Reproductive morphophysiology of an iteroparous batch spawner fish: from early follicle development to ovulation.

Batch spawner fishes develop successive clutches of oocytes which allows them to participate in many reproductive cycles during their adult life (iteroparous) and spawn in multiple events within each breeding cycle. Here, ovarian follicular development was morpho-functionally analyzed in females of the iteroparous batch spawner fish Gymnocorymbus ternetzi. To obtain better insights into the reproductive morpho-physiology in batch spawners, the objective of this research was to analyze the dynamics of the follicular development, with its hormonal regulation between two active reproduction events. We found that over 16 days, follicles progressed asynchronously to chromatin nucleolus, Primary and Secondary growth stages of oogenesis with progressive secretion of 17ß-estradiol (E2). During the end of secondary growth, the increase in 17α,20ß-dihydroxy-4-pregnen-3-one (17,20ß-p) was measured relative to the maturation process of the ovarian follicles (e.g., nuclear migration and its rupture during the resumption of meiosis). Interestingly, an additional increase in E2 was observed after fish reproduction, probably related to the recruitment of new batch follicles for secondary growth. We also measured the high values of multiple condition factor post-reproduction measurements, reflecting more energy invested during the pre-reproductive process. We also quantified high concentrations of 17,20ß-p, probably related to the recruitment of a new batch of oogonia to meiosis, presumably secreted by post-ovulatory follicles, after fish reproduction. We finally found that fish without exposure to reproductive stimulus developed a regression phase at day 24, characterized by massive follicle atresia, that allow them to recycle energy and constitutive materials of the follicles invested during oogenesis for another reproductive cycle.

Sex differences in prolactin levels and clinical outcomes in patients with a first psychotic episode.

AIM: To analyze the clinical, neurocognitive, and functional impact of prolactin levels according to sex in patients with a First Episode Psychosis (FEP). METHODS: We measured prolactin levels in 221 non-affective FEP patients treated with antipsychotics (AP) and 224 healthy controls, at baseline and 2-year follow-up. We examined whether the relationships between clinical and functional variables were mediated by prolactin, controlling for antipsychotic use, according to sex. RESULTS: Prolactin levels were higher in patients when compared to controls at both time points. Baseline factors associated with prolactin were chlorpromazine equivalents, attention, and executive functioning. In the FEP group, prolactin levels were associated with functioning and diminished expression in males, and with working memory in females. Prolactin levels (p=0.0134) played a role as a mediator between negative symptomatology (p=0.086) and functional outcome (p=0.008) only in FEP male patients at baseline. CONCLUSIONS: Prolactin plays a role in the functionality and clinical symptomatology of FEP patients. Our results suggest that pharmacological counselling in patients with hyperprolactinemia at baseline and negative symptomatology might improve their functional and clinical outcomes.

Neurocognitive and social cognitive correlates of social exclusion in psychotic disorders: a 20-year follow-up cohort study.

PURPOSE: Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. METHODS: A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. RESULTS: The total scores on the measures of cognition and social exclusion were strongly associated (ß = - .469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). CONCLUSION: The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders.

SURGICAL SITE INFECTION IN RESECTIONS OF DIGESTIVE SYSTEM TUMOURS.

Postoperative infectious complications are extremely important to surgeons and the entire medical care team. Among these complications, surgical site infection (SSI) appears to be one of the earliest and most prevalent events and is considered an inherent complication of surgical procedures. In oncological patients submitted to resections of digestive system tumors, there is a confluence of several risk factors for SSI, making it necessary to establish measures to maximize the control of this condition to provide a better prognosis for these patients. Some risk factors for SSI are the manipulation of structures hosting the highest density of pathogenic microorganisms, such as the colon, the patient's performance status, the patient's nutritional status, the use of chemotherapy and/or radiotherapy, and the surgical procedure itself, which tends to last longer and be more complex than surgeries for benign conditions of the digestive system. Therefore, this review sought to provide a qualitative analysis and a summary of the literature regarding the SSI of postoperative tumor patients who underwent surgical resection and were well-structured postoperatively, to provide objective data on this problem, and alert about the well-structured needs of individualized pre-, peri-, and post-protocols to avoid the development of these events.

Characterization of Liquid Dosage Forms of Atenolol and Enalapril Maleate for Oral and Enteral Feeding Administration.

