Neurofeedback for alcohol addiction: Changes in resting state network activity✰.

Alcohol dependence continues to be a major global burden despite significant research progress and treatment development. The aim of this study was to investigate whether neurofeedback training can alter resting state fMRI activity in brain regions that play a crucial role in addiction disorders in patients with alcohol dependence. For this purpose, a total of 52 patients were recruited for the present study, randomized, and divided into an active and a sham group. Patients in the active group received three sessions of neurofeedback training. We compared the resting state data in the active group as part of the NF training on six measurement days. When comparing the results of the active group from neurofeedback day 3 with baseline 1, a significant reduction in activated voxels in the ventral attention network area was seen. This suggests that reduced activity over the course of therapy in subjects may lead to greater independence from external stimuli. Overall, a global decrease in activated voxels within all three analysed networks compared to baseline was observed in the study. The use of resting-state data as potential biomarkers, as activity changes within these networks, may be to help restore cognitive processes and alcohol abuse-related craving and emotions.

MRI analysis of neurodevelopmental anatomy in myelomeningocele: prenatal vs postnatal repair.

OBJECTIVE: Prenatal myelomeningocele (MMC) repair offers improved motor function and decreased rates of cerebrospinal fluid (CSF) diversion compared to than postnatal repair. However, comparative analysis of other associated neuroanatomical findings is lacking. The purpose of this study is to use magnetic resonance imaging (MRI) imaging to compare characteristic Chiari II malformation stigmata in patients who underwent fetal MMC repair vs. postnatal repair. METHODS: A retrospective review was performed of neonates who underwent prenatal or postnatal MMC repair at our institution and had postnatal MRIs. We analyzed anatomical findings characteristically seen with Chiari II malformation on brain MRI in patients who underwent prenatal MMC repair vs. postnatal repair. RESULTS: CSF diversion was required in 24% of prenatal cohort vs. 67% of postnatal cohort (p = 0.002), and syrinx was present in 12% of prenatal cohort compared to 42% in postnatal cohort (p = 0.03). Corpus callosum (CC) morphology was abnormal in 52% of prenatal cohort vs. 53% of postnatal cohort (p = 0.92), while falx morphology was normal in 92% of the prenatal cohort vs. 34% of the postnatal cohort (p = <0.001). Prenatal cohort patients had shorter tentorium to foramen magnum distance than postnatal cohort patients (18.4mm vs. 22.4mm, p = 0.01), overall larger foramen magnum diameter (22.9mm vs. 18.9mm, p < 0.001), and a smaller mean degree of hindbrain herniation (1.5mm vs. 8.7mm, p < 0.001). Finally, the cerebral aqueduct was patent in 79% of prenatal cohort vs. 100% of postnatal cohort (p = 0.007). There was no significant difference in presence of gray matter heterotopia, presence of septum pellucidum, or size of massa intermedia between the two cohorts. CONCLUSIONS: We report baseline variations in developmental neuroanatomy in patients with MMC including rates of CC dysgenesis, gray matter heterotopia and additional cranial and spinal MRI findings. We found that prenatal surgery results in changes to infratentorial anatomy, with minimal effect on supratentorial brain development. This information will be useful in myelomeningocele counseling and in understanding how prenatal repair of myelomeningocele affects brain development. This article is protected by copyright. All rights reserved.

[Glyphosate detection in the duodenal fluid of horses with gastric ulcer syndrome]. / Glyphosatnachweis in der Duoden­alflüssigkeit bei Pferden mit Magenulzerasyndrom.

