In vitro evaluation of the color stability and surface roughness of a new composite flow

The aim of this study was to evaluate the color stability and the surface roughness of a bulk-fill composite flow (SDR® Plus) by comparison to an ORMOCER-based composite (Ceram.x® Universal SphereTEC?) in order to confirm the validity of using SDR® Plus

A Prospective Multicenter Study Evaluating Learning Curves and Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography Among Advanced Endoscopy Trainees: The Rapid Assessment of Trainee Endoscopy Skills (RATES) Study

Background and aims Based on the Next Accreditation System, trainee assessment should occur on a continuous basis with individualized feedback. We aimed to validate endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) learning curves among advanced endoscopy trainees (AETs) using a large national sample of training programs and to develop a centralized database that allows assessment of performance in relation to peers. Methods ASGE recognized training programs were invited to participate and AETs were graded on ERCP and EUS exams using a validated competency assessment tool that assesses technical and cognitive competence in a continuous fashion. Grading for each skill was done using a 4-point scoring system and a comprehensive data collection and reporting system was built to create learning curves using cumulative sum analysis. Individual results and benchmarking to peers were shared with AETs and trainers quarterly. Results Of the 62 programs invited, 20 programs and 22 AETs participated in this study. At the end of training, median number of EUS and ERCP performed/AET was 300 (range 155-650) and 350 (125-500). Overall, 3786 exams were graded (EUS:1137; ERCP–biliary 2280, pancreatic 369). Learning curves for individual endpoints, and overall technical/cognitive aspects in EUS and ERCP demonstrated substantial variability and were successfully shared with all programs. The majority of trainees achieved overall technical (EUS: 82%; ERCP: 60%) and cognitive (EUS: 76%; ERCP: 100%) competence at conclusion of training. Conclusions These results demonstrate the feasibility of establishing a centralized database to report individualized learning curves and confirm the substantial variability in time to achieve competence among AETs in EUS and ERCP

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416

Effet de la vitamine D sur les marqueurs métaboliques et la fonction musculaire : étude chez des sujets libanais âgés, normo-pondéraux ou obèses

