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In this qualitative study, we explored Portuguese adolescents' perceptions of diet, sustainability, and health through six focus group discussions (FGDs). Fifty-five adolescents (10-18 years) participated. FGDs focused on sustainability in food choices and its health impact, with our primary interest in their perceptions. Results showed a limited comprehension of "sustainable/sustainability," especially among younger participants. Those aware of sustainability recognized its diverse aspects, including health, economic, and ecological domains. Some adolescents recognized the link between health and sustainability in their diets, emphasizing the need for food literacy. These findings emphasize the importance of public health and sustainable policies among Portuguese adolescents.
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Dieta Saludable , Grupos Focales , Instituciones Académicas , Humanos , Portugal , Adolescente , Femenino , Masculino , Niño , Investigación Cualitativa , Conocimientos, Actitudes y Práctica en Salud , Dieta , Preferencias Alimentarias , PercepciónRESUMEN
BACKGROUND: This is a time of rapid change in the profession of pharmacy. Anecdotally, there are concerns that the pace, extent and rate of practice evolution are lagging. There is little evidence documenting the influencers and mechanisms that drive practice changes forward in pharmacy in Canada. METHODS: An exploratory qualitative method was selected, using both one-on-one interviews with self-categorized typical pharmacists and larger focus groups to provide context and confirmation of themes generated through interviews. Data were analyzed and coded using a constant-comparative iterative method, in order to generate themes related to the factors influencing pharmacists to actually change their practice. RESULTS: A total of 46 pharmacists meeting inclusion criteria participated in this study in focus groups, interviews or both. Nine themes were identified: 1) permission, 2) process pointers, 3) practice/rehearsal, 4) positive reinforcement, 5) personalized attention, 6) peer referencing, 7) physician acceptance, 8) patients' expectations and 9) professional identity supportive of a truly clinical role. One theme that did not emerge was payment, or remuneration, as a specific or isolated motivational factor for change. INTERPRETATION: The complexity of practice change in pharmacy and the multiple factors highlighted in this study point to a more deliberate and concerted effort being needed by diverse pharmacy organizations (educators, regulators, employers, professional associations, etc.) to support pharmacists through the change management process. CONCLUSIONS: The "9 Ps of practice change" identified through this study can provide pharmacists with guidance in terms of how to better support evolution of the profession in a more time-efficient and effective manner.
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BACKGROUND: The pace of practice change in community pharmacy over the past decade has been significant, yet there is little evidence documenting implementation of change in the profession. METHODS: Kotter's change management model was selected as a theoretical framework for this exploratory qualitative study. Community pharmacists were interviewed using a semistructured protocol based on Kotter's model. Data were analyzed and coded using a constant-comparative iterative method aligned with the stages of change management outlined by Kotter. RESULTS: Twelve community pharmacists were interviewed. Three key themes emerged: 1) the profession has successfully established the urgency to, and created a climate conducive for, change; 2) the profession has been less successful in engaging and enabling the profession to actually implement change; and 3) legislative changes (for example, expansion of pharmacists' scope of practice) may have occurred prematurely, prior to other earlier stages of the change process being consolidated. INTERPRETATION: As noted by most participants, allowing change is not implementing change: pharmacists reported feeling underprepared and lacking confidence to actually make change in their practices and believe that more emphasis on practical, specific implementation tactics is needed. CONCLUSIONS: Change management is complex and time and resource intensive. There is a need to provide personalized, detailed, context-specific implementation strategies to pharmacists to allow them to take full advantage of expanded scope of practice.
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Turnpenny-Fry Syndrome (TPFS) is a rare genetic disorder characterized by a severe developmental delay and a distinctive facial gestalt. It is caused by mutations in the Polycomb Group Ring Finger Protein 2 (PCGF2) gene, which is also known to play a role in numerous tumor types. Up to date, there have been no published case reports of patients with TPFS and concomitant malignancies. The present case describes the clinical evaluation and follow-up of a male infant with severe global developmental delay (GDD) and a distinctive phenotype. At 4 years of age, clinical exome sequencing confirmed the diagnosis of TPFS. Posteriorly, at 5 years of age, the patient was also diagnosed with T-cell acute lymphoblastic leukemia (ALL). Given the scarce literature regarding this syndrome, the authors expect that this case report will provide valuable information that could improve the follow-up of patients with TPFS. Furthermore, this case highlights the necessity for the appropriate diagnosis of developmental disorders, to ensure adequate care, surveillance of comorbidities and proper genetic counselling.
