Biomarkers at the Individual and Biochemical Level: Effects of Pure and Formulated Lambda-Cyhalothrin in Boana pulchella Tadpoles (Duméril and Bibron, 1841).

We compared the effects of lambda-cyhalothrin as the pure active ingredient and as a formulated product (Zero®), on the larval stage of the autochthonous species Boana pulchella. We evaluated ecotoxicological endpoints, behavioral and developmental alterations, and the biochemical detoxifying, neurotoxic, and oxidative stress responses, covering a wide concentration range from environmental to high application levels. Both pyrethroid preparations displayed similar ecotoxicity (median lethal concentration of ~0.5 mg/L), with the lethal effect of Zero® being more pronounced than that of the active ingredient. Sublethal behavioral alterations in natatory activity were observed at 1000 times lower concentrations, indicating the ecological hazard of tadpole exposure to this pyrethroid at environmentally relevant concentrations. Biochemical endpoints in B. pulchella larvae showed significant responses to lambda-cyhalothrin in the ng/L range; these responses were different for the pure or the formulated product, and they were variable at higher concentrations. Principal components analysis confirmed the prevalence of biochemical responses as early endpoints at the lowest lambda-cyhalothrin concentrations; the Integrated Biomarker Response Index proportionally increased with pyrethroid concentration in a similar way for the pure and the formulated products. We conclude that lambda-cyhalothrin is of concern from an environmental perspective, with particular emphasis on autochthonous anuran development. The battery of biochemical biomarkers included in our study showed a consistent integrated biomarker response, indicating that this is a potent tool for monitoring impacts on amphibians. Environ Toxicol Chem 2024;00:1-11. © 2024 SETAC.

Free-Standing, Water-Resistant, and Conductivity-Enhanced PEDOT:PSS Films from In Situ Polymerization of 3-Hydroxymethyl-3-Methyl-Oxetane.

Free-standing films based on conducting polymers, such as poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS), offer many benefits over traditional metal electrodes for applications in flexible electronics. However, to ensure structural integrity when contacting aqueous environments and high levels of electrical conductivity, solution-processed polymers require additives that act as crosslinking agents and conductivity enhancers. In this work, a new approach is presented to fabricate water-resistant free-standing films of PEDOT:PSS and simultaneously increase their conductivity, using an oxetane compound as an additive. It is shown that at moderate temperatures, oxetane polymerizes within the PEDOT:PSS acidic medium, forming hydroxymethyl-substituted polyether compounds that form a network upon crosslinking with PSS. The polymer composite films show self-sustainability, structural stability in aqueous environments, and enhanced conductivity. Finally, the potential of the free-standing films as health-monitoring electrodes, specifically for human electrocardiography, is explored.

Tribomechanical Properties of PVA/Nomex® Composite Hydrogels for Articular Cartilage Repair.

Due to the increasing prevalence of articular cartilage diseases and limitations faced by current therapeutic methodologies, there is an unmet need for new materials to replace damaged cartilage. In this work, poly(vinyl alcohol) (PVA) hydrogels were reinforced with different amounts of Nomex® (known for its high mechanical toughness, flexibility, and resilience) and sterilized by gamma irradiation. Samples were studied concerning morphology, chemical structure, thermal behavior, water content, wettability, mechanical properties, and rheological and tribological behavior. Overall, it was found that the incorporation of aramid nanostructures improved the hydrogel's mechanical performance, likely due to the reinforcement's intrinsic strength and hydrogen bonding to PVA chains. Additionally, the sterilization of the materials also led to superior mechanical properties, possibly related to the increased crosslinking density through the hydrogen bonding caused by the irradiation. The water content, wettability, and tribological performance of PVA hydrogels were not compromised by either the reinforcement or the sterilization process. The best-performing composite, containing 1.5% wt. of Nomex®, did not induce cytotoxicity in human chondrocytes. Plugs of this hydrogel were inserted in porcine femoral heads and tested in an anatomical hip simulator. No significant changes were observed in the hydrogel or cartilage, demonstrating the material's potential to be used in cartilage replacement.

