miRNAs from Inflamed Gingiva Link Gene Signaling to Increased MET Expression.

Several array-based microRNA (miRNA) expression studies independently showed increased expression of miRNAs hsa-miR-130a-3p, -142-3p, -144-3p, -144-5p, -223-3p, -17-5p, and -30e-5p in gingiva affected by periodontal inflammation. We aimed to determine direct target genes and signaling pathways regulated by these miRNAs to identify processes relevant to gingival inflammatory responses and tissue homeostasis. We transfected miRNA mimics (mirVana) for each of the 7 miRNAs separately into human primary gingival fibroblasts cultured from 3 different donors. Following RNA sequencing, differential gene expression and second-generation gene set enrichment analyses were performed. miRNA inhibition and upregulation was validated at the transcript and protein levels using quantitative reverse transcriptase polymerase chain reaction, Western blotting, and reporter gene assays. All 7 miRNAs significantly increased expression of the gene MET proto-oncogene, receptor tyrosine kinase (MET). Expression of known periodontitis risk genes CPEB1, ABCA1, and ATP6V1C1 was significantly repressed by hsa-miR-130a-3p, -144-3p, and -144-5p, respectively. The genes WASL, ENPP5, ARL6IP1, and IDH1 showed the most significant and strongest downregulation after hsa-miR-142-3p, -17-5p, -223-3p, and -30e-5p transfection, respectively. The most significantly regulated gene set of each miRNA related to cell cycle (hsa-miRNA-144-3p and -5p [Padj = 4 × 10-40 and Padj = 4 × 10-6], -miR-17-5p [Padj = 9.5 × 10-23], -miR-30e-5p [Padj = 8.2 × 10-18], -miR-130a-3p [Padj = 5 × 10-15]), integrin cell surface interaction (-miR-223-3p [Padj = 2.4 × 10-7]), and interferon signaling (-miR-142-3p [Padj = 5 × 10-11]). At the end of acute inflammation, gingival miRNAs bring together complex regulatory networks that lead to increased expression of the gene MET. This underscores the importance of mesenchymal cell migration and invasion during gingival tissue remodeling and proliferation in restoring periodontal tissue homeostasis after active inflammation. MET, a receptor of the mitogenic hepatocyte growth factor fibroblast secreted, is a core gene of this process.

Evaluating automated infrared thermography and vulva exposure tracking as components of an estrus detection platform in a commercial dairy herd.

The primary objective of this study was to develop an automated infrared thermography platform (Estrus BenchMark) capable of measuring skin temperature and tail movements as a means of identifying cows in estrus. The secondary objective was to evaluate the accuracy of Estrus BenchMark to detect estrus compared to in-line milk progesterone (P4) analysis (Herd Navigator System) in a commercial dairy herd managed under a robotic milking system. Data were collected on forty-six cows from 45 to 120 d after calving. Cows were flagged in estrus when milk P4 fell below 5 ng/mL. The Estrus BenchMark true positive estrus alerts (Sensitivity; Se%) were compared to Herd Navigator System estrus alerts at different time-windows (±12 h, ±24 h, ±48 h, and ±72 h) relative to the Estrus BenchMark estrus alerts for all the estrus alerts (AE) and confidence-quality estrus (CQE; >80% quality) alerts identified by Herd Navigator System. The Estrus BenchMark captured skin temperature and tail movements resulting in vulva exposure (left tail movements, LTail; right tail movements, RTail; and pooled tail movements, PTail) for each milking event. Skin temperature tended to increase when the milk P4 concentration (Least-Squares Means ±â€¯SE) dropped for AE (estrus day [d 0]; P4; 3.51 ±â€¯0.05 ng/mL, Skin temperature; 33.31 ±â€¯2.38 °C) compared with d -7 (P4; 20.22 ±â€¯0.73 ng/mL; Skin temperature: 32.05 ±â€¯3.77 °C). The increase in skin temperature, however, was significant in cows with CQE > 80% at d 0 (32.75 ±â€¯0.29 °C) compared to d -7 (31.80 ±â€¯0.28 °C). The prevalence of tail movements to expose vulva was greater (P = 0.01) in AE at d 0 (LTail: 62.50%; PTail; 68.75%; and RTail: 56.25%) compared with d -7 (LTail: 18.75%; PTail: 9.37%: and RTail: 9.37%), and d +4 (LTail: 9.37%; PTail: 9.37%; and RTail: 12.5%). Moreover, the higher prevalence of tail movements at d 0 was observed in cows with CQE > 80% (LTail; 65%, PTail; 80%, and RTail; 70%) compared to those with CQE < 80%. The highest Estrus BenchMark Youden index (YJ; 0.45), diagnostic odds ratio (DOR; 9.04), and Efficiency (0.77) were achieved for AE in a ±48 h window and at ±72 h window for CQE (YJ; 0.66, DOR; 25.29, and Efficiency 0.76) relative to Herd Navigator System estrus alerts. The highest Estrus BenchMark resulted in 58% estrus detection rates for AE and 80% for cows with CQE compared to the Herd Navigator System.

