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1.
Healthcare (Basel) ; 12(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38998898

RESUMO

This scoping review aims to map the evidence on moral distress of nurses working in paediatric healthcare settings from homecare to hospital. It was conducted according to the Joanna Briggs Institute. International databases were searched according to the specific thesaurus and free search terms. Independent screening and analysis were conducted using Rayyan QCRI. This review considered a total of 54 studies, including quantitative and qualitative studies, systematic reviews, and grey literature; English and Portuguese languages were included. Moral distress is a phenomenon discussed in nursing literature and in the paediatric context but is considered absent from discussion in clinical practice. It is caused by disproportionate care associated with overtreatment. Nurses can present a variety of symptoms, characterising moral distress as a highly subjective experience. The paediatric contexts of practice should promote a healthy ethical climate and work towards a moral community built with peer support, education, communication, leadership, and management involvement. Moral distress is still a complex and challenging multidimensional concept, and the aim should be to promote a culture of prevention of the devastating consequences of moral distress and work towards moral resilience.

2.
FASEB J ; 38(14): e23818, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-38989572

RESUMO

The association between cardiac fibrosis and galectin-3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin-3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese-infarcted rats. The inhibitor of galectin-3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4-phenylbutyric acid (4-PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight-obese patients who suffered a first MI showed higher circulating galectin-3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal-weight patients. A correlation was observed between galectin-3 levels and extracellular volume. Obese-infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin-3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin-3. Both MCP and 4-PBA not only reduced cardiac fibrosis, oxidative stress, galectin-3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin-3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin-3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.


Assuntos
Estresse do Retículo Endoplasmático , Galectina 3 , Obesidade , Animais , Galectina 3/metabolismo , Obesidade/metabolismo , Obesidade/complicações , Masculino , Ratos , Humanos , Pectinas/farmacologia , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/complicações , Feminino , Fibrose , Ratos Wistar , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Fenilbutiratos/farmacologia , Autofagia , Miocárdio/metabolismo , Miocárdio/patologia , Galectinas/metabolismo , Idoso , Proteínas Sanguíneas/metabolismo
3.
Support Care Cancer ; 32(8): 517, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014284

RESUMO

OBJECTIVE: To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). RESEARCH METHODS AND PROCEDURES: In this cohort study, patients (≥ 18 years old) with CRC were followed for 36 months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. RESULTS: A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2 years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). CONCLUSION: The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.


Assuntos
Composição Corporal , Neoplasias Colorretais , Comorbidade , Humanos , Masculino , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Pessoa de Meia-Idade , Feminino , Idoso , Estudos de Coortes , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Fatores Etários
4.
Genes (Basel) ; 15(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38927713

RESUMO

Members of the SOX (SRY-related HMG box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular modelsBy providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.


Assuntos
Carcinogênese , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Carcinogênese/genética , Transição Epitelial-Mesenquimal/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Regulação Neoplásica da Expressão Gênica , Animais
5.
Sci Rep ; 14(1): 10829, 2024 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734789

RESUMO

Patients with colorectal cancer (CRC) often exhibit changes in body composition (BC) which are associated with poorer clinical outcomes. Many studies group colon and rectal cancers together, irrespective of staging, potentially affecting assessment and treatment strategies. Our study aimed to compare BC in patients with CRC focusing on tumor location and metastasis presence. A total of 635 individuals were evaluated, with a mean age of 61.8 ± 12.4 years and 50.2% female. The majority had rectal cancer as the primary cancer site (51.0%), and 23.6% had metastatic disease. The first regression model showed tumor site and metastasis as independent factors influencing skeletal muscle (SM), skeletal muscle index (SMI), and visceral adipose tissue variability (all p values < 0.05). The second model, adjusted for BMI, indicated tumor site as the primary factor affecting SMI variations (adjusted R2 = 0.50 p < 0.001), with colon tumors inversely associated with SM (standardized ß - 2.15(- 3.3; - 0.9) p < 0.001). A third model, considering all the confounders from the directed acyclic graphs, was constructed and the found association remained independent. Our findings highlight significant BC variations in patients with CRC, influenced by tumor location and metastases presence, underscoring the need for location-specific assessment in CRC management.


