mass index 18.5–24.9 kg/m², N = 173), overweight (body mass index 25–29.9 kg/m², N = 159) to obese (body mass index > 30 kg/m², N = 155) weight categories. We assessed restrained eating using the Dutch Eating Behavior Questionnaire and obtained fasting morning plasma insulin and glucose on all subjects.ResultsIn men, but not in women, restrained eating was related to homeostatic model assessment of insulin resistance (HOMA-IR) (p < 0.0001). Furthermore, HOMA-IR was significantly higher in men who were high- versus low-restrained eaters (p = 0.0006).ConclusionsThis study is the first to report sex differences with regard to the relationship between restrained eating and insulin resistance. Our results suggest that high restrained eating is associated with insulin resistance in men but not in women.     

Association of major dietary patterns with socioeconomic and lifestyle factors of adult women living in Tehran,Iran

ObjectivesTo detect major dietary patterns and their relation with demographic, socioeconomic, and lifestyle factors in adult women living in Tehran, Iran.MethodsIn a cross-sectional study, 460 women 20–50 y of age were selected by a stratified random-sampling method. Factor analysis was conducted to ascertain the major dietary patterns, and analysis of covariance was fitted to assess the relation between demographic, socioeconomic, and lifestyle variables and adherence to major dietary patterns.ResultsTwo major dietary patterns were extracted: healthy and unhealthy. After adjustment for confounders, age (b = 0.31, P < 0.01), university degree (b = 0.85, P < 0.01), housing size >20 m²/head (b = 0.30, P < 0.01), total family income US >$500/mo (b = 0.25, P < 0.05), physical activity (b = 0.01, P < 0.05), and history of hypertension (b = 0.36, P < 0.05) were positively associated and duration of residence in Tehran (b = ?0.01, P < 0.05) was negatively associated with a healthy dietary pattern. Conversely, ethnicity (Turk versus Fars; b = 0.30, P < 0.01) and smoking (b = 0.64, P < 0.01) were positively associated and age (b = ?0.33, P < 0.01) was negatively associated with an unhealthy dietary pattern.ConclusionOur findings support the association between demographic, socioeconomic, lifestyle factors and dietary patterns of the studied women. Therefore, it is suggested these factors should be considered in future studies on the association between dietary patterns and disease.     

Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients

IntroductionNo therapy has yet proven effective in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment.MethodWe conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: death and/or ICU admissions.ResultsPatients with TCZ (n = 20) had a higher Charlson comorbidity index (5.3 [±2.4] vs 3.4 [±2.6], P = 0.014), presented with more severe forms (higher level of oxygen therapy at 13 L/min vs 6 L/min, P < 0.001), and had poorer biological findings (severe lymphopenia: 676/mm³ vs 914/mm³, P = 0.037 and higher CRP level: 158 mg/L vs 105 mg/L, P = 0.017) than patients without TCZ (n = 25). However, death and/or ICU admissions were higher in patients without TCZ than in the TCZ group (72% vs 25%, P = 0.002).ConclusionDespite the small sample size and retrospective nature of the work, this result strongly suggests that TCZ may reduce the number of ICU admissions and/or mortality in patients with severe SARS-CoV-2 pneumonia.     

High serum copper level is associated with an increased risk of preeclampsia in Asians: A meta-analysis

Epidemiological studies evaluating the associations between serum copper and ratios of Cu/Zn and the preeclampsia (PE) risk in Asian population have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize the relationships. We hypothesize that higher serum copper and ratios of Cu/Zn may increase the PE risk. A systematic literature search was performed in PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), VIP (Database of Chinese Scientific and Technical Periodicals) and Wangfang databases for relevant studies up to November 2016. Pooled standardized mean difference (SMD) was calculated with random effects model. The results showed that PE patients had a higher serum copper level [SMD (95% CI): 1.05 (0.34, 1.77), Z = 2.88, P for Z = 0.004; I² = 96.9%, P for I²< 0.0001] compared with healthy pregnancy controls. In subgroup analyses, a higher serum copper level in PE patients was observed in case–control studies [SMD (95% CI): 1.39 (0.44, 2.34)]. No significant difference was found between PE patients and healthy pregnancy controls for ratios of Cu/Zn [(SMD (95% CI): 0.26 (−0.77, 1.29), Z = 0.49, P for Z = 0.625; I² = 95.8%, P for I²< 0.0001)]. In conclusion, our meta-analysis indicates that a higher serum copper level is associated with an increased risk of PE. Further studies are needed to confirm these results in future research.     