Periodontitis Risk Variants at SIGLEC5 Impair ERG and MAFB Binding.

Periodontitis is a common complex inflammatory disease of the oral cavity. It is characterized by inflammation of gingival tissues and alveolar bone loss. Recently, a genome-wide association study and 2 genome-wide association study meta-analyses found 2 associated regions (haplotype blocks) at the inhibitory immune receptor gene SIGLEC5 to increase the risk for periodontitis. The aims of the current study were the identification of the putative causal variants underlying these associations, characterization of their molecular biological effects, and validation of SIGLEC5 as the target gene. We mapped the associated single-nucleotide polymorphisms to DNA elements with predictive features of regulatory functions and screened the associated alleles for transcription factor (TF) binding sites. Antibody electrophoretic mobility shift assays (EMSAs) with allele-specific probes were used to identify TF binding and to quantify allele-specific effects on binding affinities. Luciferase reporter assays were used to quantify the effect directions and allele-specific strength of the associated regulatory elements. We used CRISPR-dCas9 gene activation to validate SIGLEC5 as a target of the association. EMSA in peripheral blood mononuclear cells showed that E-26 transformation-specific TF-related gene (ERG) binds at rs11084095, with almost complete loss of binding at the minor A-allele. Allele-specific reporter genes showed enhancer function of the DNA sequence at rs11084095, which was abrogated in the background of the A-allele. EMSA in B lymphocytes showed that TF MAF bZIP (MAFB) binds at the common G-allele of rs4284742, whereas the minor A-allele reduced TF binding by 69%, corresponding to 9-fold reduction of luciferase reporter gene activity by the A-allele. Using CRISPR-dCas9, we showed that the enhancer at rs4284742 strongly activated SIGLEC5 expression, validating this gene as the target gene of the association. We conclude that rs11084095 and rs4284742 are putatively causal for the genome-wide significant associations with periodontitis at SIGLEC5 that impair ERG and MAFB binding, respectively.

BACH1 Binding Links the Genetic Risk for Severe Periodontitis with ST8SIA1.

Genome-wide association studies identified various loci associated with periodontal diseases, but assigning causal alleles remains difficult. Likewise, the generation of biological meaning underlying a statistical association has been challenging. Here, we characterized the genetic association at the gene ST8SIA1 that increases the risk for severe periodontitis in smokers. We used CRISPR/dCas9 activation and RNA-sequencing to identify genetic interaction partners of ST8SIA1 and to determine its function in the cell. We used reporter gene assays to identify regulatory elements at the associated single-nucleotide polymorphisms (SNPs) and to determine effect directions and allele-specific changes of enhancer activity. Antibody electrophoretic mobility shift assays proved allele-specific transcription factor binding at the putative causal SNPs. We found the reported periodontitis risk gene ABCA1 as the top upregulated gene following ST8SIA1 activation. Gene set enrichment analysis showed highest effects on integrin cell surface interactions (area under the curve [AUC] = 0.85; q = 4.9 × 10-6) and cell cycle regulation (AUC = 0.89; q = 1.6 × 10-5). We identified 2 associated repressor elements in the introns of ST8SIA1 that bind the transcriptional repressor BACH1. The putative causative variant rs2012722 decreased BACH1 binding by 40%. We also pinpointed ST8SIA1 as the target gene of the association. ST8SIA1 inhibits cell adhesion with extracellular matrix proteins, integrins, and cell cycle, as well as enhances apoptosis. Likewise, tobacco smoke reportedly results in an inhibition of cell adhesion and a decrease in integrin-positive cells and cell growth. We conclude that impaired ST8SIA1 repression, independently caused by reduced BACH1 binding at the effect T allele, as well as by tobacco smoke, contributes to higher ST8SIA1 levels, and in smokers who carry the effect T allele, both factors would be additive with damaging effects on the gingival barrier integrity. The activity of ST8SIA1 is also linked with the periodontitis risk gene ABCA1.

