Essential contribution of macrophage Tie2 signal mediated autophagy in laser-induced choroidal neovascularization.

Autophagy plays critical roles in various ocular diseases, including age-related macular degeneration (AMD). Tie2-expressing macrophages (TEMs) play crucial roles in angiogenesis. To investigate the role of TEMs and autophagy in the development of AMD, we employed macrophage-specific Tie2 knockout mice and used a laser-induced choroidal neovascularization (CNV). The results showed that TEMs can promote CNV formation by up-regulating the level of autophagy. These results were further verified by in vitro cell experiments that peritoneal macrophages from Tie2 knockout mice can inhibit the expression of autophagy-related factors and inhibit the expression of angiogenic factor of VEGF by activating AMPK signaling pathway. Our results suggest that TEMs and macrophage Tie2 signal mediated-autophagy play critical role in experimental CNV, and they may be novel preventive targets for AMD treatment.

Robotic transanal minimally invasive surgery - technical, oncological and patient outcomes from a single institution.

AIM: Robotic transanal minimally invasive surgery (R-TAMIS) is gaining traction around the globe as an alternative to laparoscopic conventional TAMIS for local excision of benign and early malignant rectal lesions. The aim was to analyse patient and oncological outcomes of R-TAMIS for consecutive cases in a single centre. METHODS: A prospective analysis of consecutive R-TAMIS procedures over a 12-month period was performed. Data were collated from hospital databases and theatre registers. RESULTS: Eleven patients (six men, five women), mean age 69.81 years (51-92 years), underwent R-TAMIS over 12 months utilizing a da Vinci Xi platform. The mean lesion size was 36 mm (20-60 mm) with a mean distance from the anal verge of 7.5 cm (3-14 cm). Five lesions were posterior in anatomical location, four anterior, one right lateral and one left lateral. All procedures were performed in the lithotomy position using a GelPOINT Path Platform. Mean operative time was 64 min (40-100 min). Complete resection was achieved in 10/11 patients with two patients being upgraded to a diagnosis of adenocarcinoma. Nine patients were diagnosed with dysplastic lesions. Four patients had a false positive diagnosis of an invasive tumour on MRI. Six patients required suturing for full-thickness resections. One patient had a postoperative bleed requiring repeat endoscopy and clipping. One patient (full-thickness resection of T3 tumour) proceeded to a formal resection without difficulty with no residual disease (T0N0, 0/22). One patient with a fully resected T2 tumour is undergoing a surveillance protocol. The mean length of stay was 1 day with two patients having a length of stay of 2 days and one patient of 4 days. CONCLUSION: R-TAMIS could potentially represent a safe novel approach for local resection of rectal lesions.

Outcomes of completion total mesorectal excision are not compromised by prior transanal minimally invasive surgery.

AIM: Transanal minimally invasive surgery (TAMIS) is used increasingly often as an organ-preserving treatment for early rectal cancer. If final pathology reveals unfavourable histological prognostic features, completion total mesorectal excision (cTME) is recommended. This study is the first to investigate the results of cTME after TAMIS. METHOD: Data were retrieved from the prospective database of the Elisabeth-TweeSteden Hospital. Completion TME patients were case matched with a control group of patients undergoing primary TME (pTME). Primary and secondary outcomes were surgical outcomes and oncological outcomes, respectively. RESULTS: From 2011 to 2017, 20 patients underwent cTME and were compared with 40 patients undergoing pTME. There were no significant differences in operating time (238 min vs 226 min, P = 0.53), blood loss (137 ml vs. 158 ml, P = 0.88) or complications (45% vs 55%, P = 0.07) between both groups. There was no 90-day mortality in the cTME group. The mesorectal fascia was incomplete in three patients (15%) in the cTME group compared with no breaches in the pTME group (P = 0.083). There were no local recurrences in either group. In three patients (15%), distant metastases were detected after cTME compared with one patient (2.5%) in the pTME group (P = 0.069). After cTME patients had a 1- and 5-year disease-free survival of 85% compared with 97.5% for the pTME group (P = 0.062). CONCLUSION: Completion TME surgery after TAMIS is not associated with increased peri- or postoperative morbidity or mortality compared with pTME surgery. After cTME surgery patients have a similar disease-free and overall survival when compared with patients undergoing pTME.

A multi-centre randomized controlled trial of open vs closed management of the rectal defect after transanal endoscopic microsurgery.

