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Objetivos: Descrever o desfecho do transplante de células tronco hematopoiéticas (TCTH) em pacientes (pts) com anemia de fanconi (AF) que desenvolveram síndrome mielodisplásica (SMD) ou leucemia mieloide aguda (LMA). Material e métodos: Análise retrospectiva dos prontuários médicos dos pts com AF em fase de SMD/LMA que foram submetidos ao TCTH entre janeiro de 2012 e dezembro de 2023. Resultados: Foram analisados 35 pts, a maioria do sexo masculino (n = 20). A mediana de idade foi 17 anos (2‒44 anos), sendo 51% menores de 18 anos (n = 17). Doze pts fizeram uso de andrógeno na fase de aplasia. Quinze pts foram transplantados com citopenia refratária (n = 15), seis pts com SMD com Excesso de Blastos tipo 1 (EB1); quatro com SMD tipo 2 (EB2) e dez com LMA. A maioria dos pts transplantados em fase avançada (SMD-EB2/LMA) recebeu esquema FLAG pré TMO (n = 12). Os doadores foram haploidênticos (n = 17), não aparentados (n = 11) e aparentados compatíveis (n = 7). Todos receberam medula óssea. Os regimes de condicionamento foram feitos com CY + FLU + TBI (NAP), FLU + TBI (Haplo). Quinze pts utilizaram seroterapia (ATG n = 10/Campath n = 5). Nenhum rejeitou. Nove pts tiveram recaída da doença após TCTH, com mediana de 240 dias (80‒1691 dias). Seis pts foram retransplantados, 1 fez uso de azacitidina como manutenção pós transplante e 1 usou venetoclax, mas todos evoluíram para óbito. A mediana de follow-up foi 3,6 anos (14 dias‒11,8 anos). A sobrevida global em 5 anos foi 51,4%. Dez pts morreram numa mediana de 138 dias após o TCTH (85‒1102 dias) e 3 pts morreram durante o condicionamento. A sobrevida livre de recaída foi 67,3% e a SG em 5 anos para pts em fase avançada foi 32,4%, com taxa de recidiva em 5 anos de 25%. As causas de óbito foram infecção fúngica invasiva (n = 5), progressão da doença (n = 4), infecções (bacteriana/viral n = 3), DECHa (n = 2), neoplasia (n = 1) e toxicidade medicamentosa (n = 1). Discussão: A AF é a causa hereditária mais frequente de falência de medula óssea. A incidência de SMD é 11% a 34% e a de LMA é de 10% a 37%, com taxas de sobrevida após o TCTH de 57% e 36% respectivamente, inferiores se comparados aos pts com LMA não portadores de AF. A adolescência ou a idade adulta jovem são os períodos mais comuns de evolução clonal. O uso de andrógenos tem resposta hematológica em cerca de 80% dos pts e não tem associação com evolução clonal, conforme a literatura. Neste estudo, quase a metade dos pacientes tinham mais de 18 anos e a SG foi semelhante às publicações anteriores (SG em 5 anos: 42%). O tratamento de pts com SMD e LMA tem altas taxas de recaída, pois os pts não toleram quimioterapia intensiva além da quimio resistência intrínseca. O esquema FLAG pré TCTH usa quimioterapia de baixa intensidade e a taxa de recidiva nesta população foi inferior à descrita na literatura (taxa de recidiva em 5 anos: 40%). As infecções fúngicas invasivas são uma preocupação devido à grande mortalidade associada. Conclusão: A AF continua sendo um desafio, devido ao alto risco de neoplasias secundárias. Mas estes resultados indicam que apesar do TCTH ser a única opção com possibilidade curativa para falência de medula óssea, a morte por infecção e recaída permanecem um grande problema. Mais estudos são necessários para determinar o melhor regime de condicionamento ou terapêutica de manutenção e profilática pós TCTH.

Objetivo: A má função do enxerto (PGF) após o Transplante de Células Tronco Hematopoiéticas (TCTH) é definida por citopenias dependentes de transfusões de sangue e/ou suporte de G-CSF, apesar do quimerismo completo do doador. O objetivo deste trabalho é descrever o uso do Eltrombopag (EPAG) para PGF em pacientes (pts) pediátricos submetidos a TCTH entre 2009 e 2023. Métodos: Análise retrospectiva de prontuários médicos. Resultados: 30 pts desenvolveram PGF após o TCTH e foram tratados com EPAG. A maioria eram do sexo masculino (n = 20) e a medina de idade no TCTH foi 8,1 anos (6m‒17,4a). Os diagnósticos foram: erros inatos de imunidade (n = 12), falência medular (n = 11) e leucemias agudas (n = 7). Os doadores foram haploidênticos (n = 16), não aparentados (n = 12) ou aparentados compatíveis (n = 2). Medula óssea foi a fonte de células predominante (n = 27) e a maioria dos pts recebeu condicionamento de intensidade reduzida (n = 20). A mediana de células CD34 infundidas foi de 4,94×106/kg (1,56–12,6×106/kg). O EPAG foi iniciado em uma mediana de 116 dias após o TCTH (42d‒9,3a), devido à trombocitopenia persistente, com anemia e neutropenia concomitantes em 7 e 8 pts, respectivamente. A dose inicial foi de 25 mg/dia, e eventualmente aumentada para 150 mg/dia em caso de falta de resposta, nas crianças mais velhas. Dois pts morreram no primeiro mês após o início do EPAG e não foram avaliáveis para resposta. 28 pcts sobreviveram mais de 3 meses após o início do EPAG, com 22 exibindo uma resposta hematológica. A mediana de tempo para resposta foi de 110 dias. Entre os respondedores, o EPAG foi descontinuado sem recaídas, e todos os pacientes permaneceram vivos e bem em um acompanhamento médio de 37 meses após o EPAG. Seis pts não responderam ao EPAG. Entre eles, 3 foram submetidos a um 2º TCTH, enquanto 3 pacientes morreram (2 por complicações infecciosas e 1 por recidiva da doença), ocorrendo pelo menos 4 meses após a descontinuação do EPAG. A sobrevida global (SG) de 2 anos foi de 82% (95% IC: 0,55‒0,95). Todos os efeitos colaterais foram leves e não levaram à descontinuação do EPAG. Discussão: A má função do enxerto tem incidência variável de 5% a 26% e aumenta as taxas de morbimortalidade pós TCTH, principalmente associada à infecções. As causas da PGF são incertas e os pts apresentam hipocelularidade medular intensa relacionada a um déficit na capacidade de produção plaquetária. No presente estudo, todos os pacientes tinham plaquetopenia. O EPAG se mostrou eficaz no tratamento da citopenia tardia em pacientes submetidos ao TCTH, corroborando os dados publicados. A mediana de tempo para resposta ao EPAG é 3 meses de tratamento e os resultados dos não respondedores refletiram impacto na SG. Além disso, podemos destacar, uma maior prevalência da PGF em pts que realizaram transplante com doador alternativo (haploidêntico), o que é descrito na literatura, possivelmente associado ao uso da CFA pós. Conclusão: O EPAG demonstrou ser uma opção terapêutica viável para pts com citopenias persistentes após o TCTH. No entanto, é importante notar que o tempo médio para a resposta foi cerca de 3 meses, portanto, é crucial que os pts recebam suporte adequado durante esse período. Mais estudos são necessários para confirmar esses achados e determinar a melhor abordagem de tratamento para essa população específica.

