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1.
Cerebellum ; 23(2): 341-354, 2024 Apr.
Article in English | MEDLINE | ID: mdl-36802021

ABSTRACT

Impairment of hand motor function is a frequent consequence after a stroke and strongly determines the ability to regain a self-determined life. An influential research strategy for improving motor deficits is the combined application of behavioral training and non-invasive brain stimulation of the motor cortex (M1). However, a convincing clinical translation of the present stimulation strategies has not been achieved yet. One alternative and innovative approach is to target the functionally relevant brain network-based architecture, e.g., the dynamic interactions within the cortico-cerebellar system during learning. Here, we tested a sequential multifocal stimulation strategy targeting the cortico-cerebellar loop. Anodal transcranial direct current stimulation (tDCS) was applied simultaneously to a hand-based motor training in N = 11 chronic stroke survivors during four training sessions on two consecutive days. The tested conditions were: sequential multifocal (M1-cerebellum (CB)-M1-CB) vs. monofocal control stimulation (M1-sham-M1-sham). Additionally, skill retention was assessed 1 and 10 days after the training phase. Paired-pulse transcranial magnetic stimulation data were recorded to characterize stimulation response determining features. The application of CB-tDCS boosted motor behavior in the early training phase in comparison to the control condition. No faciliatory effects on the late training phase or skill retention were detected. Stimulation response variability was related to the magnitude of baseline motor ability and short intracortical inhibition (SICI). The present findings suggest a learning phase-specific role of the cerebellar cortex during the acquisition of a motor skill in stroke and that personalized stimulation strategies encompassing several nodes of the underlying brain network should be considered.


Subject(s)
Stroke , Transcranial Direct Current Stimulation , Humans , Motor Skills/physiology , Hand , Stroke/therapy , Cerebellum/physiology
2.
Med Chem ; 17(8): 844-855, 2021.
Article in English | MEDLINE | ID: mdl-34061007

ABSTRACT

BACKGROUND: Alzheimer´s disease (AD) is characterized by a progressive neuronal degeneration caused by two pathological hallmarks, hyperphosphorylated tau protein aggregated into tau filaments and amyloid precursor protein derived beta amyloid peptides aggregated into extracellular amyloid plaques. All attempts so far to find effective drugs failed in clinical trials. AD is a multifactorial disease, so that selective drugs to target one AD-relevant structure alone may not be sufficient. OBJECTIVE: We built novel furopyridines with various substitution patterns to evaluate them as protein kinases inhibitors of enzymes related to tau pathology. METHODS: Furopyridine derivatives were synthesized and purified using column chromatography. The protein kinase inhibitory properties were determined in ATP-competition assays with determined affinity constants for the most active compounds. RESULTS: The compounds were prepared in simple two-component reactions of substituted 1,4- dihydropyridines and respective quinones to obtain various substitutions of the molecular furopyridine scaffold. The substituent effects on the determined kinase inhibitory properties of cdk1, cdk2, Fyn, JNK3 and gsk-3ß are discussed. CONCLUSION: Various 3-substitutions were found most sensitive for the protein kinase inhibition depending on the length, nature and a substituent positioning within. We identified compounds as inhibitors of several kinases as a tool to potentially combat the disease progress in a multitargeting approach.


Subject(s)
Alzheimer Disease/drug therapy , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Pyridines/chemistry , Pyridines/pharmacology , tau Proteins/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Phosphorylation/drug effects , Protein Kinase Inhibitors/therapeutic use , Pyridines/therapeutic use , Structure-Activity Relationship
3.
Opt Express ; 27(25): 36731-36740, 2019 Dec 09.
Article in English | MEDLINE | ID: mdl-31873446

ABSTRACT

Precision interferometry is the leading method for extremely sensitive measurements in gravitational wave astronomy. Thermal noise of dielectric coatings poses a limitation to the sensitivity of these interferometers. To decrease coating thermal noise, new crystalline GaAs/AlGaAs multilayer mirrors have been developed. To date, the surface figure and thickness uniformity of these alternative low-loss coatings has not been investigated. Surface figure errors, for example, cause small angle scattering and thereby limit the sensitivity of an interferometer. Here we measure the surface figure of highly reflective, substrate-transferred, crystalline GaAs/AlGaAs coatings with a custom scanning reflectance system. We exploit the fact that the reflectivity varies with the thickness of the coating. To increase penetration into the coating, we used a 1550 nm laser on a highly reflective coating designed for a center wavelength of 1064 nm. The RMS thickness variation of a two inch optic was measured to be 0.41 ± 0.05 nm. This result is within 10% of the thickness uniformity, of 0.37 nm RMS, achieved with ion-beam sputtered coatings for the aLIGO detector. We additionally measured a lower limit of the laser induced damage threshold of 64 MW/cm 2 for GaAs/AlGaAs coatings at a wavelength of 1064 nm.