AIM: Transanal endoscopic microsurgery (TEM) is a technically challenging strategy that allows expanded indications for local excision of rectal lesions. Transluminal suturing is difficult, so open management of the resultant defect is appealing. Expert opinion suggests there is more pain when the defect is left open. The aim of this study was to determine if closure of the defect created during full thickness excision of rectal lesions with TEM leads to less postoperative pain compared to leaving the defect open. METHOD: At the time of surgery, patients undergoing a full thickness TEM were randomized to sutured (TEM-S) or open (TEM-O) management of the rectal defect. At five Canadian academic colorectal surgery centres, experienced TEM surgeons enrolled patients ≥ 18 years treated by full thickness TEM. The primary outcome was postoperative pain measured by the visual analogue scale. Secondary outcomes included postoperative pain medication use and 30-day postoperative complications, including bleeding, infection and hospital readmission. RESULTS: Between March 2012 and October 2013, 50 patients were enrolled and randomized to sutured (TEM-S, n = 28) or open (TEM-O, n = 22) management of the rectal defect. There was no difference between the two study groups in postoperative pain on postoperative day 1 (2.8 vs 2.6, P = 0.76), day 3 (2.8 vs 2.1, P = 0.23) and day 7 (2.8 vs 1.7, P = 0.10). CONCLUSION: In this multicentre randomized controlled trial, there was no difference in postoperative pain between sutured or open defect management in patients having a full thickness excision with TEM.

The effect of proctoring on the learning curve of transanal minimally invasive surgery for local excision of rectal neoplasms.

BACKGROUND: The current method of choice for local resection of benign and selected malignant rectal tumors is transanal endoscopic microsurgery. Transanal minimally invasive surgery (TAMIS) yields similar oncological results and better patient reported outcomes when compared to transanal endoscopic micro surgery. However, due to the technical complexity of TAMIS, a significant learning curve has been suggested. Data on the surgical learning curve are limited. The aim of our study was to investigate surgeon specific learning curves for TAMIS procedures for the local excision of selected rectal tumors, and analyze the effects of proctoring on operating time and outcome. METHODS: The current study was prospective of all TAMIS procedures performed by two surgeons from October 2010 to November 2017. Margin positivity, specimen fragmentation, adverse events and operative time were evaluated with a cumulative sum analysis to determine the number of procedures required to reach proficiency. Cumulative sum (CUSUM) analysis was used to determine trends in changes over time. RESULTS: The earliest adopter, surgeon A, performed 103 procedures, was not proctored and developed the standardized institutional program. Surgeon B, performed 26 cases, had the benefit of a proctorship and availability of a standardized program. The CUSUM curve for operative time showed a change after 36 cases for surgeon A and after 10 cases for surgeon B. For margin positivity proficiency was reached after 31 and 6 cases for surgeon A and B, respectively. The complications curve for surgeon A showed a three-phase learning curve with a decrease after the 26th case whereas surgeon B only had one (3.8%) complication in the learning phase with no change point in the CUSUM curve. Comparing pre- and post-proficiency periods there was a decrease in operating time for both surgeon A (84.4 ± 47.3 to 55.9 ± 30.1 min) and surgeon B (90.6 ± 64.to 53 ± 26.5 min; p < 0.001). Overall margin positivity rates decreased non significantly from 21.7 to 4.8% (p = 0.23). Complications were higher in the pre-proficiency period (21.7% vs. 13.0%; p = 0.02). Surgeon A had significantly more postoperative complications in pre-proficiency phase when compared to surgeon B (25% vs. none, p < 0.001), in the post-proficiency phase there was no statistically significant difference between both surgeons (p = 0.08). CONCLUSIONS: Our results suggest that to reach satisfactory results for TAMIS, 18-31 procedures are required. Standardized institutional operative protocols together with proficient proctorship may contribute to a shorter learning curve with fewer cases (6-10) required to reach proficiency.

Pro-angiogenic TIE-2-expressing monocytes/TEMs as a biomarker of the effect of sorafenib in patients with advanced hepatocellular carcinoma.

