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Next-generation sequencing (NGS) assays can sensitively detect somatic variation, and increasingly can enable the identification of complex structural rearrangements. A subset of infantile spindle cell sarcomas, particularly congenital mesoblastic nephromas with classic or mixed histology, have structural rearrangement in the form of internal tandem duplications (ITD) involving EGFR. We performed prospective analysis to identify EGFR ITD through clinical or research studies, as well as retrospective analysis to quantify the frequency of EGFR ITD in pediatric sarcomas. Within our institution, three tumors with EGFR ITD were prospectively identified, all occurring in patients less than 1 year of age at diagnosis, including two renal tumors and one mediastinal soft tissue tumor. These three cases exhibited both cellular and mixed cellular and classic histology. All patients had no evidence of disease progression off therapy, despite incomplete resection. To extend our analysis and quantify the frequency of EGFR ITD in pediatric sarcomas, we retrospectively analyzed a cohort of tumors (n = 90) that were previously negative for clinical RT-PCR-based fusion testing. We identified EGFR ITD in three analyzed cases, all in patients less than 1 year of age (n = 18; 3/18, 17%). Here we expand the spectrum of tumors with EGFR ITD to congenital soft tissue tumors and report an unusual example of an EGFR ITD in a tumor with cellular congenital mesoblastic nephroma histology. We also highlight the importance of appropriate test selection and bioinformatic analysis for identification of this genomic alteration that is unexpectedly common in congenital and infantile spindle cell tumors.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Physical review / B 106(5), 054435 (2022). doi:10.1103/PhysRevB.106.054435, In ferromagnetic multilayers, a single laser pulse with a fluence above an optical nucleation threshold can create magnetic skyrmions, which are randomly distributed over the area of the laser spot. However, in order to study the dynamics of skyrmions and for their application in future data technology, a controllable localization of the skyrmion nucleation sites is crucial. Here, it is demonstrated that patterned reflective masks behind a thin magnetic film can be designed to locally tailor the optical excitation amplitudes reached, leading to spatially controlled skyrmion nucleation on the nanometer scale. Using x-ray microscopy, the influence of nanopatterned backside aluminum masks on the optical excitation is studied in two sample geometries with varying layer sequence of substrate and magnetic Co/Pt multilayer. Surprisingly, the masks' effect on suppressing or enhancing skyrmion nucleation reverses when changing this sequence. Moreover, optical near-field enhancements additionally affect the spatial arrangement of the nucleated skyrmions. Simulations of the spatial modulation of the laser excitation and the following heat transfer across the interfaces in the two sample geometries are employed to explain these observations. The results demonstrate a reliable approach to add nanometer-scale spatial control to optically induced magnetization processes on ultrafast timescales., Published by Inst., Woodbury, NY

We use the PAL FEL to obtain time and energy-resolved coherent diffractive images of the insulator-metal phase transition in VO2 with femtosecond time, and nanometer spatial resolution, enabling us to directly visualize the phase transition.

Synpolydactyly 1 (SPD; MIM# 186000), also called syndactyly type II (SDTY2), is a genetic limb malformation characterized by polydactyly with syndactyly involving the webbing of the third and fourth fingers, and the fourth and fifth toes. It is caused by heterozygous alterations in HOXD13 with incomplete penetrance and phenotypic variability. In our study, a five-generation family with an SPD phenotype was enrolled in our Rare Disease Genomics Protocol. A comprehensive examination of three generations using Illumina short-read whole-genome sequencing (WGS) did not identify any causative variants. Subsequent WGS using Pacific Biosciences (PacBio) long-read HiFi Circular Consensus Sequencing (CCS) revealed a heterozygous 27-bp duplication in the polyalanine tract of HOXD13. Sanger sequencing of all available family members confirmed that the variant segregates with affected individuals. Re-analysis of an unrelated family with a similar SPD phenotype uncovered a 21-bp (7-alanine) duplication in the same region of HOXD13. Although ExpansionHunter identified these events in most individuals in a retrospective analysis, low sequence coverage due to high GC content in the HOXD13 polyalanine tract makes detection of these events challenging. Our findings highlight the value of long-read WGS in elucidating the molecular etiology of congenital limb malformation disorders. This article is protected by copyright. All rights reserved.

