Does the use of bisphosphonates during pregnancy affect fetal outcomes? A systematic review.

PURPOSE: This systematic review aimed to determine the effects of maternal exposure to bisphosphonates (BPs) during pregnancy on neonatal outcomes. It aimed to disclosfe the impact of BPs on neonates and identify aspects that require further investigation. METHODS: A comprehensive search of PubMed, Science Direct, LILACS, EMBASE, and Web of Science was conducted until August 2022, with no time restrictions. The selection criteria included studies published in English that evaluated pregnant women who were exposed to BPs. RESULTS: From an initial pool of 2169 studies, 13 met the inclusion criteria for this systematic review. These studies collectively included 106 women (108 pregnancies) who were exposed to BPs either before orduring pregnancy. A summary of the key characteristics of the selected studies and the risk of bias assessment are provided. Exposure to BPs occurs at various stages of pregnancy, with different indications for BP treatment. The most frequently reported neonatal outcomes were spontaneous abortion, congenital malformations, hypocalcemia, preterm birth, and low birth weight. CONCLUSION: Although previous reports have linked BPs before or during pregnancy with adverse neonatal outcomes, these associations should be interpreted with caution. Given the complexity of these findings, further research is necessary to provide more definitive insights to guide clinical decisions regarding the use of BPs in pregnant women.

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding.

Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.

Is There a Bias Towards Males in the Diagnosis of Autism? A Systematic Review and Meta-Analysis.

Autism is more frequently diagnosed in males, with evidence suggesting that females are more likely to be misdiagnosed or underdiagnosed. Possibly, the male/female ratio imbalance relates to phenotypic and camouflaging differences between genders. Here, we performed a comprehensive approach to phenotypic and camouflaging research in autism addressed in two studies. First (Study 1 - Phenotypic Differences in Autism), we conducted a systematic review and meta-analysis of gender differences in autism phenotype. The electronic datasets Pubmed, Scopus, Web of Science, and PsychInfo were searched. We included 67 articles that compared females and males in autism core symptoms, and in cognitive, socioemotional, and behavioural phenotypes. Autistic males exhibited more severe symptoms and social interaction difficulties on standard clinical measures than females, who, in turn, exhibited more cognitive and behavioural difficulties. Considering the hypothesis of camouflaging possibly underlying these differences, we then conducted a meta-analysis of gender differences in camouflaging (Study 2 - Camouflaging Differences in Autism). The same datasets as the first study were searched. Ten studies were included. Females used more compensation and masking camouflage strategies than males. The results support the argument of a bias in clinical procedures towards males and the importance of considering a 'female autism phenotype'-potentially involving camouflaging-in the diagnostic process.

Osteoinductive activity of photobiomodulation in an organotypic bone model.

Photobiomodulation (PBM) is a technique that harnesses non-ionizing light at specific wavelengths, triggering the modulation of metabolic pathways, engendering favourable biological outcomes that reduce inflammation and foster enhanced tissue healing and regeneration. PBM holds significant promise for bone tissue applications due to its non-invasive nature and ability to stimulate cellular activity and vascularization within the healing framework. Notwithstanding, the impact of PBM on bone functionality remains largely undisclosed, particularly in the absence of influencing factors such as pathologies or regenerative therapies. This study aims to investigate the potential effects of PBM using red (660 nm) (RED) and near-infrared (808 nm) (NIR) wavelengths within an ex vivo bone culture system - the organotypic embryonic chicken femur model. A continuous irradiation mode was used, administering a total energy dose of 1.0 J, at an intensity of 100 mW for 10 s, which was repeated four times over the course of the 11-day culture period. The primary focus is on characterizing the expression of pivotal osteoblastic genes, the maturation and deposition of collagen, and the formation of bone mineral. Exposing femora to both RED and NIR wavelengths led to a notable increase in the expression of osteochondrogenic transcription factors (i.e., SOX9 and RUNX2), correlating with enhanced mineralization. Notably, NIR irradiation further elevated the expression of bone matrix-related genes and fostered enhanced deposition and maturation of fibrillar collagen. This study demonstrates that PBM has the potential to enhance osteogenic functionality within a translational organotypic bone culture system, with the NIR wavelength showing remarkable capabilities in augmenting the formation and maturation of the collagenous matrix.