INTRODUCTION: The hay producing plants, concentrate, straw and meadows could be contaminated by the aerosols of glyphosate based herbicide during spraying process of crops and pre-harvest desiccation treatment of cereals. The aim of this study is to investigate the concentration of glyphosate in the duodenal fluid of horses with gastric ulcer syndrome. The stomach and duodenum of referred untreated horse patients (n=92) with colic, weight loss, diarrhoea, anemia or performance intolerance were endoscopically examined right after the admission. Duodenal fluid (40 ml) was collected from the duodenal region where the papilla duodeni major is located. Hematology and clinical chemistry data were examined. The concentration of glyphosate in serum and duodenal fluid samples were analysed using a competitive ELISA and control analysis had also been done with HPLC. Statistical differences between groups were determined by the non-parametric Mann-Whitney-test using a significant level of p≤0,05. Glyphosate was detected in all duodenal fluid (median 12,2 ng/ml; 1st quartile 4,0 ng/ml; 3rd quartile 19,3 ng/ml; min 0,6 ng/ml; max. 192,9 ng/ml) and blood samples (1,79 ng/ml; 1,0 ng/ml; 2,8 ng/ml; 0,2 ng/ml; 3,7 ng/ml) of all horses. Glyphosate concentrations of duodenal fluid samples are significantly higher than in blood samples (Mann Whitney U-test, p≤0,05). The concentration of glyphosate in the duodenal fluid was significantly higher in horses with squamous gastric disease (grade 4/4; n=11/92) compared to horses with normal squamous mucosa (grade 0/4, n=10/92) (median: 19,8 ng/ml versus 8,4 ng/ml). Horses with glandular gastric disease and a grade 4/4 (n=9/92) had higher concentrations of glyphosate in the duodenal fluid than horses with normal glandular mucosa (grade 0/4; n=9/92) (median: 19,2 versus 11,1). The Gamma-Glutamyltransferase (GGT) enzyme activity is significantly higher in the group of horses with lower concentration of glyphosate in the duodenal fluid (≤12,2 ng/ml) compared with the group with higher concentration of glyphosate (>12,2 ng/ml) (median 279,5 versus 101,9 U/L). During autumn the horses had higher concentrations of glyphosate in duodenal fluid (n=18; median 14,3) compared with lower concentrations in spring time (n=34; median 8,1 ng/ml). Horses kept around big cities had significantly higher concentrations of glyphosate in the duodenal fluid in comparison to horses living in the countryside (medians 17,8 ng/ml versus 7,5 ng/ml).

INTRODUCTION: L'herbicide glyphosate, y compris le surfactant, est utilisé contre les mauvaises herbes dans l'agriculture, les maisons, les jardins et les parcs, les bords de route ainsi que sur les remblais des voies ferrées. La pulvérisation de cet herbicide engendre sa dispersion et donc la contamination des champs, des prairies et des pâturages et, par conséquent, des céréales, du foin, de la paille et du haylage, entraînant ainsi une ingestion orale chez les chevaux. Afin de déterminer l'étendue de l'utilisation du glyphosate dans la région du centre de l'Allemagne et d'identifier un éventuel facteur de risque pour le déclenchement du syndrome de l'ulcère gastrique, le liquide duodénal a été testé par rapport au glyphosate chez des patients équins. Les chevaux référés et non traités (n=92) présentant des antécédents de colique, d>amaigrissement, de diarrhée, d>anémie ou de baisse de performance ont été soumis à une gastroduodénoscopie le jour de leur admission. La graduation des lésions des muqueuses de l'estomac et du duodénum a été effectuée, 40 ml de liquide duodénal ont été aspirés et 20 ml de sang ont été prélevés en parallèle. Des analyses hématologiques et chimiques du sang ainsi que des analyses chimiques du liquide duodénal ont été effectuées. Le glyphosate a été détecté dans le sérum et le liquide duodénal à l'aide d'un test ELISA direct et compétitif et, parallèlement, d'une chromatographie liquide haute performance. Le glyphosate a été détecté dans le liquide duodénal (médiane 12,2 ng/ml, 1er quartile 4,0 ng/ml ; 3e quartile 19,3 ng/ml ; min 0,6 ng/ml ; max 192,9 ng/ml) et dans le sang (1,79 ng/ml ; 1,0 ng/ml ; 2,8 ng/ml ; 0,2 ng/ml ; 3,7 ng/ml) de tous les chevaux étudiés. La concentration de glyphosate dans le liquide duodénal est significativement plus élevée que dans le sang (test U de Mann Whitney, p≤0,05). Les chevaux présentant des lésions cutanées (n=11/92) ou glandulaires (n=9/92) de la muqueuse gastrique de grade 4/4 présentaient des concentrations de glyphosate dans le liquide duodénal significativement plus élevées ou plus élevées que ceux de grade 0/4 (n=10 et 9 respectivement) (médiane : 19,8 ng/ml versus 8,4 ng/ml ou 19,2 ng/ml versus 11,1 ng/ml). L'activité de la gamma-glutamyltransférase (GGT) dans le liquide duodénal était significativement plus élevée (médiane de 279,5 U/L) dans le groupe de chevaux présentant une faible concentration de glyphosate (≤12,2 ng/ml) que dans le groupe de chevaux présentant une concentration plus élevée de glyphosate (>12,2 ng/ml) (médiane de 101,9 U/L). La concentration de glyphosate était plus élevée pendant l'automne (n=18 ; médiane 14,3 ng/ml) et plus faible au printemps (n=34 ; médiane 8,1 ng/ml). Des concentrations significativement plus élevées de glyphosate dans le liquide duodénal ont été mesurées chez les chevaux détenus autour des grandes villes (17,8 ng/ml) par rapport aux chevaux vivant dans les zones rurales (7,5 ng/ml).

Bis[2-(Methacryloyloxy) Ethyl] Phosphate as a Primer for Enamel and Dentine.

