Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex.

Neurodevelopmental disorders (NDDs) affect 7-14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into NDD etiology. Whole-genome bisulfite sequencing was used to examine DNA cytosine methylation in 49 human cortex samples from 3 different NDDs (autism spectrum disorder, Rett syndrome, and Dup15q syndrome) and matched controls. Integration of methylation changes across NDDs with relevant genomic and genetic datasets revealed differentially methylated regions (DMRs) unique to each type of NDD but with shared regulatory functions in neurons and microglia. NDD DMRs were enriched within promoter regions and for transcription factor binding sites with identified methylation sensitivity. DMRs from all 3 disorders were enriched for ontologies related to nervous system development and genes with disrupted expression in brain from neurodevelopmental or neuropsychiatric disorders. Genes associated with NDD DMRs showed expression patterns indicating an important role for altered microglial function during brain development. These findings demonstrate an NDD epigenomic signature in human cortex that will aid in defining therapeutic targets and early biomarkers at the interface of genetic and environmental NDD risk factors.

Optimal Positioning of Inertial Measurement Units in a Smart Shirt for Determining Respiratory Volume.

Tidal volume can be estimated using the surface motions of the upper body induced by respiration. However, the precision and instrumentation of such estimation must be improved to allow widespread application. In this study, respiration induced changes in parameters that can be recorded with inertial measurement units are examined to determine tidal volumes. Based on the data of an optical motion capture system, the optimal positions of inertial measurement units (IMU) in a smart shirt for sets of 4, 5 or 6 sensors were determined. The errors observed indicate the potential to determine tidal volumes using IMUs in a smart shirt.Clinical Relevance- The measurement of respiratory volumes via a low-cost and unobtrusive smart shirt would be a major advance in clinical diagnostics. In particular, conventional methods are expensive, and uncomfortable for conscious patients if measurement is desired over an extended period. A smart-shirt based on inertial sensors would allow a comfortable measurement and could be used in many clinical scenarios - from sleep apnoea monitoring to homecare and respiratory monitoring of comatose patients.

Effects of Intra-Abdominal Pressure on Lung Mechanics during Laparoscopic Gynaecology.

Investigating the relations between surgical actions and physiological reactions of the patient is essential for developing pre-emptive model-based systems. In this study, the effects of insufflating abdominal cavity with CO2 in laparoscopic gynaecology on the respiration system were analysed. Real-time recordings of anaesthesiology and surgical data of five subjects were acquired and processed, and the correlation between lung mechanics and the intra-abdominal pressure was evaluated. Alterations of ventilation settings undertaken by the anaesthesiologist were also considered. Experimental results demonstrated the high correlation with a mean Pearson coefficient of 0.931.Clinical Relevance- This study demonstrates the effects of intra-abdominal pressure during laparoscopy on lung mechanics and enables developing predictive models to promote a greater awareness in operating rooms.

An alternative way to measure respiration induced changes of circumferences: a pilot study.

Various measurement systems can be used to obtain dynamic circumferences of the human upper body, but each of these systems has disadvantages. In this feasibility study we introduce a non-invasive and wearable thoracic belt to measure dynamic changes of circumferences of thorax or abdomen. To evaluate this approach, five subjects undertook various breaths of disparate tidal volumes, which were measured by the belt and simultaneously by a motion capture system which provided a reference metric.The results of the belt concurred with the reference system. A coefficient of determination (adjusted R2) of 0.99 and a mean squared error of less than 0.87 mm2 showed that the belt is capable of measuring changes accurately and a couple of respiratory parameters, such as the respiratory rate, can be obtained.Clinical Relevance-The introduced system links surface motions of the upper body with the underlying respiratory mechanics. Thus it provides some respiratory parameters without the disadvantages of a facemask or a mouthpiece. The system could allow the analysis of breathing status in some clinical applications and could be used for low-cost monitoring in homecare or to analyse respiratory parameters during sports.

