Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies

Background Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. Methods We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria. Results A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence. Conclusion In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility

Effect of dietary crude protein source on hormone and follicle characteristics in beef heifers

Ground, raw soybeans (SB), or dried distillers grain plus solubles (DDGS) were utilized in heifer development diets to determine the effect of dietary fat and protein source on hormone and follicle characteristics and ADG. The experiment was conducted over 2 yr with 100 June-born heifers (199 ± 2 kg initial BW, n = 50 per yr). The experimental periods were 157 and 207 d in yr 1 and 2, respectively. Heifers were provided a dietary supplement (DM basis) of 1.23 kg of SB and 0.40 kg of corn or 1.65 kg of DDGS between weaning and breeding. Estrus was synchronized with 2 injections of PGF2α 14 d apart. Dominant follicles were measured and aspirated via transvaginal ultrasonography 60 h after the second PGF2α injection. Heifers were exposed to bulls beginning 14 d after aspiration for 45 d. Heifer ADG was greater (P = 0.02) for DDGS heifers in yr 1, but was similar (P = 0.47) in yr 2. However, there was no difference (P = 0.35) in final BW in either year. There was no difference (P ≥ 0.67) in follicle size, follicle hormone concentrations, or pregnancy rate (88%) between yr 1 and 2. Serum estrogen at 48 or 60 h after PGF2α injection were similar (P ≥ 0.91); however, LH at 60 h in yr 2 tended to be greater (P = 0.07) for DDGS heifers. The percentage of heifers experiencing an LH surge 48 and 60 h after PGF2α injection was not affected (P ≥ 0.40) by treatment. Calf production was not affected (P ≥ 0.20) by developmental diet. In summary, DDGS and SB have similar effects on hormone and follicle characteristics at the inclusion rates used in these studies

Hybrid Fiber Layup and Fiber-Reinforced Polymeric Composites Produced Therefrom

Embodiments of a hybrid fiber layup used to form a fiber-reinforced polymeric composite, and a fiber-reinforced polymeric composite produced therefrom are disclosed. The hybrid fiber layup comprises one or more dry fiber strips and one or more prepreg fiber strips arranged side by side within each layer, wherein the prepreg fiber strips comprise fiber material impregnated with polymer resin and the dry fiber strips comprise fiber material without impregnated polymer resin

Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2α elicits increased intracellular reactive oxygen species and promotes receptormediated activation of PINK–Parkin mitophagy. These findings place the mitochondrium as a novel target in response to luteolytic mediator, PGF2α. Understanding intracellular processes occurring during early luteolysis may serve as a target for improving fertility

MRCK-1 Drives Apical Constriction in C. elegans by Linking Developmental Patterning to Force Generation

Apical constriction is a change in cell shape that drives key morphogenetic events including gastrulation and neural tube formation. Apical force-producing actomyosin networks drive apical constriction by contracting while connected to cell-cell junctions. The mechanisms by which developmental patterning regulates these actomyosin networks and associated junctions with spatial precision are not fully understood. Here, we identify a myosin light chain kinase MRCK-1 as a key regulator of C. elegans gastrulation that integrates spatial and developmental patterning information. We show that MRCK-1 is required for activation of contractile actomyosin dynamics and elevated cortical tension in the apical cell cortex of endodermal precursor cells. MRCK-1 is apically localized by active Cdc42 at the external, cell-cell contact-free surfaces of apically constricting cells, downstream of cell fate determination mechanisms. We establish that the junctional components α-catenin, β-catenin, and cadherin become highly enriched at the apical junctions of apically-constricting cells, and that MRCK-1 and myosin activity are required in vivo for this enrichment. Taken together, our results define mechanisms that position a myosin activator to a specific cell surface where it both locally increases cortical tension and locally enriches junctional components to facilitate apical constriction. These results reveal crucial links that can tie spatial information to local force generation to drive morphogenesis

Effects of 17β-Estradiol on Distribution of Pituitary Isoforms of Luteinizing Hormone and Follicle-Stimulating Hormone during the Follicular Phase of the Bovine Estrous Cycle

