Inhibitory effect of intragastric glucose on gastric acid secretion and gastric emptying of liquids in man

Intragastric glucose inhibits gastric acid secretion and gastric emptying in man. To determine if these effects are mediated by somatostatin—a known inhibitor of gastric acid production, gastrin secretion, and gastric motility—the plasma somatostatin-like immunoreactivity (SLI) levels were determined in healthy human subjects after an intragastric load of 30% glucose solution. These findings were compared with results after an instillation of distilled water. Following the glucose load, the intragastric acid concentration, the acid output, and the fractional gastric emptying rate declined significantly (P<0.01) before either the plasma glucose or plasma insulin levels had increased. Neither the gastrin nor SLI plasma concentrations changed after the water or glucose load. These findings suggest that the suppression of gastric acid secretion and inhibition of the rate of gastric emptying that occur with intragastric glucose are mediated by factors other than changes in the peripheral circulating levels of SLI, gastrin, insulin, or glucose.     

Orbitofrontal cortex neurons as a common target for classic and glutamatergic antipsychotic drugs

Until recently, all known antipsychotic drugs were thought to block the dopamine D2 receptor. New evidence that agonists of the metabotropic glutamate 2/3 (mGlu2/3) receptors ameliorate psychotic and affective symptoms of schizophrenia suggests that compounds with different molecular targets may act on a common cellular target to treat schizophrenia. We hypothesized that normalizing the activity of neurons in the orbitofrontal cortex (OFC), a region that is increasingly implicated in the pathophysiology of schizophrenia, presents such a target. We disrupted OFC activity in behaving rats with a use-dependent NMDA antagonist to model the NMDA hypofunction state that may occur in schizophrenia. This systemic treatment increased the activity of most pyramidal cells while inhibiting the activity of putative inhibitory GABA interneurons and increasing behavioral stereotypy. A similar pattern of OFC firing disruption was observed after amphetamine, which models a dopamine hyperactivity state in schizophrenia and which produces a pattern of firing disruption different from those of NMDA antagonists in other prefrontal cortex regions. Antipsychotic drugs haloperidol and clozapine, which target monoamine receptors, as well as an mGlu2/3 agonist and an mGlu5 receptor modulator proposed to have antipsychotic efficacy, reversed the impact of NMDA hypofunction on OFC cells and on behavior. A similar pattern of normalization of OFC activity was observed when treatments were given after amphetamine. Thus, proven or putative antipsychotic drugs with different mechanisms of action similarly reduced the impact of NMDA hypofunction and dopamine hyperfunction on OFC neurons, suggesting that these neurons are a candidate target for the therapeutic effects of antipsychotic medications.     

Nanofiller-conjugated percolating conductive network modified polymerization reaction characteristics of aromatic thermosetting copolyester resin

Deliberately controlled interfacial interactions between incorporated nanofiller particles and host polymer backbone chains constitute a critical element in the realm of polymer nanocomposites with tailorable multifunctional properties. We demonstrate the physicochemical effects induced by graphene nanoplatelets (GNP) of different sizes on the condensation polymerization reaction of aromatic thermosetting copolyester (ATSP) through the formation of electrically conductive percolating networks as enabled by interfacial interactions. Carboxylic acid and acetoxy-capped precursor oligomers of ATSP are solid-state mixed with chemically pristine GNP particles at various loading levels. Upon in situ endothermic condensation polymerization reaction, crosslinked backbone of the ATSP foam matrix is formed while the carbonaceous nanofillers are incorporated into the polymer network via covalent conjugation with functional end-groups of the oligomers. The controlled GNP size promotes different electrical percolation thresholds and ultimate electrical conductivities. Microstructural analysis demonstrates GNP distributions in the matrix as well as morphological modifications induced by the formation of conductive percolating GNP networks. Cure characteristics reveal the thermochemical changes prompted in the polymerization processes for GNP content above the requirement for percolation formation. Chemical spectroscopy of the ATSP nanocomposite morphology exhibits the formation of a robust interfacial coupling mechanism between the GNPs and ATSP backbone. The findings here may guide the developmental efforts of nanocomposites through better identifying roles of the morphology and content of nanofillers in polymerization processes.

