The role of single nucleotide variant rs3819817 of the Histidine Ammonia-Lyase gene and 25-Hydroxyvitamin D on bone mineral density, adiposity markers, and skin pigmentation, in Mexican population.

PURPOSE: Vitamin D (VD) deficiency and osteoporosis have become a global public health problem. A variant in the Histidine Ammonia-Lyase (HAL) gene has been associated with VD levels and bone mineral density (BMD). However, whether this variant has an influence on VD levels and BMD in Mexican adults remain unclear. METHODS: This cross-sectional analysis included 1,905 adults participating in the Health Worker Cohort Study and 164 indigenous postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort. The rs3819817 variant was genotyped by TaqMan probe assay. Total 25 hydroxyvitamin D levels were measured by DiaSorin Liaison. BMD at the different sites was assessed through dual-energy X-ray absorptiometry. Linear and logistic regression models were performed to evaluate the associations of interest. RESULTS: The prevalence of VD deficiency was 41%, showing differences between sexes. Obesity and skin pigmentation were associated with lower levels of VD in males and females. rs3819817-T allele was associated with low levels of 25-hydroxyvitamin D, VD deficiency, and hip and femoral neck BMD values (g/cm2). We found two interactions with VD levels, one between adiposity and rs3819817-T allele (P = 0.017) and another between skin pigmentation and rs3819817-T allele (P = 0.019). In indigenous postmenopausal women, we observed higher VD levels in the southern region compared to the northern region (P < 0.001); however, we did not observe differences by genotype. CONCLUSION: Our findings confirm that the genetic variant rs3819817 has an essential function in VD levels and BMD and suggests a role in skin pigmentation in the Mexican population.

COVID-19 fatality in Mexico's indigenous populations.

OBJECTIVE: The aim of the study was to explore the factors that could explain the differences in fatality rates among indigenous groups with COVID-19 diagnosis compared with the rest of the population in Mexico. STUDY DESIGN: We analyzed the public data of COVID-19 surveillance, of the Mexican Ministry of Health, to estimate COVID-19 fatality rates by ethnicity. METHODS: We explored associated factors using Cox proportional hazards models stratified by outpatient and hospital management at diagnosis; analysis was conducted in three scenarios: national level, states with 89% of the indigenous population, and South Pacific region. RESULTS: A total of 412,017 COVID-19 cases were included, with 1.1% of the indigenous population. The crude fatality rate per 1000 person-weeks was 64.8% higher among indigenous than among non-indigenous people (29.97 vs. 18.18, respectively), and it increased more than twice within outpatients (5.99 vs. 2.64, respectively). Cox analysis revealed that indigenous people who received outpatient management had higher fatality rate than non-indigenous outpatients, at the national level (hazard ratio [HR] = 1.63; 95% confidence interval [CI] = 1.34-1.98), within the subgroup of 13 states (HR = 1.66; 95% CI = 1.33-2.07), and in the South Pacific region (HR = 2.35; 95% CI = 1.49-3.69). Factors associated with higher fatality rates among non-indigenous and indigenous outpatients were age, sex, and comorbidities. CONCLUSIONS: COVID-19 fatality is higher among indigenous populations, particularly within cases managed as outpatients.

Association between vitamin D deficiency and common variants of Vitamin D binding protein gene among Mexican Mestizo and indigenous postmenopausal women.

PURPOSE: Vitamin D deficiency (VDD) and polymorphisms in the group-specific component (GC) gene are known to be associated in different populations. However, the effects of such genetic variants may vary across different populations. Thus, the objective of this study was to estimate the association between Vitamin D-Binding Protein (VDBP) haplotypes and VDD in mestizo postmenopausal women and Mexican Amerindian ethnic groups. METHODS: This was a cross-sectional study of 726 postmenopausal Mexican women from the Health Workers Cohort Study (HWCS) and 166 postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort in Mexico. GC polymorphisms (rs7045 and rs4588) were analyzed by TaqMan probes. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by Chemiluminescent Microparticle Immuno Assay. RESULTS: The prevalence of VDD serum 25(OH)D < 20 ng/mL was 43.7% in mestizo women and 44.6% in indigenous women. In HWCS, the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were associated with VDD. In addition, women from the HWCS, carrying the haplotypes GC2/2 and GC1f/2 had higher odds of VDD (OR = 2.83, 95% CI 1.14, 7.02; and OR = 2.30, 95% CI 1.40, 3.78, respectively) compared to women with haplotype 1f/1 s. These associations were not statistically significant in the MAIS cohort. CONCLUSIONS: Our results show genetic association of the analyzed SNPs and related haplotypes, on the GC gene, with VDD in mestizo Mexican postmenopausal women. Moreover, a high prevalence of VDD with high genetic variability within the country was observed. Our results support the need for national policies for preventing VDD.