Use of rainbow trout skin treated with glutaraldehyde as a mesh for abdominal hernioplasty in rats.

PURPOSE: To test the use of rainbow trout skin as a surgical mesh in abdominal hernioplasties in rats. METHODS: The experiment involved 20 Wistar rats receiving implants of trout skin processed for disinfection in 0.5% glutaraldehyde and preserved in 100% glycerin. The animals were divided into four groups, divided at 7, 15, 30, and 90 days postoperatively. Clinical and infrared thermography evaluations were performed, and after euthanasia, assessments of adhesion formations and sample collection for histological evaluation were conducted. RESULTS: The implant was observed to be intact, ensuring the integrity of the abdominal wall, support for the viscera, and normal mobility for the rats for up to 90 days. Low rates of clinical alterations were observed, with an intense inflammatory reaction up to day 7, chronic inflammation and the onset of angiogenesis at day 15, and a low inflammatory reaction with collagenous infiltrate and fibrosis at day 30. At day 90, the implants showed a collagenous and fibrotic infiltrate with a minimal inflammatory infiltrate. CONCLUSIONS: The surgical mesh of trout skin performed well, making it a potential alternative for surgical procedures in muscle aponeurotic corrections in the abdominal wall.

Mechanisms Mediating the Combined Toxicity of Paraquat and Maneb in SH-SY5Y Neuroblastoma Cells.

Epidemiological and experimental studies have demonstrated that combined exposure to the pesticides paraquat (PQ) and maneb (MB) increases the risk of developing Parkinson's disease. However, the mechanisms mediating the toxicity induced by combined exposure to these pesticides are not well understood. The aim of this study was to investigate the mechanism(s) of neurotoxicity induced by exposure to the pesticides PQ and MB isolated or in association (PQ + MB) in SH-SY5Y neuroblastoma cells. PQ + MB exposure for 24 and 48 h decreased cell viability and disrupted cell membrane integrity. In addition, PQ + MB exposure for 12 h decreased the mitochondrial membrane potential. PQ alone increased reactive oxygen species (ROS) and superoxide anion generation and decreased the activity of mitochondrial complexes I and II at 12 h of exposure. MB alone increased ROS generation and depleted intracellular glutathione (GSH) within 6 h of exposure. In contrast, MB exposure for 12 h increased the GSH levels, the glutamate cysteine ligase (GCL, the rate-limiting enzyme in the GSH synthesis pathway) activity, and increased nuclear Nrf2 staining. Pretreatment with buthionine sulfoximine (BSO, a GCL inhibitor) abolished the MB-mediated GSH increase, indicating that MB increases GSH synthesis by upregulating GCL, probably by the activation of the Nrf2/ARE pathway. BSO pretreatment, which did not modify cell viability per se, rendered cells more sensitive to MB-induced toxicity. In contrast, treatment with the antioxidant N-acetylcysteine protected cells from MB-induced toxicity. These findings show that the combined exposure of SH-SY5Y cells to PQ and MB induced a cytotoxic effect higher than that observed when cells were subjected to individual exposures. Such a higher effect seems to be related to additive toxic events resulting from PQ and MB exposures. Thus, our study contributes to a better understanding of the toxicity of PQ and MB in combined exposures.

Executive dysfunction and cortical variations among intimate partner violence perpetrators and the association with sexism.

Malfunctioning in executive functioning has been proposed as a risk factor for intimate partner violence (IPV). This is not only due to its effects on behavioral regulation but also because of its association with other variables such as sexism. Executive dysfunctions have been associated with frontal and prefrontal cortical thickness. Therefore, our first aim was to assess differences in cortical thickness in frontal and prefrontal regions, as well as levels of sexism, between two groups of IPV perpetrators (with and without executive dysfunctions) and a control group of non-violent men. Second, we analyzed whether the cortical thickness in the frontal and prefrontal regions would explain sexism scores. Our results indicate that IPV perpetrators classified as dysexecutive exhibited a lower cortical thickness in the right rostral anterior cingulate superior frontal bilaterally, caudal middle frontal bilaterally, right medial orbitofrontal, right paracentral, and precentral bilaterally when compared with controls. Furthermore, they exhibited higher levels of sexism than the rest of the groups. Most importantly, in the brain structures that distinguished between groups, lower thickness was associated with higher sexism scores. This research emphasizes the need to incorporate neuroimaging techniques to develop accurate IPV profiles or subtypes based on neuropsychological functioning.

