A human septin octamer complex sensitive to membrane curvature drives membrane deformation with a specific mesh-like organization.

Septins are cytoskeletal proteins interacting with the inner plasma membrane and other cytoskeletal partners. Being key in membrane remodeling processes, they often localize at specific micrometric curvatures. To analyze the behavior of human septins at the membrane and decouple their role from other partners, we used a combination of bottom-up in vitro methods. We assayed their ultrastructural organization, their curvature sensitivity, as well as their role in membrane reshaping. On membranes, human septins organize into a two-layered mesh of orthogonal filaments, instead of generating parallel sheets of filaments observed for budding yeast septins. This peculiar mesh organization is sensitive to micrometric curvature and drives membrane reshaping as well. The observed membrane deformations together with the filamentous organization are recapitulated in a coarse-grained computed simulation to understand their mechanisms. Our results highlight the specific organization and behavior of animal septins at the membrane as opposed to those of fungal proteins.

Diagnostic Performance of Positron Emission Tomography with Fibroblast-Activating Protein Inhibitors in Gastric Cancer: A Systematic Review and Meta-Analysis.

Various papers have introduced the use of positron emission tomography (PET) with [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitor (FAPi) radiopharmaceuticals in different subtypes of gastric cancer (GC). Our aim was to assess the diagnostic performance of this novel molecular imaging technique in GC with a systematic review and meta-analysis. A straightforward literature search of papers concerning the diagnostic performance of FAP-targeted PET imaging was performed. Original articles evaluating this novel molecular imaging examination in both newly diagnosed GC patients and GC patients with disease relapse were included. The systematic review included nine original studies, and eight of them were also eligible for meta-analysis. The quantitative synthesis provided pooled detection rates of 95% and 97% for the assessment of primary tumor and distant metastases, respectively, and a pooled sensitivity and specificity of 74% and 89%, respectively, for regional lymph node metastases. Significant statistical heterogeneity among the included studies was found only in the analysis of the primary tumor detection rate (I2 = 64%). Conclusions: Beyond the limitations of this systematic review and meta-analysis (i.e., all the included studies were conducted in Asia, and using [18F]FDG PET/CT as a comparator of the index test), the quantitative data provided demonstrate the promising diagnostic performance of FAP-targeted PET imaging in GC. Nevertheless, more prospective multicentric studies are needed to confirm the excellent performances of FAP-targeted PET in this cluster of patients.

Interaction of Bacteria, Immune Cells, and Surface Topography in Periprosthetic Joint Infections.

The incidence of periprosthetic joint infections (PJIs) is ~2% of total procedures and it is expected to rise due to an ageing population. Despite the large burden PJI has on both the individual and society, the immune response to the most commonly isolated pathogens, i.e., Staphylococcus aureus and Staphylococcus epidermidis, remains incompletely understood. In this work, we integrate the analysis of synovial fluids from patients undergoing hip and knee replacement surgery with in-vitro experimental data obtained using a newly developed platform, mimicking the environment of periprosthetic implants. We found that the presence of an implant, even in patients undergoing aseptic revisions, is sufficient to induce an immune response, which is significantly different between septic and aseptic revisions. This difference is confirmed by the presence of pro- and anti-inflammatory cytokines in synovial fluids. Moreover, we discovered that the immune response is also dependent on the type of bacteria and the topography of the implant surface. While S. epidermidis seems to be able to hide better from the attack of the immune system when cultured on rough surfaces (indicative of uncemented prostheses), S. aureus reacts differently depending on the contact surface it is exposed to. The experiments we performed in-vitro also showed a higher biofilm formation on rough surfaces compared to flat ones for both species, suggesting that the topography of the implant could influence both biofilm formation and the consequent immune response.

Stress Analysis and Q-Factor of Free-Standing (La,Sr)MnO3 Oxide Resonators.

