The effect of dietary omega-3 and -6 polyunsaturated fatty acids on ovine ovarian function and the pre-implantation embryo

There is considerable interest in the beneficial role of dietary polyunsaturated fatty acids (PUFA) on reproduction in ruminants. Detailed information regarding the mechanisms behind this beneficial effect is limited. The main objective of this thesis was to test the effects of dietary supplementation with omega-3 (n-3) or -6 (n-6) PUFA on gene expression, fatty acid (FA) composition and steroidogenesis in granulosa and theca cells and pre-implantation embryo development. A previous study in our laboratory reported increased follicular-fluid progesterone concentrations in ewes fed an n-3 compared to an n-6 PUFA-enriched diet, but detected no differential effect of n-3 and n-6 PUFA enriched high-density lipoproteins (HDL) on granulosa cell steroidogenesis in vitro. Also, n-6 PUFA enriched HDL reduced early embryo development, but in the absence of a net uptake of FA. In view of these observations it was hypothesised that (i) effects of n-3 PUFA on ovarian steroidogenesis are mediated by theca rather than granulosa cells and (ii) during embryo culture lipids are acquired solely from the albumin fraction of serum, so that albumin delivered n- 3 and n-6 PUFA would exert a greater differential effect on embryo development than either LDL or HDL delivered PUFA. Initial investigations into granulosa cell gene expression profiles using an ovine gonad-targeted cDNA macroarray were unsuccessful, highlighted by subsequent qRTPCR analysis. A thorough investigation confirmed that inconsistencies were due to poor array hybridisation. In vitro data confirmed that n-3 PUFA, via delivery by HDL, increase progesterone production solely in theca cells and that this is associated with an increase in STAR transcript expression. We also demonstrate that albumin is the only serum fraction that leads to a net uptake of FA during embryo culture. PUFA enriched serum and albumin accelerated the development of embryos and increased the yield of morphologically poorer quality blastocysts with increased transcript expression for the antioxidant enzyme SOD1. Important differential effects of n-3 and n-6 PUFA on ovarian steroidogenesis acting solely on theca cells are identified, but differentially effects of PUFA on embryo development are less apparent

The effect of dietary omega-3 and -6 polyunsaturated fatty acids on ovine ovarian function and the pre-implantation embryo

There is considerable interest in the beneficial role of dietary polyunsaturated fatty acids (PUFA) on reproduction in ruminants. Detailed information regarding the mechanisms behind this beneficial effect is limited. The main objective of this thesis was to test the effects of dietary supplementation with omega-3 (n-3) or -6 (n-6) PUFA on gene expression, fatty acid (FA) composition and steroidogenesis in granulosa and theca cells and pre-implantation embryo development. A previous study in our laboratory reported increased follicular-fluid progesterone concentrations in ewes fed an n-3 compared to an n-6 PUFA-enriched diet, but detected no differential effect of n-3 and n-6 PUFA enriched high-density lipoproteins (HDL) on granulosa cell steroidogenesis in vitro. Also, n-6 PUFA enriched HDL reduced early embryo development, but in the absence of a net uptake of FA. In view of these observations it was hypothesised that (i) effects of n-3 PUFA on ovarian steroidogenesis are mediated by theca rather than granulosa cells and (ii) during embryo culture lipids are acquired solely from the albumin fraction of serum, so that albumin delivered n- 3 and n-6 PUFA would exert a greater differential effect on embryo development than either LDL or HDL delivered PUFA. Initial investigations into granulosa cell gene expression profiles using an ovine gonad-targeted cDNA macroarray were unsuccessful, highlighted by subsequent qRTPCR analysis. A thorough investigation confirmed that inconsistencies were due to poor array hybridisation. In vitro data confirmed that n-3 PUFA, via delivery by HDL, increase progesterone production solely in theca cells and that this is associated with an increase in STAR transcript expression. We also demonstrate that albumin is the only serum fraction that leads to a net uptake of FA during embryo culture. PUFA enriched serum and albumin accelerated the development of embryos and increased the yield of morphologically poorer quality blastocysts with increased transcript expression for the antioxidant enzyme SOD1. Important differential effects of n-3 and n-6 PUFA on ovarian steroidogenesis acting solely on theca cells are identified, but differentially effects of PUFA on embryo development are less apparent

O debate em torno da eficácia dos programas de transferência de renda no Brasil (1995-2009) para a redução da desigualdade de renda e pobreza

