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1.
Fam Pract ; 41(2): 168-174, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38300765

RESUMO

BACKGROUND: There is a need for a deeper understanding of the barriers to research in family medicine (FM) and to consider the perceptions and perspectives of professionals. Our study aims to provide a strategic view for research capacity building in FM. We included the perspective of family physician researchers (FPR) on the existing barriers to investigation in this context. OBJECTIVES: To understand and characterize the barriers to research in FM (personal and structural), from the perspective of Portuguese family physicians who are researchers. METHODS: A qualitative study, of phenomenological nature, was performed, through the conduction of semi-structured interviews with FPR, from 2019 to 2022. Data analysis and thematic coding were done on MAxQDA®, with inductive and deductive approaches, until data saturation was reached. RESULTS: A total of 12 family physicians/researchers were interviewed. Seven main themes were identified as barriers to research: time, professional valorization, funding, ethics committees, infrastructure, management/institutions, and participants. Each theme is divided into subthemes that make it possible to assess how a barrier can affect researchers in performing research activities. CONCLUSION: Our study highlights the identification of 7 main barriers. Structuring them into sub-themes not only improved the organization of our results but also provided robust support for the next phase, namely the application of a survey with the aim of gaining a deeper insight into the repercussions that these barriers to FPR have at a national level. This research is crucial to laying the foundations for a policy document that offers well-defined and tailored recommendations to address the barriers we have uncovered.


Assuntos
Medicina de Família e Comunidade , Médicos de Família , Humanos , Portugal , Pesquisadores , Pesquisa Qualitativa
2.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674150

RESUMO

Saracatinib (AZD0530) is a dual Src/Abl inhibitor initially developed by AstraZeneca for cancer treatment; however, data from 2006 to 2024 reveal that this drug has been tested not only for cancer treatment, but also for the treatment of other diseases. Despite the promising pre-clinical results and the tolerability shown in phase I trials, where a maximum tolerated dose of 175 mg was defined, phase II clinical data demonstrated a low therapeutic action against several cancers and an elevated rate of adverse effects. Recently, pre-clinical research aimed at reducing the toxic effects and enhancing the therapeutic performance of saracatinib using nanoparticles and different pharmacological combinations has shown promising results. Concomitantly, saracatinib was repurposed to treat Alzheimer's disease, targeting Fyn. It showed great clinical results and required a lower daily dose than that defined for cancer treatment, 125 mg and 175 mg, respectively. In addition to Alzheimer's disease, this Src inhibitor has also been studied in relation to other health conditions such as pulmonary and liver fibrosis and even for analgesic and anti-allergic functions. Although saracatinib is still not approved by the Food and Drug Administration (FDA), the large number of alternative uses for saracatinib and the elevated number of pre-clinical and clinical trials performed suggest the huge potential of this drug for the treatment of different kinds of diseases.


Assuntos
Benzodioxóis , Reposicionamento de Medicamentos , Quinazolinas , Humanos , Reposicionamento de Medicamentos/métodos , Quinazolinas/uso terapêutico , Quinazolinas/química , Quinazolinas/farmacologia , Benzodioxóis/uso terapêutico , Benzodioxóis/química , Benzodioxóis/farmacologia , Animais , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/efeitos adversos , Doença de Alzheimer/tratamento farmacológico , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismo , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/química
3.
Mem Inst Oswaldo Cruz ; 118: e220259, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37531506

RESUMO

BACKGROUND: Chikungunya is a mosquito-borne virus that has been causing large outbreaks in the Americas since 2014. In Brazil, Asian-Caribbean (AC) and East-Central-South-African (ECSA) genotypes have been detected and lead to large outbreaks in several Brazilian states. In Rio Grande do Sul (RS), the southernmost state of Brazil, the first cases were reported in 2016. OBJECTIVES AND METHODS: We employed genome sequencing and epidemiological investigation to characterise the Chikungunya fever (CHIKF) burden in RS between 2017-2021. FINDINGS: We detected an increasing CHIKF burden linked to travel associated introductions and communitary transmission of distinct lineages of the ECSA genotype during this period. MAIN CONCLUSIONS: Until 2020, CHIKV introductions were most travel associated and transmission was limited. Then, in 2021, the largest outbreak occurred in the state associated with the introduction of a new ECSA lineage. CHIKV outbreaks are likely to occur in the near future due to abundant competent vectors and a susceptible population, exposing more than 11 million inhabitants to an increasing infection risk.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Animais , Humanos , Vírus Chikungunya/genética , Brasil/epidemiologia , Viagem , Filogenia , Mosquitos Vetores , Surtos de Doenças , Genótipo
4.
Dev Biol ; 473: 90-96, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33581137

