Cardiovascular risk assessment in Portugal's primary health care system: SCORE vs. SCORE2.

INTRODUCTION AND OBJECTIVES: The 2021 European Society of Cardiology guidelines on cardiovascular disease (CVD) prevention introduced the more accurate SCORE2 risk model as a replacement for the earlier SCORE, which is still used in primary care software in Portugal. Our objective is to determine whether the difference between risk assessment using SCORE and SCORE2, in the same patient population, is statistically significant. METHODS: A total of 1642 patients aged 40-65 without previous CVD, from the medical records of two Family Health Units, were included in this cross-sectional study. SCORE and SCORE2 were calculated using the variables gender, age, smoking status, lipid profile and systolic blood pressure. A statistical analysis was performed on the results. RESULTS: Using SCORE, 98% of the patients were in the low-moderate risk categories and 2% in the high or very high risk categories. When using SCORE2, the corresponding percentages were 55% and 45%, respectively. Reclassification with SCORE2 into higher categories was more often observed in younger (under 50 years of age) and male patients. With SCORE, 38.61% of patients were within the LDL-C target range; this figure fell to 20.28% with SCORE2. These differences are statistically significant (p<0.0001). CONCLUSION: Our findings show that a significant number of patients in this cohort who were classified through SCORE at lower risk levels were reclassified into higher risk categories with SCORE2. Similarly, the number of patients within the LDL-C target range for LDL-C was also lower using SCORE2.

Methodologies and Challenges for Optimal Sensor Placement in Historical Masonry Buildings.

As ageing structures and infrastructures become a global concern, structural health monitoring (SHM) is seen as a crucial tool for their cost-effective maintenance. Promising results obtained for modern and conventional constructions suggested the application of SHM to historical masonry buildings as well. However, this presents peculiar shortcomings and open challenges. One of the most relevant aspects that deserve more research is the optimisation of the sensor placement to tackle well-known issues in ambient vibration testing for such buildings. The present paper focuses on the application of optimal sensor placement (OSP) strategies for dynamic identification in historical masonry buildings. While OSP techniques have been extensively studied in various structural contexts, their application in historical masonry buildings remains relatively limited. This paper discusses the challenges and opportunities of OSP in this specific context, analysing and discussing real-world examples, as well as a numerical benchmark application to illustrate its complexities. This article aims to shed light on the progress and issues associated with OSP in masonry historical buildings, providing a detailed problem formulation, identifying ongoing challenges and presenting promising solutions for future improvements.

Severe Pediatric Sleep Apnea: Drug-Induced Sleep Endoscopy Based Surgery.

Although adenotonsillectomy is the recommended treatment of obstructive sleep apnea (OSA) in children, some patients with preoperative severe OSA (Apnea-hypopnea index/AHI > 10) remain symptomatic after surgery and may need further workup. This study aims to: (1) analyse preoperative factors and its relation with surgical failure/persistent OSA (AHI > 5 after adenotonsillectomy) in severe pediatric OSA; (2) determine the levels of airway collapse during DISE (drug induced sleep endoscopy) in cases of surgical failure; (3) evaluate the efficacy of targeted surgery based on DISE findings. This retrospective study was conducted between August and September 2020. Across 9 years (from 2011 to 2020), all children diagnosed with severe OSA in our Hospital underwent adenotonsillectomy and repeated type 1 polysomnography (PSG) 3 months after surgery. Cases of surgical failure underwent DISE for planning eventual directed surgery. Chi-square test was used to assess the relationship between persistent OSA and preoperative patients' characteristics. 80 cases of severe pediatric OSA were diagnosed (68.8% males; mean age: 4.3 years-standard deviation: 2.49; mean AHI: 16.3-standard deviation 7.14) in the aforementioned period. We found a significant association between surgical failure (11.3% of cases; mean AHI: 6.9-SD 0.91) and obesity (p = 0.002; confidence level of 95%). Neither preoperative AHI nor other PSG parameters were associated with surgical failure. In cases of surgical failure, epiglottis collapse was present in every DISEs and adenoid tissue was present in 66% of children. All cases of surgical failure had directed surgery and surgical cure (AHI ≤ 5) was obtained in 100% of cases. This study suggests that obesity is the strongest predictor of surgical failure in children with severe OSA who undergo adenotonsillectomy. Epiglottis collapse and presence of adenoid tissue are the most common findings in postoperative DISEs of children with persistent OSA after primary surgery. DISE based surgery seems a safe and effective tool to manage persistent OSA after adenotonsillectomy.

