Using Patient-Derived Induced Pluripotent Stem Cells to Identify Parkinson's Disease-Relevant Phenotypes.

PURPOSE OF REVIEW: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting older individuals. The specific cause underlying dopaminergic (DA) neuron loss in the substantia nigra, a pathological hallmark of PD, remains elusive. Here, we highlight peer-reviewed reports using induced pluripotent stem cells (iPSCs) to model PD in vitro and discuss the potential disease-relevant phenotypes that may lead to a better understanding of PD etiology. Benefits of iPSCs are that they retain the genetic background of the donor individual and can be differentiated into specialized neurons to facilitate disease modeling. RECENT FINDINGS: Mitochondrial dysfunction, oxidative stress, ER stress, and alpha-synuclein accumulation are common phenotypes observed in PD iPSC-derived neurons. New culturing technologies, such as directed reprogramming and midbrain organoids, offer innovative ways of investigating intraneuronal mechanisms of PD pathology. PD patient-derived iPSCs are an evolving resource to understand PD pathology and identify therapeutic targets.

Guidelines for the provision and assessment of nutrition support therapy in the pediatric critically Ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition

This document represents the first collaboration between two organizations, American Society of Parenteral and Enteral Nutrition and the Society of Critical Care Medicine, to describe best practices in nutrition therapy in critically ill children. The target of these guidelines is intended to be the pediatric (> 1 mo and < 18 yr) critically ill patient expected to require a length of stay greater than 2 or 3 days in a PICU admitting medical, surgical, and cardiac patients. In total, 2,032 citations were scanned for relevance. The PubMed/Medline search resulted in 960 citations for clinical trials and 925 citations for cohort studies. The EMBASE search for clinical trials culled 1,661 citations. In total, the search for clinical trials yielded 1,107 citations, whereas the cohort search yielded 925. After careful review, 16 randomized controlled trials and 37 cohort studies appeared to answer one of the eight preidentified question groups for this guideline. We used the Grading of Recommendations, Assessment, Development and Evaluation criteria to adjust the evidence grade based on assessment of the quality of study design and execution. These guidelines are not intended for neonates or adult patients. The guidelines reiterate the importance of nutritional assessment, particularly the detection of malnourished patients who are most vulnerable and therefore potentially may benefit from timely intervention. There is a need for renewed focus on accurate estimation of energy needs and attention to optimizing protein intake. Indirect calorimetry, where feasible, and cautious use of estimating equations and increased surveillance for unintended caloric underfeeding and overfeeding are recommended. Optimal protein intake and its correlation with clinical outcomes are areas of great interest. The optimal route and timing of nutrient delivery is an area of intense debate and investigations. Enteral nutrition remains the preferred route for nutrient delivery. Several strategies to optimize enteral nutrition during critical illness have emerged. The role of supplemental parenteral nutrition has been highlighted, and a delayed approach appears to be beneficial. Immunonutrition cannot be currently recommended. Overall, the pediatric critical care population is heterogeneous, and a nuanced approach to individualizing nutrition support with the aim of improving clinical outcomes is necessary.

European Society for Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Neurological Impairment

OBJECTIVES: Feeding difficulties are frequent in children with neurological impairments and can be associated with undernutrition, growth failure, micronutrients deficiencies, osteopenia, and nutritional comorbidities. Gastrointestinal problems including gastroesophageal reflux disease, constipation, and dysphagia are also frequent in this population and affect quality of life and nutritional status. There is currently a lack of a systematic approach to the care of these patients. With this report, European Society of Gastroenterology, Hepatology and Nutrition aims to develop uniform guidelines for the management of the gastroenterological and nutritional problems in children with neurological impairment. METHODS: Thirty-one clinical questions addressing the diagnosis, treatment, and prognosis of common gastrointestinal and nutritional problems in neurological impaired children were formulated. Questions aimed to assess the nutritional management including nutritional status, identifying undernutrition, monitoring nutritional status, and defining nutritional requirements; to classify gastrointestinal issues including oropharyngeal dysfunctions, motor and sensory function, gastroesophageal reflux disease, and constipation; to evaluate the indications for nutritional rehabilitation including enteral feeding and percutaneous gastrostomy/jejunostomy; to define indications for surgical interventions (eg, Nissen Fundoplication, esophagogastric disconnection); and finally to consider ethical issues related to digestive and nutritional problems in the severely neurologically impaired children. A systematic literature search was performed from 1980 to October 2015 using MEDLINE. The approach of the Grading of Recommendations Assessment, Development, and Evaluation was applied to evaluate the outcomes. During 2 consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation using the nominal voting technique. Expert opinion was applied to support the recommendations where no randomized controlled trials were available

In vitro corrosion resistance of high-palladium dental casting alloys.

