A Circular Economy Approach to Integrate Divergent Ruminant Production Systems: Using Dairy Cow Feed Leftovers to Enhance the Out-of-Season Reproductive Performance in Goats.

Based on a circular economy approach, we evaluated the possible effect of targeted supplementation with leftover feed from dairy cows (i.e., intensive system) on the reproductive performance of crossbred/rangeland goats (i.e., extensive system) in arid Northern Mexico. During the deep-anestrous season (i.e., March-April, 25° North), multiparous goats (n = 38) with a similar body weight (BW) and body condition score (BCS) were randomly assigned to two groups: (1) supplemented group (SG; n = 19; BCS: 1.76 ± 0.07; BW: 43.7 ± 1.8 kg), receiving 400 g goat d-1 of dairy-cow-feed leftovers prior to grazing; and (2) non-supplemented group (NS; n = 19; BCS: 1.76 ± 0.06; BW: 44.3 ± 2.5 kg). Both groups were directed to the rangeland for a period of ≈8 h. While the experimental period lasted 36 d, the experimental breeding considered 11 d (d0-d10). The anovulatory status of goats was ultrasonographically confirmed on days -20, -10, and -1 prior to male-female interaction. Previously, bucks were separated for 3 weeks from the experimental females and received exogenous testosterone every third day (i.e., 50 mg i.m.) prior to mating. With respect to the response variables, namely BW, BCS, blood glucose levels (BGLs), estrus induction (GIE, %), latency to estrus (LTE, h), estrus duration (ED, h), and luteal tissue volume (LTV, mm), no differences (p > 0.05) occurred between experimental groups. However, the response variables, namely goats ovulating (GO, %; 78.9 vs. 47.3), total number of corpuses luteum (TNCL, n; 27 vs. 13), ovulation rate (OR, n; 1.42 vs. 0.73), multiple ovulation (MO, %; 73.3 vs. 55.5), and pregnancy rate on d 36 (PRd36, %, 68.4 vs. 36.8), favored (p < 0.05) the SG over the NS goats. Our results demonstrate that connecting the circularity of two divergent ruminant production systems (i.e., cow-intensive and goat-extensive) by using dairy cows' feed leftovers as a targeted supplementation strategy in anestrous goats under a marginal-rangeland production system enhanced out-of-season reproductive outcomes (i.e., ovulation rate and pregnancy rate), thus benefiting marginal goat producers and their families.

Targeted Glutamate Supply Boosts Insulin Concentrations, Ovarian Activity, and Ovulation Rate in Yearling Goats during the Anestrous Season.

The neuroendocrine regulation of the seasonal reproductive axis requires the integration of internal and external signals to ensure synchronized physiological and behavioral responses. Seasonal reproductive changes contribute to intermittent production, which poses challenges for optimizing goat product yields. Consequently, a significant objective in seasonal reproduction research is to attain continuous reproduction and enhance profitability in goat farming. Glutamate plays a crucial role as a modulator in several reproductive and metabolic processes. Hence, the aim of this study was to evaluate the potential impact of exogenous glutamate administration on serum insulin concentration and ovarian function during the out-of-season period in yearling goats. During the anestrous season, animals were randomly located in individual pens to form two experimental groups: (1) glutamate (n = 10, live weight (LW) = 29.1 ± 1.02 kg, body condition score (BCS) = 3.4 ± 0.2 units) and (2) control (n = 10; LW = 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2), with no differences (p < 0.05) regarding LW and BCS. Then, goats were estrus-synchronized, and blood sampling was carried out for insulin quantification. Ovaries were ultrasonographically scanned to assess ovulation rate (OR), number of antral follicles (AFs), and total ovarian activity (TOA = OR + AF). The research outcomes support our working hypothesis. Certainly, our study confirms that those yearling goats treated with exogenous glutamate displayed the largest (p < 0.05) insulin concentrations across time as well as an augmented (p < 0.05) out-of-season ovarian activity.