The main role of vitamin D is to control the homeostasis of the phosphorus and calcium status of the body. Recent observational studies have shown that vitamin D is also able to regulate insulin secretion and insulin sensitivity, thus playing an important role in the regulation of glucose homeostasis. In addition, vitamin D has been shown to modulate muscle health. For example, vitamin D deficiency negatively influences muscle mass and muscle function in the elderly. Studies have clearly shown that correcting vitamin D deficiencies improves muscle contractile function and muscle strength in this population. In addition, the level of physical activity decreases with age, that negatively affects muscle mass and contractile function, and leads to weight gain, mainly due to increased body fat. However, studies have found that overweight seniors are characterized by lower blood vitamin D levels, lower muscle mass and strength compared to a reference age population.The main objective of this work was to evaluate the effects of vitamin D supplementation on glucose homeostasis and insulin resistance index, as well as on appendicular muscle mass (ASMM) and muscle strength in normal weight or overweight older people. This work is based on a randomized controlled trial, performed in single blind. In terms of results, we show that vitamin D intake in normal or overweight elderly subjects, characterized by a low vitamin D status, improved short-term fasting glucose and insulin resistance markers. The increase in serum 25-hydroxyvitamin D [25 (OH) D] after supplementation resulted in a significant decrease in fasting insulin levels and in HOMA-IR index. We were able to identify a correlation between low serum concentrations of [25 (OH) D] and a decrease in glucose tolerance and an increased risk of type 2 diabetes.Regarding muscle markers, we have shown that vitamin D supplementation has beneficial implications on appendicular muscle mass and fat mass in elderly men and women. However, we found no significant effect on muscle strength. We also found that overweight subjects had a lower serum [25 (OH) D] at baseline. In addition the increase in muscle mass after vitamin D intake was lower in this group than in normal weight subjects.Overall, this work shows that it is necessary to monitor the vitamin D status in older people, especially in overweight subjects.Le rôle principal de la vitamine D est de contrôler l'homéostasie phosphocalcique de l’organisme. Les études observationnelles récentes ont montré que la vitamine D est également capable de réguler la sécrétion d'insuline et la sensibilité à l'insuline, jouant ainsi un rôle important dans la régulation de l'homéostasie du glucose. De plus, il a été montré que la vitamine D exerce un effet sur la santé musculaire. A titre d’exemple, un déficit en vitamine D influence négativement la masse et la fonction musculaires chez les personnes âgées. Il est à noter que selon certaines études, la correction d’une déficience en vitamine D est capable d’améliorer la fonction contractile et la force musculaires dans cette population. En outre, le niveau d'activité physique diminue avec l'âge, ce qui affecte négativement la masse et les capacités musculaires, et conduit à une prise de poids, principalement sous forme de masse grasse. Or, des études ont révélé que les personnes âgées en surpoids étaient caractérisées par des concentrations sanguines de vitamine D plus basses, une masse et une force musculaire plus faibles comparativement à une population de référence de même âge.Aussi l’objectif principal de la thèse était d’évaluer les effets d’un apport complémentaire de vitamine D sur l’homéostasie du glucose et l’indice de résistance à l’insuline, ainsi que sur la masse musculaire appendiculaire (ASMM) et la force musculaire chez des personnes âgées normo-pondérales ou en surpoids. Ces travaux sont basés sur un essai contrôlé randomisé, réalisé en simple aveugle. En termes de résultats, nous avons montré qu’un apport de vitamine D chez des sujets âgés normo-pondéraux ou en surpoids ayant de faibles statuts a permis d’améliorer à court terme la glycémie à jeun et les marqueurs de résistance à l'insuline. L’augmentation du taux sérique de 25-hydroxyvitamine D [25 (OH) D] après la complémentation a entraîné une baisse significative des taux d’insuline à jeun et de l’indice HOMA-IR. Nous avons pu identifier une corrélation entre de faibles concentrations sériques de [25 (OH) D] et une diminution de la tolérance au glucose et un risque accru de diabète de type 2.Concernant les marqueurs musculaires, nous avons observé qu'une complémentation en vitamine D influençait bénéfiquement la masse musculaire appendiculaire et la masse grasse chez les hommes et les femmes âgés en surpoids. Cependant, nous n'avons trouvé aucun effet significatif sur la force musculaire. Nous avons également relevé que les sujets âgés sarcopéniques en surpoids étaient caractérisés par un taux sérique de [25 (OH) D] inférieur au départ de l’étude. De plus, l’augmentation de la masse musculaire après un apport de vitamine D restait inférieure à celle des sujets normo-pondéraux.Ce travail de thèse montre qu’il semble nécessaire de surveiller le statut en vitamine D chez le sujet âgé surtout lorsqu’il est en surpoids

Effect of vitamin D on metabolic markers and muscle function : study in normal weight or overweight elderly Lebanese subjects

