Abernethy syndrome as a cause of liver transplantation.

Congenital portosystemic shunts are rare abnormalities in which blood flow from the liver is diverted to the systemic circulation. We would like to present the case of a 48-year-old male, during his neurological follow-up he was diagnosed with a congenital intrahepatic portosystemic shunt. Embolization of the portosystemic communicating veins was attempted on two occasions, but without success. Due to the poor clinical course, the patient was presented to our transplant committee and a liver transplant was decided upon.

Systemic inflammation biomarkers during angioedema attacks in hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks. Methods: Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured. Results: Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for D-dimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema. Conclusion: The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE.

Localized pemphigus vulgaris on scalp: an atypical presentation.

We present two middle-aged patients with pruritic, crusted scalp erosions. Skin biopsy showed epidermal acantholysis with IgG and C3 intercellular deposits on direct immunofluorescence, leading to the diagnosis of localized pemphigus vulgaris. Resolution of the lesions without relapse occurred after low doses of oral prednisone and intralesional triamcinolone acetonide.

Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration.

Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN+ long-term repopulating HSCs (LT-HSCs; CD150+CD48-LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN- LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN+ LT-HSCs were more quiescent compared to EMCN- LT-HSCs. Emcn-/- and Emcn+/+ mice displayed comparable steady-state hematopoiesis, as well as frequencies, transcriptional programs, and long-term multi-lineage repopulating capacity of their LT-HSCs. Complementary functional analyses further revealed increased cell cycle entry upon treatment with 5-fluorouracil and reduced granulocyte colony-stimulating factor (GCSF) mobilization of Emcn-/- LT-HSCs, demonstrating that EMCN expression by LT-HSCs associates with quiescence in response to hematopoietic stress and is indispensable for effective LT-HSC mobilization. Transplantation of wild-type bone marrow cells into Emcn-/- or Emcn+/+ recipients demonstrated that EMCN is essential for endothelial cell-dependent maintenance/self-renewal of the LT-HSC pool and sustained blood cell production post-transplant.

The Structural Biology of Catalase Evolution.

Catalases are essential enzymes for removal of hydrogen peroxide, enabling aerobic and anaerobic metabolism in an oxygenated atmosphere. Monofunctional heme catalases, catalase-peroxidases, and manganese catalases, evolved independently more than two billion years ago, constituting a classic example of convergent evolution. Herein, the diversity of catalase sequences is analyzed through sequence similarity networks, providing the context for sequence distribution of major catalase families, and showing that many divergent catalase families remain to be experimentally studied.

Prenatal Screening for Chagas Disease in the Province of Guadalajara, Spain.

Introduction Chagas disease is caused by the protozoan Trypanosoma cruzi. It is endemic in 21 countries in Central and South America. Spain is the only nonendemic country with the highest number of Chagas disease cases outside the Americas. The only transmission mechanism in Spain is vertical transmission. Materials and methods We reviewed the records of pregnant women from endemic countries who underwent prenatal care at the Hospital Universitario de Guadalajara, from January 1, 2009, to December 31, 2022, to determine the rate of Chagas disease screening and vertical transmission. Results Out of a total of 1,681 pregnant women from endemic countries, prenatal screening was conducted on 316 (18.7%) of them. According to our study, the prevalence of the disease in the population of pregnant women from endemic countries is 0.95% with a 95% confidence interval (ranging from 0.32% to 2.75%), with three out of the 316 screened women testing positive for the disease. All positive cases were among Bolivian women. Vertical transmission was not observed in any of the cases. However, because of the small sample size, this study cannot conclusively determine the vertical transmission rate in the province of Guadalajara. Conclusions Implementing regulated prenatal screening protocols for Chagas disease at regional or national levels is necessary to increase the rate of prenatal screening. Additionally, increasing awareness of this condition among healthcare professionals and at-risk populations could further improve prenatal screening rates and treatment adherence.

Time-encoded ASL reveals lower cerebral blood flow in the early AD continuum.