Targeting deoxycytidine kinase improves symptoms in mouse models of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease driven by lymphocyte activation against myelin autoantigens in the central nervous system leading to demyelination and neurodegeneration. The deoxyribonucleoside salvage pathway with the rate-limiting enzyme deoxycytidine kinase (dCK) captures extracellular deoxyribonucleosides for use in intracellular deoxyribonucleotide metabolism. Previous studies have shown that deoxyribonucleoside salvage activity is enriched in lymphocytes and required for early lymphocyte development. However, specific roles for the deoxyribonucleoside salvage pathway and dCK in autoimmune diseases such as MS are unknown. Here we demonstrate that dCK activity is necessary for the development of clinical symptoms in the MOG35-55 and MOG1-125 experimental autoimmune encephalomyelitis (EAE) mouse models of MS. During EAE disease, deoxyribonucleoside salvage activity is elevated in the spleen and lymph nodes. Targeting dCK with the small molecule dCK inhibitor TRE-515 limits disease severity when treatments are started at disease induction or when symptoms first appear. EAE mice treated with TRE-515 have significantly fewer infiltrating leukocytes in the spinal cord, and TRE-515 blocks activation-induced B and T cell proliferation and MOG35-55 -specific T cell expansion without affecting innate immune cells or naïve T and B cell populations. Our results demonstrate that targeting dCK limits symptoms in EAE mice and suggest that dCK activity is required for MOG35-55 -specific lymphocyte activation-induced proliferation.

Signaling Pathways That Drive 18F-FDG Accumulation in Cancer.

18F-FDG measures glucose consumption and is an integral part of cancer management. Most cancer types upregulate their glucose consumption, yielding elevated 18F-FDG PET accumulation in those cancer cells. The biochemical pathway through which 18F-FDG accumulates in cancer cells is well established. However, beyond well-known regulators such as c-Myc, PI3K/PKB, and HIF1α, the proteins and signaling pathways that cancer cells modulate to activate the facilitated glucose transporters and hexokinase enzymes that drive elevated 18F-FDG accumulation are less well understood. Understanding these signaling pathways could yield additional biologic insights from 18F-FDG PET scans and could suggest new uses of 18F-FDG PET in the management of cancer. Work over the past 5 years, building on studies from years prior, has identified new proteins and signaling pathways that drive glucose consumption in cancer. Here, we review these recent studies and discuss current limitations to our understanding of glucose consumption in cancer.

Modelling the antimicrobial pharmacodynamics for bacterial strains with versus without acquired resistance to fluoroquinolones or cephalosporins.

OBJECTIVES: Antimicrobial resistance threatens therapeutic options for human and animal bacterial diseases worldwide. Current antimicrobial treatment regimens were designed against bacterial strains that were fully susceptible to them. To expand the useable lifetime of existing antimicrobial drug classes by modifying treatment regimens, data are needed on the antimicrobial pharmacodynamics (PD) against strains with reduced susceptibility. In this study, we generated and mathematically modelled the PD of the fluoroquinolone ciprofloxacin and the cephalosporin ceftriaxone against non-typhoidal Salmonella enterica subsp. enterica strains with varying levels of acquired resistance. METHODS: We included Salmonella strains across categories of reduced susceptibility to fluoroquinolones or cephalosporins reported to date, including isolates from human infections, food-animal products sold in retail, and food-animal production. We generated PD data for each drug and strain via time-kill assay. Mathematical models were compared in their fit to represent the PD. The best-fit model's parameter values across the strain susceptibility categories were compared. RESULTS: The inhibitory baseline sigmoid Imax (or Emax) model was best fit for the PD of each antimicrobial against a majority of the strains. There were statistically significant differences in the PD parameter values across the strain susceptibility categories for each antimicrobial. CONCLUSION: The results demonstrate predictable multiparameter changes in the PD of these first-line antimicrobials depending on the Salmonella strain's susceptibility phenotype and specific genes conferring reduced susceptibility. The generated PD parameter estimates could be used to optimise treatment regimens against infections by strains with reduced susceptibility.