Metabolic Evaluation of Lupin-Enriched Yogurt by Nuclear Magnetic Resonance Metabolomics.

Untargeted nuclear magnetic resonance (NMR) metabolomics was used to evaluate compositional changes during yogurt fermentation upon lupin enrichment compared to traditional conditions. Lupin significantly changed the sample metabolic profile and its time course dynamics, seemingly delaying microbial action. The levels of organic and amino acids were significantly altered, along with those of some sugars, nucleotides, and choline compounds. Lupin seemed to favor acetate and formate synthesis, compared to that of citrate and fumarate; a higher formate levels may suggest increased levels of Streptococcus thermophilus action, compared toLactobacillus bulgaricus. Lupin-yogurt was poorer in hippurate, lactose (and hence lactate), galactose, glucose-1-phosphate, and galactose-1-phosphate, containing higher orotate levels (possibly related to increased uridine derivatives), among other differences. Trigonelline was confirmed as a lupin marker, possibly together with glutamate and histidine. Other metabolite trajectories remained unchanged upon lupin addition, unveiling unaffected underlying processes. These results demonstrate the usefulness of untargeted NMR metabolomics to understand/develop new foodstuffs and their production processes, highlighting the identity of a variety of bioactive metabolites with importance for human health.

COVID-19 in Portugal: A Pandemic Redesigned by the Media.

The news media in Portugal played an important role during the COVID-19 pandemic by providing people with important and up-to-date health information. However, the number of news reports did not always correspond to the severity of the pandemic. There was significant media attention at the beginning of the pandemic (in early 2020), but media coverage soon declined, and the Portuguese media began to report on a greater diversity of topics. The present study assessed the evolution of news reports in Portugal during the period of the COVID-19 pandemic by analysis of epidemiological data (cases, deaths, and hospitalizations) and television news lineups from the three major generalist television channels, RTP1, SIC, TVI. The study period was from March 2020 (when the first lockdown was instituted) to March 2021 (when there was the second gradual withdrawal of restrictions). Our results indicated that there was intense media coverage of COVID-19 during the first phase of the pandemic, even though epidemiological data showed there was not a severe health crisis at that time. However, the number of news stories about the pandemic soon declined, and this number was much lower during the worst period of the pandemic. Hence, the intensity of coverage of the COVID-19 pandemic in the Portuguese media provided a distorted image of the actual pandemic. All things considered, we strongly advise for the inclusion of a communication plan that would help address future health emergency crisis. All things considered, we recommend that in future health crisis there is a planned communication strategy that takes into account media relations.

Nutrition and Food Literacy: Framing the Challenges to Health Communication.

Nutrition and food literacy are two important concepts that are often used interchangeably, but they are not synonymous. Nutrition refers to the study of how food affects the body, while food literacy refers to the knowledge, skills, and attitudes necessary to make informed decisions about food and its impact on health. Despite the growing awareness of the importance of food literacy, food illiteracy remains a global issue, affecting people of all ages, backgrounds, and socioeconomic status. Food illiteracy has serious health implications as it contributes to health inequities, particularly among vulnerable populations. In addition, food literacy is a complex and multidisciplinary field, and there are numerous challenges to health communication that must be addressed to effectively promote food literacy and improve health outcomes. Addressing food illiteracy and the challenges to health communication is essential to promote health equity and improve health outcomes for all populations.

Changing human hair fibre colour and shape from the follicle.