Genetic and functional evidence for a role for SLC11A1 in susceptibility to otitis media in early childhood in a Western Australian population

Otitis media (OM) is a common disease in early childhood characterised by inflammation of the middle ear. Susceptibility to recurrent acute OM (rAOM; ⩾3 episodes AOM in 6 months) and chronic OM with effusion (COME; middle ear effusion ⩾3 months) is 40–70% heritable. Three bacterial pathogens commonly associated with OM, Streptococcus pneumoniae (Sp), non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mc), have been observed within adenoids and as facultative intracellular pathogens that invade and survive in mononuclear cells. Case/pseudo-control conditional logistic regression analysis of variants in the SLC11A1 gene, initially identified for its role in resistance to intra-macrophage pathogens in mice, revealed association with OM at four polymorphisms (P_best = 0.025) in 531 families (660 affected children) from the Western Australian Family Study of Otitis Media. This included association at the functional promoter GTn polymorphism (rs34448891) with alleles that regulate high (allele 3; odds ratio = 1.2, 95% CI 1.00–1.44, P = 0.04) versus low (allele 2; odds ratio = 0.83, 95% CI 0.69–0.99, P = 0.04) SLC11A1 expression. Haplotype and stepwise conditional logistic regression analyses support a single genetic effect in the proximal region of SLC11A1, with the haplotype 3_C_C_G across rs34448891_rs2276631_rs3731865_rs2695343 significantly (P = 0.008) over-transmitted to affected offspring. Stratified analysis showed no association with OM in children who had undergone adenoidectomy (296 children), whereas children with adenoids intact (364 children) showed improved significance at the GTn polymorphism (allele 3: odds ratio = 1.38, 95% CI = 1.10–1.75, P = 0.006). Quantitative RT/PCR demonstrated high expression of SLC11A1 in mononuclear cells isolated from adenoid tissue, with a trend for decreased expression with increasing copies of GTn allele 2. Expression of SLC11A1 was enhanced at 12 (P = 1.2 × 10⁻³) and 24 h (P < 1.0 × 10⁻⁴) after infection of Mono-Mac-6 cells with NTHi. This study identifies SLC11A1 as a novel candidate for OM susceptibility, particularly in children with adenoids intact. Further analysis in other cohorts is required to validate these observations.     

Source of drug resistant Plasmodium falciparum in a potential malaria elimination site in Saudi Arabia

A major challenge to the success of malaria control program in Saudi Arabia is the high influx of expatriates and holy visitors from malaria endemic countries. In the present study we examined whether drug resistant parasite genotypes reported in Jazan region, southwest of Saudi Arabia are imported or developed locally. We examined 178 Plasmodium falciparum isolates for alleles of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), associated with Sulfadoxine-Pyrimethamine (SP) resistance, and three microsatellites flanking each gene. In addition, we examined a neutral polymorphic gene (Pfg377). We compared the dhfr and dhps haplotypes in Jazan, using network analysis, to an existing similar data set of 94 P. falciparum isolates from eastern Sudan. In Jazan, double mutant dhfr allele (51I, 108N) occurred with a prevalence of 33%. The vast majority (99%) of dhps were wild-type alleles. The mean expected heterozygosity (H_e) of microsatellites around mutant dhfr alleles (H_e = 0.312; n = 60) was lower (P ? 0.05) than that around the wild-type allele (H_e = 0.834; n = 116). Also, the mutant dhfr isolates showed high H_e for dhps (H_e = 0.80) and the non-drug resistance locus Pfg377 (H_e = 0.63) indicative of selection for mutant dhfr only. The predominant double mutant dhfr haplotype in Jazan (73%), was prevalent among P. falciparum in east Africa. Network analysis suggests the mutant haplotype of dhfr gene was possibly introduced into Jazan from East Africa. The absence of mutations in dhps as well as triple mutant dhfr haplotype associated with SP failure support the current use of SP as a partner with artesunate as a first line therapy in Saudi Arabia. However, the close relationship between the major mutant dhfr haplotype in Sudan and Saudi Arabia, favour the hypothesis of recent migration as a source of the major resistant dhfr lineage. Thus, regular monitoring of the dhfr and dhps haplotypes is of high priority to guard possible importation of high level SP resistant lineages.     

