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Leishmaniasis is a complex disease caused by infection with different Leishmania parasites. The number of medications used for its treatment is still limited and the discovery of new drugs is a valuable approach. In this context, here we describe the in vitro leishmanicidal activity and the in silico interaction between trypanothione reductase (TryR) and (-)-5-demethoxygrandisin B from the leaves of Virola surinamensis (Rol.) Warb. The compound (-)-5-demethoxygrandisin B was isolated from V. surinamensis leaves, a plant found in the Brazilian Amazon, and it was characterized as (7R,8S,7R,8S)-3,4,5,3,4-pentamethoxy-7,7-epoxylignan. In vitro antileishmanial activity was examined against Leishmania amazonensis, covering both promastigote and intracellular amastigote phases. Cytotoxicity and nitrite production were gauged using BALB/c peritoneal macrophages. Moreover, transmission electron microscopy was applied to probe ultrastructural alterations, and flow cytometry assessed the shifts in the mitochondrial membrane potential. In silico methods such as molecular docking and molecular dynamics assessed the interaction between the most stable configuration of (-)-5-demethoxygrandisin B and TryR from L. infantum (PDB ID 2JK6). As a result, the (-)-5-demethoxygrandisin B was active against promastigote (IC50 7.0 µM) and intracellular amastigote (IC50 26.04 µM) forms of L. amazonensis, with acceptable selectivity indexes. (-)-5-demethoxygrandisin B caused ultrastructural changes in promastigotes, including mitochondrial swelling, altered kDNA patterns, vacuoles, vesicular structures, autophagosomes, and enlarged flagellar pockets. It reduced the mitochondria membrane potential and formed bonds with important residues in the TryR enzyme. The molecular dynamics simulations showed stability and favorable interaction with TryR. The compound targets L. amazonensis mitochondria via TryR enzyme inhibition.

Abstract Background A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells. Methods We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results. Results We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown. Conclusions Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.

Objective: This study aimed to assess the cause of acute pharyngitis and determine the duration of severe and moderate symptoms based on the aetiology. Design: Prospective observational study. Site: One urban health care centre. Participants: Patients aged 15 or older with acute pharyngitis were included. Interventions: Bacterial identification was carried out in the microbiology lab using MALDI-TOF in two throat samples. Patients received a symptom diary to return after one week. Main measurements: Number of days with severe symptoms, scoring 5 or more in any of the symptoms included in the symptom diary, and moderate symptoms, scoring 3 or more. Results: Among the 149 patients recruited, beta-haemolytic streptococcus group A (GABHS) was the most common aetiology. Symptoms and signs alone as well as the mean Centor score cannot distinguish between GABHS and other bacterial causes in patients with acute pharyngitis. However, there was a trend indicating that infections caused by Streptococcus dysgalactiae and Streptococcus agalactiae presented more severe symptoms, whereas infections attributed to the Streptococcus anginosus group, Fusobacterium spp., and those where oropharyngeal microbiota was isolated tended to have milder symptoms. S. dysgalactiae infections showed a trend towards longer severe and moderate symptom duration. Conclusion: GABHS was the most prevalent, but group C streptococcus caused more severe and prolonged symptoms. Resumen: Objetivo: Evaluar la etiología de los episodios de faringitis aguda y determinar la duración de los síntomas graves y moderados según la etiología. Métodos: Estudio observacional prospectivo. Emplazamiento: Un centro de salud urbano. Participantes: Se incluyeron pacientes de 15 años o más con faringitis aguda. Intervenciones: Se realizó identificación bacteriana en el laboratorio de microbiología utilizando MALDI-TOF en 2 muestras faríngeas. Los pacientes recibieron un diario de síntomas que devolvieron a la semana. Medidas prinicpales: Número de días con síntomas graves, aquellas puntuaciones de 5 o más en cualquiera de los síntomas del diario de síntomas, y síntomas moderados con puntuaciones de 3 o más. Resultados: Entre los 149 pacientes incluidos, el estreptococo beta-hemolítico del grupo A (EBHGA) fue la etiología más común. Tanto los síntomas y signos como la puntuación media de la escala de Centor no permiten distinguir la infección de EBHGA de las otras causas bacterianas en pacientes con faringitis aguda. Sin embargo, se observó una tendencia en que las infecciones por S. dysgalactiae y agalactiae presentaban síntomas más graves, mientras que S. grupo anginosus, Fusobacterium spp. y aquellos con microbiota orofaringea solían presentar síntomas más leves. Las infecciones por S. dysgalactiae mostraron una tendencia hacia una mayor duración de síntomas graves y moderados. Conclusión: El EBHGA es el más prevalente, pero el estreptococo del grupo C causa síntomas más graves y prolongados.

