Evaluation of Reproductive Histology Response of Adult Fasciola hepatica in Goats Vaccinated with Cathepsin L Phage-Exposed Mimotopes.

Fasciolosis, a globally re-emerging zoonotic disease, is mostly caused by the parasitic infection with Fasciola hepatica, often known as the liver fluke. This disease has a considerable impact on livestock productivity. This study aimed to evaluate the fluke burdens and faecal egg counts in goats that were administered phage clones of cathepsin L mimotopes and then infected with F. hepatica metacercariae. Additionally, the impact of vaccination on the histology of the reproductive system, specifically related to egg generation in adult parasites, was examined. A total of twenty-four goats, which were raised in sheds, were divided into four groups consisting of six animals each. These groups were randomly assigned. The goats were then subjected to two rounds of vaccination. Each vaccination involved the administration of 1 × 1013 phage particles containing specific mimotopes for cathepsin L2 (group 1: PPIRNGK), cathepsin L1 (group 2: DPWWLKQ), and cathepsin L1 (group 3: SGTFLFS). The immunisations were carried out on weeks 0 and 4, and the Quil A adjuvant was used in combination with the mimotopes. The control group was administered phosphate-buffered saline (PBS) (group 4). At week 6, all groups were orally infected with 200 metacercariae of F. hepatica. At week 22 following the initial immunisation, the subjects were euthanised, and adult F. hepatica specimens were retrieved from the bile ducts and liver tissue, and subsequently quantified. The specimens underwent whole-mount histology for the examination of the reproductive system, including the testis, ovary, vitellaria, Mehlis' gland, and uterus. The mean fluke burdens following the challenge were seen to decrease by 50.4%, 62.2%, and 75.3% (p < 0.05) in goats that received vaccinations containing cathepsin L2 PPIRNGK, cathepsin L1 DPWWLKQ, and cathepsin L1 SGTFLFS, respectively. Animals that received vaccination exhibited a significant reduction in the production of parasite eggs. The levels of IgG1 and IgG2 isotypes in vaccinated goats were significantly higher than in the control group, indicating that protection is associated with the induction of a mixed Th1/Th2 immune response. The administration of cathepsin L to goats exhibits a modest level of efficacy in inducing histological impairment in the reproductive organs of liver flukes, resulting in a reduction in egg output.

Latin-American guidelines of recommendations at discharge from an acute coronary syndrome.

The diagnostic criteria, treatments at the time of admission, and drugs used in patients with acute coronary syndrome are well defined in countless guidelines. However, there is uncertainty about the measures to recommend during patient discharge planning. This document brings together the most recent evidence and the standardized and optimal treatment for patients at the time of discharge from hospitalization for an acute coronary syndrome, for comprehensive and safe care in the patient's transition between care from the acute event to the outpatient care, with the aim of optimizing the recovery of viable myocardium, guaranteeing the most appropriate secondary prevention, reducing the risk of a new coronary event and mortality, as well as the adequate reintegration of patients into daily life.

Los criterios diagnósticos, los tratamientos en el momento de la admisión y los fármacos utilizados en pacientes con síndrome coronario agudo están bien definidos en innumerables guías. Sin embargo, existe incertidumbre acerca de las medidas para recomendar durante la planificación del egreso de los pacientes. Este documento reúne las evidencias más recientes y el tratamiento estandarizado y óptimo para los pacientes al momento del egreso de una hospitalización por un síndrome coronario agudo, para un cuidado integral y seguro en la transición del paciente entre la atención del evento agudo y el cuidado ambulatorio, con el objetivo de optimizar la recuperación de miocardio viable, garantizar la prevención secundaria más adecuada, reducir el riesgo de un nuevo evento coronario y la mortalidad, así como la adecuada reinserción de los pacientes en la vida cotidiana.

Safety of Plasma Rich in Growth Factors (PRGF) as additive to healthy human sperm samples: a pilot study.

