[Disulfiram encephalopathy: an underrecognized complication of accidental overdose]. / Disulfiramencefalopathie: een mogelijke complicatie bij accidentele overdosering.

In this paper we discuss the case of a 52-year-old man who consulted the emergency department because of confusion. Based on anamnesis, clinical presentation, various technical investigations and recovery after discontinuation of disulfiram, the diagnosis of disulfiram encephalopathy is made. This is a less common but serious complication of a frequently used therapy and underscores the importance of early recognition and careful but also controlled prescription of disulfiram. We describe the pathophysiology behind this complication and reflect on some important numbers.

Biochemical Changes in the Niche Following Tumor Cell Invasion.

Metastatic cancer is the leading cause of all cancer related deaths. Prostate cancer (PCa) metastasizes preferentially to the bone marrow, specifically within the endosteal niche. Endosteal cells secrete homing molecules that may recruit PCa cells to the bone marrow. Once there, the biochemical signature of this niche regulates PCa fate including cellular dormancy or cell cycle arrest, reactivation and resistance to chemotherapeutics. Growth factors, interleukins, adhesion molecules, as well as extra-cellular matrix proteins can collectively change the phenotype of PCa cells. Understanding the biochemical signature of endosteal niche parasitism by PCa is imperative for the establishment of new and innovative therapeutic strategies. This review seeks to summarize these important niche signatures and the potential therapeutic approaches to target metastatic PCa within the bone marrow hematopoietic stem cell (HSC) niche. J. Cell. Biochem. 118: 1956-1964, 2017. © 2016 Wiley Periodicals, Inc.

Body fat evolution as predictor of retinal microvasculature in children.

OBJECTIVES: Microvascular changes may represent an underlying mechanism through which overweight contributes to cardiovascular disease development. Therefore, the aim of this study was to investigate whether changes in children's body fat over time are associated with the retinal microvasculature, a marker of cardiovascular aging. METHODS: In a longitudinal design, 171 healthy Flemish children (53.8% boys) were followed-up for 7 years (2008-2015), aged 2.7-8.1 years at baseline.Z-scores of body mass index (zBMI; 4.1% overweight), waist circumference (zWC) and fat mass index (zFMI by BODPOD) were obtained using standardized protocols during each visit. Retinal arteriolar (central retinal arteriolar equivalent (CRAE)) and venular equivalents (central retinal venular equivalent (CRVE)) were measured from digital retinal photographs (2015) using IVAN software. Cross-sectional and longitudinal associations between changes in body fat and retinal microvasculature were explored using multivariable regression analysis, while controlling for age, sex, mean arterial pressure, alternate retinal caliber, physical activity, diet and birth weight. RESULTS: In cross-sectional analysis, children with high zFMI had a higher CRVE, but only in boys (ß=0.25, P=0.02). In addition, boys with high zFMI had also a lower CRAE to CRVE ratio (ß=-0.26, P=0.03). No associations were seen with the CRAE, or between zBMI or zWC and the retinal microvasculature. Only changes in zFMI over time were found to be positively associated with the CRVE in boys (ß=0.38, P=0.01). CONCLUSIONS: Our analysis over a 7-year period shows that changes in body fat during childhood are already associated with the CRVE (especially in boys).

Potential selection effects when estimating associations between the infancy peak or adiposity rebound and later body mass index in children.