Fusarioid fungi, particularly Neocosmospora solani and Fusarium oxysporum, are emerging as significant human pathogens, causing infections ranging from localized mycoses to life-threatening systemic diseases. Accurate identification and preservation of these fungi in clinical laboratories remain challenging because of their diverse morphologies and specific growth requirements. This study evaluated a novel milk-honey and malt agar (MHM) against conventional media for cultivating and preserving 60 clinical fusarioid isolates, including Neocosmospora spp. (n = 47), Bisifusarium spp. (n = 5), and Fusarium spp. (n = 8). Compared with Sabouraud dextrose 2 % agar (SDA) and malt extract agar (ME2), MHM significantly increased conidia production (p < 0.0001, mean = 3.4 × 10 3 , standard deviation (SD) = ±1.3 × 10 3 ), with results similar to those of carnation leaf agar (CLA). MHM facilitated superior preservation of fusarioid viability for up to one year at room temperature on slant cultures and over two years on swabs in Amies gel with charcoal, outperforming current methods such as Castellani (water) or cryopreservation. Morphological characterization of fusarioid fungi grown on MHM revealed distinct growth patterns and conidial structures for Neocosmospora, Bisifusarium, and Fusarium species, aiding in identifying these genera. The superior performance of MHM in stimulating conidiation, maintaining viability, and preserving morphology underscore its potential as a reference medium for medically relevant fusarioid fungi, with broad implications for clinical mycology laboratories and resource-limited settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Rheumatic and Musculoskeletal Diseases (RMDs) are very common and can negatively impact patients' quality of life. The current care of patients with RMDs is episodic, based on a few yearly doctor visits, which may not provide an adequate picture of the patient's condition. Researchers have hypothesized that RMDs could be passively monitored using smartphones or sensors, however, there are no datasets to support this development. We introduce the COTIDIANA Dataset: a holistic, multimodal, multidimensional, and open-access resource that gathers data on mobility and physical activity, finger dexterity, and mental health, key dimensions affected by RMDs. We gathered smartphone and self-reported data from 31 patients and 28 age-matched controls, including inertial sensors, keyboard metrics, communication logs, and reference tests/scales. A preliminary analysis showed the potential for extracted metrics to predict RMD diagnosis and condition characteristics. Our dataset shall enable the community to create mobile and wearable-based solutions for patients with RMDs.

Background: Parkinson's disease (PD) ranks second in global neurodegenerative disorders. The "Parkinson's Real-world Impact assesSMent (PRISM)" study addressed the disease burden and treatment of European PD patients. Yet, the burden on Portuguese PD patients remains unexplored. Here, we outline the demographics, clinical features, and impact of PD in the Portuguese PRISM cohort., Methods: Descriptive analysis of the PRISM Portuguese cohort (80 patients) was performed, emphasizing socio-demographic data, anti-PD medication usage, PD impact on patients' lives and healthcare resources utilization., Results: The predominant comorbidities in the Portuguese PD cohort (55 % male; mean age 66.2 years; mean disease duration 8.8 years) included depression (26.3 %) and anxiety (26.3 %). Levodopa was the initial prescribed anti-PD medication for 88 % of patients. Among Portuguese PDP, dopamine agonists (DA), monoamine oxidase-B (MAO-B) inhibitors, and catechol-O-methyltransferase (COMT) inhibitors were used by 50 %, 44.4 %, and 18.3 %, respectively. Portuguese PDP experienced impaired quality of life (PDQ-39 score: 31.3 ± 16.8), various non-motor symptoms, namely sadness/blues (65.4 %), urinary urgency (63.5 %), high/low sex interest (57.7 %), while 56 % reported at least one impulse control behavior. Additionally, 30.8 % retired early due to PD and 31.8 % reduced hours in daily activities. Mental health appointments were attended by 31 %, primarily in psychiatry (19 %) and psychology (6 %), and psychotherapy., Conclusion: This study uncovers the burden of PD among Portuguese patients, revealing current treatment methods, impact on daily life and healthcare resources employed in Portugal. It emphasizes the need for personalized clinical strategies at national and international levels to improve long-term health outcomes and quality of life of PD patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Helena C. Brigas reports financial support and writing assistance were provided by BIAL Portela & CA SA. Ana Margarida Rodrigues reports a relationship with BIAL Portela & CA SA that includes: consulting or advisory and speaking and lecture fees. Ana Margarida Rodrigues reports a relationship with AbbVie that includes: speaking and lecture fees. Ana Margarida Rodrigues reports a relationship with Zambon S.A that includes: speaking and lecture fees. Ana Morgadinho reports a relationship with BIAL Portela & CA SA that includes: consulting or advisory and speaking and lecture fees. Ana Morgadinho reports a relationship with Zambon S.A that includes: consulting or advisory and speaking and lecture fees. Miguel F. Gago reports a relationship with BIAL Portela & CA SA that includes: consulting or advisory and speaking and lecture fees. Miguel F. Gago reports a relationship with AbbVie Inc that includes: consulting or advisory. Miguel F. Gago reports a relationship with Zambon S.A that includes: consulting or advisory and speaking and lecture fees. Rita M. Simoes reports a relationship with BIAL Portela & CA SA that includes: consulting or advisory and speaking and lecture fees. Rita M. Simoes reports a relationship with AbbVie Inc that includes: consulting or advisory and speaking and lecture fees. Rita M. Simoes reports a relationship with Stada that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aplastic anaemia in infants and young children presents unique challenges due to high prevalence of inherited bone marrow failure syndromes (IBMFS) in this age group. The objective of this study is assessing clinical characteristics and outcomes of haematopoietic cell transplantation in children ≤5 years with bone marrow failure syndromes. We analysied 106 patients (66% males), median age 4.6 years, including 40 with Fanconi anaemia (FA), 32 with Acquired Severe Aplastic anaemia (aSAA), 15 with Diamond-Blackfan Anaemia, 11 with Amegakaryocytic Purpura and 8 with other IBMFS. Molecular testing was limited (39%), with 25.4% confirmed genetically. Retrospective longitudinal study across three paediatric transplantation centres (1982-2020). Overall survival (OS) was 76.4% over a median 10-year follow-up. OS rates were similar between aSAA and IBMFS (FA 77.5%, other IBMFS 76.5%). Transplant-related mortality (TRM) was lower in aSAA (9.4%) compared with IBMFS (16.2%). Recent years showed improved outcomes, with TRM declining post-2010. Choice of stem cell source impacted OS, favouring bone marrow over umbilical cord, but showing encouraging results with haploidentical. Late complications were common, including endocrine-metabolic issues and delayed neuropsychomotor development. Diagnosing and managing bone marrow failures in young children pose significant challenges. Despite advancements in transplant practices, ongoing vigilance and comprehensive care are necessary to improve long-term survival rates., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: The MDS-UPDRS has been available in English since 2008, showing satisfactory clinimetric results and being proposed as the new official benchmark scale for Parkinson's disease (PD), being cited as a core instrument for PD in the National Institutes of Neurological Disorders and Stroke Common Data Elements program. For this reason, the MDS created guidelines for development of MDS-UPDRS official, clinimetrically validated translations., Objective: This study presents the formal process used to obtain the officially approved Portuguese version of the MDS-UPDRS., Methods: The study consisted of three phases: (1) Independent translation by Portuguese and Brazilian teams followed by a challenging consensus process that this article particularly emphasizes; (2) Cognitive pretest involving raters and patients from both Portugal and Brazil; (3) Validation test with a sample of 367 native Portuguese-speaking PD patients., Results: The overall factor structure of the Portuguese version was consistent with the English version based on a comparative fit index ≥0.96 for all four parts of the MDS-UPDRS., Conclusion: This version can be designated as the official Portuguese version of the MDS-UPDRS., (© 2024 International Parkinson and Movement Disorder Society.)

