Patients suffering from dystrophic epidermolysis bullosa are prone to developing autoantibodies against skin proteins: A longitudinal confirmational study.

Epidermolysis bullosa (EB) is a heritable skin blistering disease caused by variants in genes coding for proteins that secure cell-cell adhesion and attachment of the epidermis to the dermis. Interestingly, several proteins involved in inherited EB are also associated with autoimmune blistering diseases (AIBD). In this study, we present a long-term follow-up of 15 patients suffering from recessive dystrophic or junctional EB. From these patients, 62 sera were analysed for the presence of autoantibodies associated with AIBD. We show that patients suffering from recessive dystrophic EB (RDEB) are more susceptible to developing autoantibodies against skin proteins than patients suffering from junctional EB (70% vs. 20%, respectively). Interestingly, no correlation with age was observed. Most patients showed reactivity to Type XVII collagen/linear IgA bullous dermatosis autoantigen (n = 5; 33%), followed by BP230 (n = 4; 27%), Type VII collagen (n = 4; 27%) and laminin-332 (n = 1; 7%). The pathogenicity of these autoantibodies remains a subject for future experiments.

A randomized clinical trial on zirconia versus titanium implants in maxillary single tooth replacement.

OBJECTIVES: This RCT aimed to compare zirconia and titanium dental implants in the maxillary premolar region. The comparison was based on marginal bone level (MBL) changes, clinical parameters, aesthetic outcomes, and patient related outcome measures (PROMs) 1 year after prosthetic loading. MATERIALS AND METHODS: Fifty patients were randomly assigned to receive either a zirconia (ZrO2, n = 25) implant or a titanium (Ti, n = 25) bone-level implant. Implants were provided with a lithium disilicate crown 3 months after placement. Follow-up was at 1 month and after 1 year. The primary outcome pertained to changes in MBL. Reported secondary outcomes consisted of implant survival, peri-implant tissue health, aesthetics, and PROMs. RESULTS: Mean MBL change after 1 year was 0.01 mm (SD = 0.45; min = 0.72, max = 0.86) for ZrO2 and -0.09 mm (SD = 0.34; min = 0.53, max = -1.06) for Ti (p = .439). Scores for the other clinical outcome parameters and PROMs were generally favorable, with no significant differences. However, significant differences were found for the aesthetic outcomes regarding two criteria: (a) level of facial mucosa (p = .022), in favor of Ti, and (b) root convexity/soft tissue color and texture (p = .005) in favor of ZrO2. CONCLUSION AND CLINICAL IMPLICATIONS: The ZrO2 and Ti implant types used in this study, replacing a single missing maxillary premolar, show a comparable outcome in terms of MBL change after 1 year. Clinical and aesthetic parameters, as well as PROMs, are favorable and similar between both implant types after 1 year of prosthetic loading. These short-term study results suggest that both are suitable for clinical use.

[Ceramic implants: the state of art]. / Keramische implantaten: de stand van zaken.

A multitude of biomaterials have been used for the production of implants through the years. Titanium or titanium alloy have been regarded as the 'gold standard' for years. However, potential risks and disadvantages regarding biocompatibility and aesthetics have also been reported for the use of titanium in dental implantology. As such, there is need for an alternative material. Zirconia may be regarded as a possible alternative. It is a ceramic with high fracture toughness and other positive qualities, such as beings metal-free, biocompatible, and white, which is aesthetically desirable. Short-term study results of contemporary zirconia implants are promising and comparable to titanium implants. Nevertheless, the material is relatively brittle and susceptible to surface defects. However, no long-term clinical results exists and possible complications are unknown. Long-term clinical research is needed before zirconia implants routine use may be endorsed.

Health and quality of life differ between community living older people with and without remaining teeth who recently received formal home care: a cross sectional study.