Association of RMND1/CCDC170-ESR1 single nucleotide polymorphisms with hip fracture and osteoporosis in postmenopausal women.

OBJECTIVE: This study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) on the RMND1, CCDC170, and ESR1 genes with osteoporosis or hip fracture in a postmenopausal Mexican population. METHODS: We included a group of 400 postmenopausal women from the Health Workers Cohort Study from the Mexican Institute of Social Security. As a replication sample, we recruited 423 postmenopausal women from the National Institute of Rehabilitation. Demographic data were collected through a structured questionnaire. Bone mineral density was assessed using dual X-ray absorptiometry. Individuals were classified as normal, osteopenia, osteoporosis, and fracture, according to World Health Organization criteria. Genotyping was performed using predesigned TaqMan Probes. Linear regression analysis was used to investigate association. RESULTS: All of the analyzed SNPs showed association with at least one of the phenotypes of the study groups. In addition, we observed a region with linkage disequilibrium within the ESR1 gene in all groups. CONCLUSION: This study shows that an association of the SNPs can exist with osteopenia, osteoporosis, or fragility fracture. Our results agree with data published elsewhere, supporting the potential of these loci for the identification of the population at risk. However, additional studies are required to determine the extent of this association for other geographic regions of Mexico.

Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

Dietary patterns are associated with bone mineral density in an urban Mexican adult population.

UNLABELLED: Several types of nutrients and foods affect bone mineral density (BMD). However, these nutrients occur together in food groups and dietary patterns, and the overall effects of dietary patterns are not yet well known. INTRODUCTION: We evaluated the associations between dietary patterns and BMD among adults participating in the Health Workers Cohort Study. METHODS: In a cross-sectional analysis, we examined 6915 Mexican adults aged 20-80 years. All participants completed a validated self-administered food frequency questionnaire (FFQ) and had total, hip, and spine BMD measurements assessed by dual-energy X-ray absorptiometry (DXA). The FFQ included 116 foods, which were grouped into 22 categories and entered into a factor analysis to derive dietary patterns. RESULTS: Three dietary patterns emerged-a Prudent, a Refined foods, and a Dairy and fish pattern. After adjustment for potential confounders, those in the highest quintile of the Prudent pattern had lower odds (OR) of low spine BMD (OR = 0.80; 95 % CI 0.68, 0.94; P for trend = 0.031) compared to those in the lowest quintile. In contrast, participants in the highest quintile of the Refined foods pattern had greater odds of low total BMD (OR = 1.74; 95 % CI 1.10, 2.76; P for trend = 0.016) than those in the lowest quintile. Finally, participants in the highest quintile of the Dairy and fish dietary pattern had significantly lower likelihood of having low BMD. CONCLUSION: This study identified specific dietary patterns associated with BMD among a Mexican adult population and highlights the importance of promoting food-based prevention strategies for maintaining bone health.

Distribution and factors associated with salivary secretory leukocyte protease inhibitor concentrations.

OBJECTIVES: This cross-sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men. METHODS: Extracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA-based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively. RESULTS: Among men aged 18-73 years, the median SLPI concentration was 492.0 ng ml-1 (range: 2.3-1919.9). In multivariable modeling, men in Brazil and younger men (18-30 years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94-7.59, and aOR 3.84; 95% CI: 1.98-7.43, respectively]. Men with a self-reported sexually transmitted diseases diagnosis in the past 6 months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1-7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15-0.79). Similar results were observed for linear regression models. CONCLUSIONS: Secretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.