Thermo-test devices are rarely used outside specialized pain centres because of high acquisition costs. Recently, a new, portable device ("Q-Sense") was introduced, which is less expensive but has reduced cooling capacity (20°C). We assessed the reliability/validity of the "Q-Sense" by comparing it with the Thermal Sensory Analyzer (TSA).Using a phantom-skin model, the physical characteristics of both devices were compared. The clinical performance was assessed in a multicentre study by performing Quantitative Sensory Testing (QST) in 121 healthy volunteers and 83 diabetic patients (Eudra-Med-No. CIV-12-05-006501).Both device types showed ~40% slower temperature ramps for heating/cooling than nominal data. Cold/warm detection thresholds (CDT, WDT) and heat pain thresholds (HPT) of healthy subjects did not differ between device types. Cold pain thresholds (CPT) were biased for Q-Sense by a floor effect (p .001). According to intraclass correlation coefficients (ICC), agreement between TSA and Q-Sense was good/excellent for CDT (ICC = 0.894) and WDT (ICC = 0.898), moderate for HPT (ICC = 0.525) and poor for CPT (ICC = 0.305). In diabetic patients, the sensitivity of Q-Sense to detect cold hypoesthesia was reduced in males60 years. Moderate correlations between thermal detection thresholds and morphological data from skin biopsies (n = 51) were similar for both devices.Physical characteristics of both thermo-test devices are similarly limited by the poor temperature conduction of the skin. The Q-Sense is useful for thermal detection thresholds but of limited use for pain thresholds. For full clinical use, the lower cut-off temperature should be set to ≤18°C.High purchase costs prevent a widespread use of thermo-test devices for diagnosing small fibre neuropathy. The air-cooled "Q-Sense" could be a lower cost alternative, but its technical/clinical performance needs to be assessed because of its restricted cut-off for cooling (20°C). This study provides critical information on the physical characteristics and the clinical validity/reliability of the Q-Sense compared to the "Thermal Sensory Analyzer" (TSA). We recommend lowering the cut-off value of the Q-Sense to ≤18°C for its full clinical use.

Seit 2015 konnen Ellenbogenendoprothesen und Radiuskopfprothesen inklusive der Hemiprothese des distalen Humerus und des Capitulumersatzes im Ellenbogen im Ellenbogenendoprothesenregister der Deutschen Vereinigung fur Schulter- und Ellenbogenchirurgie e. V. (DVSE) dokumentiert werden. Die bis 2018 dokumentierten Primarbogen wurden fur die vorliegende Arbeit ausgewertet. Insgesamt wurden 73 Ellenbogenendoprothesen und 56 Radiuskopfprothesen erfasst. Bei den Ellenbogenendoprothesen wurden eine Hemiprothese des distalen Humerus, 63 gekoppelte Totalendoprothesen ohne und 9 Totalendoprothesen mit Radiuskopfersatz implantiert. Von den 56 Radiuskopfprothesen wurde eine Monobloc- und 55 modulare Prothesen implantiert. Daten zur Geschlechterverteilung, Alter, Operationsindikation, operationstechnischen Details und Fruhkomplikationen wurden ausgewertet. Die bereits dokumentierten 73 Ellenbogenendoprothesen und 56 Radiuskopfprothesen stellen bereits einen guten Anfang dar. Die detaillierte Datenerhebung wird uns bei guter Dokumentation in Zukunft Analysen an groseren Kohorten erlauben.

This study investigated the clinical characteristics and somatosensory profiles of patients suffering from leprosy in Mumbai, India. A cross-sectional deep profiling study was conducted in 86 patients with leprosy (with and without pain) using an extensive battery of phenotyping measures including structured clinical examination, psychological state (General Health Questionnaire [GHQ-12]), and a quality-of-life condition-specific instrument (Brief Pain Inventory—short form). Quantitative sensory testing was performed according to the protocol of the German Research Network on Neuropathic Pain (DFNS) to assess the somatosensory profiles in the ulnar nerve innervation territory of all participants (dorsum of the hand). Reference data from 50 healthy Indian subjects were within the range of published DFNS values. Somatosensory profiles in leprosy patients with clinically or electroneurographically diagnosed neuropathy (with and without pain) revealed a profile of sensory loss to thermal and tactile stimuli combined with preservation of vibration and deep pressure detection. Sensory gain phenomena were not generally observed in patients with leprosy. In the group of subclinical neuropathy, a high degree of impaired thermal sensation was found, which could be clinically deployed to enhance identification of leprosy neuropathy at an early stage. Quantitative sensory testing can effectively document leprosy-associated neuropathy but does not distinguish between patients with or without pain. Patients with leprosy and neuropathic pain reported a poor quality of life and less psychological well-being compared with the pain-free patients with leprosy neuropathy.

