Practical Machine Learning Strategies. I. Correcting the MMFF Molecular Mechanics Model to More Accurately Provide Conformational Energy Differences in Flexible Organic Molecules.

A correction to the MMFF molecular mechanics model, based on a neural network trained to reproduce conformer energy differences obtained from ωB97X-V/6-311+G(2df,2p)[6-311G*]//MMFF calculations is described. It is supported for molecules containing H, C, N, O, F, S, Cl, and Br. The correction adds only slightly to the cost of MMFF, and the resulting corrected model is several orders of magnitude faster than ωB97X-V/6-311+G(2df,2p)[6-311G*].

Recovery of fibrinogen concentrate after intraosseous application is equivalent to the intravenous route in a porcine model of hemodilution.

Background: Fibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead.

A comparison of a bovine albumin/glutaraldehyde glue versus fibrin sealant for hernia mesh fixation in experimental onlay and IPOM repair in rats.

Background: Research in hernia repair has targeted new atraumatic mesh fixation to reduce major complications such as chronic pain and adhesion formation. The efficacy and safety of two surgical adhesives, viz. Artiss® (FS, fibrin sealant containing 4 IU thrombin) and Bioglue® (AGG, bovine serum albumin/glutaraldehyde glue), were evaluated in this study.

Endotoxin causes functional endoplasmic reticulum failure, possibly mediated by mitochondria.

Inflammatory response has recently been shown to induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which either recovers proper ER function or activates apoptosis. Here we show that endotoxin (lipopolysaccharide = LPS) can lead to functional ER failure tentatively via a mitochondrion-dependent pathway in livers of rats. Histological examination did not reveal significant damage to liver in form of necroses.

Efficient calculation of heats of formation.

An efficient procedure has been devised for calculating heats of formation of uncharged, closed-shell molecules comprising H, C, N, O, F, S, Cl, and Br. Known as T1, it follows the G3(MP2) recipe, by substituting an HF/6-31G* for the MP2/6-31G* geometry, eliminating both the HF/6-31G* frequency and QCISD(T)/6-31G* energy and approximating the MP2/G3MP2large energy using dual basis set RI-MP2 techniques. Taken together, these changes reduce computation time by 2-3 orders of magnitude.

Invited article: physical and chemical analyses of impregnated cathodes operated in a plasma environment.

Destructive analyses of impregnated-cathode assemblies from an ion thruster life test were performed to characterize erosion and degradation after 30,472 h of operation. Post-test inspection of each cathode included examination of the emitter (insert), orifice plate, cathode tube, heater, anode assembly, insulator, and propellant isolator. The discharge-cathode assembly experienced significant erosion due to ion sputtering from the discharge plasma.

The total synthesis of roquefortine C and a rationale for the thermodynamic stability of isoroquefortine C over roquefortine C.

The first total synthesis of roquefortine C is achieved by implementation of a novel elimination strategy to construct the thermodynamically unstable E-dehydrohistidine moiety. Molecular modeling studies are presented which explain the instability of the roquefortine C structure compared to that of isoroquefortine C.

Adverse effects associated with the use of porcine cross-linked collagen implants in an experimental model of incisional hernia repair.

Background: Porcine cross-linked collagen (PermaCol, PCL; TSL, Aldershot, United Kingdom) has been proposed as permanent biomaterial in incisional hernia repair. We evaluated the biocompatibility of PCL in an established animal model.

Material And Methods: In 10 Sprague Dawley rats, two hernias per animal were created in the abdominal wall left and right of the linea alba (1.

Cyanoacrylate tissue sealant impairs tissue integration of macroporous mesh in experimental hernia repair.

Background: Tissue sealants have been proposed as an alternative to permanent fixation devices in hernia repair with the aim of reducing perforation-associated complications and chronic pain. Sealants can be divided into three main categories: synthetic glues (e.g.

Opposite effects of endotoxin on mitochondrial and endoplasmic reticulum functions.

In this study, we determined functional integrity and reactive oxygen species generation in mitochondria and endoplasmic reticulum in liver of rats subjected to endotoxic shock to clarify whether intracellular reactive oxygen species (ROS) destabilize cellular integrity causing necrosis in rats challenged with lipopolysaccharide (LPS). LPS caused drastically increased plasma levels of alanine aminotransferase, suggesting damage to plasma membranes of liver cells. Liver necrosis was confirmed by histological examination.

Adverse effects of porcine small intestine submucosa implants in experimental ventral hernia repair.