4.
Nat Metab ; 1(3): 371-389, 2019 03.
Article in English | MEDLINE | ID: mdl-32694718

ABSTRACT

Obesity promotes the development of insulin resistance and increases the incidence of colitis-associated cancer (CAC), but whether a blunted insulin action specifically in intestinal epithelial cells (IECs) affects CAC is unknown. Here, we show that obesity impairs insulin sensitivity in IECs and that mice with IEC-specific inactivation of the insulin and IGF1 receptors exhibit enhanced CAC development as a consequence of impaired restoration of gut barrier function. Blunted insulin signalling retains the transcription factor FOXO1 in the nucleus to inhibit expression of Dsc3, thereby impairing desmosome formation and epithelial integrity. Both IEC-specific nuclear FoxO1ADA expression and IEC-specific Dsc3 inactivation recapitulate the impaired intestinal integrity and increased CAC burden. Spontaneous colonic tumour formation and compromised intestinal integrity are also observed upon IEC-specific coexpression of FoxO1ADA and a stable Myc variant, thus suggesting a molecular mechanism through which impaired insulin action and nuclear FOXO1 in IECs promotes CAC.


Subject(s)
Colonic Neoplasms/prevention & control , Forkhead Box Protein O1/metabolism , Insulin-Like Growth Factor I/metabolism , Insulin/metabolism , Intestinal Mucosa/metabolism , Animals , Colonic Neoplasms/metabolism , Diet, High-Fat , Gene Expression Regulation/physiology , Humans , Insulin/physiology , Intestinal Mucosa/cytology , Mice , Mice, Inbred C57BL , Signal Transduction
5.
PLoS One ; 13(3): e0194216, 2018.
Article in English | MEDLINE | ID: mdl-29522560

ABSTRACT

Dollar spot is one of the most common diseases of golf course turfgrass and numerous fungicide applications are often required to provide adequate control. Weather-based disease warning systems have been developed to more accurately time fungicide applications; however, they tend to be ineffective and are not currently in widespread use. The primary objective of this research was to develop a new weather-based disease warning system to more accurately advise fungicide applications to control dollar spot activity across a broad geographic and climactic range. The new dollar spot warning system was developed from data collected at field sites in Madison, WI and Stillwater, OK in 2008 and warning system validation sites were established in Madison, WI, Stillwater, OK, Knoxville, TN, State College, PA, Starkville, MS, and Storrs, CT between 2011 and 2016. A meta-analysis of all site-years was conducted and the most effective warning system for dollar spot development consisted of a five-day moving average of relative humidity and average daily temperature. Using this model the highest effective probability that provided dollar spot control similar to that of a calendar-based program across the numerous sites and years was 20%. Additional analysis found that the 20% spray threshold provided comparable control to the calendar-based program while reducing fungicide usage by up to 30%, though further refinement may be needed as practitioners implement this warning system in a range of environments not tested here. The weather-based dollar spot warning system presented here will likely become an important tool for implementing precision disease management strategies for future turfgrass managers, especially as financial and regulatory pressures increase the need to reduce pesticide usage on golf course turfgrass.


Subject(s)
Fungicides, Industrial , Plant Diseases/microbiology , Plant Diseases/prevention & control , Poaceae/microbiology , Weather , Fungicides, Industrial/pharmacology , Models, Statistical , Poaceae/drug effects , ROC Curve , Reproducibility of Results
6.
Rev Sci Instrum ; 88(11): 115008, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29195374

ABSTRACT

In this paper, the sensor noise of two geophone configurations (L-22D and L-4C geophones from Sercel with custom built amplifiers) was measured by performing two huddle tests. It is shown that the accuracy of the results can be significantly improved by performing the huddle test in a seismically quiet environment and by using a large number of reference sensors to remove the seismic foreground signal from the data. Using these two techniques, the measured sensor noise of the two geophone configurations matched the calculated predictions remarkably well in the bandwidth of interest (0.01 Hz-100 Hz). Low noise operational amplifiers OPA188 were utilized to amplify the L-4C geophone to give a sensor that was characterized to be near Johnson noise limited in the bandwidth of interest with a noise value of 10-11 m/Hz at 1 Hz.