Association of human leukocyte antigen DP/DQ gene polymorphisms with chronic hepatitis B in Chinese Han and Uygur populations

Several genome-wide association studies (GWAS) have shown that human leukocyte antigen (HLA) DP/DQ gene polymorphisms are associated with susceptibility to chronic hepatitis B virus (HBV) infection. We clarified the roles of the HLA-DP/DQ gene in HBV infection in different nationalities. Three single nucleotide polymorphisms (SNPs) in HLA-DP (rs9277471, rs9277535 and rs9277542) and the SNP rs9272346 in HLA-DQ were studied. In total, 779 patients were recruited to this study, including 400 Chinese Han and 399 Uygurs. The rs9277535 variant genotypes were directly associated with HBV persistence compared to healthy controls in an additive model of the Chinese Han population (odds ratio [OR] = 1.88, 95% confidence interval [CI] = 1.03–3.41, P = 0.040), and in a recessive model of the Chinese female population (OR = 2.02, 95% CI = 1.26–3.24, P = 0.003). In addition, rs9277471 and rs9277542 variant genotypes significantly decreased the risk of HBV infection compared to healthy controls in an additive model of the Chinese Han population (OR = 0.53, 95% CI = 0.29–0.98, P = 0.042; OR = 0.53, 95% CI = 0.29–0.97, P = 0.039) and in a dominant model of the Chinese female population (OR = 0.50, 95% CI = 0.31–0.80, P = 0.004; OR = 0.49, 95% CI = 0.31–0.79, P = 0.003). The GG genotype of rs9277346 was associated with HBV infection in the Chinese Han population (additive model: OR = 0.38, 95%CI = 017–0.82, P = 0.014; recessive model: OR = 0.41, 95% CI = 0.19–0.86, P = 0.019) and in males (additive model: OR = 0.31, 95% CI = 0.14–0.65, P = 0.002; dominant model: OR = 0.65, 95% CI = 0.43–0.97, P = 0.034; recessive model: OR = 0.36, 95% CI = 0.18–0.73, P = 0.005). In addition, allele G of rs9277346 was marginally related to a reduction in risk for HBV infection in the Uygur population. Our study suggests that HLA-DP/DQ polymorphisms can affect susceptibility and resistance to HBV infection in Chinese populations, and are possibly linked to race and sex.     

Perceived effectiveness of HPV test as a primary screening modality among US providers

BackgroundThe human papillomavirus (HPV) test, administered alone without the Papanicolaou (Pap) test, was recently recognized as a cervical cancer screening option in the United States by the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology, and the Food and Drug Administration has approved an HPV test for primary screening.MethodsSurveys of US internists, family practitioners, nurse practitioners, and obstetrician–gynecologists were conducted in 2009 and 2012 to investigate providers' perceptions of the effectiveness of the HPV test administered alone as a population-based screening modality (2009: N = 1040, 141–494 per provider group; 2012: N = 1039, 155–435 per provider group).ResultsThe majority in each provider group agreed that the HPV test administered alone is an effective screening modality in 2009 (75.3%–86.1%) and 2012 (79.5%–91.8%), and agreement rose significantly during this time period among family practitioners (χ² = 15.26, df = 1, p < 0.001) and nurse practitioners (χ² = 4.53, df = 1, p = 0.033).ConclusionsAgreement that the HPV test administered alone is an effective cervical cancer screening modality was widespread among providers in both 2009 and 2012, however implementation of guidelines for screening with the HPV test may be influenced by many other factors including reimbursement and patient preferences.     

Relationships between depression,gender, and unhealthy weight loss practices among overweight or obese college students

IntroductionUnhealthy weight loss practices are common among female college students. It is unknown if these practices are also most common among women in the subset of overweight or obese college students or if these practices are related to depression. We examined the relationship between gender, depression, and unhealthy weight loss practices among overweight or obese college students.MethodsStudents (body mass index between 25.0 and 34.9 kg/m²) from three Southern California universities (M_age = 22 years, SD = 4; 70% women) were recruited from May 2011 to May 2012 for participation in a weight loss clinical trial (N = 404). Logistic regressions were performed with baseline data to assess the cross-sectional relationship between self-reported unhealthy weight loss practices and gender and depression as measured by the Center for Epidemiologic Studies Depression short form.ResultsTwenty-nine percent of participants reported engaging in at least one unhealthy weight loss behavior (e.g., fasting, purging) over the last 30 days, with no differences by gender. Self-report of at least one unhealthy weight loss behavior was associated with report of symptoms of depression (e^B = 1.14 [confidence interval, CI: 1.08–1.20]), adjusting for potential confounders. Interactions between gender and depression were not significant (e^B = 1.04 [CI: 0.93–1.16]).ConclusionAmong an overweight or obese sample of college students, unhealthy weight loss practices were equally common in both genders, and students with depressive symptomatology were at greatest risk. Obesity interventions targeting overweight or obese college students should educate both men and women about the dangers of unhealthy weight loss practices. In addition, screening for depression can help identify students who would benefit from additional supportive and coping strategies and resources.     