Assuntos
Composição Corporal , Neoplasias Colorretais , Estadiamento de Neoplasias , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Colorretais/patologia , Idoso , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Gordura Intra-Abdominal , Índice de Massa Corporal
6.
J Periodontal Res ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757372

RESUMO

AIM: Evidence suggests that translocation of oral pathogens through the oral-gut axis may induce intestinal dysbiosis. This study aimed to evaluate the impact of a highly leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice. METHODS: Eight-week-old male C57BL6 mice were divided into control (n = 16) and JP2 groups (n = 19), which received intragastric gavage with PBS and with a suspension of Aa JP2 (HK921), respectively, twice a week for 4 weeks. Colonic lamina propria, fecal material, serum, gingival tissues, and mandibles were obtained for analyses of leukocyte populations, inflammatory mediators, mucosal integrity, alveolar bone loss, and gut microbiota. Differences between groups for these parameters were examined by non-parametric tests. RESULTS: The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in Aa JP2-infected mice than in controls (p < .05). In contrast, infected animals showed higher abundance of Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium, higher levels of IL-6 expression in colonic tissues, and higher splenic MPO activity than controls (p < .05). No differences in tight junction expression, serum endotoxin levels, and colonic inflammatory cytokines were observed between groups. Infected animals presented also slightly more alveolar bone loss and gingival IL-6 levels than controls (p < .05). CONCLUSION: Based on this model, intragastric administration of Aa JP2 is associated with changes in the gut ecosystem of healthy hosts, characterized by less live/recruited myeloid cells, enrichment of the gut microbiota with pathobionts and decrease in commensals. Negligible levels of colonic pro-inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes.

7.
Clin Nutr ; 43(7): 1667-1674, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38815492

RESUMO

BACKGROUND & AIMS: Although it is widely recognized that muscle quality significantly influences adverse outcomes in patients with cancer, the precise definition of muscle quality remains elusive. The muscle quality index (MQI), also known as muscle-specific strength, is a relatively recent functional concept of muscle quality. It is obtained through the ratio of muscle strength to muscle mass, but its predictive value in patients with cancer remains unknown. In this study, we explored the prognostic significance of MQI in patients with cancer. Furthermore, we introduce and assess the prognostic potential of a novel muscle quality metric: the strength-to-muscle-radiodensity index (SMRi). METHODS: A secondary analysis was conducted on a prospective cohort study. CT scans were opportunistically used to assess body composition parameters, including skeletal muscle mass (SM in cm2) and muscle radiodensity (SMD in HU) at the third lumbar vertebra (L3). Handgrip strength (HGS) was measured. MQICT was calculated using the ratio of HGS to SM (cm2). SMRi was calculated as the ratio of HGS to SMD (HU). For analysis purposes, low MQICT and SMRi were defined using two approaches: statistical cutoffs associated with survival, and median-based distribution data. RESULTS: A total of 250 patients were included (52.8% females, 52% adults, 20-90 years). Gastrointestinal tumors and stage III-IV were the most frequent diagnosis and stages. SMRi and MQICT were strongly positively correlated (ρ = 0.71 P < 0.001). Individual components of MQICT and SMRi were also positively correlated. Patients with both low MQICT and SMRi had shorter survival (log-rank P = 0.023 and P = 0.003, respectively). When applying median distribution cutoffs, SMRi emerged as the most accurate predictor of mortality (HR adjusted 3.18, 95% CI 1.50 to 6.75, C-index: 0.71), when compared to MQICT (HR adjusted 1.49, 95% CI 0.77 to 2.87, C-index: 0.68). CONCLUSION: This study introduces the concept and potential prognostic significance of the SMRi. The physiological and clinical implications of this new index warrant further investigation across a spectrum of diseases, including cancer.