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OBJECTIVE: To adapt four dietary patterns for children and adolescents, and study their associations with sustainability (greenhouse-gas emissions-GHGE and land use-LU), and health (body mass index-BMI) indicators. RESEARCH METHODS & PROCEDURES: Dietary intake of children (3-9y) and adolescents (10-17y) from the National Food, Nutrition and Physical Activity Survey 2015-2016, Portugal (n = 1153) was assessed through two non-consecutive interviews: one-day food diaries (children), and 24-h recalls (adolescents), using an automated multiple-pass method, including a picture book for portion sizes estimation. Adherence to the Eat-Lancet and World Health Organization (WHO) recommendations, Mediterranean and Atlantic diets were evaluated using adapted versions for pediatrics of the World Index for Sustainability and Health (WISH), Diet Quality Index (DQI), Mediterranean Diet Score (MDS) and Southern-European Atlantic Diet (SEAD), respectively. Diet-related GHGE and LU were estimated using the SHARP-Indicators database. BMI (measured) z-scores were classified according to WHO criteria. A standardized weighted health-sustainability composite index was created (BMI + 0.5*GHGE+0.5*LU). Adjusted linear regression models were computed. RESULTS: WISH, DQI, MDS, and SEAD had weighted mean scores (range) of 50 (0-130), 24 (9-36), 20 (8-32), and 17 (8-32), respectively. All dietary patterns were associated with lower environmental impact, particularly in children, but not with BMI. Only MDS explained both health and sustainability indicators in childhood (composite index: sd.ß = -0·223,95%CI:-0·347,-0·072,R2 = 25.1 %), and adolescence (composite index: sd.ß = -0·159,95%CI:-0·315,-0·003,R2 = 31.3 %). CONCLUSION: The Mediterranean diet was the most related to (higher) environmental sustainability and (lower) BMI. However, in children (not adolescents), the WISH, DQI, and SEAD showed then same associations.
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Índice de Masa Corporal , Dieta , Ejercicio Físico , Humanos , Niño , Adolescente , Masculino , Femenino , Portugal , Dieta/estadística & datos numéricos , Preescolar , Encuestas Nutricionales , Dieta Mediterránea/estadística & datos numéricos , Conservación de los Recursos Naturales , Patrones DietéticosRESUMEN
Biopolymeric nanoparticles (NPs) have gained significant attention in several areas as an alternative to synthetic polymeric NPs due to growing environmental and immunological concerns. Among the most promising biopolymers is poly(lactic acid) (PLA), with a reported high degree of biocompatibility and biodegradability. In this work, PLA NPs were synthesized according to a controlled gelation process using a combination of single-emulsion and nanoprecipitation methods. This study evaluated the influence of several experimental parameters for accurate control of the PLA NPs' size distribution and aggregation. Tip sonication (as the stirring method), a PLA concentration of 10 mg/mL, a PVA concentration of 2.5 mg/mL, and low-molecular-weight PLA (Mw = 5000) were established as the best experimental conditions to obtain monodisperse PLA NPs. After gelification process optimization, flutamide (FLU) was used as a model drug to evaluate the encapsulation capability of the PLA NPs. The results showed an encapsulation efficiency of 44% for this cytostatic compound. Furthermore, preliminary cell viability tests showed that the FLU@PLA NPs allowed cell viabilities above 90% up to a concentration of 20 mg/L. The comprehensive findings showcase that the PLA NPs fabricated using this straightforward gelification method hold promise for encapsulating cytostatic compounds, offering a novel avenue for precise drug delivery in cancer therapy.