RESUMO

During development glial cell are crucially important for the establishment of neuronal networks. Proliferation and migration of glial cells can be modulated by neurons, and in turn glial cells can differentiate to assume key roles such as axonal wrapping and targeting. To explore the roles of actin cytoskeletal rearrangements in glial cells, we studied the function of Rho1 in Drosophila developing visual system. We show that the Pebble (RhoGEF)/Rho1/Anillin pathway is required for glia proliferation and to prevent the formation of large polyploid perineurial glial cells, which can still migrate into the eye disc if generated. Surprisingly, this Rho1 pathway is not necessary to establish the total glial membrane area or for the differentiation of the polyploid perineurial cells. The resulting polyploid wrapping glial cells are able to initiate wrapping of axons in the basal eye disc, however the arrangement and density of glia nuclei and membrane processes in the optic stalk are altered and the ensheathing of the photoreceptor axonal fascicles is reduced.


Assuntos
Axônios/fisiologia , Proteínas de Drosophila/metabolismo , Neuroglia/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Axônios/metabolismo , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Proteínas Contráteis/metabolismo , Drosophila melanogaster/metabolismo , Olho/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Neurogênese , Neuroglia/fisiologia , Neurônios/metabolismo , Poliploidia
5.
Endocr Pract ; 28(9): 911-917, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35660466

RESUMO

OBJECTIVE: Mild androgen insensitivity syndrome (MAIS) belongs to the androgen insensitivity syndrome (AIS) spectrum, an X-linked genetic disease that is the most common cause of differences in sex development. Unfortunately, AIS studies mainly focus on the partial and complete phenotypes, and the mild phenotype (MAIS) has been barely reported. Our purpose is to explore the MAIS facets, clinical features, and molecular aspects. METHODS: We collected all reported MAIS cases in the medical literature and presented them based on the phenotype and molecular diagnosis. RESULTS: We identified 49 different androgen receptor (AR) mutations in 69 individuals in the literature. We compared the AR mutations presented in individuals with MAIS with AR mutations previously reported in other AIS phenotypes (partial and complete) regarding the type, location, genotype-phenotype correlation, and functional studies. CONCLUSION: This review provides a landscape of the mild phenotype of AIS. Most patients with MAIS present with male factor infertility. Therefore, AR gene sequencing should be considered during male factor infertility investigation, even in males with typically male external genitalia. In addition, MAIS can be part of other medical conditions, such as X-linked spinal and bulbar muscular atrophy (Kennedy disease).


Assuntos
Síndrome de Resistência a Andrógenos , Infertilidade , Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/genética , Humanos , Masculino , Mutação , Fenótipo , Receptores Androgênicos/genética
6.
J Pediatr Gastroenterol Nutr ; 71(6): 734-739, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32804906

RESUMO

OBJECTIVES: The aim of the study was to describe the experience with teduglutide of several Spanish hospitals in pediatric patients with SBS (SBS). METHODS: Seventeen pediatric patients with intestinal failure associated with SBS were treated with teduglutide. Patients received 0.05 mg ·â€Škg ·â€Šday of subcutaneous teduglutide. Patients' demographics and changes in parenteral nutrition (PN) needs, fecal losses, and citrulline level initially and at 3, 6, and 12 months were collected, as well as any adverse events. RESULTS: Patients were receiving 55 ml ·â€Škg ·â€Šday and 33 kcal ·â€Škg ·â€Šday of parenteral supplementation on average at baseline (2 patients received only hydroelectrolytic solution). A total of 12/17 patients achieved parenteral independence: 3 patients after 3 months of treatment, 4 patients at 6 months, and 5 after 12 months. One patient discontinued treatment 1 year after the beginning as no changes in parenteral support or fecal losses were obtained. All others decreased their intravenous requirements by 50%. One patient suffered an episode of cholecystitis, and another one with a pre-existing cardiac disease, developed a cardiac decompensation. CONCLUSIONS: Teduglutide seems to be a safe and effective treatment in the pediatric SBS population with better results than in the pivotal study as well as in the adult population.