Sorafenib, a multi-kinase inhibitor, inhibits tumor angiogenesis and is the first-line systemic therapy for patients with advanced hepatocellular carcinoma (HCC). However, due to its limited effects and frequent occurrence of side effects, biomarkers are needed to predict the effects of sorafenib. We considered the possibility of using TIE-2-expressing monocytes (TEMs) to predict the response in sorafenib-treated patients with advanced HCC. TEMs serve as a diagnostic marker of HCC and are related to angiogenesis. We analyzed 25 advanced HCC patients and prospectively evaluated TEMs before (Pre TEMs) and at 1 month after initial therapy (T1m TEMs). The radiologic response was evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Median survival time (MST) was significantly longer in the partial response/stable disease (PR/SD) group (21.8 months) than in the PD group (8.7 months). ΔTEMs (changes of T1m TEMs compared to Pre TEMs) were significantly lower in the PR/SD group than in the PD group. MST of the ΔTEMs low group (14.2 months) was significantly longer than that of the high group (8.7 months). Univariate and multivariate Cox regression analyses showed that ΔTEMs [hazard ratio (HR) = 8.53, 95% confidence interval (CI) = 1.51-48.16, p = 0.015] and Child-Pugh class (HR = 5.59, 95% CI = 1.06-29.63, p = 0.043) were independently associated with overall survival. Our results suggest that ΔTEMs could serve as a biomarker for predicting radiologic response and overall survival in sorafenib-treated patients with advanced HCC.

Tspan2: a tetraspanin protein involved in oligodendrogenesis and cancer metastasis.

Tetraspanin 2 (Tspan2) is one of the less well-characterised members of the tetraspanin superfamily, and its precise function in different human tissue types remains to be explored. Initial studies have highlighted its possible association in neuroinflammation and carcinogenesis. In the central nervous system, Tspan2 may contribute to the early stages of the oligodendrocyte differentiation into myelin-forming glia. Furthermore, in human lung cancer, Tspan2 could be involved in the progression of the tumour metastasis by modulating cancer cell motility and invasion functions. In this review, we discuss the available evidence for the potential role of Tspan2 and introduce possible strategies for disease targeting.

Integration of Tactical EMS in the National Park Service.

The National Park Service (NPS) has domestic responsibility for emergency medical services (EMS) in remote and sometimes tactical situations in 417 units covering over 34 million hectares (84 million acres). The crossover between conflicting patient care priorities and complex medical decision making in the tactical, technical, and wilderness/remote environments often has many similarities. Patient care in these diverse locations, when compared with military settings, has slightly different variables but often similar corresponding risks to the patients and providers. The NPS developed a Tactical EMS (TEMS) program that closely integrated many principles from: 1) Tactical Combat Casualty Care (TCCC); 2) Tactical Emergency Casualty Care (TECC); 3) and other established federal and civilian TEMS programs. Combining these best practices into the NPS TEMS Program allowed for standardized training and implementation across not only the NPS, but also paralleled other military/federal/civilian TEMS programs. This synchronization is critical when an injury occurs in a joint tactical operation, either planned (drug interdiction) or unplanned (active shooter response), so that patient care can be uniform and efficient. The components identified for a sustainable TEMS program began with strong medical oversight, protocol development with defined phases of care, identifying specialized equipment, and organized implementation with trained TEMS instructors. Ongoing TEMS program management is continuously improving situationally appropriate training and integrating current best practices as new research, equipment, and tactics are developed. The NPS TEMS Program continues to provide ongoing training to ensure optimal patient care in tactical and other NPS settings.

Peripheral Blood CD38 Bright CD8+ Effector Memory T Cells Predict Acute Graft-versus-Host Disease.

Acute graft-versus-host disease (aGVHD) is mediated by allogeneic T cell responses. We hypothesized that increases of peripheral blood-activated CD8+ effector memory T (TEM) cells would be observed after hematopoietic stem cell transplantation (HSCT) before onset of aGVHD symptoms. Blood was collected twice weekly after HSCT for 7 weeks in 49 consecutive pediatric and adult HSCT recipients. Samples were incubated with fluorochrome-conjugated antibodies against CD45, CD3, CD8, CD38, CD45RA, and CCR7 and analyzed using flow cytometry. TEM cells were defined as CD3+ CD8+ CCR7- CD45RA(-) lymphocytes. CD38 expression was used as a marker of T cell activation. Patients were followed for 100 days for development of aGVHD. Twenty-three patients developed grade 1 to 4 aGVHD at a median of 37 days (range, 15 to 79 days) after HCST. Absolute CD38 bright CD8+ TEM of > 35 cells/µL predicted aGVHD at a median of 8 days (range, 1 to 34) before aGVHD onset with a sensitivity of 82.6% and specificity of 91.6%. The cumulative incidence of aGVHD was 90% in patients with absolute CD38 bright CD8+ TEM >35 cells/µL and 15% in patients without (P < .0001). Quantification of CD38 bright CD8+ TEM cells may predict aGVHD in children and young adult HSCT recipients.

