Adipose Tissue Dysfunction and the Role of Adipocyte-Derived Extracellular Vesicles in Obesity and Metabolic Syndrome.

Obesity is a major public health issue that is associated with metabolic diseases including diabetes mellitus type 2 and metabolic syndrome. This pathology leads to detrimental cardiovascular health and secondary effects, such as lipotoxicity, inflammation, and oxidative stress. Recently, extracellular vesicles (EVs) have been highlighted as novel players participating in human physiology and pathophysiology. In obesity, adipose tissue is related to the active shedding of adipocyte-derived extracellular vesicles (AdEVs). The current review explores and highlights the role of AdEVs and their cargo in obesity and metabolic syndrome. AdEVs are proposed to play an important role in obesity and its comorbidities. AdEVs are biological nanoparticles mainly shed by visceral and subcutaneous adipose tissue, acting in physiological and pathophysiological conditions, and also carrying different cargo biomolecules, such as RNA, microRNA (miRNA), proteins, and lipids, among others. RNA and miRNA have local and systemic effects affecting gene expression in target cell types via paracrine and endocrine actions. State of the art analyses identified some miRNAs, such as miR-222, miR-23b, miR-4429, miR-148b, and miR-4269, that could potentially affect cell pathways involved in obesity-related comorbidities, such as chronic inflammation and fibrosis. Similarly, AdEVs-proteins (RBP4, perilipin-A, FABP, mimecan, TGFBI) and AdEVs-lipids (sphingolipids) have been linked to the obesity pathophysiology. The current knowledge about AdEVs along with further research would support and reveal novel pathways, potential biomarkers, and therapeutic options in obesity.

Attenuated mutants of Salmonella enterica Typhimurium mediate melanoma regression via an immune response.

The lack of effective treatment options for an increasing number of cancer cases highlights the need for new anticancer therapeutic strategies. Immunotherapy mediated by Salmonella enterica Typhimurium is a promising anticancer treatment. Candidate strains for anticancer therapy must be attenuated while retaining their antitumor activity. Here, we investigated the attenuation and antitumor efficacy of two S. enterica Typhimurium mutants, ΔtolRA and ΔihfABpmi, in a murine melanoma model. Results showed high attenuation of ΔtolRA in the Galleria mellonella model, and invasion and survival in tumor cells. However, it showed weak antitumor effects in vitro and in vivo. Contrastingly, lower attenuation of the attenuated ΔihfABpmi strain resulted in regression of tumor mass in all mice, approximately 6 days after the first treatment. The therapeutic response induced by ΔihfABpmi was accompanied with macrophage accumulation of antitumor phenotype (M1) and significant increase in the mRNAs of proinflammatory mediators (TNF-α, IL-6, and iNOS) and an apoptosis inducer (Bax). Our findings indicate that the attenuated ΔihfABpmi exerts its antitumor activity by inducing macrophage infiltration or reprogramming the immunosuppressed tumor microenvironment to an activated state, suggesting that attenuated S. enterica Typhimurium strains based on nucleoid-associated protein genes deletion could be immunotherapeutic against cancer.

Clinically Relevant Topics and New Tendencies in Childhood Nutrition during the First 2 Years of Life: A Survey among Primary Care Spanish Paediatricians.

A multicenter cross-sectional study was conducted among 245 experienced Spanish paediatricians, who completed an online survey based on clinically relevant topics in nutrition during the first two years of life and their recommendations to parents in daily clinical practice. Most participants advise about the choking risk associated with baby-led weaning (BLW) and more than 60% consider that infants can receive an insufficient variety and quantity of nutrients with this practice. The general opinion is that there is a lack of evidence for delaying the introduction of gluten and other allergenic foods in the complementary feeding of healthy infants. Most participants agree/strongly agree that two servings of dairy products are the adequate daily amount in a diversified diet and 93.4% disagree/strongly disagree with the use of vegetal beverages under 1 year of life. There is a general agreement to avoid added salt and sugar before 12 months of life, the consideration that organic foods do not have a better nutritional profile than non-organic ones, and the limitations of vegetarian diets especially for adequate provision of micronutrients. Overall, there is an adequate knowledge of the new trends by paediatricians and younger ones seemed more in favor of them and interested in receiving more information on most topics.

