Multicomponent Synthesis of Polyphenols and Their In Vitro Evaluation as Potential \u3b2-Amyloid Aggregation Inhibitors

While plant polyphenols possess a variety of biological properties, exploration of chemical diversity around them is still problematic. Here, an example of application of the Ugi multicomponent reaction to the combinatorial assembly of artificial, yet \u201cnatural-like\u201d, polyphenols is presented. The synthesized compounds represent a second-generation library directed to the inhibition of \u3b2-amyloid protein aggregation. Chiral enantiopure compounds, and polyphenol-\u3b2-lactam hybrids have been prepared too. The biochemical assays have highlighted the importance of the key pharmacophores in these compounds. A lead for inhibition of aggregation of truncated protein A\u3b2pE3-42 was selected

A Multi-Criteria Methodology to Support Public Administration Decision Making Concerning Sustainable Energy Action Plans

For municipalities that have joined the Covenant of Mayors promoted by the European Commission, the Sustainable Energy Action Plan (SEAP) represents a strategic tool for achieving the greenhouse gas reductions required by 2020. So far as the energy retrofit actions in their residential building stock are concerned, which in the small-to-medium municipalities are responsible for more than 60% of CO2 emissions, the scenarios for intervening are normally decided on the basis of an economic (cost/performance) analysis. This type of analysis, however, does not take into account important aspects for small and medium-sized communities such as social aspects, environmental impacts, local economic development and employment. A more comprehensive and effective tool to support the choices of public administrators is the multi-criteria analysis. This study proposes a methodology that integrates multi-criteria analysis in order to support Public Administration/Local Authorities in programming Sustainable Energy Action Plans with a more targeted approach to sustainability. The methodology, based on the ELECTRE III method, was applied to a medium-size municipality in the Lombardy region of Italy. The results obtained with this approach are discussed in this pape

Identification of a high affinity binding site for abscisic acid on human lanthionine synthetase component C-like protein 2

Lanthionine synthetase component C-like protein 2 (LANCL2) has been identified as the mammalian receptor mediating the functional effects of the universal stress hormone abscisic acid (ABA) in mammals. ABA stimulates insulin independent glucose uptake in myocytes and adipocytes via LANCL2 binding in vitro, improves glucose tolerance in vivo and induces brown fat activity in vitro and in vivo. The emerging role of the ABA/LANCL2 system in glucose and lipid metabolism makes it an attractive target for pharmacological interventions in diabetes mellitus and the metabolic syndrome. The aim of this study was to investigate the presence of ABA binding site(s) on LANCL2 and identify the amino acid residues involved in ABA binding. Equilibrium binding assays ([3H]-ABA saturation binding and surface plasmon resonance analysis) suggested multiple ABA-binding sites, prompting us to perform a computational study that indicated one putative high-affinity and two low-affinity binding sites. Site-directed mutagenesis (single mutant R118I, triple mutants R118I/R22I/K362I and R118I/S41A/E46I) and equilibrium binding experiments on the mutated LANCL2 proteins identified a high-affinity ABA-binding site involving R118, with a KD of 2.6 nM ± 1.2 nM, as determined by surface plasmon resonance. Scatchard plot analysis of binding curves from both types of equilibrium binding assays revealed a Hill coefficient >1, suggesting cooperativity of ABA binding to LANCL2. Identification of the high-affinity ABA-binding site is expected to allow the design of ABA agonists/antagonists, which will help to understand the role of the ABA/LANCL2 system in human physiology and disease

The acute phase management of spinal cord injury affecting polytrauma patients : the ASAP study