7.
J Eur Acad Dermatol Venereol ; 31 Suppl 4: 12-30, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28656731

ABSTRACT

BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment and rehabilitation in different European countries. METHODS: A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks (synonyms: insurance against work accidents and occupational injuries; statutory social accident insurance)]. Legal standards for the assessment of occupationally triggered diseases with a genetic background differ between different countries, however, in most European member states recognition as OSD is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. CONCLUSION: OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness of this fact and further efforts for standardization are necessary.


Subject(s)
Occupational Diseases/therapy , Skin Diseases/therapy , Europe/epidemiology , Humans , Occupational Diseases/epidemiology , Skin Diseases/epidemiology , Surveys and Questionnaires
9.
Hautarzt ; 68(5): 377-384, 2017 May.
Article in German | MEDLINE | ID: mdl-28361252

ABSTRACT

BACKGROUND: The incidence of skin cancer continues to increase. However, little is known about the dermatosurgical characteristics of the patients. PATIENTS AND METHODS: In this single center, retrospective study, dermatosurgical reports of all patients treated because of basal cell carcinomas (BCC), squamous cell carcinomas (SCC), and malignant melanoma (MM) between 2004 and 2013 were analyzed. RESULTS: During the observed period, the number of operated BCC rose by a factor of 1.86 and the number of MM by a factor of 2.3. In comparison to BCC/MM, there was a disproportionately high increase of SCC by a factor of 4.02. The average age was 71.5 ± 13.4 years (minimum: 14 years; maximum: 104 years), whereupon a significant increase of male age and a significant decrease of female age occurred. Almost 70% of all tumors were located in the head and neck area. The nose was most commonly treated. CONCLUSIONS: During the last 10 years, the cohort of dermatosurgical patients changed in the tumor center. This should be verified in multicenter studies.


Subject(s)
Cancer Care Facilities/statistics & numerical data , Dermatologic Surgical Procedures/statistics & numerical data , Skin Neoplasms/epidemiology , Skin Neoplasms/surgery , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Cohort Studies , Female , Germany/epidemiology , Humans , Male , Middle Aged , Prevalence , Risk Factors , Sex Distribution , Young Adult
10.
Physiol Biochem Zool ; 90(2): 257-272, 2017.
Article in English | MEDLINE | ID: mdl-28277961

ABSTRACT

Sharks migrate annually over large distances and occupy a wide variety of habitats, complicating analysis of lifestyle and diet. A biogeochemical technique often used to reconstruct shark diet and environment preferences is stable isotope analysis, which is minimally invasive and integrates through time and space. There are previous studies that focus on isotopic analysis of shark soft tissues, but there are limited applications to shark teeth. However, shark teeth offer an advantage of multiple ecological snapshots and minimum invasiveness during removal because of their distinct conveyor belt tooth replacement system. In this study, we analyze δ13C and δ15N values of the organic matrix in leopard shark teeth (Triakis semifasciata) from a captive experiment and report discrimination factors as well as incorporation rates. We found differences in tooth discrimination factors for individuals fed different prey sources (mean ± SD; Δ13Csquid = 4.7‰ ± 0.5‰, Δ13Ctilapia = 3.1‰ ± 1.0‰, Δ15Nsquid = 2.0‰ ± 0.7‰, Δ15Ntilapia = 2.8‰ ± 0.6‰). In addition, these values differed from previously published discrimination factors for plasma, red blood cells, and muscle of the same leopard sharks. Incorporation rates of shark teeth were similar for carbon and nitrogen (mean ± SE; λC = 0.021 ± 0.009, λN = 0.024 ± 0.007) and comparable to those of plasma. We emphasize the difference in biological parameters on the basis of tissue substrate and diet items to interpret stable isotope data and apply our results to stable isotope values from blue shark (Prionace glauca) teeth to illustrate the importance of biological parameters to interpret the complex ecology of a migratory shark.


