Ocular phenotype and genetical analysis in patients with retinopathy of prematurity

Background Retinopathy of prematurity (ROP) is a multifactorial retinal disease, involving both environmental and genetic factors; The purpose of this study is to evaluate the clinical presentations and genetic variants in Chinese patients with ROP. Methods A total of 36 patients diagnosed with ROP were enrolled in this study, their medical and ophthalmic histories were obtained, and comprehensive clinical examinations were performed. Genomic DNA was isolated from peripheral blood of ROP patients, polymerase chain reaction and direct sequencing of the associated pathogenic genes (FZD4, TSPAN12, and NDP) were performed. Results All patients exhibited the clinical manifestations of ROP. No mutations were detected in the TSPAN12 and NDP genes in all patients; Interestingly, three novel missense mutations were identified in the FZD4 gene (p.A2P, p.L79M, and p.Y378C) in four patients, for a detection rate of 11.1% (4/36). Conclusions This study expands the genotypic spectrum of FZD4 gene in ROP patients, and our findings underscore the importance of obtaining molecular analyses and comprehensive health screening for this retinal disease.

Depression and psychological distress in elders are influenced by the antioxidant enzyme SOD2

Introduction: Depression and psychological stress have high prevalence and incidence rates, affecting the individual welfare and increasing the risks for non-infectious chronic diseases. Studies have shown relations between inflammation and oxidative stress. In genetics, the single nucleotide polymorphism (SNP), inside the superoxide dismutase gene (Val16Ala-SOD2), is an important study subject to comprehend the risks of developing depression because its different genotypes can impact the balance between superoxide and hydrogen peroxide. The genotype VV favors the superoxide, the AA favors the peroxide and the AV generates similar amounts. Objectives: Evaluate the relation between oxidative unbalance, generated by Val16Ala-SOD2 SNP, and the rates of depression in elders. Methods: The study, approved by the ethics committee of UFSM, was a case-control analysis to examine the association between Val16Ala-SOD2 SNP, depression and stress in elders. Genetical analysis was made by polymerase chain reactions. The sample had 612 elders from Gravataí (RS). Depression was diagnosed using the geriatric depression scale- 15 and the stress by self perception. Statistical analysis was made by SSPS. Results: From the 612 elders (with similar ages and lifestyles), 115 were diagnosed with depression; the other 497 composed the control group. The analyses showed significantly higher frequency of the genotype VV in those who had depression, compared with the allele A. Conclusion: The results indicate strong association of the Val16Ala-SOD2 SNP, the risks of depression and psychological stress, probably due to the increasing oxidative stress and inflammatory state associated with the recessive genotype, VV.

Lignin Degradation and Its Use in Signaling Development by the Coprophilous Ascomycete Podospora anserina

The filamentous fungus Podospora anserina is a good model to study the breakdown of lignocellulose, owing to its ease of culture and genetical analysis. Here, we show that the fungus is able to use a wide range of lignocellulosic materials as food sources. Using color assays, spectroscopy and pyrolysis–gas chromatography mass spectrometry, we confirm that this ascomycete is able to degrade lignin, primarily by hydrolyzing β–O-4 linkages, which facilitates its nutrient uptake. We show that the limited weight loss that is promoted when attacking Miscanthus giganteus is due to a developmental blockage rather than an inefficiency of its enzymes. Finally, we show that lignin, and, more generally, phenolics, including degradation products of lignin, greatly stimulate the growth and fertility of the fungus in liquid cultures. Analyses of the CATΔΔΔΔΔ mutant lacking all its catalases, pro-oxidants and antioxidants indicate that improved growth and fertility of the fungus is likely caused by augmented reactive oxygen species levels triggered by the presence of phenolics.