Wolf–Hirschhorn syndrome (WHS) is a rare but recurrent microdeletion syndrome associated with hemizygosity of an interstitial segment of Chromosome 4 (4p16.3). Consistent with historical reports in which overlapping deletions defined a minimal critical region in WHS patients, recent reports from exome sequence analysis have provided further evidence that haploinsufficiency of a specific gene within this critical region, NSD2 (WHSC1), is causal for many features of the syndrome. In this report, we describe three unrelated patients with loss-of-function alterations in NSD2 who presented clinically with WHS features including intrauterine growth retardation and global developmental delay. Two of the three patients also had overlapping features of failure to thrive, short stature, constipation, and hypotonia. This series adds additional cases to expand the phenotypic spectrum of WHS and reports novel NSD2 variants.

Nylon monofilaments may substitute for German Research Network on Neuropathic Pain standards in tactile but not pinprick testing. Ramped stimuli are faster but underestimate thresholds due to reaction time artefacts., Introduction: Quantitative sensory testing is used to assess somatosensory function in humans. The protocol of the German Research Network on Neuropathic Pain (DFNS) provides comprehensive normative values using defined tools; however, some of these may not be feasible in low-resource settings. Objectives: To compare the standard DFNS devices for assessment of mechanosensory function to a low resource tool, the Sorri-Bauru-monofilaments. Methods: Mechanical detection thresholds (MDT), pain thresholds (MPT), and suprathreshold pinprick ratings (pain sensitivity: MPS) were measured over cheek, hand dorsum, and fingertip in 13 healthy subjects (7 female, aged 21–44 years). Mechanical detection threshold was assessed with DFNS standard glass monofilaments (0.25–512 mN, 0.5 mm tip) and nylon monofilaments (Sorri-Bauru; 0.5–3000 mN). MPT was assessed with DFNS standard cylindrical probes (8–512 mN, 0.25 mm tip), Sorri-Bauru monofilaments, and with ramped stimuli using an electronic von Frey aesthesiometer (10 mN/s or 100 mN/s, 0.20 mm tip). MPS was measured in response to stepped and ramped pinpricks (128 and 256 mN). Results: Mechanical detection thresholds were the same for DFNS and Sorri-Bauru monofilaments. For MPT, Sorri-Bauru filaments yielded lower values than PinPricks over face but not hand. Pain thresholds were higher at all test sites for ramped than stepped pinpricks (P < 0.01). Suprathreshold ratings were lower for ramped than stepped pinpricks (P < 0.05). Conclusion: Sorri-Bauru filaments are acceptable substitutes for DFNS standards in estimating tactile sensitivity, but are not consistent with standard probes for pinprick sensitivity because of their nonstandardized tips. Ramped stimuli overestimated MPT and underestimated MPS due to reaction time artefacts and therefore need their own normative values.

We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. (2019) at the genomic level using a different sequencing technology platform. The configuration of this gene fusion predicts the production of a kinase-activating JAK2 fusion protein, which would normally lead to a diagnosis of Philadelphia chromosome–like B-ALL (Ph-like B-ALL). However, the unusual presentation of eosinophilia led us to demonstrate the presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence in situ hybridization (FISH) studies with morphologic correlation. Therefore, we believe this disease, in fact, represents blast crisis arising from an underlying myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty in differentiating Ph-like B-ALL and myeloid/lymphoid neoplasm with eosinophilia and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the diagnosis of MLN-EGR relies on the hematologic presentations and the identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also define Ph-like B-ALL. Yet, our case does not conform to either condition. Therefore, the assessment for lineage restriction of gene rearrangements to reflect the pathophysiologic difference between B-ALL and MLN-EGR in blast crisis is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR with novel gene fusions.

Background: The purpose of this study was to characterize patients with chronic temporomandibular disorders (TMD) in terms of existing hyperalgesia against cold, heat and pressure. Methods: The extent of hyperalgesia for pressure and thermal sensation in TMD patients was determined by the use of the painDETECT questionnaire ("Is cold or heat in this area occasionally painful?” “Does slight pressure in this area, e.g., with a finger, trigger pain?") and experimental somatosensory testing against thermal and pressure stimuli (Quantitative Sensory Testing; QST). In addition, we explored psychological comorbidity among the chronic TMD patients (hospital anxiety and depression scale, HADS-D and coping strategies questionnaire, CSQ). Results: Nineteen patients with chronic TMD and 38 healthy subjects participated in the study. N = 12 patients had a painDETECT score ≤ 12, n = 3 patients had a painDETECT score of 13–18 and n = 4 patients had a painDETECT score ≥ 19. TMD patients with painDETECT scores ≥19 had moderately, strong or very strong enhancement of thermal and pressure pain perception, whereas patients with painDETECT scores 13–18 and ≤ 12 responded these questions with “never”, “hardly noticed” or “slightly painful” (p

