Epigenome-wide association study of DNA methylation in maternal blood leukocytes with BMI in pregnancy and gestational weight gain.

OBJECTIVES: We aimed to discover CpG sites with differential DNA methylation in peripheral blood leukocytes associated with body mass index (BMI) in pregnancy and gestational weight gain (GWG) in women of European and South Asian ancestry. Furthermore, we aimed to investigate how the identified sites were associated with methylation quantitative trait loci, gene ontology, and cardiometabolic parameters. METHODS: In the Epigenetics in pregnancy (EPIPREG) sample we quantified maternal DNA methylation in peripheral blood leukocytes in gestational week 28 with Illumina's MethylationEPIC BeadChip. In women with European (n = 303) and South Asian (n = 164) ancestry, we performed an epigenome-wide association study of BMI in gestational week 28 and GWG between gestational weeks 15 and 28 using a meta-analysis approach. Replication was performed in the Norwegian Mother, Father, and Child Cohort Study, the Study of Assisted Reproductive Technologies (MoBa-START) (n = 877, mainly European/Norwegian). RESULTS: We identified one CpG site significantly associated with GWG (p 5.8 × 10-8) and five CpG sites associated with BMI at gestational week 28 (p from 4.0 × 10-8 to 2.1 × 10-10). Of these, we were able to replicate three in MoBa-START; cg02786370, cg19758958 and cg10472537. Two sites are located in genes previously associated with blood pressure and BMI. DNA methylation at the three replicated CpG sites were associated with levels of blood pressure, lipids and glucose in EPIPREG (p from 1.2 × 10-8 to 0.04). CONCLUSIONS: We identified five CpG sites associated with BMI at gestational week 28, and one with GWG. Three of the sites were replicated in an independent cohort. Several genetic variants were associated with DNA methylation at cg02786379 and cg16733643 suggesting a genetic component influencing differential methylation. The identified CpG sites were associated with cardiometabolic traits. GOV REGISTRATION NO: Not applicable.

Semi-automatic artifact quantification in thermal ablation probe and algorithms for the evaluation of metal artifact reduction.

OBJECTIVES: To compare metal artifacts and evaluation of metal artifact reduction algorithms during probe positioning in computed tomography (CT)-guided microwave ablation (MWA), cryoablation (CRYO), and radiofrequency ablation (RFA). MATERIALS AND METHODS: Using CT guidance, individual MWA, CRYO, and RFA ablation probes were placed into the livers of 15 pigs. CT imaging was then performed to determine the probe's position within the test subject's liver. Filtered back projection (B30f) and iterative reconstructions (I30-1) were both used with and without dedicated iterative metal artifact reduction (iMAR) to generate images from the initial data sets. Semi-automatic segmentation-based quantitative evaluation was conducted to estimate artifact percentage within the liver, while qualitative evaluation of metal artifact extent and overall image quality was performed by two observers using a 5-point Likert scale: 1-none, 2-mild, 3-moderate, 4-severe, 5-non-diagnostic. RESULTS: Among MWA, RFA, and CRYO, compared with non-iMAR in B30f reconstruction, the largest extent of artifact volume percentages were observed for CRYO (11.5-17.9%), followed by MWA (4.7-6.6%) and lastly in RFA (5.5-6.2%). iMAR significantly reduces metal artifacts for CRYO and MWA quantitatively (p = 0.0020; p = 0.0036, respectively) and qualitatively (p = 0.0001, p = 0.0005), but not for RFA. No significant reduction in metal artifact percentage was seen after applying iterative reconstructions (p > 0.05). Noise, contrast-to-noise-ratio, or overall image quality did not differ between probe types, irrespective of the application of iterative reconstruction and iMAR. CONCLUSION: A dedicated metal artifact algorithm may decrease metal artifacts and improves image quality significantly for MWA and CRYO probes. Their application alongside with dedicated metal artifact algorithm should be considered during CT-guided positioning.

Distributed Global Debris Thickness Estimates Reveal Debris Significantly Impacts Glacier Mass Balance.