The limited availability of pharmaceutical formulations tailored for cardiovascular diseases in both pediatric and geriatric populations generates the need for compounded dosage forms to guarantee precise dosing and medication adherence. This study aimed to analyze the physicochemical properties and stability of formulations of atenolol and enalapril maleate prepared with a proprietary oral vehicle, SuspendIt®. To this end, palatability, injectability, pH, rheological behavior, and physical, microbiological, and chemical stability over a 180-day storage period at 25 °C and 5 °C were evaluated. Injectability tests confirmed the suitable use of both formulations for administration through enteral feeding tubes. By using a potentiometric electronic tongue, it was confirmed that the SuspendIt® vehicle effectively served as a bitter-blocking strategy for atenolol and enalapril maleate. Adequate stability throughout the storage period was confirmed in terms of the mechanical properties, pH, and effectiveness of the preservative system. The atenolol concentration remained above 90% of the initial amount, while the concentration of enalapril maleate decreased to 88% after 90 days of storage at 25 °C. In summary, the atenolol formulation maintained suitable chemical, physical, and microbiological stability after 180 days at both storage temperatures, while the enalapril maleate formulation remained stable up to 60 days at 25 °C and for 180 days at 5 °C.

Assessment of Albumin-Incorporating Scores at Hepatocellular Carcinoma Diagnosis Using Machine Learning Techniques: An Evaluation of Prognostic Relevance.

Hepatocellular carcinoma (HCC) presents high mortality rates worldwide, with limited evidence on prognostic factors at diagnosis. This study evaluates the utility of common scores incorporating albumin as predictors of mortality at HCC diagnosis using Machine Learning techniques. They are also compared to other scores and variables commonly used. A retrospective cohort study was conducted with 191 patients from Virgen de la Luz Hospital of Cuenca and University Hospital of Guadalajara. Demographic, analytical, and tumor-specific variables were included. Various Machine Learning algorithms were implemented, with eXtreme Gradient Boosting (XGB) as the reference method. In the predictive model developed, the Barcelona Clinic Liver Cancer score was the best predictor of mortality, closely followed by the Platelet-Albumin-Bilirubin and Albumin-Bilirubin scores. Albumin levels alone also showed high relevance. Other scores, such as C-Reactive Protein/albumin and Child-Pugh performed less effectively. XGB proved to be the most accurate method across the metrics analyzed, outperforming other ML algorithms. In conclusion, the Barcelona Clinic Liver Cancer, Platelet-Albumin-Bilirubin and Albumin-Bilirubin scores are highly reliable for assessing survival at HCC diagnosis. The XGB-developed model proved to be the most reliable for this purpose compared to the other proposed methods.

Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: Discover study.

BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.

Are bodybuilding and cross-training practices dangerous for promoting orofacial injuries? A scoping review.

Bodybuilding and cross-training exercises bring health benefits. However, orofacial injuries can occur during practice. This study aimed to map, analyze, interpret, and synthesize data from studies on the main orofacial injuries resulting from bodybuilding and cross-training practices. This scoping review followed the Joanna Briggs Institute and PRISMA-ScR methods, with high-sensitivity searches in PubMed, Web of Science, Scopus, ScienceDirect, Embase, Virtual Health Library and the Google Scholar. Original scientific articles published up to May 2024 were included, which evaluated the presence of self-reported or professionally diagnosed orofacial injuries by bodybuilding and cross-training practitioners aged 18 years or older. Literature reviews, editorials, and guidelines were excluded. Tables and figures were used to map and summarize the results. Out of 30.485 potentially eligible articles, four were included. The main orofacial injuries identified in both bodybuilding and cross-training practitioners were dental damage (n = 4), temporomandibular joint (TMJ) disorders (n = 3), and traumas to oral soft tissues (n = 2) and facial soft tissues (n = 2). Dental damage and TMJ disorders were the most prevalent conditions among bodybuilding and cross-training practitioners. Therefore, dental damage and TMJ disorders were the most prevalent conditions among bodybuilding and cross-training practitioners. However, further prospective studies with more in-depth methodological designs and fewer biases are necessary.

Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome.