Le rôle principal de la vitamine D est de contrôler l'homéostasie phosphocalcique de l’organisme. Les études observationnelles récentes ont montré que la vitamine D est également capable de réguler la sécrétion d'insuline et la sensibilité à l'insuline, jouant ainsi un rôle important dans la régulation de l'homéostasie du glucose. De plus, il a été montré que la vitamine D exerce un effet sur la santé musculaire. A titre d’exemple, un déficit en vitamine D influence négativement la masse et la fonction musculaires chez les personnes âgées. Il est à noter que selon certaines études, la correction d’une déficience en vitamine D est capable d’améliorer la fonction contractile et la force musculaires dans cette population. En outre, le niveau d'activité physique diminue avec l'âge, ce qui affecte négativement la masse et les capacités musculaires, et conduit à une prise de poids, principalement sous forme de masse grasse. Or, des études ont révélé que les personnes âgées en surpoids étaient caractérisées par des concentrations sanguines de vitamine D plus basses, une masse et une force musculaire plus faibles comparativement à une population de référence de même âge.Aussi l’objectif principal de la thèse était d’évaluer les effets d’un apport complémentaire de vitamine D sur l’homéostasie du glucose et l’indice de résistance à l’insuline, ainsi que sur la masse musculaire appendiculaire (ASMM) et la force musculaire chez des personnes âgées normo-pondérales ou en surpoids. Ces travaux sont basés sur un essai contrôlé randomisé, réalisé en simple aveugle. En termes de résultats, nous avons montré qu’un apport de vitamine D chez des sujets âgés normo-pondéraux ou en surpoids ayant de faibles statuts a permis d’améliorer à court terme la glycémie à jeun et les marqueurs de résistance à l'insuline. L’augmentation du taux sérique de 25-hydroxyvitamine D [25 (OH) D] après la complémentation a entraîné une baisse significative des taux d’insuline à jeun et de l’indice HOMA-IR. Nous avons pu identifier une corrélation entre de faibles concentrations sériques de [25 (OH) D] et une diminution de la tolérance au glucose et un risque accru de diabète de type 2.Concernant les marqueurs musculaires, nous avons observé qu'une complémentation en vitamine D influençait bénéfiquement la masse musculaire appendiculaire et la masse grasse chez les hommes et les femmes âgés en surpoids. Cependant, nous n'avons trouvé aucun effet significatif sur la force musculaire. Nous avons également relevé que les sujets âgés sarcopéniques en surpoids étaient caractérisés par un taux sérique de [25 (OH) D] inférieur au départ de l’étude. De plus, l’augmentation de la masse musculaire après un apport de vitamine D restait inférieure à celle des sujets normo-pondéraux.Ce travail de thèse montre qu’il semble nécessaire de surveiller le statut en vitamine D chez le sujet âgé surtout lorsqu’il est en surpoids.The main role of vitamin D is to control the homeostasis of the phosphorus and calcium status of the body. Recent observational studies have shown that vitamin D is also able to regulate insulin secretion and insulin sensitivity, thus playing an important role in the regulation of glucose homeostasis. In addition, vitamin D has been shown to modulate muscle health. For example, vitamin D deficiency negatively influences muscle mass and muscle function in the elderly. Studies have clearly shown that correcting vitamin D deficiencies improves muscle contractile function and muscle strength in this population. In addition, the level of physical activity decreases with age, that negatively affects muscle mass and contractile function, and leads to weight gain, mainly due to increased body fat. However, studies have found that overweight seniors are characterized by lower blood vitamin D levels, lower muscle mass and strength compared to a reference age population.The main objective of this work was to evaluate the effects of vitamin D supplementation on glucose homeostasis and insulin resistance index, as well as on appendicular muscle mass (ASMM) and muscle strength in normal weight or overweight older people. This work is based on a randomized controlled trial, performed in single blind. In terms of results, we show that vitamin D intake in normal or overweight elderly subjects, characterized by a low vitamin D status, improved short-term fasting glucose and insulin resistance markers. The increase in serum 25-hydroxyvitamin D [25 (OH) D] after supplementation resulted in a significant decrease in fasting insulin levels and in HOMA-IR index. We were able to identify a correlation between low serum concentrations of [25 (OH) D] and a decrease in glucose tolerance and an increased risk of type 2 diabetes.Regarding muscle markers, we have shown that vitamin D supplementation has beneficial implications on appendicular muscle mass and fat mass in elderly men and women. However, we found no significant effect on muscle strength. We also found that overweight subjects had a lower serum [25 (OH) D] at baseline. In addition the increase in muscle mass after vitamin D intake was lower in this group than in normal weight subjects.Overall, this work shows that it is necessary to monitor the vitamin D status in older people, especially in overweight subjects

Effect of Vitamin D Supplementation on Inflammatory Markers in Non-Obese Lebanese Patients with Type 2 Diabetes: A Randomized Controlled Trial

International audienceBackground: A low serum 25-hydroxyvitamin D (25(OH) D) concentration has been associated with a higher risk of type 2 diabetes mellitus (T2DM), especially in older people. Our aim in this randomized controlled trial was to evaluate the effect of vitamin D treatment on inflammatory markers in non-obese Lebanese patients with T2DM, living in Beirut, Lebanon. Methods: Non-Obese patients with T2DM (n= 88), deficient/insufficient in vitamin D, were randomly assigned into one of two groups-a treatment group receiving 30,000 IU cholecalciferol/week for a period of six months, and a placebo group. Serum concentrations of TNF-alpha, high-sensitivity C-reactive protein (hs-CRP), and Interleukin-6 (IL-6) were the primary outcomes. A homeostatic model of insulin resistance (HOMA-IR) was assessed, in addition to serum concentrations of fasting blood glucose (FBG), HbA1C, (25(OH) D), and PTH. Results: The vitamin D group showed higher blood levels of (25(OH) D) (p< 0.0001), and a significant reduction in hs-CRP and TNF-alpha concentrations (p< 0.0001) compared to placebo. The decrease perceived in IL-6 concentrations was not significant (p= 0.1). No significant changes were seen in FBG (p= 0.9) and HbA1c levels (p= 0.85). Conclusion: Six months of vitamin D supplementation led to a decrease in some inflammatory markers in patients with T2DM. Additional studies with a larger sample and a longer period are advised in this regard. This trial was registered at ClinicalTrial.gov; Identifier number: NCT 03782805

