First report on classical biological control releases of the larval parasitoid Ganaspis brasiliensis against Drosophila suzukii in northern Italy

Current management strategy of the invasive fruit fly Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) exploits different tools but relies mainly on chemical control. In the invaded areas, the local natural enemy community mostly consists of generalist pupal parasitoids unable to control the pest efficiently. Conversely, in the pest native area, there are more specialized sympatric larval parasitoids attacking D. suzukii. Following foreign explorations and quarantine risk assessments, the larval endoparasitoid Ganaspis brasiliensis (Ihering) (Hymenoptera: Figitidae) was selected as the best candidate for classical biological control programs. In 2021, the first ever propagative biocontrol program using a Japanese G1 lineage of G. brasiliensis started in Italy. Here we report the results of the first year of releases in the province of Trento (Northeast Italy), wherein G. brasiliensis was released in 12 locations. Pre- and post-release samplings on fresh and fallen fruits were performed around the release points to assess the recapture rate, the impact of the exotic parasitoid on D. suzukii and its potential interactions with local non-target species. After releases, G. brasiliensis was recovered at 50% of the locations. The exotic parasitoid only emerged from D. suzukii, mostly from fresh fruit still on the plant. Post-overwintering monitoring revealed the presence of a four G. brasiliensis individuals at two release locations

Individuals with prediabetes identified by HbA1c undergoing coronary angiography have worse cardiometabolic profile than those identified by fasting glucose

Background: Type 2 diabetes mellitus has well known deleterious effects on coronary artery disease (CAD). the role of milder hyperglycemic states such as prediabetes (PD) on CAD is debatable. Glycated hemoglobin (HbA1c) has recently been advocated as a diagnostic tool for diabetes mellitus (DM) and PD. This study aims to assess the cardiometabolic risk profile and coronary lesions of patients with PD undergoing coronary angiography identified either by fasting plasma glucose (FPG) or HbA1c levels.Methods: We studied 514 individuals without previously known glucose disturbances. Their glycemic status was assessed by FPG and HbA1c (HPLC) and classified according to ADA guidelines, using each parameter independently, as having normal glucose tolerance (N), PD, or DM. CAD was defined as stenosis greater than 50% in one major coronary vessel or branch. Framingham score was calculated.Results: Subjects with PD had a similar frequency of CAD compared do N individuals by both FPG (61 vs. 59.3%) and HbA1c (55.4 vs 61.2%) (p non-significant for linear-by-linear association). PD individuals identified by FPG had worse HOMA2B (mean [95% CI] 65.4 [60.9-69.9] vs. 76.6 [71.4-81.9]) and HOMA2-IR (1.10 [0.98-1.22] vs. 0.80 [0.72-0.89]) when compared to N controls. PD individuals identified by HbA1c had higher frequency of Framingham risk above 20% (25.4 vs 11.8%), arterial hypertension (87.8 vs 72.6%), and dyslipidemia (83.8 vs 72%) compared to N individuals. PD associated with an increased number of coronary lesions only when diagnosed by HbA1c (median [interquartile interval] 2 [0-4] PD versus 1 [0-3.75] N, p = 0.03 for trend).Conclusions: HbA1c was more effective than FPG in identifying individuals with PD associated with high cardiovascular risk profile in a sample of individuals undergoing coronary angiography.Universidade Federal de São Paulo, Endocrinol Unit, Diabet Ctr, São Paulo, BrazilUniv Estado Bahia, Dept Ciencias Vida, Colegiado Med, BR-41150000 Salvador, BA, BrazilCtr Endocrinol Estado Bahia CEDEBA, Salvador, BA, BrazilUniversidade Federal de São Paulo, Endocrinol Unit, Diabet Ctr, São Paulo, BrazilWeb of Scienc

Association of classical risk factors and coronary artery disease in type 2 diabetic patients submitted to coronary angiography

Background: Coronary artery disease (CAD) is the leading cause of death among individuals with type 2 diabetes (T2DM). T2DM accelerates atherosclerosis alongside classical risk factors such as dyslipidemia and hypertension. This study aims to investigate the association of hyperglycemia and associated risk factors with CAD in outpatients with T2DM undergoing coronary angiography.Methods: 818 individuals referred to coronary angiography were evaluated for glucose disturbances. After exclusion of those with prediabetes, 347 individuals with T2DM and 94 normoglycemic controls were studied for BMI, blood pressure, fasting plasma glucose, HbA1c, lipids, HOMA, adiponectin, Framingham risk score, number of clinically significant coronary lesions (stenosis > 50%).Results: Among T2DM subjects, those with CAD (n = 237) had worse glycemic control (fasting glucose 162.3 + 69.8 vs. 143.4 + 48.9 mg/dL, p = 0.004; HbA1c 8.03 + 1.91 vs. 7.59 + 1.55%, p = 0.03), lower HDL (39.2 + 13.2 vs. 44.4 + 15.9 mg/dL, p = 0.003), and higher triglycerides (140 [106-204] vs. 121 [78.5-184.25] mg/dL, p = 0.002), reached more often therapeutic goals for LDL (63.4% vs. 51.4%, p = 0.037) and less often goals for HDL (26.6% vs. 37.3%, p = 0.04), when compared to CAD-free individuals (n = 110). the same differences were not seen in normoglycemic controls. in T2DM subjects HbA1c tertiles were associated with progressively higher number of significant coronary lesions (median number of lesions 2 [A1c 8.2%]; p = 0.01 for trend).Conclusions: Classic risk factors such as glycemic control and lipid profile were associated with presence of CAD in T2DM subjects undergoing coronary angiography. Glycemic control is progressively associated with number and extent of coronary lesions in patients with T2DM.Universidade Federal de São Paulo UNIFESP, Escola Paulista Med, Ctr Diabet, BR-04039002 São Paulo, BrazilCEDEBA, BR-41820000 Salvador, BA, BrazilUniversidade Federal de São Paulo UNIFESP, Escola Paulista Med, Ctr Diabet, BR-04039002 São Paulo, BrazilWeb of Scienc