Publisher Copyright: © 2022, The Author(s).Background: Few data on the management of acute phase of traumatic spinal cord injury (tSCI) in patients suffering polytrauma are available. As the therapeutic choices in the first hours may have a deep impact on outcome of tSCI patients, we conducted an international survey investigating this topic. Methods: The survey was composed of 29 items. The main endpoints of the survey were to examine: (1) the hemodynamic and respiratory management, (2) the coagulation management, (3) the timing of magnetic resonance imaging (MRI) and spinal surgery, (4) the use of corticosteroid therapy, (5) the role of intraspinal pressure (ISP)/spinal cord perfusion pressure (SCPP) monitoring and (6) the utilization of therapeutic hypothermia. Results: There were 171 respondents from 139 centers worldwide. A target mean arterial pressure (MAP) target of 80–90 mmHg was chosen in almost half of the cases [n = 84 (49.1%)]. A temporary reduction in the target MAP, for the time strictly necessary to achieve bleeding control in polytrauma, was accepted by most respondents [n = 100 (58.5%)]. Sixty-one respondents (35.7%) considered acceptable a hemoglobin (Hb) level of 7 g/dl in tSCI polytraumatized patients. An arterial partial pressure of oxygen (PaO2) of 80–100 mmHg [n = 94 (55%)] and an arterial partial pressure of carbon dioxide (PaCO2) of 35–40 mmHg [n = 130 (76%)] were chosen in most cases. A little more than half of respondents considered safe a platelet (PLT) count > 100.000/mm3 [n = 99 (57.9%)] and prothrombin time (PT)/activated partial thromboplastin time (aPTT) < 1.5 times the normal control [n = 85 (49.7%)] in patients needing spinal surgery. MRI [n = 160 (93.6%)] and spinal surgery [n = 158 (92.4%)] should be performed after intracranial, hemodynamic, and respiratory stabilization by most respondents. Corticosteroids [n = 103 (60.2%)], ISP/SCPP monitoring [n = 148 (86.5%)], and therapeutic hypothermia [n = 137 (80%)] were not utilized by most respondents. Conclusions: Our survey has shown a great worldwide variability in clinical practices for acute phase management of tSCI patients with polytrauma. These findings can be helpful to define future research in order to optimize the care of patients suffering tSCI.Peer reviewe

The acute phase management of spinal cord injury affecting polytrauma patients: the ASAP study

Background: Few data on the management of acute phase of traumatic spinal cord injury (tSCI) in patients suffering polytrauma are available. As the therapeutic choices in the first hours may have a deep impact on outcome of tSCI patients, we conducted an international survey investigating this topic. Methods: The survey was composed of 29 items. The main endpoints of the survey were to examine: (1) the hemodynamic and respiratory management, (2) the coagulation management, (3) the timing of magnetic resonance imaging (MRI) and spinal surgery, (4) the use of corticosteroid therapy, (5) the role of intraspinal pressure (ISP)/spinal cord perfusion pressure (SCPP) monitoring and (6) the utilization of therapeutic hypothermia. Results: There were 171 respondents from 139 centers worldwide. A target mean arterial pressure (MAP) target of 80–90&nbsp;mmHg was chosen in almost half of the cases [n = 84 (49.1%)]. A temporary reduction in the target MAP, for the time strictly necessary to achieve bleeding control in polytrauma, was accepted by most respondents [n = 100 (58.5%)]. Sixty-one respondents (35.7%) considered acceptable a hemoglobin (Hb) level of 7&nbsp;g/dl in tSCI polytraumatized patients. An arterial partial pressure of oxygen (PaO2) of 80–100&nbsp;mmHg [n = 94 (55%)] and an arterial partial pressure of carbon dioxide (PaCO2) of 35–40&nbsp;mmHg [n = 130 (76%)] were chosen in most cases. A little more than half of respondents considered safe a platelet (PLT) count &gt; 100.000/mm3 [n = 99 (57.9%)] and prothrombin time (PT)/activated partial thromboplastin time (aPTT) &lt; 1.5 times the normal control [n = 85 (49.7%)] in patients needing spinal surgery. MRI [n = 160 (93.6%)] and spinal surgery [n = 158 (92.4%)] should be performed after intracranial, hemodynamic, and respiratory stabilization by most respondents. Corticosteroids [n = 103 (60.2%)], ISP/SCPP monitoring [n = 148 (86.5%)], and therapeutic hypothermia [n = 137 (80%)] were not utilized by most respondents. Conclusions: Our survey has shown a great worldwide variability in clinical practices for acute phase management of tSCI patients with polytrauma. These findings can be helpful to define future research in order to optimize the care of patients suffering tSCI