Assuntos
Fármacos Gastrointestinais , Peptídeos , Síndrome do Intestino Curto , Adulto , Criança , Fármacos Gastrointestinais/uso terapêutico , Humanos , Nutrição Parenteral , Peptídeos/uso terapêutico , Síndrome do Intestino Curto/tratamento farmacológico
7.
Epidemiol Infect ; 146(5): 571-576, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29477155

RESUMO

Although serological assays have been widely used for the diagnosis of canine visceral leishmaniasis (CVL), they present different performances depending on the clinical profile of the dogs. This study evaluated the accuracy of serological tests, immunochromatographic (Dual Path Platform: DPP®) and enzyme-linked immunosorbent (ELISA EIE®), for CVL in relation to the detection of Leishmania DNA through real-time polymerase chain reaction (real-time PCR) in samples from symptomatic and asymptomatic dogs from a non-endemic area in the state of Rio Grande do Sul, Southern Brazil. Serum from 140 dogs (39 symptomatic and 101 asymptomatic) was tested by DPP and ELISA followed by real-time PCR. From a total of 140 samples evaluated, Leishmania DNA was detected by real-time PCR in 41.4% (58/140). Moreover, 67.2% of samples positive in real-time PCR were positive in both DPP and ELISA (39/58), showing moderate agreement between methods. In the symptomatic group, one sample non-reactive in both serological assays was positive in real-time PCR, whereas in the asymptomatic group, 17.8% non-reactive or undetermined samples in serological assays were positive in the molecular method. Leishmania DNA was not detected in 17.9% reactive samples by serological assays from the symptomatic group, and in 3.9% from asymptomatic dogs. Real-time PCR demonstrated greater homogeneity between symptomatic and asymptomatic groups compared with DPP and ELISA. The molecular method can help to establish the correct CVL diagnosis, particularly in asymptomatic dogs, avoiding undesirable euthanasia.


Assuntos
Cromatografia de Afinidade/veterinária , Doenças do Cão/diagnóstico , Ensaio de Imunoadsorção Enzimática/veterinária , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Animais , Infecções Assintomáticas , Brasil , Cromatografia de Afinidade/métodos , Doenças do Cão/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Leishmaniose Visceral/parasitologia , Reação em Cadeia da Polimerase em Tempo Real/métodos
8.
Pediatr Emerg Care ; 34(6): 409-412, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29851917

RESUMO

PURPOSE: The aims of this study were to analyze the characteristics of patients with acute liver failure (ALF) in our center and evaluate the prognostic value of the Pediatric End-Stage Liver Disease (PELD) score calculated at admission. METHODS: A retrospective analysis of patients with ALF younger than 15 years between 2005 and 2013 was performed. Information collected included age, sex, etiology of ALF, laboratory tests, PELD score, stage of encephalopathy, and need for liver support devices such as MARS and/or liver transplant (LT) and survival. A poor prognosis was defined as the need for LT or death. RESULTS: Twenty patients (10 male patients, 50%) with a median age of 2.6 years (3 days-14.5 y old) were included. Acute liver failure was of indeterminate cause in 5 cases (25%). Within the recognized causes, the most frequent were viral hepatitis (herpes simplex virus, adenovirus, influenza B, Epstein-Barr virus), autoimmune hepatitis, and metabolopathies. Sixty percent presented with encephalopathy at diagnosis. Four patients were aided by a MARS liver support device. Six patients received a total of 7 transplants, all from deceased donors. The rate of spontaneous recovery was 45%. Currently 13 patients (65%) are living, 4 of them with an LT. Six patients died because of ALF. The mean PELD score of patients with spontaneous recovery was 15.31 (5.3-27.6) compared with a mean of 29.5 (17.2-39.4) in LT patients and 31.55 (15.8-52.4) for nonsurvivors (P = 0.013). CONCLUSIONS: High PELD scores at diagnosis were accurate predictors of a poor prognosis in our patients with ALF. This model may help in the clinical management of this entity, although prospective validation is needed.


