Xenotransplantation of Mitochondrial Electron Transfer Enzyme, Ndi1, in Myocardial Reperfusion Injury

A significant consequence of ischemia/reperfusion (I/R) is mitochondrial respiratory dysfunction, leading to energetic deficits and cellular toxicity from reactive oxygen species (ROS). Mammalian complex I, a NADH-quinone oxidoreductase enzyme, is a multiple subunit enzyme that oxidizes NADH and pumps protons across the inner membrane. Damage to complex I leads to superoxide production which further damages complex I as well as other proteins, lipids and mtDNA. The yeast, S. cerevisiae, expresses internal rotenone insensitive NADH-quinone oxidoreductase (Ndi1); a single 56kDa polypeptide which, like the multi-subunit mammalian complex I, serves as the entry site of electrons to the respiratory chain, but without proton pumping. Heterologous expression of Ndi1 in mammalian cells results in protein localization to the inner mitochondrial membrane which can function in parallel with endogenous complex I to oxidize NADH and pass electrons to ubiquinone. Expression of Ndi1 in HL-1 cardiomyocytes and in neonatal rat ventricular myocytes protected the cells from simulated ischemia/reperfusion (sI/R), accompanied by lower ROS production, and preservation of ATP levels and NAD+/NADH ratios. We next generated a fusion protein of Ndi1 and the 11aa protein transduction domain from HIV TAT. TAT-Ndi1 entered cardiomyocytes and localized to mitochondrial membranes. Furthermore, TAT-Ndi1 introduced into Langendorff-perfused rat hearts also localized to mitochondria. Perfusion of TAT-Ndi1 before 30 min no-flow ischemia and up to 2 hr reperfusion suppressed ROS production and preserved ATP stores. Importantly, TAT-Ndi1 infused before ischemia reduced infarct size by 62%; TAT-Ndi1 infused at the onset of reperfusion was equally cardioprotective. These results indicate that restoring NADH oxidation and electron flow at reperfusion can profoundly ameliorate reperfusion injury

Tetra-amelia and lung hypo/aplasia syndrome: New case report and review

Tetra-amelia is a rare malformation that may be associated with other anomalies and is usually inherited in an autosomal recessive pattern. We describe a fetus, born to a nonconsanguineous couple, with tetra-amelia, bilateral cleft lip and palate and bilateral lung agenesis, without other anomalies. Karyotype was normal (46,XX) and premature centromere separation was excluded. No mutation was identified upon molecular analysis of WNT3, HS6ST1, and HS6ST3. We reviewed the literature and the differential diagnosis to clarify the clinical delineation of conditions associated with tetra-amelia. The present report describes the sixth family with this pattern of malformations and reinforces the evidence that the ldquotetra-amelia and lung hypo/aplasia syndromerdquo is a distinct autosomal recessive condition, with no identified gene thus far. © 2008 Wiley-Liss, Inc

Does the white coat influence satisfaction, trust and empathy in the doctor-patient relationship in the General and Family Medicine consultation? Interventional study

Objectives To understand the influence of the white coat on patient satisfaction, opinions about medical clothing, perception about confidence, empathy and medical knowledge and the satisfaction and comfort level of physicians in consultation. Setting An interventional study was conducted with a representative sample of the population attending primary care in central Portugal. Participants The sample was composed by 286 patients divided into two groups exposed or not to a doctor wearing a white coat. The first and last patients in consultation every day for 10 consecutive days were included. Interventions Every other day the volunteer physicians consulted with or without the use of a white coat. At the end of the consultation, a questionnaire was distributed to the patient with simple questions with a Likert scale response, the Portuguese version of the ‘Trust in physician’ scale and the Jefferson Scale of Patient Perceptions of Physician Empathy - Portuguese Version (JSPPPE-VP scale). A questionnaire was also distributed to the physician. Outcomes Planned and measured primary outcomes were patient satisfaction, trust and perception about empathy and secondary outcomes were opinion about medical clothing, satisfaction and comfort level of physicians in consultation. Results The sample was homogeneous in terms of sociodemographic variables. There were no statistically significant differences between the groups in terms of satisfaction, trust, empathy and knowledge perceived by the patients. There were differences in the opinion of the patients about the white coat, and when the physician was wearing the white coat this group of patients tended to think that this was the only acceptable attire for the physician (p<0.001). But when the family physician was in consultation without the white coat, this group of patients tended to agree that communication was easier (p=0.001). Conclusions There was no significant impact of the white coat in patient satisfaction, empathy and confidence in the family physician. Trial registration number ClinicalTrials. gov ID number: NCT0396541

Investigating the role of symptom valorisation in tuberculosis patient delay in urban areas in Portugal