Supraglacial debris affects glacier mass balance as a thin layer enhances surface melting, while a thick layer reduces it. While many glaciers are debris-covered, global glacier models do not account for debris because its thickness is unknown. We provide the first globally distributed debris thickness estimates using a novel approach combining sub-debris melt and surface temperature inversion methods. Results are evaluated against observations from 22 glaciers. We find the median global debris thickness is ∼0.15 ± 0.06 m. In all regions, the net effect of accounting for debris is a reduction in sub-debris melt, on average, by 37%, which can impact regional mass balance by up to 0.40 m water equivalent (w.e.) yr-1. We also find recent observations of similar thinning rates over debris-covered and clean ice glacier tongues is primarily due to differences in ice dynamics. Our results demonstrate the importance of accounting for debris in glacier modeling efforts.

Radiological management of postoperative lymphorrhea.

PURPOSE: Postoperative lymphorrhea can occur after different surgical procedures and may prolong the hospital stay due to the need for specific treatment. In this work, the therapeutic significance of the radiological management of postoperative lymphorrhea was assessed and illustrated. METHOD: A standardized search of the literature was performed in PubMed applying the Medical Subject Headings (MeSH) term "lymphangiography." For the review, the inclusion criterion was "studies with original data on Lipiodol-based Conventional Lymphangiography (CL) with subsequent Percutaneous Lymphatic Intervention (PLI)." Different exclusion criteria were defined (e.g., studies with <15 patients). The collected data comprised of clinical background and indications, procedural aspects and types of PLI, and outcomes. In the form of a pictorial essay, each author illustrated a clinical case with CL and/or PLI. RESULTS: Seven studies (corresponding to evidence level 4 [Oxford Centre for Evidence-Based Medicine]) accounting for 196 patients were included in the synthesis and analysis of data. Preceding surgery resulting in postoperative lymphorrhea included different surgical procedures such as extended oncologic surgery or vascular surgery. Central (e.g., chylothorax) and peripheral (e.g., lymphocele) types of postoperative lymphorrhea with a drainage volume of 100-4000 ml/day underwent CL with subsequent PLI. The intervals between "preceding surgery and CL" and between "CL and PLI" were 2-330 days and 0-5 days, respectively. CL was performed before PLI to visualize the lymphatic pathology (e.g., leakage point or inflow lymph ducts), applying fluoroscopy, radiography, and/or computed tomography (CT). In total, seven different types of PLI were identified: (1) thoracic duct (or thoracic inflow lymph duct) embolization, (2) thoracic duct (or thoracic inflow lymph duct) maceration, (3) leakage point direct embolization, (4) inflow lymph node interstitial embolization, (5) inflow lymph duct (other than thoracic) embolization, (6) inflow lymph duct (other than thoracic) maceration, and (7) transvenous retrograde lymph duct embolization. CL-associated and PLI-associated technical success rates were 97-100% and 89-100%, respectively. The clinical success rate of CL and PLI was 73-95%. CL-associated and PLI-associated major complication rates were 0-3% and 0-5%, respectively. The combined CL- and PLI-associated 30-day mortality rate was 0%, and the overall mortality rate was 3% (corresponding to six patients). In the pictorial essay, the spectrum of CL and/or PLI was illustrated. CONCLUSION: The radiological management of postoperative lymphorrhea is feasible, safe, and effective. Standardized radiological treatments embedded in an interdisciplinary concept are a step towards improving outcomes.

Standardized artificially created stable pertrochanteric femur fractures present more homogenous results compared to osteotomies for orthopaedic implant testing.

BACKGROUND: With regard to biomechanical testing of orthopaedic implants, there is no consensus on whether artificial creation of standardized bone fractures or their simulation by means of osteotomies result in more realistic outcomes. Therefore, the aim of this study was to artificially create and analyze in an appropriate setting the biomechanical behavior of standardized stable pertrochanteric fractures versus their simulation via osteotomizing. METHODS: Eight pairs of fresh-frozen human cadaveric femora aged 72.7 ± 14.9 years (range 48-89 years) were assigned in paired fashion to two study groups. In Group 1, stable pertrochanteric fractures AO/OTA 31-A1 were artificially created via constant force application on the anterior cortex of the femur through a blunt guillotine blade. The same fracture type was simulated in Group 2 by means of osteotomies. All femora were implanted with a dynamic hip screw and biomechanically tested in 20° adduction under progressively increasing physiologic cyclic axial loading at 2 Hz, starting at 500 N and increasing at a rate of 0.1 N/cycle. Femoral head fragment movements with respect to the shaft were monitored by means of optical motion tracking. RESULTS: Cycles/failure load at 15° varus deformation, 10 mm leg shortening and 15° femoral head rotation around neck axis were 11324 ± 848/1632.4 ± 584.8 N, 11052 ± 1573/1605.2 ± 657.3 N and 11849 ± 1120/1684.9 ± 612.0 N in Group 1, and 10971 ± 2019/1597.1 ± 701.9 N, 10681 ± 1868/1568.1 ± 686.8 N and 10017 ± 4081/1501.7 ± 908.1 N in Group 2, respectively, with no significant differences between the two groups, p ≥ 0.233. CONCLUSION: From a biomechanical perspective, by resulting in more consistent outcomes under dynamic loading, standardized artificial stable pertrochanteric femur fracture creation may be more suitable for orthopaedic implant testing compared to osteotomizing the bone.