Physicochemical effects induced by graphene nanoplatelets on the in situ polycondensation reaction of aromatic thermosetting copolyester through the formation of conductive percolating network assembled via interfacial interactions.     

Community Factors and Hospital Readmission Rates

Objective

To examine the relationship between community factors and hospital readmission rates.

Data Sources/Study Setting

We examined all hospitals with publicly reported 30-day readmission rates for patients discharged during July 1, 2007, to June 30, 2010, with acute myocardial infarction (AMI), heart failure (HF), or pneumonia (PN). We linked these to publicly available county data from the Area Resource File, the Census, Nursing Home Compare, and the Neilsen PopFacts datasets.

Study Design

We used hierarchical linear models to assess the effect of county demographic, access to care, and nursing home quality characteristics on the pooled 30-day risk-standardized readmission rate.

Data Collection/Extraction Methods

Not applicable.

Principal Findings

The study sample included 4,073 hospitals. Fifty-eight percent of national variation in hospital readmission rates was explained by the county in which the hospital was located. In multivariable analysis, a number of county characteristics were found to be independently associated with higher readmission rates, the strongest associations being for measures of access to care. These county characteristics explained almost half of the total variation across counties.

Conclusions

Community factors, as measured by county characteristics, explain a substantial amount of variation in hospital readmission rates.     

Treatment of heterotopic caesarean scar pregnancy complicated with post termination increase in size of residual mass and morbidly adherent placenta

We report a case of a secundipara with heterotopic cesarean scar pregnancy (HCSP) treated with potassium chloride injection into the ectopic embryo followed by sac aspiration. The remaining “mass” increased in size threefold and was surrounded by a rich vascular network. An arteriovenous malformation was suspected; however, appropriate treatment was precluded because of the viability of the ectopic gestation. Sonographic examination revealed a morbidly adherent placenta, and attempt to resect the mass laparoscopically was complicated by bleeding that required hysterectomy. This case illustrates a complication of the intervention performed to preserve the intrauterine gestation in case of HCSP. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46 :227–230, 2018     

Probabilistic hazard assessment for skin sensitization potency by dose–response modeling using feature elimination instead of quantitative structure–activity relationships

Supervised learning methods promise to improve integrated testing strategies (ITS), but must be adjusted to handle high dimensionality and dose–response data. ITS approaches are currently fueled by the increasing mechanistic understanding of adverse outcome pathways (AOP) and the development of tests reflecting these mechanisms. Simple approaches to combine skin sensitization data sets, such as weight of evidence, fail due to problems in information redundancy and high dimensionality. The problem is further amplified when potency information (dose/response) of hazards would be estimated. Skin sensitization currently serves as the foster child for AOP and ITS development, as legislative pressures combined with a very good mechanistic understanding of contact dermatitis have led to test development and relatively large high‐quality data sets. We curated such a data set and combined a recursive variable selection algorithm to evaluate the information available through in silico, in chemico and in vitro assays. Chemical similarity alone could not cluster chemicals' potency, and in vitro models consistently ranked high in recursive feature elimination. This allows reducing the number of tests included in an ITS. Next, we analyzed with a hidden Markov model that takes advantage of an intrinsic inter‐relationship among the local lymph node assay classes, i.e. the monotonous connection between local lymph node assay and dose. The dose‐informed random forest/hidden Markov model was superior to the dose‐naive random forest model on all data sets. Although balanced accuracy improvement may seem small, this obscures the actual improvement in misclassifications as the dose‐informed hidden Markov model strongly reduced " false‐negatives" (i.e. extreme sensitizers as non‐sensitizer) on all data sets. Copyright © 2015 John Wiley & Sons, Ltd.