Tidal volume via circumferences of the upper body: a pilot study.

The gold standard for tidal volume measurement is spirometry. Based on retrospective data, this study evaluates different geometric lung models in their ability to deliver accurate tidal volumes from changes in thoracic and abdominal circumference. The geometric lung models showed good coefficients of determination (adjusted R2 >0.97) compared to the tidal volumes measured by a body plethysmograph. Tidal volumes obtained by circumference changes might be used in surveillance systems to analyze respiration without a face mask.

An investigation on heat transfer to the implant-bone interface due to abutment preparation with high-speed cutting instruments.

Excessive heat generation at the implant-bone interface may cause irreversible bone damage and loss of osseointegration. The effect of heat generation in vitro at the implant surface caused by abutment reduction with medium- and extra-fine-grain diamond and tungsten burs in a high-speed dental turbine was examined. Titanium-alloy abutments connected to a titanium-alloy cylindrical implant embedded in an acrylic-resin mandible in a 37 degrees C water bath were reduced horizontally and vertically. Temperature changes were recorded via embedded thermocouples at the cervix and apex of the implant surface. Analysis of variance for repeated measures was used to compare seven treatment groups. Thirty seconds of continuous cutting with standard turbine coolant caused a mean temperature increase of 1 degrees C with a maximum of 2 degrees C. Similar tungsten cutting caused a mean increase of 2 degrees C with a maximum of 4.7 degrees C, significantly higher than diamond reduction. Additional air-water spray for continuous tungsten cutting had no significant effect, while intermittent cutting for 15-second increments reduced the temperature increase by 75%. Thus, abutment reduction with medium-grit diamonds using intermittent pressure and normal turbine coolant is unlikely to cause an interface-temperature increase sufficient to cause irreversible bone damage and compromise osseointegration.

An investigation of heat transfer to the implant-bone interface related to exothermic heat generation during setting of autopolymerizing acrylic resins applied directly to an implant abutment.

Excessive heat generation at the implant-bone interface may cause bone damage and compromise osseointegration. Autopolymerizing acrylic resins are commonly used intraorally to join impression copings and suprastructure components for soldering. The effect of heat generation at the implant surface related to the exothermic setting reaction of autopolymerizing acrylic resins applied to an attached abutment was examined in vitro. Two brands of autopolymerizing acrylic resin, Duralay and GC Pattern Resin, were compared. Acrylic resin was applied to a titanium alloy abutment connected to a titanium alloy cylindric implant in varying controlled volumes, with both bulk application and brush paint-on techniques. The implant was embedded in an acrylic resin mandible in a 37 degrees C water bath. Temperature changes were recorded via embedded thermocouples at the cervical and apical of the implant surface. Analysis of variance for repeated measures was used to compare treatment groups. A mean maximum increase in temperature of 4 to 5 degrees C was seen at the implant cervical for both materials, with a maximum temperature increase of 6 degrees C. No difference between Duralay and GC Pattern Resin was seen, except for bulk application to medium-sized copper bands at the implant cervical (P < .05). No difference between the bulk and brush techniques was seen for all options, except for GC, where bulk application to medium-sized copper bands produced higher temperatures than the brush technique (P < .05). Spray coolant reduced temperatures for bulk application of both Duralay and GC (P < .05).

Removable partial denture with a lateral rotational path of insertion.

A removable partial denture with a lateral path of insertion is useful when unsightly facial clasps are objectional to the patient. Rounded rest seat preparations allow extensions of the minor connector to rotate laterally into embrasure undercuts, providing retention. Guiding planes on the contralateral side ensure a different path of withdrawal from the retentive elements. A Kennedy Class IV arch with a long edentulous span is used to illustrate the denture design.

Fatal Clostridium difficile enteritis caused by the BI/NAP1/027 strain: a case series of ileal C. difficile infections.