The objective of this study was to examine the influence of 17β-estradiol (E2) on distribution of LH and FSH isoforms during the follicular phase of the bovine estrous cycle prior to the preovulatory surges of LH and FSH. On Day 16 of the estrous cycle (Day 0 = estrus), intact controls (CONT; n = 4) were treated with prostaglandin F2α (PGF2α) to induce luteal regression and initiation of the follicular phase. Other cows were also treated with PGF2α and either ovariectomized (OVX; n = 5) or ovariectomized and given E2 implants (OVXE; n = 6) to mimic the pattern of increasing E2 concentrations during the follicular phase of the estrous cycle. Pituitaries were collected 40 h after treatment with PGF2α, or ovariectomy (0 h). Aliquots of pituitary extracts were chromatofocused on pH 10.5-4.0 gradients. The LH resolved into thirteen isoforms (designated A-L and S, beginning with the most basic form) while FSH resolved into nine isoforms (designated I-IX, beginning with the most basic form). The percentage of LH as isoform F (elution pH = 9.32 + 0.01) was greater (p \u3c 0.05) in the OVX group (48.5%) than in the OVXE group (45.0% ). LH isoforms I (elution pH = 6.98 ± 0.01) and J (elution pH = 6.48 ± 0.01) were more abundant (p \u3c 0.05) in cows from the OVXE (2.3 and 5.8%, respectively) than the OVX group (1.4 and 3.7%, respectively). Distribution of LH isoforms in cows from the three groups did not differ (p \u3e 0.10). Distribution of FSH isoforms were similar (p \u3e 0.05) among all groups. In summary, removal of the ovary (OVX) resulted in a slight increase in percentage of the basic LH isoform F, while removal of the ovary and administration of E2 (OVXE) in a pattern that mimicked increasing concentrations of E2 during the follicular phase of the estrous cycle resulted in a slight increase in the percentage of acidic LH isoforms (I and J). There was no influence of ovariectomy or treatment with E2 on distribution of FSH isoforms in the pituitary. Thus, gonadotropin heterogeneity does not appear to change significantly during the follicular phase of the bovine estrous cycle

Assessing the infection burden and associated risk factors in children under 5 across Jaipurs urban slums: A feasibility study using a One Health approach

Purpose: Infectious diseases are one of the leading causes of death among children under five (U5s) across both India & globally. This is worse in slum environments with poor access to water, sanitation & hygiene (WASH), good nutrition & a safe built environment. / Globally, a One Health (e.g. human, animal & environment) approach is increasingly advocated by WHO, FAO & OIE to reduce infections & antimicrobial resistance. As U5s living in peri-urban slums are exposed to household and community owned companion & livestock animals and pests, the CHIP Consortium hypothesized that utilizing a One Health approach to co-produce behavior change & slum upgrading interventions may reduce this burden where other WASH & nutrition interventions have failed. / This study aimed to assess the feasibility of utilising a One Health approach to assess U5 infection & risk factor prevalence in Jaipurs urban slums prior to undertaking prospective cohort studies involving culture and culture independent sampling of U5s and animals across our study sites in Jaipur, Jakarta & Antofagasta. / Methods: We administered a Rapid Household Survey to 25 purposely selected households across six slums. The questionnaire evaluated infection prevalence, health seeking behaviors, the built environment, presence of animals & pests, and individual to household-level demographics. Associations were calculated using correlations among continuous variables to show strength of significance between continuous variables. / Results: We found a high incidence of infections in children under five at 40%. This was most significantly correlated with accessibility of sanitary toilets (r = .62) and household expenditure. Vaccination coverage and child characteristics (such as size) were minimally correlated, while the presence of animals (pets or pests) was not correlated; the latter was likely due to the design of the survey. / Conclusion: This study found a higher infection prevalence than previous studies. We also found higher correlations with infection incidence among household-level characteristics, indicating that effective interventions need to address both the built and socio-economic environments. A pilot prospective cohort study, which includes researcher observations for the presence of animals to account for inconsistencies in the survey, is now underway

Developing GIS-based eastern equine encephalitis vector-host models in Tuskegee, Alabama

<p>Abstract</p> <p>Background</p> <p>A site near Tuskegee, Alabama was examined for vector-host activities of eastern equine encephalomyelitis virus (EEEV). Land cover maps of the study site were created in ArcInfo 9.2^®from QuickBird data encompassing visible and near-infrared (NIR) band information (0.45 to 0.72 μm) acquired July 15, 2008. Georeferenced mosquito and bird sampling sites, and their associated land cover attributes from the study site, were overlaid onto the satellite data. SAS 9.1.4^®was used to explore univariate statistics and to generate regression models using the field and remote-sampled mosquito and bird data. Regression models indicated that <it>Culex erracticus </it>and Northern Cardinals were the most abundant mosquito and bird species, respectively. Spatial linear prediction models were then generated in Geostatistical Analyst Extension of ArcGIS 9.2^®. Additionally, a model of the study site was generated, based on a Digital Elevation Model (DEM), using ArcScene extension of ArcGIS 9.2^®.</p> <p>Results</p> <p>For total mosquito count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 5.041 km, nugget of 6.325 km, lag size of 7.076 km, and range of 31.43 km, using 12 lags. For total adult <it>Cx. erracticus </it>count, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 5.764 km, nugget of 6.114 km, lag size of 7.472 km, and range of 32.62 km, using 12 lags. For the total bird count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 4.998 km, nugget of 5.413 km, lag size of 7.549 km and range of 35.27 km, using 12 lags. For the Northern Cardinal count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 6.387 km, nugget of 5.935 km, lag size of 8.549 km and a range of 41.38 km, using 12 lags. Results of the DEM analyses indicated a statistically significant inverse linear relationship between total sampled mosquito data and elevation (R²= -.4262; p < .0001), with a standard deviation (SD) of 10.46, and total sampled bird data and elevation (R²= -.5111; p < .0001), with a SD of 22.97. DEM statistics also indicated a significant inverse linear relationship between total sampled <it>Cx. erracticus </it>data and elevation (R²= -.4711; p < .0001), with a SD of 11.16, and the total sampled Northern Cardinal data and elevation (R²= -.5831; p < .0001), SD of 11.42.</p> <p>Conclusion</p> <p>These data demonstrate that GIS/remote sensing models and spatial statistics can capture space-varying functional relationships between field-sampled mosquito and bird parameters for determining risk for EEEV transmission.</p