Deep Learning Framework for Controlling Work Sequence in Collaborative Human-Robot Assembly Processes.

The human-robot collaboration (HRC) solutions presented so far have the disadvantage that the interaction between humans and robots is based on the human's state or on specific gestures purposely performed by the human, thus increasing the time required to perform a task and slowing down the pace of human labor, making such solutions uninteresting. In this study, a different concept of the HRC system is introduced, consisting of an HRC framework for managing assembly processes that are executed simultaneously or individually by humans and robots. This HRC framework based on deep learning models uses only one type of data, RGB camera data, to make predictions about the collaborative workspace and human action, and consequently manage the assembly process. To validate the HRC framework, an industrial HRC demonstrator was built to assemble a mechanical component. Four different HRC frameworks were created based on the convolutional neural network (CNN) model structures: Faster R-CNN ResNet-50 and ResNet-101, YOLOv2 and YOLOv3. The HRC framework with YOLOv3 structure showed the best performance, showing a mean average performance of 72.26% and allowed the HRC industrial demonstrator to successfully complete all assembly tasks within a desired time window. The HRC framework has proven effective for industrial assembly applications.

Fractional CO2 Laser versus Fractional Radiofrequency for Skin Striae Treatment: Study Protocol for a Randomized Controlled Trial.

Striae are common dermal lesions associated with physiological and psychological alterations, affecting the quality of life. This proposed randomized controlled trial protocol will evaluate the clinical efficacy and treatment safety of fractional CO2 laser versus fractional radiofrequency (FRF) in clinical trials. We will randomly allocate 60 subjects who present abdominal striae into two different groups for the treatment, which will be performed once a month for a 3-month period. The results will be assessed by quartile scoring criteria; by comparing digital photos taken before and after each treatment; and also, by the measurement of cutaneous temperature, skin pH, and elasticity before and after the treatment. This paper describes the rationale and the design of the randomized controlled trial, which may provide evidence for clinical application of the methodology and the quality related to the efficacy and safety of fractional CO2 laser versus the FRF protocol for striae treatment.

A Narrative Review of Current Striae Treatments.

Striae (striae cutis distensae) are a common disfiguring skin condition, characterised by the appearance of linear bands on the skin, with an atrophic look. The striae development is still unknown, being more common in women than in men. The prevalence of this condition ranges from 50% to 90%. Regarding treatment, there are various treatment strategies currently available for stretch marks, including topical preparations such as tretinoin and glycolic acid, and also laser. The goal of this work is to discover the main treatments available for striae management. For that, a search was performed based on the definition of specific scientific keywords, by exploring PubMed, ScienceDirect and Biblioteca Virtual em Saúde (BVS). MeSH thesaurus (Medical Subject Headings) descriptors were used. The results indicate that, to date, no treatment is fully effective. More clinical trials are needed to validate the efficacy of these therapies and their long-term use in this type of skin lesion.

Treatment of otomycosis with clotrimazole: results accordingly with the fungus isolated.

BACKGROUND: Otomycosis is usually caused by Candida spp or Aspergillus spp. While Candida is usually multissensitive to available antifungals, Aspergillus is not. Topical antifungals for otomycosis that are available in Portugal are scarce, and systemic treatments have too many interactions and contraindications. OBJECTIVES: Determine otomycosis epidemiology, microbiology and treatment results. METHODS: Observational study that included patients followed in Professor Doutor Fernando Fonseca Hospital, between 2011 and 2020. Otomycosis diagnosis was obtained through ear drainage culture, and every case was treated with 1% clotrimazole ear drops plus ear cleaning once per week. RESULTS: Aspergillus was found in ear drainage culture in 43.9% of patients and Candida in the remaining. There was a significant statistical difference between patients with otomycosis caused by Aspergillus versus Candida in treatment duration from 25.0 days (16.5-43.0) versus 14.0 days (7.0-18.5) (p < .001), respectively. CONCLUSIONS: Otomycosis was more frequently caused by Candida, and this type of otomycosis is treated faster with clotrimazole 10 mg/dL plus ear cleaning, when compared with otomycosis by Aspergillus. SIGNIFICANCE: If otomycosis causative agent is identified or suspected, a prediction of the time needed till the resolution of otomycosis can be made, when clotrimazole ear drops are used.

Epithelial-Mesenchymal Plasticity Induced by Discontinuous Exposure to TGFß1 Promotes Tumour Growth.

Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity, favouring tumour growth. We developed an EMT model by on and off exposure of epithelial EpH4 cells (E-cells) to TGFß1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia by using RNA sequencing, immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays as well as cell xenografts in nude mice. Phenotypic reverted epithelial cells (RE-cells) obtained after MET induction presented epithelial morphologies and proliferation rates resembling E cells. However, the RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a uniquely heterogeneous mixture of cell subpopulations with a high self-renewal ability. RE cell heterogeneity was stably maintained for long periods after TGFß1 removal both in vitro and in large tumours derived from the nude mice. Overall, we show that phenotypic reverted epithelial cells (RE cells) do not return to the molecular and functional epithelial state and present mesenchymal features related to aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cell reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour growth-promoting factor in vivo.

Characterisation of an Atrx Conditional Knockout Mouse Model: Atrx Loss Causes Endocrine Dysfunction Rather Than Pancreatic Neuroendocrine Tumour.

ATRX is a chromatin remodeller that maintains telomere homeostasis. Loss of ATRX is described in approximately 10% of pancreatic neuroendocrine tumours (PanNETs) and associated with poorer prognostic features. Here, we present a genetically engineered mouse model (GEMM) addressing the role of Atrx loss (AtrxKO) in pancreatic ß cells, evaluating a large cohort of ageing mice (for up to 24 months (mo.)). Atrx loss did not cause PanNET formation but rather resulted in worsening of ageing-related pancreatic inflammation and endocrine dysfunction in the first year of life. Histopathological evaluation highlighted an exacerbated prevalence and intensity of pancreatic inflammation, ageing features, and hepatic steatosis in AtrxKO mice. Homozygous floxed mice presented hyperglycaemia, increased weights, and glucose intolerance after 6 months, but alterations in insulinaemia were not detected. Floxed individuals presented an improper growth of their pancreatic endocrine fraction that may explain such an endocrine imbalance. A pilot study of BRACO-19 administration to AtrxKO mice resulted in telomere instability, reinforcing the involvement of Atrx in the maintenance of ß cell telomere homeostasis. Thereby, a non-obese dysglycaemic GEMM of disrupted Atrx is here presented as potentially useful for metabolic studies and putative candidate for inserting additional tumourigenic genetic events.

Unilateral vocal fold paralysis as a port complication.

Unilateral vocal fold paralysis (UVFP) is a frequent finding in otorhinolaryngology practice, but its occurrence as a port complication was very rarely described in English Literature. The authors report a 55-year-old woman with a pancreatic adenocarcinoma who presented a left vocal fold paralysis that occurred concurrently with a venous thrombosis of the left subclavian vein, where a totally implantable venous-access had been previously placed. Although the patient's oncologic disease, that could mislead to a neoplastic cause of the UVFP, the authors came across with an unusual etiology and to their best knowledge, it is the first case of irreversible UVFP associated with onsite thrombosis of the vessel where a port was implanted. The objective of this article is to present and discuss this rare case of UVFP secondary to a port complication and to review the main mechanisms of iatrogenic vocal fold paralysis related to these devices.

Biotinylated Polymer-Ruthenium Conjugates: In Vitro and In Vivo Studies in a Triple-Negative Breast Cancer Model.

The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(η5-CpR)(P)(2,2'-bipy-4,4'-PLA-biotin)][CF3SO3], where R is -H or -CH3 and P is P(C6H5)3, P(C6H4F)3 or P(C6H4OCH3)3, were tested against triple-negative breast cancer cells MDA-MB-231 showing IC50 values between 2.3-14.6 µM, much better than cisplatin, a classical chemotherapeutic drug, in the same experimental conditions. We selected compound 1 (where R is H and P is P(C6H5)3), for further studies as it was the one showing the best biological effect. In a competitive assay with biotin, we showed that cell uptake via SMVT receptors seems to be the main transport route into the cells for this compound, validating the strategy of including biotin in the design of the compound. The effects of the compound on the hallmarks of cancer show that the compound leads to apoptosis, interferes with proliferation by affecting the formation of cell colonies in a dose-dependent manner and disrupts the cell cytoskeleton. Preliminary in vivo assays in N: NIH(S)II-nu/nu mice show that the concentrations of compound 1 used in this experiment (maximum 4 mg/kg) are safe to use in vivo, although some signs of liver toxicity are already found. In addition, the new compound shows a tendency to control tumor growth, although not significantly. In sum, we showed that compound 1 shows promising anti-cancer effects, bringing a new avenue for triple-negative breast cancer therapy.

Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells.

Serine tRNAs (tRNASer) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at testing whether increasing tRNASer abundance could foster tumor establishment through activation of the UPR. In order to do so, firstly we confirmed that the expression of tRNA-Ser-AGA-2-1 [hereafter tRNASer(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNASer(AGA) in early stage tumorigenesis, we induced its upregulation in a non-tumoral bronchial cell line, BEAS-2B. Upregulation of this tRNA increased cellular proliferation and protein synthesis rate, driven by eIF2α dephosphorylation and ATF4 activation downstream of PERK signaling. Futhermore, tRNASer(AGA) enhanced transformation potential in vitro, and promoted the establishment of slow growing tumors with aggressive features in nude mice. Our work highlights the importance of studying tRNA deregulation on early stage tumorigenesis, as they may be potential malignancy and aggressiveness biomarkers.

Multisensor Inspection of Laser-Brazed Joints in the Automotive Industry.

Automobile laser brazing remains a complex process whose results are affected by several process variables that may result in nonacceptable welds. A multisensory customized inspection system is proposed, with two distinct non-destructive techniques: the potential drop method and eddy current testing. New probes were designed, simulated, produced, and experimentally validated in automobile's laser-brazed weld beads with artificially introduced defects. The numerical simulations allowed the development of a new four-point probe configuration in a non-conventional orthogonal shape demonstrating a superior performance in both simulation and experimental validation. The dedicated inspection system allowed the detection of porosities, cracks, and lack of bonding defects, demonstrating the redundancy and complementarity these two techniques provide.

Sensorineural Hearing Loss and Systemic Autoimmune Disease: The Experience of a Systemic Immune-Mediated Diseases Unit.

Background Autoimmune inner ear disease (AIED) represents less than 1% of all cases of sensorineural hearing loss (SNHL) but its frequency may be underestimated due to lack of specific clinical and laboratory criteria. AIED can be associated with a systemic autoimmune disease (SAID) in 15%-30% of the cases. The objective of the present study was to characterize the clinical and prognostic factors of a cohort of patients with AIED. Materials and methods The authors conducted a retrospective descriptive analysis of a cohort of patients with AIED referred from the otorhinolaryngology department to a systemic immune-mediated diseases unit between March 2013 and November 2020. A consecutive sample of 39 patients with suspected AIED was referred. SNHL was defined as a fall of the hearing threshold of at least 30 decibels in three consecutive frequencies. Eight patients were excluded for not meeting the audiometric criteria or having confounding factors. The remaining 31 patients were included with a total of 50 affected ears. To classify the intensity of hearing loss, an arithmetic mean of pure tone was calculated. Normal hearing or mild hearing loss at the last pure tone audiometry of the follow-up were an indicator of good prognosis and were considered the outcome of interest. Results Thirty-two percent of the patients had an associated SAID. There were no differences regarding demographic and clinical characteristics when comparing patients with AIED alone and patients with AIED and a SAID, except for the positivity of antinuclear antibodies (ANA). ANA positivity was superior in patients with the association of AIED and a SAID when compared with patients with AIED alone (90% vs 50%; p=0.037). The SAID was diagnosed after the AIED in 70% of the patients, in which diagnosis of the SAID occurred a median of 4,2 (IQR 0.8-5.1) years after the diagnosis of the AIED. Normal audiometric evaluation or a mild hearing loss was achieved in 31% of the ears at the last audiometric evaluation. A normal audiometry or a mild hearing loss at the time of diagnosis was independently associated with a better outcome (31%, 14%, CI 1.71-273.69; p=0.018). Bilateral hearing loss was independently associated with a worse outcome (54%, 79%, CI 0.01-0.84; p=0.035). The use of systemic corticosteroids (p=0.941), transtympanic corticosteroids (p=0.700) and non-steroid immunomodulator drugs (p=0.986) did not affect prognosis. The presence of a SIAD did not affect the prognosis (p=0.986). Conclusions In this cohort, SAID was present in one-third of the patients with AIED. A good prognosis was achieved in one-third of the patients. A normal audiometry or mild disease at presentation was associated with a good outcome, whilst bilateral involvement was associated with a bad one. Association of a SAID did not seem to influence the hearing-related prognosis. Positivity of ANA antibodies may justify performing a complementary investigation to determine the presence of a SAID.