Assuntos
Doença Hepática Terminal/diagnóstico , Falência Hepática Aguda/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/terapia , Transplante de Fígado/estatística & dados numéricos , Masculino , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
9.
Korean J Parasitol ; 56(1): 11-19, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29529845

RESUMO

In Brazil, visceral leishmaniasis (VL) is expanding and becoming urbanized, especially in non-endemic areas such as the State of Rio Grande do Sul. Considering that infected dogs are the main reservoir for zoonotic VL, this study evaluated the prevalence of canine visceral leishmaniasis (CVL) in the metropolitan area of Porto Alegre, a new area of expansion of VL in Brazil. Serum and plasma from 405 asymptomatic dogs from the municipalities of Canoas (n=107), São Leopoldo (n=216), and Novo Hamburgo (n=82) were tested for CVL using immunochromatographic (DPP®) and ELISA EIE® assays (2 assays officially adopted by the Brazilian government for the diagnosis of CVL) and real-time PCR to confirm the results. There was no agreement among serological and real-time PCR results, indicating that the Leishmania infection in asymptomatic animals with low parasite load, confirmed by negative parasitological tests (smears and parasite culture), need to be evaluated by molecular methods. The prevalence of LVC in the metropolitan region of Porto Alegre, confirmed by real-time PCR was 4% (5.6% in Canoas and 4.6% in São Leopoldo). The use of molecular method is essential for accurate diagnosis of CVL, especially in asymptomatic dogs in non-endemic areas.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/diagnóstico , Doenças do Cão/parasitologia , Leishmaniose/diagnóstico , Leishmaniose/veterinária , Parasitologia/métodos , Animais , Biomarcadores/sangue , Brasil/epidemiologia , Cromatografia de Afinidade , Estudos Transversais , DNA de Protozoário/isolamento & purificação , Doenças do Cão/epidemiologia , Cães , Ensaio de Imunoadsorção Enzimática , Leishmania infantum/imunologia , Leishmaniose/epidemiologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real
10.
Rev Gaucha Enferm ; 38(3): e0006, 2018 Mar 12.
Artigo em Português, Inglês | MEDLINE | ID: mdl-29538604

RESUMO

OBJECTIVE: To analyze the maternal perception about the paternal care and to understand how this care Is made effective In practical actions in the care of the child/adolescent with chronic disease in the family routine. METHODS: Exploratory-descriptive, qualitative study, carried out at the pediatric outpatient clinic of a public hospital in the state of Paraíba, between November/2013 and April/2014, with 10 mothers whose children had more than six months of diagnosis. Semi-structured interview subsidized the data collection, which was submitted to thematic analysis. RESULTS: Parents participated in activities such as routine care of the child, medication management, leisure, binomial support and household chores. They took on different roles in the care depending on the availability of time and the maternal freedom given for their participation. Among the separated couples, the distance between parents in the care reflected on the child's health. CONCLUSION: It is important to involve fathers in the care of the child with chronic diseases. However, there is a need for a greater involvement of fathers in the performance of this care.


Assuntos
Cuidado da Criança , Doença Crônica , Pai , Mães/psicologia , Relações Pais-Filho , Adolescente , Brasil , Criança , Cuidado da Criança/psicologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa
11.
Sensors (Basel) ; 17(11)2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29104229

RESUMO

The typical layout in a piezoresistive tactile sensor arranges individual sensors to form an array with M rows and N columns. While this layout reduces the wiring involved, it does not allow the values of the sensor resistors to be measured individually due to the appearance of crosstalk caused by the nonidealities of the array reading circuits. In this paper, two reading methods that minimize errors resulting from this phenomenon are assessed by designing an electronic system for array reading, and the results are compared to those obtained using the traditional method, obviating the nonidealities of the reading circuit. The different models were compared by testing the system with an array of discrete resistors. The system was later connected to a tactile sensor with 8 × 7 taxels.