Fragility fractures are a major problem in our aging society leading to early death and loss of independence for activities of daily living. Physical activity in a long-term follow-up of Portuguese women over 50 years with a fragility fracture was associated with better physical function and quality of life., Purpose: To evaluate the long-term impact of physical activity on physical function and health-related quality of life (HRQoL) in women ≥ 50 years old who suffered a fragility fracture., Methods: We evaluated the association of physical activity with physical function and HRQoL in women ≥ 50 years old who self-reported at least one low-impact fracture ≥ 40 years old from the EpiDoC cohort, a population-based cohort. Self-reported data regarding sociodemographics, clinical, and lifestyle behaviors were collected through a semi-structured questionnaire at baseline during a face-to-face clinical interview. During a long-term follow-up, a phone interview was conducted to evaluate physical activity (using a non-validated scale developed for the EpiDoC study), physical function (Health Assessment Questionnaire), and HRQoL (European Quality of Life - 5 Dimension). Women were divided into three groups according to the frequency of physical activity (non-frequent = 0 times/week, frequent = 1-2 times/week, or very frequent =  ≥ 3 times/week). The association of physical activity frequency (non-frequent, frequent, and very frequent) with physical function and HRQoL over time was assessed through linear mixed models considering varying intercepts for each woman., Results: This study followed 323 post-fracture women, during a mean follow-up of 3.9 ± 3.5 years. Frequent (β =  - 0.1419 [- 0.2783, - 0.0064]) and very frequent (β =  - 0.1908 [- 0.2944, - 0.0881]) physical exercise were associated with improvements in physical function relative to non-frequent physical exercise adjusted for BMI, multimorbidity, hospitalizations, alcohol and smoking habits, and the number of fragility fractures at baseline. As for HRQoL, a positive association was found for exercise frequency, specifically frequent (β = 0.1305 [0.0646, 0.1958]) and very frequent (β = 0.1354 [0.0856, 0.1859]) suggesting improvements for HRQoL, in this follow-up period., Conclusions: These findings based on longitudinal data with long-term follow-up suggest that regular physical activity is associated with better function and HRQol among middle-aged and older post-fracture osteoporotic Portuguese women., (© 2024. The Author(s).)

The development of new analgesics has been challenging. Candidate drugs often have limited clinical utility due to side effects that arise because many drug targets are involved in signaling pathways other than pain transduction. Here, we explored the potential of targeting protein-protein interactions (PPIs) that mediate pain signaling as an approach to developing drugs to treat chronic pain. We reviewed the approaches used to identify small molecules and peptide modulators of PPIs and their ability to decrease pain-like behaviors in rodent animal models. We analyzed data from rodent and human sensory nerve tissues to build associated signaling networks and assessed both validated and potential interactions and the structures of the interacting domains that could inform the design of synthetic peptides and small molecules. This resource identifies PPIs that could be explored for the development of new analgesics, particularly between scaffolding proteins and receptors for various growth factors and neurotransmitters, as well as ion channels and other enzymes. Targeting the adaptor function of CBL by blocking interactions between its proline-rich carboxyl-terminal domain and its SH3-domain-containing protein partners, such as GRB2, could disrupt endosomal signaling induced by pain-associated growth factors. This approach would leave intact its E3-ligase functions, which are mediated by other domains and are critical for other cellular functions. This potential of PPI modulators to be more selective may mitigate side effects and improve the clinical management of pain.

Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by the Sporothrix clinical clade species, including Sporothrix brasiliensis and Sporothrix schenckii sensu stricto . Due to its zoonotic transmission in Brazil, S. brasiliensis represents a significant health threat to humans and domestic animals. Itraconazole, terbinafine, and amphotericin B are the most used antifungals for treating sporotrichosis. However, many strains of S. brasiliensis and S. schenckii have shown resistance to these agents, highlighting the importance of finding new therapeutic options. Here, we demonstrate that milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, is a possible therapeutic alternative for the treatment of sporotrichosis, as observed by its fungicidal activity in vitro against different strains of S. brasiliensis and S. schenckii . Fluorescent miltefosine localizes to the Sporothrix cell membrane and mitochondria and causes cell death through increased permeabilization. Milteforan decreases S. brasiliensis fungal burden in A549 pulmonary cells and bone marrow-derived macrophages and also has an immunomodulatory effect by decreasing TNF-α, IL-6, and IL-10 production. Our results suggest milteforan as a possible alternative to treat feline sporotrichosis., Importance: Sporotrichosis is an endemic disease in Latin America caused by different species of Sporothrix. This fungus can infect domestic animals, mainly cats and eventually dogs, as well as humans. Few drugs are available to treat this disease, such as itraconazole, terbinafine, and amphotericin B, but resistance to these agents has risen in the last few years. Alternative new therapeutic options to treat sporotrichosis are essential. Here, we propose milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, as a possible therapeutic alternative for treating sporotrichosis. Milteforan decreases S. brasiliensis fungal burden in human and mouse cells and has an immunomodulatory effect by decreasing several cytokine production., Competing Interests: The authors declare no conflict of interest.

