Female Sexual Function Index Adaptation for Breast Cancer Patients (FSFI-BC): Brazilian Portuguese Translation and Cultural Adaptation.

BACKGROUND: The assessment of female sexual function after diagnosis and treatment of breast cancer is relevant, as cancer can negatively affect sexuality and, therefore, quality of life. Instruments assessing female sexuality can be useful in clinical practice. However, there are few validated instruments available for this purpose. This study aimed to translate the Female Sexual Function Index Adaptation for Breast Cancer Patients (FSFI-BC) into Brazilian Portuguese and culturally adapt it for use in Brazil. PATIENTS AND METHODS: Translation and cross-cultural adaptation followed the linguistic validation process, according to international guidelines. The instrument was translated and back-translated by independent translators. Sixty women aged 25 to 70 years who had been diagnosed and surgically treated for breast cancer at least 6 months previously participated in the cultural adaptation process. Participants were stratified into sexually active or inactive. Internal consistency was analyzed using Cronbach's alpha coefficient. RESULTS: Mean participant age was 52.5 years. For sexually active women, reliability analysis (Cronbach's alpha) showed excellent internal consistency between the items of the subscales 'Desire/Arousal' (α = 0.912) and 'Orgasm' (α = 0.904), and good internal consistency for 'Lubrication' (α = 0.814) and 'Pain' (α = 0.839). For sexually inactive women, excellent internal consistency was observed between the items of the subscale 'Reason for Inactivity - difficulty lubricating' (α = 0.930), and good internal consistency for the other subscales. The instrument had face and content validity. CONCLUSIONS: FSFI-BC was translated and culturally adapted to the context of the Brazilian population.

Antioxidant activity of the main phenolics found in red fruits: An in vitro and in silico study.

The current study analysed the antioxidant capacity of the main phenolics found in red fruits. In total, there were analysed the antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl radical, nitric oxide and superoxide radicals (DPPH, NO and O2-, respectively) of 23 phenolics. Regarding DPPH, anthocyanins, (-)-epicatechin and kaempferol 3-O-rutinoside were the most active, while isorhamnetin 3-O-glucoside was the least active. Anthocyanins, (-)-epicatechin, quercetin 3-O-glucoside and caffeic acid showed the strongest potential against NO, while ρ-hydroxybenzoic acid was the less efficient. Regarding the O2- assay, quercetin aglycone and their derivatives were the best ones, while cyanidin aglycone did not show any potential to quench this radical. To deeper explore the biological potential of the most promising compounds, docking molecular and ADME studies were also done. The obtained data is another support regarding the biological potential of phenolics and might be useful in encouraging their use and incorporation in new products.

Genetic profile of Brazilian patients with LAMA2-related dystrophies.

LAMA2-related dystrophies (LAMA2-RD) constitute a rare neuromuscular disorder with a broad spectrum of phenotypic severity. Our understanding of the genotype-phenotype correlations in this condition remains incomplete, and reliable clinical data for clinical trial readiness is limited. In this retrospective study, we reviewed the genetic data and medical records of 114 LAMA2-RD patients enrolled at seven research centers in Brazil. We identified 58 different pathogenic variants, including 21 novel ones. Six variants were more prevalent and were present in 81.5% of the patients. Notably, the c.1255del, c.2049_2050del, c.3976 C>T, c.5234+1G>A, and c.4739dup variants were found in patients unable to walk and without cortical malformation. In contrast, the c.2461A>C variant was present in patients who could walk unassisted. Among ambulatory patients, missense variants were more prevalent (p < 0.0001). Although no specific hotspot regions existed in the LAMA2, 51% of point mutations were in the LN domain, and 88% of the missense variants were found within this domain. Functional analysis was performed in one intronic variant (c.4960-17C>A) and revealed an out-of-frame transcript, indicating that the variant creates a cryptic splicing site (AG). Our study has shed light on crucial phenotype-genotype correlations and provided valuable insights, particularly regarding the Latin American population.

Steroidal epoxides as anticancer agents in lung, prostate and breast cancers: The case of 1,2-epoxysteroids.

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of cancer.

Post-mortem detection of hemoplasmas (hemotropic Mycoplasma spp.) in South American fur seal (Arctocephalus australis) sampled in Rio Grande do Sul State, southern Brazil.

