Splenic Artery Infarct Requiring Surgery: A Rare Complication of COVID-19 Infection.

Introduction. Coronavirus disease (COVID-19) from SARS-CoV-2 infection is linked to a hypercoagulable state, leading to arterial and venous thrombotic events, of which pulmonary embolism is the most frequent. However, arterial thromboembolisms may also occur as visceral infracts in unusual sites, such as the renal, splenic, and intestinal arteries. Case Report. A 46-year-old unvaccinated male with a COVID-19 infection was admitted to the COVID-19 isolation ward with symptoms of respiratory infection. He complained of epigastric pain and fever for several days; radiological imaging of the abdomen revealed complete splenic arterial occlusion due to a large infarct. He was treated with low molecular weight heparin (enoxaparin) in therapeutic doses, resulting in minimal improvement. However, the pain worsened, and eventually, a laparotomy and splenectomy were performed. He was hospitalized for another 36 days before he was discharged in good condition. A second surgery was performed to remove a noninfected encapsulated hematoma from the subdiaphragmatic space. The patient remained healthy afterward, with no relapses. Discussion. Although rare, the number of cases of visceral infarcts in COVID-19 patients has increased. Splenic artery infarct is an exceptional case of acute abdominal pain that can be treated successfully with anticoagulant medication. Splenectomy may be required to manage refractory pain after failure of conservative management.

Translational Control by 4E-BP1/2 Suppressor Proteins Regulates Mitochondrial Biosynthesis and Function during CD8+ T Cell Proliferation.

CD8+ T cell proliferation and differentiation into effector and memory states are high-energy processes associated with changes in cellular metabolism. CD28-mediated costimulation of T cells activates the PI3K/AKT/mammalian target of rapamycin signaling pathway and induces eukaryotic translation initiation factor 4E-dependent translation through the derepression by 4E-BP1 and 4E-BP2. In this study, we demonstrate that 4E-BP1/2 proteins are required for optimum proliferation of mouse CD8+ T cells and the development of an antiviral effector function. We show that translation of genes encoding mitochondrial biogenesis is impaired in T cells derived from 4E-BP1/2-deficient mice. Our findings demonstrate an unanticipated role for 4E-BPs in regulating a metabolic program that is required for cell growth and biosynthesis during the early stages of CD8+ T cell expansion.

Tankyrase represses autoinflammation through the attenuation of TLR2 signaling.

Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response.

GEF-H1 Is Required for Colchicine Inhibition of Neutrophil Rolling and Recruitment in Mouse Models of Gout.

Gout is a painful arthritic inflammatory disease caused by buildup of monosodium urate (MSU) crystals in the joints. Colchicine, a microtubule-depolymerizing agent that is used in prophylaxis and treatment of acute gout flare, alleviates the painful inflammatory response to MSU crystals. Using i.p. and intra-articular mouse models of gout-like inflammation, we found that GEF-H1/GEF-H1/AHRGEF2, a microtubule-associated Rho-GEF, was necessary for the inhibitory effect of colchicine on neutrophil recruitment. GEF-H1 was required for neutrophil polarization in response to colchicine, characterized by uropod formation, accumulation of F-actin and myosin L chain at the leading edge, and accumulation of phosphorylated myosin L chain, flotillin-2, and P-selectin glycoprotein ligand-1 (PSGL-1) in the uropod. Wild-type neutrophils that were pre-exposed to colchicine failed to roll or accumulate on activated endothelial monolayers, whereas GEF-H1 knockout (GEF-H1-/-) neutrophils were unaffected by treatment with colchicine. In vivo, colchicine blocked MSU-induced recruitment of neutrophils to the peritoneum and the synovium in wild-type mice, but not in GEF-H1-/- mice. Inhibition of macrophage IL-1ß production by colchicine was independent of GEF-H1, supporting a neutrophil-intrinsic mode of action. Our results suggest that the anti-inflammatory effects of colchicine in acute gout-like inflammation can be accounted for by inhibition of neutrophil-rolling interactions with the inflamed vasculature and occurs through GEF-H1-dependent neutrophil stimulation by colchicine. These results contribute to our understanding of the therapeutic action of colchicine, and could inform the application of this drug in other conditions.