Evaluation of infrared thermography combined with behavioral biometrics for estrus detection in naturally cycling dairy cows.

Low estrus detection rates (>50%) are associated to extended calving intervals, low economic profit and reduced longevity in Holstein dairy cows. The objective of this study was to evaluate the accuracy of infrared thermography and behavioral biometrics combined as potential estrus alerts in naturally (not induced) cycling dairy cows housed in a tie-stall barn. Eighteen first lactation cows were subjected to transrectal ultrasonography to determine spontaneous ovulation. The dominant follicle (DF) disappearance was used retrospectively as an indirect indicator of ovulation, and to establish the estrus period (48-24 h prior the DF disappearance). Raw skin temperature (Raw IR) and residual skin temperature (Res IR) were recorded using an infrared camera at the Vulva area with the tail (Vtail), Vulva area without the tail (Vnotail), and Vulva's external lips (Vlips) at AM and PM milking from Day 14 until two days after ovulation was confirmed. Behavioral biometrics were recorded on the same schedule as infrared scan. Behavioral biometrics included large hip movements (L-hip), small hip movements (S-hip), large tail movements and small tail movements to compare behavioral changes between estrus and nonestrus periods. Significant increases in Raw IR skin temperature were observed two days prior to ovulation (Vtail; 35.93 ±â€¯0.27 °C, Vnotail; 35.59 ±â€¯0.27 °C, and Vlips; 35.35 ±â€¯0.27 °C) compared to d -5 (Proestrus; Vtail; 35.29 ±â€¯0.27 °C, Vnotail; 34.93 ±â€¯0.31 °C, and Vlips; 34.68 ±â€¯0.27 °C). No significant changes were found for behavioral parameters with the exception of S-hip movements, which increased at two days before ovulation (d -2; 11.13 ±â€¯1.44 Events/5min) compared to d -5 (7.30 ±â€¯1.02 Events/5min). To evaluate the accuracy of thermal and behavioral biometrics, receiver operating characteristic curve analysis was performed using Youden index (YJ), diagnostic odds ratio, positive likelihood ratio (LR+), Sensitivity, Specificity and Positive predicted value to score the estrus alerts. The greatest accuracy achieved using thermal parameters was for Res IR Vtail PM (YJ = 0.34) and L-hip PM (YJ = 0.27) for behavioral biometrics. Combining thermal and behavioral parameters did not improve the YJ index score but reduced the false-positive occurrence observed by increasing the diagnostic odds ratio (26.62), LR+ (12.47), Specificity (0.97) and positive predicted value (0.90) in a Res IR Vtail PM, S-hip AM, S-hip PM combination. The combination of thermal and behavioral parameters increased the accuracy of estrus detection compared to either thermal or behavioral biometrics, independently in naturally cycling cows during milking.

Entamoeba gingivalis Exerts Severe Pathogenic Effects on the Oral Mucosa.