Subject(s)
Carbon/metabolism , Nitrogen/metabolism , Sharks/physiology , Tooth/chemistry , Animal Feed , Animals , Carbon Isotopes , Nitrogen Isotopes , Tooth/metabolism
11.
Klin Monbl Augenheilkd ; 233(12): 1324-1330, 2016 Dec.
Article in German | MEDLINE | ID: mdl-27984838

ABSTRACT

Optical coherence tomography (OCT) uses interference to image the retina with high axial resolution. In the last 25 years, new technologies have permitted a steady increase in imaging speed, which made it possible to enlarge the imaged field and to avoid motion artefacts. The speed and precision of retinal imaging is now limited by photodamage of the retina caused by the focused OCT beam and by the speed of the scanning mechanics. Full-field swept-source (FF-SS)-OCT decreases irradiance on the retina and dispenses moving parts by using a camera to acquire the full volume of the retina in parallel. Here we show that FF-SS-OCT is rapid and precise enough to image pulsation in the retina induced by the heart beat. Series of OCT volumes 1.8 × 0.7 mm wide and 1.8 mm deep were recorded in young volunteers over a few cycles of the heart beat. Morphology of the retinal vessels, blood flow and tissue motion as caused by vessel pulsation were calculated from the OCT data. FF-SS-OCT was able to visualise the main structures of the neuronal retina, including vessels and small capillaries and without any motion artefacts. Information on three different dynamic processes was obtained from only one recorded series of OCT volumes: pulsation of blood flow and blood pressure in retinal vessels as well as pulsation of the choroid. Delays between arterial and venous pulse and delay between pulsation in retinal and choroidal vessels were calculated. With a time resolution of 0.5 ms, FF-SS-OCT is able to visualise previously unmeasurably fast changes in the retina, including the propagation of pulse waves.


Subject(s)
Blood Flow Velocity/physiology , Blood Pressure/physiology , Image Interpretation, Computer-Assisted/methods , Pulsatile Flow/physiology , Retinal Vessels/physiology , Tomography, Optical Coherence/methods , Angiography/methods , Diagnostic Techniques, Ophthalmological , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity , Young Adult
12.
Int J Surg Case Rep ; 28: 348-351, 2016.
Article in English | MEDLINE | ID: mdl-27792978

ABSTRACT

INTRODUCTION: The clinical presentation of patients with soft-tissue sarcoma is highly variable. Most patients present with a painless mass, typically one that is increasing in size, and few have systemic symptoms such as fever, weight loss, or malaise. Soft tissue sarcomas can initially present as, or even be misdiagnosed as, deep venous thrombosis (DVT), leading to a late diagnosis. CASE REPORT: A 51-year-old woman presented to the hospital with complaints of pain and swelling in her left thigh, interpreted as an infected hematoma with an associated deep vein thrombosis and treated accordingly. The patient presented to our emergency department two more times. In the last visit and due to an unresolving clinical scenario a MRI and surgical byopsies were made that confirmed a sarcoma diagnosis. DISCUSSION: When a patient presents with an expanding, nontraumatic mass simulating a haematoma, several other differential diagnoses should be considered including aneurysm, bleeding tendency, chronic expanding haematoma and soft-tissue sarcoma. The growth of the tumor undetected while being treated for the DVT and then posteriorly for the hematoma, was without a doubt dismal to the patient, so earlier diagnosis would have been preferable. CONCLUSION: When a patient presents with an unusual history of hematoma in the extremities, it is necessary to consider the possibility of a malignant soft tissue tumor.

13.
Diagn Interv Imaging ; 97(4): 411-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26947187

ABSTRACT

PURPOSE: The purpose of our prospective study was to assess the presentation of Schmorl's nodes (SN) on magnetic resonance imaging (MRI) and investigate their possible association with demographic and clinical findings. MATERIALS AND METHODS: Three hundred and thirty-three patients were prospectively included. Thirteen (3.9%) patients were excluded because of contraindication to MRI and/or Scheuermann's disease. The final study population included 320 patients. T1-weighted and short TI inversion recovery sequences were performed to assess SN prevalence, the vertebral level and their anatomical distribution in vertebra. Medical history was recorded focusing on previous diseases including degenerative, rheumatoid and neoplastic disease, and any existing spinal traumatism. Epidemiological information was also obtained, including age, gender, ethnicity, professional and sporting activity. RESULTS: The final study population included 320 patients (172 men, 148 women) with a mean age of 54 years±17.5 (SD) (range: 19-87 years). A total of 421 SN were found in 158/320 patients (49.4%). SN were localized in thoracic spine for 48%, in lumbar spine for 46% and cervical spine for 6%. The middle part of the thoracic vertebra was the most affected area (80%), mostly in the middle superior endplate (41%). SN were more frequently observed in manual workers who worked more than 10 years (P<0.0001) and less frequently in patients of the 30-39-year-old age group (P=0.0048). No significant associations were found with gender (P=0.17) and remarkable medical history (P=0.21). SN were less frequently observed in patients with sport activities of 1-5hours/week (P=0.04) and those with an African origin (P<0.0001). CONCLUSION: Our study suggests a potential role for ethnical and physical factors in the pathogenesis of SN. Furthers studies are mandatory to evaluate their clinical relevance, especially in patients such as Caucasian manual workers in whom SN have a high prevalence.


