Effects of topical insulin on second-degree burn wound healing: brief report.

BACKGROUND: Burns are classified according to their mechanism of injury, depth, affected body area, affected region or part of the body, and extent of the lesions. Topical insulin modulates the healing process. However, studies evaluating the effects of topical insulin treatment on burns in human patients are lacking. PURPOSE: The purpose of this study was to investigate the effects of topical insulin on healing time of second-degree burns. METHODS: In this nonrandomized clinical trial, patients with second-degree burns were allocated to a control group (CG) or an intervention group (IG) in which wounds were treated with 1% silver sulfadiazine and topical insulin, respectively. RESULTS: Healing time was significantly shorter in the IG relative to the CG (9.1 ± 1.9 days and 12.7 ± 3.3 days, respectively; P < .05). The estimated burn area was similar in both groups (CG 1.44 ± 1.0%; IG 1.42 ± 0.53%). CONCLUSION: In this study, topical insulin reduced healing time in second-degree burns. Further investigation is warranted to support wider use in clinical practice.

The Imidazacridine Derivative LPSF/AC-05 Induces Apoptosis, Cell Cycle Arrest, and Topoisomerase II Inhibition in Breast Cancer, Leukemia, and Lymphoma.

INTRODUCTION: Cancer is the major cause of morbidity and mortality worldwide. Current treatments for both solid and hematological tumors are associated with severe adverse effects and drug resistance, necessitating the development of novel selective antineoplastic drugs. METHODS: The present study describes the antitumor activity of the imidazacridine derivative 5-acridin-9-ylmethylidene-2-thioxoimidazolidin-4-one (LPSF/AC05) in breast cancer, leuke-mia, and lymphoma cells. Cytotoxicity assays were performed in PBMC and in breast cancer, leukemia, and lymphoma cell lines using the MTT method. Changes in cell cycle progression and apoptosis were assessed using flow cytometry. Moreover, topoisomerase II inhibition as-says were performed. LPSF/AC05 exhibited cytotoxicity in six of the nine cell lines tested. RESULTS: The best results for leukemia and lymphoma were observed in the Toledo, Jurkat, and Raji cell lines (IC50 = 27.18, 31.04, and 33.36 M, respectively). For breast cancer, the best re-sults were observed in the triple-negative cell line MDA-MB-231 (IC50 = 27.54 µM). The compound showed excellent selectivity, with no toxicity to normal human cells (IC50 > 100M; selectivity index > 3). Cell death was primarily induced by apoptosis in all cell lines. Furthermore, LPSF/AC05 treatmentinduced cell cycle arrest at the G0/G1 phase in leuke-mia/lymphoma and at the G2/M phase in breast cancer. CONCLUSION: Finally, topoisomerase II was inhibited. These results indicate the potential ap-plication of LPSF/AC05 in cancer therapy.

Therapeutic potential of hydantoin and thiohydantoin compounds against Schistosoma mansoni: An integrated in vitro, DNA, ultrastructural, and ADMET in silico approach.

The study aimed to conduct in vitro biological assessments of hydantoin and thiohydantoin compounds against mature Schistosoma mansoni worms, evaluate their cytotoxic effects and predict their pharmacokinetic parameters using computational methods. The compounds showed low in vitro cytotoxicity and were not considered hemolytic. Antiparasitic activity against adult S. mansoni worms was tested with all compounds at concentrations ranging from 200 to 6.25 µM. Compounds SC01, SC02, and SC03 exhibited low activity. Compounds SC04, SC05, SC06 and SC07 caused 100 % mortality within 24 h of incubation at a concentration of 100 and 200 µM. Thiohydantoin SC04 exhibited the highest activity, resulting in 100 % mortality after 24 h of incubation at a concentration of 50 µM and IC50 of 28 µM. In the ultrastructural analysis (SEM), the compound SC04 (200 µM) induced integumentary changes, formation of integumentary blisters, and destruction of tubercles and spicules. Therefore, the SC04 compound shows promise as an antiparasitic against S. mansoni.

Molecular Modeling of Single- and Double-Hydrocarbon-Stapled Coiled-Coil Inhibitors against Bcr-Abl: Toward a Treatment Strategy for CML.