Industrial effluents, especially those containing dyes, have become the main cause of contamination of water resources. In this context, Brazilian bentonite/MgO composites, with excellent adsorptive properties, were prepared and investigated for their effectiveness in removing cationic and anionic dyes from aqueous solutions. The new adsorbents were obtained using Brazilian bentonites and MgO using the mechanochemical method followed by heat treatment (at 700 °C for 4 h). Different characterization techniques were used for the chemical, mineralogical, thermal, surface, and morphological analysis of the raw clays and the composites. The experimental adsorption isotherms were quantified under different conditions of initial concentration, contact time, pH, adsorbent dosage, and temperature variation to interpret the adsorption mechanism of the crystal violet (CV) and Congo red (CR) dyes. The modeling results were obtained from the empirical Sips equation and Pseudo Second Order (PSO) kinetics, indicating that the adsorption of molecules is a heterogeneous phenomenon that occurs in a monolayer on the surface (n s  > 1), with the adsorption rate determined by chemisorption. The composites showed the best removal efficiency performance compared to the raw bentonites, with an increase of 12% for the CV dye and 46% for the CR dye. In addition, the q max values obtained were 423.02 mg/g and 479.86 mg/g (AM01). This research underscores the potential of Brazilian bentonite/MgO composites as a promising solution for the removal of cationic and anionic dyes from water, offering hope for future applications in the field of environmental engineering and materials science., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The efficacy of GLP1 receptor agonists (GLP1-RAs) in treating polycystic ovarian syndrome (PCOS) remains unclear. While GLP1-RAs are known to promote weight loss in patients with diabetes and living with obesity, their impact on weight reduction and hormonal regulation in women with PCOS is understudied. Therefore, we aimed to assess the efficacy of GLP1-RAs in PCOS women living with obesity through a meta-analysis, comparing their effects to placebo., Hypothesis: The use of GLP1-RAs in PCOS women living with obesity can reduce body mass index and waist circumference as well as improve hyperinsulinism, and hyperandrogenism as well as normalize total testosterone, total cholesterol and HOMA-IR markers in PCOS women living with obesity., Methods: We systematically searched the PubMed, Cochrane Central, Scopus and Embase databases to identify randomized controlled trials (RCT) comparing GLP1-RAs versus placebo among women diagnosed with PCOS based on the Rotterdam Criteria. Our primary outcomes of interest included body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. We performed data extraction and quality assessment for studies that met the inclusion criteria. We pooled mean difference (MD) and 95 % confidence intervals (CI) with a random-effect model for continuous endpoints., Results: We included 176 participants from four RCTs. Semaglutide and Liraglutide were used in 23 (13 %) and 103 (58 %) participants, respectively. GLP1-RAs use was associated with a significant reduction in waist circumference (MD: -5.16 cm; 95 % CI: -6.11 to -4.21; p ˂ 0.00001), body mass index (BMI) (MD: -2.42; 95 % CI: -3.10 to -1.74; p ˂ 0.00001), serum triglycerides (MD: -0.20; 95 % CI: -0.30 to -0.11; p ˂ 0.00001) and total testosterone levels (MD: -1.33; 95 % CI: -2.55 to -0.12; p = 0.03) when compared to placebo. There was no significant difference in total cholesterol (MD: -0.04; 95 % CI: -0.10 to 0.01; p = 0.15) and HOMA-IR (MD: -0.30; 95 % CI: -0.92 to 0.32; p = 0.35) levels. Adverse events information was available for 112 patients, where 49 had light side effects such as nausea and abdominal pain., Conclusion: The use of GLP1-RAs demonstrates efficacy in reducing BMI, triglycerides, waist circumference and total testosterone. There was no significant difference in total cholesterol and HOMA-IR levels. These results signify its viability as a favourable treatment option for managing PCOS symptoms in women living with obesity., Competing Interests: Declaration of competing interest All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the influence in torrefaction of the chemical structure of biomasses from nine poplar commercial SRC clones, evaluated through analytical pyrolysis. The chemical data were integrated into a dataset including LHV gain, representative of torrefaction aptitude and six chemical variables obtained through analytical pyrolysis, which were: (i) CH 2 Cl 2 extractives; (ii) total extractives; (iii) Py-lignin; (iv) holocellulose; (v) (syringil/guaiacyl) ratio; and (vi) (pentosan/hexosan) ratio. Significant univariate and bivariate linear relations were obtained with LHV gain from torrefaction as dependent variable vs. Py-lignin, CH 2 Cl 2 extractives and (cP/cH) ratio. Representative results were: (i) a negative correlation of -0.82 and -0.76 between LHV gain and the (pentosan/hexosan) ratio and Py-lignin, respectively, and (ii) a positive correlation of 0.79 between LHV gain and CH 2 Cl 2 extractive amounts. Factorial and discriminant analysis allowed for clustering the tested clones in three groups, evidencing relevant influences of (S/G) ratio, Py-lignin, and, to a lesser extent, (cP/cH) ratio in the classification of these groups, clearly showing the impact of chemical variables of feedstock in torrefaction. The results contribute: (i) to the validation of use of the expedite analytical pyrolysis technique for classification of biomasses in accordance with their torrefaction aptitude and, thereby, (ii) to optimizing strategies in technological issues as diverse as poplar clone genetic breeding and modeling biomass torrefaction and pyrolysis.

