Description of a new endemic Enteromius (Teleostei: Cyprinidae) from the upper Malagarazi in Burundi: Lessons for a protected area under implementation.

Recent collecting efforts in the upper Malagarazi basin (2013-2022) allowed for an integrative study based on qualitative (colour), quantitative (meristic and metric), and barcoding gene [mtDNA, cytochrome c oxidase (COI)] data of specimens similar to Enteromius sp. 'ascutelatus', being a previously identified, potentially, new species. Based on these data, the present study confirms its identification as a new species for science, which is here formally described as Enteromius nzigidaherai sp. nov. This new species belongs to the group of Enteromius species for which the last unbranched ray of the dorsal fin is flexible and devoid of serrations along its posterior edge. This species has a horizontal series of black spots at the midlateral level of the sides. Three congeneric species, known from the Congo basin sensu lato, with two of them also found in the upper Malagarazi basin, are most similar to it. However, E. nzigidaherai sp. nov. is distinguished from the two sympatric upper Malagarazi species, that is, E. quadrilineatus and E. lineomaculatus, at least by two meristics and two morphometrics. It is also distinguished from E. urostigma, known from the upper Congo basin, by two meristics and one, apparently related, morphometric. In addition, a barcoding (mtDNA, COI) study revealed that the specimens of E. nzigidaherai sp. nov. form a well-supported, separate lineage, with a K2P genetic distance of more than 10% with specimens identified as E. quadrilineatus and E. lineomaculatus, both originating from the upper Malagarazi basin and for which tissue samples were available. Finally, the new species was found to be endemic to the upper reaches of two left bank affluents of the upper Malagarazi basin: the Muyovozi and the Kinwa. However, both affluents are threatened by human activities, which seem to have resulted in its local disappearance as recent intensive collecting efforts in the latter affluent have remained unsuccessful. The species should thus be considered Critically Endangered (CR) according to IUCN criteria B1ab(ii,iv)c(i,iii). Therefore, it is hoped that the present description draws renewed attention to the importance of aquatic protection in the region by highlighting the need for the effective establishment of the Malagarazi Nature Reserve and concern for its optimal delimitation to efficiently protect the entire ichthyofauna of the upper Malagarazi, without excluding the fish species confined to its affluent rivers.

Hidden species diversity in the Enteromius Cope, 1867 (Teleostei: Cyprinidae) from the Aruwimi basin (Middle Congo) in the Okapi Wildlife Reserve (Democratic Republic of the Congo).

Two new African minnow species, Enteromius cerinus sp. nov. and Enteromius ruforum sp. nov., are described for science from the Angadiko River, a left-bank sub-affluent of first order of the Nepoko River, draining the north-eastern part of the Okapi Wildlife Reserve (OWR). Both new species belong to the group of Enteromius for which the last unbranched dorsal-fin ray is flexible and underrated. Within this morphological group, both are most similar to Enteromius kamolondoensis, especially in life colour pattern characteristics. However, Enteromius cerinus sp. nov. differs from E. kamolondoensis by its low number of circumpeduncular scales, 10-11 (vs. 12), low maximum body depth, 22.8%-25.7% standard length (Ls) (vs. 26.1%-30.0%), and long anterior and posterior barbel lengths, 32.6%-35.3% head length (LH) (vs. 23.6%-27.2%) and 41.6%-43.9% LH (vs. 30.3%-34.9%), respectively. Further, E. ruforum sp. nov. is also easily distinguished from E. kamolondoensis by its high maximum body depth, 30.6%-33.3% Ls (vs. 26.1%-30.0%), and small, isometric, eye diameter, 26.2%-28.0% LH (vs. 29.1%-31.9%). A barcoding study (mtDNA, cytochrome oxidase subunit I [COI]) revealed that specimens of both new species form lineages well differentiated from those of other available species. As such, (i) E. cerinus sp. nov. diverges from E. kamolondoensis by a K2P genetic distance (GD) of 10.3% and (ii) E. ruforum sp. nov. by a K2P GD of 11.2%. To the present day, the fish fauna of the left-bank sub-affluents of the Nepoko River, in general, remains poorly known or undocumented. Unfortunately, at the same time, multiple anthropogenic impacts are affecting this fauna, such as (i) the destruction of habitats along the river banks for agriculture and fishing and (ii) the use of illegal fishing practices, such as fishing with plant-based ichthyotoxins during ecopage, which is combined with dam building. As a result of the demographic growth, this ecopage results in overfishing and thus is threatening both new species in particular, but all other co-occurring fish species as well. Both new species, E. cerinus sp. nov. and E. ruforum sp. nov., should thus be considered Vulnerable (VU) according to IUCN criterion D2. It is therefore hoped that their discovery highlights the urgent need for a better protection and further in situ exploration of the reserve's freshwater (fish) biodiversity, in general, and that of those small sub-affluents, in particular.

Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer.

BACKGROUND: Molecular profiling in upper tract urothelial carcinoma (UTUC) with synchronous or metachronous urothelial bladder cancer (UBC) is scarce. We intended to assess immunohistochemical (IHC) and genetic differences between UTUC-only and UTUC with synchronous or metachronous UBC (UTUC + UBC) and evaluate the effect of subsequent UBC on the outcome of UTUC patients stratified by luminal-basal subtypes. METHODS: A retrospective cohort of UTUC was divided into UTUC-only (n = 71) and UTUC + UBC (n = 43). IHC expression of cytokeratin 5/6 (CK5/6), CK20, GATA3, and p53 was evaluated to assess relevant subtypes. Genetic characterization comprised TERTp, FGFR3, RAS, and TP53 status. Kaplan-Meier and Cox regression analyses estimated the effect of clinicopathological variables and molecular profiles on progression-free survival (PFS) and overall survival (OS) of UTUC patients. RESULTS: No meaningful differences were detected among both subgroups according to luminal-basal stratification and genetic analysis. UTUC + UBC was independently associated with a worse PFS when stratified by luminal-basal phenotype (HR 3.570, CI 95% 1.508-8.453, p = 0.004) but with no impact in OS (HR 1.279, CI 95% 0.513-3.190, p = 0.597). CONCLUSIONS: This study reveals that both subgroups exhibited equivalent genomic features and luminal-basal subtypes. The involvement of the bladder relates to shorter PFS but does not seem to influence the survival outcome of UTUC, independently of the IHC phenotype.

Latent Class Analysis Reveals, in patient profiles, COVID-19-related better prognosis by calcifediol treatment than glucocorticoids.

Calcifediol and glucocorticoids have been repositioned for the treatment of COVID-19 and may reduce severity, the need for intensive care unit admission and death. OBJECTIVE: to identify class or profiles of patients hospitalized and treated with COVID-19 pneumonia using latent class clustering methods to assess the clinical and prognostic relevance of the resulting patients' profiles. Poor prognosis was defined as death or need for ICU admission, good prognosis, the opposite. With special interest in differential responses to calcifediol. SETTING: Reina Sofia University Hospital, Córdoba Spain. PATIENTS: Retrospective observational cohort study of patients admitted for COVID-19. CLINICALTRIALS: gov public database (NCT05819918). INCLUSION CRITERIA: (i) Age ≥ 18 and ≤ 90 years, (ii) Pneumonia characterized by the presence of infiltrates on chest X-ray or CT scan, (iii) SARS-CoV-2 infection, confirmed, and (iv) CURB Scale 65 >1. DESIGN: Latent class analysis, for obtaining homogeneous clusters, without specifying a priori the belonging group, and selecting the optimal number of clusters by minimizing information criteria. Evaluating the differences between groups for each variable by means of chi-square, Fisher's exact test and Kruskal-Wallis test. RESULTS: 707 patients hospitalized from 10 March 2020 until 4 March 2022 were included. For the treatment variable, differences were found between class 3 (60 % treated with calcifediol only) and classes 1 (less than 1 % calcifediol only vs. 82 % treated with both), 2 (less than 1 % calcifediol only vs. 82 % treated with both) and 4 (1 % calcifediol only vs. 84 % treated with both). Class 3, (60 % with calcifediol), had a significantly better prognosis compared to patients treated with glucocorticoids alone (OR: 15.2, 95 % CI: [3.73-142], p<0.001) or no treatment (OR: 7.38, 95 % CI: [2.63-30.2], p<0.001). CONCLUSIONS: our real-life study shows that calcifediol treatment significantly reduces the need for ICU admission and improved prognosis in patients hospitalized for COVID-19 pneumonia, especially in the profile of patients receiving it without glucocorticoids.

Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer.

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2- mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell's subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2- mBC.

Comparison between hemodynamic effects of remimazolam and propofol during general anesthesia: a systematic review and meta-analysis.

INTRODUCTION: The need for safe anesthetic agents with minimal side effects has led to the development of remimazolam, a new benzodiazepine designed to be an alternative to the commonly used drug propofol, which has significant hemodynamic effects. This study aims to compare the hemodynamic effects of remimazolam with propofol during general anesthesia. EVIDENCE ACQUISITION: A systematic search was conducted in Embase, Web of Science, Cochrane Library, Scopus, and PubMed databases on 13/02/2023, following the recommendations of Cochrane Handbook and the PRISMA statement. The measure of association used was Risk Ratio (RR) or standardized mean difference, with 95% confidence intervals (CI) and 95% Prediction intervals (PI). An additional search was conducted on 04/09/2023. A Trial Sequential Analysis and a GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence table were conducted based on the editor's recommendation. EVIDENCE SYNTHESIS: After applying eligibility criteria and removing duplicates, 16 randomized clinical trials comprising 1951 patients were included in the meta-analysis. Significant associations favoring remimazolam over propofol were observed in the following aspects: intraoperative hypotension events (RR=0.47; 95% CI=0.41 to 0.54; 95% PI=0.40 to 0.55); frequency of vasoactive drug administration (RR=0.54; 95% CI=0.46 to 0.64; 95% PI=0.41 to 0.74); intraoperative bradycardia (RR=0.39; 95% CI=0.27 to 0.57; 95% PI=0.26 to 0.66); mean arterial pressure at induction (MD=7.77; 95% CI=6.00 to 9.55; 95% PI=4.39 to 11.15); heart rate at induction (MD=6.40; 95% CI=4.07 to 8.73; 95% PI=0.33 to 12.48); and heart rate at intubation (MD=6.06; 95% CI=2.33 to 9.78; 95% PI=-5.59 to 17.71). CONCLUSIONS: This study provides evidence that remimazolam induces fewer cardiorespiratory depressant effects and has a more favorable side effect profile compared to propofol during general anaesthesia.

Morphometric Assessment of the Hip Joint in a Functional Dysplastic Rabbit Model.

The present study investigates the morphometric changes in the hip joint in a surgically induced rabbit model of hip dysplasia through the sectioning of the ligamentum capitis femoris and pelvic limb immobilization. A total of seventeen rabbits were evaluated using radiographic and computed tomographic imaging to measure the following parameters: the femoral angles of anteversion and inclination, length and width indexes of the neck of the femur, and acetabular depth and ventroversion. Significant differences in femoral anteversion angle and acetabular depth were observed, particularly in the group of hip instability surgery with pelvic limb immobilization. The results have shown the influence of hip joint instability in the promotion of femoral anteversion and acetabular shallowing. These findings provide a foundation for future research on naturally occurring or experimentally induced hip dysplasia in rabbits and underscore the model's potential for studying the biomechanical and developmental aspects of hip joint disorders.

End-to-side neurorrhaphy in the reconstruction of peripheral segmental neural loss: an experimental study.

PURPOSE: To evaluate the effects on peripheral neural regeneration of the end-to-side embracing repair technique compared to the autograft repair technique in Wistar rats. METHODS: Fifteen male Wistar rats were divided into three groups with five animals each: denervated group (GD), autograft group (GA), and embracing group (EG). For the evaluation, the grasping test, electroneuromyography (ENMG), and muscle weight assessment were used. RESULTS: Muscle weight assessment and ENMG did not show significant neural regeneration at the end of 12 weeks in the DG and GE groups, but only in GA. The grasping test showed an increase in strength between the surgery and the fourth week in all groups, and only the GA maintained this trend until the 12th week. CONCLUSIONS: The present study indicates that the neural regeneration observed in the end-to-side embracing neurorrhaphy technique, in the repair of segmental neural loss, is inferior to autograft repair in Wistar rats.

Mesenchymal Stem Cells and Their Derived Products in Ageing and Diseases.

Despite the enormous efforts of the pharmaceutical industry in the generation of new drugs (55 new ones last year) [...].