Hemotropic mycoplasmas are bacteria that attaches to erythrocytes surface, which some species presents zoonotic concerns. In the suborder Pinnipedia, genera Otaria and Arctocephalus are prominent in Brazil. This study investigated the occurrence of hemoplasmas in Arctocephalus sp. and Otaria flavescens found dead along the coast of a Southern Brazilian State. DNA from 135 spleen samples were extracted and subjected to conventional PCR protocols, targeting the 16 S rRNA and 23 S rRNA gene. Three (2.22 %) Arctocephalus australis were positive in the 16 S rRNA gene, and no samples amplified in the 23 S rRNA gene. Samples from this study clustered with Zalophus californianus and Arctocephalus tropicalis mycoplasmas on a Bayesian phylogenetic analysis. Genetic diversity analysis suggested distinct genotypes, indicating A. australis as a new host for hemoplasma, and also a potential putative novel hemoplasma genotype. These findings raises future awareness for pinnipeds conservation, and adds Mycoplasma spp. to be taken into consideration when clinically evaluating rescued animals.

The use of peptides for immunodiagnosis of human Chagas disease.

Chagas disease, caused by the protozoa Trypanosoma cruzi, continues to be a serious public health problem in Latin America, worsened by the limitations in its detection. Given the importance of developing new diagnostic methods for this disease, the present review aimed to verify the number of publications dedicated to research on peptides that demonstrate their usefulness in serodiagnosis. To this end, a bibliographic survey was conducted on the PubMed platform using the keyword "peptide" or "epitope" combined with "Chagas disease" or "Trypanosoma cruzi"; "diagno*" or "serodiagnosis" or "immunodiagnosis", without period restriction. An increasing number of publications on studies employing peptides in ELISA and rapid tests assays was verified, which confirms the expansion of research in this field. It is possible to observe that many of the peptides tested so far originate from proteins widely used in the diagnosis of Chagas, and many of them are part of commercial tests developed. In this sense, as expected, promising results were obtained for several peptides when tested in ELISA, as many of them exhibited sensitivity and specificity values above 90%. Furthermore, some peptides have been tested in several studies, confirming their diagnostic potential. Despite the promising results observed, it is possible to emphasize the need for extensive testing of peptides, using different serological panels, in order to confirm their potential. The importance of producing an effective assay capable of detecting the clinical stages of the disease, as well as new immunogenic antigens that enable new serological diagnostic tools for Chagas disease, is evident.

Learning demands of diabetes self-management: a qualitative study with people who use insulin.

OBJECTIVE: to understand the experiences with diabetes mellitus management of people who use insulin, in order to identify possible factors that may influence adherence to self-care and thus define their learning demands for diabetes self-management. METHOD: this is a qualitative study carried out using individual semi-structured interviews online. The interviews were recorded, transcribed and evaluated using Atlas.ti® software by means of Thematic Content Analysis, using the Health Beliefs Model as a theoretical framework. RESULTS: 11 people living with diabetes and using insulin took part in the study. Four categories were identified: understanding diabetes, how to deal with diabetes, difficulties related to insulin use and emotional adaptation. CONCLUSION: the perception of the severity of the disease, its complications and the benefits of adhering to treatment positively influences adherence to self-care behaviors. Although the study participants have lived with diabetes for many years, they are not exempt from difficulties related to insulin use and disease management, reinforcing the importance of continuing health education. In this sense, the findings of this study guide important educational themes to be worked on by health professionals to promote autonomy in diabetes self-management. BACKGROUND: (1) Perceived severity of diabetes positively influences self-care. (2) Continued health education for people who use insulin is essential. (3) The importance of recognizing the benefits of insulin in adherence to treatment. (4) Emotional aspects in diabetes management should be considered in health education.

Correction: Understanding the Role of Growth Factors in Modulating Stem Cell Tenogenesis.

[This corrects the article DOI: 10.1371/journal.pone.0083734.].

Psychosocial Factors Associated With Vulvodynia.

OBJECTIVES: We set out to identify the psychosocial factors associated with vulvodynia and the effects on sexuality, mental health, and quality of life. MATERIALS AND METHODS: PubMed, LILACS, Embase, CINAHL, Web of Science, Scopus, and PsycINFO were searched in August 2023. Two authors selected and extracted the data independently. The risk of bias was assessed using the Newcastle-Ottawa Scale for Observational Studies. To rank the strength of evidence, the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) approach was utilized. RESULTS: A total of 3,182 articles were identified. Twenty-two observational studies (8 cohorts and 14 case-controls) met the eligibility criteria and were included, comprising 2,624 patients. Vulvodynia has been associated with psychological factors (anxiety and depression) and social factors (childhood exposure to physical and sexual abuse, posttraumatic stress, and domestic abuse). Concerning sexual function, the most frequent outcomes were dyspareunia and sexual dysfunction. Only one study assessed quality of life, which showed that women with chronic vulvar pain had greater difficulty performing physical activities and experienced negative moods and feelings. The assessment of the risk of bias showed that the average quality of studies was good to excellent. However, the studies failed to select the nonexposed cohort or control group to describe the results, and often, the study population was rather small, which made it impossible to carry out a meta-analysis. CONCLUSIONS: The certainty of evidence for the associations between anxiety and depression, vulvodynia, and sexual functioning suggests that combating these factors could improve overall quality of life in vulvodynia patients.