OBJECTIVE: The objective of this study was to characterize the in vitro corrosion behavior of five high-palladium dental alloys in two media using a potentiodynamic polarization technique. METHODS: Potentiodynamic cyclic polarization between -1000 and +1000 mV (SCE), 12 h open-circuit potential measurement, and linear polarization were performed on cast specimens of three Pd-Cu-Ga alloys and two Pd-Ga alloys in deaerated 0.09% NaCl solution and Fusayama artificial saliva at 37 degrees C. Zero-current potential, corrosion current density, open-circuit potential, and polarization resistance were determined. The Kruskal-Wallis test and the Mann-Whitney U-test were used to analyze the numeric findings. RESULTS: The Pd-Cu-Ga and Pd-Ga alloys in both the as-cast and heat-treated conditions showed spontaneous passive behavior under electrochemical conditions similar to those in the oral environment. The Pd-Cu-Ga alloys Liberty and Spartan Plus exhibited increased activity in the Fusayama artificial saliva after the porcelain-firing heat treatment, which may have arisen from internal oxidation of casting defects. Heat-treated Freedom Plus had an unstable oxide film to form on the surface during anodic polarization and may have a limited tendency for pitting corrosion in the Fusayama artificial saliva. The two heat-treated Pd-Ga alloys remained passive in the test media. As a group, the high-palladium alloys exhibited satisfactory corrosion resistance. SIGNIFICANCE: Corrosion of high-palladium alloys in the oral environment involves a release of ions that is related to their biocompatibility. Knowledge of the in vitro corrosion behavior of these alloys may lead to better understanding of any biologically adverse effects in vivo.

Effects of three soldering techniques on the strength of high-palladium alloy solder joints.

STATEMENT OF PROBLEM: Little information is available on the optimum technique for soldering high-palladium alloys, which have gained considerable popularity for prosthodontic applications. PURPOSE: The objective of this study was to compare the flexural stress at the proportional limit of four noble dental alloy specimens soldered with torch, oven, and infrared-techniques. MATERIALS AND METHODS: The high-palladium alloys studied were Legacy XT (Jelenko), Freedom Plus (Jelenko), and IS 85 (Williams/Ivoclar). A gold-palladium alloy, Olympia (Jelenko), served as the control. Thirty round bars, 18 x 3 mm, were cast from each alloy, cut in half, aligned, and joined using Olympia Pre solder (Jelenko) for the gas-oxygen torch and the infrared technique and Alboro LF solder (Jelenko) for the oven technique. Each soldered bar was subjected to three-point bending, and the maximum elastic stress or strength of the solder joint was calculated at the proportional limit. Data were analyzed by two-way ANOVA and the Ryan-Einot-Gabriel-Welsch (REGW) multiple range test at the 0.05 level of significance. RESULTS: There was no significant difference between torch and oven-soldering, but both were significantly different from the infrared technique. ANOVA showed a significant difference between alloys, but this difference could not be detected with the REGW test. SEM examination of the fracture surfaces revealed grooves associated with the path of crack propagation. X-ray energy-dispersive spectroscopic analysis failed to detect copper in the solders, and there were no significant changes in the solder compositions after the melting procedures. CONCLUSIONS: All three techniques can yield satisfactory solder joints in high-palladium alloys. These joints should be well-polished to achieve optimal strength.

Metallurgical structure and microhardness of four new palladium-based alloys.

PURPOSE: This investigation compared the Vickers hardness and microstructures of four recently marketed, palladium-based alloys for metal-ceramic restorations. MATERIALS AND METHODS: Wax patterns simulating copings for maxillary central incisors were invested in a fine-grained, carbon-free, phosphate-bonded investment. Following burnout, the palladium alloys were fused with a gas-oxygen torch, centrifugally cast, and bench-cooled. Representative castings were embedded in transparent metallographic resin and sectioned to yield two mirror-image specimens. The specimens were evaluated in either the as-cast condition or following heat treatment simulating the firing cycles for Vita VMK porcelain. Vickers hardness measurements (n = 50) were made using a 1-kg load, and photomicrographs of polished and etched specimens were obtained with a scanning electron microscope. RESULTS: The measured values of microhardness for the as-cast alloys were in excellent agreement with values reported by the manufacturer. The hardness in the as-cast condition was significantly greater for the Pd-Cu-Ga-In alloy, compared with the other three alloys, which did not contain copper. For the three high-palladium (> or = 75 wt%) alloys, there were small (4%-8%) decreases in hardness following heat treatment, whereas a larger decrease (13%) in hardness occurred for the Pd-Ag-In-Sn alloy after heat treatment. The porcelain firing cycles caused microstructural homogenization for all four alloys, and the relatively thick near-surface oxidation region in the Pd-Cu-Ga-In and Pd-Ag-In-Sn alloys was not observed in the two heat-treated Pd-Ga-Ag-In-Au alloys. CONCLUSIONS: The multiphasic microstructures of these alloys may have some significance for the in vitro and clinical corrosion behavior and the metal-ceramic bond strength. The hardness for the three high-palladium alloys may be controlled by submicroscopic precipitates that remain unaltered by heat treatment. The significantly greater hardness for the Pd-Cu-Ga-In alloy may cause greater difficulty for finishing castings in the dental laboratory compared with the other three alloys studied. The strengthening mechanism for the Pd-Ag-In-Sn alloy has significant temperature dependence, which might be exploited to achieve optimum mechanical properties.

