Pinch2 regulates myelination in the mouse central nervous system.

The extensive morphological changes of oligodendrocytes during axon ensheathment and myelination involve assembly of the Ilk-Parvin-Pinch (IPP) heterotrimeric complex of proteins to relay essential mechanical and biochemical signals between integrins and the actin cytoskeleton. Binding of Pinch1 and Pinch2 isoforms to Ilk is mutually exclusive and allows the formation of distinct IPP complexes with specific signaling properties. Using tissue-specific conditional gene ablation in mice, we reveal an essential role for Pinch2 during central nervous system myelination. Unlike Pinch1 gene ablation, loss of Pinch2 in oligodendrocytes results in hypermyelination and in the formation of pathological myelin outfoldings in white matter regions. These structural changes concur with inhibition of Rho GTPase RhoA and Cdc42 activities and phenocopy aspects of myelin pathology observed in corresponding mouse mutants. We propose a dual role for Pinch2 in preventing an excess of myelin wraps through RhoA-dependent control of membrane growth and in fostering myelin stability via Cdc42-dependent organization of cytoskeletal septins. Together, these findings indicate that IPP complexes containing Pinch2 act as a crucial cell-autonomous molecular hub ensuring synchronous control of key signaling networks during developmental myelination.

The Panorama of Cleft Lip and Palate Live Birth in Brazil: Follow-up of a 10-Year Period and Inequalities in the Health System.

OBJECTIVE: To provide the prevalence and an overview of cleft lip and palate (CL/P) in the period of 2008 to 2017, as well as the profile of care provided for this condition in Brazil. DESIGN: Cross-sectional study of epidemiological character. SETTING: Brazilian government website. PARTICIPANTS: National Live Birth and Hospital Information System. INTERVENTION: Organization of the end databases and performance-based statistical analysis. MAIN OUTCOME MEASURE(S): Analysis of the prevalence of CL/P in newborns, sociodemographic condition of the mothers, surgical procedures and hospitalizations, and specialized hospitals in Brazil within a 10-year period. RESULTS: The average prevalence of CL/P in Brazil was ∼52 children per 100 000 live births in the covered period, corresponding to 1 per 1924 newborns. The presence of cleft was associated with preterm birth, being underweight, and the male gender. The highest prevalence was found in the South region, while the lowest was found in the Northeast region, with increasing rates in the North region of Brazil. The states with the highest prevalence were not those with a great number of hospitalizations and surgical procedures for live births with CL/P. CONCLUSION: In the 10-year study period, the prevalence of CL/P was 0.52 newborns per 1000 live births, a result which differs among the states of Brazil. The need to reinforce the national monitoring of the prevalence and surgical procedures of cleft patients have also emphasized the need to improve public medical care for CL/P subjects.

Unique noncoding variants upstream of PRDM13 are associated with a spectrum of developmental retinal dystrophies including progressive bifocal chorioretinal atrophy.

The autosomal dominant progressive bifocal chorioretinal atrophy (PBCRA) disease locus has been mapped to chromosome 6q14-16.2 that overlaps the North Carolina macular dystrophy (NCMD) locus MCDR1. NCMD is a nonprogressive developmental macular dystrophy, in which variants upstream of PRDM13 have been implicated. Whole genome sequencing was performed to interrogate structural variants (SVs) and single nucleotide variants (SNVs) in eight individuals, six affected individuals from two families with PBCRA, and two individuals from an additional family with a related developmental macular dystrophy. A SNV (chr6:100,046,804T>C), located 7.8 kb upstream of the PRDM13 gene, was shared by all PBCRA-affected individuals in the disease locus. Haplotype analysis suggested that the variant arose independently in the two families. The two affected individuals from Family 3 were screened for rare variants in the PBCRA and NCMD loci. This revealed a de novo variant in the proband, 21 bp from the first SNV (chr6:100,046,783A>C). This study expands the noncoding variant spectrum upstream of PRDM13 and suggests altered spatio-temporal expression of PRDM13 as a candidate disease mechanism in the phenotypically distinct but related conditions, NCMD and PBCRA.

Telerehabilitation-based trunk exercise training for motor symptoms of individuals with Parkinson's disease: A randomized controlled clinical trial.

BACKGROUND: Poor gait and static balance performance may be associated with trunk muscles in individuals with Parkinson's disease. AIM: The study aims at evaluating the effects of a home-based trunk exercise program on gait and balance performance in Parkinson's disease. METHODS: A randomized controlled trial was conducted with 28 individuals with Parkinson's disease with Hoehn & Yahr stage II-IV. The control group (n = 14) performed upper and lower limb exercises, while the experimental group (n = 14) engaged in a trunk exercise program. Both groups performed home-based exercises three times daily for 3 weeks. At the end of interventions (post-training) and 4 weeks after post-training (follow-up), static balance (force plate) and gait (motion capture system) were evaluated. Mixed analysis of variance compared time × group interaction (α = 5%). RESULTS: No time × group interaction was observed in the center of pressure displacement, center of pressure mean velocity, and anteroposterior and mediolateral center of pressure range during bipedal support with eyes opened and closed; and gait speed, hip, knee, and ankle range of motion during gait analysis. No intragroup differences were found. CONCLUSION: Trunk strengthening exercises did not improve gait and balance compared with upper and lower limb exercises. The non-adherence rate (33%) to the remote intervention may have also hindered our results.

