Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila.

Adenosine (Ado) is an important signaling molecule involved in stress responses. Studies in mammalian models have shown that Ado regulates signaling mechanisms involved in "danger-sensing" and tissue-protection. Yet, little is known about the role of Ado signaling in Drosophila. In the present study, we observed lower extracellular Ado concentration and suppressed expression of Ado transporters in flies expressing mutant huntingtin protein (mHTT). We altered Ado signaling using genetic tools and found that the overexpression of Ado metabolic enzymes, as well as the suppression of Ado receptor (AdoR) and transporters (ENTs), were able to minimize mHTT-induced mortality. We also identified the downstream targets of the AdoR pathway, the modifier of mdg4 (Mod(mdg4)) and heat-shock protein 70 (Hsp70), which modulated the formation of mHTT aggregates. Finally, we showed that a decrease in Ado signaling affects other Drosophila stress reactions, including paraquat and heat-shock treatments. Our study provides important insights into how Ado regulates stress responses in Drosophila.

Patient Satisfaction and Clinical Complications after Endoscopic or Surgical Saphenous Vein Harvesting.

BACKGROUND: Endoscopic saphenous vein harvesting (EVH) for coronary artery bypass grafting (CABG) has been developed to reduce leg wound problems. This study was undertaken to evaluate postoperative complications and patient's subjective satisfaction comparing EVH and surgical vein harvesting (SVH). METHODS: From January to December 2017, patients undergoing elective cardiac surgery (CABG, CABG + Valve repair or replacement) underwent saphenous vein graft harvesting either by EVH (n = 136) or SVH (n = 104). Clinical follow-up was scheduled for day 7 and > 45 days after surgery. Primary end points were divided into two subgroups. The first one included postoperative extent of subjective pain and satisfaction with the cosmetic results described by the patients themselves, while the second subgroup included objective postoperative complications including wound healing disturbances, hematoma, and neuropathy. Secondary end point was length of hospital stay. RESULTS: At 7 days follow-up, EVH patients were more satisfied with the cosmetic results than those of the SVH group (p < 0.001) and expressed a significant tendency toward lower subjective pain compared with the SVH patients (p < 0.001), exhibited significantly lower cellulitis (p-0.002), neuropathy (p-0.005), and superficial wound healing disturbance (p-0.007). During further follow-up at > 45 days, patients with EVH were still more satisfied with the cosmetic results (p < 0.001) and expressed lower subjective pain (p < 0.001), while the other objective wound parameters did not show significant differences between both groups. Mean length of hospital stay of EVH patients was 0.7 days less compared with SVH patients. CONCLUSIONS: Our findings demonstrate the noninferiority of EVH in the short term and in the early medium term.

Endocarditis: An Ever Increasing Problem in Cardiac Surgery.

BACKGROUND: Endocarditis remains one of the most threatening diagnoses in cardiac surgery and is still increasing. Particularly, device-related as well as prosthetic endocarditis appears to be on the rise. Early mortality and periprocedural complications are high jeopardizing the success of surgical efforts. We looked at the development of the numbers and the distribution of endocarditis in an all-comer analysis. METHODS: From 2003 to 2017, 752 patients with endocarditis were transferred to our cardiosurgical institution (mean age 65 ± 13 years; mean logistic EuroSCORE 28.01%; males 74.33%). A total of 89.49% of them were surgically treated; 30.01% redo cases thereof; and 9.17% had been operated previously for acute endocarditis. RESULTS: While the total number of cardiosurgical procedures remained relatively stable throughout the years, 20 patients were admitted in 2003 and 79 in 2017 yielding more than fourfold increase (p < 0.001). Early mortality of all patients was 25.1%. Septic emboli occurred in 23.7% and 43.8% cerebral emboli thereof. A significant increase of aortic, mitral, and tricuspid valves involvement was observed (p < 0.001). An increase of device-related endocarditis was also noted (p < 0.001). CONCLUSION: Endocarditis remains a serious problem with high early mortality and morbidity. The vast increase of electrophysiological device implantations has resulted in an increase of tricuspid valve involvement. Liberalization of endocarditis prophylaxis, that is, more restrictive use of antibiotics in 2007 may have at least partially contributed to an increase of the individual risk to suffer from acute endocarditis. A renaissance of a stricter endocarditis-prophylaxis may thus be considered.

Nonmammalian Models of Huntington's Disease.

Flies, worms, yeast and more recently zebra fish have all been engineered to express expanded polyglutamine repeat versions of Huntingtin with various resulting pathologies including early death, neurodegeneration, and loss of motor function. Each of these models present particular features that make it useful in studying the mechanisms of polyglutamine pathology. However, one particular unbiased readout of mHTT pathology is functional loss of motor control. Loss of motor control is prominent in patients, but it remains unresolved whether pathogenic symptoms in patients result from overt degeneration and loss of neurons or from malfunctioning of surviving neurons as the pathogenic insult builds up. This is why a functional assay such as motor control can be uniquely powerful in revealing early as well as late neurological deficits and does not rely on assumptions such as that the level of inclusions or the degree of neuronal loss can be equated with the level of pathology. Drosophila is well suited for such assays because it contains a functioning nervous system with many parallels to the human condition. In addition, the ability to readily express mHTT transgenes in different tissues and subsets of neurons allows one the possibility of isolating a particular effect to a subset of neurons where one can correlate subcellular events in response to mHTT challenge with pathology at both the cellular and organismal levels. Here we describe methods to monitor the degree of motor function disruption in Drosophila models of HD and we include a brief summary of other nonmammalian models of HD and discussion of their unique strengths.