INTRODUCTION: Natural hair curvature and colour are genetically determined human traits, that we intentionally change by applying thermal and chemical treatments to the fibre. Presently, those cosmetic methodologies act externally and their recurrent use is quite detrimental to hair fibre quality and even to our health. OBJECTIVES: This work represents a disruptive concept to modify natural hair colour and curvature. We aim to model the fibre phenotype as it is actively produced in the follicle through the topical delivery of specific bioactive molecules to the scalp. METHODS: Transcriptome differences between curly and straight hairs were identified by microarray. In scalp samples, the most variable transcripts were mapped by in situ hybridization. Then, by using appropriate cellular models, we screened a chemical library of 1200 generic drugs, searching for molecules that could lead to changes in either fibre colour or curvature. A pilot-scale, single-centre, investigator-initiated, prospective, blind, bilateral (split-scalp) placebo-controlled clinical study with the intervention of cosmetics was conducted to obtain a proof of concept (RNEC n.92938). RESULTS: We found 85 genes transcribed significantly different between curly and straight hair, not previously associated with this human trait. Next, we mapped some of the most variable genes to the inner root sheath of follicles, reinforcing the role of this cell layer in fibre shape moulding. From the drug library screening, we selected 3 and 4 hits as modulators of melanin synthesis and gene transcription, respectively, to be further tested in 33 volunteers. The intentional specific hair change occurred: 8 of 14 volunteers exhibited colour changes, and 16 of 19 volunteers presented curvature modifications, by the end of the study. CONCLUSION: The promising results obtained are the first step towards future cosmetics, complementary or alternative to current methodologies, taking hair styling to a new level: changing hair from the inside out.

Alendronate induces skeletal alterations in the chicken embryonic development model.

Alendronate, a nitrogen-containing bisphosphonate, has reported long-term clinical success in the management of distinct bone-related conditions, particularly in the modulation of post-menopausal osteoporosis. Nonetheless, whether the inhibitory activity over osteoclastic cells' functionality is widely acknowledged, contradictory evidence arises from the assessment of alendronate activity over osteoblastic populations. This may be of particular relevance in situations in which bone formation exceeds bone resorption, with further emphasis on embryonic development, since alendronate can cross the placental barrier and alendronate-based therapies are being extended into women of reproductive age. Accordingly, the present study aims to assess the effects of alendronate, at distinct concentrations (1.5E-10M to 1.5E-7M) on bone tissue development, within a translational animal model - the embryonic chicken development model. Embryos, at the beginning of osteogenesis (day 7) were exposed to different alendronate concentrations for 4 days. Embryos were following characterized for skeletal development by histomorphometric analysis upon histochemical staining, microtomographic analysis, and gene expression assessment of genes related to osteoclastogenic/osteoclastic and osteoblastogenic/osteogenic differentiation, as well as to the immuno-inflammatory activation. The findings revealed that exposure to alendronate had a dose-dependent impact on skeletal growth and mineralization. This effect was evidenced by diminished bone volume and reduced bone surface parameters, with the 1.5E-7M concentration leading to a remarkable reduction of over 50%. Additionally, a decreased osteoclastogenic/osteoclastic gene expression was verified, associated with a diminished osteoblastogenic/osteogenic program - within the 30-50% range for 1.5E-7 M, supporting the diminished bone formation process. An increased inflammatory activation may contribute, at least in part, to the attained outcomes. Overall present findings suggest a negative influence of alendronate on the embryonic bone development process in a dose-dependent manner, highlighting the potential risk of alendronate use during embryonic development.

Tumor Lipid Signatures Are Descriptive of Acquisition of Therapy Resistance in an Endocrine-Related Breast Cancer Mouse Model.

The lipid metabolism adaptations of estrogen and progesterone receptor-positive breast cancer tumors from a mouse syngeneic model are investigated in relation to differences across the transition from hormone-dependent (HD) to hormone-independent (HI) tumor growth and the acquisition of endocrine therapy (ET) resistance (HIR tumors). Results are articulated with reported polar metabolome results to complete a metabolic picture of the above transitions and suggest markers of tumor progression and aggressiveness. Untargeted nuclear magnetic resonance metabolomics was used to analyze tumor and mammary tissue lipid extracts. Tumor progression (HD-HI-HIR) was accompanied by increased nonesterified cholesterol forms and phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelins, and plasmalogens) and decreased relative contents of triglycerides and fatty acids. Predominating fatty acids became shorter and more saturated on average. These results were consistent with gradually more activated cholesterol synthesis, ß-oxidation, and phospholipid biosynthesis to sustain tumor growth, as well as an increase in cholesterol (possibly oxysterol) forms. Particular compound levels and ratios were identified as potential endocrine tumor HD-HI-HIR progression markers, supporting new hypotheses to explain acquired ET resistance.