Analysis of the BRAF V600E mutation in primary cutaneous melanoma

ABSTRACT. BRAF V600E is the most common mutation in cutaneous melanomas, and has been described in 30-72% of such cases. This mutation results in the substitution of valine for glutamic acid at position 600 of the BRAF protein, which consequently becomes constitutively activated. The present study investigated the BRAF V600E mutation frequency and its clinical implications in a group of 77 primary cutaneous melanoma patients treated in a cancer reference center in Brazil. Mutation analysis 2841 BRAF V600E mutation of primary cutaneous melanomas in Brazil ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (2): 2840-2848 (2014) was accomplished by polymerase chain reaction, restriction fragment length polymorphism, and automated DNA sequencing. The chi-squared and Fischer exact tests were used for comparative analyses. The BRAF V600E mutation was detected in 54/77 (70.1%) melanoma subjects. However, no statistically significant association was found between the presence of the mutation and clinical or prognostic parameters. Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors

Broadening the phenotype of TARDBP mutations: the TARDBP Ala382Thr mutation and Parkinson’s disease in Sardinia

Mutations in the TARDBP gene are a cause of autosomal dominant amyotrophic lateral sclerosis (ALS) and of frontotemporal lobar degeneration (FTLD), but they have not been found so far in patients with Parkinson’s disease (PD). A founder TARDBP mutation (p.Ala382Thr) was recently identified as the cause of ~30% of ALS cases in Sardinia, a Mediterranean genetic isolate. We studied 327 consecutive Sardinian patients with clinically diagnosed PD (88 familial, 239 sporadic) and 578 Sardinian controls. One family with FTLD and parkinsonism was also included. The p.Ala382Thr heterozygous mutation was detected in eight unrelated PD patients (2.5%). The three patients from the FTLD/parkinsonism family also carried this mutation. Within the control group, there were three heterozygous mutation carriers. During follow-up, one of these individuals developed motoneuron disease and another, a rapidly progressive dementia; the third remains healthy at the age of 79 but two close relatives developed motoneuron disease and dementia. The eight PD patients carrying the p.Ala382Thr mutation had all sporadic disease presentation. Their average onset age was 70.0 years (SD 9.4, range 51–79), which is later but not significantly different from that of the patients who did not carry this mutation. In conclusion, we expand the clinical spectrum associated with TARDBP mutations to FTLD with parkinsonism without motoneuron disease and to clinically definite PD. The TDP-43 protein might be directly involved in a broader neurodegenerative spectrum, including not only motoneuron disease and FTLD but also PD

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

Background and purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. Results Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. Conclusions The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation

Genomic and biological study of fusion genes as resistance mechanisms to EGFR inhibitors

The clinical significance of gene fusions detected by DNA-based next generation sequencing remains unclear as resistance mechanisms to EGFR tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer. By studying EGFR inhibitor-resistant patients treated with a combination of an EGFR inhibitor and a drug targeting the putative resistance-causing fusion oncogene, we identify patients who benefit and those who do not from this treatment approach. Through evaluation including RNA-seq of potential drug resistance-imparting fusion oncogenes in 504 patients with EGFR mutant lung cancer, we identify only a minority of them as functional, potentially capable of imparting EGFR inhibitor resistance. We further functionally validate fusion oncogenes in vitro using CRISPR-based editing of EGFR mutant cell lines and use these models to identify known and unknown drug resistance mechanisms to combination therapies. Collectively, our results partially reveal the complex nature of fusion oncogenes as potential drug resistance mechanisms and highlight approaches that can be undertaken to determine their functional significance.</p

Action to protect the independence and integrity of global health research

Storeng KT, Abimbola S, Balabanova D, et al. Action to protect the independence and integrity of global health research. BMJ GLOBAL HEALTH. 2019;4(3): e001746

Intermediate Rotterdam: Urban regeneration in time of crisis

The thesis is developed around the concept of the “intermediate city”. In fact, during this precarious phase set by the economical crisis and worsened by the shrinking condition of the city, it is necessary for Rotterdam to work in an “intermediate dimension” in several terms: of scale, time, financing and also location, focussing more on those parts of the city that have been neglected for a long time, in favour of concentrated interventions in the downtown and in the suburban edges, thus addressing limited targets of population. Two complementary strategies, based on the same principles but with different processes and hypothesis, are proposed in order to depict an alternative model of urban regeneration as a basis for a more sustainable development.European Postgraduate Masters in UrbanismUrbanismArchitectur