Polypeptide aggregation into amyloid is linked with several debilitating human diseases. Despite the inherent risk of aggregation-induced cytotoxicity, bacteria control the export of amyloid-prone subunits and assemble adhesive amyloid fibres during biofilm formation. An Escherichia protein, CsgC potently inhibits amyloid formation of curli amyloid proteins. Here we unlock its mechanism of action, and show that CsgC strongly inhibits primary nucleation via electrostatically-guided molecular encounters, which expands the conformational distribution of disordered curli subunits. This delays the formation of higher order intermediates and maintains amyloidogenic subunits in a secretion-competent form. New structural insight also reveal that CsgC is part of diverse family of bacterial amyloid inhibitors. Curli assembly is therefore not only arrested in the periplasm, but the preservation of conformational flexibility also enables efficient secretion to the cell surface. Understanding how bacteria safely handle amyloidogenic polypeptides contribute towards efforts to control aggregation in disease-causing amyloids and amyloid-based biotechnological applications.

Histopathology of tissue samples is used to determine the progression of cancer usually by staining and visual analysis. It is recognised that disease progression from healthy tissue to cancerous is accompanied by spectral signature changes in the infrared range. In this work, FTIR spectroscopic imaging in transmission using a focal plane array (96 x 96 pixels) has been applied to the characterisation of Barrett's esophageal adenocarcinoma. Spectral images were acquired in transmission mode. To correct optical aberrations, infrared transparent lenses were used of the same material as the slide on which biopsies were fixed. The lenses acted as an immersion objective, reducing scattering and improving spatial resolution.A novel mapping approach is presented where spectral images obtained with added lens are stitched together such that the dataset contained a representative section of the esophageal tissue. Images were also acquired in transmission mode using high-magnification optics for enhanced spatial resolution, and were also acquired using a germanium micro-ATR objective for comparison. The reduction of scattering was assessed using k-means clustering. The same tissue section map, which contained a region of high grade dysplasia was analysed using hierarchical clustering analysis. A reduction of the trough at 1077 cm -1 in the second derivative spectra was identified as an indicator of high grade dysplasia.In addition, the spatial resolution obtained with the added lens using high-magnification optics was assessed by measurements of a sharp interface of polymer laminate, which was also compared with the spatial resolution achieved in micro ATR-FTIR imaging. The resolution was determined from the change in absorbance of spectral bands from one side of the polymer interface to the other. In transmission mode using the lens, it was determined to be 12 µm and using micro-ATR, the resolution was 3 µm for the band at ca. 6 µm The spatial resolution was also assessed with and without the added lens, in normal and high-magnification mode using a USAF target.Spectroscopic images of cells in transmission using two lenses are also presented, which are necessary for correcting chromatic aberration and refraction in both the condenser and objective. The use of lenses is shown to be necessary in obtaining high-quality spectroscopic images of cells in transmission mode and proves the applicability of the pseudo hemisphere approach for this and other microfluidic systems.2

An application of disrelation mapping to Fourier transform infrared (FT-IR) spectroscopic imaging datasets is provided to reveal different H-bonded water species within a mammalian cell. 2D correlation analysis revealed a disrelation peak at (3420 cm, 3220 cm), showing the existence of a specific water band at around 3220 cm whose variation of absorbance did not follow the trend of water molecules with a well-coordinated H-bonding network. Disrelation maps constructed with disrelation intensities between (3420 cm, 3220 cm) and (3420 cm, 1540 cm) reveal that the disruption of the water network occurs around the interfacial regions between the cell and media, indicating the disintegration of the H-bonding network of bulk water due to the entrapment of water by the protein inside the cell. This hydration effect also becomes apparent around the area adjacent to the cellular nucleus, reflecting the fact that protein synthesis mainly occurs in this region. These results clearly show the presence of different molecular states of water inside living cells, which are not readily identified by conventional analysis methods.

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.

Objective: The primary objective of this systematic review and meta-analysis was to elucidate the rate of venous thromboembolism (VTE) after endovenous interventions for varicose veins in the presence of pharmacological and mechanical thromboprophylaxis versus mechanical thromboprophylaxis alone. Background: The VTE rate after endovenous procedures for varicose veins is higher than other day-case procedures and could be reduced with pharmacological thromboprophylaxis. Methods: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines with a registered protocol (PROSPERO: CRD42021274963). Studies of endovenous intervention for superficial venous incompetence reporting the predefined outcomes with at least 30 patients were eligible. Data were pooled with a fixed effects model. Results: There were 221 trials included in the review (47 randomized trial arms, 105 prospective cohort studies, and 69 retrospective studies). In randomized trial arms, the rate of deep venous thrombosis with additional pharmacological thromboprophylaxis was 0.52% (95% CI, 0.23%–1.19%) (9 studies, 1095 patients, 2 events) versus 2.26% (95% CI, 1.81%–2.82%) (38 studies, 6951 patients, 69 events) with mechanical thromboprophylaxis alone. The rate of pulmonary embolism in randomized trial arms with additional pharmacological thromboprophylaxis was 0.45% (95% CI, 0.09–2.35) (5 studies, 460 participants, 1 event) versus 0.23% (95% CI, 0.1%–0.52%) (28 studies, 4834 participants, 3 events) for mechanical measures alone. The rate of EHIT grade III to IV was 0.35% (95% CI, 0.09–1.40) versus 0.88% (95% CI, 0.28%–2.70%). There was 1 VTE-related mortality and 1 instance of major bleeding, with low rates of minor bleeding. Conclusions: There is a significant reduction in the rate of DVT with additional pharmacological thromboprophylaxis and routine prescription of anticoagulation after endovenous varicose vein intervention should be considered. VTE risk for individual study participants is heterogeneous and risk stratification in future randomized interventional studies is critical to establish the clinical effectiveness and safety of additional pharmacological thromboprophylaxis.