OBJECTIVE: The aim of our study was to assess if the addition of PRGF to healthy human sperm affects its motility and vitality. METHODS: This was a prospective study, with 44 sperm donors on whom sperm analysis was performed. Nine mL of blood was collected and PRGF was obtained using PRGF-Endoret® technology. The influence of different dilutions of PRGF (5%, 10%, 20%, 40%) applied to 15 sperm donors was compared, and sperm motility was assessed after 30 minutes. In the second part of the study, 29 sperm donors were studied to analyze the influence of 20% dilution of PRGF at 15, 30 and 45 minutes in fresh and thawed sperm samples. Motility was assessed after the addition of PRGF and after analysis each aliquot was frozen. After thawing, concentration and motility were assessed at the same time periods. RESULTS: There were no differences in sperm motility in fresh samples between dilutions of PRGF when assessed 30 minutes after administration, nor between them, nor when compared to the control group immediately prior to treatment. No trend was observed between motility and PRGF dilution in linear regression analysis. There were no significant differences in thawed samples. CONCLUSIONS: The administration of 20% PRGF dilution had no effect on sperm motility compared to samples without PRGF. In addition, there was no change in sperm vitality when comparing samples with and without PRGF. More studies focusing on subnormal sperm samples, analyzing different PRGF concentrations and increasing the number of study variables are needed.

Proteomic Profiling Identifies Candidate Diagnostic Biomarkers of Hydrosalpinx in Endometrial Fluid: A Pilot Study.

Hydrosalpinx is a fluid occlusion and distension of the fallopian tubes, often resulting from pelvic inflammatory disease, which reduces the success of artificial reproductive technologies (ARTs) by 50%. Tubal factors account for approximately 25% of infertility cases, but their underlying molecular mechanisms and functional impact on other reproductive tissues remain poorly understood. This proteomic profiling study applied sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) to study hydrosalpinx cyst fluid and pre- and post-salpingectomy endometrial fluid. Among the 967 proteins identified, we found 19 and 17 candidate biomarkers for hydrosalpinx in pre- and post-salpingectomy endometrial fluid, respectively. Salpingectomy significantly affected 76 endometrial proteins, providing insights into the enhanced immune response and inflammation present prior to intervention, and enhanced coagulation cascades and wound healing processes occurring one month after intervention. These findings confirmed that salpingectomy reverses the hydrosalpinx-related functional impairments in the endometrium and set a foundation for further biomarker validation and the development of less-invasive diagnostic strategies for hydrosalpinx.

Semen processing using magnetic-activated cell sorting before ICSI is deemed safe for obstetric and perinatal outcomes: a retrospective multicentre study.

RESEARCH QUESTION: Is magnetic-activated cell sorting (MACS) a safe semen sample processing technique for newborns and mothers when used for semen processing prior to intracytoplasmic sperm injection (ICSI) cycles? DESIGN: This retrospective multicentre cohort study involved patients undergoing ICSI cycles with either donor or autologous oocytes from January 2008 to February 2020. They were divided into two groups: those who underwent standard semen preparation (reference group) and those who had an added MACS procedure (MACS group). A total of 25,356 deliveries were assessed in the case of cycles using donor oocytes, and 19,703 deliveries from cycles using autologous oocytes. Of these, 20,439 and 15,917, respectively, were singleton deliveries. Obstetric and perinatal outcomes were retrospectively assessed. All means, rates and incidences were computed per live newborn in each study group. RESULTS: There were no significant differences between the main obstetric and perinatal morbidities affecting the mothers' and newborns' well-being between groups using either donated or autologous oocytes. There was a significant increase in the incidence of gestational anaemia in both subpopulations (donor oocytes P = 0.01; autologous oocytes P < 0.001). However, this incidence was within the estimated prevalence for gestational anaemia in the general population. There was a statistically significant decrease in preterm (P = 0.02) and very preterm (P = 0.01) birth rates in the MACS group in cycles using donor oocytes. CONCLUSIONS: The use of MACS during semen preparation before ICSI using either donor or autologous oocytes appears to be safe for the mothers' and newborns' well-being during pregnancy and birth. Nevertheless, a close follow-up of these parameters in the future is advised, especially concerning anaemia, in order to detect even smaller effect sizes.

How Are BMI, Nutrition, and Physical Exercise Related? An Application of Ordinal Logistic Regression.

BACKGROUND: This paper performs a detailed ordinal logistic regression study in an evaluation of a survey at a university in South Texas, USA. We show that, for categorical data in our case, ordinal logistic regression works well. METHODS: The survey was designed according to the guidelines in diet and lifestyle from the American Heart Association and the United States Department of Agriculture and was sent out to all registered students at Texas A&M International University in Laredo, Texas. Data analysis included 601 students' results from the survey. Data analysis was conducted in Rstudio. RESULTS: The results showed that, compared with students who do not have enough whole grain food and exercise, those who have enough in both tend to have normal BMIs. As age increases, BMI tends to be out of the normal range. CONCLUSIONS: Because BMI in this research has three categories, applying an ordinal logistic regression model to describe the relationship between an ordered categorical response variable and more explanatory variables has several advantages compared with other models, such as the linear regression model.

