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The epithelium serves as a highly selective barrier at mucosal surfaces. Upon injury, epithelial wound closure is orchestrated by a series of events that emanate from the epithelium itself as well as by the temporal recruitment of immune cells into the wound bed. Epithelial cells adjoining the wound flatten out, migrate, and proliferate to rapidly cover denuded surfaces and re-establish mucosal homeostasis. This process is highly regulated by proteins and lipids, proresolving mediators such as Annexin A1 protein and resolvins released into the epithelial milieu by the epithelium itself and infiltrating innate immune cells including neutrophils and macrophages. Failure to achieve these finely tuned processes is observed in chronic inflammatory diseases that are associated with non-healing wounds. An improved understanding of mechanisms that mediate repair is important in the development of therapeutics aimed to promote mucosal wound repair.

Background Anastomotic leakage represents a major complication following resections in colorectal surgery. Among others, intestinal inflammation such as in inflammatory bowel disease is a significant risk factor for disturbed anastomotic healing. Despite technical advancements and several decades of focused research, the underlying mechanisms remain incompletely understood. Animal experiments will remain the backbone of this research in the near future. Here, instructions on a standardized and reproducible murine model of preoperative colitis and colorectal anastomosis formation are provided to amplify research on anastomotic healing during inflammatory disease. Methods We demonstrate the combination of experimental colitis and colorectal anastomosis formation in a mouse model. The model allows for monitoring of anastomotic healing during inflammatory disease through functional outcomes, clinical scores, and endoscopy and histopathological examination, as well as molecular analysis. Discussion Postoperative weight loss is used as a parameter to monitor general recovery. Functional stability can be measured by recording bursting pressure and location. Anastomotic healing can be evaluated macroscopically from the luminal side by endoscopic scoring and from the extraluminal side by assessing adhesion and abscess formation or presence of dehiscence. Histologic examination allows for detailed evaluation of the healing process. Conclusion The murine model presented in this paper combines adjustable levels of experimental colitis with a standardized method for colorectal anastomosis formation. Extensive options for sample analysis and evaluation of clinical outcomes allow for detailed research of the mechanisms behind defective anastomotic healing.

Neutrophil transepithelial migration (TEM) during acute inflammation is associated with mucosal injury. Using models of acute mucosal injury in vitro and in vivo, we describe a new mechanism by which neutrophils infiltrating the intestinal mucosa disrupt epithelial homeostasis. We report that junctional adhesion molecule-like protein (JAML) is cleaved from neutrophil surface by zinc metalloproteases during TEM. Neutrophil-derived soluble JAML binds to the epithelial tight junction protein coxsackie-adenovirus receptor (CAR) resulting in compromised barrier and inhibition of wound repair, through decreased epithelial proliferation. The deleterious effects of JAML on barrier and wound repair are reversed with an anti-JAML monoclonal antibody that inhibits JAML–CAR binding. JAML released from transmigrating neutrophils across inflamed epithelia may thus promote recruitment of leukocytes and aid in clearance of invading microorganisms. However, sustained release of JAML under pathologic conditions associated with persistence of large numbers of infiltrated neutrophils would compromise intestinal barrier and inhibit mucosal healing. Thus, targeting JAML–CAR interactions may improve mucosal healing responses under conditions of dysregulated neutrophil recruitment.

Purpose Minimally invasive surgery is increasingly utilized in treatment for refractory or complicated Crohn’s disease, and new developments aim at further reducing the abdominal trauma and improving the outcome. This review evaluates current literature about minimally invasive surgery for patients with Crohn’s disease, latest advances in single-incision surgery, and methods of specimen extraction. Methods Literature was reviewed with focus on the following topics: indications, surgical procedures, conversions, complications, and short- as well as long-term outcomes of laparoscopic compared to open surgery for refractory, complicated, and recurrent Crohn’s disease. Results Short-term benefits such as shorter hospital stay and faster postoperative recovery are accompanied by long-term benefits such as better cosmetic results and lower treatment-associated morbidity. Single-incision surgery and minimally invasive methods of specimen extraction help to further reduce the surgical trauma and are gradually implemented in the treatment. Conclusion In experienced centers, laparoscopic surgery for Crohn’s disease is safe and as feasible as open operations, even for selected cases with operations for complicated or recurrent disease. However, accurate analysis of the data is complicated by the heterogeneity of clinical presentations as well as the variety of performed procedures. Additional long-term data are needed for evaluation of true benefits of the new techniques.