Background Proximal radial fractures are common elbow injuries. Because of the fracture pattern, stability criteria, or plate configuration, a plate position outside the "safe zone" (SZ) may be required in some cases when performing a radial head plate osteosynthesis. We examined the gross anatomy of the radial head and analyzed different so-called low-profile and precontoured radial head and neck plates with respect to the SZ. Materials and methods Macroscopic measurements of the radial head and neck of 22 formalin-fixed human cadaveric upper extremities were obtained. The SZ was determined by maximum forearm rotation. If the edge of a plate could be extended beyond the respective SZ boundary without jeopardizing the proximal radioulnar joint (PRUJ) in maximum forearm rotation, a new plate-specific SZ boundary was set. Results The mean SZ was 133° (SD, 14°). Among the 5 plates studied, only the 2 radial neck designs allowed the anterior edge of the plate to partially pass the lesser sigmoid notch of the ulna and consequently afforded a significant extension of the SZ in maximum pronation. All 3 radial head designs had to remain within the SZ to avoid interference with the PRUJ. A safe plate position depends on individual plate dimensions, particularly the proximal plate width, and the diameter of the radial head. The smaller the head diameter, the more accurately a plate must be placed within the SZ. Conclusions If an extension of the SZ in radial head plate osteosynthesis is not essential, we recommend respecting the SZ to minimize the possibility of interference with the PRUJ.

Purpose To investigate the course and variability of the radial nerve along the lateral humerus in relation to the center of rotation of the elbow joint in the context of lateral pin placement for hinged external fixation. Methods A total of 95 formalin-fixed upper extremities were dissected. The course of the radial nerve along the lateral aspect of the humerus was measured at 3 landmarks with respect to the center of rotation of the elbow. We analyzed the data and the landmark positions correlated with the length of the humerus. Results The measured positions of 3 landmarks of the radial nerve in the lateral aspect of the humerus ranged from 19% to 43% of the length of the humerus and were located, on average, 6.0, 9.7, and 13.5 cm from the lateral center of rotation. Conclusions These data help predict the humeral course of the radial nerve and define a safe zone for pin implantation. However, because of variability in the course of the radial nerve, a safe zone cannot fully ensure prevention of iatrogenic injury to the nerve. The safest method of pin application remains mini-open dissection and visual implantation. Clinical relevance Based on this cadaveric study, it is not possible to define a rational safe zone. The safest method of pin application for dynamic external fixation of the elbow is to perform a mini-open dissection with direct visualization.

Sleep disturbances are highly prevalent in chronic pain patients. Understanding their relationship has become an important research topic since poor sleep and pain are assumed to closely interact. To date, human experimental studies exploring the impact of sleep disruption/deprivation on pain perception have yielded conflicting results. This inconsistency may be due to the large heterogeneity of study populations and study protocols previously used. In addition, none of the previous studies investigated the entire spectrum of nociceptive modalities. To address these shortcomings, a standardized comprehensive quantitative sensory protocol was used in order to compare the somatosensory profile of 14 healthy subjects (6 female, 8 male, 23.5 ± 4.1 year; mean ± SD) after a night of total sleep deprivation (TSD) and a night of habitual sleep in a cross-over design. One night of TSD significantly increased the level of sleepiness (P

Pain and other sensory signs in patients with restless legs syndrome (RLS) are still poorly understood, as most investigations focus on motor system dysfunctions. This study aimed to investigate somatosensory changes in patients with primary RLS and the restoration of somatosensory function by guideline-based treatment. Forty previously untreated RLS patients were investigated unilaterally over hand and foot using quantitative sensory testing (QST) and were compared with 40 age- and gender-matched healthy subjects. The predominant finding in RLS patients was 3- to 4-fold increase of sensitivity to pinprick stimuli in both extremities (hand: P

Hintergrund Die dynamischen Fixateure haben sich in der Therapie der Ellenbogeninstabilitaten etabliert. Bei der Fixierung der Systeme am Oberarm mittels Pins ist der N. radialis gefahrdet. Durch die direkte und indirekte Lasion des Nervs kann es zu temporaren aber auch dauerhaften Lahmungserscheinungen mit schwerwiegenden Konsequenzen fur den Patienten kommen. Ziel der vorliegenden Studie war es, den Verlauf des N. radialis in Relation zum Drehzentrum des Ellenbogengelenks darzustellen und die Variabilitat des Verlaufs zu analysieren.

The terms 'persistent idiopathic facial pain' (PIFP) and 'atypical odontalgia' (AO) are currently used as exclusion diagnoses for chronic toothache and chronic facial pain. Knowledge about these pain conditions in medical and dental practices is of crucial importance for the prevention of iatrogenic tissue damage by not-indicated invasive interventions, such as endodontic treatment and tooth extraction. In the present paper, etiology and pathogenesis, differential diagnostic criteria, and diagnostic approaches will be explained and relevant therapeutic principles will be outlined.