Platelet transfusions in adult ICU patients with thrombocytopenia: A sub-study of the PLOT-ICU inception cohort study.

BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 109/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 1011 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 1011 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 109/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

Drug to genome to drug: a computational large-scale chemogenomics screening for novel drug candidates against sporotrichosis.

Sporotrichosis is recognized as the predominant subcutaneous mycosis in South America, attributed to pathogenic species within the Sporothrix genus. Notably, in Brazil, Sporothrix brasiliensis emerges as the principal species, exhibiting significant sapronotic, zoonotic and enzootic epidemic potential. Consequently, the discovery of novel therapeutic agents for the treatment of sporotrichosis is imperative. The present study is dedicated to the repositioning of pharmaceuticals for sporotrichosis therapy. To achieve this goal, we designed a pipeline with the following steps: (a) compilation and preparation of Sporothrix genome data; (b) identification of orthologous proteins among the species; (c) identification of homologous proteins in publicly available drug-target databases; (d) selection of Sporothrix essential targets using validated genes from Saccharomyces cerevisiae; (e) molecular modeling studies; and (f) experimental validation of selected candidates. Based on this approach, we were able to prioritize eight drugs for in vitro experimental validation. Among the evaluated compounds, everolimus and bifonazole demonstrated minimum inhibitory concentration (MIC) values of 0.5 µg/mL and 4.0 µg/mL, respectively. Subsequently, molecular docking studies suggest that bifonazole and everolimus may target specific proteins within S. brasiliensis- namely, sterol 14-α-demethylase and serine/threonine-protein kinase TOR, respectively. These findings shed light on the potential binding affinities and binding modes of bifonazole and everolimus with their probable targets, providing a preliminary understanding of the antifungal mechanism of action of these compounds. In conclusion, our research advances the understanding of the therapeutic potential of bifonazole and everolimus, supporting their further investigation as antifungal agents for sporotrichosis in prospective hit-to-lead and preclinical investigations.

Treatment Strategies for Bile Leak Following Pediatric Liver Transplantation.

There are no standard management protocols for the treatment of bile leak (BL) after liver transplantation. The objective of this study is to describe treatment options for BL after pediatric LT. METHODS: Retrospective analysis (January 2010-March 2023). VARIABLES STUDIED: preoperative data, status at diagnosis, and postoperative outcome. Four groups: observation (n = 9), percutaneous transhepatic cholangiography (PTC, n = 38), ERCP (2), and surgery (n = 27). RESULTS: Nine hundred and thirty-one pediatric liver transplantation (859 LDLT and 72 DDT); 78 (8.3%) patients had BL, all in LDLT. The median (IQR) peritoneal bilirubin (PB) level and fluid-to-serum bilirubin ratio (FSBR) at diagnosis was 14.40 mg/dL (8.5-29), and 10.7 (4.1-23.7). Patients who required surgery for treatment underwent the procedure earlier, at a median of 14 days (IQR: 7-19) versus 22 days for PTC (IQR: 15-27, p = 0.002). PB and FSBR were significantly lower in the observation group. In 11 cases, conservative management had resolution of the BL in an average time of 35 days, and 38 patients underwent PTC in a median time of 22 days (15-27). Twenty-seven (34.6%) patients were reoperated as initial treatment for BL in a median time of 17 days (1-108 days); 25 (33%) patients evolved with biliary stricture, 5 (18.5%) after surgery, and 20 (52.6%) after PTC (p = 0.01). CONCLUSION: Patients with BL who were observed presented significantly lower levels of PB and FSBR versus those who underwent PTC or surgery. Patients treated with PTC presented higher rates of biliary stricture during the follow-up.

