Effects of pirfenidone on experimental head injury in rats

Traumatic brain injury (TBI) continues to be a significant public healthcare concern. Neuroinflammation that occurs in the secondary phase of TBI leads to cognitive and physical dysfunction. A number of therapeutic modalities have been evaluated in an attempt to find a suitable treatment. The only drug approved for the treatment of idiopathic pulmonary fibrosis, pirfenidone, has been evaluated for its antifibrotic, anti-inflammatory, and anti-oxidant properties for various disorders, but this is the first study to examine its effects in an experimental TBI model. Twenty-four Wistar rats were randomly divided into three groups: control, trauma, and pirfenidone. The two latter groups underwent experimental diffuse cortical injury mimicking TBI. Neurological assessment was performed using the Garcia test, histological analysis was performed to examine neuroprotective and anti-inflammatory effects, and biochemical analyses of neuron-specific enolase (NSE), S-100B, caspase-3, and thiobarbituric acid reactive substances were performed. The pirfenidone group had a better Garcia test score (P=0.001), an increased anti-inflammatory effect (P<0.001), and an enhanced neuroprotective effect (P=0.007) along with decreased NSE, S100B, and TBARS levels compared to the trauma group. However, pirfenidone did not show a beneficial effect on caspase-3 levels. Pirfenidone may help decrease mortality and morbidity rates after TBI through its anti-inflammatory and antioxidant effects.     

Internalized Stigma in Pediatric Psoriasis: A Comparative Multicenter Study

BackgroundInternalized stigma, adoption of negative attitudes and stereotypes of the society regarding persons'' illness, has not been studied previously in pediatric psoriasis patients.ObjectiveWe aimed to investigate the internalized stigma in pediatric psoriasis patients and to determine differences according to factors affecting internalized stigma compared to adult psoriasis patients.MethodsThis multicenter, cross-sectional, comparative study included 125 pediatric (55 female, 70 male; mean age±standard deviation [SD], 14.59±2.87 years) and 1,235 adult psoriasis patients (577 female, 658 male; mean age±SD, 43.3±13.7 years). Psoriasis Internalized Stigma Scale (PISS), Dermatology Life Quality Index (DLQI), Perceived Health Status (PHS), and the General Health Questionnaire (GHQ)-12 were the scales used in the study.ResultsThe mean PISS was 58.48±14.9 in pediatric group. When PISS subscales of groups were compared, the pediatric group had significantly higher stigma resistance (p=0.01) whereas adult group had higher scores of alienation (p=0.01) and stereotype endorsement (p=0.04). There was a strong correlation between mean values of PISS and DLQI (r=0.423, p=0.001). High internalized stigma scores had no relation to either the severity or localization of disease in pediatric group. However, poor PHS (p=0.007) and low-income levels (p=0.03) in both groups, and body mass index (r=0.181, p=0.04) in the pediatric group were related to high PISS scores.ConclusionInternalized stigma in pediatric patients is as high as adults and is related to poor quality of life, general health, and psychological illnesses. Unlike adults, internalized stigma was mainly determined by psoriasis per se, rather than disease severity or involvement of visible body parts, genitalia or folds.     

The effects of isotretinoin therapy on the biliary system

The aim of the present study was to investigate the potential effects of isotretinoin on the biliary system in patients with acne vulgaris receiving isotretinoin therapy. This was a preliminary retrospective study involving 40 patients with severe acne vulgaris who attended the dermatology clinic and were administered different doses (20 or 30 mg/day) of isotretinoin. Serum levels of AST, ALT, ALP, GGT, total bilirubin, direct bilirubin, and indirect bilirubin at the beginning and at the first month of therapy were scanned, recorded, and statistically analyzed. Total and indirect bilirubin levels at the first month of treatment in 30 patients, receiving isotretinoin at a dose of 20 mg/day, were significantly lower compared to the baseline values (p = .02 and p = .03, respectively), whereas AST and GGT serum levels were significantly higher (p = .003 and p = .006 respectively). No significant reduction in total and indirect bilirubin levels was detectable at the first month of treatment in 10 patients receiving isotretinoin at a dose of 30 mg/day; however, AST, ALP, and GGT levels were significantly elevated in these patients (p = .023; p = .004; and p = .001, respectively). To our knowledge, there is no previous study investigating the effects of isotretinoin on the biliary system, and, therefore, the present study is a preliminary one. Our findings implicate that low dose (20 mg/day) isotretinoin therapy can potentially reduce total and indirect bilirubin levels. Long‐term, large‐scale, prospective studies with patients receiving different doses of isotretinoin may provide more reliable information regarding the bilirubin lowering effects of isotretinoin and optimum dosing for achieving this clinical effect.     

Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

     

Correction to: Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Journal of Neurology - The original version of this article unfortunately contained a mistake.     

Self-Healing Systems in Silicon Anodes for Li-Ion Batteries

Self-healing is the capability of materials to repair themselves after the damage has occurred, usually through the interaction between molecules or chains. Physical and chemical processes are applied for the preparation of self-healing systems. There are different approaches for these systems, such as heterogeneous systems, shape memory effects, hydrogen bonding or covalent–bond interaction, diffusion, and flow dynamics. Self-healing mechanisms can occur in particular through heat and light exposure or through reconnection without a direct effect. The applications of these systems display an increasing trend in both the R&D and industry sectors. Moreover, self-healing systems and their energy storage applications are currently gaining great importance. This review aims to provide general information on recent developments in self-healing materials and their battery applications given the critical importance of self-healing systems for lithium-ion batteries (LIBs). In the first part of the review, an introduction about self-healing mechanisms and design strategies for self-healing materials is given. Then, selected important healing materials in the literature for the anodes of LIBs are mentioned in the second part. The results and future perspectives are stated in the conclusion section.     

Serious lower extremity venous injury management with ligation: prospective overview of 63 patients

Management of lower extremity venous trauma using repair or ligation has been an area of controversy during the past decades. However, in unstable patients or if primary repair is technically impossible as a result of extensive disruption of the vein, ligation is recommended. This study investigated the effects of venous ligation on major veins in the lower extremities when primary repair is impossible as a result of extensive laceration of the vein. Between January 2001 and April 2004, 63 patients with Grade III and IV venous injuries were observed prospectively. Compression ultrasonography was performed postoperatively on the fifth day, once before discharge, and at the 3-month visit to assess deep vein thrombosis (DVT) and the patency of arterial repair. If DVT was present, the patient was given an oral anticoagulant (warfarin Na) for 3 months (international normalized ratio, 2.0-3.0), and Class II compression stockings (Sigvaris-212, Ganzoni, Switzerland) were used for 1 year. Follow-up visits occurred at 1, 3, 6, and 12 months and at 6-month intervals thereafter. Combined arterial and venous injuries were present in 50 (79.4%) patients and pure venous injuries were present in 13 (20.6%) patients. DVT developed in 49 patients (77.7%; postoperative n = 37 [58.7%], late n = 12 [19%]). Three arterial restenoses (4.7%) and one pseudoaneurysm (1.6%) of the superficial femoral artery developed. Five early (prophylactic) and two late (compartment syndrome) fasciotomies were performed. Postoperative edema was seen in 56 (88.8%) patients and wound infection was seen in 19 patients (30.1%; n=18 superficial, n=1 deep). Two amputations (3.2%) were performed. One patient (1.7%) died as a result of irreversible shock. After a median of 18 months, 25 patients were classified with Clinical Etiology, Anatomy, Pathology classification: 10 legs C-0, seven legs C-2, and eight legs C-3. No severe postthrombophlebitic syndrome was observed. Early leg swelling after venous ligation was the most common morbidity. We observed no significant sequelae of chronic venous insufficiency, and venous ligation had no detrimental effect on associated arterial repair. In cases of DVT, anticoagulation with low-molecular-weight heparin and oral anticoagulants should begin immediately and continue for 3 months along with compression stocking support for 1 year.     

Effect of EDTA,Sodium Hypochlorite,and Chlorhexidine Gluconate with or without Surface Modifiers on Dentin Microhardness

Introduction

This study aimed to evaluate the effects of root canal irrigants on the microhardness of root canal dentin in the presence and absence of surface-modifying agents.

Methods

Forty-eight root halves were prepared by longitudinal splitting of the distal roots of 24 freshly extracted mandibular human third molars and embedded in autopolymerizing acrylic resin, leaving the dentin surface exposed. After polishing, the microhardness values of the untreated dentin surfaces were recorded by using Vickers tester at the mid-root level. The root halves were randomly assigned to 6 groups composed of 8 samples each and treated for 5 minutes with one of the following irrigants: 17% EDTA, REDTA, 2% chlorhexidine gluconate (CHX), 2% CHX with surface modifiers (CHX-Plus), 6% NaOCl, or 6% NaOCl with surface modifiers (Chlor-XTRA). After surface treatment, dentin microhardness values were recorded at close proximity to the initial indentation areas. Experimental data were statistically analyzed by using the t test and one-way analysis of variance, followed by Tukey honestly significant difference test at α = 0.05.

Results

EDTA, REDTA, NaOCl, and Chlor-XTRA significantly decreased the microhardness of root dentin compared with intact controls (P < .05).

Conclusions

The addition of surface modifiers to the irrigants did not affect the microhardness of the samples.