High-sensitivity nanomechanical sensors are mostly based on silicon technology and related materials. The use of functional materials, such as complex oxides having strong interplay between structural, electronic, and magnetic properties, may open possibilities for developing new mechanical transduction schemes and for further enhancement of the device performances. The integration of these materials into micro/nano-electro-mechanical systems (MEMS/NEMS) is still at its very beginning and critical basic aspects related to the stress state and the quality factors of mechanical resonators made from epitaxial oxide thin films need to be investigated. Here, suspended micro-bridges are realized from single-crystal thin films of (La0.7 ,Sr0.3 )MnO3 (LSMO), a prototypical complex oxide showing ferromagnetic ground state at room temperature. These devices are characterized in terms of resonance frequency, stress state, and Q-factor. LSMO resonators are highly stressed, with a maximum value of ≈260 MPa. The temperature dependence of their mechanical resonance is discussed considering both thermal strain and the temperature-dependent Young's modulus. The measured Q-factors reach few tens of thousands at room temperature, with indications of further improvements by optimizing the fabrication protocols. These results demonstrate that complex oxides are suitable to realize high Q-factor mechanical resonators, paving the way toward the development of full-oxide MEMS/NEMS sensors.

Ripple Patterns Spontaneously Emerge through Sequential Wrinkling Interference in Polymer Bilayers.

We report the formation of "ripple" patterns by the sequential superposition of nonorthogonal surface waves excited by the spontaneous buckling of polymeric bilayers. Albeit of a different nature and micron scale compared to the familiar sedimentary ripples caused by gentle wave oscillations, we find commonalities in their topography, defects, and bifurcations. The patterns are rationalized in terms of a defect density that depends on the relative angle between generations, and a constant in-plane bending angle that depends on skin thickness. A minimal wave summation model enables the design of ripple and checkerboard surfaces by tuning material properties and fabrication process.

Phase behaviour of model triglyceride ternary blends: triolein, tripalmitin and tristearin.

We investigate the phase behavior of model ternary triacylglycerol blends, comprising triolein (C57H104O6, OOO), tripalmitin (C51H98O6, PPP) and tristearin (C57H110O6, SSS), building upon extensive characterisation of single and binary mixtures, in order to rigorously map the thermal transitions of model natural 'fats'. A combination of calorimetry, X-ray diffraction, and FTIR spectroscopy is employed to determine crystallisation and melting temperatures and identify the corresponding phases in the complex ternary system. We recover the eutectic behaviour of SSS-PPP blends and the invariability of OOO neat transitions, and resolve the complex ß' + ß ternary surface, reflecting the roles of unsaturation and polymorphism of its constituents. Our results provide a representation of the OOO:PPP:SSS:temperature phase behaviour into a triangular prism, consistent with binary pair-wise data, which can inform a range of food science, cosmetic, pharmaceutical and cleaning applications that depend strongly on the physical-chemistry of such multicomponent 'triglycerides'.

Planar Nanoactuators Based on VO2 Phase Transition.

Actuation at micro- and nanoscale often requires large displacements and applied forces. The high work energy density that lies inside many phase transitions is an appealing feature for developing new actuating schemes, especially if the transition is reversible and scalable into small actuating domains. Here, we show the fabrication of a planar nanomechanical actuator having chevron-type geometry and based on the phase transition of VO2. This device is thermally activated through heating just above room temperature to trigger the VO2 crystalline symmetry change associated with the metal-insulator transition. The large lattice expansion of VO2 phase transition, compared to standard materials, is further amplified by the chevron-type geometry. DC and AC operation of the device are discussed.

Robotic Treatment for Large Duodenal Gastrointestinal Stromal Tumor.