Clostridium difficile generally causes diarrhoea and colitis. Small-bowel infections are considered to be rare. Twelve cases of ileal C. difficile infections are presented, including the first reported case proven to be caused by the hypervirulent BI/NAP1/027 strain. This case series suggests that small bowel involvement in C. difficile infections may be more frequent than previously thought.

Efficient factor VIII affinity purification using a small synthetic ligand.

BACKGROUND: Hemophilia A is currently treated by infusions of the coagulation factor (F) VIII, of which production and purification remain a challenging task. Current purification procedures using immunoaffinity chromatography are cumbersome, expensive, and suffer from the instability of the applied antibody ligands, which elute along with the product and contaminate it. Recently, FVIII was purified using octapeptide ligands, but their use is limited due to the low resistance to proteases. OBJECTIVE: Our goal was to develop and evaluate a novel ligand for FVIII purification, overcoming the drawbacks of current procedures. METHODS: Peptide ligands were screened for binding of (125)I-plasma-derived-FVIII (pdFVIII) in a microbead assay. A selected ligand-coated Toyopearl resin was then used for pdFVIII purification from cell-conditioned Delbucco's modified Eagle's medium (DMEM) containing fetal bovine serum. The proteolytic stability of ligand was measured by incubating with human serum and proteinase K, and its cytotoxicity towards human OV-MZ-6 cells was assayed. RESULTS: A high-affinity octapeptidic FVIII ligand was modified into the small, highly stable and non-toxic peptidomimetic ligand L4 by rational and combinatorial design without affecting its affinity for FVIII. Using ligand L4-coated Toyopearl resin, pdFVIII was isolated from cell-conditioned medium with high purity and 89% column retention after elution with a mild buffer containing 0.6 m NaCl at pH 6.8. CONCLUSIONS: Ligand L4 offers a valuable alternative to antibody-based procedures for laboratory and industrial production. Its synthesis by established solid-phase procedures is straightforward and considerably cheaper than the biotechnological production of antibodies, and safety concerns associated with the use of biological material are overcome.

Splinting osseointegrated implants and natural teeth in rehabilitation of partially edentulous patients. Part I: laboratory and clinical studies.

A significant clinical consideration in the restoration of partial edentulism with implant and tooth-supported prostheses is whether implants and natural teeth abutments should be splinted, and if so, in what manner. This article presents a review of laboratory and clinical studies related to splinting. Stress analysis studies reveal high stress concentration around the implant neck when rigidly connected to teeth. This was not borne out in in vivo studies in short-span bridges. While stress absorbing elements have been advocated to redistribute and reduce stress concentration away from the implant neck where bone resorption is often seen, finite element analysis and photo-elastic studies demonstrate that such stress absorbing elements may be effective only when their resiliency is in the same order of magnitude as the periodontal ligament. Clinical studies reporting life table statistics in combined implant and tooth restorations do not show adverse effects of splinting teeth to implants. These studies, however, are mostly short-term reports on survival with results that are as yet inconclusive. The issue of connecting with rigid or non-rigid connectors remains unresolved with a growing body of information favouring retrievable short-span rigid connection to non-mobile teeth. Root intrusion is a potential clinical hazard of non-rigid connection.

Splinting osseointegrated implants and natural teeth in rehabilitation of partially edentulous patients. Part II: principles and applications.

Lone standing splinted implant segments are accepted as optimal. However, in the treatment of partial edentulism, clinical reality often predicates the consideration of splinting teeth and implants due to variables of tooth/implant location and available bone support. This article presents a review on biomechanical aspects of splinting teeth and some considerations of splinting teeth and implants. A proposed classification of splinting applicable to both teeth and implants is presented as well as a discussion of the clinical aspects of splinting illustrated with clinical cases.

[Direct detection of Herpes simplex virus using monoclonal antibodies in pregnant women]. / Direktnachweis von Herpes simplex Viren mit monoklonalen Antikörpern bei Schwangeren.