Exploring the recovery journey of COVID-19 critical care survivors during the first year after hospital discharge.

Objectives: To explore the longitudinal recovery of patients admitted to critical care following COVID-19 over the year following hospital discharge. To understand the important aspects of the patients' recovery process and key elements of their caregivers' experiences during this time. Design: A longitudinal qualitative study using semi-structured interviews. Setting: Two acute hospitals in South East England and follow-up in the community. Participants: Six COVID-19 critical care survivors from the first wave of the pandemic (March-May 2020) and five relatives were interviewed 3 months after hospital discharge. The same six survivors and one relative were interviewed again at 1 year. Interviews were transcribed verbatim, anonymised and a reflexive thematic analysis was conducted. Results: Three themes were developed: (1) 'The cycle of guilt, fear and stigma'; (2) 'Facing the uncertainties of recovery' and (3) 'Coping with lingering symptoms - the new norm'. The first theme highlights survivors' reluctance to share their experiences associated with contracting the disease. The second theme, explores challenges faced by the survivors and their relatives in navigating the recovery process, given the unknown nature of the illness. The final theme illustrates the mechanisms survivors develop to come to terms with the remnants of their illness and critical care stay. Conclusions: The longitudinal nature of the study highlighted the persisting symptoms of long COVID-19, their impact on survivors and coping methods amidst the ongoing pandemic. Further research into the experiences of those affected in the first and subsequent waves of the COVID-19 pandemic, is desirable to help guide the formulation of the optimally supported recovery pathways.

The Effect of Phenolic-Rich Extracts of Rubus fruticosus, R. ulmifolius and Morus nigra on Oxidative Stress and Caco-2 Inhibition Growth.

Currently, a clear interest has been given to berries due to their richness in active metabolites, including anthocyanins and non-coloured phenolics. Therefore, the main aim of the present work is to investigate the phenolic profile, antioxidant abilities, and antiproliferative effects on normal human dermal fibroblasts (NHDF) and human colon carcinoma cell line (Caco-2) cells of phenolic-rich extracts from three red fruits highly appreciated by consumers: two species of blackberries (Rubus fruticosus and Rubus ulmifolius) and one species of mulberry (Morus nigra). A total of 19 different phenolics were identified and quantified by HPLC-DAD-ESI/MSn and HPLC-DAD, respectively. Focusing on the biological potential of the phenolic-rich extracts, all of them revealed notable scavenging abilities. Concerning the antiproliferative properties, R. fruticosus presented a cytotoxic selectivity for Caco-2 cells compared to NHDF cells. To deeper explore the biological potential, combinations with positive controls (ascorbic acid and 5-fluorouracil) were also conducted. Finally, the obtained data are another piece of evidence that the combination of phenolic-rich extracts from natural plants with positive controls may reduce clinical therapy costs and the possible toxicity of chemical drugs.

Side effects of COVID-19 vaccines in paediatric patients: a review systematic and meta-analysis protocol.

INTRODUCTION: The paediatric population represents a quarter of the world's population, and like adult patients, they have also suffered immeasurably from the SARS-CoV-2 pandemic. Immunisation is an effective strategy for reducing the number of COVID-19 cases. With the advancements in vaccination for younger age groups, parents or guardians have raised doubts and questions about adverse effects and the number of doses required. Therefore, systematic reviews focusing on this population are needed to consolidate evidence that can help in decision-making and clinical practice. This protocol aims to assess the safety of COVID-19 vaccines in paediatric patients and evaluate the correlation between the number of vaccine doses and side effects. METHODS AND ANALYSIS: We will search the PubMed, ClinicalTrials.gov, Web of Science, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature, Scopus and Cochrane databases for randomised and quasi-randomised clinical trials that list the adverse effects of the COVID-19 vaccine and assess its correlation with the number of doses, without any language restrictions. Two reviewers will select the studies according to the inclusion and exclusion criteria, extract data and asses for risk of bias using the Cochrane risk-of-bias tool. The Review Software Manager (RevMan V.5.4.1) will be used to synthesise the data. We will use the Working Group's Grading of Recommendations Assessment, Development and Evaluations to grade the strength of the evidence of the results. ETHICS AND DISSEMINATION: Formal ethical approval is not required as no primary data are collected. This systematic review will be disseminated through a peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42023390077.