Faecal concentrations of ceftiofur metabolites in finisher pigs administered intramuscularly with ceftiofur.

The objective of this study was to determine the effects of dietary fibre level and source on faecal ceftiofur metabolites concentrations after intramuscular administration of therapeutic ceftiofur hydrochloride in finisher pigs. Pens of finisher pigs (n = 36), with an equal number of barrows and gilts, were randomly assigned to 1 of 3 dietary treatment groups: basal diet composed of corn grain and soy bean meal with no supplement and formulated to contain 8.7% neutral detergent fibre (NDF), supplemented with 20% distillers dried grains with solubles (a byproduct of the ethanol production from corn grain) formulated to contain 13.6% NDF, primarily insoluble fibre or supplemented with 14.5% sugar beet pulp formulated to contain 13.6% NDF. Faecal samples were collected 6-8 hr after ceftiofur injection from treated and untreated pen-mate pigs on days 1 and 3 of the 3-day treatment regimen. Faecal concentrations of ceftiofur metabolites, including the major metabolite, desfuroylceftiofur, were analysed by reverse-phase high pressure liquid chromatography with ultraviolet detection. Overall, the faecal concentrations of ceftiofur metabolites did not differ significantly between the dietary treatments. The mean concentrations of metabolites tended to be lower (p = .1) on day 3 compared to day 1 of the 3-day treatment regimen. Faecal concentrations of metabolites were not affected by the gender of the finisher pigs. The concentrations of ceftiofur metabolites in the faeces are likely reflective of the microbial activity in the hindgut. Our data suggest that the fibre level and source used in the study did not affect the faecal concentrations of ceftiofur metabolites.

Mathematical modeling of the 'inoculum effect': six applicable models and the MIC advancement point concept.

Antimicrobial treatment regimens against bacterial pathogens are designed using the drug's minimum inhibitory concentration (MIC) measured at a bacterial density of 5.7 log10(colony-forming units (CFU)/mL) in vitro. However, MIC changes with pathogen density, which varies among infectious diseases and during treatment. Incorporating this into treatment design requires realistic mathematical models of the relationships. We compared the MIC-density relationships for Gram-negative Escherichia coli and non-typhoidal Salmonella enterica subsp. enterica and Gram-positive Staphylococcus aureus and Streptococcus pneumonia (for n = 4 drug-susceptible strains per (sub)species and 1-8 log10(CFU/mL) densities), for antimicrobial classes with bactericidal activity against the (sub)species: ß-lactams (ceftriaxone and oxacillin), fluoroquinolones (ciprofloxacin), aminoglycosides (gentamicin), glycopeptides (vancomycin) and oxazolidinones (linezolid). Fitting six candidate mathematical models to the log2(MIC) vs. log10(CFU/mL) curves did not identify one model best capturing the relationships across the pathogen-antimicrobial combinations. Gompertz and logistic models (rather than a previously proposed Michaelis-Menten model) fitted best most often. Importantly, the bacterial density after which the MIC sharply increases (an MIC advancement-point density) and that density's intra-(sub)species range evidently depended on the antimicrobial mechanism of action. Capturing these dependencies for the disease-pathogen-antimicrobial combination could help determine the MICs for which bacterial densities are most informative for treatment regimen design.