Intensive Induction Chemotherapy versus Hypomethylating Agents in Combination with Venetoclax in NPM1-mutant AML.

While intensive induction chemotherapy (IC) remains the standard of care for younger patients with acute myeloid leukemia (AML), data from older patients shows that hypomethylating agents + venetoclax (HMA/VEN) can lead to durable remissions among patients with NPM1 mutations. Whether IC or HMA/VEN is superior in patients ≥60 years-old with NPM1-mutant AML is unknown. To compare IC and HMA/VEN, we performed an international, multicenter retrospective cohort study of patients with newly diagnosed, NPM1-mutant AML.We included 221 patients (147 IC, 74 HMA/VEN) with previously untreated NPM1-mutant AML. Composite complete remission (cCR; defined as CR + CR with incomplete count recovery [CRi]) rate was similar for IC and HMA/VEN (cCR: 85% vs. 74%; p=0.067). While OS was favorable with IC in unselected patients compared to HMA/VEN (24-month OS 59% [95% CI: 52-69%] vs. 38% [95% CI 27-55%]; p=0.013), it was not statistically different among patients 60-75 years-old (60% [95% CI 52-70%] vs. 44% [95% CI 29-66%]; p=0.069) and patients who received an allogeneic stem cell transplant (70% [95% CI: 58-85%] vs. 66% [95% CI: 44-100%]; p=0.56). Subgroup analyses suggested that patients with normal cytogenetics (24-month OS with IC 65% [95% 56-74%] vs. 40% [95% CI: 26-60%] with HMA/VEN; p=0.009) and without FLT3-ITD mutations might benefit from IC compared with HMA/VEN (24-month OS: 68% [95% CI: 59-79%] vs. 43% [95% CI: 29-63%]; p=0.008). In multivariable analysis, OS was not statistically different for patients treated with IC and HMA/VEN (hazard ratio for death HMA/VEN vs. IC: 0.71; 95% CI: 0.40-1.27; p=0.25).

Epigenetic regulation of major histocompatibility complexes in gastrointestinal malignancies and the potential for clinical interception.

BACKGROUND: Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes. MAIN BODY: By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions. CONCLUSION: The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.

The impact of clinical genome sequencing in a global population with suspected rare genetic disease.

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.

Intraepithelial CD15 infiltration identifies high grade anal dysplasia in people with HIV.

Men who have sex with men (MSM) with HIV are at high risk for squamous intraepithelial lesion (SIL) and anal cancer. Identifying local immunological mechanisms involved in the development of anal dysplasia could aid treatment and diagnostics. Here we studied 111 anal biopsies obtained from 101 MSM with HIV, who participated in an anal screening program. We first assessed multiple immune subsets by flow cytometry, in addition to histological examination, in a discovery cohort (n = 54). Selected molecules were further evaluated by immunohistochemistry in a validation cohort (n = 47). Pathological samples were characterized by the presence of Resident Memory T cells with low expression of CD103 and by changes in Natural Killer cell subsets, affecting residency and activation. Furthermore, potentially immune suppressive subsets, including CD15+CD16+ mature neutrophils, gradually increased as the anal lesion progressed. Immunohistochemistry confirmed the association between the presence of CD15 in the epithelium and SIL diagnosis, with a sensitivity of 80% and specificity of 71% (AUC 0.762) for the correlation with high-grade SIL. A complex immunological environment with imbalanced proportions of resident effectors and immune suppressive subsets characterizes pathological samples. Neutrophil infiltration, determined by CD15 staining, may represent a valuable pathological marker associated with the grade of dysplasia.

Improvement of digital Gabor holographic microscopy using a lens in plankton studies.

This work utilizes a Gabor Holographic Optical Scheme integrated with a microscope objective and a thin convex plane lens. This bi-telecentric lens system corrects spherical aberration from the objective, maintains consistent magnification across various reconstruction distances, and ensures a plane incidence on CMOS. Depending on the focal lengths of the objective and lens, the final image can be enlarged or reduced compared to the classic Gabor system, resulting in high-quality reconstructed phase images without spherical aberration. This setup was employed to capture phase distribution and intensity images of planktonic objects, such as copepods, achieving superior image quality.