Assuntos
Composição Corporal , Força da Mão , Músculo Esquelético , Neoplasias , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Estudos Prospectivos , Idoso , Força da Mão/fisiologia , Neoplasias/mortalidade , Neoplasias/diagnóstico por imagem , Neoplasias/fisiopatologia , Prognóstico , Tomografia Computadorizada por Raios X/métodos , Força Muscular/fisiologia , Adulto , Sarcopenia/diagnóstico por imagem , Sarcopenia/fisiopatologia , Idoso de 80 Anos ou mais
8.
Acta Med Port ; 37(4): 316, 2024 Apr 01.
Artigo em Português | MEDLINE | ID: mdl-38631062

RESUMO

On page 5, 3rd paragraph, line 7, where it reads, (in red): "(...) considering the international recommendation (1:10 000)8" It should read (in blue): "(...) considering the international recommendation (0.5:10 000)8" Still on page 5, 5th paragraph, line 8, where it reads, (in red): "(...) in the 40 - 50-year age group" It should read (in blue): "(...) below the 40 - 50-year age group" On page 8, key of Table 1, line 5, where it reads, (in red): "1: PORTATA 2021;" It should read (in blue): "1: PORDATA 2021;" Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20321.


Na página 5, 3º parágrafo, linha 7, onde se lê, (a vermelho): "(...) considering the international recommendation (1:10 000)8" Deverá ler-se (a azul): "(...) considering the international recommendation (0.5:10 000)8" Ainda na página 5, 5º parágrafo, linha 8, onde se lê, (a vermelho): "(...) in the 40 - 50-year age group" Deverá ler-se (a azul): "(...) below the 40 - 50-year age group" Na página 8, legenda da Tabela 1, linha 5, onde se lê, (a vermelho): "1: PORTATA 2021;" Deverá ler-se (a azul): "1: PORDATA 2021;" Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20321.

9.
Physiother Res Int ; 29(2): e2084, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38529736

RESUMO

BACKGROUND AND OBJECTIVE: Individuals after stroke are likely to deal with the possible development of sarcopenia and reduced physical activity levels. The purpose of this study was to compare sarcopenia of individuals with chronic stroke who were stratified according to their physical activity levels, and to evaluate the relationship between sarcopenia and physical activity levels. MATERIALS AND METHODS: This cross-sectional study was conducted with individuals after chronic stroke recruited from the general community. Individuals were submitted to sarcopenia screening (SARC-F questionnaire) and assessment of physical activity levels (Human Activity Profile questionnaire) to classify the individuals as impaired, moderately active, and active according to their Adjusted Activity Status (AAS). ANOVA was used to investigate the sarcopenia between groups and Pearson's coefficient to investigate the association among variables. RESULTS: Fifty-four individuals with a mean age of 56 ± 17.4 years were included. Twenty-one percent of the individuals were screened for sarcopenia. Inactive individuals had higher mean scores in the SARC-F (3.6 ± 2.1 points), whereas moderately active and active individuals presented lower mean scores in the same questionnaire, being 1.2 ± 1.1 points and 0.5 ± 0.7 points, respectively. A statistically significant inverse and high association was found between sarcopenia and physical activity levels (r = -0.716; p < 0.01). CONCLUSION: Sarcopenia was found to be higher in individuals after chronic stroke with lower physical activity levels considered inactive when compared to individuals with higher physical activity levels. Furthermore, there was an inverse relationship between sarcopenia and physical activity level in stroke survivors.


Assuntos
Sarcopenia , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Estudos Transversais , Inquéritos e Questionários , Exercício Físico , Avaliação Geriátrica
10.
Methods Cell Biol ; 185: 151-164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556446

RESUMO

Cardiovascular disease (CVD) is the main cause of death worldwide, with myocardial infarction (MI) being the most prevalent pathology involved in CVD. MI is characterized by a deficiency in oxygen supply to the myocardium, thereby promoting ventricular remodeling of the ischemic and remote zone of the heart. Cardiac remodeling associated with MI could promote the development of heart failure and finally death. For these reasons, it is important to develop animal models that mimic human cardiac disease which could help to identify new mechanisms involved in the pathology and, consequently, develop new therapeutic strategies. We herein describe in detail a protocol for MI induction with low mortality rate (<15%) in rats by ligation of the left anterior descending artery. In addition, we also describe two imaging techniques which allow to evaluate cardiac structure and function-including deformation parameters in rats such as transthoracic echocardiography and cardiac magnetic resonance. This animal model could be useful for acute and chronic studies and for evaluating the potential usefulness of different treatments.