Go with the flow: GEF-H1 mediated shear stress mechanotransduction in neutrophils.

Neutrophils in circulation experience significant shear forces due to blood flow when they tether to the vascular endothelium. Biochemical and biophysical responses of neutrophils to the physical force of flowing blood modulate their behavior and promote tissue recruitment under pro-inflammatory conditions. Neutrophil mechanotransduction responses occur through mechanisms that are not yet fully understood. In our recent work, we showed that GEF-H1, a RhoA specific guanine nucleotide exchange factor (GEF), is required to maintain neutrophil motility and migration in response to shear stress. GEF-H1 re-localizes to flottilin-rich uropods in neutrophils in response to fluid shear stress and promotes spreading and crawling on activated endothelial cells. GEF-H1 drives cellular contractility through myosin light chain (MLC) phosphorylation downstream of the Rho-ROCK signaling axis. We propose that GEF-H1-dependent cell spreading and crawling in shear stress-dependent neutrophil recruitment from the vasculature are due to the specific localization of Rho-induced contractility in the uropod.

Timed Regulation of 3BP2 Induction Is Critical for Sustaining CD8+ T Cell Expansion and Differentiation.

Successful anti-viral response requires the sustained activation and expansion of CD8+ T cells for periods that far exceed the time limit of physical T cell interaction with antigen-presenting cells (APCs). The expanding CD8+ T cell pool generates the effector and memory cell populations that provide viral clearance and long-term immunity, respectively. Here, we demonstrate that 3BP2 is recruited in cytoplasmic microclusters and nucleates a signaling complex that facilitates MHC:peptide-independent activation of signaling pathways downstream of the TCR. We show that induction of the adaptor molecule 3BP2 is a sensor of TCR signal strength and is critical for sustaining CD8+ T cell proliferation and regulating effector and memory differentiation.

The Main Anatomical Variations of the Pancreatic Duct System: Review of the Literature and Its Importance in Surgical Practice.

Anatomical variations or anomalies of the pancreatic ducts are important in the planning and performance of endoscopic retrograde cholangiopancreatography (ERCP) and surgical procedures of the pancreas. Normal pancreatic duct anatomy occurs in approximately 94.3% of cases, and multiple variations have been described for the remaining 5.7%. The purpose of this study was to review the literature on the pancreatic duct anatomy and to underline its importance in daily invasive endoscopic and surgical practice. Two main databases were searched for suitable articles published from 2000 to 2017, and results concerning more than 8,200 patients were included in the review. The most common anatomical variation was that of pancreas divisum, which appeared in approximately 4.5% of cases.

Assessing phytotoxicity of trace element-contaminated soils phytomanaged with gentle remediation options at ten European field trials.

Gentle remediation options (GRO), i.e. in situ stabilisation, (aided) phytoextraction and (aided) phytostabilisation, were implemented at ten European sites contaminated with trace elements (TE) from various anthropogenic sources: mining, atmospheric fallout, landfill leachates, wood preservatives, dredged-sediments, and dumped wastes. To assess the performance of the GRO options, topsoil was collected from each field trial, potted, and cultivated with lettuce (Lactuca sativa L.) for 48days. Shoot dry weight (DW) yield, photosynthesis efficiency and major element and TE concentrations in the soil pore water and lettuce shoots were measured. GRO implementation had a limited effect on TE concentrations in the soil pore water, although use of multivariate Co-inertia Analysis revealed a clear amelioration effect in phytomanaged soils. Phytomanagement increased shoot DW yield at all industrial and mine sites, whereas in agricultural soils improvements were produced in one out of five sites. Photosynthesis efficiency was less sensitive than changes in shoot biomass and did not discriminate changes in soil conditions. Based on lettuce shoot DW yield, compost amendment followed by phytoextraction yielded better results than phytostabilisation; moreover shoot ionome data proved that, depending on initial soil conditions, recurrent compost application may be required to maintain crop production with common shoot nutrient concentrations.

The Main Anatomic Variations of the Hepatic Artery and Their Importance in Surgical Practice: Review of the Literature.