Dental resin composites are commonly used in the restorative management of teeth via adhesive bonding, which has evolved significantly over the past few decades. Although current self-etch bonding systems decrease the number of clinical steps, the acidic functional monomers employed exhibit a limited extent of demineralization of enamel in comparison to phosphoric acid etchants, and the resultant superficial ionic interactions are prone to hydrolysis. This study evaluates the etching of primers constituted with bis[2-(methacryloyloxy) ethyl] phosphate (BMEP) of dental hard tissue, interfacial characteristics, and inhibition of endogenous enzymes. We examine the incorporation of 2 concentrations of BMEP in the formulation of experimental primers used with a hydrophobic adhesive to constitute a 2-step self-etching bonding system and compare to a commercial 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP)-containing system. The interaction of the primer with enamel and dentine was characterized using scanning electron, confocal laser scanning, and Raman microscopy while the polymerization reaction between the BMEP primers and hydroxyapatite was evaluated by Fourier-transform infrared spectroscopy. The inhibitory effect against matrix metalloproteinase (MMP) enzymes of these primers was studied and percentage of inhibition analyzed using 1-way analysis of variance and Tukey's post hoc test (P < 0.05). Results of the scanning electron microscopy micrographs demonstrated potent etching of both enamel and dentine with the formation of longer resin tags with BMEP primers compared to the 10-MDP-based system. The BMEP polymerized on interaction with pure hydroxyapatite in the dark, while the 10-MDP primer exhibited the formation of salts. Furthermore, BMEP primers were able to inhibit MMP activity in a dose-dependent manner. BMEP could be used as a self-etching primer on enamel and dentine, and the high degree of polymerization in the presence of hydroxyapatite can contribute to an increased quality of the resin polymer network, prompting resistance to gelatinolytic and collagenolytic degradation.

Aspects of transition cow metabolomics-Part I: Effects of a metaphylactic butaphosphan and cyanocobalamin treatment on the metabolome in liver, blood, and urine in cows with different liver metabotypes.

Dairy cows in modern production systems are at risk to develop metabolic disorders during the transition period. Reasons for individual differences in susceptibility, as well as the underlying pathomechanisms, are still only partially understood. The development of metaphylactic treatment protocols is needed. In this context, an on-farm prospective 3-fold blinded randomized study involving 80 German Holstein cows was performed throughout 1 yr. The trial involved a thorough recording of the production and clinical traits, clinical chemistry, and liver biopsies and blood and urine sampling at d 14 (mean: 12 d, range: 1-26 d) antepartum (AP), and d 7 (7, 4-13) and 28 (28, 23-34) postpartum (PP) for metabolomics analyses. Two groups received a treatment with butaphosphan and cyanocobalamin (BCC) at either the dosage recommended by the manufacturer or the double dosage (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin (Catosal, Bayer Animal Health), n = 20 in each group, parity: 4.2 ± 2.0 and 3.4 ± 1.3, respectively (mean ± SD)] and one group a placebo treatment (NaCl 0.9%, n = 40, parity: 4.0 ± 1.9). The animals were treated at 6 time points (7, 6, and 5 d AP, and 1, 2, and 3 d PP) via intravenous injection. Mass spectroscopy-based targeted metabolomics analysis of blood plasma and liver samples were performed using the AbsoluteIDQ p180 kit (Biocrates Life Sciences), whereas the urine samples were analyzed by nuclear magnetic resonance spectroscopy. Statistical analysis was performed using multivariate [partial least squares discriminant analysis (PLS-DA)] and univariate methods (linear mixed model). Multivariate data analysis (PLS-DA plots) of the liver metabolome revealed 3 different metabotypes (A = medium, B = minor, C = large alterations in liver metabolome profile between AP and PP status). Metabotype B animals were characterized by higher PP lipomobilization (stronger PP body condition decrease and higher blood bilirubin, fatty acids, gamma-glutamyltransferase, and triglyceride levels) and a higher occurrence of transition cow diseases, compared with the animals in metabotype C. Analysis of the feeding data showed that the period of metabotype B animals (calving in a distinct time frame) was characterized by a decreased grass silage quality. The PP liver metabolome of the metabotype C animals was characterized by higher concentrations of AA, acylcarnitines, lysoPC and sphingomyelins compared with metabotype B. For the metaphylactic treatment with BCC a dose-dependent effect was confirmed, differing between the metabotypes. In all matrices and metabotypes at various time points significant treatment effects were observed, with different profiles in clinical chemistry and as well in metabolomics data. The most clear-cut treatment effect was observed in metabotype B in the liver at 7 d PP, characterized by an increase in several acylcarnitines and phosphatidylcholines, indicating a more efficient influx and oxidation of fatty acids in mitochondria and thereby an increase in energy supply and more efficient triglyceride export in the liver. The results from the liver metabolomics analysis support the application of an indication-based metaphylactic treatment with BCC.

