Characterization of the thymus in Lrp4 myasthenia gravis: Four cases

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Most patients have pathogenic autoantibodies against the acetylcholine receptor (AChR). In the last years a novel subpopulation of MG patients has been described that harbors antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4), another postsynaptic neuromuscular antigen. In early-onset AChR MG (EOMG), the thymus plays an important role in immunopathogenesis, and early thymectomy is beneficial. It is still unknown if the thymus plays any role in Lrp4-MG. In this pilot study, we compared thymus samples from four patients with Lrp4-MG (one pre-treated with immunosuppressive drugs), four non-MG controls and five EOMG patients (not pretreated with immunosuppressive drugs). Immunohistochemistry of the Lrp4-MG thymi revealed normal architecture, with normal numbers and distribution of B-cells, lymphoid follicles and Hassall's corpuscles. Primary CD23⁺ lymphoid follicles were similarly infrequent in Lrp4-MG and control thymic sections. In none of the control or Lrp4-MG thymi did we find secondary follicles with CD10⁺ germinal centers. These were evident in 2 of the 5 EOMG thymi, where primary lymphoid follicles were also more frequent on average, thus showing considerable heterogeneity between patients. Even if characteristic pathological thymic changes were not observed in the Lrp4 subgroup, we cannot exclude a role for the thymus in Lrp4-MG pathogenesis, since one Lrp4-MG patient went into clinical remission after thymectomy alone (at one year follow-up) and one more improved after thymectomy in combination with immunosuppressive therapy.     

Validación psicométrica de la Escala de gravedad de fatiga en médicos residentes mexicanos

Resident physicians are continually exposed to fatigue, which can lead to work, academic and personal problems, so it is important to have reliable and valid instruments to measure it. One of the most used is Fatigue Severity Scale, but, there are versions with different number of items in different populations. Therefore, the purpose of this work was to translate, adapt culturally relevant and compare versions with different numbers of items, to identify the most appropriate in Mexican resident physicians. With three different groups of participants; first one for translation by seven expert judges in the language, second for psychometric validation with 100 resident physicians, and third for confirmatory factor analysis and invariance test by type of program (specialty and high specialty) with 182 resident physicians. Distribution, discrimination, reliability and factor structure of the scale were tested in an exploratory and confirmatory analysis, leaving a final scale of 6 items with good fit (X²[9] = 9,39, p = 0,40; CFI = 0,99; RMSEA = 0,02), with a reliability = 0,91 and strict factorial invariance by type of residence program.     

Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price

Background Spending on biological agents has risen dramatically due to the high cost of the drugs and the increased prevalence of spondyloarthritis. Objective To evaluate the annual cost per patient and cost for each biological drug for treating patients with spondyloarthritis from 2009 to 2016, and to calculate factors that affect treatment cost, such as optimizing therapies by monitoring drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts or negotiated rebates in biologicals acquired by the pharmacy department. Method Retrospective, observational study in a Spanish tertiary hospital. Main outcome Annual cost per patient and per drug. Factors that influenced the costs and socio-demographic parameters and disease activity. Results A total of 129, 215, and 224 patients were treated in 2009, 2013, and 2016, respectively. The annual cost per patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The introduction of new drugs drives economic competition, leading to total savings per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90% in 2016. The number of patients with optimized therapies reached 47.5% in 2016, which led to cost savings of EUR798,614, in addition to savings from official discounts and rebates of EUR252,706 and savings from optimized therapies of EUR545,908 in 2016. Conclusion The cost of biological treatments declined after official discounts, negotiated rebates, and optimized therapies, leading to a significant decrease in the annual cost per patient. The greatest contribution to economic savings in biological therapy according to our study was biological therapy optimization.     

Effect of olive cultivar on bioaccessibility and antioxidant activity of phenolic fraction of virgin olive oil

Aim

This study aims to characterize the phenolic profile and antioxidant capacity of seven monovarietal virgin olive oils (VOOs) and evaluate their in vitro gastrointestinal stability.

Methods

‘Picual’, ‘Blanqueta’, ‘Sevillana’, ‘Habichuelero’, and ‘Chetoui’ olive cultivars were selected for VOO extraction. The oils were subjected to in vitro digestion. The recovery index (RI) of phenolic compounds after each digestion step and the bioaccessibility index (BI) were evaluated. In addition, the antioxidant activity of the bioaccessible fraction (BF) of VOOs was determined by DPPH, ABTS, and ORAC assays, as well as by studying the intracellular reactive oxygen species in Caco-2 cells.

Results

Differences were found in the composition of phenolic compounds in VOOs depending on cultivars. During the digestive process, important losses of phenolic compounds were observed between the buccal and duodenal steps, unlike HTy and Ty, which presented increased recovery due to the hydrolysis of secoiridoid derivatives. Differences in the bioaccessibility of phenolic compounds were found between varieties of VOOs. ‘Sevillana’ VOO had the highest total bioaccessibility (36%), followed by the ‘Picual’ (19%), ‘Chetoui’ (17%), ‘Habichuelero’ (10%), and ‘Blanqueta’ (8%) varieties. The BF of all the varieties of VOO showed similar radical ABTS scavenging capacity, ‘Chetoui’, and ‘Blanqueta’-BF having the highest radical DPPH scavenging capacity, and ‘Habichuelero’ and ‘Picual’-BF showing protective effects against the peroxyl radical measured by ORAC_FL assay. All VOO-BFs presented decreases in ROS levels in Caco-2 cells.