Physician roles in tactical emergency medical support: the first 20 years.

BACKGROUND: The benefits of Tactical Emergency Medical Support (TEMS) elements are providing injury prevention, immediate care of injuries, and medical augmentation of the success of dangerous law enforcement operations. TEMS is recognized by civilian Special Weapons and Tactics (SWAT) and various other law enforcement agencies around the country as a vital addition to such SWAT teams. The integration of specially trained TEMS personnel has become a key component of law enforcement special operations. OBJECTIVE: Our aim was to review the published literature to identify if there is a role for physicians within TEMS elements with regard to its establishment and progression, and to characterize the level of physician-specific support provided in the tactical environment for civilian tactical law enforcement teams. DISCUSSION: Physician presence as part of TEMS elements is increasing in number and popularity as the realization of the benefits provided by such physicians has become more apparent. The inclusion of physicians as active and participating members of TEMS elements is a critical measure to be taken for tactical law enforcement units. Physicians provide an added level of medical expertise to TEMS elements in rural and urban settings compared with law enforcement personnel with medic training. CONCLUSIONS: Physician involvement is an essential element of a successful TEMS program. There is a need for more physicians to become involved as TEMS personnel for specialized tactical teams to spread the time commitment and increase their availability to tactical units on a daily basis.

Maximizing micro-grid energy output with modified chaos grasshopper algorithms.

This study presents a Modified version of Chaos Grasshopper Algorithm (MCGA) as a solution to the Techno-Economic Energy Management Strategy (TEMS) problem in microgrids. Our main contribution is the optimization of parameters to minimize the overall daily electricity price in an integrated clean energy micro-grid, incorporating fuel cell, battery storage, and photovoltaic systems. Through comparative simulations with established methods (HOMER, GAMS, GWO, and MILPA), we demonstrate the superiority of our proposed strategy. The results reveal that MCGA surpasses these methods, yielding significantly improved optimal solutions for the overall daily electricity price. Notably, the MCGA approach exhibits high precision, flexibility, and adaptability to power prices and environmental constraints, leading to accurate and flexible solutions. Thus, our proposed approach offers a promising and effective solution for the TEMS problem in microgrids, with the potential to greatly enhance microgrid performance.

Transanal endoscopic microsurgery: a new technique for completion proctectomy.

AIM: Following subtotal colectomy, the retained rectal stump is a potential source of morbidity. Although restorative ileal pouch-anal anastomosis is the gold standard for ulcerative colitis, up to 14% of patients will opt for a permanent ileostomy and undergo completion proctectomy, traditionally by an abdomino-perineal approach, which itself carries significant morbidity. We describe a new technique of perineal proctectomy using transanal endoscopic microsurgery (TEMS) equipment. To our knowledge, this technique has not previously been described in the literature. METHOD: Twelve patients, mean (SD) age 66 (±13) years, underwent TEMS proctectomy, performed by a single surgeon between January 2007 and October 2011. Excision began with an intersphincteric dissection following which the TEMS (WOLF) proctoscope was inserted and close rectal dissection was performed, entering the peritoneal cavity (if the top of the stump was intraperitoneal). Following perineal extraction of the specimen, the external sphincter and skin were closed with an absorbable suture. RESULTS: Nine patients had inflammatory bowel disease, two had neoplasia and one had intractable radiation proctitis. The mean (SD) rectal stump length was 17.8 (±6.1) cm and the peritoneal cavity was entered in nine patients, with no small-bowel injury. The median postoperative hospital stay was 5.5 days. In four patients there was delayed healing of the perineal wound. There was no perioperative mortality. CONCLUSION: TEMS perineal proctectomy is a novel, but safe, technique that may avoid the need for a traditional abdominoperineal approach in selected patients.

Radical vs. Local Excision in Rectal Carcinoma T1N0M0: Recurrence and Mortality Rates.

