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EGR1 controls divergent cellular responses of distinctive nucleus pulposus cell types
Get PDFBackground
Immediate early genes (IEGs) encode transcription factors which serve as first line response modules to altered conditions and mediate appropriate cell responses. The immediate early response gene EGR1 is involved in physiological adaptation of numerous different cell types. We have previously shown a role for EGR1 in controlling processes supporting chondrogenic differentiation. We recently established a unique set of phenotypically distinct cell lines from the human nucleus pulposus (NP). Extensive characterization showed that these NP cellular subtypes represented progenitor-like cell types and more functionally mature cells.
Methods
To further understanding of cellular heterogeneity in the NP, we analyzed the response of these cell subtypes to anabolic and catabolic factors. Here, we test the hypothesis that physiological responses of distinct NP cell types are mediated by EGR1 and reflect specification of cell function using an RNA interference-based experimental approach.
Results
We show that distinct NP cell types rapidly induce EGR1 exposure to either growth factors or inflammatory cytokines. In addition, we show that mRNA profiles induced in response to anabolic or catabolic conditions are cell type specific: the more mature NP cell type produced a strong and more specialized transcriptional response to IL-1β than the NP progenitor cells and aspects of this response were controlled by EGR1.
Conclusions
Our current findings provide important substantiation of differential functionality among NP cellular subtypes. Additionally, the data shows that early transcriptional programming initiated by EGR1 is essentially restrained by the cells’ epigenome as it was determined during development and differentiation. These studies begin to define functional distinctions among cells of the NP and will ultimately contribute to defining functional phenotypes within the adult intervertebral disc.info:eu-repo/semantics/publishedVersio
Endovascular Abdominal Aneurysm Repair in Women: What are the Differences Between the Genders?
Get PDFIntroduction:
Abdominal aortic aneurysm has a lower incidence in the female population, but a higher complication rate. It was been hypothesized that some anatomical differences of abdominal aortic aneurysm in women could be responsible for that. We proposed to analyze our data to understand the differences in the clinical and anatomical characteristics and the outcomes of patients undergoing endovascular aneurysm repair, according to gender.
Methods:
A retrospective analysis of patients undergoing endovascular aneurysm repair between 2001-2013 was performed. Patients were divided according gender and evaluated regarding age, atherosclerotic risk factors, aneurysm anatomic features, endograft type, anesthesic risk classification, length of stay, reinterventions and mortality. Two statistical studies were performed, first comparing women and men (Group A) and a second one comparing women and men, adjusted by age (Group B).
Results:
Of the 171 patients, only 5.8% (n=10) were females. Women were older (P<0.05) and the number of women with no atherosclerotic risk factor was significantly higher. The comparison adjusted by age revealed women with statistically less smoking history, less cerebrovascular disease and ischemic heart disease. Women had a trend to more complex anatomy, with more iliac intern artery aneurysms, larger aneurysm diameter and neck angulations statistically more elevated. No other variables were statistically different between age groups, neither reintervention nor mortality rates.
Conclusion:
Our study showed a clear difference in the clinical characteristics of women. The female population was statistically older, and when compared with men adjusted by age, had less atherosclerotic risk factors and less target organ disease. Women showed a more complex anatomy but with the same outcomes.info:eu-repo/semantics/publishedVersio
VASCULAR LYMPHATIC MALFORMATION WITH UNCOMMON LOCALIZATION
Get PDFIntrodução: As malformações vasculares linfáticas são entidades raras que afetam os vasos linfáticos. Os autores relatam um caso clínico de uma malformação linfática abdomino-pélvica.
Caso Clínico: 28 anos, Gesta 2, Para 1. Encaminhada à Unidade de Diagnóstico Pré-Natal, às 20 semanas, por imagem ecográfica sugestiva de malformação linfática abdomino-pélvica, confirmada por ressonância magnética fetal. Estudo citogenético fetal normal. Consulta de Cirurgia Pediátrica para informar o casal do prognóstico. Cesariana eletiva às 38 semanas. Observação do recém-nascido confirmou o diagnóstico pré-natal. A criança foi submetida, aos 18 meses, a esclerote¬rapia intralesional. Aos 4 anos, foi efetuada exérese cirúrgica da lesão por desenvolvimento de sintomas. Apresentou sempre desenvolvimento e crescimento normais.
Discussão/Conclusões: O diagnóstico pré-natal é ecográfico; a ressonância magnética fetal permite confirmar o diagnóstico e define com maior rigor a extensão das lesões. Deve manter-se vigilância clínica e ecográfica, para deteção de sinais de descompensação ou hidrópsia e de compressão das estruturas adjacentes
Implications for patients waiting for a kidney transplant of using the calculated panel reactive antibody (cPRA)
Get PDFIntroduction: Kidney transplant improves survival even in highly‑sensitized (HS) patients. To overcome their disadvantage in accessing transplantation, those with high Complement Dependent Cytotoxic PRA (CDC‑PRA) receive additional points during allocation. Whether this strategy reaches all HS patients and how long they wait for a transplant is largely undetermined.
