The potential of five c-miRNAs as serum biomarkers for Late-Onset Alzheimer's disease diagnosis: miR-10a-5p, miR-29b-2-5p, miR-125a-5p, miR-342-3p, and miR-708-5p.

The nervous system is rich in miRNAs, indicating an important role of these molecules in regulating processes associated with cognition, memory, and others. Therefore, qualitative and quantitative imbalances involving such miRNAs may be involved in dementia contexts, including Late-Onset Alzheimer's Disease (LOAD). To test the viability of circulating miRNAs (c-miRNAs) as biomarkers for LOAD, we proceed accordingly to the following reasoning. The first stage was to discover and identify profile of c-miRNAs by RNA sequencing (RNA-Seq). For this purpose, blood serum samples were used from LOAD patients (n = 5) and cognitively healthy elderly control group (CTRL_CH) (n = 5), all over 70 years old. We identified seven c-miRNAs differentially expressed (p ≤ 0.05) in the serum of LOAD patients compared to CTRL_CH (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p, miR-380-5p and miR-340-3p). Of these, five (p ≤ 0.01) were selected for in silico analysis (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p), for which 44 relevant target genes were found regulated by these c-miRNAs and related to LOAD. Through the analysis of these target genes in databases, it was possible to observe that they have functions related to the development and progress of LOAD, directly or indirectly connecting the different Alzheimer's pathways. Thus, this work found five promising serum c-miRNAs as options for biomarkers contributing to LOAD diagnosis. Our study shows the complex network between these molecules and LOAD, supporting the relevance of studies using c-miRNAs in dementia contexts.

Hyper-physiologic mechanical cues, as an osteoarthritis disease-relevant environmental perturbation, cause a critical shift in set points of methylation at transcriptionally active CpG sites in neo-cartilage organoids.

BACKGROUND: Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stiffness, pain, and a significant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (Guilak in Best Pract Res Clin Rheumatol 25:815-823, 2011). It has been shown that post-mitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative impact on cellular performance. We hypothesize that hyper-physiologic mechanical loading leads to the accumulation of altered epigenetic markers in articular chondrocytes, resulting in a loss of the tightly regulated balance of gene expression that leads to a dysregulated state characteristic of the OA disease state. RESULTS: We showed that hyper-physiological loading evokes consistent changes in CpGs associated with expression changes (ML-tCpGs) in ITGA5, CAV1, and CD44, among other genes, which together act in pathways such as anatomical structure morphogenesis (GO:0009653) and response to wound healing (GO:0042060). Moreover, by comparing the ML-tCpGs and their associated pathways to tCpGs in OA pathophysiology (OA-tCpGs), we observed a modest but particular interconnected overlap with notable genes such as CD44 and ITGA5. These genes could indeed represent lasting detrimental changes to the phenotypic state of chondrocytes due to mechanical perturbations that occurred earlier in life. The latter is further suggested by the association between methylation levels of ML-tCpGs mapped to CD44 and OA severity. CONCLUSION: Our findings confirm that hyper-physiological mechanical cues evoke changes to the methylome-wide landscape of chondrocytes, concomitant with detrimental changes in positional gene expression levels (ML-tCpGs). Since CAV1, ITGA5, and CD44 are subject to such changes and are central and overlapping with OA-tCpGs of primary chondrocytes, we propose that accumulation of hyper-physiological mechanical cues can evoke long-lasting, detrimental changes in set points of gene expression that influence the phenotypic healthy state of chondrocytes. Future studies are necessary to confirm this hypothesis.

Implications of clinical simulation in motivation for learning: scoping review.