12.
Am J Med Genet A ; 164A(2): 542-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24311220

RESUMO

Shah-Waardenburg syndrome or Waardenburg syndrome type 4 (WS4) is a neurocristopathy characterized by the association of deafness, depigmentation and Hirschsprung disease. Three disease-causing genes have been identified so far for WS4: EDNRB, EDN3, and SOX10. SOX10 mutations, found in 45-55% of WS4 patients, are inherited in autosomal dominant way. In addition, mutations in SOX10 are also responsible for an extended syndrome involving peripheral and central neurological phenotypes, referred to as PCWH (peripheral demyelinating neuropathy, central dysmyelinating leucodystrophy, Waardenburg syndrome, Hirschsprung disease). Such mutations are mostly private, and a high intra- and inter-familial variability exists. In this report, we present a patient with WS4 and a second with PCWH due to SOX10 mutations supporting again the genetic and phenotypic heterogeneity of these syndromes. Interestingly, the WS4 family carries an insertion of 19 nucleotides in exon 5 of SOX10, which results in distinct phenotypes along three different generations: hypopigmentation in the maternal grandmother, hearing loss in the mother, and WS4 in the proband. Since mosaicism cannot explain the three different related-WS features observed in this family, we propose as the most plausible explanation the existence of additional molecular events, acting in an additive or multiplicative fashion, in genes or regulatory regions unidentified so far. On the other hand, the PCWH case was due to a de novo deletion in exon 5 of the gene. Efforts should be devoted to unravel the mechanisms underlying the intrafamilial phenotypic variability observed in the families affected, and to identify new genes responsible for the still unsolved WS4 cases.


Assuntos
Mutação , Fatores de Transcrição SOXE/genética , Síndrome de Waardenburg/diagnóstico , Síndrome de Waardenburg/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Pré-Escolar , Análise Mutacional de DNA , Éxons , Ordem dos Genes , Doença de Hirschsprung , Humanos , Masculino , Dados de Sequência Molecular , Fenótipo , Espanha
13.
Acta Med Port ; 37(2): 110-118, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37314201

RESUMO

INTRODUCTION: There are several barriers discouraging clinicians from undertaking research, including insufficient funding, lack of time, organizational issues and lack of support. The strengthening of research capacity is perceived from three levels: characteristics of the researcher, the environment, and organizational issues. To date, Portugal is lacking studies on this subject. The aim of this study was to identify the best practices to promote research in Portuguese Primary Health Care. METHODS: We conducted a qualitative study using semi-structured interviews with family doctors with broadly recognized research work and other stakeholders. We selected a sample by convenience and snowball sampling. From a total of 14 doctors invited by email, 12 responded positively, and we subsequently included two other stakeholders. We conducted the interviews in digital or face-to-face formats. Two team members handled the coding of interviews independently. We kept all recordings and transcripts confidential, only accessible to researchers. RESULTS: We identified 16 strategies: 1) increasing institutional support; 2) creating support structures; 3) redefining the residency program; 4) investing in research training; 5) redefining curriculum evaluation; 6) establishing dedicated time for research; 7) increasing funding; 8) improving access to research data; 9) being a research driver; 10) establishing a research culture; 11) working in collaboration; 12) creating formally organized research groups; 13) creating autonomous research centers; 14) improving the definition of the research subjects and study designs; 15) reviewing procedures for ethics' committees; and 16) reviewing the current selection of articles for publication. CONCLUSION: Overall, a greater proportion of interviewees identified the following as the most relevant strategies for research promotion: institutional support, including technical and scientific support from public institutions, private entities and academic centers; the reorganization of working hours with protected time for research; increased funding directed towards research and breaking isolation in research, promoting teamwork with clinicians within the same area or from different professional backgrounds.


Assuntos
Pesquisa sobre Serviços de Saúde , Médicos , Humanos , Portugal , Pesquisa Qualitativa
14.
Andrology ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38923406

RESUMO

BACKGROUND: Androgen insensitivity syndrome (AIS) is a common condition among individuals with differences of sexual development (DSD) and results from germline allelic variants in the androgen receptor (AR) gene. Understanding the phenotypic consequences of AR allelic variants that disrupt the activation function 2 (AF2) region is essential to grasping its clinical significance. OBJECTIVES: This study aims to provide insights into the phenotypic characteristics and clinical impact of AR mutations affecting the AF2 region in AIS patients. We achieve this by reviewing reported AR variants in the AF2 region among individuals with AIS, including identifying a new phenotype associated with the c.2138T>C variant (p.Leu713Pro) in the AR gene. MATERIALS AND METHODS: We comprehensively reviewed AR variants within the AF2 region reported in AIS and applied molecular dynamics simulations to assess the impact of the p.Leu713Pro variant on protein dynamics. RESULTS: Our review of reported AR variants in the AF2 region revealed a spectrum of phenotypic outcomes in AIS patients. Molecular dynamics simulations indicated that the p.Leu713Pro variant significantly alters the local dynamics of the AR protein and disrupts the correlation and covariance between variables. DISCUSSION: The diverse phenotypic presentations observed among individuals with AR variants in the AF2 region highlight the complexity of AIS. The altered protein dynamics resulting from the p.Leu713Pro variant further emphasize the importance of the AF2 region in AR function. CONCLUSION: Our study provides valuable insights into AR mutations' phenotypic characteristics and clinical impact on the AF2 region in AIS. Moreover, the disruption of protein dynamics underscores the significance of the AF2 region in AR function and its role in the pathogenesis of AIS.