Background: Zoonotic sporotrichosis caused by Sporothrix brasiliensis has become the main subcutaneous mycosis in Brazil. Minas Gerais (MG) is located in southeast Brazil and since 2015 has experienced an epidemic of zoonotic sporotrichosis., Objectives: This study aimed to reconstruct the epidemiological scenario of sporotrichosis from S. brasiliensis in recent epizooty in the Metropolitan Region of Belo Horizonte (MRBH), MG., Methods: A total of 95 Sporothrix spp. isolates (Sporothirx brasiliensis n = 74, S. schenckii n = 11 and S. globosa n = 10) were subjected to Amplified Fragment Length Polymorphism (AFLP) genotyping and mating-type analysis to determine genetic diversity and population structure. Of these, 46 S. brasiliensis isolates were recovered from animals (cats n = 41 and dogs n = 5) from MRBH., Results: Our study describes the high interspecific differentiation power of AFLP-based genotyping between the main phylogenetic Sporothrix groups. S. brasiliensis presents high genetic variability and pronounced population structure with geographically focused outbreaks in Brazil. The genetic groups include older genotypes from the prolonged epidemic in Southeast (Rio de Janeiro and São Paulo), South (Rio Grande do Sul), Northeast (Pernambuco) and new genotypes from the MRBH. Furthermore, we provide evidence of heterothallism mating strategy in pathogenic Sporothrix species. Genotypes originating in Rio de Janeiro and Pernambuco carry the predominant MAT1-2 idiomorph as opposed to genotypes from Rio Grande do Sul, which have the MAT1-1 idiomorph. We observed an overwhelming occurrence of MAT1-1 among MRBH isolates., Conclusion: Our study provides clear evidence of the predominance of a genetic group profile circulating in animals in Minas Gerais, independent of that disseminated from Rio de Janeiro. Our data can help us understand the genetic population processes that drive the evolution of this fungus in Minas Gerais and contribute to future mitigation actions for this ongoing epidemic., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background Aims: Adequate re-establishment of thymopoiesis is critical for long-term immune reconstitution after hematopoietic cell transplantation (HCT), potentially impacting patient survival rates. This study aimed to evaluate immune reconstitution in pediatric HCT recipients by quantifying recent thymic emigrants (RTEs), specifically CD3 + CD31 + CD45RA + cells., Methods: We conducted a retrospective analysis of 186 pediatric patients transplanted between 2013 and 2020, undergoing their first allogeneic HCT, who were alive in the first 100 days after transplantation with immune recovery evaluation at three time points: day 100, day 180 and day 360 after HCT. We analyzed the distribution of peripheral blood subsets of T, B and natural killer lymphocytes and assessed the impact of underlying disease, HCT type, stem cell source, recipient age, conditioning regimen, graft-versus-host disease (GVHD) occurrence and cytomegalovirus (CMV) reactivation on immune recovery., Results: At day 100, patients under 10 years exhibited higher RTE CD4 + and CD8 + CD31 + CD45RA + counts compared with older patients (5.3 versus 2.2 cells/µL, P = 0.022 and 48 versus 72.8 cells/µL, P = 0.049, respectively). Patients with haploidentical HCT had lower RTE CD4 + counts compared with those with unrelated or related donors (2.4 versus 4.4 versus 7.9 cells/µL, P = 0.024). Administration of rabbit anti-thymocyte globulin negatively impacted RTE CD4 + production (median, 6.5 versus 2.4 cells/µL, P = 0.007). At day 180, the presence of GVHD had a negative influence on RTE production (11.7 versus 56.8 cells/µL, P < 0.001), particularly higher-grade acute GVHD (without, 56.8 cells/µL, grade 1-2, 28.1 cells/µL, grade 3-4, 6.0 cells/µL, P < 0.001). Patients with CMV reactivation had higher CD8 + CD31 + CD45RA + compared with those without reactivation (median, 204.6 versus 100.2 cells/µL, P = 0.022). At day 360, no variables significantly affected RTE recovery. Overall survival at 5-year follow-up was 87.7%, with a median of 1170 days (range, 122-3316). Multivariate analysis showed that age >10 years (P = 0.038), negative CMV donor serology (P = 0.0029) and acute GVHD (P = 0.0026) had a negative impact on survival., Conclusions: This study highlights variations in RTE production based on patient age, donor type and immunosuppression regimen employed., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Mammalian Ste-20-like Kinases 1 and 2 (MST1/2) are core serine-threonine kinases of the Hippo pathway regulating several cellular processes, including cell cycle arrest and cell death. Here, we discovered a novel alternative splicing variant of the MST2 encoding gene, STK3, in malignant cells and tumor datasets. This variant, named STK3 ∆7 or MST2 ∆7 (for mRNA or protein, respectively), resulted from the skipping of exon 7. MST2 ∆7 exhibited increased ubiquitylation and interaction with the E3 ubiquitin-protein ligase CHIP compared to the full-length protein (MST2 FL ). Exon 7 in STK3 encodes a segment within the kinase domain, and its exclusion compromised MST2 interaction with and phosphorylation of MOB, a major MST1/2 substrate. Nevertheless, MST2 ∆7 was capable of interacting with MST1 and MST2 FL . Unlike MST2 FL , overexpression of MST2 ∆7 did not lead to increased cell death and growth arrest. Strikingly, we observed the exclusion of STK3 exon 7 in 3.2-15% of tumor samples from patients of several types of cancer, while STK3 ∆7 was seldomly found in healthy tissues. Our study identified a novel STK3 splicing variant with loss of function and the potential to disturb tissue homeostasis by impacting on MST2 activities in the regulation of cell death and quiescence., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The IgG response against SARS-CoV-2 infection can persist for over six months (long response; LR). However, among 30% of those infected, the duration can be as short as three months or less (short response; SR). The present study assembled serological data on the anti-SARS-CoV-2 IgG response duration of two previous studies and integrated these results with the plasmatic cytokine levels and genetic profile of 10 immune-relevant SNPs that were also previously published, along with the plasmatic total IgG, IgA, and IgM levels, allowing for the genetic, clinical, immunological, and epidemiological aspects of the post-COVID-19 IgG response duration to be understood. The SR was associated with previous mild acute COVID-19 and with an SNP (rs2228145) in IL6R related to low gene expression. Additionally, among the SR subgroup, no statistically significant Spearman correlations were observed between the plasma levels of IL-17A and the Th17 regulatory cytokines IFN-γ (rs = 0.2399; p = 0.1043), IL-4 (rs = 0.0273; p = 0.8554), and IL-2 (rs = 0.2204; p = 0.1365), while among the LR subgroup, weaker but statistically significant Spearman correlations were observed between the plasma levels of IL-17A and IFN-γ (rs = 0.3873; p = 0.0016), IL-4 (rs = 0.2671; p = 0.0328), and IL-2 (rs = 0.3959; p = 0.0012). These results suggest that the Th17 response mediated by the IL-6 pathway has a role in the prolonged IgG response to SARS-CoV-2 infection.