Observa o debate em torno das políticas de transferência de renda focalizadas no Brasil no período 1995-2009. Apresenta o contexto histórico e teórico da economia mundial na década anterior a este período, bem como um acompanhamento das principais políticas de transferência de renda no Brasil a partir de então e, por fim, faz uma reflexão sobre opiniões de alguns economistas e cientistas sociais sobre o tema para chegar a conclusão de que há divergências em alguns pressupostos. A conclusão do trabalho aponta a necessidade da implementação de tais programas ao mesmo tempo em que se faz necessária uma melhora nas políticas referentes principalmente ao emprego e ao consumo dos mais pobres a fim de que se possa prevenir e diminuir o número de pessoas em situação de vulnerabilidade

Are interventions to reduce the impact of arsenic contamination of groundwater on human health in developing countries effective? A systematic review

BackgroundWithin developing countries, groundwater provides an alternative drinking source to polluted surface water. However, the presence of arsenic in some groundwater sources has resulted in chronic worldwide poisoning. The aim of this review was to determine the effectiveness of field-based technologies for the removal of arsenic from groundwater in developing countries.MethodsA structured search strategy was conducted in a range of databases. Titles, abstracts and full texts were screened using pre-defined inclusion criteria. Included studies were quality appraised prior to data extraction. The primary outcome was the percentage of effluent water samples meeting WHO guidelines for arsenic concentrations (≤0.01 mg/L). Secondary outcomes included: (a) arsenic concentrations in effluent water samples meeting the national guideline limit (≤0.05 mg/L), (b) arsenic concentrations in human tissue, and (c) knowledge and attitudes related to the interventions.ResultsFifty-one reports, evaluating 50 different technologies, were included. Sixty-seven percent (n = 34) of studies were conducted in Bangladesh. Fifty of the included reports were appraised as ‘weak’, with one ‘strong’ report of a randomised-controlled trial.In summary, the effectiveness of the oxidation and filtration interventions is poor, while the evidence for coagulation, co-precipitation and filtration, subterranean and membrane and electrolytic methods is mixed. Evidence regarding adsorption and zero valent iron interventions is more persuasive with most results suggesting good evidence of effectiveness (i.e. ≥95% of samples with arsenic concentrations ≤0.01 mg/L). In particular, activated alumina and sono/three-kolshi/gagri/pitcher filters have ≥95% of samples meeting national guidelines. Disappointingly, only one study reports excellent evidence of effectiveness: BRAC (2000) for activated alumina (i.e. ≥95% of samples with arsenic concentrations ≤0.01 mg/L).The success of each technology was highly dependent on context, especially their acceptability to users, a sense of ownership and expectations of women’s roles in society.ConclusionsMost studies were poorly conducted and reported. Consequently, although some technologies met national guidelines, the evidence-base for decision-making regarding arsenic mitigation technologies at household- and community-level is weak. To improve this situation, primary research needs to be commissioned with adequate sample sizes, testing the impact of key contextual factors, using valid tools for analysis, and meeting standards for completeness of reporting

Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local protection in the colon from primary C. difficile infection (CDI). Alternatively, by immunising orally, the ileum (main immune inductive site) can be directly targeted to confer protection in the large intestine. The gut commensal, non-toxigenic C. difficile (NTCD) was previously tested in animal models as an oral vaccine for natural delivery of an engineered toxin chimera to the small intestine and successfully induced toxin-neutralising antibodies. We investigated whether NTCD could be further exploited to induce antibodies that block the adherence of C. difficile to epithelial cells to target the first stage of pathogenesis. In NTCD strain T7, the colonisation factor, CD0873, and a domain of TcdB were overexpressed. Following oral immunisation of hamsters with spores of recombinant strain, T7-0873 or T7-TcdB, intestinal and systemic responses were investigated. Vaccination with T7-0873 successfully induced intestinal antibodies that significantly reduced adhesion of toxigenic C. difficile to Caco-2 cells, and these responses were mirrored in sera. Additional engineering of NTCD is now warranted to further develop this vaccine

Sexual and gender minority health in Chile: findings from the 2016–2017 Health Survey

OBJECTIVE: To expose visibility of the health concerns of sexual and gender minority groups in Chile, as well as to provide a platform to advocate for policies that support the health and well-being of SGM people in the country. METHODS: The health conditions and risk factors of participants identified as sexual and gender minority were compared to those identified as cisgender heterosexual using data from the 2016-2017 National Health Survey. RESULTS: Despite reporting higher self-rated health than heterosexual men, gay men had a higher risk of lifetime diagnosis of sexually transmitted infections. Compared to heterosexual women, the prevalence of depression was higher among bisexual women, who were also less likely to have been tested for HIV. Moreover, transgender participants were more likely to report depression and worse self-rated health than cisgender heterosexual participants. CONCLUSION: Small sample sizes of sexual and gender minority subgroups might have obscured some differences that would have been observable in larger samples. Despite this, we found statistically significant sexual and/or gender identity differences in several health areas, especially mental, sexual, and overall health