INTRODUCTION: Cerebral blood flow (CBF) is reduced in cognitively impaired (CI) Alzheimer's disease (AD) patients. We checked the sensitivity of time-encoded arterial spin labeling (te-ASL) in measuring CBF alterations in individuals with positive AD biomarkers and associations with relevant biomarkers in cognitively unimpaired (CU) individuals. METHODS: We compared te-ASL with single-postlabel delay (PLD) ASL in measuring CBF in 59 adults across the AD continuum, classified as CU amyloid beta (Aß) negative (-), CU Aß positive (+), and CI Aß+. We sought associations of CBF with biomarkers of AD, cerebrovascular disease, synaptic dysfunction, neurodegeneration, and cognition in CU participants. RESULTS: te-ASL was more sensitive at detecting CBF reduction in the CU Aß+ and CI Aß+ groups. In CU participants, lower CBF was associated with altered biomarkers of Aß, tau, synaptic dysfunction, and neurodegeneration. DISCUSSION: CBF reduction occurs early in the AD continuum. te-ASL is more sensitive than single-PLD ASL at detecting CBF changes in AD. HIGHLIGHTS: Lower CBF can be detected in CU subjects in the early AD continuum. te-ASL is more sensitive than single-PLD ASL at detecting CBF alterations in AD. CBF is linked to biomarkers of AD, synaptic dysfunction, and neurodegeneration.

Relative Acceleration and Maximum Velocity in Rugby Players According to Age Category and Playing Position.

ABSTRACT: Zabaloy, S, Freitas, TT, Alcaraz, PE, Gálvez-González, J, Pereira, LA, Comyns, T, Loturco, I, and Healy, R. Relative acceleration and maximum velocity in rugby players according to age category and playing position. J Strength Cond Res XX(X): 000-000, 2024-This study aimed to: (a) assess the intrasession reliability of the acceleration time constant (i.e., τ) and τ-derived measures; (b) analyze the influence of τ and maximum velocity (Vmax) on 40-m sprint performance and to compare various sprint-related outcomes among rugby players from different playing positions and age categories; and (c) explore the associations between τ and several sprint performance metrics. A total of 300 male rugby players volunteered to participate in this study and were divided into age categories (i.e., under-14 [U14]: n = 91, age: 12.6 ± 0.5 years; under-16 [U16]: n = 85, age: 14.8 ± 0.5 years; under-18 [U18]: n = 75, age: 16.6 ± 0.5 years; and Seniors: n = 49, age: 24.2 ± 4.1 years). The results demonstrated good to excellent reliability for all measured parameters (intraclass correlation coefficient >0.75 and coefficient of variation <9.0%). Younger players (i.e., U14 and U16) displayed lower τ values (effect size: moderate to large; p < 0.02) compared with their older peers (i.e., U18 and Seniors), regardless of their playing position. Moreover, τ was associated with sprint performance metrics at varying levels of correlations (Rho: small to almost perfect; p < 0.001). In conclusion, younger players exhibited lower τ values than their older counterparts, irrespective of their playing positions. The model employed in this study demonstrated its accuracy in assessing several key sprint performance metrics, offering insights that can enhance sprint training programs for rugby players, which can be based on the associations observed among these different variables.

Examining tactical sprint actions and distribution among playing positions attending to match status in soccer: Implications for specific training.

The study aimed to analyze the tactical sprint actions performed by Spanish professional soccer players, considering their playing positions and the match status at the time of each action. Thirty-two Spanish male professional soccer players from a LaLiga Spanish Second Division (LaLiga SmarthBank) team participated in this study. Actions above 85% of the players' maximum velocity during 42 official matches were collected by an optical tracking system ChyronHego® and were synchronized using Mediacoach software (LaLiga, Madrid, Spain). Then, actios were analyzed trough an observation instrument designed to assess the type of tactical action performed by players. Central defenders (CD) and wide defenders (WD) were mainly involved in recovery runs. Central midfielders (CM) also frequently performed recovery runs and pressing actions. Wide midfielders (WM) were often engaged in runs in behind/penetrate actions, while forwards (F) had a diverse range of sprint actions, including pressing, runs in behind/penetrate, and breaking into the box. It was observed that F performed fewer chase actions than expected. On the other hand, CD, WD, and CM engaged in a greater number of recovery run actions than expected. CD also performed more close down/interception actions than expected, while CM, WM, and F performed fewer close down/interception actions than expected. When their team was losing, WM performed more recovery run actions than expected. CM made more runs with the ball when their team was winning CD showed a higher frequency of breaks into the box when their team was winning. These findings provide valuable information regarding the tactical aspects of sprinting in soccer, facilitating the design of specific training tasks that not only address the physical demands associated with each playing position but also considering the tactical context in which sprints occur.