BACKGROUND: Duodenal gastrointestinal stromal tumors (D-GISTs) represent a rare entity.1 Surgery is the primary treatment choice for localized or potentially resectable D-GISTs. The main principle is the complete excision of the lesion with microscopically negative margins, without performing lymph node dissection.2 Nevertheless, the best surgical choice is still controversial since the strategy depends not only on the tumor size but also on its anatomic location.3,4 As a result, surgical management ranges from a major resection such as pancreaticoduodenectomy to more conservative procedures.5-8 This video presents a duodenal sparing robotic resection of a large GIST of the second-third duodenal portion. METHODS: A 49-year-old healthy female complained episodes of melena. Endoscopy with endoscopic ultrasound identified a 6-cm lesion of the second-third portion of the duodenum with recent bleeding, arising from muscolaris propria. A computed tomography scan confirmed a large mass suspected to be a GIST without metastases or involvement of the ampulla of Vater. On the basis of these findings, after a multidisciplinary consultation, she was offered robotic surgery with a radical intent. RESULTS: A duodenal-sparing da Vinci®Si™ resection with robot-sewn primary duodenal closure was performed. After an uneventful postoperative course, the patient was discharged on post-operative day 7. Final pathology revealed a high-grade risk D-GIST with free margins: adjuvant Imatinib was recommended.9 At 4 years follow-up, no recurrence has been detected. CONCLUSIONS: A robotic approach might be considered in cases of large D-GISTs amenable to a conservative R0 surgery. This system provides several technical advantages that facilitate otherwise complex resection and reconstruction.10.

Orthogonal wave superposition of wrinkled, plasma-oxidised, polydimethylsiloxane surfaces.

We report a versatile approach to generate 2D dual-frequency patterns on soft substrates by superposition of 1D single-frequency wrinkles. Wave superposition is achieved by applying sequential orthogonal strains to elastomeric coupons, as opposed to the application of a (simultaneous) biaxial strain field. First, a 1D wrinkling pattern is induced by the well-known mechanical instability of a bilayer formed by oxygen plasma-oxidation of a (pre-strained) polydimethylsiloxane elastomer. The wrinkled surface formed upon strain release is then replicated to obtain a stress-free substrate, and stretched in the direction perpendicular to the first generation. Subsequent plasma exposure and mechanical relaxation (with independent process parameters) yield a prescribed second-generation wrinkling, whose profile and dependence on the first generation we examine in detail. By independently varying plasma oxidation and strain parameters in both directions, we demonstrate the formation of a wide array of topographies, including arrays of symmetric 2D checkerboard patterns with exceptional area coverage with respect to those formed by simultaneous 2D wrinkling. While the resulting topographies cannot be explained in terms of a simple orthogonal wave superposition, we show that, by accounting for the orthogonal prestrain experienced by the first wrinkling generation, the resulting 2D patterns can be readily calculated from 1D wrinkling behaviour.

Macrophages on the wrinkle: Exploring microscale interactions with substrate topography.

Macrophages play pivotal roles in the immune response, participating in both inflammatory and pro-healing processes. Like other cells, macrophages continually survey their microenvironment through mechanosensing, adapting their intracellular organization in response to mechanical signals. In this study, we elucidate how macrophages perceive the topographical cues of wrinkled surfaces through actin-based structures, which align with the main pattern direction, thus modulating cell cytoskeletal dynamics. Given that such alterations may regulate mechanosensitive gene expression programs, exploring cellular responses to biomaterial design becomes crucial for developing biomaterials that mitigate adverse reactions.

Clinical, epidemiological, and therapeutic hallmarks of pyoderma gangrenosum: a case series of 35 patients.

BACKGROUND: Over the past few decades, advances in medical research and diagnostic tools have shed light on some aspects of pyoderma gangrenosum (PG). Nevertheless, the multifactorial etiology, pathogenesis, and optimal management strategies for PG need to be further investigated. To address these knowledge gaps and contribute to a better understanding of this complex dermatological disorder, we collected epidemiological, clinical, and therapeutic aspects of a case series of PG patients occurring in our department over the past 10 years. METHODS: We performed a single-centered, retrospective, observational study analyzing all cases with a diagnosis of PG observed at the Dermatology clinic of the Fondazione Policlinico A. Gemelli IRCCS Catholic University from January 1, 2013, to January 1, 2023. For each case, we retrieved demographic data, the presence of other skin and systemic conditions, and the histopathological and clinical characteristics of PG, such as clinical variant, number of lesions, disease localization, previous therapy, response to treatment, and occurrence of relapse. RESULTS: We included 35 patients, 22 females and 13 males with a mean age of 40.0 years. Twenty patients (57.1%) had multiple localizations of disease, and the most commonly involved site was the lower limbs (85.7%). The lesions were mainly associated with inflammatory bowel diseases (51.4%) and hidradenitis suppurativa (37.1%). Clinical resolution with complete re-epithelialization was achieved in 25 patients (71.4%) with an average time of 20.8 months. On average, patients who underwent therapy with biological drugs had better outcomes. CONCLUSIONS: PG is a severe, rare, and pleomorphic disease associated with a broad spectrum of conditions. Corticosteroids remain the primary first-line approach for severe forms, but using biological immunosuppressants is promising.