OBJECTIVE: To identify, synthesize, and analyze the scientific knowledge produced regarding the implications of using clinical simulation for undergraduate nursing or medical students' motivation for learning. METHODS: The search for articles was conducted between July 28 and August 3, 2022, on the PubMed/MEDLINE, Scopus, Web of Science, and SciELO databases. The following was used for the search: P - undergraduate students attending Nursing or Medicine courses; C - motivation for learning, and C - skills and clinical simulation laboratory. The following research question guided the study: "What are the implications of clinical simulation on the motivation for learning of undergraduate students of nursing and medicine?" Of the 1,783 articles found, 13 were included in the sample for analysis. All stages of the selection process were carried out by two independent evaluators. The results were presented as charts and a discursive report. RESULTS: The studies analyzed indicated the beneficial effects of clinical simulation on students' motivation, in addition to other gains such as competencies, technical and non-technical skills, knowledge, belonging, autonomy, clinical judgment, critical and reflective thinking, self-efficacy and decreased anxiety, self-management, and improvements in learning and learning climate. CONCLUSION: Clinical simulation provides a positive learning environment favorable to the development of technical and interpersonal skills and competencies, and raising the level of motivational qualities.

Acute anodal transcranial direct current stimulation improves the performance of professional rowers.

Introduction: The aim of the present study was to evaluate the influence of acute transcranial direct current stimulation (tDCS) on physical and subjective responses in professional rowing during the 2,000-m time trial test. Methods: Seven rowers (age 20.86 ± 4.49 years; weight 71.66 ± 7.97 kg) participated in this randomized triple-blind trial with a crossover experimental design. The protocol consists of 2 days with different conditions (anodal and sham). The tDCS anodic stimulation conducted was 2 mA for 20 min in the left temporal cortex (2.5 cm from the F7 zone and 2.5 cm from the T3 zone), targeting the left insular cortex. In the sham moment, the participants experienced 30 s of stimulation. Afterward, they performed a standardized progressive warm-up for 15 min, following the Brazilian Rowing Confederation's assessment protocols, and rested for 3 min before the test started. All procedures were made on an indoor rowing machine, which allowed the capture of performance variables such as time performed, power in watts (W), pace (m/min), and stroke rate (strokes/min). The ratings of perceived exertion [Borg scale (CR-20)] were recorded in each 2-min during the test. Results: The results presented differences in power [Z: -2.371; p = 0.018; effect size (ES) = -0.896 (large)] and pace [Z: -2.371; p = 0.018; ES = -0.896 (large)] and time performance [Z: -1.612; p = 0.107; ES = -0.609 (large)] throughout the protocol for the anodal moment. Discussion: However, no differences for the other variables were found. According to the results, the current tDCS with the present protocol improved the physical performance at the 2,000-m time trial Test providing ergogenic aid.

Effects of bi-hemispheric anodal transcranial direct current stimulation on soccer player performance: a triple-blinded, controlled, and randomized study.

The search for increased performance and physical performance are linked to the use of ergogenic resources. The vertical jump is one of the measures commonly used to evaluate the performance of lower limbs in athletes. Transcranial direct current stimulation (tDCS) is a non-invasive, safe, economically viable technique that can modulate cortical excitability, which can influence the increase in the performance of athletes in general. This study aimed to investigate whether the use of tDCS on the primary motor cortex (M1) improves the performance of soccer players. A cross-sectional study was conducted. Twenty-seven players were randomized into three groups: Active tDCS group (n = 9), Sham group (n = 9), and control group (n = 9). Stimulation was applied at 2 mA for 15 min using a cephalic mount. Visual Pain Scale (VAS) and Subjective Recovery Scale (SRS) were monitored before and after tDCS. In addition, the participants performed the Countermovement Jump (CMJ) before and after the stimulation intercalated with Heart Rate (HR) and Rating of Perceived Exertion (RPE CR-10). No differences were found in any of the performance variables analyzed (p > 0.05) nor in the responses of HR (p > 0.05), RPE (p > 0.05), VAS (p > 0.05), and SRS (p > 0.05) between groups. The tDCS in M1 did not change the performance of the vertical jump, and there was no improvement in the subjective scales. New studies should also be developed with different stimulus intensities in different cortical areas and sports modalities.

Interaction of the antifungal ketoconazole and its diphenylphosphine derivatives with lipid bilayers: Insights into their antifungal action.