DNA damage targeted therapy for advanced breast cancer.

Breast cancer (BC) is the most prevalent malignancy affecting women worldwide, including Portugal. While the majority of BC cases are sporadic, hereditary forms account for 5-10% of cases. The most common inherited mutations associated with BC are germline mutations in the BReast CAncer (BRCA) 1/2 gene (gBRCA1/2). They are found in approximately 5-6% of BC patients and are inherited in an autosomal dominant manner, primarily affecting younger women. Pathogenic variants within BRCA1/2 genes elevate the risk of both breast and ovarian cancers and give rise to distinct clinical phenotypes. BRCA proteins play a key role in maintaining genome integrity by facilitating the repair of double-strand breaks through the homologous recombination (HR) pathway. Therefore, any mutation that impairs the function of BRCA proteins can result in the accumulation of DNA damage, genomic instability, and potentially contribute to cancer development and progression. Testing for gBRCA1/2 status is relevant for treatment planning, as it can provide insights into the likely response to therapy involving platinum-based chemotherapy and poly[adenosine diphosphate (ADP)-ribose] polymerase inhibitors (PARPi). The aim of this review was to investigate the impact of HR deficiency in BC, focusing on BRCA mutations and their impact on the modulation of responses to platinum and PARPi therapy, and to share the experience of Unidade Local de Saúde Santa Maria in the management of metastatic BC patients with DNA damage targeted therapy, including those with the Portuguese c.156_157insAlu BRCA2 founder mutation.

Calcifediol or Corticosteroids in the Treatment of COVID-19: An Observational Study.

Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. OBJECTIVE: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. DESIGN, PATIENTS AND SETTING: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). INTERVENTIONS: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. MEASUREMENTS: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. RESULTS: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. INTERPRETATION: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation.

Chemical reversion of age-related oocyte dysfunction fails to enhance embryo development in a bovine model of postovulatory aging.

PURPOSE: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline. METHODS: Bovine immature oocytes were matured in vitro for 23 h (young) and 30 h (aged). Postovulatory aged oocytes (control group) and embryos obtained after fertilization were examined and compared with oocytes supplemented with either 2 µM of resveratrol or 6 µM phloretin (treatment groups) during IVM. RESULTS: Aged oocytes had a significantly lower mitochondrial mass and proportion of mitochondrial clustered pattern, lower ooplasmic volume, higher ROS, lower sirtuin-1 protein level, and a lower blastocyst rate in comparison to young oocytes, indicating that postovulatory oocytes have a lower quality and developmental competence, thus validating our experimental model. Supplementation of IVM medium with antioxidants prevented the generation of ROS and restored the active mitochondrial mass and pattern characteristic of younger oocytes. Moreover, sirtuin-1 protein levels were also restored but only following incubation with resveratrol. Despite these findings, the blastocyst rate of treatment groups was not significantly different from the control group, indicating that resveratrol and phloretin could not restore the oocyte competence of postovulatory aged oocytes. CONCLUSION: Resveratrol and phloretin can both revert the age-related oxidative stress and mitochondrial dysfunction during postovulatory aging but were insufficient to enhance embryo developmental rates under our experimental conditions.

Characterization of expression patterns and dynamic relocation of Notch proteins during acrosome reaction of bull spermatozoa.

Notch is a conserved cell-signaling pathway involved in spermatogenesis regulation. This study firstly evaluated the presence, localization patterns, acquisition origin and relation to acrosome reaction of Notch proteins in bull sperm. Western Blot analysis detected all Notch proteins in ejaculated bull sperm, and immunostaining described their specific sperm localization. Recovery of sperm from different segments showed that Notch proteins have testicular origin (NOTCH1, NOTCH2, DLL4), are sequentially acquired during sperm maturation along epididymal transit (NOTCH3, DLL3, JAGGED1-2), or post-ejaculation (DLL1, NOTCH4). Testis NOTCH2 is ubiquitously expressed in all germ-cell lines, whereas DLL4 is expressed in round and elongated spermatids during the Golgi, Cap, Acrosome and Maturation phases. In vitro spontaneous and induced sperm acrosome reaction induce consistent sperm regional relocation of NOTCH2, DLL4 and JAGGED1, and these relocation patterns are significantly associated to sperm acrosome status. NOTCH2 and JAGGED1 are relocated from the head apical to the post-equatorial regions, whereas DLL4 is lost along with the acrosome, evidencing that sperm spatial redistribution of NOTCH2 and JAGGED1 is linked to acrosome reaction onset, whereas DLL4 loss is linked to AR completion. Overall, results prompt for a relevant Notch role in bull sperm acrosome testicular development, epididymal maturation and acrosome reaction.