Abstract This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses’ use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15–0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29–1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17–1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in β-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.

En algunos casos de infecciones, es frecuente observar inclusiones gigantes en los leucocitos. Sin embargo, estas inclusiones también pueden estar relacionadas con trastornos genéticos raros, como el síndrome de Chédiak–Higashi (SCH). Para realizar un diagnóstico diferencial entre estos grupos de patologías, es necesario realizar estudios genéticos específicos. Dada la dificultad y especifidad de la confirmación diagnóstica, es esencial analizar los antecedentes clínicos y patológicos del paciente, con el fin de obtener una orientación diagnóstica.

Giant inclusions in leukocytes is a common feature that can be observed in some infections but can be also related to rare genetic disorders such as Chédiak-Higashi syndrome (CHS). A differential diagnosis between these groups of diseases has to be performed using specific genetic tests. Clinical and pathological history is relevant for a diagnostic orientation due to the difficulty and specificity of the diagnostic confirmation.

Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown impressive results in EGFR mutant lung cancer (LC) patients in terms of disease control rate with a positive impact on overall survival. Nevertheless, after months of treatment with targeted therapy, progression inevitably occurs. Some patients develop oligoprogression and local treatment is required for optimal disease control while maintaining EGFR-TKIs. This work features a clinical case of a patient harboring an EGFR mutant LC undergoing oligoprogression to EGFR-TKIs, first into the brain and afterward to the primary tumor, requiring local ablative strategies, including primary tumor resection three years after the start of osimertinib. Currently, the patient is still alive and continues with a complete response upon EGFR-TKIs maintenance. Hence, oligoprogression, even in driven oncogenic tumors, represents a distinct biological entity and potential curative disease that deserves particular consideration in multidisciplinary tumor boards. In this case, tumor primary resection after three years of the initial diagnosis represents a paradigm shift in the treatment of EGFR mutant patients.

Physical fitness is considered an important indicator of health in adolescents. Despite the recognized benefits of regular physical activity, recent studies indicate a decline in physical fitness among adolescents, including agility, a key component of fitness often overlooked in research. This study aimed to investigate trends in agility among urban Catalan adolescents over two decades. A total of 1439 students, aged 13–15 years, participated in the 8 × 10 m shuttle run test between 2002 and 2022. The results revealed a significant decline in agility performance across both boys (F(3,839) = 392, p < 0.001, ηp2 = 0.584) and girls (F(3,593) = 414, p < 0.001, ηp2 = 0.677) over time, with notable differences observed between consecutive five-year periods. The findings underscore the urgency of addressing declining physical fitness among adolescents and advocate for enhanced physical education programs and community-based interventions to promote regular physical activity. Recognizing the importance of agility and other aspects of physical fitness in adolescent health, policymakers, educators, and healthcare professionals are urged to collaborate on initiatives to mitigate the risk of future health issues. Further research is recommended to explore the multifaceted influences on adolescent physical fitness and develop targeted interventions to improve overall health outcomes in this population.