Pan-Enteric Capsule Endoscopy: Current Applications and Future Perspectives.

Background: The role of capsule endoscopy in the evaluation of the small bowel is well established, and current guidelines position it as a first-line test in a variety of clinical scenarios. The advent of double-headed capsules further enabled the endoscopic assessment of colonic mucosa and the opportunity for a one-step noninvasive examination of the entire bowel (pan-enteric capsule endoscopy [PCE]). Summary: We reviewed the technical procedure and preparation of patients for PCE, as well as its current clinical applications and future perspectives. In non-stricturing and non-penetrating Crohn's disease affecting the small bowel and colon, PCE monitors disease activity by assessing mucosal healing, a major treatment outcome, with a higher diagnostic yield than cross-sectional imaging or conventional colonoscopy. Also in ulcerative colitis, double-headed capsules have been used to monitor disease activity noninvasively. Currently, validated scoring systems have been specifically devised for these double-headed capsules and permit a standardized assessment of the inflammatory burden. In suspected mid-lower digestive bleeding, some exploratory studies have demonstrated the feasibility and high diagnostic yield of PCE, which may work as a filter indicating which patients may benefit of further invasive procedures, namely, for planned hemostatic procedures. The possibility of using PCE is also discussed in the context of polyposis syndromes with simultaneous involvement of the small intestine and colon. Key Messages: PCE is a feasible, effective, and safe diagnostic procedure to evaluate the small bowel and colon. It has been increasingly explored in the setting of inflammatory bowel diseases and, more recently, in suspected mid-lower digestive bleeding. PCE is expected to reduce the demand for invasive procedures and expand the scope of noninvasive intestinal evaluation in the coming future.

Introdução: O papel da endoscopia por cápsula na avaliação do intestino delgado encontra-se bem estabelecido, e as orientações atuais posicionam-na como um teste de primeira linha numa variedade de cenários clínicos. O advento das cápsulas de dupla câmara permitiu expandir a sua aplicação para a avaliação endoscópica da mucosa do cólon, oferecendo a oportunidade de um exame não invasivo de todo o intestino (endoscopia pan-entérica por cápsula, PCE). Sumário: Procedemos a uma revisão de vários aspectos do procedimento e preparação dos doentes para a PCE, bem como as aplicações clínicas atuais e as perspetivas futuras das cápsulas de dupla câmara. Na doença de Crohn não estenosante e não penetrante localizada ao intestino delgado e cólon, a PCE permite monitorizar a atividade da doença e avaliar a cicatrização da mucosa, um indicador importante da eficácia da terapêutica, com um rendimento de diagnóstico superior aos métodos convencionais, nomeadamente os exames imagiológicos ou a colonoscopia invasiva. Também na colite ulcerosa, as cápsulas de dupla câmara têm sido utilizadas para monitorizar a atividade da doença de forma não invasiva. Existem índices endoscópicos validados e especificamente concebidos para as cápsulas de dupla câmara, que permitem uma avaliação sistematizada e quantificação objetiva da atividade inflamatória. Na suspeita de hemorragia digestiva média ou baixa, alguns estudos exploratórios demonstraram a aplicabilidade e o elevado rendimento diagnóstico da PCE, podendo funcionar como um filtro de modo a permitir indicar quais os doentes que mais irão beneficiar de um procedimento invasivo subsequente, nomeadamente para a realização de procedimentos hemostáticos dirigidos. A possibilidade de utilização da PCE é também discutida no contexto das síndromes de polipose com envolvimento simultâneo do intestino delgado e do cólon. Mensagens-chave: A PCE é um procedimento diagnóstico eficaz e seguro para avaliar diretamente a mucosa do intestino delgado e cólon. A sua aplicação tem vindo a expandir-se no contexto das Doenças Inflamatórias Intestinais e, mais recentemente, na suspeita de hemorragia digestiva média ou baixa. Existe a expectativa de que no futuro próximo possamos assistir a uma redução substancial da demanda por procedimentos endoscópicos invasivos, face à utilização crescente da PCE enquanto método de diagnóstico pan-intestinal não invasivo.

Batimastat Induces Cytotoxic and Cytostatic Effects in In Vitro Models of Hematological Tumors.

