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Very little information is available on the mutational landscape of vulvar squamous cell carcinoma (VSCC), a disease that mainly affects older women. Studies focusing on the mutational patterns of the currently recognized etiopathogenic types of this tumor [human papillomavirus (HPV)-associated (HPV-A), HPV-independent (HPV-I) with TP53 mutation (HPV-I/TP53mut), and HPV-I with wild-type TP53 (HPV-I/TP53wt]) are particularly rare, and there is almost no information on the prognostic implications of these abnormalities. Whole-exome DNA sequencing of 60 VSCC and matched normal tissues from each patient was performed. HPV detection, immunohistochemistry (IHC) for p16, p53, and mismatch repair proteins were also performed. Ten tumors (16.7%) were classified as HPV-A, 37 (61.7%) as HPV-I/TP53mut, and 13 (21.6%) as HPV-I/TP53wt. TP53 was the most frequently mutated gene (66.7%), followed by FAT1 (28.3%), CDKN2A (25.0%), RNF213 (23.3%), NFE2L2 (20%) and PIK3CA (20%). All the 60 tumors (100%) were DNA mismatch repair proficient. Seventeen tumors (28.3%) showed CCND1 gain. Bivariate analysis, adjusted for FIGO stage, revealed that TP53 mutation, CCND1 gain, and the combination of the two alterations were strongly associated with impaired recurrence-free survival (hazard ratio=4.4, p<0.001) and disease-specific survival (hazard ratio=6.1, p=0.002). Similar results were obtained when p53 IHC status was used instead of TP53 status and when considering only HPV-I VSCC. However, in the latter category, p53 IHC maintained its prognostic impact only in combination with CCND1 gains. All tumors carried at least one potentially actionable genomic alteration. In conclusion, VSCCs with CCND1 gain represent a prognostically adverse category among HPV-I/TP53mut tumors. All patients with VSCCs are potential candidates for targeted therapy.
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This article explores telecare from telehealth developments and the recent acceleration of the digital health transformation caused by the COVID-19 pandemic, focusing on the Brazilian Unified Health System (SUS). It addresses terminological issues, the scope of actions, the potential use for healthcare, and constraints and contingencies for telecare in Brazil, focusing on teleconsultations and interactions between health professionals and patients. Finally, it presents a set of propositions for the development of telecare policies and practices in Brazil, considering SUS principles, in two central themes: organizational political guidelines and operational propositions to organise services and healthcare delivery. The importance of clarifying the scope and limits of new technologies is highlighted in the attempt to avoid idealizations with proposed solutions to complex health problems. Telecare solutions should be compatible with SUS principles and with the recommended model of care, with the healthcare network coordinated and organised by primary care, ensuring access to health services and integrated and quality healthcare for the Brazilian society.
O artigo explora a teleassistência a partir dos desenvolvimentos da telessaúde e da aceleração da transformação digital na saúde provocada pela pandemia de COVID-19, com foco no Sistema Único de Saúde (SUS). Aborda questões terminológicas, escopo de ações, potencialidades do uso para atenção à saúde e condicionantes e contingências para a utilização da teleassistência no Brasil, concentrando-se nas teleconsultas e nas interações entre profissionais de saúde e pacientes. Por fim, apresenta um conjunto de proposições para o desenvolvimento das políticas e práticas de teleassistência no Brasil, tendo em vista os princípios do SUS, organizados em dois eixos estratégicos centrais: diretrizes político organizacionais e proposições operacionais e de organização dos serviços e do cuidado. Destaca-se a importância de ponderar e elucidar os alcances e os limites das novas tecnologias para evitar idealizações e deslumbramentos com suas propostas de solução para os complexos problemas de saúde. As soluções de teleassistência devem ser compatíveis com princípios e diretrizes do SUS e com o modelo de atenção preconizado, que prevê a organização da rede a partir da atenção primária, para garantir acesso, integralidade e qualidade da atenção à saúde para a sociedade brasileira.