Differential Regulation of Gonadotropin Synthesis and Release in Ovariectomized Ewes after Treatment with a Luteinizing Hormone-Releasing Hormone Antagonist

Our working hypothesis was that synthesis and release of LH, but not FSH, were solely dependent on LHRH. Twenty ovariectomized (OVX) ewes were randomly assigned to one of five treatments (n = 4 per group). Ewes were administered a low (10 μg/kg) or high (100 μg/kg) dose of LHRH antagonist (LHRH-Ant) at 24-h intervals for 3 or 6 days. Control ewes received vehicle (5% mannitol) at 24-h intervals for 6 days. Blood samples were collected every 15 min for 4 h before LHRH-Ant or vehicle and every 2 h during the period of treatment to determine concentrations of LH and FSH. Twenty-four hours after the last treatment with LHRH-Ant or vehicle, anterior pituitaries were collected and divided in half along the midsagittal plane; the number of receptors for LHRH, pituitary content of LH and FSH, and relative amounts of mRNA for α, LHβ, and FSHβ subunits were determined. Concentrations of LH in serum decreased (p \u3c 0.05) from 25.4 ± 4.3 ng/ml before LHRH-Ant to less than 0.5 ng/ml within 4 h after the first treatment of LHRH-Ant and remained low (\u3c 0.5 ng/ml) throughout the study. Serum concentrations of FSH declined gradually during the 3- or 6-day period of treatment with LHRH-Ant, from 37.3 ± 2.4 and 26.5 ± 4.8 ng/ml to 19.9 ± 1.8 and 13.7 ± 2.1 ng/ml, respectively. The magnitude of decline in serum concentrations of LH and FSH did not differ among ewes treated with low or high doses of LHRH-Ant. Pituitary content of LH was not different (p \u3e 0.10) from that in controls, whereas pituitary content of FSH was greater (p \u3c 0.01) in control ewes compared to ewes treated with LHRH-Ant. Receptors for LHRH were nondetectable (\u3c 0.018 x 10-16 mol receptor/μg protein) in pituitaries after 3 or 6 days of treatment with LHRH-Ant (low or high dose). Relative amounts of mRNA for α, LHβ, and FSHβ subunits were lower (p \u3c 0.01) after 6 days of treatment with LHRH-Ant (low or high dose) than after 3 days of treatment with LHRH-Ant (low or high dose). The LHRH was, therefore, required to maintain steady state amounts of mRNA for FSH and LH and to maintain pituitary stores of FSH but not LH. Our data support the hypothesis that differential regulation of LH and FSH release occurs in ewes. While synthesis and release of LH are dependent on LHRH, synthesis but not release of FSH appears to be dependent on LHRH

Comparison of Circulating Concentrations of Reproductive Hormones in Boars of Lines Selected for Size of Testes or Number of Ovulations and Embryonal Survival to Concentrations in Respective Control Lines

The objectives of this study were to determine whether circulating concentrations of gonadotropins and gonadal hormones of boars were altered as a result of selection of pigs for size of testes or for embryonal survival and(or) number of ovulations. Included in Exp. 1 and 2 were boars with the greatest estimated paired weight of testes (TS) and boars from a control (C) line. Concentrations of FSH were similar ( P \u3e .10) in boars from the TS and C lines. In Exp. 3, 4, and 5, circulating concentrations of FSH and 17β-estradiol (E2) were evaluated in neonates, during pubertal development, and in mature boars of lines selected for an index of number of ovulations and embryonal survival ( I ) , and data were compared to those for boars from a respective C line. Concentrations of E2 were not different in boars from the I line and those from the C line during the early neonatal period but were greater ( P \u3c .05) in boars of the C line than in those from the I line during pubertal development. Concentrations of FSH were greater ( P \u3c .05) in mature boars from the I line than in those from the C line. In summary, selection for size of testes did not influence circulating concentrations of FSH in mature boars. The secretory pattern of E2 in boars before puberty changed as a result of selection for embryonal survival and number of ovulations in females of the I line, and the different patterns of circulating E2 early in life may result in enhanced circulating concentrations of FSH in adult boars of the I line compared with boars of the C line