Anatomical variations of the hepatic artery are important in the planning and performance of abdominal surgical procedures. Normal hepatic anatomy occurs in approximately 80% of cases, for the remaining 20% multiple variations have been described. The purpose of this study was to review the existing literature on the hepatic anatomy and to stress out its importance in surgical practice. Two main databases were searched for eligible articles during the period 2000 - 2015, and results concerning more than 19,000 patients were included in the study. The most common variation was the replaced right hepatic artery (type III according to Michels classification) which is the chief source of blood supply to the bile duct.

GEF-H1 is necessary for neutrophil shear stress-induced migration during inflammation.

Leukocyte crawling and transendothelial migration (TEM) are potentiated by shear stress caused by blood flow. The mechanism that couples shear stress to migration has not been fully elucidated. We found that mice lacking GEF-H1 (GEF-H1-/-), a RhoA-specific guanine nucleotide exchange factor (GEF), displayed limited migration and recruitment of neutrophils into inflamed tissues. GEF-H1-/- leukocytes were deficient in in vivo crawling and TEM in the postcapillary venules. We demonstrated that although GEF-H1 deficiency had little impact on the migratory properties of neutrophils under static conditions, shear stress triggered GEF-H1-dependent spreading and crawling of neutrophils and relocalization of GEF-H1 to flotillin-2-rich uropods. Our results identify GEF-H1 as a component of the shear stress response machinery in neutrophils required for a fully competent immune response to bacterial infection.

Solid Serous Adenoma of the Pancreas: A Case Report and Review of the Literature.

Herein, we report a case of a solid-type serous cystadenoma of the pancreas which is the 16th case reported worldwide and the first ever reported in Greece. Magnetic resonance imaging showed a hypervascular mass in the tail of the pancreas of a 72-year-old female who presented with mild abdominal pain. Distal pancreatectomy was performed by laparotomy and histological and immunohistochemical examination revealed a solid-type serous cystadenoma of the pancreas. Preoperative diagnosis of a solid-type serous cystadenoma of the pancreas is difficult, and, due to its benign nature, simple excision of the tumor is the recommended treatment.

Correction: Ioannis Dimitriou et al, Palmaris Longus Muscle's Prevalence in Different Nations and Interesting Anatomical Variations: Review of the Literature.

[This corrects the article DOI: 10.14740/jocmr2243w.].

Agronomic Practices for Improving Gentle Remediation of Trace Element-Contaminated Soils.

The last few decades have seen the rise of Gentle soil Remediation Options (GRO), which notably include in situ contaminant stabilization ("inactivation") and plant-based (generally termed "phytoremediation") options. For trace element (TE)-contaminated sites, GRO aim to either decrease their labile pool and/or total content in the soil, thereby reducing related pollutant linkages. Much research has been dedicated to the screening and selection of TE-tolerant plant species and genotypes for application in GRO. However, the number of field trials demonstrating successful GRO remains well below the number of studies carried out at a greenhouse level. The move from greenhouse to field conditions requires incorporating agronomical knowledge into the remediation process and the ecological restoration of ecosystem services. This review summarizes agronomic practices against their demonstrated or potential positive effect on GRO performance, including plant selection, soil management practices, crop rotation, short rotation coppice, intercropping/row cropping, planting methods and plant densities, harvest and fertilization management, pest and weed control and irrigation management. Potentially negative effects of GRO, e.g., the introduction of potentially invasive species, are also discussed. Lessons learnt from long-term European field case sites are given for aiding the choice of appropriate management practices and plant species.

Selecting chemical and ecotoxicological test batteries for risk assessment of trace element-contaminated soils (phyto)managed by gentle remediation options (GRO).