The protozoan Entamoeba gingivalis colonizes the healthy oral mucosa with a prevalence of 15%. Colonization can be asymptomatic, and it is considered not pathogenic. However, it is able to invade lacerated oral mucosa, where it ingests fragments of live cells, suggesting pathogenous potential. Here, we characterized the transcriptomes of gingival cells after infection with E. gingivalis using RNA sequencing and observed pathogen interaction with the epithelial monolayer barrier by scanning electron microscopy. In epithelial and fibroblast cells, strongest differential expression showed gene set "chemokines and inflammatory molecules in myeloid cells" (area under the curve [AUC] = 0.9, effect size 5.15, adjusted P = 3.1 × 10-19) and "cell cycle and growth arrest" (AUC = 0.91, effect size = 4.56, adjusted P = 4.8 × 10-9), respectively. The most upregulated genes were TNF (fold change 430) and IL8 (fold change 359) in epithelial cells and ZN331 (fold change 18) in fibroblasts. We showed that E. gingivalis killed live epithelial cells by trogocytosis, demonstrating strong pathogenic potential.

Smoking Modifies the Genetic Risk for Early-Onset Periodontitis.

Periodontitis has low-prevalence, highly severe disease manifestations with an early onset and rapid progression. The diagnosis is based on severe destruction of the alveolar bone in adolescents and young adults. Genetic susceptibility variants and smoking are well-established risk factors, but their interactions in modifying disease susceptibility have not been studied. We aimed to identify genetic risk variants of early-onset periodontitis that unmask their effects on tobacco smoke exposure. To this end, we analyzed 79,780,573 common variants in 741 northwest Europeans diagnosed to have >30% bone loss at >2 teeth before 35 y of age, using imputed genotypes of the OmniExpress BeadChip. Never versus ever smokers were compared in a logistic regression analysis via a case-only approach. To explore the effect of tobacco smoke on the expression of the G×S-associated genes, cultures of primary gingival fibroblasts (n = 9) were exposed to cigarette smoke extract, and transcripts were quantified by reverse transcription polymerase chain reaction. We identified 16 loci for which our analysis suggested an association with G×S increased disease risk (P < 5 × 10-5). Nine loci had previously been reported to be associated with spirometric measures of pulmonary function by an earlier G×S genome-wide association study. Genome-wide significant cis expression quantitative trait loci were reported for G×S-associated single-nucleotide polymorphisms at ST8SIA1 and SOST, indicating a causal role of these genes in tobacco-related etiopathology. Notably, SOST is a negative regulator of bone growth, and ST8SIA1 has a role in tissue remodeling. Cigarette smoke extract significantly altered the expression of 2 associated genes: SSH1 (P = 5 × 10-07), which is required for NF-κB activation and innate immune responses to bacterial invasion, and ST8SIA1 (P = 0.0048). We conclude that the genetic predisposition to early-onset periodontitis is in part triggered by smoking and that tobacco smoke directly affects the expression of genes involved in bone homeostasis, tissue repair, and immune response.

Analysis of Minimally Invasive Left Thoracotomy HVAD Implantation - A Single-Center Experience.

BACKGROUND: Minimally invasive left ventricular assist device (LVAD) implantation may reduce peri-/postoperative complications and risks associated with resternotomies. In this study, we describe our first results using a minimally invasive LVAD implantation technique (lateral thoracotomy [LT] group). These results were compared with LVAD implantations done via full median sternotomy (STX group). METHODS: HVAD (HeartWare, Framingham, Massachusetts, United States) implantations in 70 patients (LT group n = 22, 52 ± 15 years old; STX group n = 48, 59 ± 11 years old) were retrospectively analyzed. Minimally invasive access via left thoracotomy was feasible in 22 patients. Peri- and postoperative analyses of survival and adverse events were performed. RESULTS: No survival differences were observed between the LT and STX group (p = 0.43). LT patients without temporary right ventricular assist device (tRVAD) showed a significantly better survival rate compared to LT patients with concomitant tRVAD implantation (p = 0.02), which could not be demonstrated in the STX group (p = 0.11). Two LT and four STX patients were successfully bridged to heart transplantation and three STX patients were successfully weaned with subsequent LVAD explantations. LVAD-related infections (n = 4 LT group vs n = 20 STX group, p = 0.04) were less likely in the LT group. No wound dehiscence occurred in the LT group, whereas five were observed in the STX group (p = 0.17). The amount of perioperative blood transfusions (within the first 7 postoperative days) did not differ in both study groups (p = 0.48). CONCLUSION: The minimally invasive approach is a viable alternative with the possibility to reduce complications and should be particularly considered for bridge-to-transplant patients.