15.
J Pers Med ; 14(5)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38793028

RESUMO

Lung cancer has the highest incidence and cancer-related mortality worldwide. In Portugal, it ranks as the fourth most common cancer, with nearly 6000 new cases being diagnosed every year. Lung cancer is the main cause of cancer-related death among males and the third cause of cancer-related death in females. Despite the globally accepted guidelines and recommendations for what would be the ideal path for a lung cancer patient, several challenges occur in real clinical management across the world. The recommendations emphasize the importance of adequate screening of high-risk individuals, a precise tumour biopsy, and an accurate final diagnosis to confirm the neoplastic nature of the nodule. A detailed histological classification of the lung tumour type and a comprehensive molecular characterization are of utmost importance for the selection of an efficacious and patient-directed therapeutic approach. However, in the context of the Portuguese clinical organization and the national healthcare system, there are still several gaps in the ideal pathway for a lung cancer patient, involving aspects ranging from the absence of a national lung cancer screening programme through difficulties in histological diagnosis and molecular characterization to challenges in therapeutic approaches. In this manuscript, we address the most relevant weaknesses, presenting several proposals for potential solutions to improve the management of lung cancer patients, helping to decisively improve their overall survival and quality of life.

16.
BMJ Open ; 14(2): e077632, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38309767

RESUMO

INTRODUCTION: The qualities of primary healthcare (PHC) make it a very relevant environment for research; however, there is still work to be done to enhance the research capabilities of family physicians in healthcare units. Considering there is no ongoing review that specifically addresses this objective, the proposed goal of this scoping review is to determine the depth of the literature on the current strategies that support research capacity building among family physicians in the context of PHC. METHODS AND ANALYSIS: The scoping review will include studies from PubMed, Scopus, Web of Science, Cochrane Library and grey literature, published from 2008 to 2023, that address strategies to promote research capacity building among family physicians in the context of PHC. Only studies published in English, Portuguese or Spanish will be considered. All study designs, including quantitative, qualitative and mixed-methods studies, will be eligible for inclusion. The literature search will be performed from January to March of 2024 and data charting will employ a descriptive-analytical method, systematically summarising study objectives, methodologies, findings and implications. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols and the review will employ the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. ETHICS AND DISSEMINATION: This review does not need ethical approval. Peer-reviewed publications, policy summaries, presentations at conferences and involvement with pertinent stakeholders are all part of our outreach approach.


Assuntos
Fortalecimento Institucional , Médicos de Família , Humanos , Confiabilidade dos Dados , Etnicidade , Projetos de Pesquisa , Atenção Primária à Saúde , Revisões Sistemáticas como Assunto , Literatura de Revisão como Assunto
17.
Mol Oncol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978350

RESUMO

Paired related homeobox 1 (PRRX1) is an inducer of epithelial-to-mesenchymal transition (EMT) in different types of cancer cells. We detected low PRRX1 expression in nevus but increased levels in primary human melanoma and cell lines carrying the BRAFV600E mutation. High expression of PRRX1 correlates with invasiveness and enrichment of genes belonging to the EMT programme. Conversely, we found that loss of PRRX1 in metastatic samples is an independent prognostic predictor of poor survival for melanoma patients. Here, we show that stable depletion of PRRX1 improves the growth of melanoma xenografts and increases the number of distant spontaneous metastases, compared to controls. We provide evidence that loss of PRRX1 counteracts the EMT phenotype, impairing the expression of other EMT-related transcription factors, causing dysregulation of the ERK and signal transducer and activator of transcription 3 (STAT3) signaling pathways, and abrogating the invasive and migratory properties of melanoma cells while triggering the up-regulation of proliferative/melanocytic genes and the expression of the neural-crest-like markers nerve growth factor receptor (NGFR; also known as neurotrophin receptor p75NTR) and neural cell adhesion molecule L1 (L1CAM). Overall, our results indicate that loss of PRRX1 triggers a switch in the invasive programme, and cells de-differentiate towards a neural crest stem cell (NCSC)-like phenotype that accounts for the metastatic aggressiveness.