INTRODUCTION: This study aims to evaluate a potential selection effect caused by exclusion of children with non-identifiable infancy peak (IP) and adiposity rebound (AR) when estimating associations between age and body mass index (BMI) at IP and AR and later weight status. SUBJECTS AND METHODS: In 4744 children with at least 4 repeated measurements of height and weight in the age interval from 0 to 8 years (37 998 measurements) participating in the IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants)/I.Family cohort study, fractional polynomial multilevel models were used to derive individual BMI trajectories. Based on these trajectories, age and BMI at IP and AR, BMI values and growth velocities at selected ages as well as the area under the BMI curve were estimated. The BMI growth measures were standardized and related to later BMI z-scores (mean age at outcome assessment: 9.2 years). RESULTS: Age and BMI at IP and AR were not identifiable in 5.4% and 7.8% of the children, respectively. These groups of children showed a significantly higher BMI growth during infancy and childhood. In the remaining sample, BMI at IP correlated almost perfectly (r⩾0.99) with BMI at ages 0.5, 1 and 1.5 years, whereas BMI at AR correlated perfectly with BMI at ages 4-6 years (r⩾0.98). In the total study group, BMI values in infancy and childhood were positively associated with later BMI z-scores where associations increased with age. Associations between BMI velocities and later BMI z-scores were largest at ages 5 and 6 years. Results differed for children with non-identifiable IP and AR, demonstrating a selection effect. CONCLUSIONS: IP and AR may not be estimable in children with higher-than-average BMI growth. Excluding these children from analyses may result in a selection bias that distorts effect estimates. BMI values at ages 1 and 5 years might be more appropriate to use as predictors for later weight status instead.

Fast and slow interactions of n-alkanols with human 5-HT3A receptors: Implications for anesthetic mechanisms.

This is part of a continuing patch-clamp study exploring molecular actions of anesthetics and systematically varied related substances on 5-HT3A receptors as prototypes of ligand-gated ion channels. Specifically, n-alkanols, related to but simpler in structure than propofol, were studied to explore the complex actions of this leading intravenous anesthetic. Outside-out patches excised from HEK 293 cells heterologously expressing human 5-HT3A receptors were superfused with even-numbered n-alkanols (ethanol through n-tetradecanol) of different concentrations. Fast solution exchange for varying durations allowed separation of drug actions by their kinetics. Compared with propofol the electrophysiological responses to n-alkanols were not much simpler. n-Alkanols produced fast and slow inhibition or potentiation of current amplitudes, and acceleration of current rise and decay time constants, depending on exposure time, concentration, and chain-length of the drug. Inhibition dominated, characterized by fast and slow processes with time constants separated by two orders of magnitude which were similar for different n-alkanols and for propofol. Absolute interaction energies for ethanol to n-dodecanol (relative to xenon) ranged from -10.8 to -37.3kJmol(-1). No two n-alkanols act completely alike. Potency increases with chain length (until cutoff) mainly because of methylene groups interacting with protein sites rather than because of their tendency to escape from the aqueous phase. Similar wash-in time constants for n-alkanols and propofol suggest similar mechanisms, dominated by the kinetics of conformational state changes rather than by binding reactions.

Usual energy and macronutrient intakes in 2-9-year-old European children.

OBJECTIVE: Valid estimates of population intakes are essential for monitoring trends as well as for nutritional interventions, but such data are rare in young children. In particular, the problem of misreporting in dietary data is usually not accounted for. Therefore, this study aims to provide accurate estimates of intake distributions in European children. DESIGN: Cross-sectional setting-based multi-centre study. SUBJECTS: A total of 9560 children aged 2-9 years from eight European countries with at least one 24-h dietary recall (24-HDR). METHODS: The 24-HDRs were classified in three reporting groups based on age- and sex-specific Goldberg cutoffs (underreports, plausible reports, overreports). Only plausible reports were considered in the final analysis (N=8611 children). The National Cancer Institute (NCI)-Method was applied to estimate population distributions of usual intakes correcting for the variance inflation in short-term dietary data. RESULTS: The prevalence of underreporting (9.5%) was higher compared with overreporting (3.4%). Exclusion of misreports resulted in a shift of the energy and absolute macronutrient intake distributions to the right, and further led to the exclusion of extreme values, that is, mean values and lower percentiles increased, whereas upper percentiles decreased. The distributions of relative macronutrient intakes (% energy intake from fat/carbohydrates/proteins) remained almost unchanged when excluding misreports. Application of the NCI-Method resulted in markedly narrower intake distributions compared with estimates based on single 24-HDRs. Mean percentages of usual energy intake from fat, carbohydrates and proteins were 32.2, 52.1 and 15.7%, respectively, suggesting the majority of European children are complying with common macronutrient intake recommendations. In contrast, total water intake (mean: 1216.7 ml per day) lay below the recommended value for >90% of the children. CONCLUSION: This study provides recent estimates of intake distributions of European children correcting for misreporting as well as for the daily variation in dietary data. These data may help to assess the adequacy of young children's diets in Europe.