The chimeric oncoprotein Bcr-Abl is the causative agent of virtually all chronic myeloid leukemias and a subset of acute lymphoblastic leukemias. As a result of the so-called Philadelphia chromosome translocation t(9;22), Bcr-Abl manifests as a constitutively active tyrosine kinase, which promotes leukemogenesis by activation of cell cycle signaling pathways. Constitutive and oncogenic activation is mediated by an N-terminal coiled-coil oligomerization domain in Bcr (Bcr-CC), presenting a therapeutic target for inhibition of Bcr-Abl activity toward the treatment of Bcr-Abl+ leukemias. Previously, we demonstrated that a rationally designed Bcr-CC mutant, CCmut3, exerts a dominant negative effect upon Bcr-Abl activity by preferential oligomerization with Bcr-CC. Moreover, we have shown that conjugation to a leukemia-specific cell-penetrating peptide (CPP-CCmut3) improves intracellular delivery and activity. However, our full-length CPP-CCmut3 construct (81 aa) is encumbered by an intrinsically high degree of conformational variability and susceptibility to proteolytic degradation relative to traditional small-molecule therapeutics. Here, we iterate a new generation of CCmut3 inhibitors against Bcr-CC-mediated Bcr-Abl assembly designed to address these constraints through incorporation of all-hydrocarbon staples spanning i and i + 7 positions in α-helix 2 (CPP-CCmut3-st). We utilize computational modeling and biomolecular simulation to evaluate single- and double-stapled CCmut3 candidates in silico for dynamics and binding energetics. We further model a truncated system characterized by the deletion of α-helix 1 and the flexible loop linker, which are known to impart high conformational variability. To study the impact of the N-terminal cyclic CPP toward model stability and inhibitor activity, we also model the full-length and truncated systems devoid of the CPP, with a cyclized CPP, and with an open-configuration CPP, for a total of six systems that comprise our library. From this library, we present lead-stapled peptide candidates to be synthesized and evaluated experimentally as our next iteration of inhibitors against Bcr-Abl.

Dietary Patterns among Smokers and Non-Smokers: Findings from the National Health and Nutritional Examination Survey (NHANES) 2017-2018.

Diet behavior and nutrition are critical for maintaining health and improving quality of life. Cigarette smoking remains the leading cause of preventable death in the United States. Poor dietary choices, such as excessively frequenting restaurants, consuming ready-to-eat foods from grocery stores, and ingesting ultra-processed foods (like frozen meals and pizzas), can adversely impact health. Despite this, research comparing dietary behaviors between smokers and non-smokers is limited. Using data from the National Health and Nutritional Examination Survey 2017-2018, we analyzed diet behavior based on smoking status. Our findings reveal that smokers had a significant increase (90%) in the frequency of consuming frozen meals/pizzas in the past 30 days compared to non-smokers (coefficient: 1.9; 95% CI: 1.4, 2.6; p-value < 0.001). Additionally, over 70% of participants, regardless of their smoking status, were unaware of MyPlate, a nutritional guide created by the United States Department of Agriculture (USDA) to encourage Americans to make healthier food choices. There is an urgent need to increase public awareness of MyPlate and promote a better understanding of healthy dietary behaviors.

Physical training minimizes immunological dysfunction, oxidative stress and tissue destruction on experimental periodontitis in rats.

The objective of this study is to investigate the effects of a moderate intensity physical training protocol, on alveolar bone morphology of rats submitted to ligature-induced periodontitis. Twenty-eight male Wistar rats were divided into four groups, considering the presence/absence of periodontitis and presence/absence of training. The training protocol was performed on a treadmill, 30 min/day, 5 days a week, for 4 weeks. In the experimental periodontal breakdown, with/without training, ligatures were placed on the lower first molars on the 14th day of the experiment, and were followed until the end of the protocol. At the end of the experiment, animals were euthanized and samples of plasma and mandibles were collected for immunoenzymatic evaluation of interleukins (IL)-1ß, IL-6, TNF-α and IL-10, evaluation of serum concentrations of C-reactive protein, analysis of lipid peroxidation (LPO) and reduced glutathione, histological and microtomographic analyses were performed. Physical training resulted in a reduced levels of IL-1ß, IL-6, TNF-α C-reactive protein and LPO and an increase in the levels of IL-10 in rats with periodontitis (p<0.05); a reduction in the inflammatory infiltrate and decreased fiber degradation was identified in histological analysis. Additionally, it was shown a decrease in vertical bone loss and an increase in the bone volume/trabecular volume ratio was identified in periodontitis+physical training group (p<0.05). Based on the results, the practice of frequent physical exercise, at moderate intensity, can contribute to the reduction of damage related to the disproportionate inflammatory response in periodontitis.

