The effect of hydroxychloroquine on platelet activation in model experiments

Journal of Thrombosis and Thrombolysis - Hydroxychloroquine (HCQ) is an antimalarial agent with pleiotropic effects and now represents a cornerstone in the management of patients with autoimmune...     

Detection of DNA mutations based on analysis of multiple wavelength excitation/emission fluorescence kinetics curves in real-time PCR

The key method for therapies of various cancer types could be the molecular-targeted therapy, based on individual gene profile for each patient. One of the main procedures used for genetic testing is the real-time polymerase chain reaction (real-time PCR).     

Cost and quality-of-life impacts of community treatment orders (CTOs) for patients with psychosis: economic evaluation of the OCTET trial

Purpose

Current RCT and meta-analyses have not found any effect of community treatment orders (CTOs) on hospital or social outcomes. Assumed positive impacts of CTOs on quality-of-life outcomes and reduced hospital costs are potentially in conflict with patient autonomy. Therefore, an analysis of the cost and quality-of-life consequences of CTOs was conducted within the OCTET trial.

Methods

The economic evaluation was carried out comparing patients (n = 328) with psychosis discharged from involuntary hospitalisation either to treatment under a CTO (CTO group) or voluntary status via Section 17 leave (non-CTO group) from the health and social care and broader societal perspectives (including cost implication of informal family care and legal procedures). Differences in costs and outcomes defined as quality-adjusted life years (QALYs) based on the EQ-5D-3L or capability-weighted life years (CWLYs) based on the OxCAP-MH were assessed over 12 months (£, 2012/13 tariffs).

Results

Mean total costs from the health and social care perspective [CTO: £35,595 (SD: £44,886); non-CTO: £36,003 (SD: £41,406)] were not statistically significantly different in any of the analyses or cost categories. Mental health hospitalisation costs contributed to more than 85% of annual health and social care costs. Informal care costs were significantly higher in the CTO group, in which there were also significantly more manager hearings and tribunals. No difference in health-related quality of life or capability wellbeing was found between the groups.

Conclusion

CTOs are unlikely to be cost-effective. No evidence supports the hypothesis that CTOs decrease hospitalisation costs or improve quality of life. Future decisions should consider impacts outside the healthcare sector such as higher informal care costs and legal procedure burden of CTOs.

     

RecQ helicase acts before RuvABC,RecG and XerC proteins during recombination in recBCD sbcBC mutants of Escherichia coli

The RecQ helicase is required by the RecF recombination pathway that is operative in recBC(D) sbcB sbcC(D) mutants of Escherichia coli. Genetic data suggest that RecQ participates in resection of DNA ends during initiation of recombination. In vitro, RecQ can unwind a variety of DNA substrates, including recombination intermediates such as D-loops and Holliday junctions. However, its potential role in processing of recombination intermediates during the late stage of the RecF pathway has not been genetically tested. Here we studied the effect of a recQ mutation on transductional recombination and DNA repair after γ-irradiation in ΔrecBCD ΔsbcB sbcC strains deficient for RuvABC, RecG and XerC proteins. RuvABC and RecG proteins process recombination intermediates in the late stage of recombination, whereas XerC is required to resolve chromosome dimers formed upon recombination. Our results do not reveal any substantial synergistic effect between the recQ mutation, on one hand, and ruvABC, recG and xerC mutations on the other. In addition, the recQ mutation suppresses chromosome segregation defects in γ-irradiated ruvABC recG and xerC mutants. These results suggest that RecQ acts upstream of RuvABC, RecG and XerC proteins, a finding that is compatible with its primary role in initiation of the RecF recombination pathway.     

Disruption of EXOC6B in a patient with developmental delay,epilepsy, and a de novo balanced t(2;8) translocation

Most balanced chromosomal aberrations are not associated with a clinical phenotype, however, in some patients they may disrupt gene structure. With the development of various next-generation sequencing techniques, fast and specific analyses of the breakpoint regions of chromosomal rearrangements are possible. Here, we report on a 19-year-old woman with a de novo balanced translocation t(2;8)(p13.2;q22.1) and a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features. By next-generation sequencing, we defined the breakpoints and found disruption of the exocyst complex component 6B (EXOC6B) gene in intron 1 on chromosome 2p13.2 involving two Alu elements with a homology of 81%. No gene was found at the respective breakpoint on chromosome 8. Expression analysis of the EXOC6B in blood lymphocytes and buccal smear revealed reduced expression in the patient in comparison with the control. Our findings in combination with one recently published case and one other patient listed in DECIPHER v5.1 indicate EXOC6B as a gene relevant for intellectual development and electrophysiological stability.     