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRß1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.

May Measurement Month 2017-2019: an analysis of blood pressure screening results from Guatemala.

In 2018, the Ministry of Public Health and Social Assistance of Guatemala published the last update of the prevalence of noncommunicable diseases (NCDs), and as in other low-income countries, the prevalence of NCD morbidity and mortality had risen. The prevalence of hypertension in Guatemala has been reported in a range from 18.7 to 22.7% which could be underestimated, because the country does not have an adequate statistical surveillance system. May Measurement Month (MMM) 2017, 2018, and 2019 in Guatemala was an opportunistic survey, which followed the methodology previously published. Blood pressure (BP) measurements were carried out in various locations, mainly hospitals and clinics (48.9%) or pharmacies (34.2%) in Guatemala City. In all patients, three BP measurements were taken after 5 min of rest and sitting in the correct recommended position. The mean of the second and third BP measurements was used for the analyses. Multiple imputation was used to impute the missing readings, based on the global MMM data. After multiple imputation, of all 3265 participants, 43.4% had hypertension. Of all participants with hypertension, 74.7% were aware of their diagnosis, 69.2% were on antihypertensive medication, and 63.1% had controlled BP (<140/90 mmHg). Of all those with hypertension, 43.6% had controlled BP. MMM is the largest hypertension survey ever carried out globally. The MMM results from Guatemala reported here provide complementary and strong data on the impact of hypertension in the country and help to make hypertension visible as a priority health problem, which requires urgent solutions.

Fasciolosis prevalence, risk factors and economic losses due to bovine liver condemnation in abattoirs in Mexico.

This study investigated the prevalence of bovine liver condemnation due to Fasciola hepatica in abattoirs and its influence on livestock productivity. It also explored risk factors such as season, breed, age and sex in the states of Puebla and Veracruz, Mexico. A total of 5281 cattle livers were inspected in two abattoirs. The overall prevalence of the parasite in cattle throughout 2020 was 24.9% (1313 out of 5281). The highest prevalence was found in Veracruz (28.5%; tropical climate), followed by Puebla (18.4%; temperate climate). The prevalence of fluke infection during the wet season was 19.0% and 25.8% in the states of Puebla and Veracruz, respectively; during the dry season, this was 18.0% and 30.2% respectively. The annual loss caused by condemnation of the liver for both abattoirs was estimated to be US$7502. Using multivariate logistic regression analysis, two models were constructed for potential association with the prevalence of condemned livers, using season, breed, age and sex as risk factors. The results indicate that season, age and sex were significantly associated with an increased risk of parasitic infection. Cattle age was the variable most strongly associated with F. hepatica infection, with the highest prevalence in cattle over three years of age as compared to younger animals, both in the states of Veracruz with a tropical climate (OR 6.443; 95% CI: 4.487-9.251) and in Puebla with a temperate climate (OR 2.854; 95% CI: 1.531-5.321). The results indicate that different factors were significantly associated with the prevalence of condemned livers, and it highlights the importance of continuous monitoring programmes for F. hepatica infection and preventing economic losses in cattle production.

Prevalence of Fatty Liver among Children under Multiple Machine Learning Models.

OBJECTIVES: To analyze the possible factors causing fatty liver in children based on ultrasound data of children in south Texas, and to establish machine learning models of fatty liver in children to provide ideas for the prevention and treatment of fatty liver in children. METHODS: The binary classification model of fatty liver problem in obese children in Texas was established under the multiple model. First, we selected important features using the CatBoost algorithm. Second, the best parameters of the algorithm were selected on the training set and the validation set by using the grid search method, and all six models were tested on the test set. The six models then were compared by area under the curve value, precision, accuracy, recall rate, and F1 score in a model evaluation. Then, two algorithms, logic regression and CatBoost, were selected to establish prediction models of fatty liver disease in children. RESULTS: We selected body mass index, height, liver size, kidney volume, glomerular filtration rate, and liver diameter as the features used in the machine learning model. The prediction models we chose showed that children with higher body mass index at the same age tended to have a greater probability of fatty liver. CONCLUSIONS: Based on the analysis of the results of the two prediction models established by logistic regression and CatBoost, we determined that the mean probability of fatty liver in severely obese children was between 74.47% and 92.22%, 73.45% and 85.41% in obese children, and slightly higher in boys than in girls, with a mean difference of 3.00% to 3.95%.