Subject(s)
Intervertebral Disc Displacement/diagnostic imaging , Magnetic Resonance Imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Intervertebral Disc Displacement/epidemiology , Male , Middle Aged , Prospective Studies , Young Adult
14.
Mol Psychiatry ; 21(1): 49-61, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26503761

ABSTRACT

The brain's serotonergic system centrally regulates several physiological processes and its dysfunction has been implicated in the pathophysiology of several neuropsychiatric disorders. While in the past our understanding of serotonergic neurotransmission has come mainly from mouse models, the development of pluripotent stem cell and induced fibroblast-to-neuron (iN) transdifferentiation technologies has revolutionized our ability to generate human neurons in vitro. Utilizing these techniques and a novel lentiviral reporter for serotonergic neurons, we identified and overexpressed key transcription factors to successfully generate human serotonergic neurons. We found that overexpressing the transcription factors NKX2.2, FEV, GATA2 and LMX1B in combination with ASCL1 and NGN2 directly and efficiently generated serotonergic neurons from human fibroblasts. Induced serotonergic neurons (iSNs) showed increased expression of specific serotonergic genes that are known to be expressed in raphe nuclei. iSNs displayed spontaneous action potentials, released serotonin in vitro and functionally responded to selective serotonin reuptake inhibitors (SSRIs). Here, we demonstrate the efficient generation of functional human serotonergic neurons from human fibroblasts as a novel tool for studying human serotonergic neurotransmission in health and disease.


Subject(s)
Cytological Techniques/methods , Fibroblasts/physiology , Serotonergic Neurons/physiology , Animals , Astrocytes/physiology , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Line , Cell Transdifferentiation/physiology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , GATA2 Transcription Factor/genetics , GATA2 Transcription Factor/metabolism , Genetic Vectors , Homeobox Protein Nkx-2.2 , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Human Embryonic Stem Cells/physiology , Humans , LIM-Homeodomain Proteins/genetics , LIM-Homeodomain Proteins/metabolism , Lentivirus/genetics , Mice , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptome , Zebrafish Proteins
16.
Int J Surg Case Rep ; 16: 59-63, 2015.
Article in English | MEDLINE | ID: mdl-26421840

ABSTRACT

INTRODUCTION: The thyroid gland is a rare site of clinically detectable tumor metastasis. As thyroid tumors are usually assumed to be primary in origin, its recognition as a secondary is difficult. PRESENTATION OF CASE: We report a case of an 80-year old female who was referred to the Department of Surgery for a symptomatic thyroid nodule. Her medical history included a radical nephrectomy for renal cell carcinoma (RCC) nine years ago. During follow-up a pancreatic nodule was noted suggestive of a neuroendocrine tumor and the von Hippel-Lindau syndrome had to be ruled out. The fine-needle aspiration biopsy (FNAB) guided by ultrasound (US) of the thyroid nodule was inconclusive and a hemithyroidectomy and isthmectomy were performed. Histological examination revealed metastasis of a clear cell carcinoma. DISCUSSION: RCC disseminates in an unpredictable manner and can show late recurrences. Although secondary involvement of the thyroid gland by RCC is rare, it is still one of the more common neoplasms to metastasize to this site. There are no specific clinical features and few characteristic findings of metastatic thyroid carcinoma on imaging studies. FNAB is a useful procedure to diagnose metastatic thyroid cancer, but one should remain suspicious when the result for malignant cells is negative or indeterminate. After thyroidectomy the diagnosis of RCC is confirmed immunohistochemically. There is a clear survival benefit if a surgical approach to the thyroid metastasis is chosen. CONCLUSION: Thyroid metastasis should be considered in patients with a thyroid nodule and positive history for RCC.