Assuntos
Infarto do Miocárdio , Função Ventricular Esquerda , Ratos , Humanos , Animais , Modelos Animais de Doenças , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio , Coração
11.
Vet Clin Pathol ; 53(1): 116-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38433106

RESUMO

A 25-year-old mixed-breed equine with separate nodular cutaneous lesions in the right thoracic limb (RTL) and right ventral abdominal region was admitted to a Veterinary Hospital in Belo Horizonte, Minas Gerais. Fine-needle aspiration cytology was performed on the RTL lesion and superficial cervical lymph node, and the results were suggestive of a malignant neoplasm known as myxosarcoma. Due to the unfavorable prognosis, the animal was euthanized. Based on the macroscopic and microscopic findings, the diagnosis of metastatic cutaneous myxosarcoma was confirmed. Although rare, this tumor should be considered as a differential diagnosis for cutaneous neoplasms in this species.


Assuntos
Doenças dos Cavalos , Mixossarcoma , Neoplasias Cutâneas , Cavalos , Animais , Mixossarcoma/patologia , Mixossarcoma/veterinária , Neoplasias Cutâneas/veterinária , Biópsia por Agulha Fina/veterinária , Prognóstico
12.
Acta Med Port ; 37(6): 419-428, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38477300

RESUMO

INTRODUCTION: Human resources in ophthalmology have recently received particular attention, and it has been questioned whether there is a sufficient number of workers. The aim of this study was to analyze and characterize Portugal's ophthalmologist population. METHODS: In this descriptive, cross-sectional study, an online questionnaire was sent to all ophthalmologists registered with the Portuguese College of Ophthalmology in December 2021. Information on the following variables was collected and analyzed: demographic factors, professional qualifications, professional activity, weekly professional activity and medium-term plans. RESULTS: Among the 910 registered ophthalmologists, a response rate of 64.7% was achieved. There were 0.9 ophthalmologists for every 10 000 inhabitants, 0.45:10 000 working in the public sector (0.35:10 000 full-time equivalent). Among the respondents, 57.6% were over 50 years old (59.6% male), 97.3% were Portuguese, 46.7% completed their residency in the Lisbon region, 27.3% complemented their programme with additional training, 9.5% had a PhD and approximately 58% lived and worked in large urban centres. Regarding professional activity, 58.5% of the respondents worked in the public sector (4.2% exclusively), while 67.9% worked in different economic sectors. The median number of weekly working hours reported was 45 hours, with those in the public sector reporting 35 hours. Private/social sector work and public sector work accounted for 12 926 hours/week and 10 808 hours/week, respectively. It was found that 31.4% of the respondents provided emergency medical services and that 52.8% performed surgical procedures more than once a week. Looking ahead, 38.7% of the ophthalmologists intended to reduce their workload within the next five years due to family reasons, fatigue and demotivation. The projected rate of retirement or cessation of activity in the next five years was estimated to be 1.7%, while an average of 20 new ophthalmologists are expected to enter the profession annually, resulting in a generational balance of 0.8%. CONCLUSION: While the number of ophthalmologists in Portugal meets the international recommendations, there is a shortage in the public sector and most ophthalmologists work in large urban centres. The number of ophthalmologists in Portugal is expected to be stable for the next five years.


Assuntos
Oftalmologistas , Portugal , Humanos , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Oftalmologistas/estatística & dados numéricos , Adulto , Oftalmologia/estatística & dados numéricos , Censos , Inquéritos e Questionários , Setor Público/estatística & dados numéricos
13.
Nutrition ; 119: 112324, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38215671