Stratification of Fabry mutations in clinical practice: a closer look at α-galactosidase A-3D structure.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage and multi-system disorder due to mutations in the α-galactosidase A (α-GalA) gene. We investigated the impact of individual amino acid exchanges in the α-GalA 3D-structure on the clinical phenotype of FD patients. PATIENTS AND METHODS: We enrolled 80 adult FD patients with α-GalA missense mutations and stratified them into three groups based on the amino acid exchange location in the α-GalA 3D-structure: patients with active site mutations, buried mutations and other mutations. Patient subgroups were deep phenotyped for clinical and laboratory parameters and FD-specific treatment. RESULTS: Patients with active site or buried mutations showed a severe phenotype with multi-organ involvement and early disease manifestation. Patients with other mutations had a milder phenotype with less organ impairment and later disease onset. α-GalA activity was lower in patients with active site or buried mutations than in those with other mutations (P < 0.01 in men; P < 0.05 in women) whilst lyso-Gb3 levels were higher (P < 0.01 in men; <0.05 in women). CONCLUSIONS: The type of amino acid exchange location in the α-GalA 3D-structure determines disease severity and temporal course of symptom onset. Patient stratification using this parameter may become a useful tool in the management of FD patients.

Inter- and intra-observer variability of the AO/OTA classification for sternal fractures: a validation study.

INTRODUCTION: Recently, a new classification system for sternal fractures has been published in the Journal of Orthopedic trauma by the Arbeitsgemeinschaft für Osteosynthesefragen (AO) foundation and the Orthopaedic Trauma Association (OTA). The aim of this study was to evaluate inter- and intra-observer variability of the AO/OTA classification for sternal fractures. MATERIALS AND METHODS: Twenty multidetector computed tomography (CT) scans of patients with sternal fractures were classified independently by six senior and six junior orthopedic trauma surgeons of two level-1 trauma centers. Assessment was done on two occasions with an interval of 6 weeks. The kappa value was calculated to determine variability. RESULTS: The inter-observer variability of the AO/OTA classification for sternal fractures showed fair-to-moderate agreement (kappa = 0.364). There was no significant difference between junior and senior surgeons. Analyses of the separate components of the classification demonstrated that agreement was lowest for classifying fracture type within the sternal body (kappa = 0.319) followed by manubrium (kappa = 0.525). The intra-observer variability showed moderate agreement with a mean kappa of 0.414. CONCLUSION: The inter- and intra-observer variability of the AO/OTA classification for sternal fractures shows fair-to-moderate agreement. The overall performance of the classification might be improved with minor modifications. LEVEL OF EVIDENCE: Diagnostic cross-sectional study (level I).

Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a transient form of diabetes characterized by impaired insulin secretion and action during pregnancy. Population-based differences in prevalence exist which could be explained by phenotypic and genetic differences. The aim of this study was to examine these differences in pregnant women from Punjab, India and Scandinavia. METHODS: Eighty-five GDM/T2D loci in European and/or Indian populations from previous studies were assessed for association with GDM based on Swedish GDM criteria in 4018 Punjabi Indian and 507 Swedish pregnant women. Selected loci were replicated in Scandinavian cohorts, Radiel (N = 398, Finnish) and STORK/STORK-G (N = 780, Norwegian). RESULTS: Punjabi Indian women had higher GDM prevalence, lower insulin secretion and better insulin sensitivity than Swedish women. There were significant frequency differences of GDM/T2D risk alleles between both populations. rs7178572 at HMG20A, previously associated with GDM in South Indian and European women, was replicated in North Indian women. The T2D risk SNP rs11605924 in the CRY2 gene was associated with increased GDM risk in Scandinavian but decreased GDM risk in Punjabi Indian women. No other overlap was seen between GDM loci in both populations. CONCLUSIONS: Gestational diabetes mellitus is more common in Indian than Swedish women, which partially can be attributed to differences in insulin secretion and action. There was marked heterogeneity in the GDM phenotypes between the populations which could only partially be explained by genetic differences.

