Mitochondrial maintenance under oxidative stress depends on mitochondrially localised α-OGG1.

Accumulation of 8-oxoguanine (8-oxoG) in mitochondrial DNA and mitochondrial dysfunction have been observed in cells deficient for the DNA glycosylase OGG1 when exposed to oxidative stress. In human cells, up to eight mRNAs for OGG1 can be generated by alternative splicing and it is still unclear which of them codes for the protein that ensures the repair of 8-oxoG in mitochondria. Here, we show that the α-OGG1 isoform, considered up to now to be exclusively nuclear, has a functional mitochondrial-targeting sequence and is imported into mitochondria. We analyse the sub-mitochondrial localisation of α-OGG1 with unprecedented resolution and show that this DNA glycosylase is associated with DNA in mitochondrial nucleoids. We show that the presence of α-OGG1 inside mitochondria and its enzymatic activity are required to preserve the mitochondrial network in cells exposed to oxidative stress. Altogether, these results unveil a new role of α-OGG1 in the mitochondria and indicate that the same isoform ensures the repair of 8-oxoG in both nuclear and mitochondrial genomes. The activity of α-OGG1 in mitochondria is sufficient for the recovery of organelle function after oxidative stress

Exploring Seipin: From Biochemistry to Bioinformatics Predictions

Seipin is a nonenzymatic protein encoded by the BSCL2 gene. It is involved in lipodystrophy and seipinopathy diseases. Named in 2001, all seipin functions are still far from being understood. Therefore, we reviewed much of the research, trying to find a pattern that could explain commonly observed features of seipin expression disorders. Likewise, this review shows how this protein seems to have tissue-specific functions. In an integrative view, we conclude by proposing a theoretical model to explain how seipin might be involved in the triacylglycerol synthesis pathway

Home motor telerehabilitation strategies in stroke survivors: a protocol for systematic review and meta analysis

Abstract Introduction: Stroke survivors need early assistance after hospital discharge in order to maximize the effects of rehabilitation; telerehabilitation in the home environment is an effective treatment strategy. Methods: A comprehensive systematic review on home telerehabilitation in stroke survivors will be carried out in Latin American and Caribbean Literature on Health Sciences (LILACS), Web of Science, Scopus, Physical therapy Evidence Database (PEDro), Scielo, System Online of Search and Analysis of Medical Literature (MEDLINE), Embase, Virtual Health Library (VHL). Two independent reviewers will perform screening, data extraction as well as risk of bias assessment through the Joanna Briggs Institute (JBI) Critical Appraisal tool. For the quality of evidence, the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) will be used. Results: The results of this review will be published in a peer-reviewed journal. Conclusions: This systematic review will provide evidence of the best form of intervention and monitoring of stroke survivors through home telerehabilitation. The evidence can help healthcare professionals and patients recognize more effective and safer therapeutic inventions. Abbreviations: JBI = Joanna Briggs Institute, GRADE = Grades of Recommendation, Assessment, Development, and Evaluation

SNPs in DNA repair genes associated to meningitis and host immune response

In vitro and in animal models, APE1, OGG1, and PARP-1 have been proposed as being involved with inflammatory response. In this work, we have investigated if the SNPs APE1 Asn148Glu, OGG1 Ser326Cys, and PARP-1 Val762Ala are associated to meningitis. The patient genotypes were investigated by PIRA-PCR or PCR-RFLP. DNA damages were detected in genomic DNA by Fpg treatment. IgG and IgA were measured from plasma and the cytokines and chemokines were measured from cerebrospinal fluid samples using Bio-Plex assays. A higher frequency (P<0.05) of APE1 Glu allele in bacterial meningitis (BM) and aseptic meningitis (AM) patients was observed. The genotypes Asn/Asn in control group and Asn/Glu in BM group was also higher. For the SNP OGG1 Ser326Cys, the genotype Cys/Cys was more frequent (P<0.05) in BM group. The frequency of PARP-1 Val/Val genotype was higher in control group (P<0.05). The occurrence of combined SNPs is significantly higher in BM patients, indicating that these SNPs may be associated to the disease. Increasing in sensitive sites to Fpg was observed in carriers of APE1 Glu allele or OGG1 Cys allele, suggesting that SNPs affect DNA repair activity. Alterations in IgG production were observed in the presence of SNPs APE1 Asn148Glu, OGG1 Ser326Cys or PARP-1 Val762Ala. Moreover, reduction in the levels of IL-6, IL-1Ra, MCP-1/CCL2 and IL-8/CXCL8 was observed in the presence of APE1 Glu allele in BM patients. In conclusion, we obtained indications of an effect of SNPs in DNA repair genes on the regulation of immune response in meningitis

High prevalence of Berardinelli-Seip Congenital Lipodystrophy in Rio Grande do Norte State, Northeast Brazil

Abstract Background Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare disease characterized by the almost complete absence of adipose tissue. Although a large number of BSCL cases was previously identified in Rio Grande do Norte (RN), a state in Northeast Brazil, its prevalence in RN regions and municipalities remains unknown. The purpose of this study was to better characterize the prevalence of BSCL in RN. Methods A descriptive study was conducted using secondary data obtained from the Association of Parents and People with BSCL of RN to determine its prevalence. The patients’ socio-demographic characteristics and geolocalization were analyzed. Results We estimated a total of 103 BSCL cases in RN, resulting in a prevalence of 3.23 per 100,000 people. The Central Potiguar mesoregion, Seridó territory, Carnaúba dos Dantas and Timbaúba dos Batistas municipalities had a much higher prevalence of BSCL, with 20.56, 20.66, 498.05 and 217.85 per 100,000 people, respectively. Conclusions Together, our results showed that BSCL is highly prevalent in RN and confirmed that our state has one of the highest prevalences of this lipodystrophy worldwide. More studies are still needed to better estimate the prevalence and incidence of BSCL in RN as well as in other states in Brazil. Trial registration Study Number 31809314.0.0000.556