Implementation of an enhanced recovery after surgery protocol for colorectal cancer in a regional hospital network supported by audit and feedback: a stepped wedge, cluster randomised trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are known to potentially improve the management and outcomes of patients undergoing colorectal surgery, with limited evidence of their implementation in hospital networks and in a large population. We aimed to assess the impact of the implementation of an ERAS protocol in colorectal cancer surgery in the entire region of Piemonte, Italy, supported by an audit and feedback (A&F) intervention. METHODS: A large, stepped wedge, cluster randomised trial enrolled patients scheduled for elective surgery at 29 general surgery units (clusters). At baseline (first 3 months), standard care was continued in all units. Thereafter, four groups of clusters began to adopt the ERAS protocol successively. By the end of the study, each cluster had a period in which standard care was maintained (control) and a period in which the protocol was applied (experimental). ERAS implementation was supported by initial training and A&F initiatives. The primary endpoint was length of stay (LOS) without outliers (>94th percentile), and the secondary endpoints were outliers for LOS, postoperative medical and surgical complications, quality of recovery and compliance with ERAS items. RESULTS: Of 2626 randomised patients, 2397 were included in the LOS analysis (1060 in the control period and 1337 in the experimental period). The mean LOS without outliers was 8.5 days during the control period (SD 3.9) and 7.5 (SD 3.5) during the experimental one. The adjusted difference between the two periods was a reduction of -0.58 days (95% CI -1.07, -0.09; p=0.021). The compliance with ERAS items increased from 52.4% to 67.3% (estimated absolute difference +13%; 95% CI 11.4%, 14.7%). No difference in the occurrence of complications was evidenced (OR 1.22; 95% CI 0.89, 1.68). CONCLUSION: Implementation of the ERAS protocol for colorectal cancer, supported by A&F approach, led to a substantial improvement in compliance and a reduction in LOS, without meaningful effects on complications. Trial registration number NCT04037787.

Breast implant surface topography triggers a chronic-like inflammatory response.

Breast implants are extensively employed for both reconstructive and esthetic purposes. However, the safety of breast implants with textured surfaces has been questioned, owing to a potential correlation with anaplastic large-cell lymphoma and the recurrence of breast cancer. This study investigates the immune response elicited by different prosthetic surfaces, focusing on the comparison between macrotextured and microtextured breast implants. Through the analysis of intraoperatively harvested periprosthetic fluids and cell culture experiments on surface replicas, we demonstrate that macrotextured surfaces elicit a more pronounced chronic-like activation of leucocytes and an increased release of inflammatory cytokines, in contrast to microtextured surfaces. In addition, in vitro fluorescent imaging of leucocytes revealed an accumulation of lymphocytes within the cavities of the macrotextured surfaces, indicating that the physical entrapment of these cells may contribute to their activation. These findings suggest that the topography of implant surfaces plays a significant role in promoting a chronic-like inflammatory environment, which could be a contributing factor in the development of lymphomas associated with a wide range of implantable devices.

Prompt or delayed appendectomy? Influence of timing of surgery for acute appendicitis.