Effect of disinfection of custom tray materials on adhesive properties of several impression material systems.

The effects of impression tray disinfection procedures on the bond strength of impression-material adhesives to two types of resin trays were evaluated with a tensile test. Autopolymerizing acrylic resin and a visible light-curing resin were formed into one-half inch cubes. A screw eye was attached to each cube before polymerization. Perforated trays were fabricated with stops to maintain an even one-eighth inch of impression material over the resin block. Hooks on the opposite side permitted attachment of the metal plate to a mechanical testing machine. Before adhesive was applied, one third of the resin specimens were immersed in a 1:213 iodophor solution; one third in a 10% sodium hypochlorite solution, and one third were kept in the "as fabricated" condition. Polysulfide, polyether, and polyvinyl siloxane impression material-adhesive systems were evaluated. The resin-impression material-metal plate couples were attached to a mechanical testing machine and tensile forces were applied at a separation rate of 5 inches per minute. Mean values for adhesive strength ranged from 3.49 kg/cm2 for the autopolymerizing acrylic resin/iodophor/polyether combination to 10.55 kg/cm2 for the autopolymerizing acrylic resin/untreated/polyvinyl siloxane combination. Differences were detected among materials and disinfecting procedure. Clinically, disinfection of resin trays may adversely affect retention of the impression material to the tray.

Effect of ultrasonic cleaning and air polishing on porcelain labial margin restorations.

This study examined porcelain labial margins after ultrasonic scaling and air polishing. Thirty metal coupons were covered with 1.5 mm thick shoulder porcelain and cemented to acrylic resin blocks. A reference mark divided each specimen into a "treated" and an "untreated" side. The specimens were treated as three groups with: (1) an air polisher; (2) an ultrasonic scaler, and (3) the ultrasonic scaler and the air polisher. Surface roughness was determined and selected specimens were observed under scanning electron microscope. Surface roughness ranged from 0.37 microns to 1.06 microns for the untreated sides and from 0.86 microns to 2.80 microns for the treated sides. Increases in roughness were 69% for the ultrasonic scaler/air-polisher; 127% for the air polisher, and 162% for the ultrasonic scaler. ANOVA indicated a significant difference between the treatments. Specimens treated with the air polisher or the ultrasonic scaler and air polisher combination were less distorted than those treated with the ultrasonic scaler alone. The data suggested that careless use of an ultrasonic scaler or air polisher could substantially alter porcelain facial margins.

Torque generated by handheld screwdrivers and mechanical torquing devices for osseointegrated implants.

This study evaluated the ability of practitioners experienced in the use of Brãnemark implant components to impart a desired torque using handheld screwdrivers. The torque output and variability of mechanical torque devices was also examined. For clinicians using handheld screwdrivers, values ranged from 0.7 to 18.1 Ncm, 1.4 to 33.7 Ncm, and 8.2 to 36.2 Ncm for the 10-Ncm, 20-Ncm, and 32-Ncm torques respectively. The manually operated mechanical torquing devices produced torque values within the tolerances specified by their respective manufacturers at all levels. Significant variation from the manufacturer's set values were noted as a function of tightening speed with the electronic torquing device. The data indicate that there is wide variation in the ability of clinicians to perceive adequate torquing forces applied to implant components. Calibrated torquing devices are mandatory if proper torquing procedures are to be accomplished.

Modification of angulated abutments to avoid unesthetic display of metal.

A procedure is described whereby the facial margin of angulated abutments are repositioned to avoid unesthetic display of metal in the anterior maxilla. The procedure is not difficult and can make a considerable difference in the patient's acceptance of the restoration.

Composite dowels and cores: effect of moisture on the fit of cast restorations.