Registration of aggressive incidents in an adolescent forensic psychiatric unit and implications for further practice.

Although aggression is part of daily life in psychiatric units for adolescents, empirical data on its prevalence are sparse. Only few studies have described prevalence of aggressive incidents in adolescent psychiatric wards, and data in forensic psychiatric care are even more limited. Available studies reported high prevalence rates of aggression, ranging from 0.4 to 2.4 incidents of aggression per day across (forensic) child and adolescent psychiatric units. Between 27 and 78 % of all admitted youth committed an aggressive act. In this study, we collected systematically registered data of all aggressive incidents from the first 2 years (2010-2012) on a newly established forensic adolescent psychiatric unit, which used a formal aggression management program embedded in the social competence model, which is based on early intervention in the 'chain of behavior' to prevent any further escalation. The inclusion of also minor aggressive incidents is unique in the literature and the clinical relevance is highlighted. A mean of one incident a day took place, with each adolescent involved in at least one incident. Notably, 1.7 aggressive incidents per month made seclusion of restraint use necessary. Based on the social competence theory, the aggression management model suggests intervening early in the cascade of aggression, in order to prevent further escalation and reduce the need for intrusive interventions. Evidence supported that aggression is a contextual event, as external factors clearly influence the incidence of aggression. Aggression management should be built on both relational and structural security.

Inhibition of Mertk Signaling Enhances Bone Healing after Tooth Extraction.

Regeneration of alveolar bone is an essential step in restoring healthy function following tooth extraction. Growth of new bone in the healing extraction socket can be variable and often unpredictable when systemic comorbidities are present, leading to the need for additional therapeutic targets to accelerate the regenerative process. One such target is the TAM family (Tyro3, Axl, Mertk) of receptor tyrosine kinases. These proteins have been shown to help resolve inflammation and maintain bone homeostasis and thus may have therapeutic benefits in bone regeneration following extraction. Treatment of mice with a pan-TAM inhibitor (RXDX-106) led to accelerated alveolar bone fill following first molar extraction in a mouse model without changing immune infiltrate. Treatment of human alveolar bone mesenchymal stem cells with RXDX-106 upregulated Wnt signaling and primed the cells for osteogenic differentiation. Differentiation of human alveolar bone mesenchymal stem cells with osteogenic media and TAM-targeted inhibitor RXDX-106 (pan-TAM), ASP-2215 (Axl specific), or MRX-2843 (Mertk specific) showed enhanced mineralization with pan-TAM or Mertk-specific inhibitors and no change with Axl-specific inhibitor. First molar extractions in Mertk-/- mice had increased alveolar bone regeneration in the extraction socket relative to wild type controls 7 d postextraction. Flow cytometry of 7-d extraction sockets showed no difference in immune cell numbers between Mertk-/- and wild type mice. RNAseq of day 7 extraction sockets showed increased innate immune-related pathways and genes associated with bone differentiation in Mertk-/- mice. Together, these results indicate that TAM receptor signaling, specifically through Mertk, can be targeted to enhance bone regeneration after injury.

[Managing aggression in a forensic psychiatric unit for adolescents: literature review and clinical implementation]. / Agressiebeleid op een forensische psychiatrische unit voor adolescenten; literatuuroverzicht en implementatie in de praktijk.