Abnormal α-synuclein deposits in skin nerves: intra- and inter-laboratory reproducibility.

BACKGROUND AND PURPOSE: Visualization of phosphorylated α-synuclein at serine 129 (p-syn) in skin nerves is a promising test for the in vivo diagnosis of synucleinopathies. Here the aim was to establish the intra- and inter-laboratory reproducibility of measurement of intraneural p-syn immunoreactivity in two laboratories with major expertise (Würzburg and Bologna). METHODS: In total, 43 patients affected by Parkinson's disease (PD 21 patients), dementia with Lewy bodies (DLB 1), rapid eye movement sleep behaviour disorder (RBD 11), multiple system atrophy (MSA-P 4) and small fibre neuropathy (SFN 6) were enrolled. Skin biopsy was performed at the C7 paravertebral spine region and distal skin sites (thigh or leg). The analysis was standardized in both laboratories and carried out blinded on a single skin section double stained with antibodies to p-syn and the pan-axonal marker protein gene product 9.5. Fifty skin sections were randomly selected for the analysis: 25 from C7 and 25 from distal sites. Differently classified sections were re-evaluated to understand the reasons for the discrepancy. RESULTS: The intra-laboratory analysis showed an excellent reproducibility both in Würzburg (concordance of classification 100% of sections; K = 1; P < 0.001) and Bologna (96% of sections; K = 0.92; P < 0.001). Inter-laboratory analysis showed reproducibility in 45 sections (90%; K = 0.8; P < 0.001) and a different classification in five sections, which was mainly due to fragmented skin samples or weak fluorescent signals. CONCLUSIONS: Analysis of p-syn showed excellent inter- and intra-laboratory reproducibility supporting the reliability of this technique. The few ascertained discordances were important to further improve the standardization of this technique.

Selective fasciotomy for acute traumatic lower leg compartment syndrome: is it feasible?

INTRODUCTION: The standard treatment for an acute compartment syndrome (ACS) of the lower leg is a four compartment fasciotomy. It can be performed through either one lateral or a lateral and medial incision. Selective fasciotomy, only opening the compartments with elevated pressure, is a less invasive procedure. The aim of this study was to describe a procedure of selective fasciotomy after pressure measurement and to determine its feasibility in a retrospective cohort study. METHODS: All patients with an ACS of the lower leg due to a proximal or tibia shaft fracture (AO 41 or 42) who received either a four compartment fasciotomy or a selective fasciotomy after pressure measurement between 2006 and 2016 were included. Every compartment with an intracompartment pressure of more than 30 mmHg was opened. The primary outcome was any missed compartment syndrome after selective fasciotomy. Secondary outcomes were reoperations for completing four compartment fasciotomy and persistent sensomotoric deficits. RESULTS: Fifty-one patients with a mean age of 43 years (6-76) were included. Of these, 41 (80%) had a selective fasciotomy. There was no missed compartment syndrome. One patient had a reoperation 8 h after primary selective fasciotomy due to ACS of the superficial and deep flexor compartment. The anterior compartment had to be released in all patients. In 67%, the release of 2 compartments was sufficient. Six patients had postoperative sensomotoric deficits at discharge with full recovery during follow-up. CONCLUSION: Selective fasciotomy is feasible and seems to be safe. Future comparative studies will have to focus on possible benefits of this less invasive treatment.

Long-term follow-up after MIPO Philos plating for proximal humerus fractures.

INTRODUCTION: Minimally invasive plate osteosynthesis (MIPO) has been described as a suitable technique for the treatment of proximal humerus fractures, but long-term functional results have never been reported. The aim of this study was to describe the long-term functional outcome and implant-related irritation after MIPO for proximal humerus fractures. METHODS: A long-term prospective cohort analysis was performed on all patients treated for a proximal humerus fracture using MIPO with a Philos plate (Synthes, Switzerland) between December 2007 and October 2010. The primary outcome was the QuickDASH score. Secondary outcome measures were the subjective shoulder value (SSV), implant related irritation and implant removal. RESULTS: Seventy-nine out of 97 patients (81%) with a mean age of 59 years were available for follow-up. The mean follow-up was 8.3 years (SD 0.8). The mean QuickDASH score was 5.6 (SD 14). The mean SSV was 92 (SD 11). Forty out of 79 patients (50.6%) had implant removal, and of those, 27/40 (67.5%) were due to implant-related irritation. On average, the implant was removed after 1.2 years (SD 0.5). In bivariate analysis, there was an association between the AO classification and the QuickDASH (p = 0.008). CONCLUSION: Treatment of proximal humerus fractures using MIPO with Philos through a deltoid split approach showed promising results. A good function can be assumed due to the excellent scores of patient oriented questionnaires. However, about one-third of the patients will have a second operation for implant removal due to implant-related irritation.