Ketoconazole (Ke) is an important antifungal drug, and two of its diphenylphosphinemethyl derivatives (KeP: Ph2PCH2-Ke and KeOP: Ph2P(O)CH2-Ke) have shown improved antifungal activity, namely against a yeast strain lacking ergosterol, suggesting alternative modes of action for azole compounds. In this context, the interactions of these compounds with a model of the cell membrane were investigated, using POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) large unilamellar vesicles and taking advantage of the intrinsic fluorescence of Ke, KeP and KeOP. Steady-state fluorescence spectra and anisotropy, including partition and aggregation studies, as well as fluorescence lifetime measurements, were carried out. In addition, the ability of the compounds to increase membrane permeability was assessed through carboxyfluorescein leakage. The membrane/water mole fraction partition coefficients (Kp,x): (3.31 ± 0.36) x105, (8.31 ± 1.60) x105 and (4.66 ± 0.72) x106, for Ke, KeP and KeOP, respectively, show that all three compounds have moderate to high affinity for the lipid bilayer. Moreover, KeP, and particularly KeOP interact more efficiently with POPC bilayers than Ke, which correlates well with their in vitro antifungal activity. Furthermore, although the three compounds disturb the lipid bilayer, KeOP is the quickest and most efficient one. Hence, the higher affinity and ability to permeabilize the membrane of KeOP when compared to that of KeP, despite the higher lipophilicity of the latter, points to an important role of Ph2P(O)CH2- oxygen. Overall, this work suggests that membrane interactions are important for the antifungal activity of these azoles and should be considered in the design of new therapeutic agents.

Genetic association between fat-to-protein ratio and traits of economic interest in early lactation Holstein cows in Brazil.

The aims of this study were to estimate the genetic parameters for fat-to-protein ratio (F:P) within the first 90 days of lactation and to examine their genetic associations with daily milk yield (MY), somatic cell score (SCS), and calving interval between the first and second calving (IFSC) and between the second and third calving (ISTC) during the first three lactations of Holstein cows. We utilized 200,626 production-related data officially recorded from 77,436 cows milked two or three times a day from 2012 to 2022, sourced from the Holstein Cattle Breeders Association of Paraná State, Brazil. The (co)variance components were estimated using animal models, adopting the restricted maximum likelihood (REML) method with single-trait analysis (for heritability and repeatability) and two-trait analysis (for genetic and phenotypic correlations), per lactation. Regardless of lactation number, heritability estimates were relatively low, ranging from 0.08 ± 0.005 to 0.10 ± 0.003 for F:P; 0.08 ± 0.01 to 0.18 ± 0.005 for MY; 0.04 ± 0.01 to 0.07 ± 0.004 for SCS; and 0.03 ± 0.01 for both IFSC and ISTC. Repeatability estimates within the same lactation were low for F:P (ranging from 0.17 ± 0.002 to 0.19 ± 0.03), high for MY (between 0.50 ± 0.003 and 0.53 ± 0.002), and moderate to high for SCS (between 0.39 ± 0.003 and 0.44 ± 0.004). Genetic correlations between F:P and MY ranged from -0.26 ± 0.03 to -0.15 ± 0.02; F:P and SCS, from -0.06 ± 0.03 to -0.03 ± 0.08; F:P and IFSC, 0.31 ± 0.01; F:P and ISTC, 0.20 ± 0.01; MY and IFSC, 0.24 ± 0.05; and MY and ISTC, 0.13 ± 0.08. The fat-to-protein ratio during early lactation showed low genetic variability, regardless of lactation number. Furthermore, it was genetically correlated with MY, IFSC, and ISTC, although there is an antagonistic and unfavorable correlation between traits that can limit genetic progress.

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

A Survey of Xylella fastidiosa in the U.S. State of Virginia Reveals Wide Distribution of Both Subspecies fastidiosa and multiplex in Grapevine.