Impairment of respiratory muscle strength in Berardinelli-Seip congenital lipodystrophy subjects

Abstract Background Berardinelli-Seip Congenital Generalized Lipodystrophy (BSCL) is an ultra-rare metabolic disease characterized by hypertriglyceridemia, hyperinsulinemia, hyperglycemia, hypoleptinemia, and diabetes mellitus. Although cardiovascular disturbances have been observed in BSCL patients, there are no studies regarding the Respiratory Muscle Strength (RMS) in this type of lipodystrophy. This study aimed to evaluate RMS in BSCL subjects compared with healthy subjects. Methods Eleven individuals with BSCL and 11 healthy subjects matched for age and gender were included in this study. The Maximum Inspiratory Pressure (MIP), Maximum Expiratory Pressure (MEP), and Peripheral Muscle Strength (PMS) were measured for three consecutive years. BSCL subjects were compared to healthy individuals for MIP, MEP, and PMS. Correlations between PMS and MIP were also analyzed. The genetic diagnosis was performed, and sociodemographic and anthropometric data were also collected. Results BSCL subjects showed significantly lower values for MIP and MEP (p <  0.0001 and p = 0.0002, respectively) in comparison to healthy subjects, but no changes in handgrip strength (p = 0.15). Additionally, we did not observe changes in MIP, MEP, and PMS two years after the first analysis, showing maintenance of respiratory dysfunction in BSCL subjects (p = 0.05; p = 0.45; p = 0.99). PMS and MIP were not correlated in these subjects (r = 0.56; p = 0.18). Conclusion BSCL subjects showed lower respiratory muscle strength when compared with healthy subjects; however, PMS was not altered. These findings were maintained at similar levels during the two years of evaluation. Our data reveal the first association of BSCL with the development of respiratory muscle weakness

Sex differences in severity of metabolic complications in patients with congenital generalized lipodystrophy

The attached file includes supplementary tables. This submission meets the Extended Data Sets and Supplemental Materials requirements that are included in author guidelines for the Journal of Clinical Endocrinology & Metabolism (Print ISSN 0021-972X, Online ISSN 1945-7197).CONTEXT: Previous data support a higher prevalence of metabolic complications in females affected with familial partial lipodystrophy than in males. However, whether there are any sex differences in the prevalence and severity of metabolic complications among patients with congenital generalized lipodystrophy (CGL) remains unclear. OBJECTIVES: To compare prevalence of metabolic complications and metabolic parameters between males and females with CGL. DESIGN: A retrospective, cross-sectional comparison. SETTINGS: Patients from two tertiary referral centers from Northeastern Brazil - Universidade Federal do Rio Grande do Norte, Natal, and Universidade Federal do Ceará, Fortaleza. PATIENTS: A total of 44 females (age 2-51 years) and 28 males (age 5-46 years) with CGL. Twenty-six (7 M, 19 F) had genotypically confirmed CGL type 1, 43 (20 M, 23 F) had CGL type 2, and 3 patients were not genotyped. MAIN OUTCOME MEASURES: Prevalence of diabetes mellitus and hypertriglyceridemia, and metabolic variables. RESULTS: Females with CGL, as compared to males, had significantly increased prevalence of diabetes (82% vs. 54%; p<0.01) and hypertriglyceridemia (91% vs. 71%; p=0.05); and had higher median fasting serum triglycerides levels (383 vs. 221 mg/dL; p=0.01), but not statistically significantly higher median hemoglobin A1c (7.9% vs. 6.5%; p=0.37) and fasting serum glucose levels (138 vs. 89 mg/dL; p=0.06). CONCLUSIONS: Compared to males, females with CGL have increased prevalence of metabolic complications, such as diabetes and hypertriglyceridemia, suggesting need for close monitoring of metabolic parameters, and early and aggressive intervention among them

Nurses' knowledge about Berardinelli-Seip Congenital Lipodystrophy

<div><p>Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive disease characterized by the almost complete absence of adipose tissue. Due to a strong founder effect that resulted in a higher prevalence of BSCL in Rio Grande do Norte (<i>RN</i>), a state in northeastern Brazil, it has been essential that health professionals develop knowledge about this disease. Nurses are often the first point of contact with patients during health care assistance. The purpose of this study was to investigate the knowledge of these professionals about BSCL in two main hospitals in <i>RN</i> state. A questionnaire was applied to 199 nurses working in the <i>Hospital Regional Mariano Coelho</i>—<i>HRMC</i> (Regional Hospital Mariano Coelho), in <i>Currais Novos–RN</i>, and in the <i>Hospital Universitário Onofre Lopes</i>—<i>HUOL</i> (University Hospital Onofre Lopes), in <i>Natal–RN</i>. This study showed that most nursing professionals do not know about the disease, although they have already received patients with BSCL in those hospitals. The nurses from <i>HRMC</i> and <i>HUOL</i> lacked knowledge of BSCL and the healthcare of these patients requires immediate improvement. Significant efforts are required to close the gap between current and needed practice patterns.</p></div

Map of the <i>Rio Grande do Norte</i> state.

<p>Geolocalization of <i>Natal</i> (1) and <i>Currais Novos</i> (2), where <i>HUOL</i> and <i>HRMC</i> hospitals are located, respectively. The map was created using the TabWin Program (DATASUS/<i>Ministério da Saúde</i>–Brazilian Ministry of Health).</p