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Blueberry muffin syndrome (BMS) in neonates, characterized by widespread nodular lesions, presents diagnostic challenges due to its diverse etiologies. Hyperleukocytosis, with leukocyte counts exceeding 100,000/µL, is a rare phenomenon associated with severe complications in neonates. Congenital leukemia (CL), a rare diagnosis within the first month of life, is linked to high mortality. This case report presents a unique case of BMS with hyperleukocytosis as the initial presentation of CL. A full-term male newborn, born after an uncomplicated pregnancy, except for Kell isoimmunization, with an Apgar score of 9/10, and an irrelevant family history, showed widespread purple nodules consistent with BMS at birth. Laboratory workup revealed mild anemia, hyperleukocytosis with immature granulocytes on peripheral blood (PB) smear, positive direct antiglobulin test, and elevated alanine aminotransferase and lactate dehydrogenase, without hyperbilirubinemia. Empirical antibiotics and hyperhydration were started, and the neonate was transferred to a level 3 neonatal intensive care unit for further evaluation. A comprehensive etiological investigation was conducted, comprising infectious, immunological, metabolic, and neoplastic factors. A skin nodule biopsy revealed an infiltrate of blast cells, indicative of leukemia cutis, and a bone marrow aspirate confirmed acute myeloid leukemia (AML). The patient successfully completed the NOPHO-DBH-2012 chemotherapy protocol at five months and remains in complete remission at nine months. This case report contributes to the literature by highlighting the diagnostic approach and management strategies for CL presenting with BMS and hyperleukocytosis. This case aims to enhance awareness and understanding of BMS as an initial manifestation of CL. Additionally, the challenges of treating leukemia in neonates, coupled with the lack of specific guidelines for this age group, further underscore the complexities in managing such patients.
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INTRODUCTION: Preterm birth is increasing worldwide, representing a major cause of death and long-term loss of human potential among survivors. Some morbidities during pregnancy are well-known risk factors for preterm labor, but it is not yet known whether deviations from adequate dietary patterns are associated with preterm delivery. Diet may be an important modulator of chronic inflammation, and pro-inflammatory diets during pregnancy were reported to be associated with preterm birth. The aim of this study was to assess the food consumption during pregnancy of Portuguese women giving birth very prematurely and the association between the food consumption and the major maternal morbidities during pregnancy related with preterm delivery. MATERIAL AND METHODS: A single-center cross-sectional observational study including consecutive Portuguese women giving birth before 33 weeks of gestation was conducted. Recall of eating habits during pregnancy was obtained within the first week after delivery, using a semi quantitative food frequency questionnaire validated for Portuguese pregnant women. RESULTS: Sixty women with a median age of 36.0 years were included. Of these, 35% were obese or overweight at the beginning of pregnancy, 41.7% and 25.0% gained excessive or insufficient weight during pregnancy, respectively. Pregnancy-induced hypertension was present in 21.7% of cases, gestational diabetes in 18.3%, chronic hypertension in 6.7%, and type 2 diabetes mellitus in 5.0%. Pregnancy-induced hypertension was significantly associated with increased daily consumption of pastry products (31.2 vs 10.0 g, p = 0.022), fast food (39.6 vs 29.7 g, p = 0.028), bread (90.0 vs 50.0 g, p = 0.005), pasta, rice and potatoes (225.7 vs 154.3 g, p = 0.012). In a multivariate analysis, only bread consumption maintained a significant, albeit weak, association (OR = 1.021; 1.003 - 1.038, p = 0.022). CONCLUSION: Pregnancy-induced hypertension was associated with increased consumption of pastry products, fast food, bread, pasta, rice, and potatoes, although only bread consumption had a weak but statistically significant association with pregnancy-induced hypertension in a multivariate analysis.
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Diabetes Mellitus Tipo 2 , Hipertensión Inducida en el Embarazo , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Adulto , Hipertensión Inducida en el Embarazo/epidemiología , Estudios Transversales , Parto , Conducta AlimentariaRESUMEN
OBJECTIVE: To describe a cohort of placenta accreta spectrum (PAS) cases from a tertiary care institution and compare the maternal outcomes before and after the creation of a multidisciplinary team (MDT). METHODS: Retrospective study using hospital databases. Identification of PAS cases with pathological confirmation between 2010 and 2021. Division in two groups: standard care (SC) group - 2010-2014; and MDT group - 2015-2021. Descriptive analysis of their characteristics and maternal outcomes. RESULTS: During the study period, there were 53 cases of PAS (24 - SC group; 29 - MDT group). Standard care group: 1 placenta increta and 3 percreta; 12.5% (3/24) had antenatal suspicion; 4 cases had a peripartum hysterectomy - one planned due to antenatal suspicion of PAS; 3 due to postpartum hemorrhage. Mean estimated blood loss (EBL) was 2,469 mL; transfusion of packed red blood cells (PRBC) in 25% (6/24) - median 7.5 units. Multidisciplinary team group: 4 cases of placenta increta and 3 percreta. The rate of antenatal suspicion was 24.1% (7/29); 9 hysterectomies were performed, 7 planned due to antenatal suspicion of PAS, 1 after intrapartum diagnosis of PAS and 1 after uterine rupture following a second trimester termination of pregnancy. The mean EBL was 1,250 mL, with transfusion of PRBC in 37.9% (11/29) - median 2 units. CONCLUSION: After the creation of the MDT, there was a reduction in the mean EBL and in the median number of PRBC units transfused, despite the higher number of invasive PAS disorders.
OBJETIVO: Descrever uma coorte de casos do espectro do acretismo placentário (PAS) de uma instituição terciária e comparar os resultados maternos antes e depois da criação de uma equipa multidisciplinar (MDT). MéTODOS: Estudo retrospectivo utilizando bancos de dados hospitalares. Identificação de casos de PAS com confirmação patológica entre 2010 e 2021. Divisão em dois grupos: grupo Standard Care (SC) 20102014; e grupo MDT 20152021. Análise descritiva de suas características e desfechos maternos. RESULTADOS: Durante o período do estudo, houve 53 casos de PAS (24 - grupo SC; 29 - grupo MDT). Grupo Standard Care: 1 placenta increta e 3 percretas; 12,5% (3/24) tiveram suspeita anteparto; 4 casos tiveram histerectomia periparto uma eletiva devido à suspeita anteparto de PAS; 3 devido a hemorragia pós-parto. A média de perda hemática estimada (EBL) foi de 2.469 mL; transfusão de concentrado eritrocitário (PRBC) em 25% (6/24) - mediana 7,5 unidades. Equipa multidisciplinar: 4 casos de placenta increta e 3 percretas. A taxa de suspeita anteparto foi de 24,1% (7/29); foram realizadas 9 histerectomias, 7 eletivas por suspeita anteparto de PAS, 1 após diagnóstico intraparto de PAS e 1 após rotura uterina após interrupção da gravidez no segundo trimestre. A EBL média foi de 1.250 mL, com transfusão de PRBC em 37,9% (11/29) - mediana de 2 unidades. CONCLUSãO: Após a criação da MDT, houve redução na média de EBL e na mediana do número de unidades de PRBC transfundidas, apesar do maior número de PAS invasivos.
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Placenta Accreta , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Placenta Accreta/terapia , Placenta Accreta/cirugía , Portugal , Cesárea , Grupo de Atención al Paciente , HisterectomíaRESUMEN
Posterior reversible encephalopathy syndrome (PRES) is a reversible clinical-radiographic abnormality. It is characterized by headache, altered consciousness, seizures, and visual disruption, in addition to characteristic white matter edema lesions in the parieto-occipital areas of the brain. Early detection and treatment are crucial to prevent irreversible damage. This paper presents the cases of three patients with PRES with concurrent diagnoses of glomerulonephritis, Guillain-Barré syndrome, and sickle cell disease. All patients experienced systemic hypertension, seizures, and altered consciousness. All patients were admitted to intensive care for decreased level of awareness or status epilepticus requiring invasive mechanical ventilation. Anticonvulsants and antihypertensive therapy were essential. No chronic complications were recorded.
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Acute fulminant cerebral edema (AFCE) is a recently identified encephalitis type associated with significant morbimortality. Described as rare, limited data exists on its early detection and treatment. This paper describes a case of AFCE that progressed to unresponsive intracranial hypertension. A previously healthy four-year-old boy presented with fever, myalgias, and neurological symptoms. Diagnostic assessments showed cerebrospinal fluid abnormalities, and despite medical interventions, his condition deteriorated rapidly and developed severe cerebral edema and herniation within 24 hours. A decompressive craniectomy was attempted to decrease intracranial pressure, without success. This case emphasizes the urgency of early AFCE recognition and effective management strategies given its severe prognosis, aiming to improve understanding and spur further research.
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INTRODUCTION: Obesity is one of the most prevalent chronic diseases in childhood, being an important public health issue. Excessive weight has been associated with autonomic dysfunction but the evidence in children is scarce. Therefore, the aim of this study was to assess the effect of overweight and obesity on the autonomic nervous system activity, in children. MATERIAL AND METHODS: Data from a cross-sectional study of 1602 children, aged 7 to 12 years, was used and 858 children were included in the analysis. Body mass index was calculated and classified according to criteria of the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and the International Obesity Task Force (IOTF). Body composition was characterized by bioelectrical impedance. Linear regression models were used to determine the association between body mass index, body composition and the autonomic nervous system activity, assessed by pupillometry. RESULTS: Average dilation velocity was higher among children with obesity, according to the CDC and percentage of body fat criteria (ß = 0.053, 95% CI = 0.005 to 0.101 and ß = 0.063, 95% CI = 0.016 to 0.109, respectively). The same trend was observed for WHO and IOTF criteria (ß = 0.045, 95% CI = -0.001 to 0.091, and ß = 0.055, 95% CI = -0.001 to 0.111, respectively). CDC and WHO body mass index z-scores were also positively associated with the values of average dilation velocity (rs = 0.030, p = 0.048; and rs = 0.027, p = 0.042, respectively). CONCLUSION: Our findings suggest an association between body mass and changes in the autonomic activity, Moreover, this study provides proof of concept for interventions targeting the prevention/treatment of obesity in children that may offer some benefit in re-establishing the balance of the autonomic nervous system, and subsequently preventing the consequences associated with the autonomic nervous system dysfunction.
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Obesidad Infantil , Humanos , Niño , Obesidad Infantil/complicaciones , Estudios Transversales , Portugal , Prevalencia , Índice de Masa Corporal , Sobrepeso , Sistema Nervioso AutónomoRESUMEN
Alzheimer's disease (AD) is a common form of dementia that leads to multiple repercussions in the patient's life. This condition's clinical characteristics include loss of memory, temporal and spatial disorientation, language or executive dysfunction, and subsequent decline of social function. Dysexecutive syndrome (DS), the second most frequent neuropsychological dysfunction in AD, affects multiple brain areas and causes cognitive, behavioral, and emotional difficulties. We aimed to analyze the association between DS and AD and elucidate possible lack of evidence that may urge further research on this theme. Especially when dealing with such a disabling disease, where new findings can directly imply a better prognosis.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Calidad de Vida , Encéfalo , Pruebas NeuropsicológicasRESUMEN
The need for adherence to a healthy and sustainable dietary pattern in the pediatric stage is discussed worldwide, being linked to a progressive incidence of noncommunicable diseases in adulthood. The aims of this systematic review were to summarize the healthy and/or sustainable dietary patterns, defined a priori, described in the literature for use during the pediatric stage; to evaluate the adherence to these dietary patterns; and identify the health-related benefits associated with adherence to these patterns. A literature search was carried out on Medline, Scopus, and Web of Science from 2010 up to 2021, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 128 articles were included according to the following criteria: participants 2-17 y old, healthy and/or sustainable dietary patterns defined by an a priori methodology; articles written in English or Portuguese; and published since 2010. Fifty instruments with 14 adaptations that measure adherence to healthy and/or sustainable dietary patterns in children and adolescents were found. The Mediterranean Diet was the most studied dietary pattern. Adherence to healthy and/or sustainable dietary patterns has wide variations worldwide. Most of the instruments described have been little studied at pediatric ages, reducing the ability to extrapolate results. Higher adherence to these dietary patterns was associated with lower body fat, waist circumference, blood pressure, and metabolic risk. There is no consensus regarding the association with BMI. No studies have proofs of the sustainability characteristics of these instruments, it being necessary to produce a new sustainable instrument or test the association of the previous ones with, for example, the ecological footprint. Further validations of these instruments in each country and more prospective studies are needed to establish temporal relations with health-related outcomes. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020221788.
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Dieta Mediterránea , Conducta Alimentaria , Adolescente , Adulto , Presión Sanguínea , Niño , Estado de Salud , Humanos , Circunferencia de la CinturaRESUMEN
Introduction: Children/adolescents with cystic fibrosis (CF) have psychological and physical difficulties that have a severe impact on their health-related quality of life (HRQoL). Aim: To evaluate the impact of CF on HRQoL in a pediatric age sample by identifying major determinants and comparing the HRQoL reports of children and their parents. Methods: A sample of 27 children/adolescents was included in a cross-sectional observational study. Inclusion criteria were age between 4 and 18 years, diagnosis of CF, and the attendance of a caregiver in patients younger than 14 years. A questionnaire was applied to assess sociodemographic data and nutritional status. HRQoL was evaluated using the Portuguese revised version of the CF questionnaire (CFQ-R). Spearman correlations were calculated to analyze the agreement between children's and parents' reports. Spearman correlations and Mann-Whitney U tests were performed to identify associations between HRQoL domains and determinants. Results: The scores of CFQ-R domains were high, with the lowest median value being 66.67. It was found positive moderate associations between children's and parents' reports in 3 domains (P < .05): eating disturbances, body image, and respiratory symptoms. The median scores were similar in the eating disturbances (approximately 80.00) and in the respiratory symptoms (83.33). However, there is a consistent difference of 14.07 in the body image domain. Current age, physical activity, and iron were positively associated with HRQoL, whereas age at diagnosis was negatively associated. Conclusion: These findings reinforce the importance to evaluate HRQoL during childhood and adolescence and to invest in this public health theme.
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Not required for Clinical Vignette.
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Hipoglucemia/etiología , Hipopituitarismo/congénito , Hipopituitarismo/diagnóstico , Ictericia Obstructiva/etiología , Hepatopatías/etiología , Encéfalo/diagnóstico por imagen , Niño , Retardo del Crecimiento Fetal , Humanos , Hipoglucemia/diagnóstico , Hipopituitarismo/complicaciones , Lactante , Recién Nacido , Hepatopatías/complicaciones , Hepatopatías/diagnóstico , Imagen por Resonancia MagnéticaRESUMEN
Hibernomas are rare lipomatous tumors derived from brown adipose tissue. Only two cases of hibernomas in the scrotum have been reported in the literature so far. Brown adipose tissue is responsible for thermogenesis in hibernating mammals and embryos. In adult humans, reminiscent brown tissue is most frequently located in the axial skeleton, scapular waist, and neck. This case report describes the finding of a testicular pouch hibernoma in a 34-year-old male who presented with a nodule in the scrotum, which was initially suspected to be a lipoma. The diagnosis was confirmed by histopathological analysis, and the patient was treated by surgical excision. Despite its rarity, hibernoma should be part of the differential diagnosis for lipoma, the most frequent benign mesenchymal neoplasm worldwide.
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BACKGROUND: Muscle invasive bladder cancer (MIBC) remains amongst the deadliest genitourinary malignancies due to treatment failure and extensive molecular heterogeneity, delaying effective targeted therapeutics. Hypoxia and nutrient deprivation, oversialylation and O-glycans shortening are salient features of aggressive tumours, creating cell surface glycoproteome fingerprints with theranostics potential. METHODS: A glycomics guided glycoproteomics workflow was employed to identify potentially targetable biomarkers using invasive bladder cancer cell models. The 5637 and T24 cells O-glycome was characterized by mass spectrometry (MS), and the obtained information was used to guide glycoproteomics experiments, combining sialidase, lectin affinity and bottom-up protein identification by nanoLC-ESI-MS/MS. Data was curated by a bioinformatics approach developed in-house, sorting clinically relevant molecular signatures based on Human Protein Atlas insights. Top-ranked targets and glycoforms were validated in cell models, bladder tumours and metastases by MS and immunoassays. Cells grown under hypoxia and glucose deprivation disclosed the contribution of tumour microenvironment to the expression of relevant biomarkers. Cancer-specificity was validated in healthy tissues by immunohistochemistry and MS in 20 types of tissues/cells of different individuals. RESULTS: Sialylated T (ST) antigens were found to be the most abundant glycans in cell lines and over 900 glycoproteins were identified potentially carrying these glycans. HOMER3, typically a cytosolic protein, emerged as a top-ranked targetable glycoprotein at the cell surface carrying short-chain O-glycans. Plasma membrane HOMER3 was observed in more aggressive primary tumours and distant metastases, being an independent predictor of worst prognosis. This phenotype was triggered by nutrient deprivation and concomitant to increased cellular invasion. T24 HOMER3 knockdown significantly decreased proliferation and, to some extent, invasion in normoxia and hypoxia; whereas HOMER3 knock-in increased its membrane expression, which was more pronounced under glucose deprivation. HOMER3 overexpression was associated with increased cell proliferation in normoxia and potentiated invasion under hypoxia. Finally, the mapping of HOMER3-glycosites by EThcD-MS/MS in bladder tumours revealed potentially targetable domains not detected in healthy tissues. CONCLUSION: HOMER3-glycoforms allow the identification of patients' subsets facing worst prognosis, holding potential to address more aggressive hypoxic cells with limited off-target effects. The molecular rationale for identifying novel bladder cancer molecular targets has been established.