OBJECTIVE: To assess oral health, health, and quality of life (QoL) of care-dependent community-living older people with and without remaining teeth who recently received formal home care. MATERIALS AND METHODS: For this cross-sectional observational study, community-living older people (≥ 65 years), who recently (< 6 months) received formal home care, were interviewed with validated questionnaires and underwent an oral examination. Oral health, general health, medicines usage, frailty (Groningen Frailty Indicator), cognition (Minimal Mental State Examination), QoL (RAND 36), and oral health-related QoL (Oral Health Impact Profile-14) were assessed. RESULTS: One hundred three out of 275 consecutive eligible older people (median age 79 [IQR (Inter Quartile Range) 72-85 years] participated in the study. Thirty-nine patients had remaining teeth and 64 were edentulous. Compared with edentulous older people, older people with remaining teeth scored significantly better on frailty, QoL, physical functioning, and general health. No significant differences were seen in cognition. Dental and periodontal problems were seen in more than half of the patients with remaining teeth. Two third of the edentulous patients did not visit their dentist regularly or at all. CONCLUSIONS: Care-dependent home-dwelling older people with remaining teeth generally were less frail, scored better on physical functioning and general health and had better QoL than edentulous older people. Dental and periodontal problems were seen in approximately 50% of the elderly. CLINICAL RELEVANCE: Notwithstanding their common dental problems, frailty, health, and QoL are better in home-dwelling older people with remaining teeth. To maintain this status, we advise not only dentists, but also health care workers and governments, to encourage people to maintain good oral health.

A systematic review and meta-analysis of 3-unit fixed dental prostheses: Are the results of 2 abutment implants comparable to the results of 2 abutment teeth?

The purpose of the systematic review and meta-analysis was to compare the performance of 3-unit bridges on teeth with 3-unit bridges on implants, evaluating survival of the bridges, survival of the teeth or implants, condition of the hard and soft tissues surrounding the supports, complications and patient-reported outcome measures (PROM) after a mean observation period of at least 1 year. A literature search was conducted using a combination of the search terms: fixed partial denture and fixed dental prostheses (FDPs). An electronic search for data published until January 2017 was undertaken using the MEDLINE, EMBASE and Cochrane Library databases. Eligibility criteria included clinical human studies, either randomised or not, interventional or observational, which evaluated the results of 3-unit FDPs on either 2 implants or 2 abutment teeth. The search identified 1686 unique references. After applying eligibility criteria, 66 articles were included in the analysis. A total of 1973 3-unit FDPs were supported by teeth, and 765 were implant-supported. No significant differences were found either in the survival of the supporting abutments (P = .52; 99% vs 98.7% survival per year) or in the survival of the prostheses (P = .34; 96.4% vs 97.4% survival per year). Both treatments show an almost equally low complication rate, but there is a low level of reporting of hard and soft tissue conditions and PROM. It is concluded that implant-supported 3-unit FDPs seem to be a reliable treatment with survival rates not significantly different from the results of teeth-supported 3-unit FDPs.

[Dissertations 25 years after date 49. A biomechanical analysis of bone around dental implants in an edentulous mandible]. / Proefschriften 25 jaar na dato 49. Biomechanische analyse van bot rond tandheelkundige implantaten in de edentate onderkaak.

Changes in the bone around permucosal endosseous implants can be caused by biomechanical factors. Computer models are used to calculate the location and magnitude of stresses in the bone. The finite element method is used for the construction and calculation of models. The ongoing development of software and hardware 25 years ago made it possible to construct more complex 3-dimensional models. The general aim of the dissertation was to develop a state-of-the-art computer model of an edentulous mandible with dental implants and then to calculate the influence of a number of parameters on the location and magnitude of stresses in the bone. Conspicuous results were that there is hardly any difference between 2 and 4 implants in the interforaminal region and that the length of implants has a negligible effect on the magnitude of stresses. Clinical studies have subsequently demonstrated that these results are in line with reality.

How to treat two adjacent missing teeth with dental implants. A systematic review on single implant-supported two-unit cantilever FDP's and results of a 5-year prospective comparative study in the aesthetic zone.

To conduct a systematic review on the clinical outcome of single implant-supported two-unit cantilever FDP's and to conduct a 5-year prospective comparative pilot study of patients with a missing central and lateral upper incisor treated with either a single implant-supported two-unit cantilever FDP or two implants with solitary implant crowns in the aesthetic zone. Medline, Embase and the Cochrane Central Register of Controlled Trials were searched (last search 1 August 2016) for eligible studies. In the comparative pilot study, an implant-cantilever group of five patients with a single implant-supported two-unit cantilever FDP (NobelReplace Groovy Regular Platform) was compared with an implant-implant group of five patients with two adjacent single implant-supported crowns (NobelReplace Groovy Regular Platform) in the aesthetic zone. Implant survival, marginal bone level (MBL) changes, pocket probing depth, papilla index and patient satisfaction were assessed during a 5-year follow-up period. Five of 276 articles were considered eligible for data extraction. Implant survival ranged from 96·6% to 100%. Marginal bone level changes were higher in the anterior region than in the posterior region. Technical complications occurred more often in the posterior than anterior region. In the 5-year comparative pilot study, no clinically significant differences in hard and soft peri-implant tissue levels occurred between both groups. Single implant-supported two-unit cantilever FDP's can be a viable alternative to the placement of two adjacent single implant crowns in the aesthetic zone. Due to technical complications, placement of two-unit cantilever crowns in the posterior region can be considered unwise.