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COVID-19 , Atención a la Salud , Accesibilidad a los Servicios de Salud , Programas Nacionales de Salud , Atención Primaria de Salud , Telemedicina , Brasil , Telemedicina/organización & administración , Telemedicina/tendencias , Humanos , COVID-19/epidemiología , Atención a la Salud/organización & administración , Programas Nacionales de Salud/organización & administración , Atención Primaria de Salud/organización & administración , Política de Salud , Calidad de la Atención de SaludRESUMEN
In most parts of the world, life expectancy is increasing thanks to improved healthcare, public health policies, nutrition, and treatment. This increase in lifespan is often not accompanied by an increase in health span, which severely affects people as they age. One notable consequence of this is the increasing prevalence of neurodegenerative diseases such as mild cognitive impairment, dementia, and Alzheimer's disease. Therefore, dietary and pharmaceutical measures must be taken to reduce the burden of such pathologies. Among the different types of nutrients found in the diet, lipids and especially polar lipids are very important for cognition due to their abundance in the brain. Amid the most studied sources of polar lipids, milk fat globule membrane (MFGM) stands out as it is abundant in industrial by-products such as buttermilk. In this narrative review, we discuss the latest, i.e. less than five years old, scientific evidence on the use of MFGM and its polar lipids in cognitive neurodevelopment in early life and their potential effect in preventing neurodegeneration in old age. We conclude that MFGM is an interesting, abundant and exploitable source of relatively inexpensive bioactive molecules that could be properly formulated and utilized in the areas of neurodevelopment and cognitive decline. Sufficiently large randomized controlled trials are required before health-related statements can be made. However, research in this area is progressing rapidly and the evidence gathered points to biological, health-promoting effects.
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Cognición , Glucolípidos , Glicoproteínas , Gotas Lipídicas , Glucolípidos/química , Gotas Lipídicas/química , Glicoproteínas/química , Humanos , Cognición/efectos de los fármacos , Animales , Lípidos/químicaRESUMEN
INTRODUCTION: Sleep-disordered breathing (SDB) is a major comorbidity in idiopathic pulmonary fibrosis (IPF) and is associated with a poor outcome. There is a lack of knowledge regarding the impact of SDB treatment on IPF. We assessed at one year: (1) the effect of CPAP and/or nocturnal oxygen therapy on IPF regarding lung function, blood mediators, and quality of life; (2) adherence to SDB treatment and SDB changes. METHODOLOGY: This is a prospective study of consecutive newly diagnosed IPF patients initiating anti-fibrotic treatment. Lung function, polysomnography, blood tests and quality of life questionnaires were performed at inclusion and after one year. Patients were classified as obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and sleep-sustained hypoxemia (SSH). SDB therapy (CPAP and/or nocturnal oxygen therapy) was initiated if needed. RESULTS: Fifty patients were enrolled (36% had OSA, 22% CSA, and 12% SSH). CPAP was started in 54% of patients and nocturnal oxygen therapy in 16%. At one-year, polysomnography found improved parameters, though 17% of patients had to add nocturnal oxygen therapy or CPAP, while 33% presented SDB onset at this second polysomnography. CPAP compliance at one year was 6.74 h/night (SD 0.74). After one year, matrix metalloproteinase-1 decreased in OSA and CSA (p = 0.029; p = 0.027), C-reactive protein in OSA (p = 0.045), and surfactant protein D in CSA group (p = 0.074). There was no significant change in lung function. CONCLUSIONS: Treatment of SBD with CPAP and NOT can be well tolerated with a high compliance. IPF patients may exhibit SDB progression and require periodic re-assessment. Further studies to evaluate the impact of SDB treatment on lung function and serological mediators are needed.
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Presión de las Vías Aéreas Positiva Contínua , Fibrosis Pulmonar Idiopática , Terapia por Inhalación de Oxígeno , Síndromes de la Apnea del Sueño , Humanos , Presión de las Vías Aéreas Positiva Contínua/métodos , Femenino , Masculino , Fibrosis Pulmonar Idiopática/terapia , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/fisiopatología , Proyectos Piloto , Anciano , Estudios Prospectivos , Síndromes de la Apnea del Sueño/terapia , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/fisiopatología , Síndromes de la Apnea del Sueño/complicaciones , Terapia por Inhalación de Oxígeno/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Polisomnografía/métodos , Calidad de VidaRESUMEN
The Tousled-like kinases 1 and 2 (TLK1/TLK2) regulate DNA replication, repair and chromatin maintenance. TLK2 variants underlie the neurodevelopmental disorder (NDD) 'Intellectual Disability, Autosomal Dominant 57' (MRD57), characterized by intellectual disability and microcephaly. Several TLK1 variants have been reported in NDDs but their functional significance is unknown. A male patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency was determined to have a heterozygous TLK1 variant (c.1435C>G, p.Q479E), as well as a mutation in MDM1 (c.1197dupT, p.K400∗). Cells expressing TLK1 p.Q479E exhibited reduced cytokine responses and elevated DNA damage, but not increased radiation sensitivity or DNA repair defects. The TLK1 p.Q479E variant impaired kinase activity but not proximal protein interactions. Our study provides the first functional characterization of NDD-associated TLK1 variants and suggests that, such as TLK2, TLK1 variants may impact development in multiple tissues and should be considered in the diagnosis of rare NDDs.