Production of tung oil epoxy resin using low frequency high power ultrasound.

Epoxy resins made from vegetable oils are an alternative to synthesize epoxy resins from renewable sources. Tung oil is rich in α -eleostearic fatty acid, which contains three double bonds producing epoxy resins with up to three epoxy groups per fatty acid. This work studied the production of tung oil epoxy resin using hydrogen peroxide as an oxidizing agent and acetic and formic acid as percarboxylic acid precursors, applying low frequency high power ultrasound. This study evaluated the effects of ultrasound power density, hydrogen peroxide concentration, acetic acid concentration, and formic acid concentration on the yield into epoxy resin, selectivity, and by-products formation. Application of ultrasound was carried out using a 19 kHz probe ultrasound (horn ultrasound) with a 1.3 cm diameter titanium probe, 500 W nominal power, 2940 W L-1 maximum effective power density applied to the reaction mixture. Ultrasound technology yielded up to 85% of epoxy resin in 3 h of reaction. The use of formic acid resulted in a slightly lower oil conversion than acetic acid but with a much higher selectivity towards epoxidized tung oil. However, using acetic acid resulted in the production of high-value by-products, such as 2-heptenal and 2,4-nonadienal. The ultrasound-assisted epoxidation showed to be particularly efficient when applied to oils containing conjugated double-bonds.

PPARα Gene Is Involved in Body Composition Variation in Response to an Aerobic Training Program in Overweight/Obese.

The objective of this study was to investigate the relationship of the polymorphism in Intron 7 G/C (rs 4253778) of the peroxisome proliferator-activated receptor alpha (PPARα) gene with the magnitude of changes in the body composition of an overweight and obese population that underwent an aerobic training program. Fifty-eight previously inactive men and women, body mass index (BMI) 31.5 ± 2.8 kg/m2, 46.5% (n = 27) genotyped as CC genotype and 53.5% (n = 31) as CA+AA, underwent a 12-week aerobic training (walking/running). Aerobic capacity (ergospirometry), body composition (DXA), and nutritional assessment were made before and 48 h after the experimental protocol. Two-way ANOVA, chi-square test, and logistic regression were used (p < 0.05). Twenty-seven volunteers (46.5%) were identified as CC genotype and 31 (53.5%) as CA+AA genotype. Time-group interaction showed that there was no difference in these between two allele groups. However, differences in distribution of respondents or nonresponders according to allele A were identified for fat mass (p ≤ 0.003), percentage fat mass (p ≤ 0.002), the waist (p ≤ 0.009), abdomen (p ≤ 0.000), and hip (p ≤ 0.001), this difference being independent for the fat mass. Meanwhile, sex, age, and nutritional management have also been found to be influential factors. It is concluded that the PPARα gene is involved in varying body composition in response to an aerobic training program.

Oxidative stress does not influence weight loss induced by aerobic training in adults: randomized clinical trials.

BACKGROUND: High levels of oxidative stress promote degradation of the cell membrane impairing cellular function in fat oxidation. However, the influence of oxidative stress on exercise-induced weight-loss has not yet been investigated. Therefore, the aim of this study was to verify the influence of a lipidic peroxidation marker (malondialdehyde, MDA) and antioxidant status (total antioxidant capacity marker, TAC) on the magnitude of weight-loss by aerobic-induced exercise in previously sedentary overweight or obese individuals. METHODS: Seventy-five physically inactive adults were randomized into experimental (N.=58) and control (N.=17) groups, who engaged in a 12-week program of aerobic training walking and/or running (3 to 5 days/week) or stretching (1 day/week), respectively. Body composition (DXA), aerobic capacity (ergospirometric) and blood collections for oxidative stress analysis (MDA and TAC) were determined before and after the experimental protocol. Two-way ANOVA for repeated measures or Friedman's test were used to evaluate differences in time/group interaction. Pearson correlation was used to verify the relationship between the variables of oxidative stress and of body composition. RESULTS: Significant reduction was found in fat body mass of experimental when compared to control group (-1.3±1.9 kg versus -0.3±1.3, P=0.04). Experimental group also altered significantly the total body mass (-1.2±4.7 kg; effect size 0.44), body mass index - BMI (-0.3±1.1 effect size 0.37), fat percentage (1.3±1.6%; effect size 0.50) and lean body mass (0.6±1.5 kg; effect size 0.32).There was increase in MDA of 2.3 µmol/L to 2.7 µmol/L (P=0.00), without changes to TAC (25.6±13.9% to 28.0±10.4%). No correlation was found between these variations in body composition with either the initial values of MDA and TAC or delta variation of these indicators of oxidative stress in response to the training program. CONCLUSIONS: Indicators of oxidative stress (MDA and TAC) does not influence the magnitude of weight-loss induced by aerobic training.

Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus.

Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development.

Genome-wide linkage and haplotype sharing analysis implicates the MCDR3 locus as a candidate region for a developmental macular disorder in association with digit abnormalities.

BACKGROUND: Developmental macular disorders are a heterogeneous group of rare retinal conditions that can cause significant visual impairment from childhood. Among these disorders, autosomal dominant North Carolina macular dystrophy (NCMD) has been mapped to 6q16 (MCDR1) with recent support for a non-coding disease mechanism of PRDM13. A second locus on 5p15-5p13 (MCDR3) has been implicated in a similar phenotype, but the disease-causing mechanism still remains unknown. METHODS: Two families affected by a dominant developmental macular disorder that closely resembles NCMD in association with digit abnormalities were included in the study. Family members with available DNA were genotyped using the Affymetrix GeneChip Human Mapping 250K Sty array. A parametric multipoint linkage analysis assuming a fully penetrant dominant model was performed using MERLIN. Haplotype sharing analysis was carried out using the non-parametric Homozygosity Haplotype method. Whole-exome sequencing was conducted on selected affected individuals. RESULTS: Linkage analysis excluded MCDR1 from the candidate regions (LOD < -2). There was suggestive linkage (LOD = 2.7) at two loci, including 9p24.1 and 5p15.32 that overlapped with MCDR3. The haplotype sharing analysis in one of the families revealed a 5 cM shared IBD segment at 5p15.32 (p value = 0.004). Whole-exome sequencing did not provide conclusive evidence for disease-causing alleles. CONCLUSIONS: These findings do not exclude that this phenotype may be allelic with NCMD MCDR3 at 5p15 and leave the possibility of a non-coding disease mechanism, in keeping with recent findings on 6q16. Further studies, including whole-genome sequencing, may help elucidate the underlying genetic cause of this phenotype and shed light on macular development and function.

Interference of medicines in laboratory exams / Interferência dos medicamentos nos exames laboratoriais

ABSTRACT Objective: Conduct a survey on the interference of drugs in laboratory tests. Methodology: To identify the interference of each medication in laboratory tests, the Municipal List of Essential Medicines (Remume) of a medium-sized municipality in the state of Minas Gerais was used along with the following sources of information: Dynamed, Micromedex® and Nursing Reference Center. Results: We observed that the majority (67.7%) of Remume drugs can interfere in one or more laboratory tests; among them, the main classes of drugs are diuretics, beta blockers, ß-lactams, sulfonamides, macrolides, tricyclic antidepressants and selective serotonin reuptake inhibitors antidepressants. Conclusion: It is extremely important to disseminate knowledge about these interferences so that health professionals are alert and know how to identify the possible changes, reducing analytical errors and subsequently misdiagnosis and erroneous monitoring. Continued education on drug interference in laboratory tests is equally important.

RESUMEN Objetivo: Llevar a cabo una encuesta acerca de la interferencia de los medicamentos en las pruebas de laboratorio. Métodos: Usamos la Relación Municipal de Medicamentos Esenciales (Remume) de una municipalidad mediana en el estado de Minas Gerais y las siguientes fuentes de información: Dynamed, Micromedex® y Nursing Reference Center. Resultados: Observamos que la mayor parte (67,7%) de los medicamentos de Remume puede interferir en una o más pruebas de laboratorio; entre ellos, las principales clases son los diuréticos, beta bloqueadores, betalactámicos, sulfonamidas, macrólidos, antidepresivos tricíclicos y antidepresivos inhibidores selectivos de la recaptación de serotonina. Conclusión: Es muy importante divulgar el conocimiento respecto a esas interferencias para que los profesionales de la salud puedan identificar las posibles alteraciones en las pruebas, reduciendo errores analíticos y diagnósticos y monitoreos equivocados. Por lo tanto, es necesaria una educación continuada acerca de las interferencias de medicamentos en las pruebas de laboratorio.

RESUMO Objetivo: Realizar um levantamento sobre a interferência dos medicamentos nos exames laboratoriais. Métodos: Utilizamos a Relação Municipal dos Medicamentos Essenciais (Remune) de um município de médio porte do estado de Minas Gerais e as seguintes fontes de informações: Dynamed, Micromedex® e Nursing Reference Center. Resultados: Observamos que a maioria (67,7%) dos medicamentos da Remune pode interferir em um ou mais exames laboratoriais; entre eles, as principais classes de medicamentos são os diuréticos, betabloqueadores, betalactâmicos, sulfonamidas, macrolídeos, antidepressivos tricíclicos e antidepressivos inibidores seletivos da recaptação de serotonina. Conclusão: É muito importante divulgar o conhecimento a respeito dessas interferências para que os profissionais da área da saúde possam identificar as possíveis alterações nos exames, reduzindo erros analíticos e diagnósticos e monitoramentos equivocados. Portanto, faz-se necessária a educação continuada sobre as interferências de medicamentos nos exames laboratoriais.