Human papillomavirus in women infected with human immunodeficiency virus: association with viral load and lymphocyte count.

Women living with human immunodeficiency virus are at an increased risk of developing cancers related to human papillomavirus (HPV). Thus, it is important to combine clinical assessments, serological screening, and HPV data for planning prevention policies. This study aimed to identify HPV and its specific types in the cervical, anal, and oral mucosa of HIV-seropositive women, associating it with viral load and lymphocyte count. Sociodemographic characteristics, health data (CD4+ and CD8+ T cell counts and viral load), and biological samples (cervical, anal, and oral) were collected from 86 HIV-positive women undergoing antiretroviral therapy. Data were classified according to the presence or absence of HPV-DNA, HPV-DNA presence at one or more anatomic sites, and level of oncogenic risk, considering low- and high-risk oncogenic HPV-DNA groups. The presence of HPV in the cervicovaginal site was 65.9%, 63.8% in anal canal, and 4.2% in oral mucosa. A viral load ≥75 HIV copies/mL was associated with the presence of HPV-DNA. There was an association between viral load and the low-risk HPV or high-risk HPV groups. We found a high prevalence of HPV infection in HIV-seropositive women, particularly in the cervical and anal mucosa, with viral load ≥75 HIV copies/mL being associated with HPV-DNA presence.

Seasonal influence on the essential oil chemical composition of Hyptis crenata Pohl ex Benth.: a valuable plant from Marajó, Brazil.

Introduction: Essential oils (EOs) from the Hyptis genus have been reported as bactericides and fungicides. However, the properties of these oils can be affected by climatic factors, as well as the collection period, which promotes changes in the chemical composition of the oil. In this context, this study aimed to evaluate the climatological influences on the chemical composition of the essential oil from the leaves of Hyptis crenata. Methods: The leaves were collected in Marajó island (Brazil) monthly for a year. The EOs were obtained by hydrodistillation and analyzed by Gas Chromatography coupled to Mass Spectrometry (GC-MS). Pearson's correlation was used to evaluate the relationship between climatic parameters, content, and chemical composition of essential oil; multivariate analysis was used to evaluate the interrelationship between samples and their chemical constituents. Results and Discussion: The constituents with the highest contents (>2.0%) in essential oils during the studied period were 1,8-cineole (28.48% ± 4.32%), α-pinene (19.58% ± 2.29%), camphor (11.98% ± 2.54%), ß-pinene (9.19% ± 1.47%), limonene (6.12% ± 3.15%), α-terpineol (2.42% ± 0.25%) and borneol (2.34% ± 0.48%). ß-Pinene significantly correlated (p < 0.05) with precipitation and humidity. According to the chemometric tools, two groups were formed: chemical profile I, marked by 1,8 cineole, α-pinene, ß-pinene, borneol, α-terpineol, and limonene, while group II (July) presented a chemical type characterized by camphor. It is understood that the species in question can be a reliable source of biologically active components during different climatic periods in the Amazon. The chemical variability could have significant implications for the pharmaceutical industry and traditional medicine.

In silico prediction of ADMET parameters and in vitro evaluation of antioxidant and cytotoxic activities promoted by indole-thiosemicarbazone compounds.

Cancer is a complex and multifactorial disease characterized by uncontrolled cell growth and is one of the main causes of death in the world. This work aimed to evaluate a small series of 10 different indole-thiosemicarbazone compounds as potential antitumor agents. This is a pioneering study. For this, the antioxidant and cytotoxic capacity against normal and tumor cells was evaluated. The results showed that the compounds were able to promote moderate to low antioxidant activity for the ABTS radical scavenging assay. ADMET in silico assays showed that the compounds exhibited good oral bioavailability. As for toxicity, they were able to promote low cytotoxicity against normal cells, in addition to not being hemolytic. The compounds showed promising in vitro antitumor activity against the T47D, MCF-7, Jurkat and DU-145 strains, not being able to inhibit the growth of the Hepg2 strain. Through this in vitro study, it can be concluded that the compounds are potential candidates for antitumor agents.