Objectives: Candida spp. is an opportunistic pathogen that causes superficial and invasive infections with nosocomial outbreaks without strict hygiene protocols. Herein, we assessed oral colonisation by Candida spp. in 209 Intensive Care Unit (ICU) patients between July 2021 and April 2022, conducting clinical, epidemiological, and microbiological characterisation of those developing oral or invasive candidiasis., Methods: Initial oral swabs were collected within 24 h of admission in the ICU, followed by collections on Days 2, 4, 6 and 8. Swabs from denture-wearing patients, abiotic surfaces, healthcare professionals' hands, and retroauricular regions were also obtained. Recovered yeasts and filamentous fungi were identified using MALDI-TOF MS and morphological characteristics, respectively. Genetic similarity of Candida spp. isolates was evaluated using Amplified fragment length polymorphism (AFLP), and the antifungal susceptibility profile was determined by broth microdilution., Results: In the study, 64.11% of patients were orally colonised by Candida spp. Of these, 80.59% were colonised within the first 24 h. Oral colonisation also occurred on subsequent days: 50%/Day 2, 26.92%/Day 4, and 11.53%/Days 6 and 8. Of the patients, 8.61% had oral candidiasis, mainly pseudomembranous. Among orally colonised patients, 2.23% developed invasive candidiasis. Besides, 89.47% of healthcare professionals evaluated were colonised. MALDI-TOF MS identified different yeast species, and C. albicans (45.34%), C. tropicalis (15.7%), and C. parapsilosis sensu stricto (9.88%) were the most prevalent. AFLP analysis indicated a high genetic correlation (≥97%) between C. parapsilosis sensu stricto isolates from patients and professionals. Three resistant C. albicans isolates were also found., Conclusion: This study reported a diversity of yeast and filamentous fungi species in ICU patients and highlighted early Candida spp. colonisation risks for invasive candidiasis, as well as the potential horizontal transmission in the nosocomial setting, emphasising the need for effective infection control measures., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options. Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi. Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B. Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale. Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml -1 and 32 to 128 µg ml -1 , respectively. Biofilms were sensitive, with a significant reduction ( P <0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml -1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml -1 . As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction. Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.

Objective: To enhance Making Every Contact Count (MECC, an opportunistic approach to health promotion), training in the Third and Social Economy (TSE, all groups and organisations primarily working towards social justice, outside of the government or household) by examining the degree to which the behavioural content of MECC training tackled significant factors influencing MECC delivery., Methods and Measures: A strategic behavioural analysis design. Semi-structured interviews with service providers ( n  = 15) and users ( n  = 5) were coded for barriers and facilitators of MECC delivery using the Theoretical Domains Framework (TDF). Existing MECC training was coded for behaviour change techniques (BCTs) and intervention functions (IFs). The degree to which BCTs and IFs addressed the key TDF domains of influences on MECC delivery in the TSE were examined using prespecified tools., Results: Seven key TDF domains of influences in MECC delivery were identified. Overall, only 9/31 linked BCTs were utilised within MECC training, with percentage utilisation of relevant BCTs for each domain ranging from 0% to 66.7%. Training adequately addressed 2/7 key domains., Conclusion: The TSE and healthcare share many common key TDF domains, although there are differences in how each are relevant. Limitations and recommendations for MECC training are discussed.