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During pregnancy, women undergo several metabolic changes to guarantee an adequate supply of glucose to the foetus. These metabolic modifications develop what is known as physiological insulin resistance. When this process is altered, however, gestational diabetes mellitus (GDM) occurs. GDM is a multifactorial disease, and genetic and environmental factors play a crucial role in its aetiopathogenesis. GDM has been linked to both macroscopic and molecular alterations in placental tissues that affect placental physiology. This review summarizes the role of the placenta in the development of GDM from a molecular perspective, including hormonal and pro-inflammatory changes. Inflammation and hormonal imbalance, the characteristics dominating the GDM microenvironment, are responsible for placental changes in size and vascularity, leading to dysregulation in maternal and foetal circulations and to complications in the newborn. In conclusion, since the hormonal mechanisms operating in GDM have not been fully elucidated, more research should be done to improve the quality of life of patients with GDM and their future children.
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Bovine mastitis is a disease wi th far - reaching consequences for the dairy industry. Staphylococcus aureus is a pathogen that is especially resistant to antibiotics. The objective of this study was to evaluate the antimicrobial activity of the essential oils Lippia citriodora (Lam.), Thy mus vulgaris (L), and a mixture of the essential oils Lippia citriodora and Thymus vulgaris (50/50 v/v), against isolates of oxacillin - resistant Staphylococcus aureus (n=15) of positive cases of bovine mastitis. For the statistical analysis, the IBM SPSS s tatistical package was used. The mixture of essential oils ( Lippia citriodora and Thymus vulgaris (50/50 v/v)) obtained the most significant antimicrobial activity in relation to pure essential oils. It is therefore concluded that the mixture of these oils boosts their antimicrobial activity ( p <0.05). The minimum inhibitory and bactericidal concentration of this mixture for the total isolations was 12 µL/L and 25 µL/mL, respectively.
La mastitis bovina es una enfermedad de gran impacto para la industria lechera. El Staphylococcus aureus es uno de los principales patógenos, especialmente aquellos resistentes a los antibióticos. El objetivo de este estudio fue evaluar la actividad antimicrobiana de los aceites esenciales de Lippia citriodora (Lam.), Thymus vulgaris (L), y una mezcla de aceites esenciales de Lippia citriodora y Thymus vulgaris (50/50 v/v), frente a aislamientos clínicos de Staph ylococcus aureus oxacilino - resistentes (n=15) de mastitis bovina. Se utilizó p rograma estadístico IBM SPSS y se concluyó la diferencia significativa a un p <0.05. La mezcla de aceites esenciales ( Lippia citriodora y Thymus vulgaris (50/50 v/v)), obtuvo la m ayor actividad antimicrobiana en relación a los aceites esenciales puros, se concluye que la mezcla de estos aceites potencia su actividad antimicrobiana ( p <0.019). La concentración mínima inhibitoria y bactericida de esta mezcla fue del 12 µL/mL y 25 µL/m L, respectivamente, y puede ser una alternativa terapéutica.
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Animales , Femenino , Bovinos , Aceites Volátiles/aislamiento & purificación , Mastitis Bovina/microbiología , Mastitis Bovina/terapia , Staphylococcus aureus/aislamiento & purificación , Farmacorresistencia Microbiana , ColombiaRESUMEN
Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.