PURPOSE: The aim of the study was to compare the clinical outcomes and histological findings in prompt and delayed appendectomy for acute appendicitis. METHODS: All patients who underwent appendectomy for histologically confirmed acute appendicitis from 2003 to 2009 were included in this study. Patients were divided into three groups according to the time of surgery after hospital admission: The early appendectomy (EA) group underwent surgery within 12 h, the early-delayed appendectomy (EDA) group between 12 and 24 h and the delayed appendectomy (DA) group more than 24 h. The perioperative data and pathological state of the appendix were evaluated and compared. RESULTS: A total of 723 patients, with histologically confirmed acute appendicitis, were included in the study: There were 518 patients in the EA group, 140 patients in the EDA group and 65 patients in the DA group. The operative times were similar in each group. Postoperative complications occurred in 49 patients (6.8 %) and were significantly higher in the DA group in comparison to the EA group (p = 0.0012) and EDA group (p = 0.003). Two patients (3 %) in the DA group died. There were no differences in the length of the hospital stay. The gangrenous appendicitis rate was significantly higher in the DA group (p < 0.05) in comparison to the EA and EDA groups. CONCLUSIONS: Performing appendectomy within 24 h from presentation does not increase the length of hospital stay or rate of complications. However, delayed appendectomy after 24 h from onset increases the rate of complications.

Robot-assisted esophagectomy with robot-sewn intrathoracic anastomosis (Ivor Lewis): surgical technique and early results.

Esophagectomy is the selected treatment for nonmetastatic esophageal and esophagogastric junction cancer, although high perioperative morbidity and mortality incur. Robot-assisted minimally invasive esophagectomy (RAMIE) effectively reduces cardiopulmonary complications compared to open esophagectomy and offers a technical advantage, especially for lymph node dissection and intrathoracic anastomosis. This article aims at describing our initial experience of Ivor Lewis RAMIE, focusing on the technique's main steps and robotic-sewn esophagogastrostomy. Prospectively collected data from all consecutive patients who underwent Ivor Lewis RAMIE for cancer was reviewed. Reconstruction was performed with a gastric conduit pull-up and a robotic-sewn intrathoracic anastomosis. Intraoperative and postoperative complications were recorded as prescribed by the Esophagectomy Complications Consensus Group (ECCG). Thirty patients underwent Ivor Lewis RAMIE with complete mediastinal lymph node dissection and robot-sewn anastomosis. No intraoperative complications nor conversion occurred. Pulmonary complications totaled 26.7%. Anastomotic leakage (ECCG, type III) and conduit necrosis (ECCG, type III) both occurred in one patient (3.3%). Chylothorax appeared in 2 patients (6.7%) (ECCG, Type IIA). Anastomotic stricture, successfully treated with endoscopic dilatations, occurred in 8 cases (26.7%). Median overall postoperative stay was 11 days (range, 6-51 days). 30 day and 90 day mortality was 0%. R0 resection was performed in 96.7% of patients with a median number of 47 retrieved lymph nodes. RAMIE with robot-sewn intrathoracic anastomosis appears to be feasible, safe and effective, with favorable perioperative results. Nevertheless, further high-quality studies are needed to define the best anastomotic technique for Ivor Lewis RAMIE.

101 contact twins in gypsum experimentally obtained from calcium carbonate enriched solutions: mineralogical implications for natural gypsum deposits.

Gypsum twins are frequently observed in nature, triggered by a wide array of impurities that are present in their depositional environments and that may exert a critical role in the selection of different twin laws. Identifying the impurities able to promote the selection of specific twin laws has relevance for geological studies aimed at interpreting the gypsum depositional environments in ancient and modern deposits. Here, the effect of calcium carbonate (CaCO3) on gypsum (CaSO4·2H2O) growth morphology has been investigated by performing temperature-controlled laboratory experiments with and without the addition of carbonate ions. The precipitation of twinned gypsum crystals has been achieved experimentally (101 contact twin law) by adding carbonate to the solution, and the involvement of rapidcreekite (Ca2SO4CO3·4H2O) in selecting the 101 gypsum contact twin law was supported, suggesting an epitaxial mechanism. Moreover, the occurrence of 101 gypsum contact twins in nature has been suggested by comparing the natural gypsum twin morphologies observed in evaporitic environments with those obtained in experiments. Finally, both orientations of the primary fluid inclusions (of the negative crystal shape) with respect to the twin plane and the main elongation of sub-crystals that form the twin are proposed as a fast and useful method (especially in geological samples) to distinguish between the 100 and 101 twin laws. The results of this study provide new insights into the mineralogical implications of twinned gypsum crystals and their potential as a tool to better understand natural gypsum deposits.

