Kinin B1 receptor gene ablation affects hypothalamic CART production

A role for the kinin B1 receptor in energy-homeostatic processes was implicated by previous works. Notably the studies where kinin B1 receptor knockout mice (B1-/-) are observed to have impaired adiposity, impaired leptin and insulin production, lower feed efficiency, protection from liver steatosis and diet induced obesity when fed a high fat diet (HFD). More particularly, in a model where the B1 receptor is expressed exclusively in the adipose tissue, it rescues the plasma insulin concentration and the weight gain seen in wild type mice. Taking into consideration that leptin participates in the formation of hypothalamic nuclei, which modulate energy expenditure, and feeding behavior, we hypothesized that these brain regions could also be altered in B1-/- mice. We observed for the first time a difference in the gene expression pattern of CART (cocaine-and-amphetamine related transcript) in the LHA (lateral hypothalamic area) resulting from the deletion of the kinin B1 receptor gene. The correlation between CART expression in the LHA and the thwarting of diet-induced obesity corroborates independent correlations between CART and obesity. Further it seems to indicate that the mechanism underlying the 'lean' phenotype of B1-/- mice is not solely stemming from changes in peripheral tissues but may also receive contributions from changes in the hypothalamic machinery involved in energy homeostasis processes

Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial

Background Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. Methods In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. Findings Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. Interpretation Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations

Atratividade de diferentes iscas e sua relação com as fases de desenvolvimento ovariano em calliphoridae e sarcophagidae (insecta, diptera) Attractiveness of differents baits and its relation with ovarian development fases in Calliphoridae ano Sarcophagidae (Insecta, Diptera)

<abstract language="eng">Attrativeness of differents baits (fish, faeces and banana) upon ovarian development fases of Calliphoridae and Sarcophagidae was evaluated. The insects were captured in Distrito Federal (urban area) and Rio de Janeiro city (beach, zoological garden, urban area and Tijuca forest). The most frequent species captured were: Calliphoridae - Chrysomya megacephala (Fabricius, 1794) 78,9% and Chtysomya puloria (Wiedemann, 1818) 5,4% - and Sarcophagidae - Sarcophagula Wulp, 1887 2,3% and Peckya chrysostoma (Wiedemann. 1830) 2,2%. Fish was more attractive to females of Calliphoridae flies in intense ovarian vitelogenesis, although banana atracted more flies with mature eggs. Faeces and fish were more atractive for Sarcophagidae in the beggining of vitelogenesis

Muscoid Diptera and their parasitoids collected from fish bait in Itumbiara, Goiás Dípteros muscóides e seus parasitóides coletados em isca de peixe em Itumbiara

<abstract language="por">Determinaram-se as espécies de parasitóides associados às moscas sinantrópicas coletados em iscas de peixe, em Itumbiara, Goiás. As pupas, obtidas pelo método de flutuação, foram individualizadas em cápsulas de gelatina até a emergência das moscas adultas ou de seus parasitóides. A porcentagem total de parasitismo foi 21,4%