Objective Bruxism is discussed as an etiological factor in the pathogenesis of orofacial and cervical pain. As the sternocleidomastoid muscle (SCM) is co-activated during clenching, our aim was to investigate, whether the muscle loading leads to peripheral or central sensitizations. Design In twenty-one healthy female volunteers, somatosensory profiles of the SCM were recorded according to the test battery of the German Research Network on Neuropathic Pain (DFNS) prior to and after an isometric muscle exercise. QST comprised thermal and mechanical stimuli. A submaximal activation of the SCM (15% MVC) was kept for 10 min in sitting position. In separate test sessions one month apart, one sham and one verum experiment were conducted in randomized order. During the muscle loading, the parameters cold detection threshold (CDT), mechanical pain sensitivity (MPS) and pressure pain treshold (PPT) were tested and experimental pain recorded by visual analogoue scales (VAS). All test sessions were performed during the follicular phase of the menstrual cycle (day 5), to avoid effects on pain perception. Data were analyzed with Repeated Measures ANOVA (SPSS 22.0) Results No significant changes were found during or after (sham) loading except for stimulus-response-function (SR, P = 0.01) and PPT (P = 0.02) in the sham test. No effect was observed in the verum experiment (P = 0.12 up to 1.0). Conclusion Prolonged low level contraction of the SCM does not evoke painful sensitization. In contrast, submaximal muscle activation seems to have a protective effect corresponding to a training effect preventing sensitization.

Aims/hypothesis Obesity is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). The cytokine osteopontin (OPN) was recently shown to be involved in obesity-induced adipose tissue inflammation and reduced insulin response. Accumulating evidence links OPN to the pathogenesis of NAFLD. Here we aimed to identify the role of OPN in obesity-associated hepatic steatosis and impaired hepatic glucose metabolism. Methods Wild-type (WT) and Opn (also known as Spp1) knockout (Opn−/−) mice were fed a high-fat or low-fat diet to study OPN effects in obesity-driven hepatic alterations. Results We show that genetic OPN deficiency protected from obesity-induced hepatic steatosis, at least in part, by downregulating hepatic triacylglycerol synthesis. Conversely, absence of OPN promoted fat storage in adipose tissue thereby preventing the obesity-induced shift to ectopic fat accumulation in the liver. Euglycaemic–hyperinsulinaemic clamp studies revealed that insulin resistance and excess hepatic glucose production in obesity were significantly attenuated in Opn−/− mice. OPN deficiency markedly improved hepatic insulin signalling as shown by enhanced insulin receptor substrate-2 phosphorylation and prevented upregulation of the major hepatic transcription factor Forkhead box O1 and its gluconeogenic target genes. In addition, obesity-driven hepatic inflammation and macrophage accumulation was blocked by OPN deficiency. Conclusions/interpretation Our data strongly emphasise OPN as mediator of obesity-associated hepatic alterations including steatosis, inflammation, insulin resistance and excess gluconeogenesis. Targeting OPN action could therefore provide a novel therapeutic strategy to prevent obesity-related complications such as NAFLD and type 2 diabetes. Electronic supplementary material The online version of this article (doi:10.1007/s00125-011-2170-0) contains supplementary material, which is available to authorised users.

Quantitative sensory testing (QST) is the standardized assessment of the somatosensory system comprising all sensory submodalities. In the German Research Network on Neuropathic Pain (DFNS), a QST-battery consisting of 13 parameters has been established and nationwide normative data have been collected. In contrast to conventional electrophysiology, QST allows detecting negative and positive sensory signs of both large and small fiber systems. However, as a subjective psychophysical method it is critically dependent on patients'/healthy subjects' cooperation thus strictly standardized protocols and instructions are needed to allow across laboratory comparisons. To facilitate more widespread use of QST, the German Pain Society (DGSS) and the DFNS have initiated a certification procedure for QST quality standards. Therefore, structural, procedural criteria and outcome parameters were establishd and are hereby presented. By maintaining high quality standards, the certification of QST is intended to contribute to a better understanding of the mechanisms behind neuropathic pain syndromes and thereby improve patient care as well as sensory assessment in clinical studies on the treatment of neuropathic pain syndromes.