The effectiveness of negative pressure therapy in burns: scoping review / A efetividade da terapia por pressãonegativa em queimaduras: revisão de escopo / La efectividad de la terapia de presiónnegativa en quemaduras: revisión del alcance

Objetivo: Mapear a produção científica a respeito do uso da terapia de pressão negativa no tratamento de queimaduras, em pacientes adultos e idosos hospitalizados. Método: Revisão de escopo seguindo o método da JBI com busca da produção científica na PubMed, Scientific Electronic Library Online, Biblioteca Virtual de Saúde e Banco de Teses da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior nos meses de março a maio de 2021. Foram incluídos estudos com pacientes adultos e idosos com queimaduras, submetidos à terapia por pressão negativa no hospital. Não houve restrição de idioma, nem período de tempo. Resultados: Foram identificadas 106 publicações e, após o processo de seleção, cinco estudos compuseram a amostra final. Os resultados demonstraram que a aplicação da terapia por pressão negativa em queimaduras constituiu-se como uma ferramenta efetiva na cicatrização de queimaduras térmicas, químicas e elétricas, destacando-se a otimização do tempo de cicatrização, formação de um tecido de granulação saudável, diminuição do edema, redução da infecção, drenagem e monitorização do edema. Conclusão: O tratamento de queimaduras utilizando a pressão negativa tem se mostrado um método efetivo, visto os benefícios que promove no processo cicatricial. Sugere-se que a temática seja mais difundida, aprofundando-se o conhecimento sobre o uso desta tecnologia. (AU)

Objective: To map the scientific production regarding the use of negative pressure wound therapy in burn treatment of hospitalized adult and aged patients. Method: Scope review following the JBI method with a search for scientific production in PubMed, the Scientific Electronic Library Online, the Virtual Health Library, and the Thesis Database of the Coordination for the Improvement of Higher Education Personnel from March to May 2021. Studies with adult and aged burn patients undergoing negative pressure wound therapy in hospitals were included. There was no language or time frame restriction. Results: 106 publications were identified and 5 studies made up the final sample after the selection process. The results demonstrated that applying negative pressure wound therapy to burns was effective in healing thermal, chemical, and electrical burns, esoecially regarding healing time optimization, healthy granulation tissue formation, edema and infection reduction, and edema drainage and monitoring. Conclusion: Burn treatment using negative pressure has proven effective, given the benefits it promotes in the healing process. The theme should be more widely spread to deepen the knowledge about the use of this technology. (AU)

Objetivo: Mapear la producción científica sobre el uso de la terapia de presión negativa en el tratamiento de quemaduras en pacientes adultos y ancianos hospitalizados. Método: Revisión de alcance siguiendo el método JBI con búsqueda de producción científica en PubMed, Biblioteca Científica Electrónica en Línea, Biblioteca Virtual en Salud y Banco de Tesis de la Coordinación para el Perfeccionamiento del Personal de Educación Superior en los meses de marzo a mayo de 2021. Se incluyeron estudios con adultos y pacientes ancianos quemados sometidos a terapia de presión negativa en el hospital. No hubo restricción de idioma ni período de tiempo. Resultados: Se identificaron 106 publicaciones y luego del proceso de selección, 5 estudios conformaron la muestra final. Los resultados demostraron que la aplicación de la terapia de presión negativa en quemaduras constituyó una herramienta eficaz en la curación de quemaduras térmicas, químicas y eléctricas, destacándose la optimización del tiempo de curación, formación de tejido de granulación sano, reducción de edema, reducción de infección, drenaje y seguimiento del edema. Conclusión: El tratamiento de quemaduras mediante presión negativa ha demostrado ser un método efectivo, dados los beneficios que promueve en el proceso de cicatrización. Se sugiere que el tema sea más difundido, profundizando el conocimiento sobre el uso de esta tecnología. (AU)

Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis.

Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have advocated an anomalous gut microbiome as the pathophysiological basis of several psychiatric and neurological conditions. Thus, our knowledge of brain-to-gut-to microbiome communication in this bidirectional axis seems to have been overlooked. This review examines the known mechanisms of the microbiome-to-gut-to-brain axis, highlighting how brain-to-gut-to-microbiome signaling may be key to understanding the cause of disrupted gut microbial communities. We show that brain disorders can alter the function of the brain-to-gut-to-microbiome axis, which will in turn contribute to disease progression, while the microbiome-to gut-to brain direction presents as a more versatile therapeutic axis, since current psychotropic/neurosurgical interventions may have unwanted side effects that further cause disruption to the gut microbiome. A consideration of the brain-to-gut-to-microbiome axis is imperative to better understand how the microbiome-gut-brain axis overall is involved in brain illnesses, and how it may be utilized as a preventive and therapeutic tool.

Knowledge about cervical cancer in young Portuguese women: a cross-sectional study.

Introduction: Health literacy is crucial to adherence to medical interventions in therapeutics, prevention, and diagnosis. The basis for literacy is knowledge. To accomplish the goals for the elimination of cervical cancer, one of the most prevalent and preventable cancers, we must understand the determinants of non-adherence and address them specifically to ensure patients' active participation. Aim: To determine women's knowledge regarding the manifestations of cervical cancer and its prevention. Materials and methods: We conducted a cross-sectional study in an urban population from northern Portugal. Women aged 18 to 30 years were randomly assigned to answer the Cervical Cancer Awareness Measure questionnaire, including questions of knowledge about the causes and symptoms of cervical cancer, prospecting for individual and social-related determinants. Results: The total number of participants was 270, with a mean age of 24.7 years. Knowledge about symptoms scored 5.4 ± 2.6, with a maximum of 12 points, and knowledge about the causes scored 5.7 ± 1.9, with a maximum of 11 points. The correlation between both was 0.334. High education, high socio-economic status, self-perception of one's capacity to recognize symptoms, and knowledge about the HPV vaccine were associated with better knowledge. Discussion: Portuguese women present low knowledge about cervical cancer, potentially affecting their health through exposure to risk situations and non-adherence to routine screening.

Risk of Eating Disorders and Social Desirability among Higher Education Students: Comparison of Nutrition Students with Other Courses.

The transition to college is a period of higher risk of the development of eating disorders, with nutrition/dietetics students representing a group of particular vulnerability. Hence, it is interesting to assess eating disorders, taking into consideration potential sources of bias, including social desirability. Our aims were to compare the risk of eating disorders between students of nutrition/dietetics and those attending other courses and to study potential social desirability biases. A total of 799 higher education students (81.7% females) aged 18 to 27 years old completed a questionnaire assessing the risk of eating disorders (EAT-26) and social desirability (composite version of the Marlowe-Crowne Social Desirability Scale). The proportion of students with a high risk of eating disorders was higher among females (14.5% vs. 8.2%, p = 0.044). Nutrition/dietetics students did not differ from those attending other courses regarding the risk of eating disorders. The social desirability bias when assessing the risk of eating disorders was overall low (EAT-26 total score: r = -0.080, p = 0.024). Social desirability correlated negatively with the Diet (r = -0.129, p < 0.001) and Bulimia and food preoccupation subscales (r = -0.180, p < 0.001) and positively with Oral self-control (r = 0.139, p < 0.001).

The contribution of brain volume to explain autonomous imbalance during recovery from acute stress in batterers.