Aspects of transition cow metabolomics-Part III: Alterations in the metabolome of liver and blood throughout the transition period in cows with different liver metabotypes.

The liver plays a central role in the postpartum (PP) energy metabolism of the transition dairy cow; however, studies describing the liver metabolome during this period were lacking. The aim of the presented study was therefore to compare the alterations in the liver and blood metabolome of transition dairy cows. For this purpose, an on-farm trial with 80 German Holstein cows (mean lactation number: 3.9; range: 2-9) was performed, with thorough documentation of clinical traits and clinical chemistry, as well as production data. Liver biopsies and blood samples were collected at d 14 (mean: 12 d, range: 1-26 d) antepartum (AP), d 7 (7, 4-13) and 28 (28, 23-34; mean, earliest-latest) PP for targeted mass spectroscopy-based metabolomics analysis using the AbsoluteIDQ p180 kit (Biocrates Life Sciences). Statistical analysis was performed using multivariate (partial least squares discriminant analysis) as well as univariate methods (linear mixed model). Multivariate data analysis of the liver metabolome revealed 3 different metabotypes (A = medium, B = minor, C = large alterations in the liver metabolome profile between AP and PP). In metabotype C, an increase of almost all acylcarnitines, lysophosphatidylcholines (lysoPC), sphingomyelins, and some phosphatidylcholines (PC, mainly at 7 d PP) was observed after calving. In contrast to metabotype C, the clinical data of the metabotype B animals indicated a higher PP lipomobilization and occurrence of transition cow diseases. The liver metabolome profile of these animals most likely mirrors a failure of adaptation to the PP state. This strong occurrence of metabotypes was much less pronounced in the blood metabolome. Additionally, differences in metabolic patterns were observed across the transition period when comparing liver and blood matrices (e.g., in different biogenic amines, acylcarnitines and sphingolipids). In summary, the blood samples at 7 d PP showed lower acylcarnitines and PC, with minor alterations and a heterogeneous pattern in AA, biogenic amines, and sphingomyelins compared with 14 d AP. In contrast to 7 d PP, the blood samples at 28 PP revealed an increase in several AA, lysoPC, PC, and sphingomyelins in comparison to the AP state, irrespective of the metabotype. In the liver biopsies metabotype B differed from metabotype C animals ante partum by following metabolites: higher α aminoadipic acid, lower AA, serotonin, taurine, and symmetric dimethylarginine levels, lower or higher concentrations of certain acylcarnitines (higher: C2, C3, C5, C4:1; lower: C12:1, C14:1-OH, C16:2), and lower lysoPC (a C16:0, C18:0, C20:3, C20:4) and hexose levels. In blood samples, fewer differences were observed, with lower serotonin, acylcarnitine C16:2, lysoPC (a C16:0, C17:0, C18:0 and C18:1), PC aa C38:0, and PC ae C42:2. The results show that the use of only the blood metabolome to assess liver metabolism may be hampered by the fact that blood profiles are influenced by the metabolism of many organs, and metabolomics analysis from liver biopsies is a more suitable method to identify distinct metabotypes. Future studies should investigate the stability and reproducibility of the metabotype and phenotypes observed, and the possible predictive value of the metabolites already differing AP between metabotype B and C.

Biochemical characterisation of carious dentine zones using Raman spectroscopy.

OBJECTIVE: Carious tissue discrimination in clinical operative caries management relies traditionally on the subjective hardness of carious dentine. Biochemical alterations within the lesion have the potential to discriminate the lesion zones objectively. This study aimed to determine the correlation between the biochemical proportions of amide I and phosphate moieties as these are the most prominent peaks found in dentine with the Knoop microhardness of carious dentine zones, using non-contact Raman spectroscopy. The null hypothesis investigated was that there was no correlation between Raman peak ratios, amide I: phosphateν1, and the Knoop microhardness within specific zones of a carious lesion. METHODS: 423 scan points from 20 carious dentine lesion samples examined using high-resolution Raman spectroscopy. The peak ratio of the characteristic vibration mode of amide I (1650 cm-1) and phosphate (960 cm-1) bands were calculated, following a straight line path through the lesion to the pulp and correlated to corresponding Knoop microhardness measurements. RESULTS: Using logistic regression analysis, clear correlations were found between the Knoop microhardness and Raman peak ratio cut-off values between caries-infected and caries-affected dentine (81.5 % sensitivity / 92.7 % specificity), with a lower specificity (2.7 %) found between caries-affected and sound dentine. CONCLUSION: This study concluded that non-contact Raman spectroscopy can be used in vitro to discriminate objectively between the different zones of a carious dentine lesion at high resolution, using the Raman peak ratios, amide I : phosphate ν1. CLINICAL SIGNIFICANCE: Specific biochemical alterations have the potential to be used in-vitro and in-vivo to identify the end-point of selective carious lesion excavation.