Fine-mapping butyrophilin family genes revealed several polymorphisms influencing viral genotype selection in hepatitis C infection.

Host-viral genetic interaction has a key role in hepatitis C infection (HCV) and maybe in the viral selection. In a preliminary GWAS analysis, we identified BTN3A2 rs9104 to be associated with HCV genotype 1. Therefore, our aim was to determine the influence of BTN family on the selection of HCV genotype. We performed a fine-mapping analysis of BTN gene region in a cohort of chronic HCV infection (N=841), validating significant results in another independent chronic HCV infection cohort (N=637), according to selection of viral genotype. BTN3A2 rs9104, BTN3A2 rs733528, BTN2A1 rs6929846, BTN2A1 rs7763910 and BTN3A3 rs13220495 were associated with viral genotype selection. Interestingly, BTN3A2 rs9104 GG genotype was closely related to genotype 1 infection (80.7% (394/488) compared with genotype 3 infection (53.5% (23/43); P=0.0001) in patients harboring IL28B-CT/TT genotype, although this effect was not observed in IL28B-CC genotype. Similarly, BTN3A3 rs13220495 CC genotype was linked to genotype 3 infection (100% (32/32)) compared to genotype 1 (87.3% (137/157); P=0.028) in patients harboring IL28B-CC genotype, but did not in IL28B-CT/TT genotype. Genetic variants in the butyrophilin family genes may alter susceptibility to infection, selecting HCV genotype and influencing disease progression. BTN3A2 rs9104 was strongly associated with genotype 1 infection and the haplotype BTN3A3 rs13220495 CC+IL28B genotype CC was universal in patients with hepatitis C genotype 3a.

Effects of ribavirin monotherapy on the viral population in patients with chronic hepatitis C genotype 1: direct sequencing and pyrosequencing of the HCV regions.

Ribavirin remains essential to chronic hepatitis C treatment. This paper investigates the influence of ribavirin priming to steady state before combined pegylated-interferon/ribavirin treatment on viral kinetics, ribavirin trough concentrations, genetic variability within HCV-core, -NS5B and -NS5A, and response to antiviral therapy. A prospective cohort study was made of 27 chronic hepatitis C genotype 1 naïve patients who received four weeks of ribavirin followed by pegIFN-α-2a/ribavirin for 48 weeks (Group A). The results obtained were compared with those for a control/historical group (Group B). In addition, direct sequencing and pyrosequencing were applied to determine ribavirin monotherapy-induced sequence changes. The rapid, early, and sustained virological response values obtained were 48%, 89%, and 52%, respectively, in Group A, and 52%, 90%, and 52% in Group B (P > 0.05). In the four-week combined treatment, the Group A patients showed a greater decrease in HCV-RNA (2.3 log10 IU/ml vs. 1.2 log10 IU/ml; P = 0.04), lower alanine aminotransferase levels (23.5 ± 1.33 U/L vs. 60.11 ± 18 U/L; P < 0.001) and higher mean ribavirin trough concentrations (3.28 ± 1.26 mg/L vs. 1.74 ± 0.7 mg/L; P = 0.001). No general increase in rates of nucleotide substitutions in the ribavirin monotherapy-treated patients was observed in NS5B, ISDR, or PKRbd, but there was a decrease in silent mutations in the HCV core (P = 0.04). This result was confirmed by pyrosequencing in the NS5A region. It is concluded that the ribavirin priming combined treatment with pegIFN-α-2a does not improve sustained virological response rates in HCV genotype 1 naïve infected patients. However, the greater reductions in viral load and alanine aminotransferase levels, together with the higher ribavirin trough concentration values obtained, could reflect the greater effectiveness of the treatment. Ribavirin does not have a mutagenic effect on the virus in patients with chronic hepatitis C.

Isolation and characterization of genetic variability in bacteria with ß-hemolytic and antifungal activity isolated from the rhizosphere of Medicago truncatula plants.