[Instantaneous wave-free ratio (iFR®) in patients with coronary artery disease]. / "Instantaneous wave-free ratio" (iFR®) bei Patienten mit koronarer Herzkrankheit.

Coronary angiography is considered as the gold standard in the morphological representation of coronary artery stenosis. Coronary angiography is often performed without preprocedural non-invasive proof of ischemia and the assessment of the severity of a coronary lesion by morphology is very subjective. Thus, invasive fractional flow reserve (FFR) measurement represents the current standard for estimation of the hemodynamic relevance of coronary artery stenosis and facilitates decision making for percutaneous coronary intervention (PCI) and stenting. The FFR-guided revascularization strategy has been classified as a class IA recommendation in the 2014 ESC/EACTS guidelines on myocardial revascularization. Both the DEFER and the FAME studies showed no treatment advantage of hemodynamically irrelevant stenosis. By use of FFR (and targeted interventions), clinical results could be improved as well as the procedure costs were reduced; however, the use in clinical practice is still limited due to the need of adenosine administration and a significant prolongation of the procedure. Instantaneous wave-free ratio (iFR®) is a new innovative approach for the determination of the hemodynamic relevance of coronary stenosis which can be obtained at rest without the use of vasodilators. Regarding periprocedural complications as well as prognosis, iFR® showed non-inferiority compared to FFR in the SWEDEHEART and DEFINE-FLAIR trials.

Photochemistry of Carboxylate on TiO2(110) Studied with Synchrotron Radiation Photoelectron Spectroscopy.

We present a dedicated synchrotron radiation photoelectron spectroscopy (SR-PES) study of a photochemical reaction on the surface of rutile TiO2(110). The photoreaction kinetics of carboxylate species (trimethyl acetate, TMA) upon irradiation by UV and soft X-rays were monitored, and we show that it is possible to control the reaction rates from UV light and soft X-rays independently. We directly observe Ti4+ → Ti3+ conversion upon irradiation, attributed to electron trapping at Ti sites close to surface OH groups formed by deprotonation of the parent molecule, trimethylacetic acid (TMAA). TMA photolysis on two surface preparations with different oxygen vacancy densities shows that the vacancy-related charge quenches the amount of charge that can be trapped at hydroxyls upon irradiation. During the initial stages of reaction the correlation between the amount of photodepleted TMA and the amount of charge trapped in the Ti 3d band gap state is nearly 1:1. A first-order kinetics analysis reveals that the reaction rate decreases with decreasing TMA coverage. There is also a coverage-dependent difference in the electronic structure of TMA moieties, primarily involving the carboxyl anchor group. These changes are consistent with a decreased hole affinity of the adsorbed TMA and hence a decreased reaction rate. This discovery adds to the previously presented picture of a reactivity that is inversely proportional to the number of surface hydroxyls, suggesting that the balance between the amounts of TMA, OH, and trapped charge needs to be considered.

Importancia de la interacción social en la retroalimentación, según residentes de Psiquiatría / The opinion of psychiatry residents about social interaction during the feedback in medical education

In Medical Education, feedback is an instrument that informs the trainees about their learning process and how to make the necessary changes. Feedback enables learners to monitor their progress and provides direction for improvement. Effective feedback is useful to improve the performance, clinical skills, communication skills, and treatment of patients. It is essential when teaching clinical interview skills to psychiatry residents. Feedback necessarily involves social interaction between teachers and trainees. Aim: To analyze the perception of psychiatry residents about social interaction during the feedback received during their training. Material and Methods: Qualitative study, using the Grounded theory method. Nine interviews were performed to adult psychiatry residents of the University of Concepción and one to a recently graduated psychiatrist. Data were analyzed using open coding. Results: We found four emerging categories: Socialization, roles and hierarchy, invitation to integration and teacher involvement. Conclusions: The effectiveness of feedback lies in the establishment of a minimal teacher-resident social relationship, in which feedback occurs naturally.

Impact of consensus contours from multiple PET segmentation methods on the accuracy of functional volume delineation.

