Event-related brain potentials in the study of inhibition: cognitive control, source localization and age-related modulations

In the previous 15 years, a variety of experimental paradigms and methods have been employed to study inhibition. In the current review, we analyze studies that have used the high temporal resolution of the event-related potential (ERP) technique to identify the temporal course of inhibition to understand the various processes that contribute to inhibition. ERP studies with a focus on normal aging are specifically analyzed because they contribute to a deeper understanding of inhibition. Three time windows are proposed to organize the ERP data collected using inhibition paradigms: the 200 ms period following stimulus onset; the period between 200 and 400 ms after stimulus onset; and the period between 400 and 800 ms after stimulus onset. In the first 200 ms, ERP inhibition research has primarily focused on N1 and P1 as the ERP components associated with inhibition. The inhibitory processing in the second time window has been associated with the N2 and P3 ERP components. Finally, in the third time window, inhibition has primarily been associated with the N400 and N450 ERP components. Source localization studies are analyzed to examine the association between the inhibition processes that are indexed by the ERP components and their functional brain areas. Inhibition can be organized in a complex functional structure that is not constrained to a specific time point but, rather, extends its activity through different time windows. This review characterizes inhibition as a set of processes rather than a unitary process

Mitochondrial interaction of fibrosis-protective 5-methoxy tryptophan enhances collagen uptake by macrophages

5-methoxy tryptophan (5-MTP) is an anti-fibrotic metabolite made by fibroblasts and epithelial cells, present in a micromolar concentrations in human blood, and is associated with the progression of fibrotic kidney disease, but the mechanism is unclear. Here, we show by microscopy and functional assays that 5-MTP influences mitochondria in human peripheral blood monocyte-derived macrophages. As a result, the mitochondrial membranes are more rigid, more branched, and are protected against oxidation. The macrophages also change their metabolism by reducing mitochondrial import of acyl-carnitines, intermediates of fatty acid metabolism, driving glucose import. Moreover, 5-MTP increases the endocytosis of collagen by macrophages, and experiments with inhibition of glucose uptake showed that this is a direct result of their altered metabolism. However, 5-MTP does not affect the macrophages following pathogenic stimulation, due to 5-MTP degradation by induced expression of indole-amine oxygenase-1 (IDO-1). Thus, 5-MTP is a fibrosis-protective metabolite that, in absence of pathogenic stimulation, promotes collagen uptake by anti-inflammatory macrophages by altering the physicochemical properties of their mitochondrial membranes

Globale Migration am Beginn des 21. Jahrhunderts : Eine Welt ohne Grenzen? Dokumentation der internationalen Fachtagung vom 30./31. Mai 2006 in Berlin

Nonafluorobutanesulfonyl azide is a highly efficient reagent for the copper-catalyzed coupling of terminal alkynes to give symmetrical and unsymmetrical 1,3-diynes in good to excellent yields and with good functional group compatibility. The reaction is extremely fast (<10 min), even at low temperature (−78 °C), and requires substoichiometric amounts of a simple copper­(I) or copper­(II) salt (2–5 mol %) and an organic base (0.6 mol %). A possible mechanistic pathway is briefly discussed on the basis of model DFT theoretical calculations. The quantitative assessment of the safety of use and shelf stability of nonafluorobutanesulfonyl azide has confirmed that this reagent is a superior and safe alternative to other electrophilic azide reagents in use today

Molecular Bases for Combinatorial Treatment Strategies in Patients with KRAS Mutant Lung Adenocarcinoma and Squamous Cell Lung Carcinoma

Innovative therapeutic agents have significantly improved outcomes, with an acceptable safety profile, in a substantial proportion of non-small cell lung cancer (NSCLC) patients in whom the malignant phenotype of the disease is determined by oncogenic molecular alterations. However, the benefit seen with these treatment models has not translated well to NSCLCs with KRAS mutations or squamous cell histology. Although efforts have been made to develop precision medicine approaches, KRAS mutant NSCLC and lung squamous cell carcinoma (LSCC) continue to display resistance to therapy. Recently, based on the results of the Phase III SQUIRE trial, the EGFR monoclonal antibody necitumumab received FDA authorization in combination with cisplatin and gemcitabine for first line treatment of patients with metastatic LSCC. Among the molecular compounds tested in KRAS mutant NSCLC patients, the MEK inhibitor, selumentinib, combined with docetaxel in second line setting, determined a progression-free survival improvement, but no overall survival advantage. Better understanding is needed in regard to signaling pathways which cooperate to induce oncogene transformation in LSCC and KRAS mutant NSCLC and could determine intrinsic or acquired resistance to necitumumab and selumetinib. Greater understanding of such pathways will provide a molecular base upon which to improve the scant clinical benefit with these compounds

Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance

Purpose: Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings. Methods: This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem–Intervention/Indicator–Comparator–Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria. Results: Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [18F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [18F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [18F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [18F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [18F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging. Conclusion: These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications

SARS-CoV-2 infection in patients with primary Sjögren syndrome: characterization and outcomes of 51 patients