18.
Nutr Hosp ; 41(3): 702-705, 2024 Jun 27.
Artigo em Espanhol | MEDLINE | ID: mdl-38726617

RESUMO

Introduction: Objectives: the prevention of central line-associated bloodstream infections is a critical aspect of care for patients with intestinal failure who are treated with parenteral nutrition. The use of taurolidine in this context is becoming increasingly popular, however there is a lack of standardization in its pediatric application. The objective of this work is to develop a guide to support its prescription. Methodology: the guide is based on a review of the literature and expert opinions from the Intestinal Failure Group of the SEGHNP. It was developed through a survey distributed to all its members, addressing aspects of usual practice with this lock solution. Results: this manuscript presents general recommendations concerning taurolidine indications, commercial presentations, appropriate forms of administration, use in special situations, adverse reactions, and contraindications in the pediatric population Conclusions: taurolidine is emerging as the primary lock solution used to prevent central line-associated bloodstream infections, proving to be safe and effective. This guide aims to optimize and standardize its use in pediatrics.


Introducción: Objetivo: la prevención de las infecciones asociadas a catéter ocupa un papel fundamental en los cuidados del paciente en situación de fracaso intestinal en tratamiento con nutrición parenteral. El empleo del sellado del catéter con taurolidina con ese fin se ha generalizado sin que exista una estandarización sobre su uso en población pediátrica. El objetivo de este trabajo es elaborar una guía clínica que sirva de apoyo en su utilización. Métodos: la guía se basa en una revisión de la literatura y en la opinión de expertos del Grupo de Trabajo de Fracaso Intestinal de la SEGHNP recogida a través de una encuesta realizada a todos sus integrantes sobre aspectos de la práctica habitual con este sellado. Resultados: este manuscrito expone unas recomendaciones en cuanto a las indicaciones, presentaciones comerciales disponibles, forma adecuada de administración, uso en situaciones especiales, reacciones adversas y contraindicaciones de la taurolidina en población pediátrica. Conclusiones: el sellado con taurolidina para la prevención de la infección asociada a catéter venoso central se ha mostrado como un tratamiento eficaz y seguro. La presente guía pretender optimizar y homogeneizar su uso en pediatría.


Assuntos
Insuficiência Intestinal , Nutrição Parenteral , Taurina , Tiadiazinas , Humanos , Tiadiazinas/uso terapêutico , Tiadiazinas/efeitos adversos , Criança , Taurina/análogos & derivados , Taurina/uso terapêutico , Nutrição Parenteral/normas , Nutrição Parenteral/métodos , Insuficiência Intestinal/terapia , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Anti-Infecciosos/uso terapêutico , Lactente , Pré-Escolar
19.
Nutrients ; 16(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38613123

RESUMO

Nosocomial infections are a frequent and serious problem in extremely low birth weight (ELBW) infants. Donor human milk (DHM) is the best alternative for feeding these babies when mother's own milk (MOM) is not available. Recently, a patented prototype of a High-Temperature Short-Time (HTST) pasteurizer adapted to a human milk bank setting showed a lesser impact on immunologic components. We designed a multicentre randomized controlled trial that investigates whether, in ELBW infants with an insufficient MOM supply, the administration of HTST pasteurized DHM reduces the incidence of confirmed catheter-associated sepsis compared to DHM pasteurized with the Holder method. From birth until 34 weeks postmenstrual age, patients included in the study received DHM, as a supplement, pasteurized by the Holder or HTST method. A total of 213 patients were randomized; 79 (HTST group) and 81 (Holder group) were included in the analysis. We found no difference in the frequency of nosocomial sepsis between the patients of the two methods-41.8% (33/79) of HTST group patients versus 45.7% (37/81) of Holder group patients, relative risk 0.91 (0.64-1.3), p = 0.62. In conclusion, when MOM is not available, supplementing during admission with DHM pasteurized by the HTST versus Holder method might not have an impact on the incidence of catheter-associated sepsis.


Assuntos
Recém-Nascido de Peso Extremamente Baixo ao Nascer , Sepse , Lactente , Recém-Nascido , Humanos , Leite Humano , Temperatura , Suplementos Nutricionais , Sepse/epidemiologia , Sepse/prevenção & controle
20.
Front Oncol ; 14: 1304690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38634051

RESUMO

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.

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