Conclusions

Our results suggest differences in the bioaccessibility of phenolics from diverse VOO varieties, which could lead to different biological properties. Therefore, this study represents a first step toward the development of novel dietary strategies focusing on the phenolic supplementation of different VOOs to preserve human health.

     

Evaporating solvents with a warm air-stream: effects on adhesive layer properties and resin-dentin bond strengths

OBJECTIVES: This study evaluated the effect of a warm or cold air-dry stream for solvent evaporation on the microtensile resin-dentin bond strength (muTBS), nanoleakage pattern (SEM), degree of conversion (DC) and solvent evaporation rates (SE) of an ethanol/water- (Adper Single Bond, [SB] 3MESPE) and an acetone-based (Prime & Bond 2.1, [PB] Dentsply), two-step etch-and-rinse adhesive system. MATERIALS AND METHODS: Adhesives were applied on demineralized dentin surfaces. For SE, a warm or cold air-dry stream (10 s) was applied prior to light-activation (10 s). Bonded sticks (0.8mm2) were tested in tension (0.5 mm/min). Two bonded sticks from each tooth were immersed in a 50% (w/v) solution of silver nitrate (24 h), photodeveloped (8 h) and analyzed by SEM. The DC and solvent evaporation rate of the adhesives were evaluated under FTIR and analytical balance, respectively. Data were analyzed by two-way ANOVA and Tukey test (alpha=0.05). RESULTS: Higher muTBS and lower nanoleakage were observed when the SE step was performed with warm air-dry stream. However, the DC of the adhesives was not altered by the use of a warm air-dry. CONCLUSIONS: The use of a warm air-dry stream seems to be a clinical tool to improve the bond strength and the quality of the hybrid layer (less nanoleakage infiltration), since it might reduce the number of pores within the adhesive layer.     

Relationship between the inclination of the coronoid process of the mandible and the electromyographic activity of the temporal muscle in skeletal Class I and II individuals

The aim of this study was to verify the relationship between the inclination of the coronoid process of the mandible, and electromyographic activity of the anterior part of the temporal muscle in skeletal Class I and II individuals. Forty-seven volunteers (mean age 24.5 +/- 3.9 years) were subdivided into two groups, according to angle ANB: Class I (n = 25) and II (n = 22). Two radiographic examinations were performed; one lateral cephalogram to measure angle ANB, and one frontal cephalogram to measure the inclination of the coronoid process. Electromyographic (EMG) examination of the anterior part of the subjects' temporal muscles was performed. Statistical analysis of the data showed that Class II individuals presented lower electromyographic activity of the anterior part of the temporal muscle. Based on the results obtained, it was concluded that the skeletal classes analyzed had no influence on the inclination of the coronoid process. The inclination of the coronoid process was not influenced by the electromyographic activity of the anterior part of the temporal muscle in Class I and II individuals; however, the lower electromyographic activity of the anterior part of the temporal muscle could be influenced by the skeletal class in Class II individuals.     

Oral complaints in progressive systemic sclerosis: two cases report

Progressive systemic sclerosis is a chronic sclerotic disease which causes diffuse, increased deposition of extracellular matrix in connective tissue with vascular abnormalities, resulting in tissue hypoxia. Aesthetic and facial dysfunction are followed by important oral and facial manifestation of disturbances such as xerostomia, the lack of saliva in the mouth, and its associated complications. Most clinical manifestations begin with tongue rigidity. The facial skin changes and bone resorption of mandible angle are often reported. Other systemic changes include the involvement of internal organs which leads to serious complications as well as disorders in the cardiac muscle and Raynaud's phenomenon. The objective of the this paper is to report two cases of systemic sclerosis in patients with oral and facial manifestations of the disease. A brief review of the literature, focusing on deontological alterations is also presented.     

Evaluation of some oral postradiotherapy sequelae in patients treated for head and neck tumors

The aim of this study was to evaluate the oral sequelae of radiotherapy in patients treated between 1999 and 2003 for head and neck tumors. One-hundred patients (24 women, 76 men) ranging in age from 30 to 83 years (mean 59.2 years) were examined. Time since radiotherapy ranged from 1 to 72 months (mean 28 months). The total mean radiation dose received by the patients was 5,955 cGy. The evaluation protocol included anamnesis, intraoral and extraoral examination, measurement of stimulated salivary flow and salivary pH. Symptoms reported by the patients included dry mouth (68%), dysphagia (38%), and dysgeusia (30%). In 64% of the patients, the mean stimulated salivary flow rate was less than 0.7 ml/min. The mean salivary pH was 6.97 (+/- 0.714). Stimulated salivary flow increased with increasing postradiotherapy time (p < 0.05). The prevalence of mucositis was associated with higher radiation doses (p < 0.05), and the prevalence of atrophic candidiasis was related to a longer post-treatment period (p < 0.05). Two cases of recurrence of the primary tumor were detected during the study. The main effect of radiotheraphy in the head and neck region was a reduction of the salivary flow rate, even though our study demonstrated that there was a modest late improvement of the salivary flow.