PK/PD targets of amikacin and gentamicin in ICU patients

ObjectivesWe aimed to evaluate the probability to achieve PK-PD targets in patients with sepsis hospitalized in the intensive care unit (ICU) after a single dose of 30 mg/kg of amikacin or 8 mg/kg of gentamicin.Patients and methodsThis single-center prospective study included 138 ICU patients with severe sepsis or septic shock with an indication for intravenous amikacin (N = 89) or gentamicin (N = 49). Maximum concentration (C_max) was measured 30 minutes after infusion completion. PK/PD objectives were respectively C_max ≥ 60 mg/L and ≥ 30 mg/L for amikacin and gentamicin for empirical therapy, and a C_max/MIC ratio ≥ 8, as per French guidelines.ResultsThe median Simplified Acute Physiology Score II was 43 and ICU case fatality rate was 34.8%. A causative bacterial agent was identified in 94 patients (68.1%). Three pathogens had acquired aminoglycoside resistance and 15 were naturally resistant. The targeted C_max for the first dose was achieved in 53 patients (59.6%) receiving amikacin, and one (2.2%) patient receiving gentamicin. C_max/MIC ratio ≥ 8 was obtained in all patients infected with susceptible pathogens (N = 72). Factors associated with C_max ≥ 60 mg/L of amikacin in multivariate analysis were dose per kg of adapted body weight (OR = 1.39, P < 0.001) and renal clearance estimated with CKD-EPI formula (OR = 0.98, P = 0.003).ConclusionsDespite high doses, amikacin and gentamicin first C_max remain dramatically low in ICU patients. However, an adequate C_max/MIC ratio was reached in all patients.     

The nucleotide changes within HBV core promoter/precore during the first 12 weeks of nucleos(t)ide treatment might be associated with a better virological response

ObjectivesWe aimed to study the dynamic changes of hepatitis B virus (HBV) core promoter/precore (CP/preC) sequences during antiviral treatment and their associations with virological responses.Materials and methodsThe baseline and 12-week CP/preC sequences (nts 1655–2014) were obtained from 52 chronic hepatitis B patients with positive hepatitis B e antigen (HBeAg), who received a 104-week lamivudine and adefovir dipivoxil combination therapy. The mutations within the CP/preC were analyzed against genotype specific reference sequences. The nucleotide change rates in individuals during therapy were analyzed in a pairwise comparison manner.ResultsThere was no significant difference of the mutation rate at each nucleotide site between baseline and week 12 of treatment (P > 0.05). The mutation rates of A1762T/G1764A and G1896A were found to decrease from 46.2% (24/52) at baseline to 36.5% (19/52) at week 12 (P = 0.426) and from 28.8% (15/52) to 21.2% (11/52) (P = 0.497), respectively. The nucleotide change rates varied from 0.0% - 7.8% in individuals [0.0% in Group 1 (N = 26); 0.3% - 7.8% in Group 2 (N = 26)] during the first 12-week treatment. HBV DNA levels in Group 2 were significantly lower than those in Group 1 throughout therapy (P < 0.01) (e.g., 1.5 ± 1.3 log₁₀ IU/ml vs. 2.6 ± 1.0 log₁₀ IU/ml at week 104, P = 0.001). At week 104 the rates of HBV DNA undetectable and HBeAg loss in Group 2 were significantly higher than those in Group 1 (P < 0.05). Along with the increased nucleotide change rates, the rate of HBV DNA undetectable at week 104 tended to increase (odds ratio = 0.323, 95% confidence interval = 0.138–0.758, P < 0.001).ConclusionOur findings suggested that the nucleotide changes within HBV CP/preC region during the first 12-week treatment might be associated with a better virological response.     

