Simultaneous glomerular filtration rate determination using inulin,iohexol, and 99mTc-DTPA demonstrates the need for customized measurement protocols

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Factors affecting the choice of first-line therapy in Parkinson’s disease patients in Wales: A population-based study

First line treatment for Parkinson’s disease (PD) is typically either L-dopa or a non-ergot dopamine agonist (DA). However, the options for the treatment of motor symptoms in PD patients have increased in the last thirty years, which have seen several new classes of PD medications introduced onto the market. The purpose of this study is to examine the changes in first line therapy of newly diagnosed Parkinson’s patients between 2000 and 2016 in Wales.A population-based study evaluated data from the Secure Anonymised Information Linkage (SAIL) Databank of residents in Wales, aged 40 years or older, newly treated with PD medications between 2000 and 2016. The data was compared across three intervals: 2000–2005, 2006–2011 and 2012–2016. Patients were classified by age at diagnosis into young: 40–60 years; mid, 61–80 years; and older >80 years. Logistic regression was undertaken to determine the predictors of PD medication prescribing.For the whole study period, the profiles of 9142 newly diagnosed PD patients were analysed. L-dopa was the most common first line therapy (80.6%), followed by non-ergot DAs (12.9%) and monoamine oxidase B (MAO-B) inhibitors (7.9%). Odds of L-dopa prescribing were greater in patients >80 years (OR = 20.46 95%CI: 16.25–25.76) and in the period 2012–2016 (OR = 1.98 95% CI: 1.70–2.29). Prescribing of non-ergot DAs significantly declined in 2012–2016 (OR = 0.42 95% CI: 0.35–0.49). Additional factors influencing first line therapy were deprivation, presence of diabetes and prior use of antidepressants. For example, PD patients residing in the least deprived area were less likely to be prescribed L-dopa compared to patients residing in the most deprived area (OR = 0.77 95% CI: 0.65–0.93).First line therapy in PD in Wales has undergone a significant switch towards L-dopa over the last 16 years. The data indicates reasonable compliance with guidelines on efficacy and safety issues related to Parkinson’s medications.     

Pediatric Palliative Care in Iran: Applying Regionalization of Health Care Systems

Background: Establishing palliative care services is a priority in the health system of Iran. Considering the necessityof integrating these services into the health system, this study aimed to explore the stakeholders’ perceptions about theprovision of a conceptual framework for palliative care services for children with cancer according to the health systemin of Iran. Methods: The present qualitative study was conducted through in-depth semi-structured interviews heldwith 29 participants including palliative care specialists, policy-makers, health care providers, the parents of childrenwith cancer selected through purposive sampling, between August 2016 and February 2017. Interviews continueduntil saturation of data. All interviews were recorded, transcribed and analyzed using MAXQDA10 software. Results:The codes extracted from interviews produced the main theme “ classes of palliative care services” with the two maincategories “comprehensive care” including, strengthening family shelter, maintaining the child in a familiar environment,achieving stability and “establishing social justice” including, easy access to services, financial relief and quality care.Conclusion: Presenting a framework based on level of palliative care services, the findings of this study paves the wayfor integrating these services into Iranian health system.     

Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: insight into the role of structure and size

Purpose

The direct effects of galacto-oligosaccharides (GOS), including Vivinal^® GOS syrup (VGOS) and purified Vivinal^® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure–activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin.

Methods

Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA.

Results

In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release.

Conclusions

This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.

     

Pseudo inferior oblique overaction,clinical findings,mechanism, and surgical outcomes

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate clinical findings of the pseudo inferior oblique overaction (IOOA) syndrome and the outcomes of strabismus surgery...     

Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques

Background

MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB).

Methods

One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients.

Results

Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy.

Conclusions

By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood–brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients.     

The effects of simvastatin on ischemia-reperfusion injury of sciatic nerve in adult rats

Severe ischemia to nerve results in fiber degeneration and reperfusion results in oxidative injury to endothelial cells and augments fiber degeneration. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, the most widely used lipid-lowering drugs, have been demonstrated to play a neuroprotective role. So we evaluated the effectiveness of simvastatin in protecting sciatic nerve from ischemia-reperfusion injury using the model of experimental nerve ischemia. Sixty adult male Sprague-Dawley rats weighing 250-300 g were used. They were divided into ten groups (N=6 per group). We used ischemia model in these groups by occluding the femoral artery and vein with a silk suture 6-0 using slipknot technique. All ischemia groups were rendered in ischemic for 3 h reperfused for various times of zero (0 h), 3 h (3 hour reperfusion), 7 days (7 day reperfusion), 14 days (14 day reperfusion). Half of the groups had experimental simvastatin (1 mg/kg) i.v. injection treatment via tail vein 1 h before ischemia. The other half experienced only ischemia-reperfusion as control groups. After euthanasia, histological samples were taken from distal part of the sciatic nerve. Sections were cut at 5 microm and then were stained with H and E and modified trichrome. We used H and E stain for edema and trichrome gomori for ischemic fiber degeneration. Samples were observed to assess their fiber degeneration and edema changes. By observation the level of fiber degeneration and endoneurial edema were also decreased in these recent groups (in both ischemia and reperfusion duration). In conclusion, pre-ischemic administration of simvastatin exhibits neuroprotective properties in ischemia-reperfusion nerve injury.