Predicting healthcare expenditure based on Adjusted Morbidity Groups to implement a needs-based capitation financing system.

BACKGROUND: Due to population aging, healthcare expenditure is projected to increase substantially in developed countries like Spain. However, prior research indicates that health status, not merely age, is a key driver of healthcare costs. This study analyzed data from over 1.25 million residents of Spain's Murcia region to develop a capitation-based healthcare financing model incorporating health status via Adjusted Morbidity Groups (AMGs). The goal was to simulate an equitable area-based healthcare budget allocation reflecting population needs. METHODS: Using 2017 data on residents' age, sex, AMG designation, and individual healthcare costs, generalized linear models were built to predict healthcare expenditure based on health status indicators. Multiple link functions and distribution families were tested, with model selection guided by information criteria, residual analysis, and goodness-of-fit statistics. The selected model was used to estimate adjusted populations and simulate capitated budgets for the 9 healthcare districts in Murcia. RESULTS: The gamma distribution with logarithmic link function provided the best model fit. Comparisons of predicted and actual average costs revealed underfunded and overfunded areas within Murcia. If implemented, the capitation model would decrease funding for most districts (up to 15.5%) while increasing it for two high-need areas, emphasizing allocation based on health status and standardized utilization rather than historical spending alone. CONCLUSIONS: AMG-based capitated budgeting could improve equity in healthcare financing across regions in Spain. By explicitly incorporating multimorbidity burden into allocation formulas, resources can be reallocated towards areas with poorer overall population health. Further policy analysis and adjustment is needed before full-scale implementation of such need-based global budgets.

A Feasible Estimation of a "Corrected" EQ-5D Social Tariff.

OBJECTIVES: To demonstrate the feasibility of estimating a social tariff free of utility curvature and probability weighting biases and to test transferability between riskless and risky contexts. METHODS: Valuations for a selection of EQ-5D-3L health states were collected from a large and representative sample (N = 1676) of the Spanish general population through computer-assisted personal interviewing. Two elicitation methods were used: the traditional time trade-off (TTO) and a novel risky-TTO procedure. Both methods are equivalent for better than death states, which allowed us to test transferability of utilities across riskless and risky contexts. Corrective procedures applied are based on rank-dependent utility theory, identifying parameter estimates at the individual level. All corrections are health-state specific, which is a unique feature of our corrective approach. RESULTS: Two corrected value sets for the EQ-5D-3L system are estimated, highlighting the feasibility of developing national tariffs under nonexpected utility theories, such as rank-dependent utility. Furthermore, transferability was not supported for at least half of the health states valued by our sample. CONCLUSIONS: It is feasible to estimate a social tariff by using interviewing techniques, sample sizes, and sample representativeness equivalent to prior studies designed to generate national value sets for the EQ-5D. Utilities obtained in distinct contexts may not be interchangeable. Our findings caution against routinely taking transferability of utility for granted.

Combined effect of SAR-endolysin LysKpV475 with polymyxin B and Salmonella bacteriophage phSE-5.

Endolysins are bacteriophage (or phage)-encoded enzymes that catalyse the peptidoglycan breakdown in the bacterial cell wall. The exogenous action of recombinant phage endolysins against Gram-positive organisms has been extensively studied. However, the outer membrane acts as a physical barrier when considering the use of recombinant endolysins to combat Gram-negative bacteria. This study aimed to evaluate the antimicrobial activity of the SAR-endolysin LysKpV475 against Gram-negative bacteria as single or combined therapies, using an outer membrane permeabilizer (polymyxin B) and a phage, free or immobilized in a pullulan matrix. In the first step, the endolysin LysKpV475 in solution, alone and combined with polymyxin B, was tested in vitro and in vivo against ten Gram-negative bacteria, including highly virulent strains and multidrug-resistant isolates. In the second step, the lyophilized LysKpV475 endolysin was combined with the phage phSE-5 and investigated, free or immobilized in a pullulan matrix, against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The bacteriostatic action of purified LysKpV475 varied between 8.125 µg ml-1 against Pseudomonas aeruginosa ATCC 27853, 16.25 µg ml-1 against S. enterica Typhimurium ATCC 13311, and 32.50 µg ml-1 against Klebsiella pneumoniae ATCC BAA-2146 and Enterobacter cloacae P2224. LysKpV475 showed bactericidal activity only for P. aeruginosa ATCC 27853 (32.50 µg ml-1) and P. aeruginosa P2307 (65.00 µg ml-1) at the tested concentrations. The effect of the LysKpV475 combined with polymyxin B increased against K. pneumoniae ATCC BAA-2146 [fractional inhibitory concentration index (FICI) 0.34; a value lower than 1.0 indicates an additive/combined effect] and S. enterica Typhimurium ATCC 13311 (FICI 0.93). A synergistic effect against S. enterica Typhimurium was also observed when the lyophilized LysKpV475 at ⅔ MIC was combined with the phage phSE-5 (m.o.i. of 100). The lyophilized LysKpV475 immobilized in a pullulan matrix maintained a significant Salmonella reduction of 2 logs after 6 h of treatment. These results demonstrate the potential of SAR-endolysins, alone or in combination with other treatments, in the free form or immobilized in solid matrices, which paves the way for their application in different areas, such as in biocontrol at the food processing stage, biosanitation of food contact surfaces and biopreservation of processed food in active food packing.