Background: The Making Every Contact Count (MECC) programme provides training and materials to support public-facing workers to encourage health-promoting behaviour change by using the day-to-day interactions between organisations and individuals. This project aimed to analyse MECC implementation through a comparative analysis of implementation stage, strategies used for implementation and enablers/barriers of the implementation process within a region in England-the North East and North Cumbria (NENC)., Methods: A mixed-methods process evaluation was conducted applying normalisation process theory and theoretical domains framework. MECC programme documents were reviewed and mapped against specific criteria (eg, implementation strategies). An online mapping survey was conducted to establish current implementation/delivery of MECC within NENC settings (eg, local government, healthcare and voluntary community sector). Qualitative research, using individual interviews and group discussions, was conducted to establish further understanding of MECC implementation., Results: Our findings were informed by reviewing documents (n=5), surveying participants (n=34), interviews (n=18) and group discussions (n=48). Overall, the implementation of MECC within the region was at an early stage, with training mostly delivered between, rather than within, organisations. Qualitative findings highlighted factors that influence stakeholders to implement MECC (eg, organisational goals that were facilitated by MECC implementation, including the prevention agenda), supported resources that facilitate the implementation of MECC (eg, logic models) and enabling factors that promote MECC sustainability across the region (eg, buy-in from leadership and management)., Conclusions: The NENC MECC programme is built around regional leadership that supports the implementation process. This process evaluation identified key influences of MECC implementation across the region. We discuss evidence-based recommendation for policy and practice that can be taken forward to develop targeted strategies to support future MECC implementation. For example, a co-ordinated infrastructure and strategy is needed to combat delivery and implementation issues identified., Competing Interests: Competing interests: AMR, BN, RW, CC, BG, TF, CH, DH, GM, EG and DO have no conflicts of interest. CR and JH are the Regional MECC Coordinator and MECC Strategy Group Chair, respectively, and supported this project in terms of recruitment and dissemination., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Cat-transmitted sporotrichosis is caused by the emerging fungal pathogen Sporothrix brasiliensis and constitutes a significant public health issue that affects people living in resource-poor urban centers in Brazil. The lack of knowledge about transmission dynamics makes it difficult to propose public health policies to contain the advance of sporotrichosis. We describe the recent emergence of 1,176 cases of sporotrichosis in cats (2016 to 2021) in the metropolitan region of Recife, Brazil, leading to significant zoonotic transmission and an overwhelming occurrence of S. brasiliensis as the etiological agent. Most cases were from cats in the cities of Olinda (408/1,176; 34.70%), Jaboatão dos Guararapes (332/1,176; 28.23%), and Recife (237/1,176; 20.15%). Molecular typing using amplified fragment length polymorphism (EcoRI-GA/MseI-AG) revealed low polymorphic information content (PIC = 0.2499) and heterozygosity (H = 0.2928), typical of an outbreak scenario. Dendrogram and multivariate cluster analysis revealed that isolates from Pernambuco are closely related to Rio de Janeiro isolates. We report a substantial occurrence of MAT1-2 idiomorphs in the metropolitan region of Recife (0:60 ratio; χ 2  = 60.000, P < 0.0001). The limited population differentiation and genetic diversity of the isolates from Pernambuco suggest a recent introduction, possibly via a founder effect, from the parental population in Rio de Janeiro. Our findings emphasize the critical importance of molecular surveillance of S. brasiliensis for outbreak response. A comprehensive one-health strategy is mandatory to control the spread of cat-transmitted sporotrichosis driven by S. brasiliensis, encompassing sanitary barriers, quick diagnosis, and treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The global diversity of fungi has been estimated between 2 to 11 million species, of which only about 155 000 have been named. Most fungi are invisible to the unaided eye, but they represent a major component of biodiversity on our planet, and play essential ecological roles, supporting life as we know it. Although approximately 20 000 fungal genera are presently recognised, the ecology of most remains undetermined. Despite all this diversity, the mycological community actively researches some fungal genera more commonly than others. This poses an interesting question: why have some fungal genera impacted mycology and related fields more than others? To address this issue, we conducted a bibliometric analysis to identify the top 100 most cited fungal genera. A thorough database search of the Web of Science, Google Scholar, and PubMed was performed to establish which genera are most cited. The most cited 10 genera are Saccharomyces , Candida , Aspergillus , Fusarium , Penicillium , Trichoderma , Botrytis , Pichia , Cryptococcus and Alternaria . Case studies are presented for the 100 most cited genera with general background, notes on their ecology and economic significance and important research advances. This paper provides a historic overview of scientific research of these genera and the prospect for further research. Citation: Bhunjun CS, Chen YJ, Phukhamsakda C, Boekhout T, Groenewald JZ, McKenzie EHC, Francisco EC, Frisvad JC, Groenewald M, Hurdeal VG, Luangsa-ard J, Perrone G, Visagie CM, Bai FY, Błaszkowski J, Braun U, de Souza FA, de Queiroz MB, Dutta AK, Gonkhom D, Goto BT, Guarnaccia V, Hagen F, Houbraken J, Lachance MA, Li JJ, Luo KY, Magurno F, Mongkolsamrit S, Robert V, Roy N, Tibpromma S, Wanasinghe DN, Wang DQ, Wei DP, Zhao CL, Aiphuk W, Ajayi-Oyetunde O, Arantes TD, Araujo JC, Begerow D, Bakhshi M, Barbosa RN, Behrens FH, Bensch K, Bezerra JDP, Bilański P, Bradley CA, Bubner B, Burgess TI, Buyck B, Čadež N, Cai L, Calaça FJS, Campbell LJ, Chaverri P, Chen YY, Chethana KWT, Coetzee B, Costa MM, Chen Q, Custódio FA, Dai YC, Damm U, de Azevedo Santiago ALCM, De Miccolis Angelini RM, Dijksterhuis J, Dissanayake AJ, Doilom M, Dong W, Alvarez-Duarte E, Fischer M, Gajanayake AJ, Gené J, Gomdola D, Gomes AAM, Hausner G, He MQ, Hou L, Iturrieta-González I, Jami F, Jankowiak R, Jayawardena RS, Kandemir H, Kiss L, Kobmoo N, Kowalski T, Landi L, Lin CG, Liu JK, Liu XB, Loizides M, Luangharn T, Maharachchikumbura SSN, Makhathini Mkhwanazi GJ, Manawasinghe IS, Marin-Felix Y, McTaggart AR, Moreau PA, Morozova OV, Mostert L, Osiewacz HD, Pem D, Phookamsak R, Pollastro S, Pordel A, Poyntner C, Phillips AJL, Phonemany M, Promputtha I, Rathnayaka AR, Rodrigues AM, Romanazzi G, Rothmann L, Salgado-Salazar C, Sandoval-Denis M, Saupe SJ, Scholler M, Scott P, Shivas RG, Silar P, Souza-Motta CM, Silva-Filho AGS, Spies CFJ, Stchigel AM, Sterflinger K, Summerbell RC, Svetasheva TY, Takamatsu S, Theelen B, Theodoro RC, Thines M, Thongklang N, Torres R, Turchetti B, van den Brule T, Wang XW, Wartchow F, Welti S, Wijesinghe SN, Wu F, Xu R, Yang ZL, Yilmaz N, Yurkov A, Zhao L, Zhao RL, Zhou N, Hyde KD, Crous PW (2024). What are the 100 most cited fungal genera? Studies in Mycology 108 : 1-411. doi: 10.3114/sim.2024.108.01., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 Westerdijk Fungal Biodiversity Institute.)

Background: Around twenty percent of meningitis survivors experience after-effects. However, very little research on their psychological impact has been conducted. This report details a small explorative investigation into these psychological impacts., Objective: To explore the impact sequelae have on the meningitis survivors affected., Methods and Measures: Thematic analysis of one-hundred individual user's blog posts, self-reporting one or more sequelae after a diagnosis of meningitis., Results: Blog posters' experiences varied greatly. Common trends in experience were mapped onto three themes. 'Struggling to Adjust to the New Normal' captures blog posters' struggles in returning to their lives post-hospitalization. 'Navigating Possibilities for Positivity' explores how blog posters either reported positive change due to their illness experience or felt a pressure, or inability, to do so. 'The Impact of Knowledge and Support' overarching two sub-themes; 'Lack of Awareness Causing Further Suffering' and 'Validation Leads to Narrative Shift'. These sub-themes contrast differences in experience blog posters reported, with and without knowledge, of the cause of their symptoms and support in dealing with the resulting difficulties., Conclusions: Consistent and structured after-care would benefit patients experiencing sequelae. Suggestions of a possible format this could take are put forward. In addition, self-regulatory models of illness perception help explain some variations in blog posters experiences, with possible intervention plans based on these models also suggested. However, limitations, including the comparatively small and highly selected sample, mean that further research is necessary to validate the findings and assess their validity, widespread applicability, and financial feasibility.