Maxillary implant-supported overdentures opposed by (partial) natural dentitions: a 5-year prospective case series study.

The aim of this study was to assess the 5-year treatment outcome of maxillary implant-retained overdentures opposed by natural antagonistic teeth. Fifty consecutive patients received maxillary overdentures supported by six dental implants. Implants were placed in the anterior region, if enough bone was present (n = 25 patients) Implant were placed in the posterior region if implant placement in the anterior region was not possible (n = 25 patients). Variables assessed included survival of implants, condition of hard and soft peri-implant tissues and patients' satisfaction. The five-year implant survival rate was 97·0% and 99·3%, and mean radiographic bone loss was 0·23 and 0·69 mm in the anterior and posterior group, respectively. Median scores for plaque, calculus, gingiva, bleeding and mean scores for pocket probing depth were low and stayed low. Patients' satisfaction after treatment was high in both groups. Within the limits of this 5-year study, it is concluded that six dental implants (placed in the anterior or posterior region) connected with a bar and opposed to natural antagonistic teeth result in acceptable results for clinical parameters and good outcomes for marginal bone level changes and patient satisfaction.

Immediate implant placement and provisionalisation in the aesthetic zone.

The aim of this retrospective study was to assess the outcome of immediate single-tooth implant placement and provisionalisation in the aesthetic zone regarding hard and soft peri-implant tissue parameters and patient-related outcome measures in a private practice. All consecutively treated patients with single-tooth immediate implant placement and provisionalisation between the period 1 January 2006 and 1 April 2013 in a referral practice in Amsterdam, the Netherlands, were included in the study. Fifty-one patients of a total of 64 could be examined at follow-up (Tfollow-up ). Radiographs were present from implant placement (Tplacement ), after definitive crown placement (Tdefinitive ), and new radiographs were taken at the follow-up appointment (Tfollow-up ). Next to this, soft tissue parameters, patients' satisfaction and professionals' aesthetic scores were measured at Tfollow-up . Implant survival was 96·9% after a mean follow-up period of 4 years following implant placement. At definitive crown placement, mean marginal bone-level loss was 0·25 mm (SD 0·19). Mean marginal bone-level loss following definitive crown placement was 0·06 mm (SD 0·10) (Tdefinitive to Tfollow-up ) after a mean follow-up period of 4 years. Plaque index, bleeding index and gingival index scores were low. Patients' satisfaction was rated very high: 9·0 (SD 0·7). Professionals aesthetic score was 16·49 (SD 1·86). From this study can be concluded that immediate placement of implants followed by immediate provisionalisation resulted in a high survival rate, minimum peri-implant bone loss, very good aesthetics and satisfied patients after a mean follow-up period of 4 years.

[An evaluation of the implementation of the 'Guidelines for oral care for patients dependent on care']. / Een evaluatie van de implementatie van de 'Richtlijn mondzorg voor zorgafhankelijke cliënten in verpleeghuizen'.

75% of older people being admitted to a nursing home are found to have oral care problems that have not been treated. Moreover, the Healthcare Inspectorate [in the Netherlands] reports that oral care for patients who depend on care in nursing homes is inadequate. The 'Guidelines for oral care for patients dependent on care in nursing homes', developed in 2007, appears to have been inadequately implemented. The goal of this research was to gain insight into the implementation of these guidelines in healthcare organisations. To that end, a questionnaire was distributed among the staff of 74 nursing homes. An analysis of the data revealed that people are -familiar with the guidelines and that oral care providers are often available. Oral care providers, however, often do not have access to reasonable dental care facilities. Patients are, moreover, generally not screened and/or monitored in accordance with the guidelines. Finally, it seems that the instruction of nurses and care-providers is insufficient. Research supports the conclusion that the nursing home staff is well-acquainted with the 'Guidelines for oral care for patients dependent on care' but that implementation of the guidelines in daily practice leaves much to be desired.

A thoroughly validated spreadsheet for calculating isotopic abundances (2H, 17O, 18O) for mixtures of waters with different isotopic compositions.