BACKGROUND: Aggressive incidents are part and parcel of everyday life in a forensic psychiatric unit for adolescents. AIM: To review the literature about the prevalence of aggressive incidents and about aggression management policy in (forensic) child and adolescent psychiatry and to explain and elaborate the aggression management protocol in a newly established unit. METHOD: The literature was reviewed systematically using PubMed and PsycINFO in order to locate studies in English and Dutch published since 1990. RESULTS: Only 10 publications reported prevalence data on aggressive incidents in child or adolescent psychiatric units. Literature about concrete policy guidelines was almost non-existent. 27% to 78% of the youngsters had been involved in some kind of aggression. The lack of clear definitions and the differences in the research designs made a reliable comparison impossible. CONCLUSION: To date, there is no evidence that a greater number of aggressive incidents occur in a forensic psychiatric unit for adolescents than in a regular adolescent psychiatric unit. Further research into both the prevalence and the characteristics of incidents is required in order to provide cues for a good policy. This policy will need to include structural and relational security measures that are firmly supported by the systematic registration of incidents and by continuous risk assessment.

Internal exposure of Flemish teenagers to environmental pollutants: Results of the Flemish Environment and Health Study 2016-2020 (FLEHS IV).

The Flemish Environment and Health Study (FLEHS) collects information on internal exposure to a broad range of environmental chemicals in the general population in Flanders, the Northern region of Belgium. The aim is to establish biomonitoring exposure distributions for the general population in support of public health and environmental policy, environmental risk assessment and risk management decisions. In 2017-2018, urine and blood samples were collected from 428 teenagers by a stratified clustered two stage randomized design. Samples were analyzed for a broad range of biomarkers related to exposure to chlorinated and newer pesticides, brominated and organophosphate flame retardants (BFR/OPFR), polychlorinated biphenyls (PCBs), bisphenols, phthalates and alternative plasticizers, per-and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), benzene, metals and trace elements. The geometric mean levels and percentiles of the distribution were estimated for each biomarker, for the whole study population and following stratification for sex, the household educational attainment and the residence area's urbanicity. Geometric means of biomarkers of lead, dichlorodiphenyltrichloroethane (DDT), PCBs, PAHs, regulated phthalates and bisphenol A (BPA) were lower than in the previous FLEHS cycles. Most biomarker levels were below health-based guidance values (HB-GVs). However, HB-GVs of urinary arsenic, blood lead, blood cadmium, sum of serum perfluorooctane sulfonate (PFOS) and perfluoro-1-hexanesulfonate (PFHxS) and the urinary pyrethroid metabolite (3-PBA) were exceeded in respectively 25%, 12%, 39.5%, 10% and 22% of the teenagers. These results suggest that the levels of exposure in the Flemish population to some environmental chemicals might be of concern. At the same time, we noticed that biomarkers for BPA substitutes, metabolites of OPFRs, an expanded list of PFAS, glyphosate and its metabolite could be measured in substantial proportions of participants. Interpretation of these levels in a health-risk context remains uncertain as HB-GVs are lacking. Household educational attainment and residential urbanicity were significant exposure determinants for many biomarkers and could influence specific biomarker levels up to 70% as shown by multiple regression analysis. The research consortium also took care of the broader external communication of results with participants, policy makers, professional groups and civil society organizations. Our study demonstrated that teenagers are exposed to a wide range of chemicals, it demonstrates the success of public policies to reduce exposure but also points to concern and further priorities and needs for follow up.

Periodontal Treatment in Cancer Patients: An Interdisciplinary Approach.