Global travel and trade in combination with climate change are expanding the geographic distribution of plant pathogens. The bacterium Xylella fastidiosa is a prime example. Native to the Americas, it has spread to Europe, Asia, and the Middle East. To assess the risk that pathogen introductions pose to crops in newly invaded areas, it is key to survey their diversity, host range, and disease incidence in relation to climatic conditions where they are already present. We performed a survey of X. fastidiosa in grapevine in Virginia using a combination of quantitative PCR, multilocus sequencing, and metagenomics. We also analyzed samples from deciduous trees with leaf scorch symptoms. X. fastidiosa subspecies fastidiosa was identified in grapevines in all regions of the state, even in Northern Virginia, where the temperature was below -9°C for 10 days per year on average in the years preceding sampling. Unexpectedly, we also found for the first time grapevine samples infected with X. fastidiosa subspecies multiplex (Xfm). The Xfm lineage found in grapevines had been previously isolated from blueberries in the Southeastern United States and was distinct from that found in deciduous trees in Virginia. The obtained results will be important for risk assessment of X. fastidiosa introductions in other parts of the world.

Identified senescence endotypes in aged cartilage are reflected in the blood metabolome.

Heterogeneous accumulation of senescent cells expressing the senescence-associated secretory phenotype (SASP) affects tissue homeostasis which leads to diseases, such as osteoarthritis (OA). In this study, we set out to characterize heterogeneity of cellular senescence within aged articular cartilage and explored the presence of corresponding metabolic profiles in blood that could function as representative biomarkers. Hereto, we set out to perform cluster analyses, using a gene-set of 131 senescence genes (N = 57) in a previously established RNA sequencing dataset of aged articular cartilage and a generated metabolic dataset in overlapping blood samples. Using unsupervised hierarchical clustering and pathway analysis, we identified two robust cellular senescent endotypes. Endotype-1 was enriched for cell proliferating pathways, expressing forkhead box protein O4 (FOXO4), RB transcriptional corepressor like 2 (RBL2), and cyclin-dependent kinase inhibitor 1B (CDKN1B); the FOXO mediated cell cycle was identified as possible target for endotype-1 patients. Endotype-2 showed enriched inflammation-associated pathways, expressed by interleukin 6 (IL6), matrix metallopeptidase (MMP)1/3, and vascular endothelial growth factor (VEGF)C and SASP pathways were identified as possible targets for endotype-2 patients. Notably, plasma-based metabolic profiles in overlapping blood samples (N = 21) showed two corresponding metabolic clusters in blood. These non-invasive metabolic profiles could function as biomarkers for patient-tailored targeting of senescence in OA.

New Host Plant Species of Grapevine Virus A Identified with Vector-Mediated Infections.

Grapevine virus A (GVA) is an economically important virus and a member of the genus Vitivirus (family Betaflexiviridae) that causes a range of symptoms with qualitative and quantitative effects on grape production. Wild and domesticated species of Vitis, including hybrids used as rootstocks, are considered important natural hosts of GVA. Mechanical transmission to some herbaceous plant species, graft transmission, and vector transmission from grape to grape by various mealybugs and soft scale insects have been reported. Under laboratory and greenhouse conditions, this study demonstrates the transmission of GVA from grapes to alternative hosts by the vine mealybug (Planococcus ficus). Results of ELISA, end-point one-step RT-PCR, and real-time RT-PCR, and in some cases electron microscopy and genome sequencing, confirmed successful transmission to three new plant species commonly found in Croatian vineyards: velvetleaf (Abutilon theophrasti), redroot pigweed (Amaranthus retroflexus), and field poppy (Papaver rhoeas), along with Chenopodium murale and the previously known host Nicotiana benthamiana, with variable infection rates. Depending on the host species, symptoms in the form of leaf reddening, yellow spots, reduced growth of lateral shoots, systemic vein clearing, foliar deformation and rugosity, and dwarfism were observed in GVA-infected plants, whereas no symptoms were observed in infected plants of A. theophrasti. Reverse transmission from these new hosts to grapevines by Pl. ficus was not successful. These results confirm four new GVA host species and open new research venues.

Unmet needs in the management of psoriasis in Latin America: a systematic review.

