Ultrasound-assisted lipolysis of the omentum in dwarf pigs.

Successful surgical treatment of medium degree obesity by subcutaneous liposuction has been reported in the literature. In obesity, most adipose tissue is visceral, mainly omental, and the resection of omentum is a mutilating procedure for the intestinal tract. Because of this, we planned to reduce omental adipose tissue by an apparently conservative approach: ultrasound-assisted lipolysis. The purpose of this study was to assess the feasibility and safety of this procedure in an animal experimental model, drawing clinical and autoptic patterns. We chose pigs because they are functionally analogous to humans, although they store less fat in the omentum, whose structure looks like a veil. Four male dwarf pigs were fed, since weaning, with hyperlipidic fodder. When they were eight months old, they were operated on under general anesthesia in our laboratory for experimental surgery. After laparotomy, the omentum was delivered and treated with ultrasound for 1 hour. Before and just after the sonication, biopsies were drawn from omentum and processed for histologic findings. After 50 days, the surviving animals were sacrificed and autopsied; specimens from omentum, liver, and spleen were histologically processed. Two animals died during the operation, while the two surviving animals were in good general condition. Macro and microscopic observations demonstrated that the ultrasound can liquefy omental fat, sparing its fibrous network in the immediate time; during the postoperative period, an intense inflammatory reaction developed; macroscopic observation evidenced fibrous adhesions of the omentum to the surrounding organs; the connective tissue network was thickened and the whole omentum was twisted on itself. The high mortality rate could be due either to the surgical learning curve or to casualty or to lethal effects of ultrasound on the cardiac conductive system; the inflammatory peritoneal reaction could be specifically due to ultrasound or to surgical handling

KRAS and ERBB-family genetic alterations affect response to PD-1 inhibitors in metastatic nonsquamous NSCLC

Background: Programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) inhibitors represent novel therapeutic options for advanced non-small cell lung cancer (NSCLC). However, approximately 50% of patients do not benefit from therapy and experience rapid disease progression. PD-L1 expression is the only approved biomarker of benefit to anti-PD-1/PD-L1 therapy. However, its weakness has been evidenced in many studies. More recently, tumor mutational burden (TMB) has proved to be a suitable biomarker, but its calculation is difficult to obtain for all patients. Methods: We tested specific NSCLC genetic alterations as potential immunotherapy biomarkers. Tumor DNA was obtained from advanced NSCLC patients treated with anti-PD-1 monoclonal antibody nivolumab (n = 44) or pembrolizumab (n = 3). The mutational status of 22 genes was assessed by targeted next-generation sequencing and the association with survival was tested in uni- and multivariate models. The association between gene mutations and clinical benefit was also investigated. Results: The most frequently mutated genes were TP53 (49%), KRAS (43%), ERBB2 (13%), SMAD4 (13%), DDR2 (13%), STK11 (9%), ERBB4 (6%), EGFR (6%), BRAF (6%), and MET (6%). We confirmed that KRASmut patients have a better response to PD-1 inhibitors, showing a longer progression-free survival (PFS) and overall survival (OS) than KRASwt patients. In addition, we observed that patients with ERBB-family mutations, including EGFR, ERBB2, and ERBB4 all failed to respond to PD-1 antibodies, independently of KRAS status. Conclusions: This study suggests that the analysis of KRAS and ERBB-family gene mutational status is valuable when assessing the clinical practice for the selection of NSCLC patients to treat with PD-1 inhibitors

Vacuolar myopathy in a dog resembling human sporadic inclusion body myositis

Sporadic inclusion body myositis (sIBM) is the most common myopathy in people over the age of 50 years. While immune-mediated inflammatory myopathies are well documented in dogs, sIBM has not been described. An 11-year-old dog with chronic and progressive neuromuscular dysfunction was evaluated for evidence of sIBM using current pathologic, immunohistochemical and electron microscopic diagnostic criteria. Vacuoles and congophilic intracellular inclusions were identified in cryostat sections of multiple muscle biopsies and immunostained with antibodies against amyloid-β peptide, amyloid-β precursor protein, and proteosome 20S of the ubiquitin–proteosome system. Cellular infiltration and increased expression of MHC Class I antigen were observed. Cytoplasmic filamentous inclusions, membranous structures, and myeloid bodies were identified ultrastructurally. These observations constitute the first evidence that both the inflammatory and degenerative features of human sIBM can occur in a non-human species

Some food toxic for pets

According to world statistics, dogs and cats are the species that owners most frequently seek assistance with potential poisonings, accounting 95–98% of all reported animal cases. Exposures occur more commonly in the summer and in December that is associated with the holiday season. The majority (>90%) of animal poisonings are accidental and acute in nature and occur near or at the animal owner's home. Feeding human foodstuff to pets may also prove dangerous for their health

Precipitation drives global variation in natural selection

Climate change has the potential to affect the ecology and evolution of every species on Earth. Although the ecological consequences of climate change are increasingly well documented, the effects of climate on the key evolutionary process driving adaptation - natural selection - are largely unknown. We report that aspects of precipitation and potential evapotranspiration, along with the North Atlantic Oscillation, predicted variation in selection across plant and animal populations throughout many terrestrial biomes, whereas temperature explained little variation. By showing that selection was influenced by climate variation, our results indicate that climate change may cause widespread alterations in selection regimes, potentially shifting evolutionary trajectories at a global scale

A comparison of different district integration for a distributed generation system for heating and cooling in an urban area

The paper proposes a comparison of different district integration options for a distributed generation system for heating and cooling in an urban area. The system considered includes several production units located close to the users, a central unit and the district heating and cooling network which can connect all the users to each other and to a central unit, where a cogeneration system and a solar plant can be placed. Thus, each user can be regarded as isolated from the others, satisfying its energy needs by means of an autonomous production unit. Alternatively, it can be connected to the others through the district heating and cooling network. When a district heating and cooling network is included in the design option the synthesis-design and operation problems cannot be solved separately, because the energy to be produced by each production site is not known in advance, as the flows through the district heating and cooling network are not defined. This paper uses a mixed integer linear programming (MILP) methodology for the multi-objective optimization of the distributed generation energy system, considering the total annual cost for owning, operating and maintaining the whole system as the economic objective function, while the total annual CO2 emissions as the environmental objective function. The energy system is optimized for different district integration option, in order to understand how they affect the optimal solutions compared with both the environmental and economic objects