HSV infections are the cause of 15%-25% of all venereal diseases. According to the rise of genital HSV infections a similar rise in seriously infected newborn babies can be expected. We obtained 159 cervix smears from 114 pregnant women for a direct test with monoclonal antibodies against HSV I and HSV II infections in the obstetrical division of the University Clinic Frankfurt. 17 (14.9%) of the 114 patients were discovered to be infected with HSV. Blood samples of 15 of these women were examined for IgG and IgM antibodies against HSV I and HSV II. Four samples were negative for IgG and IgM antibodies, 11 samples had visible IgG antibodies but no IgM antibodies could be seen. The direct proof of monoclonal antibodies is simple and quickly obtainable in any laboratory and thus is an improvement towards quick diagnosis and typing of HSV infections. An overall screening of HSV infections in pregnant women does not seem recommendable since the antepartal result does not correlate to the risk of infection during delivery.

The linear accuracy of impressions and stone dies as affected by the thickness of the impression margin.

This study compared the dimensional accuracy of impressions and dies made from a metal model simulating prepared abutments and having gingival sulci of varying widths. Measurements of the abutments, impressions, and stone dies were made using a travelling microscope, and the number of defects in each impression was recorded. The impressions and dies made from abutments with narrower sulci showed greater distortions. Analysis of variance and the Fisher PLSD post hoc test indicated significant differences between the group having a sulcular width of 0.08 mm and the groups having larger sulcular widths for the impressions and for the dies (P < .05). The large coefficient of variation occurring groups having 0.08-, 0.13-, and 0.18-mm sulcular widths demonstrated the difficulty of consistently obtaining good impressions of abutments having such narrow sulcular widths. Between 50% and 90% of abutment impressions having sulcular widths of 0.08 and 0.13 mm had defects.

Surface roughness of tooth shoulder preparations created by rotary instrumentation, hand planing, and ultrasonic oscillation.

A dentinal shoulder with a smooth surface is necessary to ensure accurate adaptation of a porcelain crown. The surface roughness of dentinal shoulders prepared with different instruments was investigated in this in vitro study. Sixty shoulders, 1 mm wide, were prepared with coarse grit diamonds in extracted formalin-stored teeth. Of these 60 shoulders 20 were further refined with fine grit, and 20 more shoulders were refined with super-fine grit diamonds. The surface roughness (Ra) of the dentinal shoulders was recorded after each procedure. Thirty surfaces were further finished and refined with a hand chisel, and the other 30 surfaces were finished with a flat-ended diamond tip held in an ultrasonic generating device; the Ra was then recorded. These shoulder preparations were examined under a scanning electron microscope. The Ra of the dentinal shoulders prepared by the ends of the different grit diamonds was not significantly different (p > 0.05). Hand planing did not improve the Ra, and ultrasonic planing significantly increased the Ra (p < 0.05). Scanning electron micrographs revealed no apparent qualitative differences between surface roughness of the shoulders prepared by the diamonds or by the hand-planed surface. However, deeper scratches were evident at ultrasonically planed surfaces.

The influence of surface loading and irradiation time during curing on mechanical properties of a composite.

PURPOSE: The aim of this study was to determine the influence of different surface loadings during curing with various irradiation times on hardness and diametral tensile strength of a light-cured composite. MATERIAL AND METHODS: A mold was fabricated to allow loading during curing of cylindrical specimens of a composite. Four surface loadings of 0, 0.35, 0.87, and 1.73 MPa and four irradiation times of 20, 40, 60, and 180 seconds were used (n = 15). Each specimen was subjected to a microhardness test and to a diametral tensile strength test. RESULTS: Surface loading during curing affected both hardness and strength properties, whereas irradiation time influenced only the hardness of the material. Both parameters gained between 15% and 20% improvement when the material was loaded with 0.87 MPa surface pressure and cured by 60-second irradiation time. Higher loading or longer irradiation times did not improve these properties. CONCLUSION: Loading composite during curing improves its mechanical properties, probably through decreasing flaws and air voids of the material.