In the present study, we analyzed the frequency of hemolytic and antifungal activities in bacterial isolates from the rhizosphere of Medicago truncatula plants. Of the 2000 bacterial colonies, 96 showed ß-hemolytic activities (frequency, 4.8 x 10(-2)). Hemolytic isolates were analyzed for their genetic diversity by using random amplification of polymorphic DNA, yielding 88 haplotypes. The similarity coefficient of Nei and Li showed a polymorphic diversity ranging from 0.3 to 1. Additionally, 8 of the hemolytic isolates showed antifungal activity toward plant pathogens, Diaporthe phaseolorum, Colletotrichum acutatum, Rhizoctonia solani, and Fusarium oxysporum. The 16S ribosomal sequencing analysis showed that antagonistic bacterial isolates corresponded to Bacillus subtilis (UM15, UM33, UM42, UM49, UM52, and UM91), Bacillus pumilus (UM24), and Bacillus licheniformis (UM88). The present results revealed a higher genetic diversity among hemolytic isolates compared to that of isolates with antifungal action.

Polymorphisms in histone deacetylases improve the predictive value of IL-28B for chronic hepatitis C therapy.

Histone deacetylases (HDACs) influence many cellular processes, including the modulation of signal transducer and activator of transcription activity (STAT) in response to interferon (IFN). To identify genetic markers that help optimize the IL-28B prediction of chronic hepatitis C (CHC) sustained virological response (SVR), we evaluated 27 single-nucleotide polymorphisms (SNPs) in HDAC1-11. Three SNPs, rs3778216, rs976552 and rs368328 in HDAC2, HDAC3 and HDAC5, respectively, were independently associated with SVR (P<0.05). The addition of these three HDAC's SNPs to the IL-28B predictive model (area under the curve (AUC)=0.630) rendered an important improvement of AUC-receiver operating characteristic value (AUC=0.747, P=0.021). Chi-squared Automatic Interaction Detector (CHAID) analysis denoted the significance of the rs3778216 C/C genotype in identifying a group of good responders despite carrying IL-28B T allele (79.2% of SVR), whereas HDAC5 G allele characterized a subgroup with poor response rate (25.5%). However, HDAC3 rs976552 did not display a relevant role for the hierarchical classification of patients. Variables related to SVR in hepatitis C virus genotype 1 (HCV-1) cohort were the same of those obtained for the overall population. Interestingly, in non-HCV-1 patients (n=56) the HDAC2 C/C genotype was the unique predictive variable related to SVR (AUC=0.733, P<0.007). Thus, these preliminary results suggest the potential usefulness of combined IL-28B and HDAC genotyping for the CHC patients' classification by likelihood of an SVR.

Screen printed flexible radiofrequency identification tag for oxygen monitoring.

In this work, a radiofrequency identification (RFID) tag with an optical indicator for the measurement of gaseous oxygen is described. It consists of an O2 sensing membrane of PtOEP together with a full electronic system for RFID communication, all printed on a flexible substrate. The membrane is excited by an LED at 385 nm wavelength and the intensity of the luminescence generated is registered by means of a digital color detector. The output data corresponding to the red coordinate of the RGB color space is directly related to the concentration of O2, and it is sent to a microcontroller. The RFID tag is designed and implemented by screen printing on a flexible substrate for the wireless transmission of the measurement to a remote reader. It can operate in both active and passive mode, obtaining the power supply from the electromagnetic waves of the RFID reader or from a small battery, respectively. This system has been fully characterized and calibrated including temperature drifts, showing a high-resolution performance that allows measurement of very low values of oxygen content. Therefore this system is perfectly suitable for its use in modified atmosphere packaging where the oxygen concentration is reduced below 2%. As the reading of the O2 concentration inside the envelope is carried out with an external RFID reader using wireless communication, there is no need for perforations for probes or wires, so the packaging remains completely closed. With the presented device, a limit of detection of 40 ppm and a resolution as low as 0.1 ppm of O2 can be reached with a low power consumption of 3.55 mA.

Associations between Macronutrients Intake and Bone Mineral Density: A Longitudinal Analysis of the Health Workers Cohort Study Participants.