Retrospective study of group A Streptococcus oropharyngeal infection diagnosis using a rapid antigenic detection test in a paediatric population from the central region of Portugal.

Group A Streptococcus (GAS) is one of the most important agents of oropharyngeal infection. To avoid unnecessary antibiotic prescription, it is recommended the confirmation of GAS infection in pharyngeal swabs using culture or rapid antigen detection test (RADT). This study aimed to retrospectively analyse the incidence of GAS oropharyngeal infection, detected by RADT, in a paediatric population in the Centre of Portugal. Data was collected from the database of the Paediatric Hospital Emergency Department (ED) regarding patients admitted with symptoms suggesting acute pharyngitis, from January 2013 to December 2018, in a total of 18,304 cases. Among these, 130 clinical files were searched for symptoms, complications and additional visits to the ED. The results showed an average GAS infection prevalence of 33%, with seasonal variation. In preschool children, especially in patients less than 3 years old, where the guidelines do not routinely encourage RADT, GAS tonsillitis assumed an unexpected importance, with 731 positive tests in a total of 3128 cases. Scarlatiniform rash and oral cavity petechiae had significant correlation with streptococcal aetiology (p < 0.05). The statistical analysis also showed that different signs and symptoms assume different weights depending on the age group of the patient. The main conclusion is that the incidence of GAS infection in the studied population is higher than generally described in preschool children, suggesting the need for a more cautious approach to children under 3 years presenting acute pharyngitis, and that RADT in this age group would contribute to a decrease in the number of unnoticed cases.

Regulation of invasion and peritoneal dissemination of ovarian cancer by mesothelin manipulation.

Peritoneal dissemination is a particular form of metastasis typically observed in ovarian cancer and the major cause for poor patient's outcome. Identification of the molecular players involved in ovarian cancer dissemination can offer an approach to develop treatment strategies to improve clinical prognosis. Here, we identified mesothelin (MSLN) as a crucial protein in the multistep process of peritoneal dissemination of ovarian cancer. We demonstrated that MSLN is overexpressed in primary and matched peritoneal metastasis of high-grade serous carcinomas (HGSC). Using several genetically engineered ovarian cancer cell lines, resulting in loss or gain of function, we found that MSLN increased cell survival in suspension and invasion of tumor cells through the mesothelial cell layer in vitro. Intraperitoneal xenografts established with MSLNhigh ovarian cancer cell lines showed enhanced tumor burden and spread within the peritoneal cavity. These findings provide strong evidences that MSLN is a key player in ovarian cancer progression by triggering peritoneal dissemination and provide support for further clinical investigation of MSLN as a therapeutic target in HGSC.

Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells.

CD44v6-containing isoforms are frequently de novo expressed in gastric cancer (GC). Whether CD44v6 has a central role in GC transformation and/or progression, whether it conditions response to therapy or whether it is only a bystander marker is still not known. Therefore, we aimed to clarify the role of CD44v6 in GC. We generated GC isogenic cell lines stably expressing CD44s or CD44v6 and tested them for different cancer hallmarks and response to cisplatin, and we further confirmed our findings in cells that endogenously express CD44v6. No correlation between overexpression of CD44v6 and the tested cancer hallmarks was observed, suggesting CD44v6 is not a driver of GC progression. Upon cisplatin treatment, CD44v6+ cells survive better and have lower apoptosis levels than CD44v6- cells, possibly due to concomitant activation of STAT3 and P38. In co-culture experiments, we discovered that CD44v6+ cells are involved in GC cell overgrowth after cisplatin treatment. In conclusion, we show that CD44v6 expression increases cell survival in response to cisplatin treatment in GC cells and that these cells override CD44v6-negative cells after cisplatin-treatment. This suggests that tumor expression of CD44v6-containing variants may condition the outcome of GC patients treated with chemotherapy.

MEX3A regulates Lgr5+ stem cell maintenance in the developing intestinal epithelium.

Intestinal stem cells (ISCs) fuel the lifelong self-renewal of the intestinal tract and are paramount for epithelial repair. In this context, the Wnt pathway component LGR5 is the most consensual ISC marker to date. Still, the effort to better understand ISC identity and regulation remains a challenge. We have generated a Mex3a knockout mouse model and show that this RNA-binding protein is crucial for the maintenance of the Lgr5+ ISC pool, as its absence disrupts epithelial turnover during postnatal development and stereotypical organoid maturation ex vivo. Transcriptomic profiling of intestinal crypts reveals that Mex3a deletion induces the peroxisome proliferator-activated receptor (PPAR) pathway, along with a decrease in Wnt signalling and loss of the Lgr5+ stem cell signature. Furthermore, we identify PPARγ activity as a molecular intermediate of MEX3A-mediated regulation. We also show that high PPARγ signalling impairs Lgr5+ ISC function, thus uncovering a new layer of post-transcriptional regulation that critically contributes to intestinal homeostasis.