Impact of Sea Warming and 17-α-Ethinylestradiol Exposure on the Lipid Metabolism of Ruditapes philippinarum Clams.

This paper reports on an NMR metabolomics study of lipophilic extracts of Ruditapes philippinarum clams exposed to the hormonal contaminant 17-α-ethinylestradiol (EE2), at 17 °C and 21 °C. The results reveal that exposure at 17 °C triggers a weak response at low EE2 concentrations, suggestive of a slight increase in membrane rigidity, followed by lipid metabolic stability at higher EE2 concentrations. On the other hand, at 21 °C, lipid metabolism begins to respond at 125 ng/L EE2, with antioxidant docosahexaenoic acid (DHA) helping to tackle high-oxidative-stress conditions, in tandem with enhanced storage of triglycerides. Exposure to 625 ng/L EE2 (highest concentration) enhances phosphatidylcholine (PtdCho) and polyunsaturated fatty acid (PUFA) levels, their direct intercorrelation suggesting PUFA incorporation in new membrane phospholipids. This should lead to increased membrane fluidity, probably aided by a decrease in cholesterol. PUFA levels, considered a measure of membrane fluidity, were strongly (and positively) correlated to intracellular glycine levels, thus identifying glycine as the main osmolyte entering the cells under high stress. Membrane fluidity also seems to elicit the loss of taurine. This work contributes to the understanding of the mechanisms of response of R. philippinarum clams to EE2 in tandem with warming while unveiling novel potential markers of stress mitigation, namely high levels of PtdCho, PUFAs (or PtdCho/glycerophosphocholine and PtdCho/acetylcholine ratios) and linoleic acid and low PUFA/glycine ratios.

Ex Vivo Osteogenesis Induced by Calcium Silicate-Based Cement Extracts.

Calcium silicate-based cements are used in a variety of clinical conditions affecting the pulp tissue, relying on their inductive effect on tissue mineralization. This work aimed to evaluate the biological response of calcium silicate-based cements with distinct properties-the fast-setting Biodentine™ and TotalFill® BC RRM™ Fast Putty, and the classical slow-setting ProRoot® MTA, in an ex vivo model of bone development. Briefly, eleven-day-old embryonic chick femurs were cultured for 10 days in organotypic conditions, being exposed to the set cements' eluates and, at the end of the culture period, evaluated for osteogenesis/bone formation by combining microtomographic analysis and histological histomorphometric assessment. ProRoot® MTA and TotalFill® extracts presented similar levels of calcium ions, although significantly lower than those released from BiodentineTM. All extracts increased the osteogenesis/tissue mineralization, assayed by microtomographic (BV/TV) and histomorphometric (% of mineralized area; % of total collagen area, and % of mature collagen area) indexes, although displaying distinct dose-dependent patterns and quantitative values. The fast-setting cements displayed better performance than that of ProRoot® MTA, with BiodentineTM presenting the best performance, within the assayed experimental model.

Glandular Odontogenic Cyst in the Anterior Mandible: A Case Report of a Conservative Approach and a Recurrence Detection.

PURPOSE: The glandular odontogenic cyst (GOC) is considered a rare developmental cyst, with an odontogenic origin and both epithelial and glandular characteristics, with less than 200 reported cases in the literature. METHODS: In the present case, a 29-year-old man was referred for evaluation of an asymptomatic slow-growing swelling in the anterior region of the mandible, with one-year history. The patient's medical history did not reveal any systemic alteration. The extraoral examination did not show enlargement of the facial contour and the intraoral examination showed vestibular and lingual swelling. Panoramic radiography and CT scan revealed a well-defined unilocular radiolucent lesion involving the inferior incisors and canines bilaterally. RESULTS: Histopathological analysis revealed multiple cysts lined by stratified epithelium with varying thickness and characteristics, in addition to duct-like structures filled with PAS-positive amorphous material, suggestive of GOC. Conservative treatment was performed through surgical curettage, peripheral ostectomy of the surgical site and apicectomy of the teeth involved in the lesion. There was one recurrence, which was detected in postoperative follow-up, leading to a new surgical approach. CONCLUSIONS: Fifteen months after the second procedure, no signs of recurrence were identified, and bone neoformation within the surgical site occurred, supporting that a conservative approach for the treatment of GOC is viable.