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Administración Intranasal , Antivirales , Neomicina , SARS-CoV-2 , Animales , Neomicina/farmacología , Neomicina/administración & dosificación , Ratones , Humanos , Antivirales/farmacología , Antivirales/administración & dosificación , SARS-CoV-2/inmunología , SARS-CoV-2/efectos de los fármacos , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/prevención & control , Mucosa Nasal/inmunología , Mucosa Nasal/virología , Mucosa Nasal/efectos de los fármacos , Modelos Animales de Enfermedad , Tratamiento Farmacológico de COVID-19 , Mesocricetus , Femenino , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/inmunologíaRESUMEN
Children and adolescents with intellectual disabilities (ID) often encounter difficulties with narrative skills. Yet, there is a lack of research focusing on how to assess these skills in this population. This study offers an overview of the tools used for assessing oral narrative skills in children and adolescents with ID, addressing key questions about common assessment tools, their characteristics, and reported evidence. A systematic review was conducted of the literature published between 2010 and 2023 in the PsycINFO, ERIC, Education, and Psychology databases. An initial 1176 studies were reviewed by abstract, of which 485 were read in full text, leading to the selection and analysis of 22 studies. Most of the identified tools involve analyzing language samples obtained using wordless picture story books. Three common tools are emphasized. Studies have primarily identified inter-rater reliability and test-criterion evidence for validity. The main tools and their characteristics are discussed in depth to aid readers in discerning suitable options for research or practical applications. The importance of reporting diverse sources of evidence for validity and reliability within this population is highlighted.
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INTRODUCTION: eConsults are asynchronous digital communications for primary care professionals to seek timely specialist advice. Potential benefits include increased primary healthcare capacity and referral efficiency. Santa Catarina Telehealth Centre in Brazil has offered eConsults for an increasing number of specialties since 2008. This study described the characteristics of this service, including referral efficiency, sustainability, and satisfaction. METHODS: Retrospective longitudinal analysis of eConsults activity data from 2015 to 2022 with three domains of the Model for Assessment of Telemedicine Applications used to structure the analysis. RESULTS: Characteristics of the application: The total number of eConsults performed in 2015 was 4764, reaching 41,178 in 2022. While 30.3% of eConsults were synchronous in 2015, only asynchronous communication remained from 2021. Clinical effectiveness: eConsults requested to refer patients to specialist care resulting in primary care management remaining above 30% of the total for all specialties from 2019 to 2022, with hematology having the highest percentage (>52%). Organizational aspects: Established workflows with local specialists responding to eConsults (cardiology, endocrinology, hematology and orthopaedics) kept a constant or increasing number of eConsults and maintained the proportion of primary care management from 2019 to 2022, once recovered from COVID-19 and funding restrictions-related reductions. Over 90% of primary care professionals are either satisfied or very satisfied with the eConsult service. CONCLUSION: Over 8 years, 223,734 consultations were conducted, with high satisfaction, demonstrating the substantial potential for increased primary care-sensitive conditions management. Hiring local specialists, fostering integrated care, and enabling sustainable workflows are key to eConsults' success.
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Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.
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Antioxidantes , Envejecimiento de la Piel , Humanos , Antioxidantes/farmacología , Rayos Ultravioleta/efectos adversos , Piel/metabolismo , Estrés OxidativoRESUMEN
BACKGROUND: Dermatitis is a skin condition caused by multiple causes, including radiotherapy treatment. Pharmacological treatments can become chronic and are not exempt from side effects. The latest recommendations of the American Academy of Dermatology establish the use of natural, nourishing, and moisturizing cosmetic products as prevention and the first therapeutic step for dermatitis. Alantel® is a cream developed to reduce redness and irritation, promote the local immune system, combat immunosenescence, and promote the healing of epidermal lesions. The objective was to evaluate the effect of a cream (Alantel) based on natural products at high concentrations for the preventive and curative treatment (at early stages) of radiation-induced dermatitis in patients with breast cancer. METHODS: Our protocol is an experimental, prospective, triple-blind, multicenter, controlled clinical trial with two parallel arms. The experimental group will be treated with Alantel, while the control group will receive another moisturizing cream. Radiotherapy oncology professionals will recruit a total of 88 patients (44 per comparison group) with breast cancer who will receive radiotherapy oncology treatment for 15 days, and they will be randomly allocated to the experimental or control group. Selected patients will be followed up for four visits by primary care physicians for up to 1 week after completion of radiotherapy. The main study variable will be the incidence rate of mild post-radiation dermatitis. An intention-to-treat analysis will be performed, applying a comparison test for independent means and proportions. A bivariate and multivariate analysis will also be developed to check the treatment effect, adjusting for predictive sociodemographic and clinical variables. DISCUSSION: By carrying out this clinical trial, it is expected to verify that Alantel cream, based on natural products at high concentrations, has advantages over a moisturizing cream for the preventive and curative treatment of RD in patients with breast cancer. The COVID-19 pandemic has been influenced by delaying the start of the study. One of the main limitations of this study will be the time required to recruit the patients from the planned sample, given that the selection criteria are restrictive and, although the study is multicenter, recruitment will be coordinated through a single service on radiotherapy oncology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04116151 . Registered on 4 October 2019.