Physical activity and sperm quality: influence in sperm donors.

PURPOSE: To ascertain whether physical activity (PA) is associated with better sperm quality in sperm donors. METHODS: A prospective case-control study was designed in an IVF center setting. A total of 207 sperm donation candidates from a relatively small geographical area were included in the study with no intervention. Donor candidates were subjected to conventional sperm analysis according to WHO criteria. Moreover, they answered a standardized questionnaire regarding their last week PA (IPAQ), with PA expressed in metabolic equivalents (METs)-min/week. Donors were classified into 4 groups: low, moderate, high and very high PA. Specific sports were included in the questionnaire. Semen samples from 43 accepted donors were used in artificial insemination by donor (AID) and IVF. The fertilization rates (FR) and pregnancy rates (PR) were studied. RESULTS: Semen volume, sperm concentration, progressive spermatozoa, non-progressive spermatozoa, total motile progressive spermatozoa and sperm morphology were similar in the four PA groups. No correlation between various semen parameters studied and METs was found. Running or cycling > 1 h/week did not influence sperm parameters. The AID PR was similar in the different PA groups. However, in IVF the mean donor FR was significantly higher in the high PA group and in the very high PA group. CONCLUSIONS: No detrimental effect was associated with PA, or even very high PA, regarding conventional sperm parameters. Moreover, a better FR was associated with high and very high PA in IVF cycles, which merits more studies.

Cumulative live birth rates in donor oocyte ICSI cycles are not improved by magnetic-activated cell sorting sperm selection.

RESEARCH QUESTION: Does magnetic-activated cell sorting (MACS) for sperm selection increase cumulative live birth rates (CLBR) or improve clinical parameters of reproductive success in couples undergoing intracytoplasmic sperm injection (ICSI) with donor oocytes? DESIGN: Retrospective multicentre observational study including data compiled from unselected couples who underwent ICSI cycles with donated oocytes in 15 Spanish IVIRMA fertility clinics (January 2008 to February 2020). Patients were divided into reference (standard semen processing, n = 40,157) and MACS (additional sperm selection step by MACS, n = 1,240) groups. CLBR were plotted on Kaplan-Meier curves and compared using the Mantel-Cox test. Proportions were compared with a generalized estimating equation model, and results were adjusted to clinically relevant variables. RESULTS: The MACS group showed a 27.1% CLBR after one embryo was transferred and 81.6% after four; the reference group had CLBR of 19.6% and 78.5%, respectively. CLBR in the MACS group was 4.2% after five oocytes were used and 75.5% after 15; for the reference group, CLBR were 7.8% and 78.3%, respectively. Kaplan-Meier curves showed statistically significant differences in CLBR per number of embryos transferred and per number of donated metaphase II oocytes between the two groups (both P < 0.0001), but not for CLBR per embryo transfer. No significant differences between groups were found for classical clinical outcomes such as pregnancy and live birth rates per embryo transfer. CONCLUSIONS: Although MACS sperm selection slightly increased the CLBR per embryo transferred compared with the reference group, this change was not clinically meaningful. MACS should not be recommended indiscriminately to all infertile patients undergoing ICSI with donated oocytes as a sperm processing add-on.

Influenza Vaccination for the Prevention of Cardiovascular Disease in the Americas: Consensus document of the Inter-American Society of Cardiology and the Word Heart Federation.

Background: Cardiovascular mortality is decreasing but remains the leading cause of death world-wide. Respiratory infections such as influenza significantly contribute to morbidity and mortality in patients with cardiovascular disease. Despite of proven benefits, influenza vaccination is not fully implemented, especially in Latin America. Objective: The aim was to develop a regional consensus with recommendations regarding influenza vaccination and cardiovascular disease. Methods: A multidisciplinary team composed by experts in the management and prevention of cardiovascular disease from the Americas, convened by the Inter-American Society of Cardiology (IASC) and the World Heart Federation (WHF), participated in the process and the formulation of statements. The modified RAND/UCLA methodology was used. This document was supported by a grant from the WHF. Results: An extensive literature search was divided into seven questions, and a total of 23 conclusions and 29 recommendations were achieved. There was no disagreement among experts in the conclusions or recommendations. Conclusions: There is a strong correlation between influenza and cardiovascular events. Influenza vaccination is not only safe and a proven strategy to reduce cardiovascular events, but it is also cost saving. We found several barriers for its global implementation and potential strategies to overcome them.

