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  • Mohr Craven posted an update 2 weeks, 5 days ago

    […].Our aim was to determine the prevalence, prognostic and predictive role of germline pathogenic/likely pathogenic variants (P/LPVs) in cancer predisposing genes in patients with pancreatic ductal adenocarcinoma (PDAC). Germline testing of 62 cancer susceptibility genes was performed on unselected patients diagnosed from 02/2003 to 01/2020 with PDAC, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated Centers. The main endpoints were prevalence of P/LPVs and overall survival (OS). P/LPVs in PDAC-associated and homologous recombination repair (HRR) genes were identified in 22 (4.0%) and 42 (7.7%) of 549 patients, respectively. P/LPVs were identified in 16 genes, including ATM (11, 2.0%) and BRCA2 (6, 1.1%), while 19 patients (3.5%) were heterozygotes for MUTYH P/LPVs and 9 (1.6%) carried the low-risk allele, CHEK2 p.(Ile157Thr). Patients carrying P/LPVs had improved OS compared to non-carriers (22.6 vs. 13.9 months, p = 0.006). In multivariate analysis, there was a trend for improved OS in P/LPV carriers (p = 0.063). The interaction term between platinum exposure and mutational status of HRR genes was not significant (p-value = 0.35). A significant proportion of patients with PDAC carries clinically relevant germline P/LPVs, irrespectively of age, family history or disease stage. The predictive role of these P/LPVs has yet to be defined. ClinicalTrials.gov Identifier NCT03982446.The interactions between Drosophila melanogaster and the parasitoid wasps that infect Drosophila species provide an important model for understanding host-parasite relationships. find more Following parasitoid infection, D. melanogaster larvae mount a response in which immune cells (hemocytes) form a capsule around the wasp egg, which then melanizes, leading to death of the parasitoid. Previous studies have found that host hemocyte load; the number of hemocytes available for the encapsulation response; and the production of lamellocytes, an infection induced hemocyte type, are major determinants of host resistance. Parasitoids have evolved various virulence mechanisms to overcome the immune response of the D. melanogaster host, including both active immune suppression by venom proteins and passive immune evasive mechanisms. We identified a previously undescribed parasitoid species, Asobara sp. AsDen, which utilizes an active virulence mechanism to infect D. melanogaster hosts. Asobara sp. AsDen infection inhibits host hemocyte expression of msn, a member of the JNK signaling pathway, which plays a role in lamellocyte production. Asobara sp. AsDen infection restricts the production of lamellocytes as assayed by hemocyte cell morphology and altered msn expression. Our findings suggest that Asobara sp. AsDen infection alters host signaling to suppress immunity.Three different diets were formulated with three levels of metabolizable energy (ME) (optimum; 2900, restricted; 2800 and low; 2700 kcal ME/kg diet) without or with (0 and 0.15%) betaine supplementation in 2 × 3 factorial design to evaluate the effect of six experimental diets on performance, proteins and lipids profiles, bioenergetics, peroxidation and meat quality of Japanese quail. Therefore, 360 quails allocated into six groups in a 23-day experiment. Dietary betaine and ME levels did not affect the performance, meat energy indices (ATP and AMP) and malondialdehyde (MDA) levels of Japanese quail meat. Dietary betaine and/or ME levels induced significant changes in serum triacylglycerol (TAG), total cholesterols (TC), low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), meat total lipids and cholesterol of Japanese quail. Optimum and restricted ME levels reduced total volatile basic nitrogen (TVBN) whereas dietary betaine increased ecosapentaenoic (EPA), docosahexaenoic acids (DHA) and glutamine concentrations in breast meat of Japanese quail. Dietary betaine and low energy diet improved cooking loss, thawing loss (ThL) and water holding capacity (WHC) in breast meat of Japanese quail. Conclusively, dietary betaine improved meat quality of Japanese quail fed diets containing either restricted or low ME by enrichments the meat with omega-3 fatty acids and reduction of lipids levels.The preslaughter stunning of bovine animals is a legal requirement in the European Union, unless the animal is being slaughtered according to religious rite. The legislation also requires the investigation and review of stunning methods in cases of failure to stun. This paper presents the results of one investigation into the possible reasons for multiple stun attempts on an animal that received five shot applications. The head was hard frozen to prevent the deformation of brain structures during splitting along the sagittal plane, and then underwent macroscopic examination to assess the likely causes of the repeated stun attempts. In this case, a pre-existing chronic disease process produced anatomical variations of the cranial cavity, increasing the thickness of the sinuses of the frontal bone to a depth of 9 cm and filling the sinuses with a fibrinous pus deposit. It was therefore concluded that the anatomical variation produced by the chronic disease process, in addition to the energy absorption provided by the thicker hide and fibrinous pus, led to the failure of the stunning equipment to achieve the desired stunned state in the animal. As the animal displayed cranial variation before slaughter, a review of the stunning systems should include a requirement that animals displaying any abnormalities should be stunned with the highest-powered cartridge available or a free bullet.Infusions and poultices prepared from the aerial parts of Baccharis heterophylla Kunth (Asteraceae) are widely used in Oaxaca (Mexico) for relieving painful and inflammatory complaints. Therefore, the antinociceptive potential of an aqueous extract (31.6-316 mg/kg, p.o.) and essential oil (30-177 µg/paw, i.pl.) of the plant was assessed using the formalin test. Both preparations inhibited the formalin-induced nociception response (100-316 mg/kg and 100-177 µg/paw, respectively) during the test’s second phase. Chemical analysis of the aqueous extract revealed that the major active components were chlorogenic acid (1), 3,4-di-O-(E)-caffeoylquinic acid (2), 3,5-di-O-(E)-caffeoylquinic acid (3), 4,5-di-O-(E)-caffeoylquinic acid (4), 3,5-di-O-(E)-caffeoylquinic acid methyl ester (5), apigenin (6), genkwanin (7), acacetin (8). Compounds 1-5 and 8 are new for B. heterophylla. A high-pressure liquid chromatographic method for quantifying chlorogenic acid (1) and di-caffeoylquinic acids 2-4 in the plant was developed and validated.

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