Acute increase of alpha-synuclein inhibits synaptic vesicle recycling evoked during intense stimulation

This work was supported by grants from the NIH/National Institute of Neurological Disorder and Stroke RO1 NS078165 (to J.R.M.), the Morton Cure Paralysis Fund (to J.R.M.), and the Branfman Family Foundation (to J.M.G.) and by a Dorothea Bennett graduate fellowship (to D.J.B.)

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Dissolution of quartz, albite, and orthoclase in H2O-saturated haplogranitic melt at 800C and 200 MPa: diffusive transport properties of granitic melts at crustal anatectic conditions.

24 pages, 14 figures, 6 tables.We have conducted experiments on dissolution of quartz, albite, orthoclase, and corundum into H2O-saturated haplogranite melt at 800 C and 200 MPa over a duration of 120–1488 h with the aim of ascertaining the diffusive transport properties of granitic melts at crustal anatectic temperatures. Cylinders of anhydrous starting glass and a single mineral phase (quartz or feldspar) were juxtaposed along flat and polished surfaces inside gold or platinum capsules with 10 wt % added H2O. Concentration profiles in glass (quenched melt) perpendicular to the mineral–glass interfaces and comparison with relevant phase diagrams suggest that melts at the interface are saturated in the dissolving phases after 384 h, and with longer durations the concentration profiles are controlled only by diffusion of components in the melt. The evolution of the concentration profiles with time indicates that uncoupled diffusion in the melt takes place along the following four linearly independent directions in oxide composition space: SiO2, Na2O, and K2O axes (Si-, Na-, and K-eigenvectors, respectively), and a direction between the Al2O3, Na2O, and K2O axes (Al-eigenvector), such that the Al/Na molar ratio is equal to that of the bulk melt and the Al/(Na þ K) molar ratio is equal to the equilibrium ASI (¼ mol. Al2O3/[Na2O þ K2O]) of the melt. Experiments in which a glass cylinder was sandwiched between two mineral cylinders—quartz and albite, quartz and K-feldspar, or albite and corundum—tested the validity of the inferred directions of uncoupled diffusion and explored longrange chemical communication in the melt via chemical potential gradients. The application of available solutions to the diffusion equations for the experimental quartz and feldspar dissolution data provides diffusivities along the directions of the Si-eigenvector and Al-eigenvector of (2 0–2 8) · 10 15 m2/s and (0 6–2 4) · 10 14 m2/s, respectively. Minimum diffusivities of alkalis [ (3–9) · 10 11 m2/s] are orders of magnitude greater than the tetrahedral components of the melt. The information provided here determines the rate at which crustal anatexis can occur when sufficient heat is supplied and diffusion is the only mass transport (mixing) process in the melt. The calculated diffusivities imply that a quartzo-feldspathic source rock with initial grain size of 2–3 mm undergoing hydrostatic, H2O-saturated melting at 800 C (infinite heat supply) could produce 20–30 vol. % of homogeneous melt in less than 1–10 years. Slower diffusion in H2O-undersaturated melts will increase this time frame.Support for this research was provided by National Science Foundation grants EAR-990165, INT-9603199, EAR-9618867, EAR-9625517, EAR-9404658, and a postdoctoral grant to A.A.V. from the Universidad de Granada, Spain. The Electron Microprobe Laboratory at the University of Oklahoma was created with US DOE grant DE-FG22-87FE1146 and upgraded with NSF grant EAR-9404658 and support from the University of Oklahoma Office of Research Administration. We thank Don Baker, Alberto Patin˜o Douce, Dennis Geist and an anonymous referee for thorough reviews that improved greatly the consistency and clarity of the manuscript.Peer reviewe