BACKGROUND: The host cellular immune response associated with two treatments for post-kala-azar dermal leishmaniasis (PKDL) - paromomycin plus miltefosine (Arm 1), and liposomal amphotericin B plus miltefosine (Arm 2) - was examined in Sudanese patients before treatment (D0), at the end of treatment (D42), and during the post-treatment period (D180). METHODS: Whole blood samples were stimulated with soluble Leishmania antigen for 24 h (whole blood assay [WBA]) and the concentrations of Th1/Th2/Th17-associated cytokines, IP-10, PDL-1 and granzyme B were determined. RESULTS: The Arm 1 treatment (98.2% cure rate) induced a Th1/Th2/Th17 response, while the Arm 2 treatment (80% cure rate) induced a Th1/Th2 response. Five Arm 2 patients relapsed and showed lower IFN-γ, TNF and IL-1ß concentrations at D0 than non-relapsers in this Arm. In patients with low-IFN-γ-production at D0, Arm 1 treatment led to a better host immune response and clinical outcome than Arm 2 treatment. CONCLUSIONS: A Th1/Th2/Th17 response was associated with a higher cure rate. Patients with low IFN-γ, TNF and IL-1ß before treatment are more likely to relapse if they undergo Arm 2-type treatment. Determining IFN-γ, TNF and IL-10 levels prior to treatment could help predict patients at higher risk of relapse/recovery from PKDL. TRIAL REGISTRATION: ClinicalTrials.gov NCT03399955, Registered 17 January 2018, https://clinicaltrials.gov/study/ NCT03399955.

High economic inequality is linked to greater moralization.

Throughout the 21st century, economic inequality is predicted to increase as we face new challenges, from changes in the technological landscape to the growing climate crisis. It is crucial we understand how these changes in inequality may affect how people think and behave. We propose that economic inequality threatens the social fabric of society, in turn increasing moralization-that is, the greater tendency to employ or emphasize morality in everyday life-as an attempt to restore order and control. Using longitudinal data from X, formerly known as Twitter, our first study demonstrates that high economic inequality is associated with greater use of moral language online (e.g. the use of words such as "disgust", "hurt", and "respect'). Study 2 then examined data from 41 regions around the world, generally showing that higher inequality has a small association with harsher moral judgments of people's everyday actions. Together these findings demonstrate that economic inequality is linked to the tendency to see the world through a moral lens.

Emotional intelligence and neurocognition profiles in first-episode psychosis: A two-year follow-up study.

Emotional intelligence (EI) and neurocognition (NC) impairments are common in first-episode psychosis (FEP), yet their evolution over time remains unclear. This study identified patient profiles in EI and NC performance in FEP. 98 adult FEP patients and 128 healthy controls (HCs) were tested on clinical, functional, EI, and NC variables at baseline and two-year follow-up (FUP). A repeated-measures ANOVA compared the effects of group (patients and HCs) and time on EI. Significant EI improvements were observed in both groups. Four groups were created based on NC and EI performance at baseline and FUP in patients: impairment in NC and EI, impairment in NC only, impairment in EI only, and no impairment. At FUP, patients impaired in NC and EI showed less cognitive reserve (CR), greater negative and positive symptoms, and poorer functional outcomes. At FUP, three group trajectories were identified: (I) maintain dual impairment (II) maintain no impairment or improve, (III) maintain sole impairment or worsen. The maintain dual impairment group had the lowest levels of CR. EI and NC impairments progress differently in FEP. Greater CR may protect against comorbid EI/NC impairment. Identifying these patient characteristics could contribute to the development of personalised interventions.

Synergistic Enhancement of Chemotherapy-Induced Cell Death and Antitumor Efficacy against Tumoral T-Cell Lymphoblasts by IMMUNEPOTENT CRP.

T-cell malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), present significant challenges to treatment due to their aggressive nature and chemoresistance. Chemotherapies remain a mainstay for their management, but the aggressiveness of these cancers and their associated toxicities pose limitations. Immunepotent CRP (ICRP), a bovine dialyzable leukocyte extract, has shown promise in inducing cytotoxicity against various cancer types, including hematological cancers. In this study, we investigated the combined effect of ICRP with a panel of chemotherapies on cell line models of T-ALL and T-LBL (CEM and L5178Y-R cells, respectively) and its impact on immune system cells (peripheral blood mononuclear cells, splenic and bone marrow cells). Our findings demonstrate that combining ICRP with chemotherapies enhances cytotoxicity against tumoral T-cell lymphoblasts. ICRP + Cyclophosphamide (CTX) cytotoxicity is induced through a caspase-, reactive oxygen species (ROS)-, and calcium-dependent mechanism involving the loss of mitochondrial membrane potential, an increase in ROS production, and caspase activation. Low doses of ICRP in combination with CTX spare non-tumoral immune cells, overcome the bone marrow-induced resistance to CTX cell death, and improves the CTX antitumor effect in vivo in syngeneic Balb/c mice challenged with L5178Y-R. This led to a reduction in tumor volume and a decrease in Ki-67 proliferation marker expression and the granulocyte/lymphocyte ratio. These results set the basis for further research into the clinical application of ICRP in combination with chemotherapeutic regimens for improving outcomes in T-cell malignancies.