[Reduction techniques for osteosynthesis of intra-articular fractures]. / Repositionstechniken bei Osteosynthesen von artikulären Frakturen.

The cornerstones for treatment of articular fractures are gentle handling of soft tissues and anatomical reconstruction of the articular surface with stable fixation, which enables a functional aftercare. By respecting these principles, satisfactory functional and radiological results with low complication rates can be achieved even for complex fracture patterns. Fracture complexity varies with the energy load during the trauma mechanism. The personality of the fracture must be recognized and totally understood by the operating trauma surgeon. The soft tissue situation in particular is of decisive importance. The definition of a fracture as a soft tissue injury that happens to have a broken bone in it is generally accepted and the local soft tissue status is seen as extremely significant. The success or failure of the treatment correlates with the correct interpretation of the overall situation. Meticulous planning is therefore an indispensable prerequisite for operative fracture treatment. Successful fracture management depends on individualized decision making with respect to optimal timing of the operative intervention, reconstruction strategy of the articular surface, choice of surgical approach, reduction maneuver technique and choice of implant. This strategy must be adapted to individual-specific fracture patterns and the patient's general condition. The aim of this article is to provide an overview of the strategy and technique in management of articular fractures, with the main focus on reduction maneuver techniques.

[Reduction techniques for minimally invasive plate osteosynthesis]. / Repositionstechniken bei minimalinvasiven Plattenosteosynthesen.

The technique of fracture treatment by minimally invasive plate osteosynthesis (MIPO) is today part of the treatment repertoire of any experienced trauma surgeon. The minimization of any additional iatrogenic damage to the tissues and the preservation of the osteogenic fracture hematoma are the decisive differences to open reduction and internal fixation (ORIF). The MIPO technique is particularly applied in metaphyseal and diaphyseal fractures, which cannot be treated with intramedullary nails as well as in fractures with critical soft tissue covering and complex fractures with metaphyseal extension fractures. In metaphyseal and diaphyseal fractures a distinction must always be made between relatively simple (A/B1 type) and more complex (B2/3 and C type) fracture forms. In simple fracture forms, which are treated with minimally invasive plate osteosynthesis, an anatomical (or at least gap-free) reduction should be strived for. In contrast, in more complex metaphyseal and diaphyseal fractures achievement of correct functional alignment (correct axis, length and rotation) is the goal of reduction. The minimally invasive approach by the trauma surgeon in MIPO fracture treatment is mainly defined by the selected gentle reduction technique. Because the fracture zone cannot be directly viewed, good knowledge of the anatomy and careful surgical planning including reduction on an adequate image basis are of decisive importance. This article introduces the principles of the reduction techniques in minimally invasive plate osteosynthesis and their practical application is described in detail.

Detection of blood Gb3 deposits as a new tool for diagnosis and therapy monitoring in patients with classic Fabry disease.

BACKGROUND: The X-linked Fabry disease (FD) is a multiorgan disorder due to alpha-galactosidase A (α-GAL) deficiency with consequent lysosomal accumulation of globotriaosylceramide (Gb3). We established the immunocytochemical detection of Gb3 in blood cells of FD patients as a new method for FD diagnostics, follow-up and treatment control. METHODS: We enrolled 67 FD patients (37 men, 30 women) and 52 healthy controls (26 men, 26 women). PBMC were isolated from whole venous blood and 3x105 cells were immunoreacted with antibodies against CD77 as a marker for Gb3. Using fluorescence microscopy, the mean percentage of Gb3 positive PBMC was determined by an investigator blinded to subject allocation. As a second method, we qualitatively assessed Gb3 positive cells in blood smears. RESULTS: Gb3 deposits were unequivocally visible in PBMC and in blood smears. Men (P < 0.001) and women (P < 0.01) with classical FD had more Gb3-positive PBMC than healthy controls, whose samples only occasionally showed positive cells. The number of Gb3 positive PBMC was negatively correlated with α-GAL activity and positively correlated with plasma lyso-Gb3 levels. Only the PBMC Gb3 load but not plasma lyso-Gb3 reflected short- and long-term effects of enzyme replacement therapy (P < 0.01). CONCLUSIONS: Gb3 can be visualized in PBMC and blood smears and can be used as a novel marker for diagnostics, follow-up and treatment control in FD.