OBJECTIVE: This study aimed to evaluate the association between macronutrient intake and bone mineral density (BMD) using non-substitution and substitution statistical approaches. DESIGN: Longitudinal analysis. SETTINGS AND PARTICIPANTS: 1,317 adults in the Health Worker Cohort Study in Mexico. MEASUREMENTS: These participants were assessed at baseline (2004-2006) and follow-up (2010-2012). Dietary intakes were assessed using validated food frequency questionnaires. BMD at the different sites was performed by dual-energy X-ray absorptiometry (DXA). Hybrid-mixed effects regression models were performed to evaluate the associations of interest. RESULTS: Cross-sectional associations were found between fiber intake and higher total hip and femoral neck BMD in women and longitudinal associations with loss of femoral neck BMD in men. An increase in 5% energy intake from carbohydrate was associated with a BMD loss at several site in women and total hip and femoral neck in men. In both sexes, an increase in 5% energy intake of animal protein or fat was associated with a site-specific BMD gain after six years. Substitution analysis showed that the energy intake replacement from fat or carbohydrate by protein had an increase in BMD at different sites in women; while in men, it was only significant when replacing carbohydrate. Substitution of protein or fat by carbohydrates was associated with lower BMD in women, and only protein replacement by carbohydrates in men. CONCLUSION: Our findings suggest that carbohydrate intake was associated with loss of BMD, while animal protein and fat intake was associated with gain of BMD among the Mexican population. Macronutrient substitutions resulted in significant associations; however, additional studies are needed to confirm these findings.

Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18.

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.

Phylogenetic analysis reveals gene conversions in multigene families of rhizobia.

Gene families are an important and intrinsic trait of rhizobial species. These gene copies can participate in non-reciprocal recombination events, also called gene conversions. Gene conversion has diverse roles, but it is usually implicated in the evolution of multigene families. Here, we searched for gene conversions in multigene families of six representative rhizobial genomes. We identified 11 gene families with different numbers of copies, genome location and function in CFN42 and CIAT652 strains of Rhizobium etli, Rhizobium sp NGR234, Mesorhizobium loti MAFF303099, Sinorhizobium meliloti 1021, and Bradyrhizobium japonicum USDA110. Gene conversions were detected by phylogenetic inference in the nifD and nifK gene families in R. etli. Sequence analysis confirmed multiple gene conversions in these two gene families. We suggest that gene conversion events have an important role in homogenizing multigene families in rhizobia.

Willingness to pay for an intervention that reduces soda consumption among a sample of middle-class adult Mexicans.

BACKGROUND: Despite the growing public awareness of the adverse health effects of sugar-sweetened beverages (SSB) consumption in Mexico, little is known about the population's intention to reduce SSB consumption and the social value of interventions to accomplish such behavioral change. Therefore, the objective of this study was to assess the willingness to pay (WTP) for an intervention that reduces soda consumption by half in Mexico. METHODS: We applied contingent valuation methods in a sample of 471 Mexican adults from a cohort study. We assessed the relative value of benefits by providing incremental information to participants in three scenarios: soda consumption reduction, + health benefits, + social benefits. To estimate factors associated with the WTP, we ran an interval regression. RESULTS: 87% of respondents reported they would like to reduce SSB consumption. High soda consumption, intention to reduce soda consumption and higher household income are associated with higher WTP. We found that the WTP increases as additional benefits are provided. The WTP, as a proportion of income, is higher for the lowest income level. CONCLUSION: The average WTP per person may be seen as the minimum amount the country should invest on interventions to reduce soda consumption.

Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women.

BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. METHODS: Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. INTERPRETATION: The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. FUNDING: GlaxoSmithKline Biologicals.

Effects of seasonal changes in feeding management under part-time grazing on the evolution of the composition and coagulation properties of raw milk from ewes.