Quantitative Sensory Testing (QST) is a psychophysical method assessing the somatosensory nervous system. A premise for comparable results between laboratories is standardized testing. Its quality can be proven by analyzing healthy subjects, because their results should lie within confidence intervals estimated from large database samples. However, it is unclear how many abnormal values can be tolerated. Based on a binomial distribution, a tool for assessing samples of healthy subjects was developed to detect inclusion errors (inclusion of nonhealthy subjects) or measuring errors (inaccuracies in single QST parameters). Sensitivity and specificity of detecting inclusion errors were assessed in 431 healthy subjects and 833 patients with neuropathic pain syndromes from the German Research Network on Neuropathic Pain (DFNS) database. Measuring errors were simulated by raising all absolute values in a single parameter by 0.5 SD. We calculated optimal cutoff values for group sizes of 16 healthy subjects, as implemented in the DFNS certification procedures. The algorithm was applied in the certification process of 18 European QST laboratories. With a specificity of 95% and a sensitivity of 60%, inclusion errors can be assumed for ≥4 abnormal values per subject, whereas ≥6 abnormal values per QST parameter and laboratory indicate measuring errors. Subsequently, in the certification process of 5 of 18 centers, inclusion or measuring errors were detected. In most cases, inclusion errors were verified and reasons for measuring errors were illuminated by the centers. This underlines the usefulness and validity of our tool in quality assurance of QST laboratories using the DFNS protocol.

Secondary hyperalgesia is believed to be a key feature of “central sensitization” and is characterized by enhanced pain to mechanical nociceptive stimuli. The aim of the present study was to characterize, using EEG, the effects of pinprick stimulation intensity on the magnitude of pinprick-elicited brain potentials [event-related potentials (ERPs)] before and after secondary hyperalgesia induced by intradermal capsaicin in humans. Pinprick-elicited ERPs and pinprick-evoked pain ratings were recorded in 19 healthy volunteers, with mechanical pinprick stimuli of varying intensities (0.25-mm probe applied with a force extending between 16 and 512 mN). The recordings were performed before (T0) and 30 min after (T1) intradermal capsaicin injection. The contralateral noninjected arm served as control. ERPs elicited by stimulation of untreated skin were characterized by 1) an early-latency negative-positive complex peaking between 120 and 250 ms after stimulus onset (N120-P240) and maximal at the vertex and 2) a long-lasting positive wave peaking 400–600 ms after stimulus onset and maximal more posterior (P500), which was correlated to perceived pinprick pain. After capsaicin injection, pinprick stimuli were perceived as more intense in the area of secondary hyperalgesia and this effect was stronger for lower compared with higher stimulus intensities. In addition, there was an enhancement of the P500 elicited by stimuli of intermediate intensity, which was significant for 64 mN. The other components of the ERPs were unaffected by capsaicin. Our results suggest that the increase in P500 magnitude after capsaicin is mediated by facilitated mechanical nociceptive pathways.

CONCLUSIONS Traumatic nerve injuries are associated with distinct changes in somatosensory function. Clinicians need to know that such aberrant sensations are normal when treating patients who hav ...

Die diffuse dermale Angiomatose (DDA) ist eine erworbene gutartige vaskulare Neubildung mit schmerzhaften, unscharf begrenzten, lividen, oft zentral exulzerierten Plaques, die an das Krankheitsbild der reaktiven Angioendotheliomatose oder der Embolia cutis medicamentosa erinnern. Histologisch dominiert ein diffuses dermales Geflecht kapillarer, regular strukturierter Gefase. Endotheliale Atypien, atypische Mitosen oder Vaskulitiszeichen fehlen. Es wird uber eine 43-jahrige Frau berichtet, die wenige Tage nach operativer Entfernung einer Unterbauchfettschurze oberhalb der Operationsnarbe eine bizarre braunlich livide, rasch wachsende DDA entwickelte, die sich innerhalb von 12 Wochen ohne Residuen spontan zuruckbildete. Bislang 4-jahrige Rezidivfreiheit.

Der Morbus Coats ist charakterisiert durch teleangiektatische und aneurysmatische Gefasveranderungen der Retina und sekundare intra- und subretinale Exsudate. Meist ist durch fruhzeitige Therapie der Visus zu erhalten. In seltenen, fulminant verlaufenden Fallen konnen eine vollstandige Amotio retinae und Erblindung auftreten. Dieser Fall ist die erste Beschreibung eines Morbus Coats bei einem DiGeorge-Syndrom. Wir berichten uber einen 8jahrigen Jungen mit einem DiGeorge-Syndrom, bei dem nach einer Tympanoplastik Typ I starke Kopfschmerzen auftraten. Durch Ophthalmoskopie, Computertomographie und Kernspintomographie konnten ein Retinoblastom ausgeschlossen und ein Morbus Coats diagnostiziert werden. Diskussion: Die Ursache des Morbus Coats ist bis heute nicht geklart. Das Zusammentreffen mit dem DiGeorge-Syndrom ist wahrscheinlich zufallig.