12- and 18-month follow-up after residential treatment of methamphetamine dependence: Influence of treatment drop-out and different treatment concepts.

This study investigates the effects of two different residential treatments and of treatment drop-out in a German methamphetamine (MA) dependent sample. 108 subjects from two addiction treatment concepts were recruited at treatment begin and followed-up at 12 (T2) and 18 (T3) months after treatment. Based on follow-up samples (n = 38 at T2, n = 25 at T3), 77.1% at T2 and 68.0% at T3 were MA abstinent. Classifying everyone, who did not participate at follow-ups as having had a relapse, showed MA-abstinence rates of 25.0% (at T2) and 15.7% (at T3). There was no difference in MA-use between treatment conditions nor between treatment completers and drop-outs. Having injected any substance predicted MA-use at T2 (p = .03). The median time of relapse was 1.5 days after hospital release. Depression scores at T2 predicted MA-use at T3 (p = .02). T2 participants that dropped out of treatment had higher craving scores at T2, than T2 subjects who completed treatment (p = .03). The results show positive effects of current inpatient treatment programs without differences between different concepts. More research is needed to clarify the impact of treatment drop-out. Attention should be paid to a successful transition from residential to outpatient services and to a reduction of study attrition.

Persistence and adherence to parenteral osteoporosis therapies: a systematic review.

Osteoporosis is a chronic disease of low bone mass and fragility. Treatment is frequently compromised by suboptimal medication compliance causing increased morbidity. This review investigates adherence and persistence to parenteral osteoporosis therapies. Findings reveal parenteral medications requiring reduced dosing frequency have higher compliance than oral therapies. This systematic review examines real-world adherence to parenteral osteoporosis therapies. We searched PubMed, Medline, and EMBASE databases for English language observational studies that examined patient adherence and/or persistence to parenteral osteoporosis treatments (teriparatide sc, ibandronate iv, zoledronic acid iv, and denosumab sc) in adults with osteoporosis published up to September 2018. Studies with only self-reported adherence or persistence data and those with less than 20 patients were excluded. Quality assessment of included studies was completed using the Newcastle-Ottawa quality assessment scale (NOS). We identified 40 eligible studies. Teriparatide was examined in 29 studies, with persistence rates of 10-87% (median 55%) at 1 year and 10-69% (median 29.5%) at 2 years, and adherence rates of 21-89% (median 53%) at 1 year and 37-68% (median 40%) at 2 years. Ten studies of zoledronic acid reported persistence rates of 34-73% (median 42%) for second dose and 20-54% (median 35.8%) for third dose. Ten studies of ibandronate adherence reported and 2-year persistence rates of 31-58% (median 47.5%) in 1 year and 13-35% (median 25%) at 2 years, and adherence rates of 21-72% (median 47.3%) and 15-58% (median 36.5%) respectively. Denosumab was reported in 19 studies, with second (1 year) and fourth (2 year) dose persistence rates of 61-100% (median 81%) and 36-99% (median 45.5%). There is substantial heterogeneity in reports of persistence and adherence rates with parenteral osteoporosis therapies. Most of the published data are from short-term studies and evaluations of long-term adherence and persistence with parenteral therapies for osteoporosis are needed.

Chemo-mechanical characterization of carious dentine using Raman microscopy and Knoop microhardness.

One of the aims in the clinical operative management of dental carious lesions is to remove selectively the highly infected and structurally denatured dentine tissue, while retaining the deeper, repairable affected and intact, healthy tissues for long-term mechanical strength. The present study examined the correlation of chemical functional groups and the microhardness through the different depths of a carious lesion using Raman spectroscopy and Knoop microhardness testing. The null hypothesis investigated was that there was no correlation between Raman peak ratios (amide I : phosphate ν1 ) and equivalent Knoop microhardness measurements. Ten freshly extracted human permanent teeth with carious dentine lesions were sectioned and examined using high-resolution Raman microscopy. The ratio of absorbency at the amide I and phosphate bands were calculated from 139 scan points through the depth of the lesions and correlated with 139 juxtaposed Knoop microhardness indentations. The results indicated a high correlation (p < 0.01) between the peak ratio and the equivalent Knoop hardness within carious dentine lesions. This study concluded that Raman spectroscopy can be used as a non-invasive analytical technology for in vitro studies to discriminate the hardness of carious dentine layers using the peak ratio as an alternative to the invasive, mechanical Knoop hardness test.