Methods: Patients on our unit’s active wait‑list for kidney transplantation in the year 2014 were analyzed. CDC‑PRA and calculated PRA (cPRA) were recorded. To obtain cPRA, antibodies in the last serum available specific for HLA‑A, ‑B or –DR with an intensity > 1000 MFI were considered. Results: The cPRA values in the population (N=551) were 0% (N=312), 1‑79% (N=118) and ≥ 80% (22%; N=121). Among these groups, the proportion of women (29.5, 55.9 and 61.2%, P 50%. Moreover, only 30% of HS by cPRA patients received the extra points designed to improve their transplantability. We consider that both CDC‑PRA and cPRA should be taken into account when defining HS status.info:eu-repo/semantics/publishedVersio
The EMBARC European Bronchiectasis Registry: protocol for an international observational study
Get PDFBronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1) a clinical history consistent with bronchiectasis; and 2) computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1) bronchiectasis due to known cystic fibrosis; 2) age <18 years; and 3) patients who are unable or unwilling to provide informed consent. The study aims to enrol 1000 patients by April 2016 across at least 20 European countries, and 10 000 patients by March 2020. Patients will undergo a comprehensive baseline assessment and will be followed up annually for up to 5 years with the goal of providing high-quality longitudinal data on outcomes, treatment patterns and quality of life. Data from the registry will be available in the form of annual reports. and will be disseminated in conference presentations and peer-reviewed publications. The European Bronchiectasis Registry aims to make a major contribution to understanding the natural history of the disease, as well as guiding evidence-based decision making and facilitating large randomised controlled trials.info:eu-repo/semantics/publishedVersio
What about vaginal extraction of the kidney? results of an online survey
Get PDFPURPOSE:
We aimed to characterize surgeons opinion about the vaginal extraction of the kidney after transperitoneal laparoscopic nephrectomy. Matherial and Methods: A 9-item questionnaire was published online (Survey Monkey TM) and publicized via email to a multidisciplinary pool of surgeons in Portugal. Data was collected and statistical analysis was performed using IBM SPSS Statistics, Version 21.0.
RESULTS:
Three hundred and fifty nine inquiries were sent, 154 surgeons completed the questionnaires (response rate of 43.0%). Fifty five point eight percent of the participants would choose the transvaginal approach for themselves or for a close relative. The most stated arguments were a better cosmesis (29.0%) expectancy of lower post operative pain (26.0%) and lower rate of incisional hernias (23.0%). Defenders of the transabdominal procedure justified with an expectancy of lower complication rate (39%), namely impairment of sexual function and fertility (22%). The female gender and the familiarity with transvaginal surgery were the stronger predictors of the option for this approach (70.6% vs 48.5%; p=0,016 and 85.3% vs 46.6%; p <0.001 respectively).
CONCLUSIONS:
Contrasting with similar surveys published on transvaginal NOTES, the vaginal specimen extraction after conventional laparoscopic nephrectomy was fairly accepted by the inquired surgeons.info:eu-repo/semantics/publishedVersio
Foramen of Winslow hernia: case report of a minimally invasive approach
Get PDFForamen of Winslow hernias account for 8% of all internal hernias. Their non-specific presentation and often late diagnosis are associated with an estimated mortality of 50%. The use of complementary diagnostic methods facilitates the diagnosis and planning of the therapeutic strategy. Urgent surgery is the appropriate treatment due to the risk of intestinal ischemia, being laparotomy the main form of approach described. Few cases of laparoscopy are referred to in the literature.info:eu-repo/semantics/publishedVersio
Advanced Glycation End Products Evolution after Pancreas-Kidney Transplantation: Plasmatic and Cutaneous Assessments
Get PDFDiabetes mellitus leads to increased Advanced Glycation End Products (AGE) production, which has been associated with secondary diabetic complications. Type 1 diabetic patients undergoing pancreas-kidney transplantation (SPKT) can restore normoglycemia and renal function, eventually decreasing AGE accumulation. We aimed to prospectively study AGE evolution after SPKT. Circulating AGE were assessed in 20 patients, at time 0 (T0), 3 months (T3), 6 months (T6), and 12 months (T12) after successful SPKT. Global AGE and carboxymethyllysine (CML) were analyzed, as well as advanced oxidation protein products (AOPP). Skin biopsies were obtained at T0 and T12. Immunohistochemistry with anti-AGE antibody evaluated skin AGE deposition. AGE mean values were 16.8 ± 6.4 μg/mL at T0; 17.1 ± 3.8 μg/mL at T3; 17.5 ± 5.6 μg/mL at T6; and 16.0 ± 5.2 μg/mL at T12. CML mean values were 0.94 ± 0.36 ng/mL at T0; 1.11 ± 0.48 ng/mL at T3; 0.99 ± 0.42 ng/mL at T6; and 0.78 ± 0.38 ng/mL at T12. AOPP mean values were 130.1 ± 76.8 μMol/L at T0; 137.3 ± 110.6 μMol/L at T3; 116.4 ± 51.2 μMol/L at T6; and 106.4 ± 57.9 μMol/L at T12. CML variation was significant (P = 0.022); AOPP variation was nearly significant (P = 0.076). Skin biopsies evolved mostly from a cytoplasmic diffuse to a peripheral interkeratinocytic immunoreaction pattern; in 7 cases, a reduction in AGE immunoreaction intensity was evident at T12. In conclusion, glycoxidation markers decrease, plasmatic and on tissues, may start early after SPKT. Studies with prolonged follow-up may confirm these data.info:eu-repo/semantics/publishedVersio