RESUMO

OBJECTIVES: To assess the concurrent and predictive validity of different combinations of Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with colorectal cancer considering different indicators of reduced muscle mass (MM) and the effects of the disease. METHODS: A secondary analysis with patients with colorectal cancer. The reduced MM was assessed by arm muscle area, arm muscle circumference, calf circumference, fat-free mass index, skeletal muscle index (SMI) and skeletal muscle. Cancer diagnosis or disease staging (TNM) was considered for the etiologic criterion referred to as the effect of the disease. The other phenotypic and etiologic criteria were also evaluated, and we analyzed 13 GLIM combinations. Concurrent validity between GLIM criteria and Patient-Generated Subjective Global Assessment was evaluated. Logistic and Cox regression were used in the predictive validation. RESULTS: For concurrent validity (n = 208), most GLIM combinations (n = 6; 54.5%) presented a moderate agreement with Patient-Generated Subjective Global Assessment and none showed satisfactory sensitivity and specificity (>80%). Reduced MM evaluated by SMI and SMI were present in the GLIM combinations associated with postoperative complications (odds ratio, ≥2.0), independent of other phenotypic and etiologic criteria. The combinations with reduced MM considering any method and fixed phenotypic criteria and TNM were associated with mortality (hazard ratio, ≥2.0). CONCLUSIONS: Satisfactory concurrent validity was not verified. The GLIM diagnosis of malnutrition was associated with postoperative complications and mortality.


Assuntos
Neoplasias Colorretais , Desnutrição , Humanos , Liderança , Gravidade do Paciente , Desnutrição/complicações , Desnutrição/diagnóstico , Músculo Esquelético , Complicações Pós-Operatórias , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Avaliação Nutricional , Estado Nutricional
14.
Amino Acids ; 56(1): 1, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285098

RESUMO

Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the α1, ß1, and γ1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 (131I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [131I]I-YIKVAV and [131I]I-YIGSR. Conversely, [131I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from - 2.12 to - 1.10. Serum protein binding assay for [131I]I-YIKVAV and [131I]I-YIGSR reached ≅ 48% and ≅ 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized α1 and ß1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.


Assuntos
Neoplasias da Mama , Animais , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Estudos Prospectivos , Distribuição Tecidual , Peptídeos/farmacologia , Laminina
15.
J Pharm Policy Pract ; 17(1): 2296551, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250517

RESUMO

Background: Monotherapy with aromatase inhibitors and fulvestrant were the standard-of-care for hormone receptor-positive (HR+)/human epidermal growth factor receptor-type2 negative (HER2-) advanced breast cancer, before integration of cyclin-dependent kinase 4/6 inhibitors. Effectiveness data is essential for regulatory action, but little is known about real-world use of aromatase inhibitors and fulvestrant. Methods: A retrospective cohort study was conducted resorting to data from a cancer registry to identify adult women with HR+/HER- advanced breast cancer exposed to aromatase inhibitors or fulvestrant (31 May 2017-31 March 2019) at the main oncology hospital in Portugal. Cases were updated with follow-up until death or cut-off (31 March 2021) and pseudoanonymized data extracted. Primary outcome was overall survival (OS) and secondary time to treatment failure (TTF), estimated using survival analysis and compared with published trials. Results: 192 patients were distributed by subgroups according to the medicine. Letrozole: OS 30.8 (95% confidence interval (CI) 20.6-41.4); TTF 11.2 (95%CI 8.7-13.7). Exemestane: OS 22.1 (95%CI 9.7-34.6); TTF 6.0 (95%CI 4.1-7.8). Fulvestrant: OS 21.6 (95%CI 16.5-26.7); TTF 5.6 (95%CI 4.5-6.6). Conclusions: Estimated effectiveness (OS) of letrozole and fulvestrant was, respectively, 3.2-3.5 months lower than reported. The clinical meaning seems uncertain and may be explained a higher proportion of worse prognostic characteristics in patients treated in the real-world.

