A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis.

Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania

Validation of age determination using otoliths of the European anchovy (Engraulis encrasicolus L.) in the Bay of Biscay

Validation of the age determination procedure using otoliths of European anchovy in the Bay of Biscay was achieved by monitoring very strong year-classes in successive spring catches and surveys, as well as the seasonal occurrence of edge types. Historical corroboration of the ageing method was obtained by cross-correlation between successive age groups by year-classes in catches and surveys (1987–2013). Summary annual growth in length is also presented. Yearly annuli consist of a hyaline zone (either single or composite) and a wide opaque zone, disrupted occasionally by some typical checks (mainly at age-0 and age-1 at peak spawning time). Age determination, given a date of capture, requires knowledge of the typical annual growth pattern of otoliths, their seasonal edge formation by ages and the most typical checks. Most opaque growth occurs in summer and is minimal (translucent) in winter. Opaque zone formation begins earlier in younger fish (in spring), and this helps distinguish age-1 from age-2þ.Versión del edito

Validation of age determination from Otoliths for Bay of Biscay anchovy

Comprehension of the annual pattern of annulus formation throughout the anchovy life span was first achieved from the observations of the strong 1982 year class which showed a neat annual progression of modal lengths passing through the fishery until the exceptional age of 5. Validation of the proposed method was subsequently obtained through monitoring of the progression of the strong 1987, 1989 and 1991 year-classes, both by spring annual surveys and by continuous sampling of the commercial catches, coupled to the monitoring of the seasonal marginal edge formation of the otoliths. Since then Age validation has been confirmed by the correlation between the pulses of recruitments (at age 1), as reflected in their relative occurrence in the population in Spring, and the abundance of those recruitments according to surveys. Typically, annual growth of anchovy otoliths of the one and two years old diminish to about 2/3-1/2 and 1/3 of that occurring in their previous ages respectively. Growth of older ages (three and four) are rather similar as, or slightly lesser than, at age 2. Maximum growth (white band formation) occurs in summer and growth detentions (with translucent annulus formation) in winter time. However the opaque edge formation begins sooner at the age of 1 (around February-March) than at older ages (May or June). During the first winter several translucent rings are occasionally formed resulting in a composite annulus formation. In addition during June/July, at peak spawning, a check is formed in many of the one year old anchovies. However, not all year classes, neither all anchovies lay down the same amount of checks and many of them may not show any. As such age determination requires the knowledge of the typical annual growth pattern of otoliths, of their seasonal edge formation by ages and of the most typical checks

Breastfeeding difficulties and risk for early breastfeeding cessation

Although breast milk is the normative feeding for infants, breastfeeding rates are lower than recommended. We investigated breastfeeding difficulties experienced by mothers in the first months after delivery and their association with early breastfeeding discontinuation. We conducted a prospective observational study. Mothers breastfeeding singleton healthy term newborns at hospital discharge were enrolled and, at three months post-delivery, were administered a questionnaire on their breastfeeding experience. Association among neonatal/maternal characteristics, breastfeeding difficulties and support after hospital discharge, and type of feeding at three months was assessed using multivariate binary logistic regression analysis. We enrolled 792 mothers, 552 completed the study. Around 70.3% of mothers experienced breastfeeding difficulties, reporting cracked nipples, perception of insufficient amount of milk, pain, and fatigue. Difficulties occurred mostly within the first month. Half of mothers with breastfeeding issues felt wellsupported by health professionals. Maternal perception of not having a sufficient amount of milk, infant\u2019s failure to thrive, mastitis, and the return to work were associated with a higher risk of nonexclusive breastfeeding at three months whereas vaginal delivery and breastfeeding support after hospital discharge were associated with a decreased risk. These results underline the importance of continued, tailored professional breastfeeding support

Predicting live birth, preterm and low birth weight infant after in-vitro fertilisation: a prospective study of 144018 treatment cycles

Background The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. Methods and Findings We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate &#60;0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia. Conclusions Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF

A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis

Background Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. Methods We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)–infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Results Micronutrients decreased the risk of TB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, −14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Conclusions Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania

MicroRNAs expression, chromosomal alterations and immunoglobulin variable Heavy chain hypermutations in Mantle Cell Lymphomas

The contribution of microRNAs (miR) to the pathogenesis of mantle cell lymphoma (MCL) is not well known.We investigated the expression of 86 mature miRs mapped to frequently altered genomic regions in MCL in CD5+/CD5 normal B cells, reactive lymph nodes, and purified tumor cells of 17 leukemic MCL, 12 nodal MCL, and 8MCL cell lines. Genomic alterations of the tumors were studied by single nucleotide polymorphism arrays and comparative genomic hybridization. Leukemic and nodal tumors showed a high number of differentially expressed miRs compared with purified normal B cells, but only some of them were commonly deregulated in both tumor types. An unsupervised analysis of miR expression profile in purified leukemic MCL cells revealed two clusters of tumors characterized by different mutational status of the immunoglobulin genes, proliferation signature, and number of genomic alterations. The expression of most miRs was not related to copy number changes in their respective chromosomal loci. Only the levels of miRs included in the miR-17-92 cluster were significantly related to genetic alterations at 13q31. Moreover, overexpression of miR-17-5p/miR-20a from this cluster was associated with high MYC mRNA levels in tumors with a more aggressive behavior. In conclusion, the miR expression pattern of MCL is deregulated in comparison with normal lymphoid cells and distinguishes two subgroups of tumors with different biological features.Postprint (updated version

Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences

Background: Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods: Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings: Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance: Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood