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Context: Propofol is a general anesthetic used in multiple clinical scenarios. Despite growing evidence supporting its use in palliative care, propofol is rarely used in palliative sedation. Reluctance toward the adoption of propofol as a sedative agent is often associated with fear of adverse events such as respiratory arrest. Objectives: We aimed to describe efficacy and safety of palliative sedation in refractory sedation with propofol using a protocol based on low, incremental dosing. Methods: A retrospective observational study featuring inpatients receiving sedative treatment with propofol in our palliative care unit in Madrid (Spain) between March 1, 2018 and February 28, 2023, following a newly developed protocol. Results: During the study period, 22 patients underwent sedation with propofol. Propofol was used successfully to control different refractory symptoms, mainly psychoexistential suffering and delirium. All patients had undergone previous failed attempts at sedation with other medications (midazolam or lemovepromazine) and presented risk factors for complicated sedation. All patients achieved satisfactory (profound) levels of sedation measured with the Ramsay Sedation Scale, but total doses varied greatly between patients. Most patients (17, 77%) received combined therapy with propofol and other sedative medications to harness synergies. The median time between start of sedation with propofol and death was 26.0 hours. No cases of apnea or death during induction were recorded. Conclusion: A protocol for palliative sedation with propofol based on low, incremental dosing, with the option of administering an initial induction bolus, shows excellent results regarding adequate levels of sedation, without observing apnea or respiratory depression. Our results promote the use of propofol to achieve palliative sedation in patients with refractory symptoms and risk factors for complicated sedation at the end of life.
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Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These factors collectively interact in complex ways, influencing disease behavior, especially among highly admixed populations like Colombians. In this study, we assessed contributing factors to breast cancer health disparities according to genetic ancestry in Colombian patients from a national cancer reference center. We collected non-tumoral paraffin embedded (FFPE) blocks from 361 women diagnosed with breast cancer at the National Cancer Institute (NCI) to estimate genetic ancestry using a 106-ancestry informative marker (AIM) panel. Differences in European, Indigenous American (IA) and African ancestry fractions were analyzed according to potential sources of breast cancer health disparities, like etiology, tumor-biology, treatment administration, and socioeconomic-related factors using a Kruskal-Wallis test. Our analysis revealed a significantly higher IA ancestry among overweight patients with larger tumors and those covered by a subsidized health insurance. Conversely, we found a significantly higher European ancestry among patients with smaller tumors, residing in middle-income households, and affiliated to the contributory health regime, whereas a higher median of African ancestry was observed among patients with either a clinical, pathological, or stable response to neoadjuvant treatment. Altogether, our results suggest that the genetic legacy among Colombian patients, measured as genetic ancestry fractions, may be reflected in many of the clinical-pathological variables and socioeconomic factors that end up contributing to health disparities for this disease.
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Neoplasias da Mama , Humanos , Feminino , Colômbia/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/etnologia , Pessoa de Meia-Idade , Adulto , Disparidades nos Níveis de Saúde , População Branca/genética , Idoso , Fatores SocioeconômicosRESUMO
Objectives: To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP). Materials and methods: Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT. Results: 344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm. Conclusion: ED after RP is a known long-term side effect with significant impact on patients' QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.ClinicalTrials.gov. Identifier: NCT01272050.
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BACKGROUND: Biomarkers play a role in identifying, managing, and predicting cancer outcomes. In lung cancer, they are used at various time points. Doubts remain regarding their accuracy for differential diagnosis and histological subtyping. A diagnostic test study was conducted. It included malignant lesions and controls with benign lesions. Before lung biopsy, all patients had the following biomarkers measured in serum (Pro-GRP,NSE,CYFRA21-1,SCC-Ag,CEA). METHODS: The predictive capacity of serum biomarkers was evaluated to discriminate between lung cancer and benign pathology. The accuracy was also assessed for distinguishing between SCLC and NSCLC and explored their ability to perform histological subtyping. RESULTS: 93 patients were included, 60 with lung cancer, 33 with benign pathology. Pro-GRP and NSE were elevated in SCLC compared with NSCLC or nonmalignant disease. The most accurate for differentiating between malignant and benign pathology were CEA and CYFRA21-1. Pro-GRP had a poor predictive capacity for distinguishing NSCLC from SCLC. However, combined with CEA and CYFRA21-1, performance improved. For SCLC, the diagnostic capacity of Pro-GRP increased by combining with biomarkers, such as NSE/CYFRA21-1. CONCLUSIONS: Biomarkers lacked the sensitivity and specificity for independent differential diagnosis or histological subtyping. However, the observed patterns in biomarker levels associated with specific histological subtypes suggest potential utility in a multi-biomarker approach or in conjunction with other diagnostic tools. This insight could guide future research to improve diagnostic accuracy and personalized treatment strategies in lung cancer.
Biomarkers are crucial for identifying, managing, and predicting outcomes in lung cancer, though they lack accuracy in differentiating histological subtypes.CEA and CYFRA21-1 were the most accurate biomarkers for distinguishing between malignant and benign pathology.Pro-GRP and NSE levels were elevated in SCLC compared to NSCLC. Pro-GRP alone had poor predictive capacity for differentiating NSCLC from SCLC, but combining it with CEA and CYFRA21-1 improved diagnostic performance.Patterns in biomarker levels suggest that a multi-biomarker approach, especially when combined with other diagnostic tools, could improve diagnostic accuracy.
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Antígenos de Neoplasias , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Queratina-19 , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Diagnóstico Diferencial , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antígenos de Neoplasias/sangue , Queratina-19/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Antígeno Carcinoembrionário/sangue , Serpinas/sangue , Fosfopiruvato Hidratase/sangue , Sensibilidade e Especificidade , AdultoRESUMO
Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.
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Introducción: Los dientes anteriores tienen una función predominante en el sistema estomatognático, esencial para la estética, la fonación y la masticación. Objetivo: Caracterizar a los adultos con guía anterior de la oclusión dentaria disfuncional según variables clínicas y epidemiológicas. Métodos: Se realizó un estudio descriptivo y transversal, desde octubre de 2021 hasta abril de 2022, en la Clínica Estomatológica Docente 3 de Octubre de Las Tunas. El universo estuvo conformado por 825 historias clínicas que contenían el diagnóstico de pacientes con bruxismo, oclusión traumática y trastornos temporomandibulares, quienes presentaban disfunción de la guía anterior de la oclusión dentaria. Mediante el muestreo no probabilístico intencional, fue seleccionada una muestra de 615 con fórmula dentaria íntegra o desdentamiento parcial de clase III de Kennedy y atención estomatológica concluida o inactivación de los procesos de caries e inflamatorios agudos. Resultados: Primaron el sexo femenino (54,8 %) y las edades de 40-49 años (33,5 %). El bruxismo prevaleció como diagnóstico clínico (41,9 %) con predominio del correspondiente al sueño (39,1 %), el secundario (51,2 %), el probable (59,7 %) y el moderado (69,4 %); entre sus clasificaciones más relevantes se destacó el sistema estomatognático disfuncional (84,4 %). Las manifestaciones clínicas dentarias predominantes fueron las facetas de desgaste (87,5 %). Conclusiones: La caracterización de los pacientes con guía anterior de la oclusión dentaria disfuncional permite establecer una panorámica actualizada de esta problemática de salud para un mejor seguimiento y tratamiento a dichos pacientes.
Introduction: Anterior teeth have a predominant function in the stomatognatic system, essential for the aesthetics, phonation and mastication. Objective: To characterize adults with anterior guide of dysfunctional dental occlusion according to clinical and epidemiological variables. Methods: A descriptive and cross-sectional study, was carried out from October, 2021 to April, 2022, in the 3 de Octubre Teaching Stomatological Clinic from Las Tunas. The universe was formed by 825 medical records that contained the diagnosis of patients with bruxism, traumatic occlusion and temporomandibular disorders who presented anterior guide of the dysfunctional dental occlusion. By means of the intentional non probabilistic sampling, a sample of 615 with entire dental formula or class III partial toothlessness of Kennedy and concluded stomatologic care or inactivation of the cavity and acute inflammatory processes was selected. Results: There was a prevalence of the female sex (54.8%) and the 40-49 age group (33.5%). Bruxism prevailed as clinical diagnosis (41.9%) with prevalence of the corresponding to sleep (39.1%), secondary (51.2%), probable (59.7%) and moderate (69.4%); among the most outstanding classifications was the dysfunctional stomatognatic system (84.4%). The predominant dental clinical manifestations were the wear facets (87.5%). Conclusions: The characterization of patients with anterior guide of the dysfunctional dental occlusion allows to establish an up-to-date panoramic of this health problem, for a better follow-up and treatment to these patients.
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The accumulation of farnesylated prelamin A has been suggested as one of the mechanisms responsible for the loss of fat in type 2 familial partial lipodystrophy due to variants in the LMNA gene. In this rare disease, fat loss appears in women after puberty, affecting sex-hormone-dependent anatomical areas. This study investigated the impact of 17-ß-estradiol on adipogenesis in murine preadipocytes subjected to a pharmacologically induced accumulation of farnesylated and non-farnesylated prelamin A. To induce the accumulation of non-farnesylated or farnesylated prelamin A, 3T3-L1 cells were treated with the farnesyltransferase inhibitor 277 or the methyltransferase inhibitor N-acetyl-S-farnesyl-l-cysteine methylester. Subsequently, the cells were induced to undergo adipocyte differentiation in the presence or absence of 17-ß-estradiol. Prelamin A accumulation was assessed through immunofluorescence, while real-time PCR and Western blot techniques were used to quantify several adipogenic genes and evaluate protein levels, respectively. The results showed that 17-ß-estradiol increased adipogenesis, although the combination of this hormone plus farnesylated prelamin A led to a reduction in the number of mature adipocytes and the expression of the different genes involved in adipogenesis. In conclusion, the influence of farnesylated prelamin A accumulation on adipogenesis manifested only in the presence of estradiol. These in vitro findings suggest a potential mechanism that could explain the characteristic phenotype in women suffering type 2 familial partial lipodystrophy.
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Lamina Tipo A , Lipodistrofia Parcial Familiar , Humanos , Feminino , Camundongos , Animais , Lipodistrofia Parcial Familiar/genética , Lipodistrofia Parcial Familiar/metabolismo , Adipogenia , Células 3T3-L1 , Proteínas Nucleares/genética , Estradiol/farmacologiaRESUMO
PURPOSE: To determine predictive factors associated with a good response (GR) to and efficacy of low-dose radiotherapy (LDRT) in patients with greater trochanteric pain syndrome (GTPS). METHODS: Patients with GTPS were irradiated on a linear accelerator with 0.5-1.0â¯Gy per fraction to a total dose of 3.0-4.0â¯Gy per series. The endpoint was subjective good response (GR) to treatment 2 months after completion of the last LDRT series, defined as complete pain relief or marked improvement assessed using the von Pannewitz score. A positive response to steroid injection (SI) was defined as pain relief of at least 7 days. Patient and treatment-related characteristics were evaluated with respect to LDRT outcomes. RESULTS: Outcomes were assessed for 71 peritrochanteric spaces (PTSs; 65 patients, 48 females, with mean age of 63 [44-91] years). Prior SI had been given to 55 (77%) PTSs and 40 PTSs received two series of LDRT. Two months after completion of LDRT, GR was reported in 42 PTSs (59%). Two series of LDRT provided a significantly higher rate of GR than one series (72.5 vs. 42% PTSs, pâ¯= 0.015). Temporary pain relief after prior SI predicted GR to LDRT compared with PTSs which had not responded to SI (73 vs. 28% PTSs, pâ¯= 0.001). A regional structural abnormality, present in 34 PTSs (48%), was associated with a reduction of GR to LDRT (44 vs. 73% PTSs, pâ¯= 0.017). CONCLUSION: LDRT is an effective treatment for GTPS. Administration of two LDRT series, prior response to SI, and absence of structural abnormalities may predict significantly better treatment outcomes.
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Bursite , Feminino , Humanos , Pessoa de Meia-Idade , Bursite/complicações , Bursite/terapia , Resultado do Tratamento , Dor/etiologia , Dor/radioterapiaRESUMO
Introducción: El sueño garantiza el bienestar físico y mental del individuo mediante retroalimentación directa. Los trastornos del sueño implican alteraciones respecto a calidad y cantidad de horas de sueño y obedecen a una alteración real de su función fisiológica que controla y opera durante el mismo. La Medicina del Sueño es una especialidad nueva, surgida en los últimos 50 años, cuyo campo de acción aborda la prevención, diagnóstico y tratamiento de los trastornos del sueño; los cuales hasta el momento se han identificado alrededor del centenar. Esta enfermedad se ha convertido en problema social crucial y creciente, difícil de abordar en la práctica médica contemporánea; debido a la complejidad en la toma de decisiones respecto a su diagnóstico y tratamiento. Esta temática requiere ser evaluada desde un enfoque interdisciplinario para reducir la morbimortalidad asociada a manifestaciones neurológicas, psicológicas, psiquiátricas, cardiovasculares y endocrinometabólicas. Objetivo: Establecer la propuesta de Consulta Interdisciplinaria de Medicina del Sueño en la provincia Camagüey. Métodos: Se efectuó una investigación cualitativa de tipo descriptivo para la selección de aspectos pertinentes a una consulta especializada proveedora de pacientes pediátricos con trastornos del sueño, en el período comprendido entre julio y diciembre de 2022, en el Centro de Inmunología y Productos Biológicos de la Universidad de Ciencias Médicas de Camagüey. El universo del grupo de trabajo estuvo integrado por ocho profesionales de las Ciencias Médicas. Se utilizaron métodos teóricos como la revisión documental, histórico-lógico, análisis y síntesis, inducción-deducción, métodos matemáticos-estadísticos y métodos computacionales. Resultados: Se conformó un algoritmo de trabajo para la atención médica, que desarrolló el ordenamiento de los elementos sustantivos propios de la analítica polisomnográfica en el contexto cubano. Logró unificar criterios y opiniones generales de manera consensuada por equipos interdisciplinarios. Conclusiones: Resulta definido el documento científico rector de la Consulta Interdisciplinaria de Medicina del Sueño en Camagüey.
Introduction: Sleep guarantees the physical and mental well-being of the individual through direct feedback. Sleep disorders involve alterations in the quality and quantity of hours of sleep and are due to a real alteration in the physiological function that controls and operates during sleep. Sleep Medicine is a new specialty, emerged in the last 50 years, whose field of action addresses the prevention, diagnosis and treatment of sleep disorders; of which around a hundred have been identified so far. This kind of disorders has become a crucial and growing social problem, difficult to address in contemporary medical practice; due to the complexity in decision-making regarding diagnosis and treatment. This topic requires being evaluated from an interdisciplinary approach to reduce morbidity and mortality associated with neurological, psychological, psychiatric, cardiovascular and endocrine-metabolic manifestations. Objective: To establish the proposal of Interdisciplinary Consultation of Sleep Medicine in the province Camagüey. Methods: A qualitative descriptive research was carried out to select aspects relevant to a specialized consultation providing pediatric patients with sleep disorders, in the period between July and December 2022, at the Center for Immunology and Biological Products of the University of Medical Sciences of Camagüey. The universe of the working group was made up of eight professionals from the Medical Sciences. Theoretical methods such as documentary review, historical-logical, analysis and synthesis, induction-deduction, mathematical-statistical methods and computational methods were used. Results: A work algorithm for medical care was formed, which developed the ordering of the substantive elements of polysomnographic analysis in the Cuban context. It manages to unify general criteria and opinions in a consensus by interdisciplinary teams. Conclusions: The governing scientific document of the Interdisciplinary Consultation of Sleep Medicine in Camagüey is defined.
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Triple negative breast cancer (TNBC) is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better prognosis and higher probability to achieve pathological complete response. Here, we explore the potential role of stromal TILs level and composition as a prognostic and predictive biomarker in TNBC. 195 Tumor biospecimens from patients diagnosed with TNBC were included. Stromal TILs (sTILs), positive CD4/CD8 cells were evaluated. Differences in clinic-pathological characteristics according to immune infiltration were assessed. The predictive and prognostic value of immune infiltration was analyzed by multivariate models. Higher immune infiltration was observed in patients with favorable clinical-pathological features. Survival analysis showed that longer overall survival times were observed in patients with a higher infiltration of sTILs (p = 0.00043), CD4 + (p = 0.0074) and CD8 + (p = 0.008). In the multivariate analysis, low levels of sTILs were found to be associated with a higher mortality hazard (HR: 1.59, 95% CI 1.01-2.48). CD4 and CD8 immune infiltration were associated with higher odds for pathological complete response (OR: 1.20, 95% CI 1.00-1.46, OR: 1.28, 1.02-1.65, respectively). Our results suggest that immune infiltration could be used as a prognostic marker for overall survival in TNBC patients.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Linfócitos do Interstício Tumoral , Colômbia , Prognóstico , Biomarcadores , Biomarcadores Tumorais/análiseRESUMO
Acquired generalised lipodystrophy (AGL) is a rare disorder characterised by the gradual loss of fat that tends to generalise over time, the origin of which is still not fully clarified. The aim of this study was to offer a detailed description of seven patients with AGL (five women, 33.8 ± 18.6 years of age), evaluated over the last 14 years, in order to augment the knowledge of this disorder. The onset of the phenotype occurred during childhood and adolescence in five cases, and in adulthood in two cases. Three patients reported infections or vaccine administration prior to the development of lipodystrophy, and two subjects reported nodular swelling. The most frequent physical features were phlebomegaly, umbilical protrusion/hernia, and acanthosis nigricans. Skinfolds and body composition analysis showed the generalised absence of fat, with the exception of one patient in whom fat loss was spared in the trunk. The loss of fat in the palms/soles was observed in five subjects. Regarding metabolic comorbidities, throughout follow-up, two patients developed type 1 diabetes and one type 2 diabetes; three also presented hypertriglyceridaemia, one of whom developed acute pancreatitis, and no macrovascular complications were observed. Only one patient showed decreased complement C4. Autoimmunity was present in all cases, and six patients manifested Hashimoto's thyroiditis, type 1 diabetes, autoimmune hepatitis, and/or celiac disease. Thus, there are certain clinical characteristics of AGL that may be considered important diagnostic criteria to differentiate this disorder from other lipodystrophy subtypes.
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The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.
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Lipodistrofia Generalizada Congênita , Lipodistrofia , Adolescente , Humanos , Adulto , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/epidemiologia , Espanha/epidemiologia , Estudos Prospectivos , Lipodistrofia/diagnóstico , Lipodistrofia/epidemiologia , Lipodistrofia/genética , SíndromeRESUMO
The Boston keratoprosthesis (BKPro) is a medical device used to restore vision in complicated cases of corneal blindness. This device is composed by a front plate of polymethylmethacrylate (PMMA) and a backplate usually made of titanium (Ti). Ti is an excellent biomaterial with numerous applications, although there are not many studies that address its interaction with ocular cells. In this regard, despite the good retention rates of the BKPro, two main complications compromise patients' vision and the viability of the prosthesis: imperfect adhesion of the corneal tissue to the upside of the backplate and infections. Thus, in this work, two topographies (smooth and rough) were generated on Ti samples and tested with or without functionalization with a dual peptide platform. This molecule consists of a branched structure that links two peptide moieties to address the main complications associated with BKPro: the well-known RGD peptide in its cyclic version (cRGD) as cell pro-adherent motif and the first 11 residues of lactoferrin (LF1-11) as antibacterial motif. Samples were physicochemically characterized, and their biological response was evaluated in vitro with human corneal keratocytes (HCKs) and against the gram-negative bacterial strain Pseudomonas aeruginosa. The physicochemical characterization allowed to verify the functionalization in a qualitative and quantitative manner. A higher amount of peptide was anchored to the rough surfaces. The studies performed using HCKs showed increased long-term proliferation on the functionalized samples. Gene expression was affected by topography and peptide functionalization. Roughness promoted α-smooth muscle actin (α-SMA) overexpression, and the coating notably increased the expression of extracellular matrix components (ECM). Such changes may favour the development of unwanted fibrosis, and thus, corneal haze. In contrast, the combination of the coating with a rough topography decreased the expression of α-SMA and ECM components, which would be desirable for the long-term success of the prosthesis. Regarding the antibacterial activity, the functionalized smooth and rough surfaces promoted the death of bacteria, as well as a perturbation in their wall definition and cellular morphology. Bacterial killing values were 58 % for smooth functionalised and 68 % for rough functionalised samples. In summary, this study suggests that the use of the dual peptide platform with cRGD and LF1-11 could be a good strategy to improve the in vitro and in vivo performance of the rough topography used in the commercial BKPro.
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Córnea , Doenças da Córnea , Humanos , Córnea/cirurgia , Titânio/farmacologia , Doenças da Córnea/cirurgia , Próteses e Implantes , Peptídeos , AntibacterianosRESUMO
Celia's encephalopathy or progressive encephalopathy with/without lipodystrophy is a neurodegenerative disease with a fatal prognosis in childhood. It is generally caused by the c.985C > T variant in the BSCL2 gene, leading to the skipping of exon 7 and resulting in an aberrant seipin protein (Celia-seipin). To precisely define the temporal evolution and the mechanisms involved in neurodegeneration, lipodystrophy and fatty liver in Celia's encephalopathy, our group has generated the first global knock-in murine model for the aberrant human transcript of BSCL2 (Bscl2Celia/Celia) using a strategy based on the Cre/loxP recombination system. In order to carry out a characterization at the neurological, adipose tissue and hepatic level, behavioral studies, brain PET, metabolic, histological and molecular studies were performed. Around 12% of homozygous and 5.4% of heterozygous knock-in mice showed severe neurological symptoms early in life, and their life expectancy was dramatically reduced. Severe generalized lipodystrophy and mild hepatic steatosis were present in these affected animals, while serum triglycerides and glucose metabolism were normal, with no insulin resistance. Furthermore, the study revealed a reduction in brain glucose uptake, along with patchy loss of Purkinje cells and the presence of intranuclear inclusions in cerebellar cortex cells. Homozygous, non-severely-affected knock-in mice showed a decrease in locomotor activity and greater anxiety compared with their wild type littermates. Bscl2Celia/Celia is the first murine model of Celia's encephalopathy which partially recapitulates the phenotype and severe neurodegenerative picture suffered by these patients. This model will provide a helpful tool to investigate both the progressive encephalopathy with/without lipodystrophy and congenital generalized lipodystrophy.
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Background and aims: The dietary pattern followed during pregnancy, specifically healthy dietary patterns such as the Mediterranean diet, is a key factor in the mother's and the offspring's health. Pregnant women dietary intake is not enough to cover the micronutrient requirements of pregnancy, and higher adherence to the Mediterranean diet may improve dietary quality and nutritional density. The aim of the present study was to describe the dietary nutrient intake and diet quality during pregnancy and to evaluate whether a high adherence to Mediterranean diet was associated with a more adequate intake of micronutrients. Methods: This was a cross-sectional study with 1,356 pregnant women selected during the routine second trimester ultrasound scan (19-23 weeks' gestation). Energy and nutrient intake were calculated using a validated 151-item semi-quantitative food frequency questionnaire and nutrient density was estimated dividing the absolute nutrient intake by total energy intake. Adherence to the Mediterranean diet was evaluated with a 17-item Mediterranean diet adherence score. The criterion used for risk of inadequate nutrient intake has been set below two thirds (2/3) of the dietary reference intakes. The differences were assessed by multivariate linear regression models adjusted for confounders. Results: A significant proportion of pregnant women had an inadequate intake of macro and micronutrient that was lower in those with high adherence to the Mediterranean diet (≥12 points, n = 122, 19%), including calcium (the Mediterranean diet high adherence 2.5% vs. low adherence 26.7%, p < 0.001), magnesium (0% vs. 7.6%, p = 0.001), iron (24.5% vs. 74.1%, p < 0.001), and vitamin B9 (0% vs. 29.8%, p < 0.001), vitamin C (0% vs. 1.9%, p = 0.033), and vitamin D (61.5% vs. 92.8%, p < 0.001) intake. High adherence to Mediterranean diet was associated with higher intake of protein, monounsaturated fatty acids, fiber, vitamins (B1, B9, C, D), calcium, magnesium, iron, zinc, phosphor, potassium, essential fatty acids, and α-linolenic acid, and with a lower intake of α-linoleic acid and trans fatty acids as compared to low adherence to Mediterranean diet. Conclusion: High adherence to Mediterranean diet was associated with higher diet quality and lower proportion of inadequate micro and macronutrient intake. The Mediterranean diet promotion, particularly among pregnant women, may be a useful and public health strategy to avoid overweight and nutrient deficiencies.
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Dieta Mediterrânea , Gravidez , Feminino , Humanos , Cálcio , Estudos Transversais , Magnésio , Gestantes , Nutrientes , Vitaminas , MicronutrientesRESUMO
Acute suppurative thyroiditis are infrequent infections, although their early and proper management are needed to reduce complications and recurrences. We review the clinical presentation, etiology, clinical outcome and management of 9 cases of thyroid infections diagnosed in children, and analyze the existence of predisposing factors for these infections.
Assuntos
Tireoidite Supurativa , Humanos , Criança , Tireoidite Supurativa/diagnóstico , Tireoidite Supurativa/terapia , Tireoidite Supurativa/complicações , Diagnóstico Diferencial , Tomada de Decisão Clínica , Doença AgudaRESUMO
PURPOSE: The determination of the programmed death ligand-1 (PD-L1) expression is part of the diagnostic algorithm for advanced non-small cell lung cancer (NSCLC) patients. We aimed to analyze the diagnostic performance of EBUS-TBNA performed as first-choice nodal staging procedure for the determination of PD-L1 expression in NSCLC patients. METHODS: Longitudinal-prospective study including NSCLC patients diagnosed between January 2018 and October 2019, for whom a primary tumor biopsy sample and an EBUS-TBNA cytological malignant sample were available. Samples with fewer than 100 malignant cells were considered inadequate. PDL-1 IHC 22C3 pharmDx antibody was used. The percentage of tumor cells expressing PD-L1, setting 1% and 50% as cutoff points, was collected. The weighted kappa coefficient was used to assess the concordance of PD-L1 expression. The PD-L1 expression was compared in precision terms. RESULTS: From a total of 43 patients, 53 pairs of samples were obtained, of which 23 (43.4%) were adequate and included for analysis. The weighted kappa coefficient for PD-L1 expression was 0.41 (95% CI 0.15-0.68) and 0.56 (95% CI 0.23-0.9) for cutoff values ≥ 1% and ≥ 50%, respectively. In advanced stages, the weighted kappa coefficient was 0.6 (95% CI 0.3-0.9) and 1 (95% CI 1-1) for PD-L1 expression cutoff values ≥ 1% and ≥ 50%, respectively. EBUS-TBNA showed a sensitivity, specificity, positive predictive value, and negative predictive value of 1 to detect PDL-1 expression ≥ 50% in advanced stages. CONCLUSION: EBUS-TBNA performed as first nodal staging procedure in advanced NSCLC patients provides reliable specimens for the detection of PD-L1 expression ≥ 50% and could guide immunotherapy.