URBANTB group: Patrícia Soares (Representative of the consortium), Mário Carreira, Sofia Pereira, Catarina Alves, Filipe Alves, Ana Rodrigues, Ana Moreira, Márcia Cardoso, Sandra Mota, Ana Gomes, Liliana Ferreira, Marta Lopes, Isabel Correia, Juan Rachadell, Maria Gameiro, Ângela Dias, Manuel Pereira, Jorge Gonçalves, Maria Gonçalves, Adriana Taveira, Celene Neves, Lucinda Silva, Maria Mendes, Maria Teixeira, Maria Pereira, Milena Piedade, Antónia Teixeira & Carlos Carvalho.Background: Diagnosis delay contributes to increased tuberculosis (TB) transmission and morbimortality. TB incidence has been decreasing in Portugal, but median patient delay (PD) has risen. Symptom valorisation may determine PD by influencing help-seeking behaviour. We aimed to analyse the association between symptom valorisation and PD, while characterising individuals who disregarded their symptoms. Methods: A cross-sectional study was conducted among TB patients in Lisbon and Oporto in 2019 - 2021. Subjects who delayed seeking care because they did not value their symptoms or thought these would go away on their own were considered to have disregarded their symptoms. PD was categorised using a 21-day cut-off, and a 30-day cut-off for sensitivity analysis. We estimated the effect of symptom valorisation on PD through a directed acyclic graph. Then, a multivariable regression analysis characterised patients that disregarded their symptoms, adjusting for relevant variables. We fitted Poisson regression models to estimate crude and adjusted prevalence ratios (PR). Results: The study included 75 patients. Median PD was 25 days (IQR 11.5-63.5), and 56.0% of participants had PD exceeding 21 days. Symptom disregard was reported by 38.7% of patients. Patients who did not value their symptoms had higher prevalence of PD exceeding 21 days compared to those who valued their symptoms [PR 1.59 (95% CI 1.05-2.42)]. The sensitivity analysis showed consistent point estimates but wider confidence intervals [PR 1.39 (95% CI 0.77-2.55)]. Being a smoker was a risk factor for symptom disregard [PR 2.35 (95% CI 1.14-4.82)], while living in Oporto [PR 0.35 (95% CI 0.16-0.75)] and having higher household incomes [PR 0.39 (95% CI 0.17-0.94)] were protective factors. Conclusions: These findings emphasise the importance of symptom valorisation in timely TB diagnosis. Patients who did not value their symptoms had longer PD, indicating a need for interventions to improve symptom recognition. Our findings also corroborate the importance of the socioeconomic determinants of health, highlighting tobacco as a risk factor both for TB and for PD.This work was supported by the Fundação para a Ciência e Tecnologia (FCT, Portugal) [Grant: PTDC/SAU-PUB/31346/2017]. The present publication was funded by Fundação para a Ciência e Tecnologia (FCT, Portugal) national support through Comprehensive Health Research Centre (CHRC) [UIDP/04923/2020].info:eu-repo/semantics/publishedVersio

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.&lt;p&gt;&lt;/p&gt; Methods: Sixty-six non-HLA SNPs showing a P value &#60;10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.&lt;p&gt;&lt;/p&gt; Conclusion: Our results suggest a role of PPARG gene in the development of SSc

TECNOLOGIA E INOVAÇÃO AO SERVIÇO DO EXERCÍCIO E SAÚDE. Exercício. Pandemia COVID-19. Tecnologia Vs. Isolamento Social

info:eu-repo/semantics/publishedVersio

Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

Papel do canal mitocondrial de potássio sensível a ATP e do poro transitório de permeabilidade mitocondrial na viabilidade celular cardíaca após isquémia e reperfusão

Tese de doutoramento em Biologia (Biologia Celular) apresentada à Fac. de Ciências e Tecnologia de Coimbr

Nutritional screening using the Mini Nutritional Assessment short form: applicability and challenges

OBJECTIVES: To evaluate the nutritional risk in elderly hospitalized patients using the mini nutritional assessment short form and to check its applicability in the hospital routine. METHODS: Cross-sectional study conducted with 253 elderly patients, both genders, aged &gt; 65 years, admitted to the Hospital of the University of S&atilde;o Paulo. Parameters assessed: demographics (age and sex), calf circumference, clinical profile (admission diagnosis, comorbidities and clinical outcome) and the nutritional risk using the Mini Nutritional Assessment short form. Statistical analysis was performed using analysis of variance (ANOVA), \u3c72 test and Spearman's rank correlation coefficient. RESULTS: 68.0% of subjects were classified as malnourished or on nutritional risk. Negative and weak correlation was found between calf circumference and length of hospital stay (r = -0.198; p = 0.002). When stratified by gender, calf circumference was positively correlated with body mass index (r = 0.698; p &lt; 0.001) and negatively with age (r = -0,271; p &lt; 0.001) and length of hospital stay (r = -454; p &lt; 0.001) among women. CONCLUSION: The Mini Nutritional Assessment short form is a practical and applicable nutritional screening tool to be used in the hospital routine.</p