Follow-up strategies for patients with splenic trauma managed non-operatively : the 2022 World Society of Emergency Surgery consensus document

Background In 2017, the World Society of Emergency Surgery published its guidelines for the management of adult and pediatric patients with splenic trauma. Several issues regarding the follow-up of patients with splenic injuries treated with NOM remained unsolved. Methods Using a modified Delphi method, we sought to explore ongoing areas of controversy in the NOM of splenic trauma and reach a consensus among a group of 48 international experts from five continents (Africa, Europe, Asia, Oceania, America) concerning optimal follow-up strategies in patients with splenic injuries treated with NOM. Results Consensus was reached on eleven clinical research questions and 28 recommendations with an agreement rate >= 80%. Mobilization after 24 h in low-grade splenic trauma patients (WSES Class I, AAST Grades I-II) was suggested, while in patients with high-grade splenic injuries (WSES Classes II-III, AAST Grades III-V), if no other contraindications to early mobilization exist, safe mobilization of the patient when three successive hemoglobins 8 h apart after the first are within 10% of each other was considered safe according to the panel. The panel suggests adult patients to be admitted to hospital for 1 day (for low-grade splenic injuries-WSES Class I, AAST Grades I-II) to 3 days (for high-grade splenic injuries-WSES Classes II-III, AAST Grades III-V), with those with high-grade injuries requiring admission to a monitored setting. In the absence of specific complications, the panel suggests DVT and VTE prophylaxis with LMWH to be started within 48-72 h from hospital admission. The panel suggests splenic artery embolization (SAE) as the first-line intervention in patients with hemodynamic stability and arterial blush on CT scan, irrespective of injury grade. Regarding patients with WSES Class II blunt splenic injuries (AAST Grade III) without contrast extravasation, a low threshold for SAE has been suggested in the presence of risk factors for NOM failure. The panel also suggested angiography and eventual SAE in all hemodynamically stable adult patients with WSES Class III injuries (AAST Grades IV-V), even in the absence of CT blush, especially when concomitant surgery that requires change of position is needed. Follow-up imaging with contrast-enhanced ultrasound/CT scan in 48-72 h post-admission of trauma in splenic injuries WSES Class II (AAST Grade III) or higher treated with NOM was considered the best strategy for timely detection of vascular complications. Conclusion This consensus document could help guide future prospective studies aiming at validating the suggested strategies through the implementation of prospective trauma databases and the subsequent production of internationally endorsed guidelines on the issue.Peer reviewe

Duodeno-pancreatic and extrahepatic biliary tree trauma: WSES-AAST guidelines

Duodeno-pancreatic and extrahepatic biliary tree injuries are rare in both adult and pediatric trauma patients, and due to their anatomical location, associated injuries are very common. Mortality is primarily related to associated injuries, but morbidity remains high even in isolated injuries. Optimal management of duodeno-bilio-pancreatic injuries is dictated primarily by hemodynamic stability, clinical presentation, and grade of injury. Endoscopic and percutaneous interventions have increased the ability to non-operatively manage these injuries. Late diagnosis and treatment are both associated to increased morbidity and mortality. Sequelae of late presentations of pancreatic injury and complications of severe pancreatic trauma are also increasingly addressed endoscopically and with interventional radiology procedures. However, for moderate and severe extrahepatic biliary and severe duodeno-pancreatic injuries, immediate operative intervention is preferred as associated injuries are frequent and commonly present with hemodynamic instability or peritonitis. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and American Association for the Surgery of Trauma (AAST) duodenal, pancreatic, and extrahepatic biliary tree trauma management guidelines