O contributo da educação física para a a formação de indivíduos fisicamente cultos: uma perspetiva portuguesa / The contribution of physical education to the training of physically educated individuals: a portuguese perspective / Las aportaciones de la educación física para la formación de individuos físicamente cultos: una perspectiva portuguesa

Resumo: Este trabalho, realizado com 150 indivíduos no final da escolaridade obrigatória e candidatos a uma licenciatura em Ciências do Desporto, pretende perceber se a Educação Física está a contribuir para a formação de indivíduos fisicamente cultos. Seguimos uma metodologia quantitativa e optámos por um questionário com três partes: a primeira de questões fechadas e de caracterização sociodemográfica da amostra; a segunda, também de questões fechadas, sobre o entendimento acerca das Finalidades da Educação Física; e a terceira composta por 25 afirmações de escolha dicotómica (verdadeiro/falso), sobre conteúdos fundamentais para uma prática autónoma de atividade física, constantes nos Programas Nacionais de Educação Física (Currículos Nacionais) para o ensino secundário. Os resultados revelam fragilidades nos conhecimentos dos indivíduos relativamente ao desenvolvimento das capacidades motoras, aos efeitos da prática de exercício físico, a procedimentos de segurança e à composição e funcionamento corporal, afastando-se do preconizado por aqueles Programas Nacionais.

Abstract: This study was carried out with 150 male students at the end of their mandatory education and with candidates to a degree in Sports Science and Physical Education. It aims to understand if Physical Education contributed to the education of physically educated individuals. We followed a quantitative methodology and administered a three-part questionnaire: close-ended questions for the sociodemographic characterization of the sample; close-ended questions on participants' understanding of the purposes of Physical Education; true-or-false questions on fundamental contents for an autonomous practice of physical activity, which are included in the National Curricula of Physical Education for secondary school. The results reveal individuals' weak knowledge of motor skills development, effects of physical exercise, safety procedures, and body composition and functioning, which is not in accordance with National Curricula.

Resumen: Este trabajo, realizado con 150 estudiantes al final de su escolaridad obligatoria y aspirantes a cursar la licenciatura en Ciencias del Deporte, pretende averiguar si la Educación Física está contribuyendo con la formación de individuos físicamente cultos. Seguimos una metodología cuantitativa y optamos por un cuestionario con tres partes: la primera con cuestiones cerradas y de caracterización sociodemográfica de los participantes; la segunda, también con cuestiones cerradas y sobre su entendimiento acerca de las finalidades de la Educación Física; y la tercera, compuesta por 25 afirmaciones de selección dicotómica (verdadero y falso), sobre contenidos fundamentales para una práctica autónoma de la actividad física y que constan en los Programas Nacionales de Educación Física (Currículos Nacionales) para el bachillerato. Los resultados revelan fragilidades en los conocimientos de los participantes en lo referente al desarrollo de las capacidades motoras, los efectos de la práctica de ejercicio físico, los procedimientos de seguridad y la composición y funcionamiento corporal, alejándose de lo preconizado en aquellos Programas Nacionales.

The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization.

The search for novel anticancer small molecules and strategies remains a challenge. Our previous studies have identified TXA1 (1-{[2-(diethylamino)ethyl]amino}-4-propoxy-9H- thioxanthen-9-one) as a hit compound, with in vitro antitumor potential by modulating autophagy and apoptosis in human tumor cell lines. In the present study, the mechanism of action and antitumor potential of the soluble salt of this molecule (TXA1.HCl) was further investigated using in vitro and mouse xenograft tumor models of NSCLC. Our results showed that TXA1.HCl affected steroid biosynthesis, increased RagD expression, and caused abnormal cellular cholesterol localization. In addition, TXA1.HCl treatment presented no toxicity to nude mice and significantly reduced the growth of human NSCLC cells xenografts in mice. Overall, this work provides new insights into the mechanism of action of TXA1, which may be relevant for the development of anticancer therapeutic strategies, which target cholesterol transport.