The influence of temperature rise on the metabolic response of Ruditapes philippinarum clams to 17-α-ethinylestradiol.

Untargeted Nuclear Magnetic Resonance metabolomics was employed to study the effects of warming conditions (17-21 °C) and exposure to 17-α-ethinylestradiol (EE2) on the polar metabolome of Ruditapes philippinarum clams, to identify metabolic markers for monitoring/prediction of deviant environmental conditions. Warming alone triggered changes in alanine/aspartate/glutamate, aromatic amino acids, taurine/hypotaurine and homarine/trigonelline pathways, as well as in energy metabolism, suggesting osmoregulatory adaptations and glycolytic/tricarboxylic acid (TCA) cycle activation, possibly accompanied to some extent by gluconeogenesis to preserve glycogen reserves. At 17 °C, the lowest EE2 concentration (5 ng/L) specifically engaged branched-chain and aromatic amino acids to activate the glycolysis/TCA cycle. Notably, a partial metabolic recovery was observed at 25 ng/L, whereas higher EE2 concentrations (125 and 625 ng/L) again induced significant metabolic disturbances. These included enhanced glycogen biosynthesis and increased lipid reserves, sustained by low-level glutathione-based antioxidative mechanisms that seemed active. At 21 °C, response to EE2 was notably weak at low/intermediate concentrations, becoming particularly significant at the highest EE2 concentration (625 ng/L), suggesting higher protection capacity of Ruditapes philippinarum clams under warming conditions. At 625 ng/L, disturbances in alanine/aspartate/glutamate and taurine/hypotaurine metabolisms were observed, with no evidence of enhanced carbohydrate/protein catabolism. This low energy function profile was accompanied by marked antioxidative mechanisms and choline compounds modulation for cell membrane protection/repair. These results help monitor clams´ response to temperature rise and EE2 exposure, paving the way for future effective guidance and prediction of environmental damaging effects.

Behavior Guidance during the Covid-19 Pandemic: Health Literacy as a Weapon against the Virus.

Portugal was hit by COVID-19 on the 2nd of March 2020. For almost two months, the country was confined due to the declaration of the emergency state. The confinement was always conveyed by the media, who clearly guided citizens toward preventive behaviors and so became a means of fighting this pandemic by helping the country stay home. Several authors recognize the importance of health communication and health literacy in fighting COVID-19. In a public health crisis like this, media are important actors in the promotion of health and prevention of disease, and they can have a central role in behavior change. To further understand how the media guided citizens toward preventive behaviors we applied a questionnaire survey to Portuguese journalists. More than 90% assumed citizens' behavior guidance. Journalists' perceptions about their work reflect a true concern with the promotion of health literacy, and their assumption of a public service mission was crucial in people's adherence to confinement. Health literacy achieved its maximum during this confinement period, not only because these were extraordinary times but also because Portuguese journalists had an exemplar behavior.

Metabolic Adaptations in an Endocrine-Related Breast Cancer Mouse Model Unveil Potential Markers of Tumor Response to Hormonal Therapy.

Breast cancer (BC) is the most common type of cancer in women and, in most cases, it is hormone-dependent (HD), thus relying on ovarian hormone activation of intracellular receptors to stimulate tumor growth. Endocrine therapy (ET) aimed at preventing hormone receptor activation is the primary treatment strategy, however, about half of the patients, develop resistance in time. This involves the development of hormone independent tumors that initially are ET-responsive (HI), which may subsequently become resistant (HIR). The mechanisms that promote the conversion of HI to HIR tumors are varied and not completely understood. The aim of this work was to characterize the metabolic adaptations accompanying this conversion through the analysis of the polar metabolomes of tumor tissue and non-compromised mammary gland from mice implanted subcutaneously with HD, HI and HIR tumors from a medroxyprogesterone acetate (MPA)-induced BC mouse model. This was carried out by nuclear magnetic resonance (NMR) spectroscopy of tissue polar extracts and data mining through multivariate and univariate statistical analysis. Initial results unveiled marked changes between global tumor profiles and non-compromised mammary gland tissues, as expected. More importantly, specific metabolic signatures were found to accompany progression from HD, through HI and to HIR tumors, impacting on amino acids, nucleotides, membrane percursors and metabolites related to oxidative stress protection mechanisms. For each transition, sets of polar metabolites are advanced as potential markers of progression, including acquisition of resistance to ET. Putative biochemical interpretation of such signatures are proposed and discussed.