Secondary perineal herniation of intraperitoneal contents represents a rare complication following procedures such as abdominoperineal rectal resection or cystectomy. We present a case of a perineal hernia formation with prolapse of an ileum neobladder following radical cystectomy and rectal resection for recurrent bladder cancer. Following consecutive resections in the anterior and posterior compartment of the lesser pelvis, the patient developed problems emptying his neobladder. Clinical examination and computed tomography revealed perineal herniation of his neobladder through the pelvic floor. Through a perineal approach, the hernial sac could be repositioned, and via a combination of absorbable and non-absorbable synthetic mesh grafts, the pelvic floor was stabilised. Follow-up review at one year after hernia fixation showed no signs of recurrence and no symptoms. In cases of extensive surgery in the lesser pelvis with associated weakness of the pelvic compartments, meshes should be considered for closure of the pelvic floor. Development of biological meshes with reduced risk of infection might be an interesting treatment option in these cases.

Background:The lateral habenula is a brain region that has been critically implicated in modulating negative emotional states and responses to aversive stimuli. Exposure to addictive drugs such as cocaine negatively impacts affective states, an effect persisting longer than acute drug effects. However, the mechanisms of this effect are poorly understood. We hypothesized that drugs of abuse, such as cocaine, may contribute to drug-induced negative affective states by altering the firing properties of lateral habenula neurons, thus changing the signaling patterns from the lateral habenula to downstream circuits.Methods:Using whole-cell current-clamp recording of acutely prepared brain slices of rats after various periods of withdrawal from cocaine self-administration, we characterized an important heterogeneous subregion of the lateral habenula based on membrane properties.Results:We found two major relevant neuronal subtypes: burst firing neurons and regular spiking neurons. We also found that lateral habenula regular spiking neurons had higher membrane excitability for at least 7 days following cocaine self-administration, likely due to a greater membrane resistance. Both the increase in lateral habenula excitability and membrane resistance returned to baseline when tested after a more prolonged period of 45 days of withdrawal.Conclusion:This is the first study to look at intrinsic lateral habenula neuron properties following cocaine exposure beyond acute drug effects. These results may help to explain how cocaine and other drugs negatively impact affect states.

Zusammenfassung Hintergrund Patienten mit komplizierter Appendizitis entwickeln postoperativ häufig septische Komplikationen. Für die Wahl der perioperativen Antibiotikaprophylaxe und die Dauer der postoperativen Antibiotikatherapie gibt es keine einheitlichen Standards. In dieser Studie sollen Zusammenhänge zwischen mikrobiologischen Abstrichen und postoperativen Komplikationen aufgezeigt werden. Methoden Es wurden Patienten mit Appendektomie und positivem intraoperativen Abstrich im Zeitraum von 2013 bis 2018 in diese Fall-Kontroll-Studie eingeschlossen. Erregerklassen und deren Resistenzmuster wurden in Erst- und Folgeabstrichen ausgewertet und jeweils in den Gruppen mit und ohne Komplikationen verglichen. Ergebnisse Insgesamt wurden im untersuchten Zeitraum 870 Patienten operiert. Ein intraoperativer Erregernachweis gelang in 102 von 210 Fällen (48,6 %) mit Verdacht auf bakterielle, peritoneale Kontamination. Die Konversion von laparoskopisch zu offen, intraabdominelle Perforation und das Vorhandensein eines Abszesses waren in der multivariaten Analyse unabhängige Risikofaktoren für Wundinfekte. Die Kombination verschiedener Erregerklassen führte zu einer deutlich erhöhten Gesamtresistenz gegenüber Ampicillin/Sulbactam sowohl in den Erstabstrichen (57 %) als auch in den Folgeabstrichen (73 %). Resistente E. - coli -Stämme kombiniert mit bestimmten Anaerobiern ließen sich auch regelhaft in postoperativen intraabdominellen Abszessen nachweisen. Piperacillin/Tazobactam war in unseren Resistenztestungen effektiv gegen 83 % der positiven Abstriche. Schlussfolgerung Die chirurgische Fokussanierung bei komplizierter Appendizitis ist weiterhin die zentrale Therapiesäule. Eine regelmäßige Überprüfung der vorliegenden Resistenzlage bei perforierter Appendizitis kann dazu beitragen, die kalkulierte antibiotische Therapie anzupassen und zu verbessern. Piperacillin/Tazobactam sollte als Reserveantibiotikum zurückhaltend eingesetzt werden. Eine valide Alternative stellen Cephalosporine der 2. oder 3. Generation in Kombination mit Metronidazol dar.