OBJECTIVE: To analyse the prognosis and outcomes of SARS-CoV-2 infection in patients with primary SS. METHODS: We searched for patients with primary SS presenting with SARS-CoV-2 infection (defined following and according to the European Centre for Disease Prevention and Control guidelines) among those included in the Big Data Sjögren Registry, an international, multicentre registry of patients diagnosed according to the 2002/2016 classification criteria. RESULTS: A total of 51 patients were included in the study (46 women, mean age at diagnosis of infection of 60 years). According to the number of patients with primary SS evaluated in the Registry (n = 8211), the estimated frequency of SARS-CoV-2 infection was 0.62% (95% CI 0.44, 0.80). All but two presented with symptoms suggestive of COVID-19, including fever (82%), cough (57%), dyspnoea (39%), fatigue/myalgias (27%) and diarrhoea (24%), and the most frequent abnormalities included raised lactate dehydrogenase (LDH) (88%), CRP (81%) and D-dimer (82%) values, and lymphopenia (70%). Infection was managed at home in 26 (51%) cases and 25 (49%) required hospitalization (five required admission to ICU, four died). Compared with patients managed at home, those requiring hospitalization had higher odds of having lymphopenia as laboratory abnormality (adjusted OR 21.22, 95% CI 2.39, 524.09). Patients with comorbidities had an older age (adjusted OR 1.05, 95% CI 1.00, 1.11) and showed a risk for hospital admission six times higher than those without (adjusted OR 6.01, 95% CI 1.72, 23.51) in the multivariate analysis. CONCLUSION: Baseline comorbidities were a key risk factor for a more complicated COVID-19 in patients with primary SS, with higher rates of hospitalization and poor outcomes in comparison with patients without comorbidities

Welfare of pigs at slaughter

The killing of pigs for human consumption (slaughtering) can take place in a slaughterhouse or on farm. The processes of slaughtering that were assessed for welfare, from the arrival of pigs until their death, were grouped into three main phases: pre-stunning (including arrival, unloading from the truck, lairage, handling and moving of pigs); stunning (including restraint); and bleeding. Stunning methods were grouped into three categories: electrical, controlled atmosphere and mechanical. Twelve welfare consequences the pigs can be exposed to during slaughter were identified: heat stress, cold stress, fatigue, prolonged thirst, prolonged hunger, impeded movement, restriction of movements, resting problem, negative social behaviour, pain, fear and respiratory distress. Welfare consequences and relevant animal-based measures were described. In total, 30 welfare hazards that could occur during slaughter were identified and characterised, most of them related to stunning and bleeding. Staff were identified as the origin of 29 hazards, which were attributed to the lack of appropriate skill sets needed to perform tasks or to fatigue. Corrective and preventive measures for these hazards were assessed: measures to correct hazards were identified, and management was shown to have a crucial role in prevention. Outcome tables linking hazards, welfare consequences, animal-based measures, origins and preventive and corrective measures were developed for each process. Mitigation measures to minimise welfare consequences are proposed.info:eu-repo/semantics/publishedVersio

Welfare of pigs during killing for purposes other than slaughter

Pigs at different stages of the production cycle may have to be killed on-farm for purposes other thanslaughter (where slaughter is dened as killing for human consumption) either individually (e.g.severely injured pigs) or on a large scale (e.g. unproductive animals or for disease control reasons).This opinion assessed the risks associated with the on-farm killing of pigs and included two phases: 1)handling and moving of pigs and 2) killing methods (including restraint). The killing methods weresubdivided into four categories: electrical methods, mechanical methods, gas mixture methods andlethal injec tion. Four welfare consequences to which pigs can be exposed to during on-farm killingwere identied: pain, fear, impeded movement and respiratory distress. Welfare consequences andrelevant animal-based measures were described. In total, 28 hazards were associated with the welfareconsequences; majority of the hazards (24) are related to Phase 2 (killing). The main hazards areassociated with lack of staff skills and training, and poor-designed and constructed facilities. Staff wasidentied as an origin of all hazards, either due to lack of skills needed to perform appropriate killing ordue to fatigue. Corrective measures were identied for 25 hazards. Outcome tables linking hazards,welfare consequences, animal-based measures, hazard origins, prevent ive and corrective measureswere developed and mitigation measures proposed.info:eu-repo/semantics/publishedVersio

Clinical oncologic applications of PET/MRI: a new horizon

Abstract: Positron emission tomography/magnetic resonance imaging (PET/MRI) leverages the high soft-tissue contrast and the functional sequences of MR with the molecular information of PET in one single, hybrid imaging technology. This technology, which was recently introduced into the clinical arena in a few medical centers worldwide, provides information about tumor biology and microenvironment. Studies on indirect PET/MRI (use of positron emission tomography/computed tomography (PET/CT) images software fused with MRI images) have already generated interesting preliminary data to pave the ground for potential applications of PET/MRI. These initial data convey that PET/MRI is promising in neuro-oncology and head &amp; neck cancer applications as well as neoplasms in the abdomen and pelvis. The pediatric and young adult oncology population requiring frequent follow-up studies as well as pregnant woman might benefit from PET/MRI due to its lower ionizing radiation dose. The indication and planning of therapeutic interventions and specifically radiation therapy in individual patients could be and to a certain extent are already facilitated by performing PET/MRI. The objective of this article is to discuss potential clinical oncology indications of PET/MRI