A new ex vivo model of the bone tissue response to the hyperglycemic environment - The embryonic chicken femur organotypic culture in high glucose conditions.

Diabetes mellitus (DM) embrace a group of chronic metabolic conditions with a high morbidity, causing deleterious effects in different tissues and organs, including bone. Hyperglycemia seems to be one of the most contributing etiological factors of bone-related alterations, altering metabolic functionality and inducing morphological adaptations. Despite the established models for the assessment of bone functionality in hyperglycemic conditions, in vitro studies present a limited representativeness given the imperfect cell-cell and cell-matrix interactions, and restricted three-dimensional spatial arrangement; while in vivo studies raise ethical issues and offer limited mechanistic characterization, given the modulatory influence of many systemic factors and/or regulatory systems. Accordingly, the aim of this study is to establish and characterize an innovative ex vivo model of the bone tissue response to hyperglycemia, reaching hand of the organotypic culture of embryonic chicken femurs in high glucose conditions, showcasing the integrative responsiveness of the model regarding hyperglycemia-induced alterations. A thorough assessment of the cellular and tissue functionality was further conducted. Results show that, in high glucose conditions, femurs presented an increased cell proliferation and enhanced collagen production, despite the altered protein synthesis, substantiated by the increased carbonyl content. Gene expression analysis evidenced that high glucose levels induced the expression of pro-inflammatory and early osteogenic markers, further impairing the expression of late osteogenic markers. Furthermore, the tissue morphological organization and matrix mineralization were significantly altered by high glucose levels, as evidenced by histological, histochemical and microtomographic evaluations. Attained data is coherent with acknowledged hyperglycemia-induced bone tissue alterations, validating the models' effectiveness, and evidencing its integrative responsiveness regarding cell proliferation, gene and protein expression, and tissue morpho-functional organization. The assessed ex vivo model conjoins the capability to access both cellular and tissue outcomes in the absence of a systemic modulatory influence, outreaching the functionality of current experimental in vitro and in vivo models of the diabetic bone condition.

[Pre-Exposure Prophylaxis for Human Immunodeficiency Virus in the Medical Curricula in Portugal: A Cross-Sectional Analysis].

INTRODUCTION: Pre-exposure prophylaxis (PrEP) has gained relevance as a method of prevention for HIV in certain people and settings. Following the publication of the guideline on PrEP prescribing in Portugal, we aimed to assess the knowledge of Portuguese Medical Students about PrEP. MATERIAL AND METHODS: An online survey was sent to Medical students of Portuguese Medical Schools. We conducted a descriptive analysis of the results and an analytic cross-sectional study to identify factors associated with "knowing about PrEP", "having had one class about PrEP" and "identifying eligible groups correctly". RESULTS: Of the 796 students that responded to the survey, 64.6% were aware of what PrEP is. Of these, 34.44% acquired this knowledge during their training. Out of the total amount of respondents, 4.77% could identify correctly and completely the eligible groups for PrEP. As the training years went by, the probability of being aware of PrEP, having had one class about PrEP, and identifying the eligible groups correctly, increased. Of the sixth-year students, 43.48% had had one class about PrEP and among the students that were aware of PrEP, 28% identified what the eligible groups were. After adjusting for the school year, we found differences between Medical Schools regarding the outcomes. The association between the different ways of learning about PrEP and the ability to correctly identify eligible groups for PrEP was not statistically significant. CONCLUSION: The differences between Medical Schools could be harmonized through changes in the medical curricula that would allow this topic to be addressed more often.