AIM: Many authors have suggested that intimate partner violence (IPV) perpetrators present an imbalance between both branches of the autonomous nervous system when coping with acute stress. Concretely, there is a predominance of the sympathetic branches over the parasympathetic ones when recovering from stress. This imbalance can be explained by their tendency toward anger rumination, and more concretely, by their focus on thoughts of revenge during this period. Unfortunately, there is a gap in the scientific literature in terms of using magnetic resonance imaging (MRI) techniques to assess which brain structures would explain this tendency of IPV perpetrators when coping with acute stress. METHOD: The main objective of this study was to assess whether the gray matter volume (GMV) of relevant brain structures, signaled in previous scientific literature, moderates the association between thoughts of revenge and sympathetic activation during the recovery period, based on skin conductance levels (SCL) after being exposed to stress, in a group of IPV perpetrators (n = 58) and non-violent men (n = 61). RESULTS: This study highlighted that the GMV of the left nucleus accumbens, right lobules of the cerebellum, and inferior temporal gyrus in IPV perpetrators moderated the association between thoughts of revenge and SCL during the recovery period. Accordingly, the higher the thoughts of revenge, the higher the sympathetic predominance (or higher SCL levels), especially among IPV perpetrators with the lowest GMV of these brain structures. Nonetheless, those variables were unrelated in the control group. CONCLUSIONS: Our study highlights the involvement of certain brain structures and how they explain the tendency of some IPV perpetrators to ruminate anger or, more precisely, to focus on thoughts of revenge when they recover from acute stress. These results reinforce the need to incorporate neuroimaging techniques during screening processes to properly understand how IPV perpetrators deal with stress, which in turn helps target their needs and design concrete intervention modules.

Living Donor Whole and Partial Liver Grafts, Deceased Donor Whole Liver and SPLIT: Outcome Comparison.

BACKGROUND: Currently, graft options for pediatric liver transplantation (PLT) include whole (WL) and partial (P) grafts, in the form of either deceased donor transplantation (DD) or living donor liver transplantation (LD). WL transplants from LD are commonly referred to as domino LT. The objective of this manuscript is to compare the outcomes of PLT performed with each of the available graft options. METHODS: Retrospective cohort study from Jan. 2010 to Dec. 2022. The variables included data on the recipients' preoperative clinical status, intraoperative technical aspects, post-operative complications, and survival studies. There were 4 groups: SPLIT (17), DD-WL (55), LD-WL (824), and LD-P (22). RESULTS: The median age and BW of the recipients was smaller in SPLIT, LD-P, and LD-WL compared to DDT-WL groups. HVOO (HR 15.87, 95% CI 1.89-133.06, P = 0.01), retransplantation (HR 7.94, 95% CI 2.63-24.02, P < 0.01), and malignancies (HR 3.08, 95% CI 1.29-7.37, P = 0.01) were independently associated with decreased patient survival. HAT (HR 27.54, 95% CI 10.44-72.68, P < 0.01) and malignancies (HR 2.42, 95% CI 1.10-5.34, P = 0.03) increased the risk of graft loss. The overall survival in this series was 91.4% (mean follow-up of 74.3 months). Patient and graft survival were not different among groups. CONCLUSION: HAT and malignancies were associated with reduced graft survival. Whole liver from living donors with MSUD presented 100% patient survival at 120 months. Even without statistical differences in survival among the studied groups, LD-P and LD-WL recipients presented a trend towards better outcomes. LEVEL OF EVIDENCE: LEVEL III.

Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensisin vitro infection.

Leishmaniases are infectious-parasitic diseases that impact public health around the world. Antileishmanial drugs presented toxicity and increase in parasitic resistance. Studies with natural products show an alternative to this effect, and several metabolites have demonstrated potential in the treatment of various diseases. Terminalia catappa is a plant species with promising pharmaceutical properties. The objective of this work was to evaluate the therapeutic potential of extracts and fractions of T. catappa on Leishmania amazonensis and investigate the immunomodulatory mechanisms associated with its action. In anti-Leishmania assays, the ethyl acetate fraction exhibited activity against promastigotes (IC50 86.07 ± 1.09 µg/mL) and low cytotoxicity (CC50 517.70 ± 1.68 µg/mL). The ethyl acetate fraction also inhibited the intracellular parasite (IC50 25.74 ± 1.08 µg/mL) with a selectivity index of 20.11. Treatment with T. catappa ethyl acetate fraction did not alter nitrite production by peritoneal macrophages stimulated with L. amazonensis, although there was a decrease in unstimulated macrophages treated at 50 µg/mL (p = 0.0048). The T. catappa ethyl acetate fraction at 100 µg/mL increased TNF-α levels (p = 0.0238) and downregulated HO-1 (p = 0.0030) and ferritin (p = 0.0002) gene expression in L. amazonensis-stimulated macrophages. Additionally, the total flavonoid and ellagic acid content for ethyl acetate fraction was 13.41 ± 1.86 mg QE/g and 79.25 mg/g, respectively. In conclusion, the T. catappa ethyl acetate fraction showed leishmanicidal activity against different forms of L. amazonensis and displayed immunomodulatory mechanisms, including TNF-α production and expression of pro and antioxidant genes.