Correction: Zanchetta et al. Effects of Electrospun Fibrous Membranes of PolyCaprolactone and Chitosan/Poly(Ethylene Oxide) on Mouse Acute Skin Lesions. Polymers 2020, 12, 1580.

In the original publication, the authors claimed that Figure 6 reporting Western blot data was erroneous as published [...].

Evaluation of heating and liming treatments in sand samples artificially contaminated with Ancylostoma spp. eggs.

Ancylostoma spp. are found worldwide. Infected dog and cat feces can contaminate soil in public places. Despite prophylactic measures being available, studies on direct remediation of Ancylostoma-contaminated soils are scarce. This study aimed to determine the impact of heat treatment and liming on the viability of Ancylostoma spp. eggs in artificially contaminated sandy soil. Sterilized sand samples were contaminated with Ancylostoma spp. eggs extracted from infected dogs' feces. Samples were heated (trial I) to 70 °C or 80 °C, then sieved after 24 hours (212, 90, 38, and 25 µm). Larval cultures were assessed for larval development following heat treatment. Five quicklime concentrations (trial II; 50, 30, 20, 10 and 5%) were used to treat sand. The effect of liming on larval cultures was assessed by measuring embryonic development. Filariform larvae were exposed to 20% quicklime (25 °C and 37 °C, 20 min). Heat treatment destroys Ancylostoma spp. eggs and prevents in vitro larval development. Liming at 50, 30, and 20% concentrations made embryonic development impossible. However, filariform larvae treated with 20% lime solution retained their motility. Heating at 70 °C and liming at 20% were sufficient to make Ancylostoma spp. egg embryogenesis impossible in experimentally contaminated sand samples.

Famílias ouvintes e filhos surdos: o papel da Libras na comunicação / Hearing families and deaf children: the role of Libras in communication / Familias oyentes y niños sordos: el papel de Lengua de Señas Brasileña em la comunicación

Introdução: A Língua Brasileira de Sinais (Libras) é uma língua de natureza visuo-motora com um sistema linguístico e estrutura gramatical próprio e sua aquisição em tempo oportuno é importante para o desenvolvimento cognitivo e comunicativo da criança surda. As famílias ouvintes de crianças surdas devem se engajar no aprendizado dessa língua, uma vez que na ausência do conhecimento da Libras, podem apresentar dificuldades de comunicação e de relacionamento com seu filho surdo. Objetivo: O objetivo deste estudo foi compreender o papel da Libras na comunicação de familiares ouvintes e seus filhos surdos atendidos em um centro de reabilitação. Métodos: Trata-se de um estudo transversal, de caráter qualitativo. Foi aplicado um roteiro de entrevista semiestruturado com 10 questões abertas a pais ouvintes de crianças surdas que participam de atendimentos em um centro de reabilitação. A análise dos dados foi realizada por meio do método análise de conteúdo. Resultados: Ao todo foram entrevistadas 10 mães de crianças surdas. As idades das mães variaram de 21 a 47 anos. Nove mães afirmaram usar a Libras em casa com seus filhos todos os dias e todas relataram usá-la em atividades cotidianas da criança. Todas as mães afirmaram que o uso da Libras trouxe benefícios para o relacionamento na díade mãe-filho. Conclusão: Os achados revelam um importante papel da Libras tanto na comunicação de familiares ouvintes e seus filhos surdos, como no cotidiano desses lares. (AU)

Introduction: The Brazilian Sign Language (Libras) is a visual-motor language with its linguistic system and grammatical structure and its timely acquisition is important for deaf children's cognitive and communicative development. Deaf children's hearing families should engage in learning this language, since not knowing Libras may lead to communication and relationship difficulties with their deaf children. Objective: This study aimed to understand the role of Libras in the communication between hearing family members and their deaf children treated at a rehabilitation center. Methods: This cross-sectional qualitative study applied a semi-structured interview with 10 open-ended questions to hearing parents of deaf children who receive care at a rehabilitation center. Data were analyzed with the content analysis method. Results: Altogether, 10 mothers of deaf children were interviewed. Their ages ranged from 21 to 47 years. Nine mothers said they used Libras at home with their children every day, and all reported using it in their child's daily activities. All mothers stated that the use of Libras brought benefits to the mother-child relationship. Conclusion: The findings highlight the important role of Libras in the daily lives and communication of hearing family members and their deaf children. (AU)

