Prevalence of asthma, allergic rhinitis and pollinosis in a city of Brazil: A monitoring study.

BACKGROUND: Allergic respiratory diseases such as asthma and allergic rhinitis have increased considerably in the last decades. OBJECTIVE: The present study estimates prevalence trends of asthma, allergic rhinitis and pollinosis in the population of a city of Southern Brazil, without restriction of age, from 2011 to 2018, using the ISAAC standardized questionnaire. METHODS: Data was collected from March to June of 2011 and during the same months in 2018, in order to verify trends in the prevalence of these allergic conditions. The total sample consisted of 3132 individuals of both sexes living in the municipality of Santo Ângelo, in the state of Rio Grande do Sul, Brazil. RESULTS: No differences were observed in the prevalence of asthma diagnosis (15.1% in 2011 and 13.8% in 2018), however the prevalence of current wheeze was significantly reduced from 24.7% in 2011 to 21.2% in 2018 (p<0.05). Regarding allergic conditions in 2011 and in 2018, a significant reduction was observed (p<0.001) in reported current rhinitis (63.3% vs. 50.5%), rhinoconjunctivitis (48.9% vs. 38.8%), hay fever (52.0% vs. 43.3%), and pollinosis (29.0% vs 17.0%). Moreover, we observed an inverse relation between age and rhinoconjunctivitis and hay fever, and all symptoms were more frequent in females. Rhinoconjunctivitis and hay fever, as well as current rhinitis and pollinosis were highly prevalent among 30-39 years-old individuals, whereas current wheeze affected mainly the age group 10-19 years-old. CONCLUSION: While the prevalence of asthma remained similar after seven years, allergic rhinitis and pollinosis declined between 2011 and 2018.

Contribution of the GSTP1 c.313A>G variant to hearing loss risk in patients exposed to platin chemotherapy during childhood.

BACKGROUND AND AIM: Ototoxicity is a potential adverse effect of chemotherapy with platin drugs, such as cisplatin and carboplatin, in children. Hearing loss (HL) affecting frequencies below 4 kHz can compromise speech perception. The aim of this study was to investigate whether genetic variants previously implicated in ototoxicity are associated with HL overall and HL below 4 kHz in pediatric oncology patients treated with cisplatin or carboplatin. MATERIALS AND METHODS: Patients given cisplatin or carboplatin for a pediatric cancer at least 5 years prior to the start of the study were enrolled. The patients underwent comprehensive audiological evaluations and genotyping to detect the presence of the GJB2 c.35delG, GSTP1 c.313A>G, and MT-RNR1 m.1555A>G polymorphisms. RESULTS: HL was identified in 31/61 patients (50.8%), including 28/42 treated with cisplatin (66.6%) and 3/19 treated with carboplatin (15.8%). HL was associated with higher mean doses of cisplatin (p = .002) and carboplatin (p = .010). The c.313A>G variant of GSTP1 (heterozygous or homozygous) was detected in 31/61 patients (50.8%). An association between this variant allele and HL involving frequencies ≤ 4 kHz was identified (p = .020; 10-fold vs. non-carriers). No associations with HL were observed for GJB2 or MT-RNR1 gene variants. CONCLUSION: The GSTP1 c.313A>G variant may increase the risk of low-frequency HL in pediatric oncology patients treated with cisplatin or carboplatin chemotherapy.

Fruit Fly (Diptera: Tephritidae) Diversity and Host Relationships in Diverse Environments Estimated with Two Sampling Methods.

Knowledge of the diversity of fruit flies is essential for understanding aspects of their community ecology. However, the effectiveness of sampling methods in representing species diversity and relationships with hosts in a diverse environment has not been adequately assessed. This study aimed to determine the optimum method to represent the diversity of fruit flies and assess their relationships with host fruits. Species of Anastrepha sampled with both traps and fruits in the same area were comprehensively analyzed. Data were analyzed by Hill's numbers (species diversity in both sampling methods), heat map graph (interaction of species with methods), and rank clocks (population fluctuations of the most abundant species). We also measured the interaction strength of the species. Our results showed that estimated parameters of species diversity in an area may differ when sampled with traps or fruits. However, the most abundant species appeared to interact similarly in both methods. Fruits of members of the families Myrtaceae and Anacardiaceae contributed highly to the presence of Anastrepha. The optimum strategy to represent Anastrepha diversity in an area is the combined use of both sampling methods.

Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors.

BACKGROUND: Wilms tumor (WT) has a not completely elucidated pathogenesis. DNA copy number alterations (CNAs) are common in cancer, and often define key pathogenic events. The aim of this work was to investigate CNAs in order to disclose new candidate genes for Wilms tumorigenesis. RESULTS: Array-CGH of 50 primary WTs without pre-chemotherapy revealed a few recurrent CNAs not previously reported, such as 7q and 20q gains, and 7p loss. Genomic amplifications were exclusively detected in 3 cases of WTs that later relapsed, which also exhibited an increased frequency of gains affecting a 16.2 Mb 1q21.1-q23.2 region, losses at 11p, 11q distal, and 16q, and WT1 deletions. Conversely, aneuploidies of chromosomes 13 and 19 were found only in WTs without further relapse. The 1q21.1-q23.2 gain associated with WT relapse harbours genes such as CHD1L, CRABP2, GJA8, MEX3A and MLLT11 that were found to be over-expressed in WTs. In addition, down-regulation of genes encompassed by focal deletions highlighted new potential tumor suppressors such as CNKSR1, MAN1C1, PAQR7 (1p36), TWIST1, SOSTDC1 (7p14.1-p12.2), BBOX and FIBIN (11p13), and PLCG2 (16q). CONCLUSION: This study confirmed the presence of CNAs previously related to WT and characterized new CNAs found only in few cases. The later were found in higher frequency in relapsed cases, suggesting that they could be associated with WT progression.

Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through LGI4 and nitric oxide signals.

Intratumoral heterogeneity (ITH) represents an obstacle for cancer diagnosis and treatment, but little is known about its functional role in cancer progression. The A Desintegrin And Metalloproteinase 23 (ADAM23) gene is epigenetically silenced in different types of tumors, and silencing is often associated with advanced disease and metastasis. Here, we show that invasive breast tumors exhibit significant ADAM23-ITH and that this heterogeneity is critical for tumor growth and metastasis. We demonstrate that while loss of ADAM23 expression enhances invasion, it causes a severe proliferative deficiency and is not itself sufficient to trigger metastasis. Rather, we observed that, in ADAM23-heterotypic environments, ADAM23-negative cells promote tumor growth and metastasis by enhancing the proliferation and invasion of adjacent A23-positive cells through the production of LGI4 (Leucine-rich Glioma Inactivated 4) and nitric oxide (NO). Ablation of LGI4 and NO in A23-negative cells significantly attenuates A23-positive cell proliferation and invasion. Our work denotes a driving role of ADAM23-ITH during disease progression, shifting the malignant phenotype from the cellular to the tissue level. Our findings also provide insights for therapeutic intervention, enforcing the need to ascertain ITH to improve cancer diagnosis and therapy.

Heteroduplex formation and S1 digestion for mapping alternative splicing sites.

The identification of alternatively spliced transcripts has contributed to a better comprehension of developmental mechanisms, tissue-specific physiological processes and human diseases. Polymerase chain reaction amplification of alternatively spliced variants commonly leads to the formation of heteroduplexes as a result of base pairing involving exons common between the two variants. S1 nuclease cleaves single-stranded loops of heteroduplexes and also nicks the opposite DNA strand. In order to establish a strategy for mapping alternative splice-prone sites in the whole transcriptome, we developed a method combining the formation of heteroduplexes between 2 distinct splicing variants and S1 nuclease digestion. For 20 consensuses identified here using this methodology, 5 revealed a conserved splice site after inspection of the cDNA alignment against the human genome (exact splice sites). For 8 other consensuses, conserved splice sites were mapped at 2 to 30 bp from the border, called proximal splice sites; for the other 7 consensuses, conserved splice sites were mapped at 40 to 800 bp, called distal splice sites. These latter cases showed a nonspecific activity of S1 nuclease in digesting double-strand DNA. From the 20 consensuses identified here, 5 were selected for reverse transcription-polymerase chain reaction validation, confirming the splice sites. These data showed the potential of the strategy in mapping splice sites. However, the lack of specificity of the S1 nuclease enzyme is a significant obstacle that impedes the use of this strategy in large-scale studies.