Introdução: A profilaxia pré-exposição (PrEP) ganhou relevância como método de prevenção do VIH em determinados indivíduos e contextos. Após a entrada em vigor das normas para prescrição em Portugal, pretendemos aferir o conhecimento em relação à PrEP entre os estudantes de Medicina em Portugal.Material e Métodos: Foi enviado um questionário online aos estudantes de Medicina das escolas médicas portuguesas. Foi feita uma análise descritiva dos resultados e um estudo transversal analítico para identificar fatores associados a "conhecer a PrEP", "ter tido uma aula de PrEP", e "identificar grupos elegíveis corretamente".Resultados: Dos 796 estudantes que responderam, 64,6% sabiam o que era a PrEP. Destes, 34,44% obteve conhecimento sobre a mesma durante a sua formação. Entre os respondentes, 4,77% identificaram correta e completamente os grupos elegíveis. Com o avançar do ano letivo, a probabilidade de conhecer a PrEP, ter tido uma aula de PrEP e identificar os grupos corretamente aumentava. No sexto ano, 43,48% tinham tido uma aula sobre PrEP e entre os que conheciam a PrEP, 28% identificaram os grupos elegíveis. Existem diferenças entre as escolas médicas após ajustamento para o ano letivo em relação aos resultados obtidos. A forma como se tomou conhecimento da PrEP não alterou de forma estatisticamente significativa a capacidade de identificar corretamente grupos elegíveisConclusão: As diferenças entre as escolas médicas poderão ser harmonizadas. Esta temática poderá ser reforçada nos respetivos currículos.

Impact of the Pd2Spm (Spermine) Complex on the Metabolism of Triple-Negative Breast Cancer Tumors of a Xenograft Mouse Model.

The interest in palladium(II) compounds as potential new anticancer drugs has increased in recent years, due to their high toxicity and acquired resistance to platinum(II)-derived agents, namely cisplatin. In fact, palladium complexes with biogenic polyamines (e.g., spermine, Pd2Spm) have been known to display favorable antineoplastic properties against distinct human breast cancer cell lines. This study describes the in vivo response of triple-negative breast cancer (TNBC) tumors to the Pd2Spm complex or to cisplatin (reference drug), compared to tumors in vehicle-treated mice. Both polar and lipophilic extracts of tumors, excised from a MDA-MB-231 cell-derived xenograft mouse model, were characterized through nuclear magnetic resonance (NMR) metabolomics. Interestingly, the results show that polar and lipophilic metabolomes clearly exhibit distinct responses for each drug, with polar metabolites showing a stronger impact of the Pd(II)-complex compared to cisplatin, whereas neither drug was observed to significantly affect tumor lipophilic metabolism. Compared to cisplatin, exposure to Pd2Spm triggered a higher number of, and more marked, variations in some amino acids, nucleotides and derivatives, membrane precursors (choline and phosphoethanolamine), dimethylamine, fumarate and guanidine acetate, a signature that may be relatable to the cytotoxicity and/or mechanism of action of the palladium complex. Putative explanatory biochemical hypotheses are advanced on the role of the new Pd2Spm complex in TNBC metabolism.

Novel Insights into Mice Multi-Organ Metabolism upon Exposure to a Potential Anticancer Pd(II)-Agent.

Pd(II)-compounds are presently regarded as promising anticancer drugs, as an alternative to Pt(II)-based drugs (e.g., cisplatin), which typically trigger severe side-effects and acquired resistance. Dinuclear Pd(II) complexes with biogenic polyamines such as spermine (Pd2Spm) have exhibited particularly beneficial cytotoxic properties, hence unveiling the importance of understanding their impact on organism metabolism. The present study reports the first nuclear magnetic resonance (NMR)-based metabolomics study to assess the in vivo impact of Pd2Spm on the metabolism of healthy mice, to identify metabolic markers with possible relation to biotoxicity/side-effects and their dynamics. The changes in the metabolic profiles of both aqueous and lipophilic extracts of mice kidney, liver, and breast tissues were evaluated, as a function of drug-exposure time, using cisplatin as a reference drug. A putative interpretation was advanced for the metabolic deviations specifically triggered by Pd2Spm, this compound generally inducing faster metabolic response and recovery to control levels for all organs tested, compared to cisplatin (except for kidney lipid metabolism). These results constitute encouraging preliminary metabolic data suggestive of potential lower negative effects of Pd2Spm administration.