RATIONALE: Oxygen and hydrogen stable isotopes are widely used tracers for studies on naturally occurring and laboratory mixtures of isotopically different waters. Although the mixing calculations are straightforward to perform, there are ample possibilities to make mistakes, especially when dealing with a large number of mixed fluids. To facilitate isotope mixing calculations and to avoid computational mistakes, a flexible tool to carry out these calculations is in demand. METHODS: We developed, in three independent efforts, spreadsheets to carry out the mixing calculations for a combination of waters with different isotopic compositions using the isotope mass balance equation. We validated our calculations by comparison of the results of the three spreadsheets for a large number of test calculations. For all the cases, we obtained identical results down to the 12(th) to 14(th) significant digit. RESULTS: We present a user-friendly, thoroughly validated spreadsheet for calculating (2) H, (17) O and (18) O stable isotopic abundances and respective isotope delta values for mixtures of waters with arbitrary isotopic compositions. The spreadsheet allows the mixing of up to 10 different waters, of which up to five can be specified using their isotopic abundances and up to five others using their isotope delta values. The spreadsheet is implemented in Microsoft Excel and is freely available from our research groups' websites. CONCLUSIONS: The present tool will be applicable in the production and characterization of singly and doubly labeled water (DLW) mother solutions, the analysis of isotope dilution measurements, the deduction of unknown isotope values of constituents for mixtures of natural waters, and many other applications.

A new high-quality set of singly ((2) H) and doubly ((2) H and (18) O) stable isotope labeled reference waters for biomedical and other isotope-labeled research.

RATIONALE: Research using water with enriched levels of the rare stable isotopes of hydrogen and/or oxygen requires well-characterized enriched reference waters. The International Atomic Energy Agency (IAEA) did have such reference waters available, but these are now exhausted. New reference waters thus had to be produced in sufficient quantity, and higher characterization quality was desired. METHODS: The reference waters have been prepared gravimetrically from three parent waters: natural water, pure (2) H water and highly (18) O-enriched water. These parent waters have been thoroughly assessed for their full isotopic compositions. To ensure the integrity and correctness of the gravimetric procedure, validation measurements have been carried out on the isotopic composition of the produced reference waters by two of our laboratories. These measurements corroborate the values obtained on the basis of gravimetric data. RESULTS: Two new sets of three reference waters enriched in the stable isotopes have been produced and certified: one set of singly labeled waters, only enriched in (2) H, and another set of Doubly Labeled Waters, enriched in both (2) H and (18) O. They cover δ(2) H and δ(18) O values in the range of 800-16000 ‰ and 100-2000 ‰, respectively. The process has led to highly accurate isotopic values for these waters. CONCLUSIONS: These reference waters are now available (called IAEA-604 to IAEA-609). They will be valuable as reference materials for all fields using isotope labeling of water, most prominently, but not exclusively, biomedical research (body composition analyses, metabolic rate measurements). The two waters with the lowest enrichments will also be useful as anchor values for isotope measurements around the natural range.

Implant decontamination with 2% chlorhexidine during surgical peri-implantitis treatment: a randomized, double-blind, controlled trial.

OBJECTIVE: The objective of this randomized, double-blind, controlled trial was to evaluate the clinical, radiographic, and microbiological effects of implant surface decontamination with a 2% chlorhexidine (CHX) solution in comparison with a 0.12% chlorhexidine + 0.05% cetylpyridinium chloride (CPC) solution during resective surgical peri-implantitis treatment. MATERIAL AND METHODS: Forty-four patients (108 implants) with peri-implantitis were treated with resective surgical treatment consisting of bone re-contouring, surface debridement and chemical decontamination, and apically repositioned flap. Patients were randomly allocated to decontamination with a 2% CHX solution (test group) or 0.12% CHX + 0.05% CPC (control group). Clinical and radiographic parameters were recorded before treatment (baseline), and at 3, 6, and 12 months after treatment. Microbiological parameters were recorded during surgery. RESULTS: Multilevel analysis showed no significant differences in bleeding, suppuration, probing pocket depth, and radiographic bone loss between control and test group over three follow-up measurements (3, 6, and 12 months) from baseline. Both decontamination procedures resulted in significant reductions in anaerobic bacterial counts on the implant surface, but no significant difference was noted between control and test group (mean log 3.37 ± 2.34 vs. 3.65 ± 2.87, P = 0.99). CONCLUSIONS: The use of a 2% CHX solution for implant surface decontamination during resective peri-implantitis therapy does not lead to improved clinical, radiographic, or microbiological results compared with a 0.12% CHX + 0.05% CPC solution. Overall, the additional use of CHX reduces anaerobic bacterial load on the implant surface better than mechanical debridement alone, but does not seem to enhance clinical treatment outcomes (ClinicalTrials.gov number NCT01852253).