Ewe raw milk composition, rennet coagulation parameters, and curd texture were monitored throughout the milk production season in 11 commercial flocks reared under a part-time grazing system. Milking season lasted from February to July. During that period, the diet of the animals shifted from indoor feeding, consisting of concentrate and forage, to an outdoor grazing diet. Lean dry matter, fat, protein, calcium, and magnesium contents increased throughout the milking season, as did rennet coagulation time, curd firmness, and curd resistance to compression. However, lean dry matter, protein content, and curd resistance to compression stabilized when sheep started to graze. Principal component analysis correlated curd resistance to compression and proteins, whereas curd firmness was highly correlated with fat content and minerals. Discriminant analysis distributed milk samples according to the feeding management. Curd firmness, fat, and magnesium turned out to be discriminant variables. Those variables reflected the evolution of the composition and coagulation parameters when fresh pasture prevailed over other feeds in the diet of the flocks. The present study shows that seasonal changes associated with feeding management influence milk technological quality and that milk of good processing quality can be obtained under part-time grazing.

Zinc Supplementation and Fortification in Mexican Children.

BACKGROUND: Zinc is an essential micronutrient for human health. Approximately 1.4% of deaths worldwide are related to zinc deficiency. In Mexico, 33% of children younger than 5 years are zinc deficient. OBJECTIVE: To give an overview of zinc supplementation and fortification in children younger than 5 years through the analysis of current regulations in Mexico, the availability of these products, and the opinion of Mexican experts in this field. METHODS: We gave an overview of zinc supplementation and fortification strategies in the Mexican pediatric population by conducting a literature review of Mexican studies and national standards concerning zinc supplementation and fortification. Semistructured interviews were conducted with personnel from the main producers of zinc supplements and fortified products and from social assistance programs in Mexico. RESULTS: Zinc supplementation in Mexico has been associated with reduction in the duration and incidence of diarrhea. Through interviews with experts, we identified several barriers in achieving adequate zinc consumption such as problems in social assistance programs that distribute zinc-fortified foods, lack of specific dietary recommendations regarding the intake of zinc, lack of regulation of nonpatented zinc supplements, and inconsistencies in public health actions due to political and administrative changes. CONCLUSION: Despite current regulation and efforts made by social assistance programs, zinc deficiency continues to be a prevalent public health issue. Mexico requires an in-depth analysis of existing barriers and alternatives in order to reduce zinc deficiency.

Mutations in E2-PePHD, NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 of hepatitis C virus genotype 1 and their relationships to pegylated interferon-ribavirin treatment responses.

Mutations in several subgenomic regions of hepatitis C virus (HCV) have been implicated in influencing the response to interferon (IFN) therapy. Sequences within HCV NS5A (PKR binding domain [PKRBD], IFN sensitivity-determining region [ISDR], and variable region 3 [V3]) were analyzed for the pretreatment serum samples of 60 HCV genotype 1-infected patients treated with pegylated IFN plus ribavirin (1b, n = 47; 1a, n = 13) but with different treatment outcomes, those with sustained virologic responses (SVR; n = 36) or nonresponders (NR; n = 24). Additionally, the sequence of the PKR/eIF-2alpha phosphorylation homology domain (E2-PePHD) region was determined for 23 patients (11 SVR and 12 NR). The presence of > 4 mutations in the PKRBD region was associated with SVR (P = 0.001) and early virologic responses (EVR; 12 weeks) (P = 0.037) but not rapid virologic responses (4 weeks). In the ISDR, the difference was almost statistically significant (68% of SVR patients with mutations versus 45% without mutations; P = 0.07). The V3 region had a very high genetic variability, but this was not related to SVR. Finally, the E2-PePHD (n = 23) region was well conserved. The presence of > 4 mutations in the PKRBD region (odds ratio [OR] = 9.9; P = 0.006) and an age of < or = 40 years (OR = 3.2; P = 0.056) were selected in a multivariate analysis as predictive factors of SVR. NS5A sequences from serum samples taken after 1 month of treatment and posttreatment were examined for 3 SVR and 15 NR patients to select treatment-resistant viral subpopulations, and it was found that in the V3 and flanking regions, the mutations increased significantly in posttreatment sera (P = 0.05). The genetic variability in the PKRBD (> 4 mutations) is a predictive factor of SVR and EVR in HCV genotype 1 patients treated with pegylated IFN and ribavirin.