Design of a multiple criteria decision analysis framework for prioritizing high-impact health technologies in a regional health service.

OBJECTIVES: This study aims to develop a framework for establishing priorities in the regional health service of Murcia, Spain, to facilitate the creation of a comprehensive multiple criteria decision analysis (MCDA) framework. This framework will aid in decision-making processes related to the assessment, reimbursement, and utilization of high-impact health technologies. METHOD: Based on the results of a review of existing frameworks for MCDA of health technologies, a set of criteria was proposed to be used in the context of evaluating high-impact health technologies. Key stakeholders within regional healthcare services, including clinical leaders and management personnel, participated in a focus group (n = 11) to discuss the proposed criteria and select the final fifteen. To elicit the weights of the criteria, two surveys were administered, one to a small sample of healthcare professionals (n = 35) and another to a larger representative sample of the general population (n = 494). RESULTS: The responses obtained from health professionals in the weighting procedure exhibited greater consistency compared to those provided by the general public. The criteria more highly weighted were "Need for intervention" and "Intervention outcomes." The weights finally assigned to each item in the multicriteria framework were derived as the equal-weighted sum of the mean weights from the two samples. CONCLUSIONS: A multi-attribute function capable of generating a composite measure (multicriteria) to assess the value of high-impact health interventions has been developed. Furthermore, it is recommended to pilot this procedure in a specific decision context to evaluate the efficacy, feasibility, usefulness, and reliability of the proposed tool.

Low Cortisone as a Novel Predictor of the Low-Renin Phenotype.

A large proportion of patients with low-renin hypertension (LRH) correspond to primary aldosteronism (PA). However, some of these subjects have low to normal aldosterone. Since low renin is driven by excessive mineralocorticoids or glucocorticoids acting on mineralocorticoid receptors (MRs), we hypothesize that a low-cortisone condition, associated classically with 11ßHSD2 deficiency, is a proxy of chronic MR activation by cortisol, which can also lead to low renin, elevated blood pressure, and renal and vascular alterations. Objective: To evaluate low cortisone as a predictor of low renin activity and its association with parameters of kidney and vascular damage. Methods: A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low plasma renin activity (<1 ng/mL × hours) and low cortisone (<25th percentile). Results: Plasma renin activity was associated with aldosterone (r = 0.36; P < .001) and cortisone (r = 0.22; P = .001). A binary logistic regression analysis showed that serum cortisone per ug/dL increase predicted the low-renin phenotype (OR 0.4, 95% CI 0.21-0.78). The receiver operating characteristic curves for cortisone showed an area under the curve of 0.6 to discriminate subjects with low renin activity from controls. The low-cortisone subjects showed higher albuminuria and PAI-1 and lower sodium excretion. The association study also showed that urinary cortisone was correlated with blood pressure and serum potassium (P < .05). Conclusion: This is the first study showing that low cortisone is a predictor of a low-renin condition. Low cortisone also predicted surrogate markers of vascular and renal damage. Since the aldosterone to renin ratio is used in the screening of PA, low cortisone values should be considered additionally to avoid false positives in the aldosterone-renin ratio calculation.