Improving masticatory performance, bite force, nutritional state and patient's satisfaction with implant overdentures: a systematic review of the literature.

Oral function with removable dentures is improved when dental implants are used for support. A variety of methods is used to measure change in masticatory performance, bite force, patient's satisfaction and nutritional state. A systematic review describing the outcome of the various methods to assess patients' appreciation has not been reported. The objective is to systematically review the literature on the possible methods to measure change in masticatory performance, bite force, patient's satisfaction and nutritional state of patients with removable dentures and to describe the outcome of these. Medline, Embase and The Cochrane Central Register of Controlled Trials were searched (last search July 1, 2014). The search was completed by hand to identify eligible studies. Two reviewers independently assessed the articles. Articles should be written in English. Study design should be prospective. The outcome should be any assessment of function/satisfaction before and at least 1 year after treatment. Study population should consist of fully edentulous subjects. Treatment should be placement of any kind of root-form implant(s) to support a mandibular and/or maxillary overdenture. Fifty-three of 920 found articles fulfilled the inclusion criteria. A variety of methods was used to measure oral function; mostly follow-up was 1 year. Most studies included mandibular overdentures, three studies included maxillary overdentures. Implant-supported dentures were accompanied by high patient's satisfaction with regard to denture comfort, but this high satisfaction was not always accompanied by improvement in general quality of life (QoL) and/or health-related QoL. Bite force improved, masseter thickness increased and muscle activity in rest decreased. Patients could chew better and eat more tough foods. No changes were seen in dietary intake, BMI and blood markers. Improvements reported after 1 year apparently decreased slightly with time, at least on the long run. Treating complete denture wearers with implants to support their denture improves their chewing efficiency, increases maximum bite force and clearly improves satisfaction. The effect on QoL is uncertain, and there is no effect on nutritional state.

[Peri-implant health in people aged 75 and over with an implant-retained overdenture in the mandibula]. / Peri-implantaire gezondheid bij 75-plussers met een overkappingsprothese op implantaten in de onderkaak.

The number of elderly patients with an implant-retained overdenture in the mandibula is increasing. There is, however, insufficient information on how these elderly people are functioning with their overdenture and on their peri--implant health. Therefore, a study was carried out among a group of people aged 75 and over who had been provided with an implant-retained overdenture in a general dental office, measuring their ability to manage independently, their general health and peri-implant health. The study revealed a high degree of ability to manage independently, despite the health problems affecting many over 75. The patients rated their prosthetic overdentures with an average grade of 8.9 ± 1.1. Plaque around the implant (73%) and bleeding on probing (68%) were frequently seen. However, progressive peri-implant bone loss was seldom seen. No relationship was evident between plaque-scores and the ability to manage independently. Except for oral hygiene instruction and/or professional cleaning of peri-implants, no serious interventions were necessary. It was concluded that this group of elderly people, provided with an implant-retained mandibular overdenture, are functioning well. Plaque around the implant and bleeding on probing are often present but progressive peri-implant bone loss is rare.

Chemotaxis and oospore formation in Phytophthora sojae are controlled by G-protein-coupled receptors with a phosphatidylinositol phosphate kinase domain.

G-protein-coupled receptors (GPCRs) are key cellular components that mediate extracellular signals into intracellular responses. Genome mining revealed that Phytophthora spp. have over 60 GPCR genes among which a prominent class of 12 encoding novel proteins with an N-terminal GPCR domain fused to a C-terminal phosphatidylinositol phosphate kinase (PIPK) domain. This study focuses on two GPCR-PIPKs (GKs) in Phytophthora sojae. PsGK4 and PsGK5 are differentially expressed during the life cycle with the highest expression in cysts and during cyst germination, and at late infection stages. In P. sojae transformants that constitutively express RFP-tagged PsGK4 and PsGK5, the fusion proteins in hyphae reside in small, rapidly moving vesicular-like structures. Functional analysis using gene silencing showed that PsGK4-silenced transformants displayed higher levels of encystment and a reduced cyst germination rate when compared with the recipient strain. Moreover, GK4 deficiency (or reduction) resulted in severe defects in zoospore chemotaxis towards isoflavones and soybean roots. In contrast, PsGK5-silenced transformants exhibited no obvious defects in asexual development but oospore production was severely impaired. Both, PsGK4- and PsGK5-silenced transformants showed reduced pathogenicity. These results point to involvement of GKs in zoospore behaviour, chemotaxis and oospore development, and suggest that PsGK4 and PsGK5 each head independent signalling pathways.