BACKGROUND: Psoriasis is a chronic, systemic inflammatory disease with a worldwide prevalence of approximately 2%. Currently, despite the difficulties faced every day by patients and physicians in low-resource countries, literature describing the exact needs of psoriasis treatment in Latin America remains scarce. OBJECTIVE: To investigate the unmet needs in psoriasis treatment in Latin America. METHODS: The authors conducted a systematic review following PRISMA statements in PubMed, Embase, and LILACS of studies published from January 2011 to March 2021 addressing challenges in psoriasis treatment in Latin America. RESULTS: The search strategy identified 3,837 articles, of which 19 were included in the final analysis. Most were from Brazil (58%; n=11), all were observational, and most were cross-sectional (84%; n=16). Difficulties faced by psoriasis patients in Latin America included the high prevalence of opportunistic and endemic infections (42% of the studies addressed this matter; n=8), delay in diagnosis (5%; n=1), work productivity impairment (16%; n=3), limited access to medication/medical care (37%; n=7), poor adherence to treatment (5%; n=1) and poor adherence to guidelines (11%; n=2). STUDY LIMITATIONS: Number and quality of studies currently available on this subject. CONCLUSIONS: Current psoriasis guidelines do not always account for epidemiological, financial, and cultural characteristics. Most studies available are from Brazil, which might not accurately represent Latin America as a whole. In a region where neglected diseases and scarce resources remain a reality, it is imperative that dermatological training be offered to primary care providers, allowing for standardized conduct and earlier diagnosis.

High-beta oscillations at EEG resting state and hyperconnectivity of pain circuitry in fibromyalgia: an exploratory cross-sectional study.

Background: Electroencephalography (EEG) has identified neural activity in specific brain regions as a potential indicator of the neural signature of chronic pain. This study compared the lagged coherence connectivity between regions of interest (ROIs) associated with the pain connectome in women with fibromyalgia (FM) and healthy women (HC). Methods: We evaluated 64 participants (49 FM and 15 HC) during resting-state EEG sessions under both eyes open (EO) and eyes closed (EC) conditions. In addition to EEG measurements, we assessed clinical and psychological symptoms and serum levels of brain-derived neurotrophic factor (BDNF). The connectivity between eight ROIs was computed across eight different EEG frequencies. Results: The FM group demonstrated increased connectivity between the left dorsolateral prefrontal cortex (DLPFC) and right anterior cingulate cortex (ACC), specifically in the beta-3 frequency band (t = 3.441, p = 0.044). When comparing the EO and EC conditions, FM patients exhibited heightened interhemispheric connectivity between insular areas (t = 3.372, p = 0.024) and between the left insula (INS) and right DLPFC (t = 3.695, p = 0.024) within the beta-3 frequency band. In the EC condition, there was a negative correlation between pain disability and connectivity in the beta-3 frequency band between the left ACC and the left primary somatosensory cortex (SI; r = -0.442, p = 0.043). In the EO condition, there was a negative correlation between central sensitization severity and lagged coherence connectivity in the alpha-2 frequency band between the right ACC and left SI (r = 0.428, p = 0.014). Moreover, in the EO-EC comparison, the lagged coherence connection between the left DLPFC and right INS, indexed by the gamma frequency band, showed a negative correlation with serum BDNF levels (r = -0.506, p = 0.012). Conclusion: These findings indicate that increased connectivity between different pain processing circuits, particularly in the beta-3 frequency band during rest, may serve as neural biomarkers for the chronic pain brain signature associated with neuroplasticity and the severity of FM symptoms.

Simulation training of caregivers at hospital discharge of patients with chronic diseases: an integrative review.

OBJECTIVE: to identify evidence about the use and effects of clinical simulation for preparing caregivers for discharging patients with chronic conditions. METHODS: an integrative peer review in the Scopus, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, ScienceDirect and Virtual Health Library databases, from July to September 2022. RESULTS: 3,218 studies were identified, with a final sample consisting of four national and two international articles. Using simulation as an educational technology contributed to caregiver preparation in home care. In most studies, using clinical simulation included using other strategies to complement training: expository dialogued class, conversation circle and audiovisual resources. FINAL CONSIDERATIONS: simulation proved to be efficient for training caregivers, with the active participation of family members and nurses in health education actions.

Supervision of professional nursing practice in Brazil: a scoping review.