Effectiveness of methamphetamine abuse treatment: Predictors of treatment completion and comparison of two residential treatment programs.

BACKGROUND: There is an increasing demand of evidence-based treatment options for methamphetamine users, but research in this field is limited. This study therefore evaluates the efficacy of two residential treatment programs for methamphetamine users. METHOD: A total of 108 patients with a history of methamphetamine abuse from two inpatient rehabilitation centers were studied for psychiatric symptoms, craving, psychosocial resources, and cognitive functioning at the start and end of therapy. Patients from one center ("amphetamine type stimulant group") received conventional group therapy plus an additional 10 h of group therapy focusing on stimulant use. Patients from the other center ("treatment as usual") received conventional group therapy only. Predictors of drop-out were estimated. RESULTS: A drop-out rate of 40.7% was observed without a significant difference between both centers. Patients remained significantly longer in treatment as usual compared to amphetamine type stimulant treatment. Irrespective of treatment program, craving and psychiatric symptoms significantly decreased while psychosocial resources, processing speed, and cognitive flexibility improved over time. Other cognitive measures yielded mixed results. History of injection drug use was a significant predictor for treatment drop-out. CONCLUSIONS: Existing treatments are effective in reducing craving and psychiatric symptoms. Additional stimulant specific groups do not appear to influence treatment completion and secondary outcome measures. Institutions should therefore offer treatment for methamphetamine users, even if they do not provide a therapy content focusing on methamphetamine. History of injection drug use should receive attention in treatment to prevent drop-out. Changes in cognitive functioning need to be further explored.

Glucocorticoid-induced osteoporosis preventive care in rheumatology patients.

Glucocorticoid-induced osteoporosis (GIOP) is common in patients prescribed with long-term glucocorticoids. Guidelines suggest patients receiving moderate-dose glucocorticoid therapy receive GIOP preventive care. Previous studies have shown preventive care rates are not optimal. We look at GIOP preventive care rates in rheumatology patients and predictors of various components of care. PURPOSE: Glucocorticoid-induced osteoporosis (GIOP) is a common concern in patients prescribed with long-term glucocorticoids. Studies have shown GIOP preventive care is not provided optimally in the general population; however, little is published on GIOP preventive care among patients with rheumatic disease. The objective of this study is to determine the proportion of rheumatology patients who received GIOP preventive care. METHODS: A population-based retrospective quality assurance study of adults seen at the University of Alberta Rheumatology Clinic was performed using the electronic outpatient medical record. Records of adult patients prescribed with prednisone from January 1st to December 31st, 2016 by a rheumatologist were initially included for review. Those who had been prescribed ≥ 7.5 mg/day for ≥ 3 months were assessed for concurrent GIOP preventive care. RESULTS: A total of 745 discreet courses of prednisone were prescribed in 433 patients with 113 meeting the above inclusion criteria. Following the prednisone prescription, 79% were taking vitamin D, 86% were taking calcium, and 50% were prescribed with osteoporosis pharmacotherapy. Twenty-five percent of patients had DXA imaging ordered by the rheumatologist within the first 6 months; of these, 86% of patients completed the DXA. CONCLUSIONS: Overall, our study shows that patients under the care of rheumatologists receive better GIOP preventative care than previously reported care in the general population. However, there is still room for improvement. In particular, men, younger patients, and rural patients seem to be at the most at risk of not receiving optimal GIOP prevention.

Self-Limiting versus Conventional Caries Removal: A Randomized Clinical Trial.

A single-blind randomized controlled clinical trial in patients with deep caries and symptoms of reversible pulpitis compared outcomes from a self-limiting excavation protocol using chemomechanical Carisolv gel/operating microscope (self-limiting) versus selective removal to leathery dentin using rotary burs (control). This was followed by pulp protection with mineral trioxide aggregate (MTA) and restoration with glass ionomer cement and resin composite, all in a single visit. The pulp sensibility and periapical health of teeth were assessed after 12 mo, in addition to the differences in bacterial tissue concentration postexcavation. Apical radiolucencies were assessed using cone beam computed tomography/periapical radiographs (CBCT/PAs) taken at baseline 0 mo (M0) and 12 mo (M12). In total, 101 restorations in 86 patients were placed and paired subsurface, and deep (postexcavation) dentin samples were obtained. DNA was extracted and bacteria-specific 16S ribosomal RNA gene quantitative polymerase chain reaction was performed. No significant difference was found in bacterial copy numbers normalized to mass of dentin ("bacterial tissue concentration") between the self-limiting (96.3% reduction) and control protocols (97.1%, P = 0.33). The probability of 12-mo success was 4 times (odds ratio [OR] = 4.33; confidence interval [CI], 1.2-15.6; P = 0.025) higher in the self-limiting protocol compared to the control (conventional excavation technique), with pulp survival rates of 73.3% and 90%, respectively ( P = 0.049). Molars had a 4 times higher probability of success compared to premolars (OR, 4.17; CI, 1.17-14.9; P = 0.028), and symptom severity did not statistically predict outcome (OR, 0.41; CI, 0.12-13.9, P = 0.153). CBCT detected significantly more periapical (PA) lesions than PA radiographs at the baseline visit ( P < 0.001). In conclusion, the self-limiting caries excavation protocol under magnification increased pulp survival rate compared to rotary bur excavation ( ClinicalTrials.gov NCT03071588).

FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms.

AIMS: To evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus. METHODS: AAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. AAA sites were incubated in the presence and absence of 50 nmol l-1 rivaroxaban. RESULTS: AAA sites showing thrombus demonstrated higher content of FXa than control. Interleukin-6 levels released from AAA [Control: median: 23.45 (interquartile range: 16.17-37.15) vs. AAA: median: 153.07 (interquartile range: 100.80-210.69) pg ml-1  mg tissue-1 , P < 0.05] and the expression levels of nitric oxide synthase 2 were significantly higher in AAA than in control. The protein expression level of NADPH oxidase subunits gp67-and gp91-phox, but did not gp47-phox, were also significantly higher in the AAA sites than in control. Addition of rivaroxaban to AAA sites explants significantly reduced the release of interleukin-6 [median: 51.61 (interquartile range: 30.87-74.03) pg ml-1  mg tissue-1 , P < 0.05 with respect to AAA alone] and the content of nitric oxide synthase 2, gp67 and gp91-phox NADPH subunits. The content of matrix metallopeptidase 9 was significantly higher in the AAA sites as compared to control. Rivaroxaban also reduced matrix metallopeptidase 9 content in AAA sites to similar levels to control. CONCLUSIONS: FXa inhibition by rivaroxaban exerted anti-inflammatory and antioxidative stress properties in human AAA sites, suggesting a role of FXa in these mechanisms associated with the pathogenesis of AAA.

Rapid Bacterial Detection during Endodontic Treatment.

Bacteria present in the root canal (RC) space following an RC treatment (RCT) can lead to persistent infections, resulting in treatment failure and the need for reintervention or extraction. Currently, there are no standardized methods in use to clinically detect bacterial presence within RC spaces. The use of paper point sampling and fluorescence staining was shown to be a rapid method, able to detect residual bacteria following treatment. The study demonstrated that Calcein acetoxymethyl (AM) proved to be a suitable dye for detecting vital bacteria within mature endodontic biofilms, with an improved sensitivity over colony-forming unit counting in a stressed biofilm model. Furthermore, in a clinical trial with primary RCTs, 53 infected teeth were sampled in vivo, and increased detection of vital cells was found when compared with colony-forming unit counting, highlighting the sensitivity of the technique in detecting low cell numbers. By combining fluorescent staining and microspectroscopy with software-based spectral analysis, successful detection of vital cells from RCs was possible after 5 min of Calcein AM incubation. Application of this technology during RCT has the potential to reduce persistent infections through vital cell detection and additional treatment. Furthermore, this technique could be applied to antimicrobial research and disinfection control in clinical settings ( ClinicalTrials.gov NCT03055975).

Energy Ordering of Molecular Orbitals.

Orbitals are invaluable in providing a model of bonding in molecules or between molecules and surfaces. Most present-day methods in computational chemistry begin by calculating the molecular orbitals of the system. To what extent have these mathematical objects analogues in the real world? To shed light on this intriguing question, we employ a photoemission tomography study on monolayers of 3,4,9,10-perylene-tetracarboxylic acid dianhydride (PTCDA) grown on three Ag surfaces. The characteristic photoelectron angular distribution enables us to assign individual molecular orbitals to the emission features. When comparing the resulting energy positions to density functional calculations, we observe deviations in the energy ordering. By performing complete active space calculations (CASSCF), we can explain the experimentally observed orbital ordering, suggesting the importance of static electron correlation beyond a (semi)local approximation. On the other hand, our results also show reality and robustness of the orbital concept, thereby making molecular orbitals accessible to experimental observations.

Treatment of behavioral and psychological symptoms of dementia: a systematic review. / Przeglad metod leczenia behawioralnych i psychologicznych symptomów otepienia (BPSD).

