Search results for: Micaela Belén Peralta

Authors: Leonardo Costa Pereira, Frederico Santos Santana, Mauro Karnikowski, Luís Sinésio Silva Neto, Aline Oliveira Gomes, Marisete Peralta Safons, Margô Gomes De Oliveira Karnikowski

Abstract:

In Brazil, projections of population aging follow all world projections, the birth rate tends to be surpassed by the mortality rate around the year 2045. Historically, the population of Brazilian blacks suffered for several centuries from the oppression of dominant classes. A group, especially of blacks, stands out in relation to territorial, historical and social aspects, and for centuries they have isolated themselves in small communities, in order to maintain their freedom and culture. The isolation of the Quilombola communities generated socioeconomic effects as well as the health of these blacks. Thus, the objective of the present study is to verify the association of body composition parameters with lower and upper limb strength and functional capacity in Quilombola remnants. The research was approved by ethics committee (1,771,159). Anthropometric evaluations of hip and waist circumference, body mass and height were performed. In order to verify the body composition, the relationship between stature and body mass (BM) was performed, generating the body mass index (BMI), as well as the dual-energy X-ray absorptiometry (DEXA) test. The Time Up and Go (TUG) test was used to evaluate the functional capacity, and a maximum repetition test (1MR) for knee extension and handgrip (HG) was applied for strength magnitude analysis. Statistical analysis was performed using the statistical package SPSS 22.0. Shapiro Wilk's normality test was performed. For the possible correlations, the suggestions of the Pearson or Spearman tests were adopted. The results obtained after the interpretation identified that the sample (n = 18) was composed of 66.7% of female individuals with mean age of 66.07 ± 8.95 years. The sample’s body fat percentage (%BF) (35.65 ± 10.73) exceeds the recommendations for age group, as well as the anthropometric parameters of hip (90.91 ± 8.44cm) and waist circumference (80.37 ± 17.5cm). The relationship between height (1.55 ± 0.1m) and body mass (63.44 ± 11.25Kg) generated a BMI of 24.16 ± 7.09Kg/m2, that was considered normal. The TUG performance was 10.71 ± 1.85s. In the 1MR test, 46.67 ± 13.06Kg and in the HG 23.93±7.96Kgf were obtained, respectively. Correlation analyzes were characterized by the high frequency of significant correlations for height, dominant arm mass (DAM), %BF, 1MR and HG variables. In addition, correlations between HG and BM (r = 0.67, p = 0.005), height (r = 0.51, p = 0.004) and DAM (r = 0.55, p = 0.026) were also observed. The strength of the lower limbs correlates with BM (r = 0.69, p = 0.003), height (r = 0.62, p = 0.01) and DAM (r = 0.772, p = 0.001). In this way, we can conclude that not only the simple spatial relationship of mass and height can influence in predictive parameters of strength or functionality, being important the verification of the conditions of the corporal composition. For this population, height seems to be a good predictor of strength and body composition.

Keywords: African Continental Ancestry Group, body composition, functional capacity, strength

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Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

Abstract:

Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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