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Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy.

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress.

A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries.

Background: Tau aggregates propagate across functionally connected neuronal networks in tauopathies as Alzheimer's disease. However, the mechanisms underlying this process are poorly understood. Different studies showed that tau release is dependent on neuronal activity and that pathological tau can be found in the extracellular space confined in extracellular vesicles or in a free form. We recently showed that metabotropic glutamate receptors and SNAP25 modulate the release of pathologic tau from human and mouse synaptosomes. Here, with the use of blocking agents such as botulinum neurotoxins (BoNTs), we plan to test the effect on the synaptic release of tau in vitro and in vivo. BoNTs enter synapses and cleave specific synaptic SNARE proteins, impairing synaptic vesicle fusion and release. We aim at demonstrating the potential of BoNTs as tools to study neurodegenerative diseases. Methods: Primary mouse hippocampal neurons were cultured in microfluidic chambers, transduced with lentiviruses expressing human tau (hTau) isoforms, and treated with BoNTs and stimulators. ELISA was used to quantify hTau in the culture media. AAVs expressing hTau were injected in the vitreous of wild‐type mice, and BoNT type A (BoNT/A) was injected in the superior colliculus (SC). Retina, SC and lateral geniculate nucleus (LGN) were analysed through immunohistochemistry. Results: Overexpression of hTau in primary neurons increases the expression of synaptic markers as compared to non‐transduced cells, while any difference is detected between wild‐type and P301S hTau. Neuronal stimulation significantly increases the release of P301S hTau, whereas BoNT/A blocks it. Preliminary in vivo data show no difference in the expression and transfer of wild type and P301S hTau in the SC and LGN. The ongoing analysis of BoNT/A injected mice will reveal any effect on tau spread in the brain. Conclusions: The release of hTau is modulated by specific SNARE proteins and differs depending on the isoform in vitro. The use of BoNT/A in vivo will help us to clarify the mechanisms modulating tau release in a complex system. Moreover, with the use of other BoNTs, we will provide novel insights into the mechanisms of synaptic tau release and identify novel molecular targets for the development of therapeutic interventions to treat tauopathies. [ABSTRACT FROM AUTHOR]

Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65-89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid-femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; P=0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10-3; P=0.009); only the latter remained significant after adjustment for confounders (P=0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; P for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; P=0.006; P=0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34+ cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa-1; P=0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34+ cells, and preserved carotid distensibility.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01725178. [ABSTRACT FROM AUTHOR]

Abstract: Epithelioid angiomyolipoma (AML) is an uncommon renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis. Extrarenal AMLs are rare, and to the best of our knowledge, this is the first reported case of a primary monotypic epithelioid AML of adrenal gland in a patient without evidence of tuberous sclerosis. The patient is a 42-year old man who presented with retroperitoneal hemorrhage resulting from spontaneous rupture of adrenal mass. Histologically, the tumor showed a prominent component of epithelioid smooth muscle cells with slightly pleomorphic nuclei, sometimes with prominent nucleoli and eosinophilic cytoplasm resembling oncocytic tumors. Epithelioid cells were positive for melanoma (HMB45 and positive MelanA) and smooth muscle markers (α-smooth muscle–specific actin), but not for epithelial markers (cytokeratin, EMA). Differential diagnosis from renal cell carcinoma, adrenal gland carcinoma, and metastatic carcinoma is often challenging because of its epithelioid morphology. Because primary and secondary malignant tumors are much more common and aggressive neoplasms, establishing the correct diagnosis has important therapeutic and prognostic implications. [Copyright &y& Elsevier]

Background: In tauopathies such as Alzheimer's disease, tau aggregates are known to propagate across functionally connected neuronal networks, but the mechanisms underlying this process are poorly understood. Several lines of evidence support the hypothesis that tau release is dependent on neuronal activity. Pathological tau can be found in the extracellular space, inside synaptic vesicles, and other synaptic compartments, or in a free form. We aim to test both in vitro and in vivo the effect of selected botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) on the release of tau from synaptic terminals. BoNTs and TeNT enter synapses and cleave different synaptic SNARE proteins, impairing synaptic vesicle fusion and release and they may affect tau spread. Method: Primary neurons were cultured in MFCs and transduced with lentiviruses expressing human tau (hTau) isoforms. Cells were treated with BoNTs and stimulating agents. The content of hTau in the culture media was quantified with an enzyme‐linked immunosorbent assay (ELISA). Adeno‐associated viral vectors (AAVs) expressing hTau were injected in the vitreous, and the superior colliculus (SC) and lateral geniculate nucleus (LGN) areas were analysed through immunohistochemistry. Result: The release of the 1N4R mutant hTau (P301S), but not the wild‐type form, is affected by botulinum neurotoxin type A (BoNT/A) and neuronal stimulation, which, respectively, significantly decreases and increases the release of P301S hTau. The AAV constructs are correctly expressed in both primary neurons and in retinal ganglion cells (RGCs), and brain sections of SC and LGN were analysed. Conclusion: Clostridial neurotoxins represent a powerful tool for the study of neurons and synapses. Using BoNT/A, we showed that hTau release is modulated by specific SNARE complex components and differs depending on the isoform. The use of other BoNT types in both in vitro and in vivo models will help us to identify the SNARE proteins involved in tau release. This approach will provide novel insights on the mechanisms controlling tau release from synaptic terminals and identify novel molecular targets for the development of therapeutic interventions to treat tauopathies. [ABSTRACT FROM AUTHOR]