OBJECTIVES: to map studies that analyze the audit process of nursing councils. METHODS: this is a scoping review, anchored in the JBI framework, with the guiding question: what is the evidence of the audit process of legal practice of nursing by class councils (COFEN/COREN system)? The searches were carried out in October and November 2022 without limitation of language and year. RESULTS: of the 9 selected studies, all are Brazilian and published from 2014 onwards. Among the topics addressed are the role, challenges, costs and difficulties in nurse auditors' daily work process, in addition to the contribution of the audit sector in Brazil. CONCLUSIONS: the studies gathered discuss aspects related to costs, challenges and difficulties, but there is no focus on corrective, disciplinary and educational activities as well as little is said about the audit process, its reporting, referral and outcomes.

Doença falciforme e o efeito modulador da vitamina D em crianças: uma revisão integrativa / Sickle cell disease and the modulating effect of vitamin D in children: an integrative review

INTRODUÇÃO: A deficiência de Vitamina D (VD) é frequente na doença falciforme (DF) em decorrência do status inflamatório crônico, danos renais, endoteliais, hiperhemólise e melanodermia. Atualmente, a suplementação desse nutriente em falcêmicos tem se mostrado importante devido sua ação sistêmica e imunológica. OBJETIVOS: Analisar o impacto da VD em crianças com DF. MÉTODOS: Trata-se de uma revisão integrativa da literatura, onde foram analisados estudos, publicados originalmente em inglês e português, dos últimos dez anos, em humanos, tendo como referência as bases de dados MEDLINE, SciELO e LILACS. A busca foi efetuada mediante a consulta ao MeSH. Os descritores utilizados foram: "children"; "vitamin D"; "sickle cell anemia"; "supplementation". Foram identificados 32 artigos a partir da frase de pesquisa. Ao aplicar os critérios de inclusão, nove artigos foram eleitos para o estudo. RESULTADOS: A partir da análise dos artigos incluídos, 6 avaliaram a prevalência da deficiência de VD em crianças com anemia falciforme e os outros três artigos relataram sobre a suplementação de VD em crianças também com anemia falciforme. Todos os estudos mostraram que as crianças tratadas com reposição de VD tiveram uma diminuição de idas ao pronto-socorro e maior estabilidade hemodinâmica durante os tratamentos. CONCLUSÃO: Outros ensaios clínicos randomizados devem ser realizados para identificar o papel da DV na qualidade de vida e na redução da morbidade falciforme. A contribuição deste artigo é reconhecer que há evidências sobre a vitamina D fora dos ensaios clínicos randomizados.

INTRODUCTION: Vitamin D (VD) deficiency is frequent in sickle cell disease (SCD) due to chronic inflammatory status, kidney and endothelial damage, hyperhemolysis and melanoderma. Currently, the supplementation of this nutrient in sickle cell patients is important due to its systemic and immunological action. Objectives: To analyze the impact of VD in children with SCD. METHODS: This is an integrative literature review, which analyzed studies, originally published in English and Portuguese, in the last ten years, in humans, using the MedLine, SciELO and LILACS databases as References. The search was performed by consulting the MeSH. The descriptors used were: "children"; "vitamin D"; "sickle cell anemia"; "supplementation". 32 articles were identified from the search phrase. When applying the inclusion criteria, nine articles were chosen for the study. RESULTS: Among the included articles, six evaluated the prevalence of VD deficiency in children with sickle cell anemia, and the other three reported on VD supplementation in children with sickle cell anemia. All studies showed that children treated with VD replacement had a decrease in emergency room visits and greater hemodynamic stability during treatments. CONCLUSION: Further randomized controlled trials should be carried out to identify the role of VD in quality of life and in the reduction of sickle cell morbidity. The contribution of this paper is to recognize that there is evidence about vitamin D outside of randomized controlled trials.