Age- and gender-matched reference values are essential for the clinical use of quantitative sensory testing (QST). To extend the standard test sites for QST-according to the German Research Network on Neuropathic Pain-to the trunk, we collected QST profiles on the back in 162 healthy subjects. Sensory profiles for standard test sites were within normal interlaboratory differences. QST revealed lower sensitivity on the upper back than the hand, and higher sensitivity on the lower back than the foot, but no systematic differences between these trunk sites. Age effects were significant for most parameters. Females exhibited lower pressure pain thresholds (PPT) than males, which was the only significant gender difference. Values outside the 95% confidence interval of healthy subjects (considered abnormal) required temperature changes of >3.3-8.2 °C for thermal detection. For cold pain thresholds, confidence intervals extended mostly beyond safety cutoffs, hence only relative reference data (left-right differences, hand-trunk differences) were sufficiently sensitive. For mechanical detection and pain thresholds, left-right differences were 1.5-2.3 times more sensitive than absolute reference data. The most sensitive parameter was PPT, where already side-to-side differences >35% were abnormal. Compared to trunk reference data, patients with postherpetic neuralgia exhibited thermal and tactile deficits and dynamic mechanical allodynia, mostly without reduced mechanical pain thresholds. This pattern deviates from other types of neuropathic pain. QST reference data for the trunk will also be useful for patients with postthoracotomy pain or chronic back pain.

A newborn with severe microcephaly and a history of parental consanguinity was referred for cytogenetic analysis and subsequently for genetic evaluation. While a 46,XY karyotype was eventually obtained, premature chromosome condensation was observed. A head MRI confirmed primary microcephaly. This combination of features focused clinical interest on the MCPH1 gene and directed genetic testing by sequence analysis and duplication/deletion studies disclosed a homozygous deletion of exons 1-11 of the MCPH1 gene. This case illustrates a strength of standard cytogenetic evaluation in directing molecular testing to a single target gene in this disorder, allowing much more rapid diagnosis at a substantial cost savings for this family.

In 1979 a "new" syndrome characterized by X-linked inheritance, hypogonadism, gynecomastia, intellectual disability, obesity, and short stature was described. The now-36-year-old propositus was recently referred to the genetics clinic for profound intellectual disability. Fragile X testing initially demonstrated a duplication of the FMR1 region, and upon further testing we identified an Xq27.3-q28 8.05 Mb-long duplication responsible for a syndrome. Our report describes the molecular and clinical aspects of the X-linked syndrome. Our results suggest that male patients with intellectual disability, hypogonadism, short stature, and gynecomastia should be further investigated for rearrangements in the Xq27.3-q28 region. In the future, when more cases of the duplication are identified, it may become possible to more accurately determine the specific genes affected by overexpression and responsible for the phenotype.

The terms 'persistent idiopathic facial pain' (PIFP) and 'atypical odontalgia' (AO) are currently used as exclusion diagnoses for chronic toothache and chronic facial pain. Knowledge about these pain conditions in medical and dental practices is of crucial importance for the prevention of iatrogenic tissue damage by not-indicated invasive interventions, such as endodontic treatment and tooth extraction. In the present paper, etiology and pathogenesis, differential diagnostic criteria, and diagnostic approaches will be explained and relevant therapeutic principles will be outlined.

Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.

The author aims to explain the differences between European countries in the proportion of women working part-time and, more generally, to develop a theoretical approach for cross-national comparison of women's employment patterns. The concepts of a ‘gender contract’ and of the ‘family and integration model’ are used. It becomes clear that, in Germany, part-time work has been an important means for the modernisation of the gender contract concerning the family and integration model during the tertiarisation process. In Finland, where a family model based on partnership dominates, the sociocultural and institutional basis for this form of employment is almost entirely lacking. Tertiarisation did not lead to an expansion of part-time employment. It is argued that sociohistorical factors related to the industrialisation process are highly significant in the explanation of these differences. It is possible to distinguish ideal-typically two different models of the development of the industrial society, in which those factors are shaped and combined in a characteristic way. These different models lead to different types of gender contract and different chracteristic patterns of labour force behaviour, by women, in the transition to a service society.