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Aloe , Productos Biológicos , Neoplasias de la Mama , Radiodermatitis , Thymus (Planta) , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/complicaciones , Manzanilla , Pandemias/prevención & control , Estudios Prospectivos , Radiodermatitis/diagnóstico , Radiodermatitis/tratamiento farmacológico , Radiodermatitis/etiología , Productos Biológicos/uso terapéutico , Resultado del TratamientoRESUMEN
Poly (3,4-ethylenedioxythiophene) (PEDOT) doped with polystyrene sulfonate (PSS) is the most used conducting polymer from energy to biomedical applications. Despite its exceptional properties, there is a need for developing new materials that can improve some of its inherent limitations, e.g., biocompatibility. In this context, doping PEDOT is propose with a robust recombinant protein with tunable properties, the consensus tetratricopeptide repeated protein (CTPR). The doping consists of an oxidative polymerization, where the PEDOT chains are stabilized by the negative charges of the CTPR protein. CTPR proteins are evaluated with three different lengths (3, 10, and 20 identical CTPR units) and optimized varied synthetic conditions. These findings revealed higher doping rate and oxidized state of the PEDOT chains when doped with the smallest scaffold (CTPR3). These PEDOT:CTPR hybrids possess ionic and electronic conductivity. Notably, PEDOT:CTPR3 displayed an electronic conductivity of 0.016 S cm-1, higher than any other reported protein-doped PEDOT. This result places PEDOT:CTPR3 at the level of PEDOT-biopolymer hybrids, and brings it closer in performance to PEDOT:PSS gold standard. Furthermore, PEDOT:CTPR3 dispersion is successfully optimized for inkjet printing, preserving its electroactivity properties after printing. This approach opens the door to the use of these novel hybrids for bioelectronics.
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Materiales Biocompatibles , Compuestos Bicíclicos Heterocíclicos con Puentes , Conductividad Eléctrica , Polímeros , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Polímeros/química , Materiales Biocompatibles/química , Poliestirenos/química , Ingeniería de Proteínas/métodos , Iones , ElectrónicaRESUMEN
This study aimed to examine the composition and properties of the invasive macroalgae R. okamurae and explore potential applications. The results showed that the seaweed biomass is mainly composed of structural carbohydrates, with alginate being the main constituent, accounting for 32 % of its total composition and with a mannuronic and guluronic acid ratio (M/G) ratio of 0.93. It also has a relatively high concentration of fucose, related to the presence of fucoidans that have important biological functions. Among the mineral contents, a high magnesium and calcium (7107 and 5504 mg/kg) concentration, and the presence of heavy metals above legislated thresholds, were notable. R. okamurae also contained a high lipid content of 17 %, mainly composed of saturated fatty acids, but with a significant fraction of n3 polyunsaturated fatty acids (18 %) resulting in a low n6/n3 ratio (0.31), that has health benefits. The protein content of R. okamurae was 12 %, with high-quality proteins, as essential amino acids (mainly leucine, phenylalanine and valine) constitute 32 % of the total amino acids. It also showed a high polyphenol content and outstanding antioxidant properties (106.88 mg TE/g). Based on these findings, R. okamurae has significant potential as a sustainable source of bioactive compounds that can add value to different sectors, including food, feed, pharmaceuticals and cosmetics.
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Phaeophyceae , Algas Marinas , Algas Marinas/química , Biomasa , Ácidos Grasos/metabolismo , Proteínas/metabolismoRESUMEN
Resumo O artigo explora a teleassistência a partir dos desenvolvimentos da telessaúde e da aceleração da transformação digital na saúde provocada pela pandemia de COVID-19, com foco no Sistema Único de Saúde (SUS). Aborda questões terminológicas, escopo de ações, potencialidades do uso para atenção à saúde e condicionantes e contingências para a utilização da teleassistência no Brasil, concentrando-se nas teleconsultas e nas interações entre profissionais de saúde e pacientes. Por fim, apresenta um conjunto de proposições para o desenvolvimento das políticas e práticas de teleassistência no Brasil, tendo em vista os princípios do SUS, organizados em dois eixos estratégicos centrais: diretrizes político organizacionais e proposições operacionais e de organização dos serviços e do cuidado. Destaca-se a importância de ponderar e elucidar os alcances e os limites das novas tecnologias para evitar idealizações e deslumbramentos com suas propostas de solução para os complexos problemas de saúde. As soluções de teleassistência devem ser compatíveis com princípios e diretrizes do SUS e com o modelo de atenção preconizado, que prevê a organização da rede a partir da atenção primária, para garantir acesso, integralidade e qualidade da atenção à saúde para a sociedade brasileira.