Microplastics Biodegradation by Estuarine and Landfill Microbiomes.

Plastic pollution poses a worldwide environmental challenge, affecting wildlife and human health. Assessing the biodegradation capabilities of natural microbiomes in environments contaminated with microplastics is crucial for mitigating the effects of plastic pollution. In this work, we evaluated the potential of landfill leachate (LL) and estuarine sediments (ES) to biodegrade polyethylene (PE), polyethylene terephthalate (PET), and polycaprolactone (PCL), under aerobic, anaerobic, thermophilic, and mesophilic conditions. PCL underwent extensive aerobic biodegradation with LL (99 ± 7%) and ES (78 ± 3%) within 50-60 days. Under anaerobic conditions, LL degraded 87 ± 19% of PCL in 60 days, whereas ES showed minimal biodegradation (3 ± 0.3%). PE and PET showed no notable degradation. Metataxonomics results (16S rRNA sequencing) revealed the presence of highly abundant thermophilic microorganisms assigned to Coprothermobacter sp. (6.8% and 28% relative abundance in anaerobic and aerobic incubations, respectively). Coprothermobacter spp. contain genes encoding two enzymes, an esterase and a thermostable monoacylglycerol lipase, that can potentially catalyze PCL hydrolysis. These results suggest that Coprothermobacter sp. may be pivotal in landfill leachate microbiomes for thermophilic PCL biodegradation across varying conditions. The anaerobic microbial community was dominated by hydrogenotrophic methanogens assigned to Methanothermobacter sp. (21%), pointing at possible syntrophic interactions with Coprothermobacter sp. (a H2-producer) during PCL biodegradation. In the aerobic experiments, fungi dominated the eukaryotic microbial community (e.g., Exophiala (41%), Penicillium (17%), and Mucor (18%)), suggesting that aerobic PCL biodegradation by LL involves collaboration between fungi and bacteria. Our findings bring insights on the microbial communities and microbial interactions mediating plastic biodegradation, offering valuable perspectives for plastic pollution mitigation.

Private vs. public emergency visits for mental health due to heat: An indirect socioeconomic assessment of heat vulnerability and healthcare access, in Curitiba, Brazil.

Few studies have explored the influence of socioeconomic status (SES) on the heat vulnerability of mental health (MH) patients. As individual socioeconomic data was unavailable, we aimed to fill this gap by using the healthcare system type as a proxy for SES. Brazilian national statistics indicate that public patients have lower SES than private. Therefore, we compared the risk of emergency department visits (EDVs) for MH between patients from both healthcare types. EDVs for MH disorders from all nine public (101,452 visits) and one large private facility (154,954) in Curitiba were assessed (2017-2021). Daily mean temperature was gathered and weighed from 3 stations. Distributed-lag non-linear model with quasi-Poisson (maximum 10-lags) was used to assess the risk. We stratified by private and public, age, and gender under moderate and extreme heat. Additionally, we calculated the attributable fraction (AF), which translates individual risks into population-representative burdens - especially useful for public policies. Random-effects meta-regression pooled the risk estimates between healthcare systems. Public patients showed significant risks immediately as temperatures started to increase. Their cumulative relative risk (RR) of MH-EDV was 7.5 % higher than the private patients (Q-Test 26.2 %) under moderate heat, suggesting their particular heat vulnerability. Differently, private patients showed significant risks only under extreme heat, when their RR became 4.3 % higher than public (Q-Test 6.2 %). These findings suggest that private patients have a relatively greater adaptation capacity to heat. However, when faced with extreme heat, their current adaptation means were potentially insufficient, so they needed and could access healthcare freely, unlike their public counterparts. MH patients would benefit from measures to reduce heat vulnerability and access barriers, increasing equity between the healthcare systems in Brazil. AF of EDVs due to extreme heat was 0.33 % (95%CI 0.16;0.50) for the total sample (859 EDVs). This corroborates that such broad population-level policies are urgently needed as climate change progresses.