Introducción: La Lengua de Señas Brasileña (Libras) es una lengua visomotora con sistema lingüístico y estructura gramatical propios y su adquisición oportuna es importante para el desarrollo cognitivo y comunicativo del niño sordo. Las familias oyentes de niños sordos deben involucrarse en el aprendizaje de este idioma, ya que en ausencia del conocimiento de Libras, pueden tener dificultades en la comunicación y las relaciones con su hijo sordo. Objetivo: El objetivo de este estudio fue comprender el papel de Libras en la comunicación de los familiares oyentes y sus hijos sordos atendidos en un centro de rehabilitación auditiva. Métodos: Se trata de un estudio transversal, cualitativo. Se aplicó un guión de entrevista semiestructurada con 10 preguntas abiertas a padres oyentes de niños sordos que participan en el cuidado en un centro de rehabilitación. El análisis de los datos se realizó mediante el método de análisis de contenido. Resultados: En total, se entrevistaron 10 madres de niños sordos. Las edades de las madres oscilaron entre 21 y 47 años. Nueve madres dijeron que usan Libras en casa con sus hijos todos los días y todas informaron que lo usan en las actividades diarias de sus hijos. Todas las madres afirmaron que el uso de Libras trajo beneficios a la relación madre-hijo. Conclusión: Los hallazgos revelan un papel importante de Libra tanto en la comunicación de los miembros oyentes de la familia y sus hijos sordos, como en la vida diaria de estos hogares. (AU)

Condrossarcoma gigante de corpo esternal: relato de caso / Giant chondrosarcoma of the sternal body: case report

Os tumores de parede torácicas são relativamente inusitados, representando 1 a 2% de todas as neoplasias, e cerca de 5% das neoplasias torácicas. Sarcomas são tumores raros e com apresentação heterogênea. São divididos em dois grandes grupos: tumores ósseos e de partes moles. A ocorrência na parede torácica é rara, representando 8% de todos os sarcomas. O tratamento de escolha é a ressecção com margens ampliadas e, quando ocorre a invasão de estruturas profundas, a toracectomia é indicada. A reconstrução do arcabouço ósseo é realizada com materiais de síntese, proporcionando estabilidade, e é seguida da reconstrução de partes moles com retalhos musculares, musculocutâneos ou locais ao acaso. Os tumores malignos primários da parede torácica correspondem a menos de 1% de todas as neoplasias e incluem grande variedade de lesões ósseas e de tecidos moles. Os condrossarcomas representam 20% dos tumores primários da parede torácica, sendo que 80% têm origem nas costelas e 20% no esterno.

Chest wall tumors are relatively uncommon, representing 1 to 2% of all neoplasms, and approximately 5% of thoracic neoplasms. Sarcomas are rare tumors with heterogeneous presentation. They are divided into two large groups: bone and soft tissue tumors. Occurrence in the chest wall is rare, representing 8% of all sarcomas. The treatment of choice is resection with wide margins and, when invasion of deep structures occurs, thoracotomy is indicated. The reconstruction of the bone framework is carried out with synthetic materials, providing stability, and is followed by the reconstruction of soft tissues with muscular, musculocutaneous, or random local flaps. Primary malignant tumors of the chest wall account for less than 1% of all neoplasms and include a wide variety of bone and soft tissue lesions. Chondrosarcomas represent 20% of primary tumors of the chest wall, with 80% originating in the ribs and 20% in the sternum.

Use of coronary artery calcium score and coronary CT angiography to guide cardiovascular prevention and treatment.

Currently, cardiovascular risk stratification to guide preventive therapy relies on clinical scores based on cardiovascular risk factors. However, the discriminative power of these scores is relatively modest. The use of coronary artery calcium score (CACS) and coronary CT angiography (CCTA) has surfaced as methods for enhancing the estimation of risk and potentially providing insights for personalized treatment in individual patients. CACS improves overall cardiovascular risk prediction and may be used to improve the yield of statin therapy in primary prevention, and possibly identify patients with a favorable risk/benefit relationship for antiplatelet therapies. CCTA holds promise to guide anti-atherosclerotic therapies and to monitor individual response to these treatments by assessing individual plaque features, quantifying total plaque volume and composition, and assessing peri-coronary adipose tissue. In this review, we aim to summarize current evidence regarding the use of CACS and CCTA for guiding lipid-lowering and antiplatelet therapy and discuss the possibility of using plaque burden and plaque phenotyping to monitor response to anti-atherosclerotic therapies.