Electrical high-frequency stimulation (HFS) of skin afferents elicits long-term potentiation (LTP)-like hyperalgesia in humans. Time courses were evaluated in the facilitating (homotopic) or facilitated (heterotopic) pathways to delineate the relative contributions of early or late LTP-like pain plasticity. HFS in healthy subjects (n=55) elicited highly significant pain increases to electrical stimuli via the conditioning electrode (to 145% of control, homotopic pain LTP) and to pinprick stimuli in adjacent skin (to 190% of control, secondary hyperalgesia). Individual time courses in subjects expressing a sufficient magnitude of hyperalgesia (>20% pain increase, n=28) revealed similar half-lives of homotopic pain LTP and secondary hyperalgesia of 6.9 h and 4.9 h (log(10) mean 0.839±0.395 and 0.687±0.306) and times to full recovery of 48 h and 24 h (log(10) mean 1.679±0.790 and 1.373±0.611). Time course and peak magnitudes were not correlated between (r=-0.19to+0.21, NS), nor within both readout (r=0.29 and 0.31, NS). In most subjects, time courses were consistent with early LTP1. Notably, in some subjects (10 of 28), estimated times to full recovery were much longer (>10 days), possibly indicating development of late LTP2-like pain plasticity. Dynamic mechanical allodynia (only present in 16 of 55 subjects) lasted for a shorter time than secondary hyperalgesia. Three different readouts of nociceptive central sensitization suggest that brief intense nociceptive input elicits early LTP1 of pain sensation (based on posttranslational modifications), but susceptible subjects may already develop longer-lasting late LTP2 (based on transcriptional modifications). These findings support the hypothesis that LTP may contribute to the development of persistent pain disorders.

The adaptor protein vinculin plays a key position in the formation of focal adhesions and regulates cell attachment. To study the turnover of vinculin in bone-derived cells, we expressed green fluorescent protein-tagged vinculin in primary bovine osteoblasts and examined the appearance of focal adhesions in cells exposed to laminar shear flow. Already 20 sec after application of shear stress fluorescently labelled focal adhesions became visible as small flashing dots at the periphery of cells. The number of newly formed focal adhesions per individual cell increased continuously over approximately 300 sec and then remained relatively stable. The assembly of focal adhesions in shear stress-stimulated osteoblasts was accompanied by a transient rise in intracellular calcium levels. The mean assembly time of an individual focal adhesion plaque was 32.2+/-2.2 sec and the mean disassembly time was 60.5+/-6.0 sec. The recruitment of vinculin to nascent focal adhesions was in the same range as the recovery half-life of GFP-vinculin at stable focal adhesions (13.0+/-2.0 sec). These data show that accumulation of GFP-vinculin in newly formed focal adhesions and its exchange from pre-existing, mature plaques are both rapid processes that occur in mechanically stimulated osteoblasts within less than one minute.

In January 2007 the American Medical Association added a new Current Procedural Terminology(R) (CPT) code, 96040, for "Medical Genetics and Genetic Counseling Services." In order to identify the impact of having this new code and to identify issues with implementation of the code, the National Society of Genetic Counselors (NSGC) CPT(R) Working Group surveyed NSGC members using an internet-based survey tool. The majority of respondents (94%) reported being aware of the new code and over half of the respondents (69%) said they were billing for genetic counseling. Approximately 24% of those billing reported using 96040. Many facilities are not using this code and the reported success of billing using 96040 is highly varied. Continued education may be beneficial to encourage reimbursement for 96040 and follow up is needed to assess the ongoing implementation and impact of the new CPT(R) code.

Some patients with myofascial pain from temporomandibular disorders (TMD) report pain in extra-trigeminal body regions. Our aim was to distinguish TMD as regional musculoskeletal pain syndrome (n=23) from a widespread pain syndrome (FMS; n=18) based on patients' tender point scores, pain drawings and quantitative sensory testing (QST) profiles. Referenced to 18 age- and gender-matched healthy subjects significant group differences for cold, pressure and pinprick pain thresholds, suprathreshold pinprick sensitivity and mechanical detection thresholds were found. Pain sensitivity in TMD patients ranged between those of FMS patients and healthy controls. The group of TMD patients was inhomogeneous with respect to their tender point count with an insensitive group (n=12) resembling healthy controls and a sensitive TMD group (n=9) resembling FMS patients. Nevertheless sensitive TMD patients did not fulfil diagnostic criteria for FMS in regard to widespread pain as shown by their pain drawings. TMD subgroups did not differ with respect to psychological parameters. The sensitive subgroup was more sensitive compared to healthy controls and to insensitive TMD patients in regard to their QST profile over all test areas as well as to their tenderness over orofacial muscles and trigeminal foramina. However, sensitive TMD patients had a short pain duration arguing against a transition from TMD to FMS over time. Data rather suggest an overlap in pathophysiology with FMS, e.g. a disturbance of central pain processing, in this subgroup of TMD patients. Those patients could be identified on the basis of their tender point count as an easy practicable screening tool.