SummaryMiniature neurotransmission is the transsynaptic process where single synaptic vesicles spontaneously released from presynaptic neurons induce miniature postsynaptic potentials. Since their discovery over 60 years ago, miniature events have been found at every chemical synapse studied. However, the in vivo necessity for these small-amplitude events has remained enigmatic. Here, we show that miniature neurotransmission is required for the normal structural maturation of Drosophila glutamatergic synapses in a developmental role that is not shared by evoked neurotransmission. Conversely, we find that increasing miniature events is sufficient to induce synaptic terminal growth. We show that miniature neurotransmission acts locally at terminals to regulate synapse maturation via a Trio guanine nucleotide exchange factor (GEF) and Rac1 GTPase molecular signaling pathway. Our results establish that miniature neurotransmission, a universal but often-overlooked feature of synapses, has unique and essential functions in vivo.

BackgroundAs Staphylococcus aureus (SA) remains one of the leading cause of infective endocarditis (IE), this study evaluates whether S. aureus is associated with more severe infections or worsened outcomes compared to non-S. aureus (NSA) organisms.MethodsAll patients undergoing valve surgery for bacterial IE between 1995 and 2013 at our institution were included in this study (n = 323). Clinical data were retrospectively collected from the chart review. Patients were stratified according to the causative organism; SA (n = 85) and NSA (n = 238). Propensity score matched pairs (n = 64) of SA versus NSA were used in the analysis.ResultsSA patients presented with more severe IE compared to NSA patients, with higher rates of preoperative vascular complications, preoperative septic shock, preoperative embolic events, preoperative stroke, and annular abscess. Among the matched pairs, there were no significant differences in 30-day (9.4% SA vs. 7.8% NSA, OR = 1.20, p = 0.76) or 1-year mortality (20.3% SA vs. 14.1% NSA, OR = 1.57, p = 0.35) groups, though late survival was significantly worse in SA patients. There was also no significant difference in postoperative morbidity between the two matched groups.ConclusionsSA IE is associated with a more severe clinical presentation than IE caused by other organisms. Despite the clearly increased preoperative risk, valvular surgery may benefit SA IE patients by moderating the post-operative mortality and morbidity.

Background Valve surgery for patients presenting with infective endocarditis (IE) complicated by stroke is thought to carry elevated risk of postoperative complications. Our aim is to compare outcomes of IE patients who undergo surgery early after diagnosis of septic cerebral emboli with patients without preoperative emboli. Methods All patients undergoing surgery for left-sided IE between 1996–2013 at our institution were reviewed. Patients undergoing surgery > 14 days after embolic stroke diagnosis (n=11) and those with purely hemorrhagic lesions were excluded from analysis (n=7). In total, 308 were included in the study and stratified according to the presence (STR, n=54) or absence of a preoperative septic cerebral embolus (NoSTR, n=254). Primary outcomes of interest were development of new postoperative stroke and 30-day mortality. Results Mean time to surgical intervention from stroke onset was 6.0 ± 4.1 days. S. aureus (39% STR vs. 21% NoSTR, p = 0.004) and annular abscess at surgery (52% STR vs. 27% NoSTR, p < 0.001) were more prevalent in STR patients. There was no significant difference in 30-day mortality (9.3% STR vs. 7.1% NoSTR, p = 0.57) or rate of new postoperative stroke [5 (9.4%) STR vs. 12 (4.7%) NoSTR, p = 0.19] between groups. Additionally, there was no difference in 10-year survival between groups (log rank p = 0.74). Conclusions Early surgical intervention in patients with IE complicated by preoperative septic cerebral emboli does not lead to significantly worse postoperative outcomes. Early surgery for IE following embolic stroke warrants consideration, particularly in patients with high-risk features such as S. aureus and/or annular abscess.