BPSD (Behavioral and Psychological Symptoms in Dementia) affects virtually all patients with dementia. The aim of this review is to present information on epidemiology, consequences and evidence-based non-pharmacological and pharmacological treatment approaches. The review also covers recent literature derived from a systematic literature Medline search on BPSD. Results indicate that BPSD are major risk factors for an earlier placement of affected individuals in nursing homes and a potentially more severe course of dementia over time. Treatment of BPSD is complex and includes both strategies.

[Reference ranges of insulin, insulin like growth factor-1 and adrenocorticotropic hormone in ponies]. / Referenzbereiche von Insulin, insulinähnlichem Wachstumsfaktor 1 (IGF-1) und adrenokortikotropem Hormon bei Ponys.

OBJECTIVES: The aim of this study was to validate a chemiluminescence immunometric assay using the IMMULITE 2000® for the determination of adrenocorticotropic hormone (ACTH), insulin and insulin-like growth factor-1 (IGF-1) from which reference ranges were calculated for ponies. MATERIAL AND METHODS: Blood samples of 130 ponies aged 3-32 years were collected in the afternoon. The reference ranges were calculated according to the Guideline EP28-A3C of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) from 2010. RESULTS: The determined intraday precision for insulin was 3.28%, for ACTH 3.35% and for IGF-1 1.84%. The interday precision (insulin: 3.45%; IGF-1: 2.89%; ACTH: 9.77%) was determined on three consecutive days, where the samples were stored at 4   °C. There was no significant loss of insulin activity nor of ACTH or IGF-1 concentration during this time. The reference ranges of insulin and IGF-1 (2.0-21.2 mU/l and 50.2-357.2 mU/l, respectively) were age independent, whereas for ACTH, an age-dependent reference range was established. Ponies aged 3-12 years had a significantly lower reference range (4.2-19.8 pg/ml) than ponies aged 13-32 years (5.0-22.6 pg/ml). CONCLUSION: The method used is suitable for the determination of ACTH, IGF-1 and insulin in serum of ponies, but the lowest detection limit for insulin is 2.0 mU/l. CLINICAL RELEVANCE: The calculated reference ranges of insulin and ACTH are helpful for the diagnosis and clinical monitoring of equine metabolic syndrome and pituitary pars intermedia dysfunction (PPID).

Exploring three-dimensional orbital imaging with energy-dependent photoemission tomography.

Recently, it has been shown that experimental data from angle-resolved photoemission spectroscopy on oriented molecular films can be utilized to retrieve real-space images of molecular orbitals in two dimensions. Here, we extend this orbital tomography technique by performing photoemission initial state scans as a function of photon energy on the example of the brickwall monolayer of 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA) on Ag(110). The overall dependence of the photocurrent on the photon energy can be well accounted for by assuming a plane wave for the final state. However, the experimental data, both for the highest occupied and the lowest unoccupied molecular orbital of PTCDA, exhibits an additional modulation attributed to final state scattering effects. Nevertheless, as these effects beyond a plane wave final state are comparably small, we are able, with extrapolations beyond the attainable photon energy range, to reconstruct three-dimensional images for both orbitals in agreement with calculations for the adsorbed molecule.

[Association between the MAOA-uVNTR polymorphism and antisocial personality traits in alcoholic men]. / Assoziation des MAOA-uVNTR-Polymorphismus mit antisozialem Verhalten bei alkoholabhängigen Männern.

AIMS: We have analysed the MAOA-uVNTR polymorphism in the promoter region of the X-chromosomal monoamine oxidase A (MAOA) gene. The first aim was to examine the association between the MAOA genotype and the alcoholic phenotype. In the second part of the paper we have analysed the association of the MAOA genotype with impulsive and aggressive behaviour. Genotypes with 3 or 5-repeat alleles (MAOA-L-genotype) were reported to be associated with impulsive and aggressive traits. METHODS: The MAOA genotype was determined in 371 male alcohol-dependent subjects and 236 male controls all of German descent. Behavioural and personality traits were evaluated using the self-report questionnaires Barratt Impulsiveness Scale (BIS), Buss Durkee Hostility Inventory (BDHI), Temperament and Character Inventory (TCI) and NEO-Five Factor Inventory (NEO-FFI). A median split in BIS, Buss Durkee Physical Assault, Buss Durkee Irritability, TCI and NEO-FFI was conducted. RESULTS: No association could be detected between the MAOA genotype and the alcoholic phenotype. Based on the results of the BIS questionnaire, we were able to make out an association between the MAOA-L genotype and higher levels of impulsivity (p = 0.043). Furthermore - without reaching statistical significance - we detected a very slight association between the MAOA-L genotype and higher scores in the BDHI subcategory physical aggression (p = 0.058). CONCLUSION: Taken together, these findings suggest that the MAOA-L genotype is to some extent associated with impulsive and antisocial personality traits in alcoholic men. Further studies on that question are needed.