Abstract This article explores telecare from telehealth developments and the recent acceleration of the digital health transformation caused by the COVID-19 pandemic, focusing on the Brazilian Unified Health System (SUS). It addresses terminological issues, the scope of actions, the potential use for healthcare, and constraints and contingencies for telecare in Brazil, focusing on teleconsultations and interactions between health professionals and patients. Finally, it presents a set of propositions for the development of telecare policies and practices in Brazil, considering SUS principles, in two central themes: organizational political guidelines and operational propositions to organise services and healthcare delivery. The importance of clarifying the scope and limits of new technologies is highlighted in the attempt to avoid idealizations with proposed solutions to complex health problems. Telecare solutions should be compatible with SUS principles and with the recommended model of care, with the healthcare network coordinated and organised by primary care, ensuring access to health services and integrated and quality healthcare for the Brazilian society.
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Early-stage colorectal carcinoma (CRC)-pT1-is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5-2%. Among these cases, approximately 6-16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/µL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management.
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Background: The Tousled-like kinases 1 and 2 (TLK1/TLK2) regulate DNA replication, repair and chromatin maintenance. TLK2 variants are associated with 'Intellectual Disability, Autosomal Dominant 57' (MRD57), a neurodevelopmental disorder (NDD) characterized by intellectual disability (ID), autism spectrum disorder (ASD) and microcephaly. Several TLK1 variants have been reported in NDDs but their functional significance is unknown. Methods: A male patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency was determined to have a novel, heterozygous variant in TLK1 (c.1435C>G, p.Q479E) by genome sequencing (GS). Single cell gel electrophoresis, western blot, flow cytometry and RNA-seq were performed in patient-derived lymphoblast cell lines. In silico, biochemical and proteomic analysis were used to determine the functional impact of the p.Q479E variant and previously reported NDD-associated TLK1 variant, p.M566T. Results: Transcriptome sequencing in patient-derived cells confirmed expression of TLK1 transcripts carrying the p.Q479E variant and revealed alterations in genes involved in class switch recombination and cytokine signaling. Cells expressing the p.Q479E variant exhibited reduced cytokine responses and higher levels of spontaneous DNA damage but not increased sensitivity to radiation or DNA repair defects. The p.Q479E and p.M566T variants impaired kinase activity but did not strongly alter localization or proximal protein interactions. Conclusion: Our study provides the first functional characterization of TLK1 variants associated with NDDs and suggests potential involvement in central nervous system and immune system development. Our results indicate that, like TLK2 variants, TLK1 variants may impact development in multiple tissues and should be considered in the diagnosis of rare NDDs.