Spectroscopic investigations of a semi-synthetic [FeFe] hydrogenase with propane di-selenol as bridging ligand in the binuclear subsite: comparison to the wild type and propane di-thiol variants.

[FeFe] Hydrogenases catalyze the reversible conversion of H2 into electrons and protons. Their catalytic site, the H-cluster, contains a generic [4Fe-4S]H cluster coupled to a [2Fe]H subsite [Fe2(ADT)(CO)3(CN)2]2-, ADT = µ(SCH2)2NH. Heterologously expressed [FeFe] hydrogenases (apo-hydrogenase) lack the [2Fe]H unit, but this can be incorporated through artificial maturation with a synthetic precursor [Fe2(ADT)(CO)4(CN)2]2-. Maturation with a [2Fe] complex in which the essential ADT amine moiety has been replaced by CH2 (PDT = propane-dithiolate) results in a low activity enzyme with structural and spectroscopic properties similar to those of the native enzyme, but with simplified redox behavior. Here, we study the effect of sulfur-to-selenium (S-to-Se) substitution in the bridging PDT ligand incorporated in the [FeFe] hydrogenase HydA1 from Chlamydomonas reinhardtii using magnetic resonance (EPR, NMR), FTIR and spectroelectrochemistry. The resulting HydA1-PDSe enzyme shows the same redox behavior as the parent HydA1-PDT. In addition, a state is observed in which extraneous CO is bound to the open coordination site of the [2Fe]H unit. This state was previously observed only in the native enzyme HydA1-ADT and not in HydA1-PDT. The spectroscopic features and redox behavior of HydA1-PDSe, resulting from maturation with [Fe2(PDSe)(CO)4(CN)2]2-, are discussed in terms of spin and charge density shifts and provide interesting insight into the electronic structure of the H-cluster. We also studied the effect of S-to-Se substitution in the [4Fe-4S] subcluster. The reduced form of HydA1 containing only the [4Fe-4Se]H cluster shows a characteristic S = 7/2 spin state which converts back into the S = 1/2 spin state upon maturation with a [2Fe]-PDT/ADT complex.

Early life stress in mice is a suitable model for Irritable Bowel Syndrome but does not predispose to colitis nor increase susceptibility to enteric infections.

Neonatal period is characterized by an immature intestinal barrier. Scattered evidence suggests that early life stressful events induce long lasting alterations of intestinal homeostasis mimicking Irritable Bowel Syndrome (IBS). Those observations highlighting defect of intestinal barrier by early life stress questioned its potential role as a risk factor for gastrointestinal disorders such as colitis and infections. In this study, we aimed to analyze if maternal separation (MS) in mice mimicks IBS main features. We next addressed whether MS could trigger or exacerbate colitis in genetically predisposed mice and/or enhance susceptibility to gastrointestinal infections in wild type mice. MS induced main features of IBS in adult wild type male mice i.e. intestinal hyperpermeability, visceral hypersensitivity, microbiota dysbiosis, bile acid malabsorption and low grade inflammation in intestine associated with a defect of Paneth cells and the ILC3 population. This breach in mucosal barrier functions in adults was associated with a systemic IgG response against commensal E. coli and increased IFNγ secretion by splenocytes. However, in IL10-/- mice, MS did not trigger nor worsen colitis. Furthermore, wild type mice submitted to MS did not show increase susceptibility to gastrointestinal infections (S. Typhimurium, L. monocytogenes or T. gondii) compared to controls. Altogether, our results identify MS in mice as a good experimental model for IBS mimicking all the main features. In addition, early life stress, even though it has long lasting consequences on intestinal homeostasis, does not constitute a facilitating factor to colitis in predisposed individuals nor to gastrointestinal infections in wild type mice.

Decoding diagnosis and lifetime consumption in alcohol dependence from grey-matter pattern information.