PURPOSE OF REVIEW: Dental care is an essential component in the comprehensive treatment for the cancer patient. As such, a review of the literature was completed to determine the relationships between periodontal and dental care in the cancer patient and provide strategic suggestions. RECENT FINDINGS: Periodontal treatment must be personalized depending on the patient's current oral health status, systemic status, and progress in treatment. Oral mucositis, periodontal status, and osteonecrosis of the jaw (ONJ) remain periodontal concerns in the cancer patient. Contributing factors of ONJ include root amputation (OR= 6.64), extraction of a single tooth (OR=3.7), severe tooth mobility (OR = 3.60), and unclosed wound (OR = 2.51). SUMMARY: Preventive maintenance, oral hygiene instruction, use of fluoride and chlorhexidine are all important therapeutic strategies. If extractions are required in patients who have received bone modifying drug infusions, flap management and primary wound closure is needed to reduce the risk of complications.

The role of hematopoietic stem cell niche in prostate cancer bone metastasis.

Approximately 80% of prostate cancers exhibit some degree of bone metastasis. The role of the bone marrow and the hematopoietic stem cell (HSC) niche in attracting metastatic cells and maintaining dormancy of disseminated tumor cells (DTCs) is an increasingly important topic towards the development of novel prostate cancer therapies. This paper reviews aspects of the HSC niche that lead to prostate cancer cell homing and dormancy in the bone marrow. This review also discusses the role of DTCs in the niche environment and discusses the role of erythropoietin in targeting DTCs within the HSC niche.

Clinical outcomes of implant therapy in ectodermal dysplasia patients: a systematic review.

The purpose of this review was to determine the outcome of oral function reconstruction in ectodermal dysplasia (ED) patients who have received dental implant therapy. A search was made of the PubMed and Web of Science databases; key words used were "(ectodermal dysplasia) AND (implant OR implants)", with supplementary retrieval key words "dental implant", "zygomatic implant", "anodontia", and "edentulous". Patient age, use of bone graft, implant site, type of implant, and survival rate of the implants were included in the subsequent data analysis. Forty-five articles published between 1988 and October 2015 were included in this analysis. The cases of a total of 96 patients were retrieved (22 children and 74 adults); these patients received a total of 701 implants. Fourteen implants were removed during a median follow-up time of 24 months. The 24-month implant survival rate was 97.9% in adult subjects and 98.6% in children. Sixty-eight percent of adult patients underwent bone augmentation prior to implant placement. Based on this review, dental implants are commonly used in the oral reconstruction of ED patients. However, long-term data on bone augmentation and implant success are needed, as well as additional clinical evidence on bone resorption, the esthetic outcomes of implant therapy, and physiological considerations in ED patients.

Regenerative Medicine for Periodontal and Peri-implant Diseases.

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions.

Microarray-based analysis of gene expression in very large gene families: the cytochrome P450 gene superfamily of Arabidopsis thaliana.

Cytochrome P450 (P450s) are heme-thiolate protein products of a very large gene superfamily, present in all kingdoms and involved in a variety of metabolic reactions. P450s are classified according to the degree of amino acid sequence identity, with P450s of the same family defined as having >40% identity, and P450s of the same subfamily having >55% identity. Currently, 273 P450 genes distributed over 45 families have been identified in Arabidopsis, and its genome is estimated to contain as many as 286. Genome-wide DNA microarrays make it possible to broadly correlate P450 gene activity with alterations in physiological or developmental states. A potential problem with microarray research is that sequence similarity between and within these families of closely related genes may lead to cross-hybridization. We designed experiments to systematically evaluate the specificity of P450 microarrays, and showed that conditions could be optimized to provide a very high degree of hybridization specificity. Under these conditions, and employing a 20% intensity value of maximum hybridization intensity as a cut-off, labeled P450 genes exhibited essentially no cross-hybridization between families and within subfamilies. We also compared the gene transcription levels of microarray probes derived from EST clones and from genomic DNA sequences for which ESTs were not available, using cDNA produced from RNA from various Arabidopsis tissue as the target. Many of the P450 genes displayed tissue-specific expression, leading to hypotheses as to the function of individual genes and their regulation. We also observed that several of the genomic sequences reported high levels of expression, highlighting the limitations of expression analysis based on ESTs alone.