Introduction: Primary augmentation mammoplasty is one of the main cosmetic surgeries in the plastic surgeon’s routine. The various performance techniques require constant study and extensive training of the specialty’s resident physicians. Methods: Review medical records of patients who underwent primary augmentation mammoplasty at the Hospital das Clínicas of the Faculdade de Medicina de Botucatu from 2017 to 2020. Results: 120 surgeries were performed during the period analyzed. There was a predominance of high-projection (75%) and subfascial (67.5%) implants. There were no major complications, with most patients (75%) not having any minor complications (p

Background Evidence shows a high rate of unnecessary antibiotic prescriptions for respiratory tract infections (RTIs) in primary care. There is increasing evidence showing that shorter courses for RTIs are safe and help in reducing antimicrobial resistance (AMR). Stopping antibiotics earlier, as soon as patients feel better, rather than completing antibiotic courses, may help reduce unnecessary exposure to antibiotics and AMR.Objectives The aim of this study was to explore the perceptions and views of primary care healthcare professionals about customising antibiotic duration for RTIs by asking patients to stop the antibiotic course when they feel better.Design Qualitative research.Setting and participants A total of 21 qualitative interviews with primary care professionals (experts and non-experts in AMR) were conducted from June to September 2023. Data were audiorecorded, transcribed and analysed thematically.Results Overall, experts seemed more amenable to tailoring the antibiotic duration for RTIs when patients feel better. They also found the dogma of ‘completing the course’ to be obsolete, as evidence is changing and reducing the duration might lead to less AMR, but claimed that evidence that this strategy is as beneficial and safe as fixed courses was unambiguous. Non-experts, however, believed the dogma of completing the course. Clinicians expressed mixed views on what feeling better might mean, supporting a shared decision-making approach when appropriate. Participants claimed good communication to professionals and patients, but were sceptical about the risk of medicalisation when asking patients to contact clinicians again for a check-up visit.Conclusions Clinicians reported positive and negative views about individualising antibiotic courses for RTIs, but, in general, experts supported a customised antibiotic duration as soon as patients feel better. The information provided by this qualitative study will allow improving the performance of a large randomised clinical trial aimed at evaluating if this strategy is safe and beneficial.

Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.

Background and aims: Numerous studies point to the comorbidity between gambling disorder (GD) and attention deficit hyperactivity disorder (ADHD). However, there is a lack of research exploring how ADHD symptoms might influence psychological treatment outcomes for GD. Therefore, we aimed to explore differences between patients with GD with and without self-reported ADHD symptoms regarding psychopathology, personality, sociodemographic and treatment outcome measures. Method: This longitudinal study included 170 patients with GD receiving cognitive behavioral therapy. Multiple self-reported instruments were used to assess clinical variables and sociodemographic measures prior to treatment. Results: A clinical profile characterized by greater GD severity, higher psychopathology and impulsivity, and less adaptive personality features was observed in patients with self-reported ADHD symptoms compared to those without. No significant differences in treatment response (measured by dropout and relapse rates) were observed between the two groups. However, patients with self-reported ADHD symptoms experienced more severe relapses (i.e., gambled more money) and GD patients who relapsed scored higher on measures of ADHD, particularly inattention. Conclusion: Individuals with GD and self-reported symptoms of ADHD may experience more severe relapses following treatment, suggesting a need for more vigilant follow-up and interventions for patients with this comorbidity.