Sperm Selection by Magnetic-Activated Cell Sorting before Microinjection of Autologous Oocytes Increases Cumulative Live Birth Rates with Limited Clinical Impact: A Retrospective Study in Unselected Males.

The application of MACS non-apoptotic sperm selection in infertility clinics is controversial since the published literature does not agree on its effect on reproductive outcomes. Therefore, it is not part of the routine clinical practice. Classical measures of reproductive success (pregnancy or live birth rates per ovarian stimulation) introduce a bias in the evaluation of a technique's effect, since only the best embryo is transferred. This retrospective, multicenter, observational study evaluated the impact of MACS on reproductive outcomes, measuring results in classical parameters and cumulative live birth rates (CLBR). Data from ICSI cycles using autologous oocyte in Spanish IVIRMA fertility clinics from January 2008 to February 2020 were divided into two groups according to their semen processing: standard practice (reference: 46,807 patients) versus an added MACS sperm selection (1779 patients). Only when measured as CLBR per embryo transferred and per MII oocyte used was the difference between groups statistically significant. There were no significant differences between MACS and reference groups on pregnancy and live birth rates. In conclusion, results suggest that non-apoptotic sperm selection by MACS on unselected males prior to ICSI with autologous oocytes has limited clinical impact, showing a subtle increase in CLBR per embryo transferred.

Vaccination with cathepsin L mimotopes of Fasciola hepatica in goats reduces worm burden, morphometric measurements, and reproductive structures.

Fasciolosis is a worldwide emergent zoonotic disease that significantly constrains the productivity of livestock. We conducted an experimental trial with four groups of five goats each, vaccinated with 1 × 1013 phage particles of cathepsin L1 (CLI: DPWWLKQ), CL1 (SGTFLFS), and CL2 (PPIRNGK) mimotopes combined with Quil A adjuvant. Animals received a booster four weeks later. The control group received phosphate-buffered saline. All animals were infected with 200 Fasciola hepatica metacercariae at week six and euthanised 16 weeks later. The percentage of significant worm reduction in CL1 (DPWWLKQ), CL1 (SGTFLFS), and CL2 (PPIRNGK) compared to the control group were 55.40%, 70.42% (P < 0.05), and 32.39%, respectively. Vaccinated animals showed a significant reduction in faecal egg production and egg viability. A significant reduction in the total biomass of parasites recovered was observed in the CL1 (DPWWLKQ) and CL1 (SGTFLFS) groups. In goats vaccinated with CL2 (PPIRNGK), fluke length and width were smaller than those in the control group. Furthermore, animals receiving CL mimotopes showed a significant reduction in the total area of reproductive structures. Goats immunised with phage-displayed mimotopes produced significantly high titres of specific IgG1 and IgG2 isotypes, indicating a mixed Th1/Th2 response. The liver fluke burdens in goats vaccinated with CL1 (DPWWLKQ) and CL1 (SGTFLFS) were significantly correlated with IgG and IgG1 levels.

The Global Ambulatory Blood Pressure Monitoring (ABPM) in Heart Failure with Preserved Ejection Fraction (HFpEF) Registry. Rationale, design and objectives.

Hypertension is a major risk factor for the development of heart failure with preserved ejection fraction (HFPEF) and blood pressure (BP) in itself is an important marker of prognosis. The association of BP levels, and hemodynamic parameters, measured by ambulatory blood pressure monitoring (ABPM), with outcomes, in patients with HFPEF is largely unknown. Patients with HFPEF have a substantial burden of co-morbidities and frailty. In addition there are marked geographic differences in HFPEF around the world. How these difference influence the association between BP and outcomes in HFPEF are unknown. The Global Ambulatory Blood Pressure Monitoring (ABPM) in Heart Failure with Preserved Ejection Fraction (HFpEF) Registry aims to assess the relevance of BP parameters, measured by ABPM, on the outcome of HFPEF patients worldwide. Additionally, the influence of other relevant factors such as frailty and co-morbidities will be assessed. Stable HFPEF patients with a previous hospitalization, will be included. Patients should be clinically and hemodynamically stable for at least 4 weeks before study inclusion. Specific data related to HF, biochemical markers, ECG and echocardiography will be collected. An ABPM and geriatric and frailty evaluation will be performed and the association with morbidity and mortality assessed. Follow up will be at least one year.