During the past decades a number of field trials with gentle remediation options (GRO) have been established on trace element (TE) contaminated sites throughout Europe. Each research group selects different methods to assess the remediation success making it difficult to compare efficacy between various sites and treatments. This study aimed at selecting a minimum risk assessment battery combining chemical and ecotoxicological assays for assessing and comparing the effectiveness of GRO implemented in seven European case studies. Two test batteries were pre-selected; a chemical one for quantifying TE exposure in untreated soils and GRO-managed soils and a biological one for characterizing soil functionality and ecotoxicity. Soil samples from field studies representing one of the main GROs (phytoextraction in Belgium, Sweden, Germany and Switzerland, aided phytoextraction in France, and aided phytostabilization or in situ stabilization/phytoexclusion in Poland, France and Austria) were collected and assessed using the selected test batteries. The best correlations were obtained between NH4NO3-extractable, followed by NaNO3-extractable TE and the ecotoxicological responses. Biometrical parameters and biomarkers of dwarf beans were the most responsive indicators for the soil treatments and changes in soil TE exposures. Plant growth was inhibited at the higher extractable TE concentrations, while plant stress enzyme activities increased with the higher TE extractability. Based on these results, a minimum risk assessment battery to compare/biomonitor the sites phytomanaged by GROs might consist of the NH4NO3 extraction and the bean Plantox test including the stress enzyme activities.

Perforation of Meckel's diverticulum by a fish bone presenting as acute appendicitis: a case report.

INTRODUCTION: Meckel's diverticulum is the commonest congenital abnormality of the gastrointestinal tract. Most of them are asymptomatic but can rarely present with forms of complications such as bleeding, obstruction, diverticulitis, intussusception and neoplasm. Patients with a perforation of Meckel's diverticulum by a foreign body are rare and may present with right iliac fossa pain, which mimics acute appendicitis. CASE PRESENTATION: A 64-year-old Greek man presented with an eight-hour history of right iliac fossa pain. On examination, our patient had tenderness in his right iliac fossa. A provisional diagnosis of acute appendicitis was made. He was taken to theatre with the option of an appendicectomy. His appendix was found to have an about normal appearance. An inflamed Meckel's diverticulum that had been perforated by a fish bone was found to be the cause of the abdominal pain. A Meckel's diverticulectomy was performed. Our patient made an uneventful recovery and was discharged after two days. CONCLUSIONS: Complications of Meckel's diverticulum can be difficult to diagnose and early recognition and timely operative intervention must occur in order to provide the best outcome for these patients. This is an interesting and unusual case of perforation of Meckel's diverticulum that highlights the importance of considering Meckel's diverticulum as a differential diagnosis in every patient presenting with acute abdomen.

TGF beta1 and TGF beta2 and their role in posthemorrhagic hydrocephalus following SAH and IVH.

OBJECTIVE: Posthemorrhagic hydrocephalus (pHC) is a serious complication following subarachnoid hemorrhage (SAH) and intraventricular hemorrhage (IVH). Besides known clinical predictors, different cytokines have drawn attention to the development of chronic hydrocephalus. Transforming growth factor (TGF) ß1 and TGF ß2 are involved in fibrogenesis, scar formation, cell survival, and tissue differentiation and may play a role in the occurrence of pHC. TGF ß1 is stored in platelets in large amount and is released in the cerebrospinal fluid (CSF) after SAH and IVH. Both TGF ß1 and TGF ß2 can be expressed by various intracranial cells. METHODS: TGF ß1 and ß2 were measured in CSF and blood samples of 42 patients with SAH or IVH with acute hydrocephalus during the first 10 days after ictus. Furthermore, albumin was measured in CSF as an indicator for the amount of blood. Patients were categorized as developing pHC requiring shunt treatment or not-developing pHC within 6 months. RESULTS: After adjusting for age, SAH resulted significantly more often in pHC than did IVH. Plasma levels of TGF ß1 showed a marked increase over time, whereas CSF levels of TGF ß1 constantly decreased. The time course of TGF ß1 and albumin in CSF was paralleled and did not correlate with the development of shunt dependent pHC. Also, TGF ß1 plasma concentrations did not correlate with shunt dependent pHC. TGF ß2 concentrations in plasma showed stable values over time without any variations. TGF ß2 in CSF described a parabolic course with a peak at day 6 after ictus. No correlation was found concerning TGF ß2 in plasma or CSF and shunt dependent pHC. CONCLUSION: TGF ß1 in CSF is derived by platelets from the cisternal or ventricular clot. TGF ß2 in CSF is derived as a general reaction of traumatized brain tissue. These data do not confirm a crucial role of TGF ß1 and TGF ß2 release in the development of pHC.

Single institution's experience in laparoscopic appendectomy as a suitable therapy for complicated appendicitis.