Field dimension and skill level constrain team tactical behaviours in small-sided and conditioned games in football

This study analysed the influence of field dimension and players’ skill level on collective tactical behaviours during small-sided and conditioned games (SSCGs). Positioning and displacement data were collected using global positioning systems (15 Hz) during SSCGs (Gk+4 v. 4+Gk) played by two groups of participants (NLP- national-level and RLP-regional-level players) on different field dimensions (small: 36.8 × 23.8 m; intermediate: 47.3 × 30.6 and large: 57.8 × 37.4 m). Team tactical performance was assessed through established dynamic team variables (effective playing space, playing length per width ratio and team separateness) and nonlinear signal processing techniques (sample entropy of distances to nearest opponents and the teams’ centroids’ mutual information). Results showed that the effective playing space and team separateness increased significantly with pitch size regardless of participant skill level (P < 0.001, η2 = 0.78 and P < 0.001, η2 = 0.65, respectively). Playing length per width ratio increased with pitch size for the NLP but was maintained at a relatively constant level by RLP across treatments indicating different playing shapes. There was significantly more irregularity in distances to nearest opponents for the NLP in small (P = 0.003) and intermediate fields (P = 0.01). Findings suggest that tactical behaviours in SSCGs are constrained by field size and skill level, which need to be considered by coaches when designing training practices

Prospects for High-Elevation Radio Detection of >100 PeV Tau Neutrinos

Tau neutrinos are expected to comprise roughly one third of both the astrophysical and cosmogenic neutrino flux, but currently the flavor ratio is poorly constrained and the expected flux at energies above $10^{17}$ eV is low. We present a detector concept aimed at measuring the diffuse flux of tau neutrinos in this energy range via a high-elevation mountaintop detector using the radio technique. The detector searches for radio signals from upgoing air showers generated by Earth-skimming tau neutrinos. Signals from several antennas in a compact array are coherently summed at the trigger level, permitting not only directional masking of anthropogenic backgrounds, but also a low trigger threshold. This design takes advantage of both the large viewing area available at high-elevation sites and the nearly full duty cycle available to radio instruments. We present trade studies that consider the station elevation, frequency band, number of antennas in the array, and the trigger threshold to develop a highly efficient station design. Such a mountaintop detector can achieve a factor of ten improvement in acceptance over existing instruments with 100 independent stations. With 1000 stations and three years of observation, it can achieve a sensitivity to an integrated $\mathcal{E}^{-2}$ flux of $<10^{-9}$ GeV cm$^{-2}$ sr$^{-1}$ s$^{-1}$, in the range of the expected flux of all-flavor cosmogenic neutrinos assuming a pure iron cosmic-ray composition.Comment: 26 pages, 11 figure

Mimicking native display of cd0873 on liposomes augments its potency as an oral vaccine against clostridioides difficile

Mucosal vaccination aims to prevent infection mainly by inducing secretory IgA (sIgA) antibody, which neutralises pathogens and enterotoxins by blocking their attachment to epithelial cells. We previously demonstrated that encapsulated protein antigen CD0873 given orally to hamsters induces neutralising antibodies locally as well as systemically, affording partial protection against Clostridioides difficile infection. The aim of this study was to determine whether displaying CD0873 on liposomes, mimicking native presentation, would drive a stronger antibody response. The recombinant form we previously tested resembles the naturally cleaved lipoprotein commencing with a cysteine but lacking lipid modification. A synthetic lipid (DHPPA-Mal) was designed for conjugation of this protein via its N-terminal cysteine to the maleimide headgroup. DHPPA-Mal was first formulated with liposomes to produce MalLipo; then, CD0873 was conjugated to headgroups protruding from the outer envelope to generate CD0873-MalLipo. The immunogenicity of CD0873-MalLipo was compared to CD0873 in hamsters. Intestinal sIgA and CD0873-specific serum IgG were induced in all vaccinated animals; however, neutralising activity was greatest for the CD0873-MalLipo group. Our data hold great promise for development of a novel oral vaccine platform driving intestinal and systemic immune responses