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

It has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these act either as anti- or pro-inflammatory drugs. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and the environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti- and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that the effects of fluoxetine treatment on inflammation and microglial function, as compared to vehicle, were dependent on the quality of the living environment. In particular, fluoxetine administered in the enriched condition increased the expression of pro-inflammatory markers compared to vehicle, while treatment in a stressful condition produced anti-inflammatory effects. These findings provide new insights regarding the effects of SSRIs on inflammation, which may be crucial to devise pharmacological strategies aimed at enhancing antidepressant efficacy by means of controlling environmental conditions

Prospective evaluation of the performance and interobserver variation in endoscopic ultrasound staging of rectal cancer

Background Treatment and prognosis of patients with rectal adenocarcinoma (RAC) are dependent on accurate locoregional staging. Objectives The aim of this study was to measure the performance characteristics of rectal endoscopic ultrasound (EUS) compared with surgical pathology, and to assess the interobserver variation of rectal EUS in the staging of RAC. Patients and methods Patients referred for rectal EUS staging of a recently diagnosed RAC were prospectively enrolled between 2012 and 2016. Tandem EUS exams were performed by two independent endosonographers (ES1 and ES2) blinded to each other’s findings. Results Ninety-five patients were enrolled. Seventy-five (79%) underwent curative intent tumor resection, including 30 without neoadjuvant therapy. In this latter group, the sensitivity, specificity, and accuracy of transrectal ultrasonography staging were 75, 83, and 82% for uT1; 50, 65, and 58% for uT2; 56, 81, and 73% for T3; 72, 44, and 63% for N0, and 38, 75, and 63% for N1, respectively. Experienced operators rendered a more accurate N stage and were less likely to overstage compared with less experienced ones (P=0.01 and 0.02, respectively). Overall, T staging agreement between endosonographers was substantial (κ=0.61) and N stage agreement was moderate (κ=0.45). Conclusion Rectal EUS is more accurate in staging T1 and T3 tumors compared with T2 tumors. Interobserver agreement of rectal EUS in rectal cancer staging is generally good

Dark microglia: A new phenotype predominantly associated with pathological states

The past decade has witnessed a revolution in our understanding of microglia. These immune cells were shown to actively remodel neuronal circuits, leading to propose new pathogenic mechanisms. To study microglial implication in the loss of synapses, the best pathological correlate of cognitive decline across chronic stress, aging, and diseases, we recently conducted ultrastructural analyses. Our work uncovered the existence of a new microglial phenotype that is rarely present under steady state conditions, in hippocampus, cerebral cortex, amygdala, and hypothalamus, but becomes abundant during chronic stress, aging, fractalkine signaling deficiency (CX3CR1 knockout mice), and Alzheimer's disease pathology (APP‐PS1 mice). Even though these cells display ultrastructural features of microglia, they are strikingly distinct from the other phenotypes described so far at the ultrastructural level. They exhibit several signs of oxidative stress, including a condensed, electron‐dense cytoplasm and nucleoplasm making them as “dark” as mitochondria, accompanied by a pronounced remodeling of their nuclear chromatin. Dark microglia appear to be much more active than the normal microglia, reaching for synaptic clefts, while extensively encircling axon terminals and dendritic spines with their highly ramified and thin processes. They stain for the myeloid cell markers IBA1 and GFP (in CX3CR1‐GFP mice), and strongly express CD11b and microglia‐specific 4D4 in their processes encircling synaptic elements, and TREM2 when they associate with amyloid plaques. Overall, these findings suggest that dark microglia, a new phenotype that we identified based on their unique properties, could play a significant role in the pathological remodeling of neuronal circuits, especially at synapses. GLIA 2016;64:826–83