Local transanal excision of early rectal carcinoma is an appealing treatment because of its low morbidity rates and better functional results than radical resection. However, this treatment approach is controversial due to its association with local recurrence when compared to the latter. This review aims to compare the local recurrence and mortality rates of local vs. radical excision in patients with T1N0M0 rectal carcinoma, based on data in the literature in the last 20 years. A PubMed, Cochrane, and Google Scholar search of published literature in the last 20 years was performed. A total of 12 studies were identified. Three were prospective, one was a population-based propensity matching study, one was a nationwide cohort study, one was a meta-analysis, and the remaining studies were retrospective/observational. The mean local recurrence rate within five years from the studies selected for local excision (LE: 12.8%) was nearly double that of radical excision (RAD: 5.0%). The five-year mean survival rate for both LE and RAD groups from the studies selected was 86%, which was equal for both groups. The main predictors of poor outcomes were older age and the presence of two or more comorbid conditions. There is a consensus amongst studies that LE is associated with inferior oncological outcomes such as postoperative complications and recurrence when compared to RAD. The higher local recurrence rates in LE are attributed to occult lymph node disease and inadequate adjunctive therapy due to suboptimal staging. There is no difference in the five-year survival rate when compared to RAD. A longer follow-up period is needed to determine whether the survival rates diverge after five years.

T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation.

Upon antigen recognition by the T cell receptor (TCR), a complex signaling network orchestrated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) regulates the transmission of the extracellular signal to the nucleus. The role of the PTPs Src-homology 2 (SH2) domain-containing phosphatase 1 (SHP1, Ptpn6) and Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2, Ptpn11) have been studied in various cell types including T cells. Whereas SHP1 acts as an essential negative regulator of the proximal steps in T cell signalling, the role of SHP2 in T cell activation is still a matter of debate. Here, we analyzed the role of the constitutively active SHP2-D61Y-mutant in T cell activation using knock-in mice expressing the mutant form Ptpn11D61Y in T cells. We observed reduced numbers of CD8+ and increased numbers of CD4+ T cells in the bone marrow and spleen of young and aged SHP2-D61Y-mutant mice as well as in Influenza A Virus (IAV)-infected mice compared to controls. In addition, we found elevated frequencies of effector memory CD8+ T cells and an upregulation of the programmed cell death protein 1 (PD-1)-receptor on both CD4+ and CD8+ T cells. Functional analysis of SHP2-D61Y-mutated T cells revealed an induction of late apoptosis/necrosis, a reduced proliferation and altered signaling upon TCR stimulation. However, the ability of D61Y-mutant mice to clear viral infection was not affected. In conclusion, our data indicate an important regulatory role of SHP2 in T cell function, where the effect is determined by the kinetics of SHP2 phosphatase activity and differs in the presence of the permanently active and the temporally regulated phosphatase. Due to interaction of SHP2 with the PD-1-receptor targeting the protein-tyrosine phosphatase might be a valuable tool to enhance T cell activities in immunotherapy.

GEC ESTRO ACROP consensus recommendations for contact brachytherapy for rectal cancer.

PURPOSE: To issue consensus recommendations for contact X-Ray brachytherapy (CXB) for rectal cancer covering pre-treatment evaluation, treatment, dosimetric issues and follow-up. These recommendations cover CXB in the definitive and palliative setting. METHODS: Members of GEC ESTRO with expertise in rectal CXB issued consensus-based recommendations for CXB based on literature review and clinical experience. Levels of evidence according to the Oxford Centre for Evidence based medicine guidance are presented where possible. RESULTS: The GEC ESTRO ACROP consensus recommendations support the use of CXB to increase the chances of clinical complete remission and cure for patients who are elderly with high surgical risk, surgically unfit or refusing surgery. For palliative treatment, the use of CXB is recommended for symptomatic relief and disease control. The use of CXB in an organ-preservation setting in surgically fit patients is recommended within the setting of a clinical trial or registry. CONCLUSIONS: The GEC ESTRO ACROP recommendations for CXB are provided. Recommendations towards standardisation of reporting and prescription are given. Practitioners are encouraged to follow these recommendations and to develop further clinical trials to examine this treatment modality and increase the evidence base for its use. The routine collection of outcomes both clinical and patient-reported is also encouraged.

Transanal Endoscopic Microsurgery (TEMS) for Rectal Cancer: Patient Decision-making, Postoperative Experience and Quality of Life.