Preliminary evaluation of the toxicological, antioxidant and antitumor activities promoted by the compounds 2,4-dihydroxy-benzylidene-thiosemicarbazones an in silico, in vitro and in vivo study.

Thiosemicarbazones are promising classes of compounds with antitumor activity. For this study, six 2,4-dihydroxy-benzylidene-thiosemicarbazones compounds were synthesized. These compounds were submitted to different assays in silico, in vitro and in vivo to evaluate the toxicological, antioxidant and antitumor effects. The in silico results were evaluated by the SwissADME and pkCSM platforms and showed that all compounds had good oral bioavailability profiles. The in vitro and in vivo toxicity assays showed that the compounds showed low cytotoxicity against different normal cells and did not promote hemolytic effects. The single dose acute toxicity test (2000 mg/kg) showed that none of the compounds were toxic to mice. In in vitro antioxidant activity assays, the compounds showed moderate to low activity, with PB17 standing out for the ABTS radical capture assay. The in vivo antioxidant activity highlighted the compounds 1, 6 and 8 that promoted a significant increase in the concentration of liver antioxidant enzymes. Finally, all compounds showed promising antitumor activity against different cell lines, especially MCF-7 and DU145 lines, in addition, they inhibited the growth of sarcoma 180 at concentrations lower than 50 mg/kg. These results showed that the evaluated compounds can be considered as potential antitumor agents.

Saliva as a Biological Fluid in SARS-CoV-2 Detection.

BACKGROUND: The polymerase chain reaction of upper respiratory tract swab samples was established as the gold standard procedure for diagnosing SARS-CoV-2 during the COVID pandemic. However, saliva collection has attracted attention as an alternative diagnostic collection method. The goal of this study was to compare the use of saliva and nasopharyngeal swab (NPS) samples for the detection of SARS-CoV-2. METHODS: Ninety-nine paired samples were evaluated for the detection of SARS-CoV-2 by saliva and swab for a qualitative diagnosis and quantitative comparison of viral particles. Furthermore, the detection limits for each sample collection technique were determined. The cycle threshold (CT) values of the saliva samples, the vaccination status, and the financial costs associated with each collection technique were compared. RESULTS: The results showed qualitative equivalence in diagnosis (96.96%) comparing saliva and swab collection, although there was low quantitative agreement. Furthermore, the detection limit test demonstrated equivalence for both collection methods. We did not observe a statistically significant association between CT values and vaccination status, indicating that the vaccine had no influence on viral load at diagnosis. Finally, we observed that the use of saliva incurs lower financial costs and requires less use of plastic materials, making it more sustainable. CONCLUSIONS: These findings support the adoption of saliva collection as a feasible and sustainable alternative to the diagnosis of COVID-19.

Case report: acute myocarditis complicated with persistent complete heart block: a clinical dilemma when myocardial inflammation remains.

Background: Atrioventricular conduction abnormalities due to acute myocarditis are typically transient and do not require ventricular pacing beyond the acute phase of myocardial inflammation. Notwithstanding, selective injury and necrosis of the heart's conduction system may lead to persistent complete heart block (CHB) requiring device implantation. Case summary: We report the case of a 23-year-old man with acute lymphocytic myocarditis complicated by cardiogenic shock, cardiac arrest due to ventricular fibrillation, and persistent CHB. Endomyocardial biopsy (EMB) showed signs of subacute myocarditis, with no evidence of granulomas or giant cells, nor criteria for eosinophilic myocarditis. Aetiological work-up found serological evidence of previous Epstein-Barr virus (EBV) infection; Borrelia burgdorferi serology for Lyme disease was negative. The real time-polymerase chain reaction (RT-PCR) of the EMB was positive for the presence of EBV DNA, but in situ hybridization for viral ribosomal RNA (rRNA) was negative. The patient progressed favourably, and left ventricle ejection fraction recovered 2 weeks after initial presentation. However, CHB persisted for more than 3 weeks, and the patient underwent definitive pacemaker implantation with left bundle branch pacing. Discussion: Persistent CHB after acute myocarditis is generally considered unlikely, but in rare circumstances the damage portended by inflammation may be irreversible. Besides the play of chance, possible mechanisms behind the apparent predilection for the conduction system of the myocardium warrant further research.