The complete amino acid sequence of the Escherichia coli alkaline phosphatase subunit [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1, isozyme 3] has been determined. The monomer contains 449 amino acid residues in a single unglycosylated polypeptide chain having a calculated Mrof 47,029. Isozyme 1 has an additional arginine residue at the NH2terminus that presumably results from variability in processing of precursor molecules. Sequence data were obtained from both manual and automatic Edman degradation of the tryptic and cyanogen bromide peptides, as well as other peptides derived therefrom. The two disulfide bonds were determined from analyses of the appropriate peptic peptides. This structure confirms earlier reports of the sequence surrounding the active-site serine and both the NH2- and COOH-terminal cyanogen bromide fragments. A secondary structure prediction places nearly half the residues in α -helical segments that have 13% and 16%, respectively, in β -strand and β -turn orientations.

Patients with complicated appendicitis frequently develop postoperative septic complications. There are no uniform standards for the choice of perioperative antibiotic prophylaxis and the duration of postoperative antibiotic treatment. The purpose of this study was to investigate associations between microbiological samples and postoperative complications.BACKGROUNDPatients with complicated appendicitis frequently develop postoperative septic complications. There are no uniform standards for the choice of perioperative antibiotic prophylaxis and the duration of postoperative antibiotic treatment. The purpose of this study was to investigate associations between microbiological samples and postoperative complications.Patients with appendectomy and positive intraoperative swabs during 2013-2018 were included in this case-control study. Pathogen classes and their resistance patterns were evaluated in initial and follow-up swabs and compared in each of the groups with and without complications.METHODSPatients with appendectomy and positive intraoperative swabs during 2013-2018 were included in this case-control study. Pathogen classes and their resistance patterns were evaluated in initial and follow-up swabs and compared in each of the groups with and without complications.A total of 870 patients underwent surgery during the period studied. Pathogen detection succeeded in 102 of 210 cases (48.6%) with suspected bacterial peritoneal contamination. Conversion from laparoscopic to open intra-abdominal perforation and the presence of an abscess were independent risk factors for wound infections in the multivariate analysis. The combination of different classes of pathogens resulted in significantly increased overall resistance to ampicillin/sulbactam in both the initial swabs (57%) and the follow-up swabs (73%). Resistant E. coli strains combined with certain anaerobes were also regularly detected in postoperative intra-abdominal abscesses. Piperacillin/tazobactam was effective against 83% of positive swabs in our resistance tests.RESULTSA total of 870 patients underwent surgery during the period studied. Pathogen detection succeeded in 102 of 210 cases (48.6%) with suspected bacterial peritoneal contamination. Conversion from laparoscopic to open intra-abdominal perforation and the presence of an abscess were independent risk factors for wound infections in the multivariate analysis. The combination of different classes of pathogens resulted in significantly increased overall resistance to ampicillin/sulbactam in both the initial swabs (57%) and the follow-up swabs (73%). Resistant E. coli strains combined with certain anaerobes were also regularly detected in postoperative intra-abdominal abscesses. Piperacillin/tazobactam was effective against 83% of positive swabs in our resistance tests.Surgical treatment for complicated appendicitis remains the central therapeutic column. A regular review of the existing resistance patterns in perforated appendicitis can help to adjust and improve antibiotic treatment. Piperacillin/tazobactam should be used cautiously as a reserve antibiotic. A valid alternative is second or third generation cephalosporins in combination with metronidazole.CONCLUSIONSurgical treatment for complicated appendicitis remains the central therapeutic column. A regular review of the existing resistance patterns in perforated appendicitis can help to adjust and improve antibiotic treatment. Piperacillin/tazobactam should be used cautiously as a reserve antibiotic. A valid alternative is second or third generation cephalosporins in combination with metronidazole.

This research presents estimations for the development of must density and titratable acidity of wine produced during the 21st century in the federal state of Baden-Wuerttemberg in southwestern Germany. The estimations were based on 30 yr long records of climate data and vintages which were then used to initialize a statistical model. The results of the statistical model were used to estimate the must density and titratable acidity of future vintages based on data from climate simulation runs from 2 regional climate models: the regional climate model REMO with A1B and A2 emission scenarios and the climate version of the local model (CLM) with the A1B emission scenario. The estimation was made for the 30 yr periods 2011−2040, 2041−2070 and 2071−2100. An increase of must density and a decrease in titratable acidity for the viticultural districts of Baden and Wuerttemberg as well as for the Bodensee area were detected. The increase in must density from one 30 yr period to the next ranged from 4 to 7° Oechsle, and the decrease in titratable acidity ranged from 0.5 to 2 g l⁻¹. Changes of these magnitudes likely will endanger the quality of established brands without appropriate grower and winemaker adaptations. The results of this study provide a detailed description of possible forthcoming climate-driven impacts on must density and titratable acidity values which can assist viticulturalists in planning adaptations to those changes.