Criteria to evaluate graduate nurse proficiencies in obtaining a health history and perform physical assessment in simulation-based education: A narrative review.

BACKGROUND: Simulation is a technique being used increasingly in healthcare education which offers opportunities to evaluate nursing proficiencies. The use of valid and reliable instruments is recognised as the foundation for a robust assessment, however competency-based health assessment courses for graduate nurses can consequently become reductionist in measuring proficiencies. OBJECTIVE: The specific review question was: In simulation-based education, what are the criteria that evaluate graduate nursing student's competence in obtaining a health history and performance of patient assessment? METHODS: Eleven studies were included in the review. Papers were critically appraised with The Joanna Briggs Institute quasi-experimental studies checklist. Bloom's taxonomy was used to structure this narrative review. RESULTS: Seven papers evaluated cognition through questionnaires and two papers used a Likert-scale to determine self-perceived knowledge. Six papers evaluated psychomotor skills with a behavioural checklist. Diversity of application was factored into the studies when testing affective skills. Three papers used Likert-scales to evaluate preparedness, six papers used Likert-scales to evaluate self-confidence and one used a Likert-scale to evaluate autonomy. Three papers used a checklist to evaluate professionalism. Four papers used faculty member/ standardised patient feedback. CONCLUSION: Reductionist evaluation instruments create a barrier when evaluating competency. The limited validity and reliability of assessment instruments in simulation, as well as the lack of standardisation of affective skills assessment, presents a challenge in simulation research. Affective skills encompass attitudes, behaviours and communication abilities, which pose a significant challenge for standardised assessments due to their subjective nature. This review of the simulation literature highlights a lack of robustness in the evaluation of the affective domain. This paper proposes that simulation assessment instruments should include the standardisation of affective domain proficiencies such as: adaptation to patients' cognitive function, ability to interpret and synthesise relevant information, ability to demonstrate clinical judgement, readiness to act, recognition of professional limitations and faculty/standardised-simulated patient feedback. The incorporation of the affective domain in standardised assessment instruments is important to ensure comprehensive assessment of simulation particularly in the development of health history and physical assessment proficiencies. Attention to all of the domains in Blooms taxonomy during simulation assessment has the potential to better prepare professionals for the patient care setting.

Exploring the Impact of Copper Oxide Substitution on Structure, Morphology, Bioactivity, and Electrical Properties of 45S5 Bioglass®.

In recent decades, the requirements for implantable medical devices have increased, but the risks of implant rejection still exist. These issues are primarily associated with poor osseointegration, leading to biofilm formation on the implant surface. This study focuses on addressing these issues by developing a biomaterial for implant coatings. 45S5 bioglass® has been widely used in tissue engineering due to its ability to form a hydroxyapatite layer, ensuring a strong bond between the hard tissue and the bioglass. In this context, 45S5 bioglasses®, modified by the incorporation of different amounts of copper oxide, from 0 to 8 mol%, were synthesized by the melt-quenching technique. The incorporation of Cu ions did not show a significant change in the glass structure. Since the bioglass exhibited the capacity for being polarized, thereby promoting the osseointegration effectiveness, the electrical properties of the prepared samples were studied using the impedance spectroscopy method, in the frequency range of 102-106 Hz and temperature range of 200-400 K. The effects of CuO on charge transport mobility were investigated. Additionally, the bioactivity of the modified bioglasses was evaluated through immersion tests in simulated body fluid. The results revealed the initiation of a Ca-P-rich layer formation on the surface within 24 h, indicating the potential of the bioglasses to enhance the bone regeneration process.

Design of a multi-epitope-based vaccine candidate against Bovine Genital Campylobacteriosis using a reverse vaccinology approach.