16.
Clin Genitourin Cancer ; 22(1): e170-e177.e1, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38061978

RESUMO

INTRODUCTION: Building on previous suboptimal survival results, we aimed to perform a study of the epidemiological status, management, and outcomes of germ cell tumors (GCT) in the Portuguese population. MATERIALS AND METHODS: Retrospective populational study of GCT cases diagnosed between 2008 and 2012 in southern Portugal. Joinpoint regression was used to compute average annual percentage change (AAPC) in incidence rate. ESMO/EAU guidelines served as references to evaluate compliance. Association between compliance with guidelines and hospital GCT case load was performed by generalized estimating equation. Survival was calculated by Kaplan-Meier and prognostic factors by Cox models. RESULTS: The study included 401 GCT male cases. The AAPC was 5.4% (IC 95% 3.3-7.4, P < .001) from 1999 (an earlier cohort published) to 2012. The median time to diagnosis was 63 days (Q25 = 33 days; Q75 = 114 days; IQR = 81 days). For stage II/III the median time to start chemotherapy was 34 days (Q25 = 22 days; Q75 = 56 days; IQR = 22 days). In 86% cases there was noncompliance with guidelines for the orchiectomy report, 6% for staging, 38% for tumor markers evaluation, 20% for treatment and 25% for chemotherapy dose intensity. The 5-year overall survival was 93.8% (95% CI, 91.3%-96.4%). Hospitals that managed ≤ 3 GCT cases/ year had higher odds for noncompliance with guidelines of blood markers, treatment and dose intensity. None of GCT healthcare access and management factors studied were associated with prognosis. CONCLUSIONS: The burden of GCT is rising in Portugal. Although survival has improved, efforts must be made to nationally enhance training and expertise in GCT and support region adapted models of centralization of care.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Portugal/epidemiologia , Estudos Retrospectivos , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/terapia , Prognóstico , Biomarcadores Tumorais , Neoplasias Testiculares/terapia , Neoplasias Testiculares/tratamento farmacológico
17.
Rev. bras. educ. méd ; 48(2): e036, 2024. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1559448

RESUMO

Resumo Introdução: A necessidade crescente de doadores de órgãos e de profissionais capacitados impulsiona novos estudos que esclareçam o entendimento e comportamento da sociedade perante a doação de órgãos. Estudantes de saúde vêm sendo alvo de estudos por seu influente papel social e, além disso, quando formados, farão parte de etapas fundamentais da doação. Contudo, evidencia-se conhecimento insuficiente dos estudantes apesar de possuírem atitude positiva. Objetivo: Este estudo teve como objetivo avaliar o grau de conhecimento, desejo e atitude perante as doações de órgãos entre os acadêmicos de Medicina e Enfermagem na cidade de Recife, em Pernambuco. Método: Trata-se de um estudo transversal realizado a partir da análise de questionários respondidos por estudantes de Enfermagem e Medicina nos últimos períodos acadêmicos. Além de dados demográficos, os estudantes foram questionados quanto ao entendimento sobre aspectos da validação de possível doador, diretrizes do protocolo de morte encefálica, motivações e opções pessoais em relação à doação de órgãos. Resultado: De fevereiro a dezembro de 2022, 218 questionários foram coletados, dos quais 208 entraram para a amostra. Dentre os estudantes, 57,2% eram do sexo masculino, a média de idade foi de 24 ± 2,7 anos. Dos graduandos, 85,1% cursavam Medicina, e 14,9%, Enfermagem. Apenas 49% dos estudantes sabiam da não necessidade de neurologista para o diagnóstico de morte encefálica. Ademais, 63% não sabiam quem é o responsável por abordar a família do potencial doador. Grande parte dos acadêmicos já considerou a possibilidade de ser doador de órgãos, representando 92,3% do total de estudantes avaliados. Dos alunos, 67% afirmaram já ter conversado com as próprias famílias sobre a doação de órgãos e que elas conheciam essa decisão. Em caso de familiar apresentar diagnóstico de morte encefálica, 83,2% dos alunos consentiram a doação. Em relação aos possíveis benefícios materiais ou emocionais para a família do doador, 86,1% julgam que a doação de órgãos pode trazer algum benefício. Conclusão: Apesar da atitude positiva, o estudo evidenciou conhecimento insuficiente dos alunos, reforçando a necessidade de ampliação do currículo das universidades e criação de cadeiras direcionadas à aquisição de conhecimento e habilidades quanto à condução de casos de morte encefálica e atuação perante os potenciais doadores.


Abstract Background: The increasing demand for organ donors and proficient experts is prompting fresh research endeavors aimed at clarifying societal perceptions and actions related to organ donation. Students from the healthcare area have been a focal point in these studies. Despite their favorable attitudes, a notable gap in knowledge among students has been underscored. Objective: To assess the level of knowledge, willingness, and attitudes toward organ donation among medical and nursing students in the city of Recife, Brazil. Methods: A cross-sectional investigation was undertaken, involving the examination of questionnaires that were answered by medical and nursing students during their last academic years. Results: Between February and December 2022, a total of 218 questionnaires were gathered, of which 208 were included in the final sample. Among the participants, 57.2% identified as male, with an average age of 24 ± 2.7 years. In terms of academic background, 85.1% were enrolled in medical school, while 14.9% were attending nursing school. A notable observation was that only 49% of the students were aware that the diagnosis of brain death does not necessarily require the involvement of a neurologist. Furthermore, a significant proportion of students (63%) were unfamiliar with the entity responsible for initiating discussions with the potential donor's family. Interestingly, 92.3% of the students had contemplated the prospect of becoming organ donors themselves. If a family member were diagnosed with brain death, a significant majority of students, specifically 83.2%, expressed their willingness to grant consent for organ donation. Conclusions: Despite the positive attitudes, this study revealed insufficient knowledge among students, thereby underscoring the need for universities to expand their curricula and establish courses aimed at acquiring knowledge and skills related to brain death cases and actions related to potential donors.

18.
Toxins (Basel) ; 15(10)2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37888620

RESUMO

Antivenom production against Loxosceles venom relies on horses being immunized and bled for plasma harvest. One horse can partake in several cycles of antivenom production, which will require years of constant venom and adjuvant inoculation and bleeding. The actual impact on the health of horses that participate in several antivenom-producing cycles is unknown. Therefore, this study aimed to evaluate the general health status of horses that underwent at least six cycles of loxoscelic antivenom production. Seven crossbred horses that had partaken in six to eight complete antivenom-producing cycles were used and established as the immunized group (IG). Under the same handling and general management, eleven horses were established as the control group (CG). The horses were evaluated regarding their general clinical status and had their blood sampled, and an ECG recorded. The IG presented lower RBC and PCV, despite keeping values within inferior limits for the species. Renal function was not impaired, and liver-related enzymes were higher than those in the CG, probably due to liver exertion from immunoglobulin synthesis. ECG showed some abnormalities in the IG, such as atrioventricular block and a wandering atrial pacemaker, corroborated by an increase in CK-MB. The cardiovascular abnormalities were mainly found in the horses that participated in several antivenom-producing cycles. The overall results indicate that these horses had some impairment of their general health status. Once available, some alternative, less toxic antigens should replace the venom for immunization of horses used for antivenom production.


Assuntos
Antivenenos , Imunização , Cavalos , Animais , Adjuvantes Imunológicos , Antígenos , Nível de Saúde
19.
Front Chem ; 11: 1271176, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901160

RESUMO

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be -2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.

20.
Int J Prosthodont ; 0(0)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37824126

RESUMO

OBJECTIVE: to identify the prevalence of and factors associated with total edentulism in the elderly Brazilian population. In addition, we sought to verify whether edentulism influences the self-perception of oral health and difficulty in eating. MATERIALS AND METHODS: This cross-sectional, population-based study used the database of the National Health Survey conducted in Brazil. The chi-square test was initially used for data analysis. Subsequently, a multivariate analysis of the Poisson multiple regression type was performed to verify the adjusted prevalence ratios. RESULTS: A total of 43,554 elderly people participated in the study, of whom 32% had completely lost their teeth. This total edentulism, based on the multivariate analysis, was associated with female gender (p < 0.001), advances age (p < 0.001), illiterate (p < 0.001), smokers (p < 0.001), and those who did not have health insurance (p < 0.001) or dental insurance (p < 0.001). Total edentulism had an impact on better self-perception of oral health (p < 0.001) and greater difficulties in eating (p = 0.001). CONCLUSION: It was concluded that total edentulism in the elderly is associated with worse socioeconomic conditions and a worse lifestyle. This condition has a negative impact on diet and positively affects self-perception of oral health.

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