Formación de posgrados en Enfermería, una necesidad para Santo Domingo de los Tsáchilas / Post-graduate Education in Nursing, a necessity for Santo Domingo de los Tsáchilas

RESUMEN Fundamento: la formación continua de los profesionales de enfermería es un mecanismo esencial en la superación personal y su desempeño laboral ya que por medio de la actualización de conocimientos podrán llevar adelante su gran responsabilidad con la sociedad al garantizar la calidad de atención en salud a los usuarios. Objetivo: determinar la necesidad de formación de posgrado en la profesión de enfermería. Métodos: se realizó un estudio transversal de enfoque cuantitativo, en los profesionales de enfermería que laboran en las distintas unidades de salud pública y del seguro social, de Santo Domingo de los Tsáchilas desde junio hasta agosto de 2018. El universo de estudio fue de 540 profesionales de enfermería, en los que se aplicó criterios de inclusión y exclusión, la muestra quedó conformada por 418. Resultados: de los profesionales que participaron en el estudio la mayoría trabaja en el segundo nivel de atención en salud, los mismos requieren posgrados ya sea en maestrías o especializaciones, se interesan por el área cuidados críticos y prefieren la modalidad de estudio semipresencial. Conclusiones: se constata la necesidad de formación de posgrado en la profesión de enfermería, misma que aportará a la actualización, profundización, perfeccionamiento de las actividades de los profesionales que influyen en la atención de enfermería y al desarrollo de competencias laborales que cada vez es más exigente.

ABSTRACT Background: continuing education of nursing professionals is an important tool for personal achievement and work performance. Updating one's professional knowledge is essential in order fulfill the social responsibility of offering quality healthcare for patients. Objective: to determine the need for post graduate education in the nursing profession. Methods: a quantitative, cross sectional study was done among nursing professionals working in different areas of public health and social security in the province of Santo Domingo de los Tsáchilas from June to August 2018. The universe of study was 540 nursing professionals in which inclusion and exclusion criteria were applied, with the sample consisting of 418. Results: majority of the professionals who participated in the study work at the second level of health care, these professionals need post-graduate study, which can be a master's degree or a specialization program. Specifically, there is preference for studying critical care and blended learning is the modality of choice by the participants of the study. Conclusions: there is a need for post-graduate studies in the nursing profession. Continuing education will upgrade, broaden and improve the performance of professionals. In addition, it will enhance the quality of nursing care and work competencies of professionals.

Unidad Nefrológica de Atención Continuada. Experiencia de un Hospital Universitario / Nephrological Unit for Continued Care. Experience of a University Hospital

Introducción: Los hospitales de día suponen una alternativa asistencial a la hospitalización convencional mejorando la eficacia de la asistencia sanitaria. Desde nuestro punto de vista, la nefrología se beneficiaria de esta modalidad de atención, ya que el paciente con enfermedad renal crónica tiene unas necesidades concretas de cuidado que conllevan al profesional de enfermería a generar una atención integral e individualizada. Por este motivo surge en nuestro servicio la creación de la Unidad Nefrológica de Atención Continuada. Objetivo: Presentar nuestra experiencia en la implantación y desarrollo de la Unidad Nefrológica de Atención Continuada en el Hospital Universitario del Henares. Material y Método: Estudio descriptivo retrospectivo de la actividad realizada en la Unidad Nefrológica de Atención Continuada entre enero-junio de 2017. Desarrollo y puesta en marcha de las distintas funciones y competencias profesionales. Resultados: En este periodo se asistieron a un total de 874 pacientes, con una media de 145,6 visitas/mes. De todas estas visitas, se atendieron 474 pacientes en programa de Diálisis Peritoneal (55% del volumen total), 149 pacientes con enfermedad renal crónica (16%), 245 pacientes con enfermedad renal crónica avanzada (18%) y 11 pacientes en tratamiento conservador (1%). Se realizaron diferentes técnicas, bien programadas en la agenda electrónica o a demanda. Conclusiones: La implantación de la Unidad Nefrológica de Atención Continuada, de forma estructurada y planificada, es una alternativa válida y necesaria en nuestro sistema sanitario. Permite aseguramos un abordaje integral de los pacientes renales y alcanzar una continuidad de cuidados con menor coste sanitario