Usefulness of a novel device to divide core needle biopsy specimens in a spatially matched fashion

We developed a novel dividing device that can split needle biopsy tissues along longitude axis aiming to achieve definitive molecular-biological and genetical analysis with reference of pathological diagnosis of the side-by-side divided tissue as spatially matched information. The aim of this study was to evaluate the feasibility and potential usefulness of the novel dividing device to provide the appropriate materials for molecular diagnosis. The new device was examined using mouse xenograft tumors. Real-time quantitative PCR and genetic test were performed to evaluate the feasibility and usefulness of the device. All the samples from needle biopsy were successfully divided into two pieces. Quality and quantity from divided samples harbor high enough to perform gene expression analysis (real-time PCR) and genetic test. Using two divided samples obtained from xenograft tumor model by needle biopsy, the % length of xenograft tumor (human origin) was significantly correlated with the % human genomic DNA (p = 0.00000608, r = 0.987), indicating that these divided samples were spatially matched. The novel longitudinally dividing device of a needle biopsy tissue was useful to provide the appropriate materials for molecular-biological and genetical analysis with reference of pathological diagnosis as spatially matched information.

Correlation of longtime efficacy maintenance PARP inhibitor therapy with pre-treatment in a single-institution experience.

e18084 Background: The use of PARP inhibitors (Olaparib-Niraparib) has shown an important benefit in PFS in patients with relapsed ovarian cancer both with gBRCA and non-BRCA mutation. Methods: This was a single-institution, retrospective cohort study of 93 patients. Clinical data were obtained by the review of the electronic medical report. The 93 patients were treated with PARP Inhibitors(PARP-I) between Apr 2014 and Dic 2019. The patients were evaluated according to age, BRCA mutation, pretreatment with Trabectedin, Bevacizumab, last line of pretreatment with Platinum-Gemcitabine+Paclitaxel versus Caelyx-Oxaliplatin, number of previous lines of chemotherapy, residual disease before PARP-I. Statistical analysis of survival was performed with Kaplan-Meyer, univariate and multivariate analysis with Cox regression. Disease Free Survival (DFS) was evaluated from the start of PARP-I therapy while Overall Survival (OS) from the diagnosis. Results: Median age was 64 (42-90), patients with germinal mutation BRCA were 34 (36.6%), 58 without mutation and 1 patient without genetical analysis. 20 (21,5%) patients were pretreated with Trabectedin plus Pegylated Liposomal Doxorubicine (PLD), while 8 (8,6%) with Trabectedin-Bevacizumab, 26 (28%) patients were pretreated with Bevacizumab +/- Trabectedin. Before PARP-I patients more frequently were pretreated with 2-3 line 60, 64.5%): in the last line of pretreatment chemotherapy 47 (50,4%) patients received PLD+-Oxaliplatin versus Carboplatin-Taxol or Carboplatin-Gemcitabine. In 64% of the patients CTscan or ecography showed residual disease > 1 cm before starting PARP-I treatment . Median follow-up was 17 months: 54 (58.1%) patients in PARP-I treatment relapsed, while 32 (34.1%) patients died. Multivariate analysis showed a significant association in the number of lines pretreatment: in more than 3 lines HR was 2.00 (CI 1.2-3.4, p = 0.012), according to residuum less or more 1 cm prior to start PARP therapy (logrank p = 0,0286). Conclusions: The administration of PARP is important for OS immediately after 2° line chemotherapy in platinum sensitive patients Logrank p = 0.0065, with higher response not significant, about OS specially if following non-anemic PLD-Oxaliplatin therapy (p = 0,0849 Logrank) Also significant is OS according to residuum less or more 1 cm prior to start PARP therapy (logrank p = 0,0286) The doses and relative reductions in PARP-I did not change efficacy.

Dystrophin gene mutations in two different ethnic families in Azerbaijan Republic

Two different mutations: deletion of 13 exons (from 8th to 20th exons) in one index patient and deletion of 45th exon in the second one were identified by molecular genetical analysis for patients with Duchenne muscle dystrophy diagnosis from different ethnic groups, residing in Azerbaijan. Taking into account reproductive age of parents, the prenatal diagnosis of fetus is recommended for the following pregnancies.