PURPOSE: The aim of this study was to evaluate the impact of consensus algorithms on segmentation results when applied to clinical PET images. In particular, whether the use of the majority vote or STAPLE algorithm could improve the accuracy and reproducibility of the segmentation provided by the combination of three semiautomatic segmentation algorithms was investigated. METHODS: Three published segmentation methods (contrast-oriented, possibility theory and adaptive thresholding) and two consensus algorithms (majority vote and STAPLE) were implemented in a single software platform (Artiview®). Four clinical datasets including different locations (thorax, breast, abdomen) or pathologies (primary NSCLC tumours, metastasis, lymphoma) were used to evaluate accuracy and reproducibility of the consensus approach in comparison with pathology as the ground truth or CT as a ground truth surrogate. RESULTS: Variability in the performance of the individual segmentation algorithms for lesions of different tumour entities reflected the variability in PET images in terms of resolution, contrast and noise. Independent of location and pathology of the lesion, however, the consensus method resulted in improved accuracy in volume segmentation compared with the worst-performing individual method in the majority of cases and was close to the best-performing method in many cases. In addition, the implementation revealed high reproducibility in the segmentation results with small changes in the respective starting conditions. There were no significant differences in the results with the STAPLE algorithm and the majority vote algorithm. CONCLUSION: This study showed that combining different PET segmentation methods by the use of a consensus algorithm offers robustness against the variable performance of individual segmentation methods and this approach would therefore be useful in radiation oncology. It might also be relevant for other scenarios such as the merging of expert recommendations in clinical routine and trials or the multiobserver generation of contours for standardization of automatic contouring.

Abordaje narrativo y estratégico en el trastorno por ansiedad social / Narrative and strategic approach in social anxiety disorder

Social anxiety disorder (SAD) has great clinical relevance due to both, the impairment it causes and co-morbidity. The standard treatment is cognitive behavioral therapy, through exposure and cognitive restructuring, and additionally the use of psychotropic drugs. However, it is necessary to broaden the conceptualization and psychotherapeutic approach, adding a narrative approach through constructivist and constructionist perspectives. From this standpoint, there are contexts of invalidation and resignation processes. Therefore, the TAS is multidimensional and has two polarities, a constitutive and an operative, that guide therapy. This model increases the understanding and reflection regarding the phenomenon and make possible new options for intervention.

El trastorno por ansiedad social (TAS) presenta una gran relevancia clínica debido al menoscabo que genera y a la co-morbilidad asociada. El tratamiento estándar consiste en la terapia cognitivo-conductual, mediante exposición y reestructuración cognitiva, más el uso de psicofármacos. No obstante, se hace necesario ampliar la conceptualización y abordaje psicoterapéutico, por lo cual las visiones constructivistas y construccionistas agregan una mirada narrativa. Desde lo narrativo, hay contextos de invalidación y procesos de renuncia. Por lo tanto, el TAS es multidimensional y posee dos polaridades que orientan la terapia; una constitutiva y una operativa. Esta conceptualización amplía la comprensión y reflexión sobre el fenómeno y permite nuevas opciones de intervención.

Psicoterapias postestructuralistas y factores de cambio: posibilidades para una práctica efectiva / Poststructuralist psychotherapies and change factors: possibilities for effective practice

The evidence in psychotherapy out come research points to the importance of the common factors in therapeutic change, which depend largely on patient participation. Models of post-structuralist orientation in systemic psychotherapy promote direct and explicitly change/common factors, as the therapeutic alliance, expectatives and extra-therapeutic factors, allowing the accommodation, relevant instance giving the consultant a decisive role for therapeutic change. The poststructuralist models are good instances formational, especially for the acquisition of skill stomobilize change factors.

La evidencia en investigación de resultados en psicoterapia señala la relevancia de los factores comunes en el cambio terapéutico, los cuales dependen en buena medida de la participación y protagonismo del paciente. Los modelos de orientación post-estructuralista en psicoterapia sistémica promueven de forma directa y explícita los factores de cambio/comunes, como la alianza terapéutica, las expectativas y los factores extra-terapéuticos, permitiendo la acomodación, instancia relevante que otorga al consultante un rol decisivo para el cambio terapéutico. Los modelos posestructuralistas son buenas instancias formativas, en especial para la adquisición de destrezas que movilicen factores de cambio.