Development of a population pharmacokinetic model for the novel long-acting injectable antipsychotic risperidone ISM®.

AIMS: The aims of this study were to develop a population pharmacokinetic (PK) model for risperidone ISM® and to investigate the relationships between active moiety exposure, as described by apparent clearance (CL40), and several covariates using all data from five clinical studies. METHODS: A population PK model was developed using active moiety concentrations from a study in healthy volunteers and two studies in patients with schizophrenia. Data from a comparative bioavailability study in medically stable patients and a Phase III study in patients with acute exacerbation of schizophrenia were then incorporated, using empirical Bayesian feedback and model refinement in NONMEM. Finally, covariate analysis was performed on CL40. RESULTS: The final model adequately described the pharmacokinetics of 6288 active moiety concentrations in 17 healthy volunteers and 430 patients with schizophrenia. This one-compartment disposition model had a complex absorption process, combining a small amount immediately entering the central active moiety compartment, two first-order absorption processes and a combined zero-order and first order process, with first-order elimination from the central compartment. Significant covariates on CL40 were BMI and sex. Goodness-of-fit (GOF) plots and visual predictive checks (VPC) confirmed acceptable description of the data. CONCLUSIONS: The population PK model adequately described active moiety concentrations from five clinical studies after risperidone ISM® administration. Relationships between active moiety exposure and covariates were defined in order to facilitate simulations for future studies. The model showed that risperidone ISM® rapidly achieves therapeutic plasma levels within the first hours after the first injection that are maintained sustainedly throughout the whole dosing interval following once-monthly gluteal injections of 100 mg and 75 mg.

Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.

OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Influence of the External Workload on Calf Muscle Strain Injuries in Professional Football Players: A Pilot Study.

BACKGROUND: The influence of external workload variables on the development of calf muscle strainsin football players has not been previously explored. HYPOTHESIS: Overloaded players would have an increased risk of calf muscle strain injury. STUDY DESIGN: Prospective observational study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 41 professional football players from 1 team were monitored for 2 consecutive seasons. Total distance covered (TD), and distances covered at high-intensity running, high sprint running, low (LACC) and high (HACC) acceleration, low (LDEC) and high (HDEC) deceleration, and at high metabolic load distance (HMLD) were monitored with GPS units. Accumulated players' external workload in the week before injury was compared with the weekly mean value of the 6 weeks before injury occurred for each player. RESULTS: Ten players (24.3%) suffered 16 calf muscle strain injuries (3.1 injuries per 1000 hours of match play; 0.5 injuries per 1000 hours of training exposure). Players with a calf muscle injury were older (p = 0.03), with higher body weight (p = 0.01) and height (p = 0.03). Injured players displayed substantially higher total training volume (p < 0.01), TD (p < 0.01), LACC (p < 0.01), LDEC (p < 0.01), HACC (p < 0.01), HDEC (p < 0.01), and HMLD (p = 0.03) in the week before injury, in comparison with the mean values of these variables in the 6 weeks before injury. CONCLUSION: A week with a higher-than-habitual external workload might increase the risk of calf muscle strain injury in professional football players. Calf muscle injuries were preceded by a week with unusually high workloads associated with accelerating and decelerating distances and higher training volumes. CLINICAL RELEVANCE: Monitoring external workload indicators may be helpful in determine players with a higher risk of calf muscle strain injury due to excessive workload during training/competition.

Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries.

Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.

Proposal and Validation of a Measurement Scale of the Acceptance of Ultra-Processed Food Products.

Today, there is an increasing consumption of ultra-processed food products (UPFs), while more healthy options are available; however, there is no scale available that can adequately measure this phenomenon. In this context, the present study aims to develop and validate a measurement scale of the consumers' acceptance of ultra-processed food products. Research data (n = 478) were analyzed using Exploratory Factor Analysis (EFA), followed by a Confirmatory Factor Analysis (CFA). The results confirm the validity of the proposed measurement scale comprising nine factors: the quality of ultra-processed food products, ability to save time, low affordable price, effortless preparation, convenience, hedonic nature, marketing strategies, satisfaction and purchase intention. The present study makes a noticeable contribution to food marketing, and food companies could consider these factors to design and commercialize ultra-processed foods.