Crystal structures of human CD40 in complex with monoclonal antibodies dacetuzumab and bleselumab.

CD40 is a member of the tumor necrosis factor receptor superfamily, and it is widely expressed on immune and non-immune cell types. The interaction between CD40 and the CD40 ligand (CD40L) plays an essential function in signaling, and the CD40/CD40L complex works as an immune checkpoint molecule. CD40 has become a therapeutic target, and a variety of agonistic/antagonistic anti-CD40 monoclonal antibodies (mAbs) have been developed. To better understand the mode of action of anti-CD40 mAbs, we determined the X-ray crystal structures of dacetuzumab (agonist) and bleselumab (antagonist) in complex with the extracellular domain of human CD40, respectively. The structure reveals that dacetuzumab binds to CD40 on the top of cysteine-rich domain 1 (CRD1), which is the domain most distant from the cell surface, and it does not compete with CD40L binding. The binding interface of bleselumab spread between CRD2 and CRD1, overlapping with the binding surface of the ligand. Our results offer important insights for future structural and functional studies of CD40 and provide clues to understanding the mechanism of biological response. These data can be applied to developing new strategies for designing antibodies with more therapeutic efficacy.

Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.

BACKGROUND: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38ß MAPK) for the treatment of facioscapulohumeral muscular dystrophy. METHODS: We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4-driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. FINDINGS: Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45·7 (SD 12·5) years. Least squares mean changes from baseline in DUX4-driven gene expression did not differ significantly between the losmapimod (0·83 [SE 0·61]) and placebo (0·40 [0·65]) groups (difference 0·43 [SE 0·56; 95% CI -1·04 to 1·89]; p=0·56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drug-related) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. INTERPRETATION: Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy. FUNDING: Fulcrum Therapeutics.

Nursing students' knowledge regarding sexuality, sex, and gender diversity in a multicenter study.

Introduction: Sexuality is an integral part of development and personality, and is important in healthcare. Nurses are among the most representative healthcare professionals. For holistic and inclusive nursing care practice and to improve equality, human rights, well-being, and health of individuals, the curricula of nursing courses must integrate broad knowledge about sexuality and its diversity. This study aimed to identify and analyze nursing students' knowledge of sexuality, sex, and gender diversity. The present study was part of a multicenter study conducted in Europe. Methods: Questionnaires were administered in three nursing schools to assess nursing students' knowledge (n = 75). Data processing was performed using Excel® software version 20 and IRaMuTeQ (R Interface pour les Analysis Multidimensionnelles de Textes et de Questionnaires) 0.7 alpha 2, allowing organization by category and subsequent thematic analysis using content analysis. Results: The textual corpus "Nursing students' knowledge about sexuality in its diversity," was divided into two sub-corpus: "Students' perception of sexuality" and "Students' perception of gender identity," originating Class 6 "Eroticism" (14.23%) and Classes 4 "Sexual Orientation" (16.07%) and 3 "Heteronormative" (16.07%), the latter with greater proximity to each other and consequently to Class 6. Similarly, Classes 1 "Gender" (20.36%) and 5 "Cisgender" (12.14%) also presented a greater interrelationship between themselves and consecutively with Class 2 "Gender Identity" (15.36%). Discussion: The analyses revealed that though nursing students possessed knowledge about sexuality and its diversity, this knowledge was elementary and did not reveal a sustained appropriation of concepts related to sexuality, sexual orientation, and gender diversity. For some questions, the absence of students' answers were noteworthy, and may be associated with their personal reservation in expressing themselves on this sensitive and intimate theme. To ensure diversity, inclusivity, and impartiality in nursing practice, it is imperative to change the curriculum plans of nursing courses to address the theme of sexuality during the training process of nurses in Europe.

Effects of vaccination with Brucella melitensis, strains Rev 1 ΔeryCD and Rev 1, on the reproductive system of young male goats.