Implicaciones de las actividades prácticas en el Laboratorio de Habilidades y Simulación relacionadas con la motivación y los sentimientos de los estudiantes / Implications of practical activities in the Skills and Simulation Laboratory on students' motivation and feelings / Implicações das atividades práticas no Laboratório de Habilidades e Simulação relacionado a motivação e sentimentos dos alunos

Objetivo: verificar las implicaciones de las actividades prácticas en el Laboratorio de Habilidad y Simulación relacionadas con la motivación y los sentimientos expresados por los estudiantes universitarios cuando regresan a las actividades presenciales luego del aislamiento social ocasionado por la pandemia del COVID-19. Método: estudio cuasiexperimental, con un solo grupo y del tipo pre y postest, realizado mediante una intervención educativa basada en el entrenamiento de habilidades en administración de medicamentos y venopunción, con estudiantes de medicina de una universidad pública brasileña. La muestra estuvo conformada por 47 estudiantes. Para la recolección de datos se utilizaron los instrumentos de caracterización y autopercepción de los individuos y la Escala de Motivación Situacional. Resultados: en la muestra, el 98% mencionó la falta de actividades prácticas durante la pandemia. El sentimiento descrito con mayor frecuencia fue la ansiedad. Después de realizar la actividad, hubo un cambio en la frecuencia de los sentimientos expresados, aunque no hubo un cambio significativo en los niveles de motivación. Regulación Externa (5,1 - 5,6), Regulación Identificada (6,1 - 6,4) y Motivación Intrínseca (5,6 - 6,0) presentaron resultados altos, demostrando similitud con los sentimientos relatados por los estudiantes. Conclusión: la motivación es fundamental para un aprendizaje efectivo y el uso de metodologías activas refuerza de manera efectiva las habilidades construidas en los estudiantes frente al proceso de aprendizaje.

Objective: to verify the implications of practical activities in the Skills and Simulation Laboratory on the motivation and feelings expressed by undergraduate students when returning to face-to-face activities after the social isolation caused by COVID-19 pandemic. Method: a quasi-experimental study, with a single group and of the pre- and post-test type, carried out through an educational intervention based on skills training on medication administration and venipuncture, with medical students from a Brazilian public university. The sample was comprised by 47 students. The instruments of students' characterization and self-perceived feelings and the Situational Motivation Scale were used for data collection. Results: in the sample, 98% mentioned the lack of practical activities during the pandemic. The most frequently described feeling was anxiety. After carrying out the activity, there was a change in the frequency of expressed feelings, although there was no significant change in motivational levels. External Regulation (5.1 - 5.6), Identified Regulation (6.1 - 6.4) and Intrinsic Motivation (5.6 - 6.0) presented high results, showing similarity to the feelings reported by the learners. Conclusion: motivation is essential for effective learning and the use of active methodologies reinforces skills built in an affective way in the students facing the learning process.

Objetivo: verificar as implicações das atividades práticas no Laboratório de Habilidade e Simulação relacionado à motivação e os sentimentos expressos pelos estudantes universitários quando regressam às atividades presenciais após o isolamento social causado pela pandemia da COVID-19. Método: estudo quase-experimental, com um único grupo, do tipo pré e pós-teste, realizado por meio de uma intervenção educacional baseada no treino de habilidades de administração de medicamentos e punção venosa, com estudantes de medicina de uma universidade pública brasileira. A amostra foi composta por 47 estudantes. Para a coleta de dados, foram utilizados os instrumentos de caracterização dos sujeitos e sentimentos autopercebidos pelos estudantes e a Escala de Motivação Situacional. Resultados: na amostra, 98% referiram falta de atividades práticas durante a pandemia. O sentimento mais frequentemente descrito foi a ansiedade. Após a realização da atividade, observou-se uma mudança na frequência dos sentimentos expressos, embora não se tenha verificado uma mudança significativa nos níveis motivacionais. A Regulação Externa (5,1 - 5,6), a Regulação (6,1 - 6,4) e a Motivação Intrínseca (5,6 - 6,0) apresentaram resultados elevados, demostrando semelhança com os sentimentos relatados pelos alunos. Conclusão: a motivação é essencial para uma aprendizagem eficaz e a utilização de metodologias ativas reforça as habilidades construídas de uma forma efetiva nos estudantes frente ao processo de aprendizagem.

Hyper-physiologic mechanical cues, as an osteoarthritis disease relevant environmental perturbation, cause a critical shift in set-points of methylation at transcriptionally active CpG sites in neo-cartilage organoids.