Background: The heterogeneity of gambling disorder (GD) has led to the identification of different subtypes, mostly including phenotypic features, with distinctive implications on the GD severity and treatment outcome. However, clustering analyses based on potential endophenotypic features, such as neuropsychological and neuroendocrine factors, are scarce so far. Aims: This study firstly aimed to identify empirical clusters in individuals with GD based on sociodemographic (i.e., age and sex), neuropsychological (i.e., cognitive flexibility, inhibitory control, decision making, working memory, attention, and set-shifting), and neuroendocrine factors regulating energy homeostasis (i.e., leptin, ghrelin, adiponectin, and liver-expressed antimicrobial peptide 2, LEAP-2). The second objective was to compare the profiles between clusters, considering the variables used for the clustering procedure and other different sociodemographic, clinical, and psychological features. Methods: 297 seeking-treatment adult outpatients with GD (93.6% males, mean age of 39.58 years old) were evaluated through a semi-structured clinical interview, self-reported psychometric assessments, and a protocolized neuropsychological battery. Plasma concentrations of neuroendocrine factors were assessed in peripheral blood after an overnight fast. Agglomerative hierarchical clustering was applied using sociodemographic, neuropsychological, and neuroendocrine variables as indicators for the grouping procedure. Comparisons between the empirical groups were performed using Chi-square tests (χ2) for categorical variables, and analysis of variance (ANOVA) for quantitative measures. Results: Three-mutually-exclusive groups were obtained, being neuropsychological features those with the greatest weight in differentiating groups. The largest cluster (Cluster 1, 65.3%) was composed by younger males with strategic and online gambling preferences, scoring higher on self-reported impulsivity traits, but with a lower cognitive impairment. Cluster 2 (18.2%) and 3 (16.5%) were characterized by a significantly higher proportion of females and older patients with non-strategic gambling preferences and a worse neuropsychological performance. Particularly, Cluster 3 had the poorest neuropsychological performance, especially in cognitive flexibility, while Cluster 2 reported the poorest inhibitory control. This latter cluster was also distinguished by a poorer self-reported emotion regulation, the highest prevalence of food addiction, as well as a metabolic profile characterized by the highest mean concentrations of leptin, adiponectin, and LEAP-2. Conclusions: To the best of our knowledge, this is the first study to identify well-differentiated GD clusters using neuropsychological and neuroendocrine features. Our findings reinforce the heterogeneous nature of the disorder and emphasize a role of potential endophenotypic features in GD subtyping. This more comprehensive characterization of GD profiles could contribute to optimize therapeutic interventions based on a medicine of precision.

En este artículo se analizan los retos (nuevos y viejos) de la investigación en comunicación en las últimas décadas, ante la rápida transformación del sistema de comunicaciones y la necesidad de redefinir su propio objeto de estudio. Los viejos paradigmas deben sustituirse por otros capaces de interpretar estos procesos. ¡Qué lejos nos va quedando el paradigma de Lasswell! Todo ello supone importantes retos académicos y epistemológicos. Se multiplican los centros, pero también se plantean incógnitas sobre la burocratización y la irrelevancia de muchas prácticas teóricas. ¿Nuestro campo de estudio debe seguir identificándose con una disciplina o debe concebirse como una postdisciplina? Mientras, las responsabilidades sociales siguen vigentes y aun se incrementan, ante la necesidad de contribuir al desarrollo cultural y a las políticas democráticas en las nuevas etapas de la comunicación. Los viejos paradigmas deben sustituirse por otros capaces de interpretar estos procesos. ¡Qué lejos nos va quedando el paradigma de Lasswell! Todo ello supone importantes retos académicos y epistemológicos. Se multiplican los centros, pero también se plantean incógnitas sobre la burocratización y la irrelevancia de muchas prácticas teóricas. ¿Nuestro campo de estudio debe seguir identificándose con una disciplina o debe concebirse como una postdisciplina? Mientras, las responsabilidades sociales siguen vigentes y aun se incrementan, ante la necesidad de contribuir al desarrollo cultural y a las políticas democráticas en las nuevas etapas de la comunicación.

Introduction: Lipodystrophy is an important complication of HIV and has different clinical manifestations, such as lipoatrophy of the face, buttocks, and limbs and accumulation of fat in the abdominal and cervical regions. Lipodystrophy has aesthetic and psychosocial consequences, stigmatizing and affecting patients’ quality of life. The objective is to evaluate the epidemiology and treatments performed in patients treated at the HIV-related Lipodystrophy Outpatient Clinic at Hospital das Clínicas da Faculdade de Medicina de Botucatu. Method: The study was conducted retrospectively, with port analysis of patients treated between June 2012 and December 2019, at Hospital das Clínicas da Faculdade de Medicina de Botucatu, in Botucatu, S P, Brazil. Results: The medical records of 153 individuals were analyzed, 79 male and 74 female patients. The mean age was 45.6 years. The referrals came from 48 cities in four states. Caucasian patients accounted for 74.5% of the consultations. The complaint of facial lipodystrophy was reported by 52.9% of the patients. The most common invasive procedure was facial filling with polymethylmethacrylate (PMMA) in 62 patients. Gluteal implants were the most common surgery on six occasions. Conclusion: The data found show a higher proportion of female patients with complaints of lipodystrophy when compared to general data of patients with HIV. The white race was predominant, and the main complaint of lipodystrophy was facial atrophy. Facial filling with PMMA was the most common procedure.