The present study evaluates the effects of vaccination with Brucella melitensis strains Rev 1 ΔeryCD and Rev 1 on the reproductive system of male goats. Three groups, each of them consisting of 15 six-month-old brucellosis-free male goats, were studied. The first group was vaccinated with the Rev 1 ΔeryCD strain, the second group received Rev 1 and the third group was inoculated with sterile physiological saline solution. The dose of both strains was of 1×109CFU/ml. Over the course of the five months of this study, three males from each group were euthanized every month. Their reproductive tracts, spleens, and lymph nodes were collected to analyze serology, bacteriology PCR, histology, and immunohistochemistry. Results show that vaccination with B. melitensis strains Rev 1 ΔeryCD and Rev 1 does not harm the reproductive system of male goats. Strain B. melitensis Rev 1 ΔeryCD displayed a lower capacity to colonize the reproductive tract than strain Rev 1, which was attributed to its limited catabolic action toward erythritol.

Bioenergetic modelling of a marine top predator's responses to changes in prey structure.

Determining how animals allocate energy, and how external factors influence this allocation, is crucial to understand species' life history requirements and response to disturbance. This response is driven in part by individuals' energy balance, prey characteristics, foraging behaviour and energy required for essential functions. We developed a bioenergetic model to estimate minimum foraging success rate (FSR), that is, the lowest possible prey capture rate for individuals to obtain the minimum energy intake needed to meet daily metabolic requirements, for female sperm whale (Physeter macrocephalus). The model was based on whales' theoretical energetic requirements using foraging and prey characteristics from animal-borne tags and stomach contents, respectively. We used this model to simulate two prey structure change scenarios: (1) decrease in mean prey size, thus lower prey energy content and (2) decrease in prey size variability, reducing the variability in prey energy content. We estimate the whales need minimum of ~14% FSR to meet their energetic requirements, and energy intake is more sensitive to energy content changes than a decrease in energy variability. To estimate vulnerability to prey structure changes, we evaluated the compensation level required to meet bioenergetic demands. Considering a minimum 14% FSR, whales would need to increase energy intake by 21% (5-35%) and 49% (27-67%) to compensate for a 15% and 30% decrease in energy content, respectively. For a 30% and 50% decrease in energy variability, whales would need to increase energy intake by 13% (0-23%) and 24% (10-35%) to meet energetic demands, respectively. Our model demonstrates how foraging and prey characteristics can be used to estimate impact of changing prey structure in top predator energetics, which can help inform bottom-up effects on marine ecosystems. We showed the importance of considering different FSR in bioenergetics models, as it can have decisive implications on estimates of energy acquired and affect the conclusions about top predator's vulnerability to possible environmental fluctuations.

Las misiones médicas al Policlínico PAMS en Chincha: evolución del modelo de misión / The medical missions to the PAMS Polyclinic in Chincha: evolution of the mission's model

RESUMEN Presentamos la experiencia del Policlínico de la Peruvian American Medical Society (PAMS) en Chincha, en la ejecución de misiones médico-educativas en la región Chincha. El Policlínico PAMS presta atención médica general y especializada a la población de la zona, seis días a la semana. Además, recibe misiones médicas que vienen generalmente de los EE. UU. Desde 2011, se han recibido 43 misiones médicas. La composición y la naturaleza de las misiones han cambiado con el tiempo. Los primeros años se atraía a especialistas con el énfasis de traer equipos e insumos para mejorar la infraestructura del Policlínico. Ahora estamos limitados por la renuencia de voluntarios de venir al Perú en parte debido a que el gobierno americano considera que viajes al Perú son de alto riesgo. Esta limitación nos ha brindado la oportunidad de hacer misiones médicas juntamente con dos excelentes universidades peruanas. La experiencia ha sido positiva.

ABSTRACT We present the experience of the Polyclinic of the Peruvian American Medical Society (PAMS) in Chincha, in the execution of medical educational missions in the Chincha region. The PAMS Polyclinic provides general and specialized medical care to the population of the area, six days a week. In addition, the Polyclinic receives medical missions generally coming from the EE.UU. Since 2011, we have received 43 medical missions. The composition and nature of the missions have changed over time. The first years attracted specialists with the emphasis on bringing equipment and supplies to improve the infrastructure of the Polyclinic. We are now limited by the reluctance of volunteers to come to Peru in part because the U.S. government considers travel to Peru to be high-risk. This limitation has given us the opportunity to do medical missions together with two excellent Peruvian universities. This experience has been positive.