Coexisting large and small vessel disease in patients with ischemic stroke of undetermined cause.

BACKGROUND AND PURPOSE: Large artery atherosclerosis (LAA) and small vessel disease (SVD) share common risk factors for stroke. We aimed at investigating the association of SVD with cerebral LAA as well as with atherosclerosis in patients with stroke likely to originate from aortic plaques. METHODS: We investigated 71 consecutive patients (48 men, mean age 64.2 ± 13 years) with ischemic stroke of undetermined cause according to the ASCO classification, who received ECG-triggered CT angiography for best available atherosclerotic plaque detection in the aorta. RESULTS: Aortic atherosclerotic plaques were detected in 54 patients (76.1%). The presence of SVD significantly correlated with the presence of aortic plaques (p < 0.001), as well as LAA (p < 0.001) and risk factors such as arterial hypertension (p = 0.032) and diabetes mellitus (p = 0.017). CONCLUSIONS: Aortic plaques are common in patients with stroke of undetermined cause. If so, SVD and LAA are often coexisting, which demonstrates the close link of macro- and microangiopathy, at least in cases of severe risk factors of atherosclerosis.

Integration of FDG-PET/CT into external beam radiation therapy planning: technical aspects and recommendations on methodological approaches.

UNLABELLED: This work addresses the clinical adoption of FDG-PET/CT for image-guided radiation therapy planning (RTP). As such, important technical and methodological aspects of PET/CT-based RTP are reviewed and practical recommendations are given for routine patient management and clinical studies. First, recent developments in PET/CT hardware that are relevant to RTP are reviewed in the context of quality control and system calibration procedures that are mandatory for a reproducible adoption of PET/CT in RTP. Second, recommendations are provided on image acquisition and reconstruction to support the standardization of imaging protocols. A major prerequisite for routine RTP is a complete and secure data transfer to the actual planning system. Third, state-of-the-art tools for image fusion and co-registration are discussed briefly in the context of PET/CT imaging pre- and post-RTP. This includes a brief review of state-of-the-art image contouring algorithms relevant to PET/CT-guided RTP. Finally, practical aspects of clinical workflow and patient management, such as patient setup and requirements for staff training are emphasized. PET/CT-guided RTP mandates attention to logistical aspects, patient set-up and acquisition parameters as well as an in-depth appreciation of quality control and protocol standardization. CONCLUSION: Upon fulfilling the requirements to perform PET/CT for RTP, a new dimension of molecular imaging can be added to traditional morphological imaging. As a consequence, PET/CT imaging will support improved RTP and better patient care. This document serves as a guidance on practical and clinically validated instructions that are deemed useful to the staff involved in PET/CT-guided RTP.

Multi-centre calibration of an adaptive thresholding method for PET-based delineation of tumour volumes in radiotherapy planning of lung cancer.

PURPOSE: To evaluate the calibration of an adaptive thresholding algorithm (contrast-oriented algorithm) for FDG PET-based delineation of tumour volumes in eleven centres with respect to scanner types and image data processing by phantom measurements. METHODS: A cylindrical phantom with spheres of different diameters was filled with FDG realizing different signal-to-background ratios and scanned using 5 Siemens Biograph PET/CT scanners, 5 Philips Gemini PET/CT scanners, and one Siemens ECAT-ART PET scanner. All scans were analysed by the contrast-oriented algorithm implemented in two different software packages. For each site, the threshold SUVs of all spheres best matching the known sphere volumes were determined. Calibration parameters a and b were calculated for each combination of scanner and image-analysis software package. In addition, "scanner-type-specific" calibration curves were determined from all values obtained for each combination of scanner type and software package. Both kinds of calibration curves were used for volume delineation of the spheres. RESULTS: Only minor differences in calibration parameters were observed for scanners of the same type (Δa ≤4%, Δb ≤14%) provided that identical imaging protocols were used whereas significant differences were found comparing calibration parameters of the ART scanner with those of scanners of different type (Δa ≤60%, Δb ≤54%). After calibration, for all scanners investigated the calculated SUV thresholds for auto-contouring did not differ significantly (all p>0.58). The resulting sphere volumes deviated by less than -7% to +8% from the true values. CONCLUSION: After multi-centre calibration the use of the contrast-oriented algorithm for FDG PET-based delineation of tumour volumes in the different centres using different scanner types and specific imaging protocols is feasible.