The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat's therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.

Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives.

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.

Seaweed Proteins: A Step towards Sustainability?

This review delves into the burgeoning field of seaweed proteins as promising alternative sources of protein. With global demand escalating and concerns over traditional protein sources' sustainability and ethics, seaweed emerges as a viable solution, offering a high protein content and minimal environmental impacts. Exploring the nutritional composition, extraction methods, functional properties, and potential health benefits of seaweed proteins, this review provides a comprehensive understanding. Seaweed contains essential amino acids, vitamins, minerals, and antioxidants. Its protein content ranges from 11% to 32% of dry weight, making it valuable for diverse dietary preferences, including vegetarian and vegan diets. Furthermore, this review underscores the sustainability and environmental advantages of seaweed protein production compared to traditional sources. Seaweed cultivation requires minimal resources, mitigating environmental issues like ocean acidification. As the review delves into specific seaweed types, extraction methodologies, and functional properties, it highlights the versatility of seaweed proteins in various food products, including plant-based meats, dairy alternatives, and nutritional supplements. Additionally, it discusses the potential health benefits associated with seaweed proteins, such as their unique amino acid profile and bioactive compounds. Overall, this review aims to provide insights into seaweed proteins' potential applications and their role in addressing global protein needs sustainably.

A Review on the use of Synthetic and Recombinant Antigens for the Immunodiagnosis of Tegumentary Leishmaniasis.

Improving the diagnostic technology used to detect tegumentary leishmaniasis (TL) is essential in view of it being a widespread, often neglected tropical disease with cases reported from the southern United States to northern Argentina. Recombinant proteins, recombinant multiepitope proteins, and synthetic peptides have been extensively researched and used in disease diagnosis. One of the benefits of applying these antigens is a measurable increase in sensitivity and specificity, which improves test accuracy. The present review aims to describe the antigens and their diagnostic effectiveness. With that in mind, a bibliographic survey was conducted on the PudMed platform using the search terms "tegumentary leishmaniasis" AND "diagno", revealing that recombinant proteins have been described and evaluated for their value in TL diagnosis since the 1990s. However, there was a spike in the number of publications using all of the antigens between 2013 and 2022, confirming an expansion in research efforts to improve diagnosis. Moreover, all of the studies involving different antigens had promising results, including improved sensitivity and specificity. These data recognize the importance of doing research with new technologies focused on developing quick, more effective diagnostic kits as early diagnosis facilitates treatment.

New Approaches to the Prevention of Visceral Leishmaniasis: A Review of Recent Patents of Potential Candidates for a Chimeric Protein Vaccine.

The development of prophylactic vaccines is important in preventing and controlling diseases such as visceral leishmaniasis (VL), in addition to being an economic measure for public health. Despite the efforts to develop a vaccine against human VL caused by Leishmania infantum, none is available, and the focus has shifted to developing vaccines against canine visceral leishmaniasis (CVL). Currently, commercially available vaccines are targeted at CVL but are not effective. Different strategies have been applied in developing and improving vaccines, such as using chimeric proteins to expand vaccine coverage. The search for patents can be a way of tracking vaccines that have the potential to be marketed. In this context, the present work presents a summary of immunological aspects relevant to VL vaccine development with a focus on the composition of chimeric protein vaccines for CVL deposited in patent banks as an important approach for biotechnological development. The resulting data could facilitate the screening and selection of antigens to compose vaccine candidates with high performance against VL.

Assessing wildfire exposure and social vulnerability at the local scale using a GIS-based approach.

Exposure and vulnerability analysis are valuable tools for wildfire management, especially important for local communities that suffer from very destructive events and that require mitigation approaches adjusted to their abilities and needs. We present a methodological procedure to analyze wildfire exposure levels, social vulnerability conditions and coping capacity at the local scale, for villages or small human settlements. The procedure was developed using GIS (Geographic Information Systems) and programming tools in R and Python, which can be adapted and updated depending on the data available. The development of accessible procedures and easily replicable methodologies facilitates knowledge transfer and supports the application of mitigation and adaptation strategies, tailored to the conditions of the exposed areas.•A step-by-step procedure for the assessment of Exposure, Vulnerability, and Coping Capacity, using Python and R programming language.•Automated processes, easily replicable and adjustable to other areas.•Indications for adapting the methodology using European/international databases.

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas.

INTRODUCTION: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients. AIMS: This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. MATERIAL AND METHODS: This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2-ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated. RESULTS/DISCUSSION: All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.