The MTHFR C677T mutation is not a risk factor recognized for HBV-related HCC in a population with a high prevalence of this genetic marker

BackgroundPolymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene can affect disease progression in HBV infection. However, the results from different reports are inconsistent. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and the outcome of HBV infection in a Tianjin Han population.MethodsTaqMan SNP genotyping was employed to determine the alleles and genotypes of MTHFR C677T in 2511 subjects from various stages of HBV infection and 549 healthy controls.ResultsOf the 3060 subjects, the genotypic frequencies were CT 48.9%, TT 29.3% and CC 21.8%; the allelic frequencies were T 53.8% and C 46.2%. There was no significant difference in genotypic or allelic distribution among the different disease groups. When either healthy subjects or self-limited subjects were used as controls, the TT genotype and the T allele conferred protective effects against hepatocellular carcinoma (HCC) (HCC vs healthy subjects: OR = 0.588, 95% CI = 0.413–0.836, P = 0.003; OR = 0.768, 95% CI = 0.645–0.915, P = 0.003, respectively. HCC vs self-limited subjects: OR = 0.598, 95% CI = 0.404–0.886, P = 0.010; OR = 0.772, 95% CI = 0.635–0.940, P = 0.010, respectively). After sub-stratification by gender, the prevalence of the TT genotype or T allele was the lowest in the male HCC group (TT 23.5%, T 49.8%). The protective effects of the TT genotype and the T allele were observed in male HCC and cirrhotic subjects (HCC vs self-limited subjects: OR = 0.470, 95% CI = 0.288–0.766, P = 0.002; OR = 0.681, 95% CI = 0.535–0.866, P = 0.002, respectively. Liver cirrhosis vs self-limited subjects: OR = 0.624, 95% CI = 0.392–0.992, P = 0.046; OR = 0.791, 95% CI = 0.627–0.998, P = 0.048, respectively), but not in female. When the subjects were stratified according to the clinical features, no statistically significant difference in the genotypic distribution was observed (P > 0.05).ConclusionsThe TT genotype and T allele of MTHFR C677T may confer a protective effect on disease progression to HCC in HBV-infected individuals, especially among male patients, in a population with a high prevalence of this genetic marker.     

Evaluating a school-based fruit and vegetable co-op in low-income children: A quasi-experimental study

The purpose of this study was to evaluate the effectiveness of a new school-based food co-op program, Brighter Bites (BB), to increase fruit and vegetable intake, and home nutrition environment among low-income 1st graders and their parents. This was a non-randomized controlled comparative effectiveness trial (2013–2015). Six schools received BB (n = 407 parent-child dyads); six comparison schools implemented a coordinated school health program (n = 310 parent-child dyads) in Houston, Texas, 2013–2015. Brighter Bites (BB) is a 16-week school-based food co-op comprising weekly distribution of fresh produce (50 servings); nutrition education in schools and for parents; and weekly recipe tastings. Measurements included parent-reported home nutrition environment surveys, and food frequency questionnaires for parent and child. Intervention effects were examined using multivariate analyses. At baseline, the sample was 71% Hispanic, 24% African American; 43% of 1st graders were overweight/obese. Children receiving BB had significant increases in intake of fruit servings (P = 0.046), vegetable servings (P = 0.049), and decreased intake of added sugars (P = 0.014). Among parents, there were significant increases in fruit consumed (P = 0.032); vegetable intake increased baseline to midpoint but not post-intervention. Among BB families, there were significant improvements in the home environment including understanding and usage of nutrition facts labels to make food purchases (P < 0.05), frequency of cooking (P = 0.007), rules and practices regarding eating family meals (P = 0.022), serving fruits (P = 0.005) and vegetables (P = 0.028) at meals, and limiting portion sizes (P = 0.016).In conclusion, a school-based food co-op model shows promising results in improving dietary habits and home nutrition environment among low-income families.     

Spectrophotometric method for determination of aluminium content in water and beverage samples employing flow-batch sequential injection system

A sensitive, precise and reliable flow-batch method for the determination of aluminium (Al) was developed using a sequential injection-monosegmented flow system incorporating a mixing chamber unit. Eriochrome cyanine R (ECR) was used as a chromogenic reagent in the presence of N,N-dodecyltrimethylammonium bromide (DTAB). The Al-ECR complex at pH 6 gave a maximum absorption at 584 nm. In-line single standard calibration and a standard addition procedure were developed employing the monosegmented flow technique. Under the optimum conditions, a linear calibration graph in the range of 0.0075–0.625 mg L⁻¹ Al was obtained with limits of detection and quantitation of 0.0020 and 0.0070 mg L⁻¹, respectively. Relative standard deviations were 0.8 and 1.3% for 0.010 and 0.025 mg L⁻¹ Al (n = 11), respectively. A sample throughput of 24 h⁻¹ using an in-line standard calibration approach and 6 h⁻¹ using four standard addition levels was achieved. The developed system was successfully applied to water samples and beverage samples. The results agreed well with those obtained from the ICP-AES method. Good recoveries between 85 and 104% were obtained.