Introduction: The daytime hospitals are an alternative to conventional hospitalization and improve the effectiveness of healthcare. From our point of view, nephrology is a specialty that should be able to benefit from this type of care, because chronic kidney disease (CKD) patients have specific care needs that lead to the nursing professional to generate comprehensive and individualized care. For this reason, the creation of the Nephrological Unit for Continued Care (NUCA) arises in our service. Aim: To present our experience in the implantation and development of a NUCA in the University Hospital of Henares. Material and Method: Retrospective descriptive study of the activity carried out at NUCA between January 1, 2017 and June 30, 2017. Development and implementation of different functions and professional competencies. Results: In this period, a total of 804 patients were attended, with an average of 145.6 visits per month. Of all these visits, 474 patients undergoing Peritoneal Dialysis (55% of total volume), 149 patients with CKD (16%), 245 patients with advanced CKD (18%) and 11 patients in conservative treatment (1%). Different techniques were carried out, either programmed by electronic agenda or by demand. Conclusions: The implantation of the NUCA, in a structured and planned way, is a valid and necessary alternative in our health system. It allows to ensure an integral approach to renal patients and achieve a continuity of care with lower healthcare costs

18F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis.

Immune cell-mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (18F-FDG and 18F-1-(2'-deoxy-2'-fluoro-arabinofuranosyl)cytosine [18F-FAC]) and hepatocyte biology (18F-2-deoxy-2-fluoroarabinose [18F-DFA]) can visualize and quantify liver-infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. Methods: Mice treated with concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with 18F-FDG, 18F-FAC, and 18F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis were imaged with 18F-FDG, 18F-FAC, and 18F-DFA PET. 18F-FAC PET was performed on mice treated with ConA and vehicle or with ConA and dexamethasone. Biopsy samples of patients with autoimmune hepatitis were immunostained for deoxycytidine kinase. Results: Hepatic accumulation of 18F-FDG and 18F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of 18F-DFA was 41% lower, in a mouse model of autoimmune hepatitis than in control mice. Increased hepatic 18F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic 18F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic 18F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic 18F-FDG accumulation by 109% and decreased hepatic 18F-DFA accumulation by 20% but had no effect on hepatic 18F-FAC accumulation (nonsignificant 2% decrease). 18F-FAC PET provided a noninvasive biomarker of the efficacy of dexamethasone for treating the autoimmune hepatitis model. Infiltrating leukocytes in liver biopsy samples from patients with autoimmune hepatitis express high levels of deoxycytidine kinase, a rate-limiting enzyme in the accumulation of 18F-FAC. Conclusion: Our data suggest that PET can be used to noninvasively visualize activated leukocytes and inflamed hepatocytes in a mouse model of autoimmune hepatitis.

Noninvasive Imaging of Drug-Induced Liver Injury with 18F-DFA PET.

Drug-induced liver failure is a significant indication for a liver transplant, and unexpected liver toxicity is a major reason that otherwise effective therapies are removed from the market. Various methods exist for monitoring liver injury but are often inadequate to predict liver failure. New diagnostic tools are needed. Methods: We evaluate in a preclinical model whether 18F-2-deoxy-2-fluoroarabinose (18F-DFA), a PET radiotracer that measures the ribose salvage pathway, can be used to monitor acetaminophen-induced liver injury and failure. Mice treated with vehicle, 100, 300, or 500 mg/kg acetaminophen for 7 or 21 h were imaged with 18F-FDG and 18F-DFA PET. Hepatic radiotracer accumulation was correlated to survival and percentage of nonnecrotic tissue in the liver. Mice treated with acetaminophen and vehicle or N-acetylcysteine were imaged with 18F-DFA PET. 18F-DFA accumulation was evaluated in human hepatocytes engrafted into the mouse liver. Results: We show that hepatic 18F-DFA accumulation is 49%-52% lower in mice treated with high-dose acetaminophen than in mice treated with low-dose acetaminophen or vehicle. Under these same conditions, hepatic 18F-FDG accumulation was unaffected. At 21 h after acetaminophen treatment, hepatic 18F-DFA accumulation can distinguish mice that will succumb to the liver injury from those that will survive it (6.2 vs. 9.7 signal to background, respectively). Hepatic 18F-DFA accumulation in this model provides a tomographic representation of hepatocyte density in the liver, with a R2 between hepatic 18F-DFA accumulation and percentage of nonnecrotic tissue of 0.70. PET imaging with 18F-DFA can be used to distinguish effective from ineffective resolution of acetaminophen-induced liver injury with N-acetylcysteine (15.6 vs. 6.2 signal to background, respectively). Human hepatocytes, in culture or engrafted into a mouse liver, have levels of ribose salvage activity similar to those of mouse hepatocytes. Conclusion: Our findings suggest that PET imaging with 18F-DFA can be used to visualize and quantify drug-induced acute liver injury and may provide information on the progression from liver injury to hepatic failure.