[Oral health in care-dependent elderly: an inventory in a nursing home in the north of the Netherlands]. / Mondgezondheid van kwetsbare ouderen: een inventarisatie in een verpleeghuis in Noord-Nederland.

When people grow old and dependent on care, it usually becomes increasingly difficult to maintain oral health. The aim of this study was to assess what changes have taken place during the last ten years in oral health and the need for dental care among patients who were admitted to a nursing home between 2002 and 2012. Results revealed that the number of patients with remaining teeth increased significantly, from 7.9% to 28.7%, and that the number of patients with implants increased from 0.0% to 3.2%. More than 80% of the patients had moderate to poor oral health upon arrival. Moreover, almost half of the patients were revealed to be non-cooperative for evaluation and/or treatment, especially those who had remaining teeth. The expectation is that as a result of the increasing number of care-dependent elderly with remaining teeth in combination with poor oral health, the demand for dental care for care-dependent elderly in nursing homes will increase harply in the coming years.

Immediate repair of bony defects in the posterior mandibular region following removal of a fractured implant: a feasible treatment?

The aim of this study was to assess whether immediate bone reconstruction after removal of a fractured dental implant in the posterior mandible provides a sound base for implant replacement, with a favourable treatment outcome and high patient satisfaction. Eight consecutive patients with a fractured implant neck were included. The implant was removed via osteotomy, following which the site was immediately repaired with a mixture of autogenous bone and bone substitute. After a 4-month healing period, sufficient bone and favourable soft tissue conditions were present, allowing implant placement with adequate primary stability. After a further 3 months, the implants were restored with an all-ceramic restoration. Patient satisfaction, the aesthetic outcome, complications, and postoperative morbidity were assessed using standardized clinical and radiographic examinations up to 5 years after crown placement. No implant failures were observed during the follow-up. Plaque accumulation, the presence of calculus, bleeding tendency, and peri-implant inflammation indices were low, indicating healthy peri-implant conditions. The mean marginal bone level change at the 5-year follow-up was - 0.17 ± 0.46 mm. All patients reported a high level of satisfaction (mean overall score 9.3 ± 0.5). In conclusion, immediate reconstruction of the hard tissue after removal of a fractured dental implant is a viable treatment option. This approach facilitates rehabilitation, reduces morbidity, and leads to favourable aesthetic outcomes.

The effect of propofol on effective brain networks.

OBJECTIVE: We compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks. METHODS: We included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks. RESULTS: Fewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0-29) compared to SPES-clinical (median: 10.0, range: 0-36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively rs = 0.77, rs = 0.70, rs = 0.55, p < 0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol. CONCLUSIONS: Our findings suggest that the number of effective network connections decreases, but network measures are only marginally affected. SIGNIFICANCE: The primary network topology is preserved under propofol.

Doubly Labelled Water analysis: preparation, memory correction, calibration and quality assurance for δ2H and δ18O measurements over four orders of magnitudes.

RATIONALE: The Doubly Labelled Water (DLW) method is an established way of determining the metabolic rate in humans and animals, with the advantage that the subjects need not be confined. The method, however, needs accurate determination of both the δ(2)H and the δ(18)O isotope values over a wide range of enrichments. METHODS: In this paper we describe a number of crucial steps in the process of isotope determination in body fluids. These steps include micro-distillation, correction of the measurements for sample-to-sample memory and calibration of the isotope scales over many orders of magnitudes. In contrast to several published protocols and guidelines, we also take highly enriched samples into account, as they are required for studying the metabolic rate of birds and small mammals. For our isotope scale calibration, we made a set of gravimetrically prepared, double labelled waters with known isotope values. Our quality assurance includes a scheme for easy calculation of the error propagation, leading to a reliable estimate of the analytical error in the metabolic rate. RESULTS: Our memory correction algorithm assumes the existence of three water "pools" that have different sizes and exchange rates with the injected samples. We show that the method can correct even huge memory signals, without the need for "true" values. CONCLUSIONS: With the presented building blocks, we show how to assure a reliable and accurate isotope analysis for the DLW method, both for human and for animal applications. Although our measurements have been performed using isotope ratio mass spectrometry, most of the procedures are also useful for laser spectrometry.