Effects of SRI-32743, a Novel Quinazoline Structure-Based Compound, on HIV-1 Tat and Cocaine Interaction with Norepinephrine Transporter.

Prolonged exposure to HIV-1 transactivator of transcription (Tat) protein dysregulates monoamine transmission, a physiological change implicated as a key factor in promoting neurocognitive disorders among people living with HIV. We have demonstrated that in vivo expression of Tat in Tat transgenic mice decreases dopamine uptake through both dopamine transporter (DAT) and norepinephrine transporter (NET) in the prefrontal cortex. Further, our novel allosteric inhibitor of monoamine transporters, SRI-32743, has been shown to attenuate Tat-inhibited dopamine transport through DAT and alleviates Tat-potentiated cognitive impairments. The current study reports the pharmacological profiles of SRI-32743 in basal and Tat-induced inhibition of human NET (hNET) function. SRI-32743 exhibited less affinity for hNET binding than desipramine, a classical NET inhibitor, but displayed similar potency for inhibiting hDAT and hNET activity. SRI-32743 concentration-dependently increased hNET affinity for [3H]DA uptake but preserved the Vmax of dopamine transport. SRI-32743 slowed the cocaine-mediated dissociation of [3H]Nisoxetine binding and reduced both [3H]DA and [3H]MPP+ efflux but did not affect d-amphetamine-mediated [3H]DA release through hNET. Finally, we determined that SRI-32743 attenuated a recombinant Tat1-86-induced decrease in [3H]DA uptake via hNET. Our findings demonstrated that SRI-32743 allosterically disrupts the recombinant Tat1-86-hNET interaction, suggesting a potential treatment for HIV-infected individuals with concurrent cocaine abuse.

Aplicabilidade de protocolo odontológico de assistência materno-infantil na atenção básica à saúde / Applicability of a maternal and child dental care protocol in basic health care / Aplicabilidad de un protocolo dental de atención materno-infantil en la atención básica de salud

A atenção materno-infantil enfrenta diversos desafios na assistência odontológica. Assim, este estudo teve por objetivo desenvolver e analisar a aplicabilidade de um Protocolo Odontológico de Assistência Materno-Infantil (POAMI) em uma unidade básica de saúde do município de Mossoró/RN. Trata-se de um estudo transversal desenvolvido com trinta gestantes de fevereiro a dezembro de 2021. Inicialmente foram aplicados na primeira consulta os questionários "Investigação do Conhecimento das Gestantes sobre sua Saúde Bucal e a do seu Bebê" (ICGSBB) e o Oral Health Impact Profile (OHIP-14). Em seguida, o POAMI foi aplicado em consultas agendadas e na última consulta o questionário ICGSBB foi reaplicado. Observou-se na primeira consulta que apenas 3,33% (n=1) das gestantes tinham conhecimentos sobre a doença periodontal (27,27% (n=6) na última consulta), 10,34% (n=3) indicavam o uso do creme dental com flúor (95,45% (n=21) na última consulta) e 55,17% (n=16) da fralda molhada para higiene bucal do bebê (100% (n=22) na última consulta). Na avaliação do OHIP-14, 23,33% (n=7) das gestantes estão classificadas dentro do nível "Médio Impacto". O POAMI demonstrou ser aplicável na atenção básica e eficaz na melhoria dos conhecimentos das gestantes, no aumento considerável da cobertura e acesso, e na motivação de boas práticas de higiene oral.

Maternal and child care faces several challenges in dental care. This study aimed to develop and analyze the applicability of a Maternal and Child Dental Care Protocol in a basic health unit in Mossoró/RN. This cross-sectional study involved 30 pregnant women from February to December 2021. Initially, the "Investigação do Conhecimento das Gestantes sobre sua Saúde Bucal e a do seu Bebê" (ICGSBB) and the Oral Health Impact Profile (OHIP-14) questionnaires were applied in their first consultation. The protocol was then applied in scheduled consultations, and the ICGSBB questionnaire was reapplied in the last consultation. In the first consultation, only 3.33% (n=1) of the pregnant women had knowledge about periodontal disease (27.27% (n=6) in the last consultation), 10.34% (n=3) indicated the use of fluoride toothpaste (95.45% (n=21) in the last consultation), and 55.17% (n=16) knew to use a wet diaper for the oral hygiene of their children (100% (n=22) in the last consultation). The OHIP-14 evaluation showed that 23.33% (n=7) of the pregnant women fell within its "medium impact" level. The protocol proved to be applicable in basic care, effectively improving pregnant women's knowledge, increasing coverage and access, and motivating good oral hygiene.