Deciphering the Contribution of Biofilm to the Pathogenesis of Peritoneal Dialysis Infections: Characterization and Microbial Behaviour on Dialysis Fluids
Get PDFInfections are major complications in peritoneal dialysis (PD) with a multifactorial etiology that comprises patient, microbial and dialytic factors. This study aimed at investigating the contribution of microbial biofilms on PD catheters to recalcitrant infections and their interplay with PD related-factors. A prospective observational study was performed on 47 patients attending Centro Hospitalar of Porto and Vila Nova de Gaia/Espinho to whom the catheter was removed due to infectious (n = 16) and non-infectious causes (n = 31). Microbial density on the catheter was assessed by culture methods and the isolated microorganisms identified by matrix-assisted laser desorption/ionization time-of-flight intact cell mass spectrometry. The effect of conventional and three biocompatible PD solutions on 16 Coagulase Negative Staphylococci (CNS) and 10 Pseudomonas aeruginosa strains planktonic growth and biofilm formation was evaluated. Cultures were positive in 87.5% of the catheters removed due infectious and 90.3% removed due to non-infectious causes. However, microbial yields were higher on the cuffs of catheters removed due to infection vs. non-infection. Staphylococci (CNS and Staphylococcus aureus) and P. aeruginosa were the predominant species: 32% and 20% in the infection and 43.3% and 22.7% in the non-infection group, respectively. In general, PD solutions had a detrimental effect on planktonic CNS and P. aeruginosa strains growth. All strains formed biofilms in the presence of PD solutions. The solutions had a more detrimental effect on P. aeruginosa than CNS strains. No major differences were observed between conventional and biocompatible solutions, although in icodextrin solution biofilm biomass was lower than in bicarbonate/lactate solution. Overall, we show that microbial biofilm is universal in PD catheters with the subclinical menace of Staphylococci and P. aeruginosa. Cuffs colonization may significantly contribute to infection. PD solutions differentially impact microbial species. This knowledge is important for the development of infection diagnosis, treatment and preventive strategies.his work received support from a Sociedade Portuguesa de Nefrologia (http://www.spnefro.pt) research grant to AR and a Fundação para a Ciência e Tecnologia (http://www.fct.pt) post doc grant (SFRH/BPD/73663/2010) to MM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio
PARTO DIFERIDO DE UM GÉMEO CAUSADOR DE CHOQUE SÉTICO NA MÃE
Get PDFDelayed interval delivery is an option in the extremely preterm twin pregnancies, in an attempt to decrease morbidity for the remaining fetuses. We report a case of diamniotic dichorionic pregnancy complicated by premature rupture of membranes of the first fetus at 20 weeks gestation. Premature delivery of the first twin occured nine days latter. Delayed interval delivery of the second twin was attempted using bed rest, tocolysis and antibiotics. Unfortunately, 14 days later spontaneous labour ensued and the birth took place with the mother presenting signs of chorioamnionitis. Septic shock occurred in the mother, with need of mechanical ventilation and aminergic support. It seems to us that it is important to present unsuccessful cases like this in order to discuss what are the optimal management options, while there is no universal agreement on this issue.O parto diferido de um gémeo é uma opção nas gestações complicadas por prematuridade extrema, como forma de tentar diminuir a morbilidade dos fetos restantes. O caso aqui apresentado é de uma gravidez bicoriónica biamniótica complicada por rotura prematura de membranas do primeiro feto às 20 semanas de gestação. O parto do primeiro gémeo ocorreu nove dias depois. O parto diferido do segundo gémeo foi tentado, recorrendo a repouso, tocólise e antibióticos. Contudo, 14 dias depois, ocorreu o parto espontâneo do segundo gémeo, com a mãe a apresentar sinais e sintomas de corioamnionite. A mãe acabou por desenvolver um choque séptico, com necessidade de ventilação mecânica e suporte aminérgico. A apresentação de casos de insucesso como este parece-nos importante, porque permite discutir as opções terapêuticas, enquanto não existir um con- senso universal sobre este assunto.info:eu-repo/semantics/publishedVersio