Background: Biomeshes made of porcine small intestine submucosa (SIS) have recently been suggested for repair of ventral hernia. A fully biodegradable combination of implant and fibrin sealant fixation was assessed in a new rat model with sutures serving as control.

Methods: In 10 Sprague-Dawley rats, two defects per animal were created in the abdominal wall left and right of the linea alba (1 cm in diameter), and the peritoneum was spared.

NON-activated protein C as post-treatment after spinal cord compression injury in rats.

Background: Neuroprotective effects of recombinant human activated Protein C (rhAPC) in models of Spinal Cord Injury (SCI) and ischemic stroke have been reported in rodents. To rule out immunogenicity of rhAPC and to possibly maintain the physiological PC/thrombin balance the use of zymogen PC in SCI might be preferable. Although activation of Protein C (PC) has been demonstrated in rats, the efficacy and drug safety of NON activated PC has not been previously tested in experimental SCI.

Different effects of endotoxic shock on the respiratory function of liver and heart mitochondria in rats.

This study was designed to clarify whether mitochondrial function/dysfunction and reactive oxygen species (ROS) production have a temporal relationship with organ failure during endotoxic shock. Adult male Sprague-Dawley rats were divided into three groups receiving 1) isotonic saline (control group, n = 16); 2) 8 mg/kg lipopolysaccharide (LPS; n = 8); or 3) 20 mg/kg LPS (n = 8) intraperitoneally under short anesthesia with 3.5% of isoflurane.

Fibrin sealing versus stapling of hernia meshes in an onlay model in the rat.

Incisional and inguinal hernia repair are among the most common procedures of general surgery. Mesh fixation by means of staples or sutures may lead to severe complications. The use of fibrin sealant (FS) has been suggested as alternative, but data on biocompatibility and adhesive strength of FS in combination with macroporous meshes is limited.

Increased plasma D-lactate is associated with the severity of hemorrhagic/traumatic shock in rats.

D-lactate is produced by indigenous bacteria in the gastrointestinal tract. Mammals do not have the enzyme systems to metabolize D-lactate rapidly. The present study was designed to determine the kinetics of circulating D-lactate levels and to examine whether the severity of shock affects circulating D-lactate levels in rats subjected to hemorrhagic/traumatic shock.

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

Background & Aims: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade.

Methods: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis.

Bridging of peripheral nerve defects with exogenous laminin-fibrin matrix in silicone tubes in a rat model.

Fibrin matrix (FM) is a biological substance involved in the comprehensive wound healing process, and has been used in local applications as a carrier of nerve growth factor (NGF) to achieve an effective local neurotrophic concentration by slow release of the factor. In the present experiment, an exogenous fibrin matrix enriched with laminin (LM) and tubulized by a silicone conduit was used to improve the bridging effect of a peripheral nerve defect in a rat model. A 10 mm nerve defect was bridged with a 14 mm silicone conduit which was prefilled either with 25 μl fibrin matrix enriched without or with laminin (0.

Kinetics of endotoxin and tumor necrosis factor appearance in portal and systemic circulation after hemorrhagic shock in rats.

Objective: This study was performed to investigate gut-derived bacterial translocation and the time course of endotoxin (lipopolysaccharide [LPS]) and tumor necrosis factor (TNF) appearance, both in portal and systemic circulation.

Summary Background Data: The significance of intestinal bacteria/endotoxin translocation or TNF formation in the development of systemic sepsis has been disputed.

Methods: A rat model of hemorrhagic shock (30-35 mm Hg for 90 min) and resuscitation was used.

Familial haemophagocytic lymphohistiocytosis. A report of three cases with unusual lung involvement.

Three cases of familial haemophagocytic lymphohistiocytosis are presented with lung infiltration by haemophagocytic histiocytes. In all patients the diagnosis was based on hepatosplenomegaly, thrombocytopenia and anaemia, abnormal increase in triglycerides, ferritin and LDH, hypofibrinogenaemia and lymphohistiocytosis with haemophagocytosis in bone marrow. Two patients died of respiratory failure due to interstitial pneumonia.

Response of the endothelium to trauma and sepsis. Adherence, cytokine effects and procoagulatory response.

Trauma and sepsis induced organ dysfunction is the result of an overwhelming inflammatory response, in which the endothelium plays a central role. Within the mediator cascade reactions involve thrombin, histamine induced endothelial "stimulation" and endotoxin/cytokine induced endothelial "activation" in the endothelial/leukocyte interactions. Adherence events beyond the physiological degree lead to endothelial damage, increase of permeability and result in organ dysfunction.