Impact and economic evaluations of a combination prevention programme for men who have sex with men in Mexico.

BACKGROUND: Despite the high-profile support for combination prevention programmes (CPPs) since 2008, there is little rigorous evidence on their impact and cost-effectiveness. In 2010, Mexico received funds from the Global Fund to implement a series of behavioural, biomedical, and structural interventions over 3 years targeted to men who have sex with men. The aims of the study were to estimate the impact of the programme across a range of outcomes and cost-effectiveness. METHODS: A quasi-experiment was designed before the implementation of the CPP, in which 24 cities were randomly selected for impact evaluation and 12 pairs of cities were matched. In practice, though, implementation of the programme was staggered over 1 year. Therefore, we used two different approaches to estimate impact: a difference-in-difference estimation comparing both groups and a dose-response approach using time exposure to the programme at the city level. FINDINGS: Results from the difference-in-difference estimation showed modest impact on condom use. However, the dose­response findings revealed a 7.5% increase in HIV testing per additional year exposed to the programme, relative to baseline coverage; an increase in awareness of HIV status among HIV-positive individuals of 6.3%; a 6.7% increase in HIV-positive individuals on treatment; and a 7% reduction in the perception of stigma/discrimination from healthcare personnel. The cost per person not exposed to an untreated HIV-positive individual was gauged to be US$400. CONCLUSIONS: The study provides evidence of the effectiveness and cost of a CPP along the HIV treatment cascade: access to HIV tests, awareness of HIV status, and antiretroviral therapy initiation.

Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation.

PURPOSE: To define clinical and pathologic predictors of local-regional recurrence (LRR) for patients treated with neoadjuvant chemotherapy and mastectomy without radiation. PATIENTS AND METHODS: We analyzed the outcome of the 150 breast cancer cases treated on prospective institutional trials with neoadjuvant chemotherapy and mastectomy without postmastectomy radiation. Clinical stage at diagnosis was I in 1%, II in 43%, IIIA in 23%, IIIB in 25%, and IV in 7%. No patient had inflammatory breast cancer. RESULTS: The median follow-up period of surviving patients was 4.1 years. The 5- and 10-year actuarial rates of LRR were both 27%. Pretreatment factors that positively correlated with LRR were increasing T stage (P <.0001) and increasing combined clinical stage (P <.0001). Pathologic and treatment factors that positively correlated with LRR were size of the residual primary tumor (P =.0048), increasing number of involved lymph nodes (P <.0001), and no use of tamoxifen (P =.0013). The LRR rate for the 18 patients with a pathologic complete response of both the primary tumor and lymph nodes (pCR) was 19% (95% confidence interval, 6% to 48%). In a forward stepwise Cox logistic regression analysis, clinical stage IIIB or greater (hazard ratio of 4.5, P <.001), pathologic involvement of four or more lymph nodes (hazard ratio of 2.7, P =.008), and no use of tamoxifen (hazard ratio of 3.9, P =.027) independently predicted for LRR. CONCLUSION: Advanced disease at presentation and positive lymph nodes after chemotherapy predict for clinically significant rates of LRR. Achievement of pCR does not preclude the need for postmastectomy radiation if warranted by the pretreatment stage of the disease.