Abstract Background COVID-19 infection, especially in cases with pneumonia, is associated with a high rate of pulmonary embolism (PE). In patients with contraindications for CT pulmonary angiography (CTPA) or non-diagnostic CTPA, perfusion single-photon emission computed tomography/computed tomography (Q-SPECT/CT) is a diagnostic alternative. The goal of this study is to develop a radiomic diagnostic system to detect PE based only on the analysis of Q-SPECT/CT scans. Methods This radiomic diagnostic system is based on a local analysis of Q-SPECT/CT volumes that includes both CT and Q-SPECT values for each volume point. We present a combined approach that uses radiomic features extracted from each scan as input into a fully connected classification neural network that optimizes a weighted cross-entropy loss trained to discriminate between three different types of image patterns (pixel sample level): healthy lungs (control group), PE and pneumonia. Four types of models using different configuration of parameters were tested. Results The proposed radiomic diagnostic system was trained on 20 patients (4,927 sets of samples of three types of image patterns) and validated in a group of 39 patients (4,410 sets of samples of three types of image patterns). In the training group, COVID-19 infection corresponded to 45% of the cases and 51.28% in the test group. In the test group, the best model for determining different types of image patterns with PE presented a sensitivity, specificity, positive predictive value and negative predictive value of 75.1%, 98.2%, 88.9% and 95.4%, respectively. The best model for detecting pneumonia presented a sensitivity, specificity, positive predictive value and negative predictive value of 94.1%, 93.6%, 85.2% and 97.6%, respectively. The area under the curve (AUC) was 0.92 for PE and 0.91 for pneumonia. When the results obtained at the pixel sample level are aggregated into regions of interest, the sensitivity of the PE increases to 85%, and all metrics improve for pneumonia. Conclusion This radiomic diagnostic system was able to identify the different lung imaging patterns and is a first step toward a comprehensive intelligent radiomic system to optimize the diagnosis of PE by Q-SPECT/CT. Highlights Artificial intelligence applied to Q-SPECT/CT is a diagnostic option in patients with contraindications to CTPA or a non-diagnostic test in times of COVID-19.

Background A doctor may recommend that a patient stop an antibiotic course before its scheduled completion time if further treatment may cause more harm than benefit.Objectives This study explores general practitioners’ (GP) opinions about the use of antibiotic deprescribing (AD) in general practice.Methods A cross-sectional, questionnaire-based study answered from February to March 2022. GPs (n = 6,083) affiliated with the largest Spanish scientific society of primary care were invited to participate. The survey included two statements related to use and fourteen views about AD rated by GPs using a 5-item Likert scale.Results Eleven hundred and seven doctors completed the surveys (18.2%), of whom 92.5% (95% confidence interval [CI] 90.8–94%) reported having used the AD strategy in their practice at least once. GPs felt very confident in using a deprescribing strategy in patients with common cold and influenza (97.6% and 93.5%, respectively) but less with acute bronchitis (45.5%); 12.1% (95% CI, 10.2–14.2%) considered this practice harmful to patients. Respondents reported using AD more frequently when they initiated the antibiotic course (96.8%; 95% CI, 95.5–97.7) than when the treatment was initiated by another doctor (52.3%; 95% CI, 49.3–55.3%). However, doctors aged >60 years were more prone to use AD compared with younger colleagues (64.5% vs. 50%; p