La atención materno-infantil enfrenta desafíos en la atención dental. El objetivo de este estudio fue desarrollar y analizar la aplicabilidad de un Protocolo Dental de Atención Materno-Infantil (POAMI) en una unidad básica de salud en Mossoró (Rio Grande do Norte, Brasil). Se trató de un estudio transversal con 30 mujeres embarazadas, en el período de febrero a diciembre de 2021. En la primera consulta, se aplicaron los cuestionarios Investigación de los Conocimientos de las Embarazadas sobre su Salud Bucodental y la de su Bebé (ICGSBB) y el Oral Health Impact Profile (OHIP-14). Luego, el protocolo se aplicó en las consultas, y el cuestionario ICGSBB se volvió a aplicar en la última consulta. En la primera consulta, solo el 3,33% (n=1) de las embarazadas tenían conocimientos sobre enfermedad periodontal (27,27%, n=6, en la última consulta), el 10,34% (n=3) de las participantes reportaron usar pasta dental con flúor (95,45%, n=21, en la última consulta) y el 55,17% (n=16) utilizaban pañal húmedo para la higiene bucal del bebé (100%, n= 22, en la última consulta). En la evaluación del OHIP-14, el 23,33% (n=7) de las embarazadas se clasificaron en el nivel "Impacto Medio". El protocolo demostró ser aplicable debido a la mejora efectiva de los conocimientos de las embarazadas, aumentando la cobertura y el acceso, y motivando buenas prácticas de higiene bucal.

Transcriptome Analysis of Stigmas of Vicia faba L. Flowers.

Pollination in angiosperms depends on complex communication between pollen grains and stigmas, classified as wet or dry, depending on the presence or absence of secretions at the stigma surface, respectively. In species with wet stigma, the cuticle is disrupted and the presence of exudates is indicative of their receptivity. Most stigma studies are focused on a few species and families, many of them with self-incompatibility systems. However, there is scarce knowledge about the stigma composition in Fabaceae, the third angiosperm family, whose stigmas have been classified as semidry. Here we report the first transcriptome profiling and DEGs of Vicia faba L. styles and stigmas from autofertile (flowers able to self-fertilize in the absence of manipulation, whose exudate is released spontaneously) and autosterile (flowers that need to be manipulated to break the cuticle and release the exudates to be receptive) inbred lines. From the 76,269 contigs obtained from the de novo assembly, only 45.1% of the sequences were annotated with at least one GO term. A total of 115,920, 75,489, and 70,801 annotations were assigned to Biological Process (BP), Cellular Component (CC), and Molecular Function (MF) categories, respectively, and 5918 differentially expressed genes (DEGs) were identified between the autofertile and the autosterile lines. Among the most enriched metabolic pathways in the DEGs subset were those related with amino acid biosynthesis, terpenoid metabolism, or signal transduction. Some DEGs have been related with previous QTLs identified for autofertility traits, and their putative functions are discussed. The results derived from this work provide an important transcriptomic reference for style-stigma processes to aid our understanding of the molecular mechanisms involved in faba bean fertilization.

Millard-Gubler Syndrome in a Patient with Preeclampsia. Case Report and Review of Combined Intra- and Extra-Axial Facial and Abducens Nerve Injuries.

Millard-Gubler syndrome is a pontine syndrome caused by a lesion in the lower pons region. It is characterised by ipsilateral facial paralysis and VI paresis and contralateral brachiocrural palsy. We present the case of a female patient, G4P2A1, at 21 weeks of gestation, with preeclampsia, complaints of blurred vision, diplopia, and right hemiparesis, in whom a clinical diagnosis of Millard-Gubler syndrome was made. Neuroimaging showed an intraparenchymal haemorrhage towards the central portion of the bulbopontine junction. An extensive aetiological study was carried out to determine the cause of the hypertensive disorder syndrome during pregnancy. The patient improved satisfactorily from the neurological deficit after delivery of an early stillbirth.

