The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.     

The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer

This study is an attempt to unify the evaluation of patients with well-differentiated thyroid cancer after ablative therapy. As such, serum thyroglobulin determinations on and off thyroid hormone (T₄) therapy and iodine 131 total body scans were examined in 53 patient studies. No metastases were found in patients whose thyroglobulin value was undetectable (< 1 ng/ml). Values during T₄ therapy that were detectable, even as low as 4.2 ng/ml, were occasionally associated with metastases. After T₄ withdrawal, thyroglobulin value and scan were obtained. Neither metastasis nor clinically detectable cancer was found in patients whose thyroglobulin value was less than 10 ng/ml while off T₄. Conversely, a value greater than 10 ng/ml was often associated with documented metastases even when the scan was negative. In summary, a thyroglobulin value less than 1 ng/ml during T₄ therapy or less than 10 ng/ml off T₄ therapy suggests successful therapy and a routine scan could be avoided unless clinically indicated. However, a value greater than 10 ng/ml suggests the presence of metastasis despite a negative scan. Thyroglobulin determination substantially improves the management of these patients.     

Juvenile rhesus monkeys have lower type 2 cytokine responses than adults after primary infection with Schistosoma mansoni

Adults and children have differences in their susceptibility to schistosomiasis. The relative influences of age-dependent innate resistance and acquired immunity in the differences between susceptibility to schistosomiasis are difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni. In contrast to the adult animals, the juvenile rhesus monkeys had low levels of interleukin (IL)-4 and IL-5 production by peripheral blood mononuclear cells after schistosome infection, as well as lower levels of parasite-antigen-specific antibody (IgG, IgM, and IgA) responses, and produced limited antigen-specific or total IgE. Juvenile animals had statistically nonsignificant increased worm burdens and tissue or fecal egg counts, compared with that of adults, whereas circulating schistosome antigens were significantly higher in infected juvenile monkeys. These results suggest that juvenile rhesus monkeys have reduced type 2 cytokine responses after primary schistosome infections and perhaps are more susceptible to parasite infection.     

Characterization of P2x1 purinoreceptors on rat platelets: effect of clopidogrel

This study aimed to determine the binding characteristics of [³H]α,β-Me-ATP, a specific ligand of the P2x1 receptors to rat platelets, and to investigate the effect of clopidogrel, a thienopyridine compound which has been found to selectively inhibit ADP-induced platelet aggregation and adenylyl cyclase ex vivo . Binding of [³H]α,β-Me-ATP to rat platelets was time-dependent and saturable. Scatchard analysis of the saturation binding data indicated that [³H]α,β-Me-ATP bound to one population of specific binding sites with high affinity ( K _D  =  23.6 ± 1.6 n m ; B _max = 690 ± 24 fmole/10⁸cells) ( n= 3). Unlabelled α,β-Me-ATP as well as 2-MeS-ADP and ADP competitively inhibited the specific binding of [³H]α,β-Me-ATP with IC₅₀ values of 19.0 ± 6.6, 103 ± 20 and 1120 ± 80 n m respectively ( n= 3). Other nucleotide analogues such as ATP, ATP-γS, UTP and GTP also antagonized [³H]α,β-Me-ATP binding. When administered orally (10 mg/kg, p.o.), clopidogrel inhibited ADP- or 2-MeS-ADP-induced platelet aggregation but did not affect the binding of [³H]α,β-Me-ATP to rat platelets ex vivo. In vitro , α,β-Me-ATP did not induce the aggregation or shape change of rat platelets and did not interfere with ADP-induced platelet aggregation.     

Low acid output in Pima Indians

Duodenal ulcer has not been observed in full-heritage Pima Indians, while gastric cancer is relatively frequent. To investigate possible underlying factors for this phenomenon, we determined gastric acid output, gastric emptying rate, and plasma levels of gastrin, pepsinogen I, and pepsinogen II in apparently healthy Pima Indian and in Caucasian controls. The Pimas had significantly lower basal and stimulated outputs of gastric acid and higher fasting and postprandial plasma gastrin concentrations than the caucasians. Plasma pepsinogen I levels were similar in the two groups, but plasma pepsinogen II was significantly higher and the ratio of pepsinogen I to pepsinogen II was significantly lower in the Pima Indians. In addition, gastric emptying of an acaloric liqid meal was significantly delayed in the Pimas. The results suggest that the absence of duodenal ulcer in Pima Indians may be related to low gastric acid production and aslow rate of gastric emptying in this population. The associated findings of hypergastrinemia, hyperpepsinogenemia II, and a low ratio of pepsinogen I to pepsinogen II suggest that the hypochlorhydria may reflect an increased pervalence of chronic gastritis in full-heritage Pima Indians. This, in turn, could represent a risk factor for the development of gastric cancer in this population.Supported in part by research Contract 1-Am-6-2219 and grant AM 13233 from the National Institutes of Health, Bethesda, Maryland     

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.     

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