Comparative evaluation of two administration schedules of cis-dichlorodiammineplatinum (DDP) in ovarian and head and neck cancers: a CMEA chemotherapy group study.

The therapeutic effectivity of two administration schedules of DDP were compared. The dose was either 100 mg/m2 infused for 4 h or 20 mg/m2 infused for 1 h on 5 consecutive days. The combined objective remission rate of the two regimens were 37/53 (23% CR ++ 44% PR) for ovarian cancer and 8/35 (9% CR + 14% PR) for head and neck cancer. WHO Grade 1-2 myelo- and nephrotoxicity was observed in 26% and 20%, respectively, out of the 105 cases evaluable for toxicity in the two groups. Nausea and vomiting was moderate to severe. Neither the remission rate nor the toxicity of the two schedules were significantly different.

The benefits of a paperless orthodontic practice.

After nearly 17 years of incorporating computer technology into our orthodontic practice, we have achieved a "paperless" orthodontic practice. The total integration of computer technology into each facet of our practice has allowed for increased efficiency, simplified clinical activities, improved communications between both patients and professional colleagues and, ultimately, the growth of our practice. This article reviews our current computerized practice management system and outlines the many advantages we have found using this technology in our practice.

Battling hepatitis C.

Treatment for patients suffering from the hepatitis C virus (HCV) can slow and sometimes stop disease progression. However, about 60% of the nearly 4 million Americans suffering from HCV fail to clear the virus with standard therapy because side effects compel them to drop out. Here's what you can do to help your patient stick with treatment and win the battle against HCV.

[New protocol combining orthodontics and implant therapy for partially edentulous adult patients. Part I: Description of the Decker protocol]. / Nouvelle approche de la thérapeutique ortho-implantaire de l'adulte partiellement édenté. Partie I : description du protocole Decker.

INTRODUCTION: The treatment of adult malocclusion is usually complex and pluridisciplinary. Its prognosis is not reliable. We present a new clinical protocol to improve the management and final result. TECHNICAL NOTE: We use a specific software (Simplant®, OMS®, Materialise Dental) and its accessory modules. It allows visualization of the expected final clinical result of the orthodontic treatment. Combined with guided-surgery, it allows placing implants at the beginning of treatment in a position that is compatible with the final position. The implants serve as absolute anchorage for dental motions during the orthodontic step; it is also used to support the final prosthesis. The treatment is thus optimized and its prognosis is improved. Finally, the reversed surgical sequences shorten the treatment thus promoting the compliance of patients.

Autosomal SNP typing of forensic samples with the GenPlex™ HID System: results of a collaborative study.

The GenPlex™ HID System (Applied Biosystems - AB) offers typing of 48 of the 52 SNPforID SNPs and amelogenin. Previous studies have shown a high reproducibility of the GenPlex™ HID System using 250-500pg DNA of good quality. An international exercise was performed by 14 laboratories (9 in Europe and 5 in the US) in order to test the robustness and reliability of the GenPlex™ HID System on forensic samples. Three samples with partly degraded DNA and 10 samples with low amounts of DNA were analyzed in duplicates using various amounts of DNA. In order to compare the performance of the GenPlex™ HID System with the most commonly used STR kits, 500pg of partly degraded DNA from three samples was typed by the laboratories using one or more STR kits. The median SNP typing success rate was 92.3% with 500pg of partly degraded DNA. Three of the fourteen laboratories counted for more than two thirds of the locus dropouts. The median percentage of discrepant results was 0.2% with 500pg degraded DNA. An increasing percentage of locus dropouts and discrepant results were observed when lower amounts of DNA were used. Different success rates were observed for the various SNPs. The rs763869 SNP was the least successful. With the exception of the MiniFiler™ kit (AB), GenPlex™ HID performed better than five other tested STR kits. When partly degraded DNA was analyzed, GenPlex™ HID showed a very low mean mach probability, while all STR kits except MiniFiler™ had very limited discriminatory power.