BACKGROUND: Bovine Genital Campylobacteriosis (BGC), a worldwide distributed venereal disease caused by Campylobacter fetus subsp. venerealis (Cfv), has a relevant negative economic impact in cattle herds. The control of BGC is hampered by the inexistence of globally available effective vaccines. The present in silico study aimed to develop a multi-epitope vaccine candidate against Cfv through reverse vaccinology. RESULTS: The analysis of Cfv strain NCTC 10354 proteome allowed the identification of 9 proteins suitable for vaccine development. From these, an outer membrane protein, OmpA, and a flagellar protein, FliK, were selected for prediction of B-cell and T-cell epitopes. The top-ranked epitopes conservancy was assessed in 31 Cfv strains. The selected epitopes were integrated to form a multi-epitope fragment of 241 amino acids, which included 2 epitopes from OmpA and 13 epitopes from FliK linked by GPGPG linkers and connected to the cholera toxin subunit B by an EAAAK linker. The vaccine candidate was predicted to be antigenic, non-toxic, non-allergenic, and soluble upon overexpression. The protein structure was predicted and optimized, and the sequence was successfully cloned in silico into a plasmid vector. Additionally, immunological simulations demonstrated the vaccine candidate's ability to stimulate an immune response. CONCLUSIONS: This study developed a novel vaccine candidate suitable for further in vitro and in vivo experimental validation, which may become a useful tool for the control of BGC.

A Case of Success: Complete Response to Radium-223 in Metastatic Castration-Resistant Prostate Cancer.

Radium-223 dichloride (Ra223) is the first targeted alpha agent approved for treating metastatic castration-resistant prostate cancer (mCRPC) with bone-exclusive disease. A benefit in overall survival and time to the first symptomatic skeletal-related event was shown in the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. However, this trial did not describe a bone scan response to Ra223, and there is no universal consensus about how it should be monitored. Furthermore, a scintigraphy flare phenomenon may lead to false-positive tracer uptake in responsive cases, thereby misleading the interpretation of imaging results.  We present the case of a 67-year-old male with mCRPC and exclusive bone disease treated with Ra223. The bone scintigraphy after the end of the treatment showed an apparent aggravation of the lesions, corresponding to a flare phenomenon, with an almost complete resolution after three months. The patient maintained a scintigraphic response for seven months.

Evening but not morning aerobic training improves sympathetic activity and baroreflex sensitivity in elderly patients with treated hypertension.

The blood pressure-lowering effect of aerobic training is preceded by improving cardiovascular autonomic control. We previously demonstrated that aerobic training conducted in the evening (ET) induces a greater decrease in blood pressure than morning training (MT). To study whether the greater blood pressure decrease after ET occurs through better cardiovascular autonomic regulation, this study aimed to compare MT versus ET on muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) in treated patients with hypertension. Elderly patients treated for hypertension were randomly allocated into MT (n = 12, 07.00-10.00 h) or ET (n = 11, 17.00-20.00 h) groups. Both groups trained for 10 weeks, 3 times/week, cycling for 45 min at moderate intensity. Beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and MSNA (microneurography) were assessed at the initial and final phases of the study at baseline and during sequential bolus infusions of sodium nitroprusside and phenylephrine (modified-Oxford technique) to evaluate cardiac and sympathetic BRS. Mean blood pressure decreased significantly after ET but not after MT (-9 ± 11 vs. -1 ± 8 mmHg, P = 0.042). MSNA decreased significantly only after ET with no change after MT (-12 ± 5 vs. -3 ± 7 bursts/100 heart beats, P = 0.013). Sympathetic BRS improved after ET but not after MT (-0.8 ± 0.7 vs. 0.0 ± 0.8 bursts/100 heart beats/mmHg, P = 0.052). Cardiac BRS improved similarly in both groups (ET: +1.7 ± 1.8 vs. MT: +1.4 ± 1.9 ms/mmHg, Pphase  ≤ 0.001). In elderly patients treated for hypertension, only ET decreased mean blood pressure and MSNA and improved sympathetic BRS. These findings revealed that the sympathetic nervous system has a key role in ET's superiority to MT in blood pressure-lowering effect. KEY POINTS: Reducing muscle nerve sympathetic activity and increasing sympathetic baroreflex sensitivity plays a key role in promoting the greater blood pressure reduction observed with evening training. These findings indicated that simply changing the timing of exercise training may offer additional benefits beyond antihypertensive medications, such as protection against sympathetic overdrive and loss of baroreflex sensitivity, independent markers of mortality. Our new findings also suggest new avenues of investigation, such as the possibility that evening aerobic training may be beneficial in other clinical conditions with sympathetic overdrive, such as congestive heart failure and hypertrophic cardiomyopathy.