Improved triamcinolone acetonide-eluting contact lenses based on cyclodextrins and high hydrostatic pressure assisted complexation.

Contact lenses (CLs) constitute an advantageous platform for the topical release of corticosteroids due to their prolonged contact with the eye. However, the lipophilic nature of corticosteroids hampers CLs' ability to release therapeutic amounts. Two approaches to improve loading and release of triamcinolone acetonide (TA) from poly(2-hydroxyethyl methacrylate)-based hydrogels were investigated: adding 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to the monomers solution before polymerization (HEMA/i-CD) and an hydrogels' post-treatment with HP-ß-CD (HEMA/p-CD). The effect of HP-ß-CD and sterilization by high hydrostatic pressure (HHP) on the hydrogel properties (water content, oxygen and ion permeability, roughness, transmittance, and stiffness) was evaluated. The HEMA/i-CD hydrogels had stronger affinity for TA, sustaining its release for one day. HHP sterilization promoted the formation of cyclodextrin-TA complexes within the hydrogels, improving their drug-loading capacity ¼60 %. Cytotoxicity and irritability tests confirmed the safety of the therapeutic CLs. TA released from the hydrogels permeated through ocular tissues ex vivo and showed anti-inflammatory activity. Finally, a previously validated mathematical model was used to estimate the ability of the TA-loaded CLs to deliver therapeutic drug concentrations to the posterior part of the eye. Overall, HP-ß-CD-containing CLs are promising candidates for the topical ocular application of TA as an alternative delivery system to intraocular injections.

The role of intimate partner violence perpetrators' resting state functional connectivity in treatment compliance and recidivism.

To expand the scientific literature on how resting state functional connectivity (rsFC) magnetic resonance imaging (MRI) (or the measurement of the strength of the coactivation of two brain regions over a sustained period of time) can be used to explain treatment compliance and recidivism among intimate partner violence (IPV) perpetrators. Therefore, our first aim was to assess whether men convicted of IPV (n = 53) presented different rsFC patterns from a control group of non-violent (n = 47) men. We also analyzed if the rsFC of IPV perpetrators before staring the intervention program could explain treatment compliance and recidivism one year after the intervention ended. The rsFC was measured by applying a whole brain analysis during a resting period, which lasted 45 min. IPV perpetrators showed higher rsFC in the occipital brain areas compared to controls. Furthermore, there was a positive association between the occipital pole (OP) and temporal lobes (ITG) and a negative association between the occipital (e.g., occipital fusiform gyrus, visual network) and both the parietal lobe regions (e.g., supramarginal gyrus, parietal operculum cortex, lingual gyrus) and the putamen in IPV perpetrators. This pattern was the opposite in the control group. The positive association between many of these occipital regions and the parietal, frontal, and temporal regions explained treatment compliance. Conversely, treatment compliance was also explained by a reduced rsFC between the rostral prefrontal cortex and the frontal gyrus and both the occipital and temporal gyrus, and between the temporal and the occipital and cerebellum areas and the sensorimotor superior networks. Last, the enhanced rsFC between the occipital regions and both the cerebellum and temporal gyrus predicted recidivism. Our results highlight that there are specific rsFC patterns that can distinguish IPV perpetrators from controls. These rsFC patterns could be useful to explain treatment compliance and recidivism among IPV perpetrators.