Prognostic Impact of Metabolic Syndrome and Steatotic Liver Disease in Hepatocellular Carcinoma Using Machine Learning Techniques.

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently represents the predominant cause of chronic liver disease and is closely linked to a significant increase in the risk of hepatocellular carcinoma (HCC), even in the absence of liver cirrhosis. In this retrospective multicenter study, machine learning (ML) methods were employed to investigate the relationship between metabolic profile and prognosis at diagnosis in a total of 219 HCC patients. The eXtreme Gradient Boosting (XGB) method demonstrated superiority in identifying mortality predictors in our patients. Etiology was the most determining prognostic factor followed by Barcelona Clinic Liver Cancer (BCLC) and Eastern Cooperative Oncology Group (ECOG) classifications. Variables related to the development of hepatic steatosis and metabolic syndrome, such as elevated levels of alkaline phosphatase (ALP), uric acid, obesity, alcohol consumption, and high blood pressure (HBP), had a significant impact on mortality prediction. This study underscores the importance of metabolic syndrome as a determining factor in the progression of HCC secondary to MASLD. The use of ML techniques provides an effective tool to improve risk stratification and individualized therapeutic management in these patients.

Coumarin/ß-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing.

Coumarins have great pharmacotherapeutic potential, presenting several biological and pharmaceutical applications, like antibiotic, fungicidal, anti-inflammatory, anticancer, anti-HIV, and healing activities, among others. These molecules are practically insoluble in water, and for biological applications, it became necessary to complex them with cyclodextrins (CDs), which influence their bioavailability in the target organism. In this work, we studied two coumarins, and it was possible to conclude that there were structural differences between 4,7-dimethyl-2H-chromen-2-one (DMC) and 7-methoxy-4-methyl-2H-chromen-2-one (MMC)/ß-CD that were solubilized in ethanol, frozen, and lyophilized (FL) and the mechanical mixtures (MM). In addition, the inclusion complex formation improved the solubility of DMC and MMC in an aqueous medium. According to the data, the inclusion complexes were formed and are more stable at a molar ratio of 2:1 coumarin/ß-CD, and hydrogen bonds along with π-π stacking interactions are responsible for the better stability, especially for (MMC)2@ß-CD. In vivo wound healing studies in mice showed faster re-epithelialization and the best deposition of collagen with the (DMC)2@ß-CD (FL) and (MMC)2@ß-CD (FL) inclusion complexes, demonstrating clearly that they have potential in wound repair. Therefore, (DMC)2@ß-CD (FL) deserves great attention because it presented excellent results, reducing the granulation tissue and mast cell density and improving collagen remodeling. Finally, the protein binding studies suggested that the anti-inflammatory activities might exert their biological function through the inhibition of MEK, providing the possibility of development of new MEK inhibitors.

Comparing the Proteomic Profiles of Extracellular Vesicles Isolated using Different Methods from Long-term Stored Plasma Samples.

BACKGROUND: The lack of standardized protocols for isolating extracellular vesicles (EVs), especially from biobank-stored blood plasma, translates to limitations for the study of new biomarkers. This study examines whether a combination of current isolation methods could enhance the specificity and purity of isolated EVs for diagnosis and personalized medicine purposes. RESULTS: EVs were isolated from healthy human plasma stored for one year by ultracentrifugation (UC), size exclusion chromatography (SEC), or SEC and UC combined (SEC + UC). The EV isolates were then characterized by transmission electron microscopy imaging, nanoparticle tracking analysis (NTA) and western blotting. Proteomic procedures were used to analyze protein contents. The presence of EV markers in all isolates was confirmed by western blotting yet this analysis revealed higher albumin expression in EVs-UC, suggesting plasma protein contamination. Proteomic analysis identified 542 proteins, SEC + UC yielding the most complex proteome at 364 proteins. Through gene ontology enrichment, we observed differences in the cellular components of EVs and plasma in that SEC + UC isolates featured higher proportions of EV proteins than those derived from the other two methods. Analysis of proteins unique to each isolation method served to identify 181 unique proteins for the combined approach, including those normally appearing in low concentrations in plasma. This indicates that with this combined method, it is possible to detect less abundant plasma proteins by proteomics in the resultant isolates. CONCLUSIONS: Our findings reveal that the SEC + UC approach yields highly pure and diverse EVs suitable for comprehensive proteomic analysis with applications for the detection of new biomarkers in biobank-stored plasma samples.

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.