OBJECTIVE: We investigated the potential of computer-based models to decode diagnosis and lifetime consumption in alcohol dependence (AD) from grey-matter pattern information. As machine-learning approaches to psychiatric neuroimaging have recently come under scrutiny due to unclear generalization and the opacity of algorithms, our investigation aimed to address a number of methodological criticisms. METHOD: Participants were adult individuals diagnosed with AD (N = 119) and substance-naïve controls (N = 97) ages 20-65 who underwent structural MRI. Machine-learning models were applied to predict diagnosis and lifetime alcohol consumption. RESULTS: A classification scheme based on regional grey matter attained 74% diagnostic accuracy and predicted lifetime consumption with high accuracy (r = 0.56, P < 10-10 ). A key advantage of the classification scheme was its algorithmic transparency, revealing cingulate, insular and inferior frontal cortices as important brain areas underlying classification. Validation of the classification scheme on data of an independent trial was successful with nearly identical accuracy, addressing the concern of generalization. Finally, compared to a blinded radiologist, computer-based classification showed higher accuracy and sensitivity, reduced age and gender biases, but lower specificity. CONCLUSION: Computer-based models applied to whole-brain grey-matter predicted diagnosis and lifetime consumption in AD with good accuracy. Computer-based classification may be particularly suited as a screening tool with high sensitivity.

[What can/should be treated in kidney tumors and when]. / Was kann/soll bei Nierentumoren wann behandelt werden.

CLINICAL/METHODICAL ISSUE: In the treatment of localized renal cell carcinoma, the lack of randomization in controlled trials on thermal ablation is a major limitation. The latter leads to significant study bias and it ultimately remains unclear whether the improved overall survival in favor of partial nephrectomy can actually be attributed to the treatment method. STANDARD RADIOLOGICAL METHODS: For T1a (≤4 cm) renal cell carcinoma without lymph node and distant metastases, excellent technical and clinical results have been described after imaging-guided radiofrequency ablation and cryoablation. METHODICAL INNOVATIONS: Low major complication rates, preservation of renal function and three-dimensional confirmation of negative ablation margins (A0 ablation) are the advantages of computed tomography (CT)-guided thermal ablation. PERFORMANCE: According to the results of controlled (non-randomized) trials on T1a renal cell cancer, the cancer-specific survival rates are comparable between ablative and surgical techniques. ACHIEVEMENTS: It is high time for prospective randomized controlled trials to define the actual value of percutaneous thermal ablation and partial nephrectomy in the treatment of T1a renal cell carcinoma. PRACTICAL RECOMMENDATIONS: Apart from localized renal cell carcinoma, angiomyolipoma and oncocytoma can be treated by thermal ablation. Transarterial embolization extends the radiological spectrum for the treatment of renal tumors, either as complementary embolization (e. g. before thermal ablation of T1a and T1b renal cell carcinoma), prophylactic embolization (e. g. angiomyolipoma >6 cm), preoperative embolization (e. g. before laparoscopic partial nephrectomy) or palliative embolization (e. g. in patients with symptomatic macrohematuria due to renal cell carcinoma).

[Definition, classification, clinical diagnosis and prognosis of fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Definition, Klassifikation, klinische Diagnose und Prognose des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: The clinical diagnosis of fibromyalgia syndrome can be established by the American College of Rheumatology (ACR) 1990 classification criteria (with examination of tender points) or without the examination of tender points by the modified preliminary diagnostic ACR 2010 or 2011 criteria.

[Etiology and pathophysiology of fibromyalgia syndrome : Updated guidelines 2017, overview of systematic review articles and overview of studies on small fiber neuropathy in FMS subgroups]. / Ätiologie und Pathophysiologie des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten sowie eine Übersicht über Studien zur Kleinfaserpathologie bei Subgruppen des FMS.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was planned for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Prospective population-based studies and systematic reviews with meta-analyses of case control studies were taken into consideration for the statements. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The statements were generated by multiple step formalized procedures. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS: Current data do not enable identification of distinct factors in the etiology and pathophysiology of fibromyalgia syndrome. Fibromyalgia syndrome can be associated with inflammatory rheumatic diseases, gene polymorphisms, life style factors (e.g. smoking, obesity and lack of physical activity), depressive disorders as well as physical and sexual abuse in childhood and adulthood. CONCLUSION: Fibromyalgia syndrome is most probably the end result of various pathogenetic factors and pathophysiological mechanisms.