Early non compliance to enhanced recovery pathway might be an alert for underlying complications following colon surgery.

PURPOSE: Early non compliance to postoperative ERAS pathway has been reported in 20-30% of patients who underwent elective colon surgery. The aim of the present study is to investigate the possible relationship between early non compliance and postoperative complications. METHODS: We reviewed a prospective database including 1391 consecutively collected patients undergoing elective colon surgery in 22 Italian hospitals between January 2017 and June 2020. Early compliance to ERAS protocol was assessed on postoperative day (POD) 2. Failure of oral feeding, urinary catheter removal, intravenous fluids stop, and adequate mobilization were indicators of non compliance. Postoperative follow-up was carried out for 30 days after hospital discharge. The association among early postoperative ERAS compliance and the occurrence of complications was assessed with uni- and multivariate analysis. RESULTS: A total of 1089 (78.3%) patients had malignancy and minimally invasive surgery was successfully performed in 1174 (84.3%) patients. Postoperative morbidity occurred in 403 (29.0%) patients. At multivariate analysis, male gender, open surgery, and each of the four non compliance indicators on POD 2 were significantly associated to postoperative complications. Morbidity progressively increased from 16.8% in patients with full compliance to ERAS protocol to 47.2% in patients with two non compliance indicators and 69.2% in patients with all four indicators (p < 0.001). CONCLUSIONS: Early non compliance to ERAS protocol was significantly associated with postoperative morbidity.

Microbial Response to Micrometer-Scale Multiaxial Wrinkled Surfaces.

We investigate the effect of micrometer-scale surface wrinkling on the attachment and proliferation of model bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli K12) and fungi (Candida albicans). Specifically, sinusoidal (1D), checkerboard (C), and herringbone (H) patterns were fabricated by mechanical wrinkling of plasma-oxidized polydimethylsiloxane (PDMS) bilayers and contrasted with flat (F) surfaces. Microbial deformation and orientation were found to correlate with the aspect ratio and commensurably with surface pattern dimensions and local pattern order. Significantly, the proliferation of P. aeruginosa could be described by a linear scaling between bacterial area coverage and available surface area, defined as a fraction of the line integral along each profile with negative curvature. However, in the early stages of proliferation (up to 6 h examined), that C and H patterns disrupt the spatial arrangement of bacteria, impeding proliferation for several hours and reducing it (by ∼50%) thereafter. Our findings suggest a simple framework to rationalize the impact of micrometer-scale topography on microbial action and demonstrate that multiaxial patterning order provides an effective strategy to delay and frustrate the early stages of bacterial proliferation.

Early Postoperative Low Compliance to Enhanced Recovery Pathway in Rectal Cancer Patients.

Early postoperative low compliance to enhanced recovery protocols has been associated with morbidity following colon surgery. The purpose of this study is to evaluate the possible causes of early postoperative low compliance to the enhanced recovery pathway and its relationship with morbidity following rectal surgery for cancer. A total of 439 consecutive patients who underwent elective surgery for rectal cancer have been included in the study. Compliance to enhanced recovery protocol on postoperative day (POD) 2 was evaluated in all patients. Indicators of compliance were naso-gastric tube and urinary catheter removal, recovery of both oral feeding and mobilization, and the stopping of intravenous fluids. Low compliance on POD 2 was defined as non- adherence to two or more items. One-third of patients had low compliance on POD 2. Removal of urinary catheter, intravenous fluids stop, and mobilization were the items with lowest adherence. Advanced age, duration of surgery, open surgery and diverting stoma were predictive factors of low compliance at multivariate analysis. Overall morbidity and major complications were significantly higher (p < 0.001) in patients with low compliance on POD 2. At multivariate analysis, failure to remove urinary catheter on POD 2 (OR = 1.83) was significantly correlated with postoperative complications. Low compliance to enhanced recovery protocol on POD 2 was significantly associated with morbidity. Failure to remove the urinary catheter was the most predictive indicator. Advanced age, long procedure, open surgery and diverting stoma were independent predictive factors of low compliance.