BACKGROUND/AIM: Transanal endoscopic microsurgery (TEMS) is a form of minimally invasive surgery for selected rectal cancers. The aim of this study was to explore the factors affecting patients' decision-making concerning the choice of surgical treatment as well as to measure the Quality of Life (QoL) post-TEMS. PATIENTS AND METHODS: Thirty-four patients with rectal cancer stage T1/T2-N0-M0 that underwent TEMS were studied. The questionnaires used included the Short Form SF12v2, Wexner Score (CCF-FIS) and the Sexual Function Questionnaire (SFQ). The patients' views on experience and treatment decision were obtained with a custom-designed questionnaire. Questionnaires were completed at a mean of 6.9 years following treatment. RESULTS: The factors that influenced the patients' decisions were: experience satisfaction (p=0.003), postoperative bowel function (p<0.001), lower incontinence score (p=0.020) and agreement of TEMS experience with preoperative information (p=0.049). Treatment experience satisfaction was associated with family support (p=0.034) and agreement with preoperative information (p=0.047), better bowel function (p=0.026) and mental QoL (MCS) (p=0.003). CONCLUSION: factors important to patients when reflecting on treatment experience are adequate and reliable information, a good QoL and the presence of family support. Clinicians should incorporate those parameters in their practice when assisting patients in making a surgical treatment choice and provide informed consent on TEMS for rectal cancer.

Team effectiveness model for science (TEMS): Using a mutual learning shared mindset to design, develop, and sustain science teams.

In this paper, we introduce the Team Effectiveness Model for Science (TEMS) and describe a multiphase set of interventions for forming a new team or developing an existing team. TEMS uses a shared mutual learning mindset as the model's central and guiding element. It shows how team mindset leads to behavior and to results and how this affects the characteristics of effective team functioning. TEMS addresses two related questions: What are the variables that contribute to effective teams? and How do the variables need to be designed to make their relevant contributions? Team models often answer the first question without fully answering the second. By addressing three gaps, TEMS contributes to enhancing science team effectiveness. Gap 1 is the absence of explicit core values, assumptions, and norms that serve as the foundation for developing and maintaining science team effectiveness. Gap 2 is the absence of a process for integrating the science and relationship aspects of a science team. Gap 3 is the absence of team processes and structures that are derived from the team's values, assumptions, and norms. Using TEMS to design new or intervene with existing teams focuses on shifting mindset, developing behavioral skills, and designing processes and structures congruent with the new mindset.

Should the rectal defect be sutured following TEMS/TAMIS carried out for neoplastic rectal lesions? A meta-analysis.

INTRODUCTION: Management of the rectal defect following transanal endoscopic microsurgery (TEMS) or minimally invasive surgery (TAMIS) carried out for excision of neoplasm in the lower rectum is controversial. We aimed to extract evidence by carrying out a meta-analysis to compare the peri- and postoperative outcomes following rectal neoplasm excision carried out by TEMS and/or TAMIS, whereby the defect is either sutured or left open. METHODS: A literature search of Ovid MEDLINE and EMBASE was performed. Full-text comparative studies published until November 2019, in English and of adult patients, whereby TEMS or TAMIS was undertaken for rectal neoplasms were included. The main outcome measures were postoperative bleeding, infection, operative time and hospital stay. FINDINGS: Three studies (one randomised controlled trial and two comparative case series) yielded 555 cases (283 in the sutured group and 272 in the open group). The incidence of postoperative bleeding was higher and statistically significant (p = 0.006) where the rectal defect was left open following excision of the neoplasm (19/272, 6.99% vs 6/283, 2.12%). There was no statistical difference between the sutured and open groups regarding infection (p = 0.27; (10/283, 3.53% vs 5/272, 1.84%, respectively), operative time (p = 0.15) or length of stay (p = 0.67). CONCLUSION: Suturing the rectal defect following excision of rectal neoplasm by TEMS/TAMIS reduces the incidence of postoperative bleeding in comparison to leaving the defect open. However, suturing makes the procedure slightly longer but there was no statistical difference between both groups when postoperative infection and length of hospital stay were compared.

TSPAN5 Enriched Microdomains Provide a Platform for Dendritic Spine Maturation through Neuroligin-1 Clustering.

Tetraspanins are a class of evolutionarily conserved transmembrane proteins with 33 members identified in mammals that have the ability to organize specific membrane domains, named tetraspanin-enriched microdomains (TEMs). Despite the relative abundance of different tetraspanins in the CNS, few studies have explored their role at synapses. Here, we investigate the function of TSPAN5, a member of the tetraspanin superfamily for which mRNA transcripts are found at high levels in the mouse brain. We demonstrate that TSPAN5 is localized in dendritic spines of pyramidal excitatory neurons and that TSPAN5 knockdown induces a dramatic decrease in spine number because of defects in the spine maturation process. Moreover, we show that TSPAN5 interacts with the postsynaptic adhesion molecule neuroligin-1, promoting its correct surface clustering. We propose that membrane compartmentalization by tetraspanins represents an additional mechanism for regulating excitatory synapses.