Combined transcatheter aortic valve and tricuspid valve-in-valve implantation in a patient with a mitral mechanical prosthesis.

Despite progressively uncommon in Western countries, rheumatic heart disease still portrays a significant global burden. In elderly or high-surgical risk patients, plurivalvular disease may require a complex percutaneous approach. Transcatheter aortic valve implantation (TAVI) in patients with previous monoleaflet mitral prosthesis is challenging due to interference between the aortic valve and the rigid mitral mechanical prosthesis "ring." Prior cases report the use of CoreValve or Edwards Sapien aortic valves in patients with adequate mitro-aortic distance. Performing a second major procedure, such as tricuspid valve-in-valve (TVIV), sequentially during a single percutaneous intervention, increases treatment complexity. An 83-year-old woman with rheumatic heart disease, with previous implantation of a Bjork-Shiley monoleaflet mitral prosthesis, and Carpentier-Edwards 29 tricuspid bioprosthesis presented with decompensated heart failure due to severe aortic stenosis and tricuspid bioprosthesis stenosis. After HeartTeam discussion, the patient was deemed as inoperable due to a prohibitive surgical risk. As an alternative, a TAVI (Navitor FlexNav) and a transcatheter TVIV replacement (Edwards Sapiens 3 Ultra) were discussed and proposed, with both techniques being performed sequentially in a single procedure. TAVI in a patient with a previous monoleaflet mitral mechanical prosthesis and TVIV may be a feasible approach in inoperable patients with plurivalvular disease.

Trends from two decades of orphan designations in paediatric rare neuromuscular diseases.

Rare diseases are characterized by substantial unmet need mostly because the majority have limited, or no treatment options and a large number also affect children. Since the inception of EU orphan regulation in 2000 the European Medicines Agency Committee for Orphan Medicinal Products has received several applications for paediatric rare neuromuscular diseases (PERAN) however treatment options remain limited. Here we discuss the results form an observational, retrospective, cross-sectional study to characterize the currently authorised orphan medicinal products (OMP) and orphan designations (OD) given to products for PERAN in the last two decades. In the EU about half of PERAN diseases have at least one active OD approved since 2000, and about half of these are for Duchenne muscular dystrophy (DMD). The large majority of PERAN diseases do not have an authorised medicine with only 6 OMP currently authorised for Spinal muscular atrophy (3); DMD (1) and Myasthenia gravis (2). One in five products have inactive or discontinued regulatory development but clinical trials are ongoing for the vast majority of PERAN diseases, and more than half are in the final stage of clinical research with significantly more products with medical plausibility based in clinical data reaching advanced stages in clinical development.

Epidemiological and Clinical Aspects of Cutaneous and Mucosal Leishmaniases in Portugal: Retrospective Analysis of Cases Diagnosed in Public Hospitals and Reported in the Literature between 2010 and 2020.

Leishmania infantum, a zoonotic vector-born parasite, is endemic in the Mediterranean region, presenting mostly as visceral (VL), but also as cutaneous (CL) and mucosal leishmaniasis (ML). This study aimed to describe the epidemiological and clinical aspects of the CL and ML cases diagnosed in mainland Portugal between 2010 and 2020. Collaboration was requested from every hospital of the Portuguese National Health System. Cases were screened through a search of diagnostic discharge codes or positive laboratory results for Leishmania infection. Simultaneously, a comprehensive literature search was performed. Descriptive statistics and hypothesis testing were performed using IBM® SPSS® Statistics. A total of 43 CL and 7 ML cases were identified, with a predominance of autochthonous cases (86%). In CL, immunosuppressed individuals constituted a significant proportion of patients (48%), and in this group, disseminated CL (22%) and simultaneous VL (54%) were common. In autochthonous cases, lesions, mostly papules/nodules (62%), were frequently observed on the head (48%). The approach to treatment was very heterogeneous. ML cases were all autochthonous, were diagnosed primarily in older immunosuppressed individuals, and were generally treated with liposomal amphotericin B. The findings suggest a need for enhanced surveillance and reporting, clinical awareness, and diagnostic capacity of these forms of leishmaniasis to mitigate underdiagnosis and improve patient outcomes. A holistic One Health approach is advocated to address the multifaceted challenges posed by leishmaniases in Portugal and beyond.