PURPOSE: Although laparoscopic appendectomy (LA) for acute appendicitis (AA) is widely performed, the value of LA for the treatment of complicated appendicitis (CA) is still controversially discussed. METHODS: In a retrospective study, we analyzed the clinical records of 404 patients who underwent LA or conversion (intention-to-treat group) or open appendectomy (OA) for AA or CA at the Alfried Krupp Hospital Essen-Rüttenscheid, Germany between January 2007 and December 2010. RESULTS: AA was treated in 64.2 % by LA and in 35.8 % by OA; the LA-to-OA conversion rate amounts to 3.7 %. CA was treated in 56 % by LA and in 44 % by OA. The LA-to-OA conversion rate here is 13.1 %, and compared to AA, it is significantly (P < 0.01) higher. Comparing LA with OA in both patient groups, we find no significant difference in the overall complication rate, the rate of postoperative intraabdominal abscesses and postoperative ileus. However, in both patient groups, the wound infection rate was significantly lower in patients who had undergone LA (AA P < 0.05 versus CA P < 0.01). In contrast to patients suffering from AA, patients with CA needed significantly less resurgery when treated by LA as compared to OA (P < 0.001). While the duration of surgery for the treatment of AA and CA was similar, the hospitalization time was significantly shorter with LA than with OA (AA P < 0.05 versus CA P < 0.001). CONCLUSIONS: The data suggest that LA is advantageous not only in the treatment of AA, but also in the therapy of CA. Thus, LA may become a proper and safe routine method if performed by an experienced surgeon.

The 3BP2 adapter protein is required for chemoattractant-mediated neutrophil activation.

3BP2 is a pleckstrin homology and Src homology 2 domain-containing adapter protein mutated in cherubism, a rare autosomal-dominant human bone disorder. Previously, we have demonstrated a functional role for 3BP2 in peripheral B cell development and in peritoneal B1 and splenic marginal zone B cell-mediated Ab responses. In this study, we show that 3BP2 is required for G protein-coupled receptor-mediated neutrophil functions. Neutrophils derived from 3BP2-deficient (Sh3bp2-/-) mice failed to polarize their actin cytoskeleton or migrate in response to a gradient of chemotactic peptide, fMLF. Sh3bp2-/- neutrophils failed to adhere, crawl, and emigrate out of the vasculature in response to fMLF superfusion. 3BP2 is required for optimal activation of Src family kinases, small GTPase Rac2, neutrophil superoxide anion production, and for Listeria monocytogenes bacterial clearance in vivo. The functional defects observed in Sh3bp2-/- neutrophils may partially be explained by the failure to fully activate Vav1 guanine nucleotide exchange factor and properly localize P-Rex1 guanine nucleotide exchange factor at the leading edge of migrating cells. Our results reveal an obligate requirement for the adapter protein 3BP2 in G protein-coupled receptor-mediated neutrophil function.

Environmental assessment of energy production based on long term commercial willow plantations in Sweden.

The present paper analyzed the environmental assessment of short rotation willow plantations in Sweden based on the standard framework of Life Cycle Assessment (LCA) from the International Standards Organisation. The analysis is focused on two alternative management regimes for willow plantations dedicated to biomass production for energy purposes. The data used included the averages of a large sample of commercial plantations. One of the scenarios is carried out under nitrogen based fertilized conditions and the other under non-fertilized management with total biomass yields (dry weight) of 140t/ha and 86t/ha over a 21 and 22-year life time respectively. The environmental profile was analyzed in terms of the potentials for abiotic depletion, acidification, eutrophication, global warming, ozone layer depletion, photochemical oxidant formation, human toxicity, fresh water aquatic ecotoxicity, marine aquatic ecotoxicity and terrestrial ecotoxicity. In addition, an energy analysis was performed using the cumulative energy demand method (CED). The application of nitrogen based fertilizers allows an increase in the biomass yield per ha of up to 40% although the contributions to almost all impact categories, particularly the eutrophication potential and toxicity potential impact categories are also considerably higher. Conversely, due to the higher biomass yields achieved with fertilization of these willow plantations, that regime presents a better overall environmental profile in terms of energy yield and global warming potential.