Objectives: We aimed to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial SpA (axSpA), peripheral SpA (pSpA) and (PsA)., Methods: The ASAS-perSpA study data were analysed. Models for the three patient groups were run separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively., Results: The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA.In axSpA, disease activity (β = -0.061), physical function (β = -0.041), female sex (β = -0.019) and fibromyalgia (FM) (β = -0.068) were associated with worse HRQoL; age (β = 0.001) and university education (β = 0.014) were associated with better HRQoL. In pSpA, disease activity (β = -0.04) and physical function (β = -0.054) were associated with worse HRQoL. In PsA, disease activity (β = -0.045), physical function (β = -0.053), axial disease (β = -0.041) and female sex (β = -0.028) were associated with worse HRQoL. In axSpA, disease activity (β = 0.889), physical function (β = 0.887), peripheral disease (β = 0.564), female sex (β = 0.812) and FM (β = 1.639) were associated with worse GH; age (β = -0.013) and university education (β = -0.274) were associated with better GH. In pSpA, physical function (β = 1.142) and female sex (β = 1.060) were associated with worse GH; university education (β = -0.611) was associated with better GH. In PsA, disease activity (β = 0.703), physical function (β = 1.025), axial involvement (β = 0.659), female sex (β = 0.924) and FM (β = 1.387) were associated with worse GH; age (β = -0.024) and university education (β = -0.856) were associated with better GH., Conclusion: Disease activity and physical function are major HRQoL and GH determinants across SpA types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs., Methods: We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other., Results: In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data., Conclusion: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response., Method: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up., Results: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis., Conclusion: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Background: Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation's demographic diversity., Methods: We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering PIK3CA , AKT1 , ESR1 , ERBB2 , BRCA1 , BRCA2 , PALB2 , TP53 , but not PTEN ) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI])., Results: Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in PIK3CA and 1.8% in AKT1 . Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the PIK3CA mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2 , or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases., Conclusion: We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives., Competing Interests: Authors TR, AG, MP, LO, CR, LL, CB, MM, & RD were employed by the company Oncoclínicas & Co. TR – Research funding: AstraZeneca, Libbs. Speaker honoraria/advisory board: AstraZeneca, Daichi-Sankyo, Novartis, MSD, Lilly, Libbs. RD declares advisory role for Roche, Foundation Medicine, received a speaker’s fee from Roche, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp & Dohme, Lilly, AstraZeneca, Janssen, Takeda, Bristol Myers Squibb, GlaxoSmithKline, Gilead, research grants from Merck, Novartis, Daiichi-Sankyo, GlaxoSmithKline and AstraZeneca, and is investor in Trialing Health, S.L. CB - Stock and Other Ownership Interests: Biomarker, MedSIR, Tummi. Speaker Honoraria: Novartis, Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, Eisai. Consulting or Advisory Role: Boehringer Ingelheim, Roche/Genentech, Novartis, GlaxoSmithKline, Eisai,Pfizer, AstraZeneca, Libbs, MSD Oncology, United Medical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Reinert, do Rego, Silva, Rodrigues, Koyama, Gonçalves, Pauletto, de Carvalho Oliveira, de Resende, Landeiro, Barrios, Mano and Dienstmann.)

Sporotrichosis is a globally distributed subcutaneous mycosis caused by dimorphic Sporothrix species commonly found in soil, mosses, and decaying plant matter. The lymphocutaneous manifestation, historically associated with occupational activities and sapronotic transmission, has recently been observed to also occur through animal contact, particularly notable in Brazil. We describe a rare case of lymphocutaneous sporotrichosis with simultaneous pulmonary complications resulting from the scratching of a southern three-banded armadillo, Tolypeutes matacus, primarily inhabiting the arid forests of South America's central region. Speciation using multiplex quantitative polymerase chain reaction (qPCR) established the etiological agent as S. schenckii s. str., while amplified fragment length polymorphism (AFLP) analysis unveiled a novel genotype circulating in the Midwest of Brazil. The patient received treatment with itraconazole (200 mg/day) for two months, leading to substantial clinical improvement of cutaneous and pulmonary symptoms. This case highlights the critical role of animal-mediated transmission in sporotrichosis epidemiology, particularly within regions with diverse armadillo species. The unusual epidemiology and genetic characteristics of this case emphasize the need for enhanced awareness and diagnostic vigilance in atypical sporotrichosis presentations., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Solid lipid nanoparticles (SLNs) represent promising nanostructures for drug delivery systems. This study successfully synthesized SLNs containing different proportions of babassu oil (BBS) and copaiba oleoresin (COPA) via the emulsification-ultrasonication method. Before SLN synthesis, the identification and quantification of methyl esters, such as lauric acid and β-caryophyllene, were performed via GC-MS analysis. These methyl esters were used as chemical markers and assisted in encapsulation efficiency experiments. A 2 2 factorial design with a center point was employed to assess the impact of stearic acid and Tween 80 on particle hydrodynamic diameter (HD) and polydispersity index (PDI). Additionally, the effects of temperature (8 ± 0.5 °C and 25 ± 1.0 °C) and time (0, 7, 15, 30, 40, and 60 days) on HD and PDI values were investigated. Zeta potential (ZP) measurements were utilized to evaluate nanoparticle stability, while transmission electron microscopy provided insights into the morphology and nanometric dimensions of the SLNs. The in vitro cytotoxic activity of the SLNs (10 µg/mL, 30 µg/mL, 40 µg/mL, and 80 µg/mL) was evaluated using the MTT assay with PC-3 and DU-145 prostate cancer cell lines. Results demonstrated that SLNs containing BBS and COPA in a 1:1 ratio exhibited a promising cytotoxic effect against prostate cancer cells, with a percentage of viable cells of 68.5% for PC-3 at a concentration of 30 µg/mL and 48% for DU-145 at a concentration of 80 µg/mL. These findings underscore the potential therapeutic applications of SLNs loaded with BBS and COPA for prostate cancer treatment.

Background: Low back pain (LBP) is a common health condition and the leading cause of years lived with disability worldwide. Most LBP episodes have a favourable prognosis, but recurrences within a year are common. Despite the individual and societal impact related to LBP recurrences, there is limited evidence on effective strategies for secondary prevention of LBP and successful implementation of intervention programmes in a real-world context. The aim of this study is to analyse the effectiveness of a tailored exercise and behavioural change programme (MyBack programme) in the secondary prevention of LBP; and evaluate acceptability, feasibility and determinants of implementation by the different stakeholders, as well as the implementation strategy of the MyBack programme in real context., Methods: This protocol describes a hybrid type I, randomized controlled trial to evaluate the effectiveness and implementation of MyBack programme in the context of primary health care. The Behaviour Change Wheel framework and FITT-VP principles will inform the development of the behaviour change and exercise component of MyBack programme, respectively. Patients who have recently recovered from an episode of non-specific LBP will be randomly assigned to MyBack and usual care group or usual care group. The primary outcome will be the risk of LBP recurrence. The secondary outcomes will include disability, pain intensity, musculoskeletal health, and health-related quality of life. Participants will be followed monthly for 1 year. Costs data related to health care use and the MyBack programme will be also collected. Implementation outcomes will be assessed in parallel with the effectiveness study using qualitative methods (focus groups with participants and health providers) and quantitative data (study enrolment and participation data; participants adherence)., Discussion: To our knowledge, this is the first study assessing the effectiveness and implementation of a tailored exercise and behaviour change programme for prevention of LBP recurrences. Despite challenges related to hybrid design, it is expected that data on the effectiveness, cost-effectiveness, and implementation of the MyBack programme may contribute to improve health care in patients at risk of LBP recurrences, contributing to direct and indirect costs reduction for patients and the health system., Trial Registration Number: NCT05841732., (© 2024. The Author(s).)