A study was undertaken to evaluate the effect of interim restorations on the dimensional stability of composite post and core buildups subjected to moisture during the fabrication of cast restorations. Dimensional change associated with composite dowel and core buildups did not significantly alter the fit of cast restorations compared with natural teeth under the same conditions. The use of composite dowels and cores for the restoration of endodontically treated teeth is not contraindicated because of potential dimensional instability of the resin when exposed to moisture. Well-fitting interim restorations for either natural teeth or composite dowel and core buildups improved the fit of cast restorations 23% to 36%.

Changes in pH of irreversible hydrocolloid impression materials during setting.

Two ophthalmic and four dental irreversible hydrocolloid materials were tested in vitro to determine the initial pH and changes in pH to completion of set over 4 minutes. The ophthalmic Moldite material became more basic during its setting whereas the ophthalmic Moldeye material remained stable throughout the setting. The other materials tested decreased in pH with time.

Apparent bond strength of nonnoble alloy-porcelain combinations.

The apparent bond strengths of four porcelains and five nonnoble alloys were determined. On the basis of the data, the following conclusions can be drawn: The use of Vita, Ceramco, or Will-Ceram porcelains with Rexillium III, Pentillium, or Bak-On-NP alloy gave similar bond strength values. With the exception of Unibond alloy, the bond strength values obtained with Biobond porcelain were lower than those obtained with the other porcelain materials. The ceramometal bond strength values obtained with Unibond alloy were similar with all of the porcelains tested. The continued availability of a bewildering array of new alloys and porcelains suggests the urgent need for research designed to determine the bonding mechanisms and compatibility of various porcelain-alloy combinations. The data from this investigation provide criteria for the rational selection of bond strength-compatible porcelains and alloys for clinical use.

Effect of metal conditioners on porcelain-alloy bond strength.

The effect of three metal conditioners on the apparent bond strength of a single porcelain to four alloys was evaluated. On the basis of the bond strength data the following conclusions can be drawn. The use of metal conditioners provided no improvement in the apparent porcelain-alloy bond strength of Biocast and Biobond alloy. The use of Unibond alloy with its recommended conditioner Uniseal gave lower bond strength values than Unibond without the conditioner. With Rexillium III alloy the use of Uniseal gave the highest bond strength values, but these were statistically equal to those obtained with the recommended coating agent (Jeneric bonding agent). With the exception of Rexillium III alloy, it appears that coating agents may have a function other than bond strength improvement. In light of the continued marketing of new alloys, bonding agents, and porcelains, further research is needed to determine the mechanism of action of bonding agents as well as the porcelain-bonding agent-alloy interaction of various commercial products. Studies designed to address these topics are in progress.

A study of the acceptability of lateral interocclusal records by the Hanau H-2 articulator.

The acceptability of lateral interocclusal records by the Hanau H-2 articulator was studied on 28 edentulous patients. Acceptability was determined in both right and left lateral jaw movements. Of the 56 lateral interocclusal records made, 39 (70%) were accepted by the Hanau model H-2 articulator.

A comparison of healing and pain following excision of inflammatory papillary hyperplasia with electrosurgery and blade-loop knives in human patients.

Twenty human patients participated in a study designed to compare electrosurgery with blade-loop knives for the excision of inflammatory papillary hyperplasia in a split-mouth study. Questionnaires were used to assess pain and patient preference during a 2-week postoperative period, and photographs were made to chronicle the healing process. Healing occurred at approximately the same rate following each procedure. The majority of subjects did not perceive a difference in discomfort with either technique on the day of surgery or at any time during follow-up. Of those who did have a preference, a significant majority favored electrosurgery on the day of treatment. This preference became statistically insignificant on the second postoperative day and beyond.

Preliminary observations on clinical use of a base metal casting alloy.

A study was conducted to develop a laboratory technique and to evaluate the clinical efficacy of a base metal casting alloy. Slight modification of recommended investing procedures is required to produce consistently well-fitting castings with the test alloy. After 12 months of clinical service, the test alloy did not differ from the control alloy in tarnish, untoward gingival response, resistance to abrasion, or tooth sensitivity.

The effect of carbon fiber orientation on the fatigue resistance and bending properties of two denture resins.

The following conclusions were made concerning the effects of carbon fiber orientation on the flexural fatigue resistance and bending properties of two denture base acrylic resins. Hi-I resin, regardless of fiber presence or orientation, was more resistant to flexural fatigue than Lucitone resin. Carbon fibers placed perpendicular to the direction of applied stress produced the most favorable combination of increased resistance to bending and to flexural fatigue. Production of properly oriented fibers that are well centered within the resin is technically difficult and yields less predictable property improvements than result from randomly dispersed fibers.