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Biomarcadores/metabolismo , Hipoxia de la Célula/genética , Glucosa/metabolismo , Glicoproteínas/metabolismo , Proteínas de Andamiaje Homer/metabolismo , Proteómica/métodos , Neoplasias de la Vejiga Urinaria/genética , Proliferación Celular , Humanos , Transfección , Microambiente TumoralRESUMEN
In guided bone tissue engineering, successful ingrowth of MSCs depends primarily on the nature of the scaffold. It is well-known that only seconds after implantation, biomaterials are coated by a layer of adsorbed proteins/peptides which modulates the subsequent cell/scaffold interactions, especially at early times after implantation. In this work, nanohydroxyapatite and collagen based composite materials (Coll/nanoHA) were modified with phosphorylated amino acid (O-phospho-L-serine-OPS) to mimic bone tissue, and induce cell differentiation. The choice for this phosphorylated amino acid is due to the fact that osteopontin is a serine-rich glycol-phosphoprotein and has been associated to the early stages of bone formation, and regeneration. Several concentrations of OPS were added to the Coll/nanoHA scaffold and physico-chemical, mechanical, and in vitro cell behavior were evaluated. Afterwards, the composite scaffold with stronger mechanical and best cellular behavior was tested in vivo, with or without previous in vitro culture of human MSC's (bone tissue engineering). The OPS signaling of the biocomposite scaffolds showed similar cellular adhesion and proliferation, but higher ALP enzyme activity (HBMSC). In vivo bone ectopic formation studies allowed for a thorough evaluation of the materials for MSC's osteogenic differentiation. The OPS-scaffolds results showed that the material could modulated mesenchymal cells behavior in favor of osteogenic differentiation into late osteoblasts that gave raised to their ECM with human bone proteins (osteopontin) and calcium deposits. Finally, OPS-modified scaffolds enhanced cell survival, engraftment, migration, and spatial distribution within the 3D matrix that could be used as a cell-loaded scaffold for tissue engineering applications and accelerate bone regeneration processes.
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OBJECTIVES: The aim of this study was to evaluate adherence to the Mediterranean dietary pattern (MDP) and its associated factors in older Portuguese adults. METHODS: A cross-sectional observational study was designed. In the context of the Nutrition UP 65 study, a national cluster sample of 1407 Portuguese individuals ≥65 y of age was analyzed. Adherence to the MDP was evaluated with the Portuguese version of the Prevention with Mediterranean Diet tool. The association between an individual's characteristics and adherence to the MDP was analyzed through hierarchical logistic regression analysis. RESULTS: In this study, 43% of participants adhered to the MDP (nâ¯=â¯609). Higher educational level (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.54-3.69), living in the center (OR, 1.35; 95% CI, 1.01-1.79), being married or living in a common-law marriage (OR, 1.54; 95% CI, 1.20-1.97), and body mass index (ORpreobese, 1.52; 95% CI, 1.02-2.25) were related with increased odds of adherence to the MDP. Otherwise, lower adherence to the MDP was found for participants who were ≥80 y of age (OR, 0.70; 95% CI, 0.52-0.94), who lived in Madeira (OR, 0.35; 95% CI, 0.14-0.89) and Azores (OR, 0.28; 95% CI, 0.08-0.99), who rated their health as moderate (OR, 0.65; 95% CI, 0.50-0.84) or as bad or very bad (OR, 0.63; 95% CI, 0.45-0.90), and those who reported six or more comorbidities (OR, 0.62; 95% CI, 0.39-0.97). CONCLUSIONS: Of the sample, 57% did not adhere to the Mediterranean diet. Potentially modifiable factors associated with lower adherence to the MDP were lower educational and health status.