Background: Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stiffness, pain, and a significant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (1). It has been shown that post-mitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative impact on cellular performance. We hypothesize that hyper-physiologic mechanical loading leads to the accumulation of altered epigenetic markers in articular chondrocytes, resulting in a loss of the tightly regulated balance of gene expression that leads to a dysregulated state characteristic of the OA disease state. Results: We showed that hyper-physiological loading evokes consistent changes in ML-tCpGs associated with expression changes in ITGA5, CAV1, and CD44, among other genes, which together act in pathways such as anatomical structure morphogenesis (GO:0009653) and response to wound healing (GO:0042060). Moreover, by comparing the ML-tCpGs and their associated pathways to tCpGs in OA pathophysiology, we observed a modest but particular interconnected overlap with notable genes such as CD44 and ITGA5. These genes could indeed represent lasting detrimental changes to the phenotypic state of chondrocytes due to mechanical perturbations that occurred earlier in life. The latter is further suggested by the association between methylation levels of ML-tCpGs mapped to CD44 and OA severity. Conclusion: Our findings confirm that hyper-physiological mechanical cues evoke changes to the methylome-wide landscape of chondrocytes, concomitant with detrimental changes in positional gene expression levels (ML-tCpGs). Since CAV1, ITGA5, and CD44 are subject to such changes and are central and overlapping with OA-tCPGs of primary chondrocytes, we propose that accumulation of hyper-physiological mechanical cues can evoke long-lasting, detrimental changes in set points of gene expression that influence the phenotypic healthy state of chondrocytes. Future studies are necessary to confirm this hypothesis.

Short communication: Impact of corn grain particle size on production performance of lactating dairy cows.

Corn grain particle size has the potential to influence the performance of lactating dairy cows and the overall profitability of a dairy farm. The objective of this study was to evaluate the productive performance of lactating cows fed diets containing finely or coarsely ground corn grain. Fifty lactating Holstein cows (n = 50; 10 primiparous and 40 multiparous), averaging (mean ± standard deviation, SD) 658 ± 64 kg of BW, 38.8 ± 7.3 kg of milk/d, and 155 ± 80 DIM, were fed diets with finely ground corn grain (FGC) or coarsely ground corn grain (CGC) in a randomized block design with a 28-d treatment period. Finely and coarsely ground corn grain had an average particle size of 660 and 915 µm, respectively. Dry matter intake (DMI) was reduced (p < 0.01) for cows fed FGC (22.1 vs. 21.2 kg d-1). Milk yield and efficiency were not affected by treatments (37.9 vs. 36.8 kg d-1; p = 0.12 and 1.78 vs. 1.79; p = 0.15). Concentrations of milk protein and fat, as well as other milk solids, were unaffected (p > 0.05) by treatments. Fecal starch (FS) concentrations were greater (p < 0.01) for cows fed CGC (7.0 vs. 4.9%), whereas plasma concentrations of D-lactate were greater (p < 0.05) for cows fed FGC (98.5 vs. 79.7 µM). Overall, feeding finely ground corn grain increased total-tract starch digestibility and reduced DMI while maintaining milk yield.

Red Fluorescent Protein Variant with a Dual-Peak Emission of Fluorescence.

The marine environment is a rich reservoir of diverse biological entities, many of which possess unique properties that are of immense value to biotechnological applications. One such example is the red fluorescent protein derived from the coral Discosoma sp. This protein, encoded by the DsRed gene, has been the subject of extensive research due to its potential applications in various fields. In the study, a variant of the red fluorescent protein was generated through random mutagenesis using the DsRed2 gene as a template. The process employed error-prone PCR (epPCR) to introduce random mutations, leading to the isolation of twelve gene variants. Among these, one variant stood out due to its unique spectral properties, exhibiting dual fluorescence emission at both 480 nm (green) and 550 nm (red). This novel variant was expressed in both Escherichia coli and zebrafish (Danio rerio) muscle, confirming the dual fluorescence emission in both model systems. One of the immediate applications of this novel protein variant is in ornamental aquaculture. The dual fluorescence can serve as a unique marker or trait, enhancing the aesthetic appeal of aquatic species in ornamental settings.