[Heterotopic gastric mucosa of the rectum. Case report with literature review]. / Rektale Magenschleimhautheterotopie. Ein Fallbericht in Zusammenschau mit der Literatur.

Heterotopic gastric mucosa is a rare finding in the rectum. Apart from two other hypotheses, a misdifferentiation of entodermal stem cells is the most widely accepted aetiopathogenetic assumption today. Due to acid secretion, the lesions predominantly manifest with hematochezia. Therapeutic options include medicinal therapy and particularly (endoscopic) removal. From the pathologist's point of view a careful evaluation is required also in terms of basically possible dysplastic or malignant changes.

An effective lifestyle intervention in overweight children: one-year follow-up after the randomized controlled trial on "Obeldicks light".

BACKGROUND & AIMS: Lifestyle interventions address primarily obese children, while interventions tailored to overweight but not obese children are scarce. The effectiveness of the lifestyle intervention "Obeldicks light" based on physical activity training, nutrition education, and behavior counseling for overweight children and their parents has been demonstrated by a randomized controlled trial. Here, we present the 12 months follow-up analysis of these children after end of intervention. METHODS: Degree of overweight (BMI and SDS-BMI), waist circumference, skinfold thickness, bioimpedance analyses (BIA), and blood pressure were determined in 76 overweight (BMI>90(th)≤97(th) percentile) children (mean age 11.8 ± 1.8years, 67% females, mean BMI 24.3 ± 1.9 kg/m(2)) participating in the evaluation study of "Obeldicks light" at onset of intervention (T0), end of 6 months intervention (T1), 6 months after end of intervention (T2) and 12 months after end of intervention (T3). Comparisons were performed on an intention-to-treat approach. RESULTS: The drop-out rate was 4% in the intervention period and additional 3% during follow-up. The children reduced significantly (p < 0.001) their SDS-BMI in the intervention period between T0 and T1 (-0.27 ± 0.23; p < 0.001). This SDS-BMI reduction remained stable at T2 (T0-T2:-0.26 ± 0.31; p < 0.001) and T3 (T0-T3:-0.26 ± 0.39; p < 0.001). SDS-BMI reductions were independent from age and gender. Body fat measured by skinfold thickness and BIA, waist circumference, and blood pressure decreased significantly in the intervention period and remained stable in the follow-up period as well. CONCLUSIONS: The lifestyle intervention "Obeldicks light" was effective in reducing degree of overweight, fat mass, waist circumference, and blood pressure both at end of intervention and in a 12 months follow-up period.

[Transcatheter valve interventions for heart valve diseases]. / Kathetergestützte Therapie von Herzklappenfehlern.

Severe aortic stenosis is a significant source of morbidity and mortality among the aging population. Due to prohibitive surgical risk, many patients are not candidates for surgery. Therefore, transcatheter aortic valve implantation has emerged as a promising technology for treating this group of high risk patients. With increasing experience, this procedure can be performed successfully and safely in selected high risk patients. Nevertheless, before widespread use and application to lower risk patients the results of randomized studies are mandatory. Primary (degenerative) and secondary (functional) mitral regurgitation (MR) is an important cause of heart failure. The double orifice technique of mitral valve repair using the MitraClip® system is one of many transcatheter approaches to treat significant MR in patients at high risk for conventional surgery. This technique is effective in reducing MR severity in patients suffering from both degenerative and functional MR. Percutaneous pulmonary valve implantation (PPVI) is an interventional treatment for adolescents and young adults with congenital heart disease. After corrective or palliative operation in infancy or early childhood, some patients regularly need reoperations for right ventricular outflow tract reconstruction. In the last decade, PPVI has evolved as an alternative treatment option with much less morbidity compared to repeated surgery.