Stem Cell Ophthalmology Treatment Study(SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy

We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study(SCOTS). SCOTS is an Institutional Review Board approved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date(www.clinicaltrials.gov Identifier NCT 01920867). SCOTS utilizes autologous bone marrow-derived stem cells(BMSCs) for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient's previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and intravitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient's visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.     

Treatment for brain arteriovenous malformation in the 1998–2011 period and review of the literature

Purpose

The results of the treatment of pial AVM provided at our neurosurgical centre are presented. Based on these results and on an overview of literary data on the efficacy and complications of each therapeutic modality, the algorithm of indications, as used at our institution, is presented.

Cohort of patients

The series comprises 195 patients, aged 9 to 87 years and treated in the years 1998–2011. The surgical group consists of 76 patients; of these, 49 patients solely received endovascular treatment, 25 were consulted and referred directly to the radiosurgical unit, and the remaining 45 were recommended to abide by the strategy of “watch and wait”.

Results

In the surgical group, serious complications were 3.9 %, at a 96.1 % therapeutic efficacy. As for AVM treated with purely endovascular methods, serious procedural complications were seen in 4.1 % of patients, with efficacy totalling 32.7 %. One observed patient suffered bleeding, resulting in death. For comparison with literary data for each modality, a survival analysis without haemorrhage following monotherapy for AVM with each particular modality was carried out.

Conclusions

Based on our analysis, we have devised the following algorithm of treatment:

1. We regard surgical treatment as the treatment of choice for AVM of Spetzler-Martin (S-M) grades I and II, and only for those grade III cases that are surgically accessible.
2. Endovascular intervention should mainly be used for preoperative embolisation, as a curative procedure for lower-grade AVM in patients with comorbidities, and as palliation only for higher-grade cases.
3. Stereotactic irradiation with Leksell Gamma Knife (LGK) is advisable, mainly for poorly accessible, deep-seated grade-III AV malformations. In the case of lower grades, the final decision is left to the properly informed patient.
4. Observation should be used as the method of choice in AVM of grades IV and V, where active therapy carries greater risk than the natural course of the disease.

     

Hypothermic anticoagulation: testing individual responses to graded severe hypothermia with thromboelastography

Selective incircuit blood cooling could be an effective anticoagulation strategy during hemodialysis. However, it is currently unknown what blood temperature would ensure sufficient anticoagulation. Similarly, no information exists about potential interindividual variability in response to graded hypothermia. Therefore, the aim of this study was to analyze effects of profound hypothermia on human coagulation. Furthermore, a mathematical relationship between blood temperatures and coagulation was sought to predict individual responses to blood cooling. It was designed as a laboratory study. Thromboelastography (TEG) measurements were taken at a temperature range of 38-12°C. To enable measurements below 20°C, the TEG device was placed into an air conditioned chamber allowing for setting of the temperatures over a wide range. The data were analyzed by regression analysis for pooled and individual measurements. Decreasing temperatures always led to a progressive reduction in blood coagulation by delaying the initiation of thrombus formation, as well as by decreasing the speed of its creation and growth. However, the response to cooling was not uniform and the interindividual variability exists. The relationship between blood temperature and coagulation is not linear but exponential (parameters R and K) and sigmoid (parameter α-angle). The lower the blood temperature, the more significant effect on blood coagulation decline. To predict an individual response of the coagulation system over a wide range of temperatures, a mathematical modeling can be used.     

Effects of low-level light therapy on xerostomia related to hyposalivation: a systematic review and meta-analysis of clinical trials

Lasers in Medical Science - Hyposalivation is a condition represented by a reduced salivary flow and may include symptoms such as mouth dryness (xerostomia), loss of taste, pain, dysphagia, and...