Mouse NK cell-mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing

Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49(+) subsets in BMC rejection by using β2-microglobulin deficient (β2m(-/-)) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind "self-MHC" were found to be the dominant subset responsible for β2m(-/-) BMC rejection. This provides in vivo evidence for host MHC class I-dependent functional education. Interestingly, all H2(d) strain mice regardless of background were able to resist significantly greater amounts of β2m(-/-), but not wild-type BMC than H2(b) mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability.     

Side of onset does not influence cognition in newly diagnosed untreated Parkinson's disease patients

BackgroundA relation between the side of motor onset and cognitive impairment in early PD has been reported, suggesting that the asymmetric degeneration affecting subcortical regions may play a pivotal role in lateralized cognitive function. However, evidences are controversial and all previous studies were performed on treated patients, though it is known that dopaminergic therapy can affect cognition in PD.MethodsSixty-nine early untreated PD patients underwent an extensive neuropsychological battery exploring memory, visuospatial and attention/executive functions. Patients were divided with respect of the side of onset (right vs. left) and further grouped according to motor phenotype (tremor vs. rigidity-bradykinesia). Multivariate analysis of variance has been carried out to compare clinical and neuropsychological data between subgroups.ResultsThere were no differences in any neuropsychological task between right-sided and left-sided onset subgroups, irrespective of tremor dominant or rigid-bradykinetic phenotype. Age at onset was significantly higher in patients with any cognitive impairment as compared with patients without (66.7 ± 3.2 vs. 56.3 ± 6.8 years, p = 0.001).ConclusionSide of motor onset is not a major determinant for developing lateralized cognitive deficits in newly diagnosed untreated PD patients.     

Parkinson’s disease: considerations for dental hygienists

Abstract: The prevalence of Parkinson’s disease (PD) is expected to double over the next 20 years owing to the increase in life expectancy. This progressive disease has several implications relating to oral health, and many are manageable with proper awareness and knowledge about the disease. This article reviews the epidemiology, pathophysiology, and characteristics of PD, as well as the treatments and oral health considerations to enable dental hygienists to undertake an informed approach to patient management strategies and provide optimal care.     

Reduction in length of stay for patients undergoing oesophageal and gastric resections with implementation of enhanced recovery packages

Introduction

The high mortality and morbidity associated with resection for oesophagogastric malignancy has resulted in a conservative approach to the postoperative management of this patient group. In August 2009 we introduced an enhanced recovery after surgery (ERAS) pathway tailored to patients undergoing resection for oesophagogastric malignancy. We aimed to assess the impact of this change in practice on standard clinical outcomes.

Methods

Two cohorts were studied of patients undergoing resection for oesophagogastric malignancy before (August 2008 – July 2009) and after (August 2009 – July 2010) the implementation of the ERAS pathway. Data were collected on demographics, interventions, length of stay, morbidity and in-hospital mortality.

Results

There were 53 and 55 oesophagogastric resections undertaken respectively for malignant disease in each of the study periods. The median length of stay for both gastric and oesophageal resection decreased from 15 to 11 days (Mann– Whitney U, p<0.001) following implementation of the ERAS pathway. There was no significant increase in morbidity (gastric resection 23.1% vs 5.3% and oesophageal resection 25.9% vs 16.7%) or mortality (gastric resection no deaths and oesophageal resection 1.8% vs 3.6%) associated with the changes. There was a significant decrease in the number of oral contrast studies used following oesophageal resection, with a reduction from 21 (77.8%) in 2008–2009 to 6 (16.7%) in 2009–2010 (chi-squared test, p<0.0001).

Conclusions

The introduction of an enhanced recovery programme following oesophagogastric surgery resulted in a significant decrease in length of median patient stay in hospital without a significant increase in associated morbidity and mortality.     

A Randomized‐Controlled Pilot Study Comparing ICD Implantation with and Without Intraoperative Defibrillation Testing in Patients with Heart Failure and Severe Left Ventricular Dysfunction: A Substudy of the RAFT Trial

Comparing ICD Implantation with and Without Intraoperative Defibrillation Testing. Introduction: The need to perform defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion is controversial. In the absence of randomized trials, some regions now perform more than half of ICD implants without DT. Methods: During the last year of enrolment in the Resynchronization for Ambulatory Heart Failure Trial, a substudy randomized patients to ICD implantation with versus without DT. Results: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Patients were similar in terms of age (65.9 ± 9.3 years vs 67.9 ± 8.9 years); LVEF (24.7 ± 4.6% vs 23.6 ± 4.6%), QRS width (154.8 ± 23.5 vs 155.8 ± 23.6 ms), and history of atrial fibrillation (5% vs 6%). All 68 patients in the DT arm tested according to the protocol achieved a successful DT (≤25 J); 96% without requiring any system modification. No patient experienced perioperative stroke, myocardial infarction, heart failure (HF), intubation or unplanned ICU stay. The length of hospital stay was not prolonged in the DT group: 20.2 ± 26.3 hours versus 21.3 ± 23.0 hours, P = 0.79. One patient in the DT arm had a failed appropriate shock and no patient suffered an arrhythmic death. The composite of HF hospitalization or all‐cause mortality occurred in 10% of patients in the no‐DT arm and 19% of patients in the DT arm (HR = 0.53, 95% CI: 0.21–1.31, P = 0.14). Conclusions: In this randomized trial, perioperative complications, failed appropriate shocks, and arrhythmic death were all uncommon regardless of DT. There was a nonsignificant increase in the risk of death or HF hospitalization with DT. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1313‐1316, December 2012)     

Stability of di-butyl-dichalcogenide-capped gold nanoparticles: experimental data and theoretical insights

Metals capped with organochalcogenides have attracted considerable interest due to their practical applications, which include catalysis, sensing, and biosensing, due to their optical, magnetic, electrochemical, adhesive, lubrication, and antibacterial properties. There are numerous reports of metals capped with organothiol molecules; however, there are few studies on metals capped with organoselenium or organotellurium. Thus, there is a gap to be filled regarding the properties of organochalcogenide systems which can be improved by replacing sulfur with selenium or tellurium. In the last decade, there has been significant development in the synthesis of selenium and tellurium compounds; however, it is difficult to find commercial applications of these compounds because there are few studies showing the feasibility of their synthesis and their advantages compared to organothiol compounds. Stability against oxidation by molecular oxygen under ambient conditions is one of the properties which can be improved by choosing the correct organochalcogenide; this can confer important advantages for many more suitable applications. This paper reports the successful synthesis and characterization of gold nanoparticles functionalized with organochalcogenide molecules (dibutyl-disulfide, dibutyl-diselenide and dibutyl-ditelluride) and evaluates the oxidation stability of the organochalcogenides. Spherical gold nanoparticles with diameters of 24 nm were capped with organochalcogenides and were investigated using X-ray photoelectron spectroscopy (XPS) to show the improved stability of organoselenium compared with organothiol and organotellurium. The results suggest that the organoselenium is a promising candidate to replace organothiol because of its enhanced stability towards oxidation by molecular oxygen under ambient conditions and its slow oxidation rate. The observed difference in the oxidation processes, as discussed, is also in agreement with theoretical calculations.

This study presents the improved stability against oxidation by molecular oxygen under ambient conditions of organoselenium compared with organothiol, and organotellurium.