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Introducción y objetivo: El cáncer de mama es la neoplasia maligna con mayor incidencia y prevalencia mundial (excluyendo tumores cutáneos no melanoma), con cifras crecientes. Por ello, cualquier tejido extraído de la mama, con independencia del motivo, debe ser enviado a estudio anatomopatológico. El objetivo de este estudio es determinar la prevalencia de lesiones premalignas y carcinoma oculto en las piezas de resección de mamas intervenidas por motivos no oncológicos durante 5 años en el Servicio de Cirugía Plástica, Estética y Reparadora del Hospital Universitario Río Hortega de Valladolid, España. Material y método: Analizamos las piezas de resección mamaria de 253 pacientes sin diagnóstico clínico de cáncer de mama clasificadas previamente en grupos de riesgo teórico creciente de neoplasia asociada, con el objetivo de identificar la prevalencia de lesiones premalignas y carcinoma oculto en nuestra población. Resultados: La prevalencia de lesiones malignas mostró un incremento progresivo desde el grupo control (2.25%): pacientes sin antecedente personal de neoplasia mamaria ni factor de riesgo genético, a los grupos A (7.07%): pacientes con antecedente de neoplasia mamaria; B (11.43%): pacientes con factor de riesgo genético; y C (16.67%): pacientes con antecedente de neoplasia mamaria y factor de riesgo genético, con una edad media al diagnóstico de 48.11 años. Conclusiones: Los resultados obtenidos se correlacionan con la literatura existente y ponen de manifiesto que el hallazgo casual de lesiones premalignas y malignas en pacientes sin diagnóstico de cáncer de mama es una realidad relativamente común, especialmente en mujeres con factores de riesgo genético y/o diagnóstico de neoplasia mamaria previa.Nivel de evidencia científica 4b Diagnóstico
Background and objective: Breast cancer is the malignancy with the highest incidence and prevalence worldwide (excluding non-melanoma skin cancer), with growing rates. This is why any tissue removed from a breast (whatever the cause) must be properly analyzed. The aim of this study is to determine the prevalence of premalignant lesions and occult carcinoma in resected breast specimens operated for non-oncological reasons over a period of 5 years in the Plastic, Aesthetic, and Reconstructive Surgery Department at the Río Hortega University Hospital in Valladolid, Spain. Methods: We analyzed the breast resection specimens belonging to 253 patients without a clinical diagnosis of breast cancer, previously classified in groups of increasing theoretical risk of breast cancer, with the aim of identifying the prevalence of premalignant lesions and occult carcinoma in our population. Results: The prevalence of malignant lesions showed a progressive increase from the control group (2.25%): patients without personal history of breast neoplasia or genetic risk factor; to groups A (7,07%): patients with history of breast neoplasia; B (11.43%): patients with genetic risk factor; and C (16.67%): patients with history of breast neoplasia and genetic risk factor, with an average age at diagnosis of 48.11 years. Conclusions: The results correlate with the existing literature show that the casual finding of premalignant and malignant lesions in patients without a diagnosis of breast cancer is relatively common, especially in women with genetic risk factors and/or a prior diagnosis of breast cancer.(AU)
Asunto(s)
Humanos , Femenino , Carcinoma , Neoplasias de la Mama/cirugía , Mamoplastia , Mastectomía , Implantes de Mama , Prevalencia , Estudios Retrospectivos , Cirugía Plástica , Neoplasias de la MamaRESUMEN
RESUMO A segurança do paciente na Atenção Primária à Saúde (APS) preocupa-se em reduzir erros e eventos adversos relacionados a assistência à saúde, porém há poucos estudos elaborados com aplicação de modelos avaliativos sobre a temática neste contexto. Este trabalho objetivou desenvolver e propor um modelo avaliativo da segurança do paciente na APS. Realizou-se um estudo de avaliabilidade por meio da análise documental, revisão de literatura, proposição dos modelos e validação dos modelos por meio da conferência de consenso. Idealmente, a teoria do programa, apresentada no Modelo Teórico, evidencia que os recursos, a cultura de segurança, os processos assistenciais e a educação permanente são componentes que viabilizam a implantação do programa, que precisam ser discutidos e aprimorados com envolvimento da gestão, dos profissionais e dos próprios pacientes/familiares e cuidadores, sendo, portanto, explorados no Modelo Lógico e assumidos como fundamentais para a oferta de cuidados mais seguros na APS quando interagem articuladamente. Na Matriz de Análise e Julgamento, esses quatro componentes assumem o mesmo peso no cálculo que determinará o grau de implantação da segurança do paciente na APS. A modelização apresentada pode ser utilizada por diversos atores, de diferentes contextos, para explorar e aprimorar a segurança do paciente na APS.
ABSTRACT Patient safety in Primary Health Care (PHC) is concerned with reducing errors and adverse events related to health care, but there are few studies developed with the application of evaluative models on the subject in this context. This study aimed to develop and propose an evaluation model of patient safety in PHC. An evaluability study was carried out through document analysis, literature review, proposition of models and validation of models through consensus conference. Ideally, the theory of the program, presented in the Theoretical Model, shows that resources, safety culture, care processes and permanent education are components that enable the implementation of the program, which need to be discussed and improved with the involvement of management, professionals and the patients/family members and caregivers themselves, being, therefore, explored in the Logical Model and assumed as fundamental for the provision of safer care in PHC when they interact articulately. In the Analysis and Judgment Matrix, these four components assume the same weight in the calculation that will determine the degree of implementation of patient safety in PHC. The modeling presented can be used by different actors, from different contexts, to explore and improve patient safety in PHC.