17.
JBR-BTR ; 97(1): 11-6, 2014.
Article in English | MEDLINE | ID: mdl-24765764

ABSTRACT

OBJECTIVE: To assess the correlation of T2 mapping abnormalities to knee pain location, in young adults with normal standard knee MRI at 3.0 Tesla. SUBJECTS AND METHODS: Twenty-three consecutive patients were included prospectively from September 2011 to April 2012. Inclusion criteria were age under 50 years old, knee pain without surgical history, and normal knee MRI at 3.0 Tesla (sagittal T1-weighted images, and sagittal, axial and coronal proton-density-weighted images with saturation of fat signal). Ten asymptomatic volunteers were also included as a control group. Patients and controls had a cartilage T2 mapping MRI sequence in addition to the standard MRI protocol. Two musculoskeletal radiologists, blinded to the patient/control condition and pain location, independently reviewed the T2 mapping images. T2 values below 40 ms were considered normal. They rated the number of hyaline cartilage lesions and their grade according to an ICRS-like score (inspired by the International Cartilage Research Society score) in each anatomical compartment (medial and lateral femoro-tibial and anterior patello-femoral joints). In addition, the T2 value of the largest lesion was measured. Patient's pain location was classified in the following categories: anterior, lateral, medial and global. T2 mapping findings were compared to pain location, and retrospectively to the initial standard sequences. Sensitivity and specificity were calculated for MRI with T2 mapping according to pain location for each reader. Kappa coefficient was calculated for inter-reader agreement. We used variance analysis in a linear regression to compare T2 values and ICRS-like classification in each compartment. RESULTS: Sensitivity of MRI with T2 mapping, according to the symptomatic compartment, was respectively: 78% and 87% for Reader 1 and Reader 2 and specificity was 70% for both readers. Kappa coefficient for T2 mapping abnormalities location and pain location was good, with a calculated value of 0.64. There was no significant correlation between ICRS-like classification and T2 values of lesions (p = 0.18). CONCLUSION: Our results suggest that T2 mapping is an interesting MRI sequence for the exploration of young patients knee pain in case of normal MRI with a standard protocol, with a good correlation between pain location and focal prolongations of the cartilage T2 relaxation time.


Subject(s)
Cartilage Diseases/diagnosis , Cartilage, Articular/pathology , Knee Joint/pathology , Magnetic Resonance Imaging/methods , Pain/pathology , Adult , Cartilage Diseases/complications , Cartilage Diseases/pathology , Female , Humans , Image Interpretation, Computer-Assisted/methods , Male , Observer Variation , Pain/etiology , Prospective Studies , Sensitivity and Specificity
18.
Knee Surg Sports Traumatol Arthrosc ; 21(10): 2200-5, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23942882

ABSTRACT

PURPOSE: Patient-specific instrumentation (PSI) technology for the implantation of total knee arthroplasty (TKA) has a rising interest in the orthopaedic community. Data of PSI are controversially discussed. The hypothesis of this paper is that the radiological accuracy of CT-based PSI is similar to the one of navigated TKA published in the literature. METHODS: Since 2010, all 301 consecutively performed PSI TKAs (GMK MyKnee©) were included in this study. The radiological assessment consisted in a preoperative and postoperative standard X-ray and long-standing X-ray. Changes from the planned to the definitively implanted component size were documented. Postoperative analysis included limb alignment and position of femoral and tibial components (for varus/valgus and flexion or tibial slope). RESULTS: The postoperative average hip-knee-ankle angle was 180.1° ± 2.0°. In the frontal plane a total of 12.4 % of outliers >3°, for the tibial components 4.1 % of outliers >3° and for the femoral components 4.8 % of outliers >3° were measured. A total of 12.3 % of outliers for posterior tibial slope and 9 % of outliers >3° for the femoral flexion were noted. 10.8 % of the 602 planned size components were adapted intraoperatively. CONCLUSION: Although it is still unknown which limb axis is the correct one for the best clinical result, a technology providing the aimed axis in a most precise way should be chosen. Comparing the outcome of the current study with the data from the literature, there does not seem to be any difference compared to computer-assisted surgery. LEVEL OF EVIDENCE: IV.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Bone Malalignment/prevention & control , Knee Joint/diagnostic imaging , Postoperative Complications/prevention & control , Preoperative Care/methods , Surgery, Computer-Assisted/methods , Tomography, X-Ray Computed , Arthroplasty, Replacement, Knee/instrumentation , Bone Malalignment/diagnostic imaging , Bone Malalignment/etiology , Follow-Up Studies , Humans , Imaging, Three-Dimensional , Knee Joint/surgery , Knee Prosthesis , Outcome Assessment, Health Care , Postoperative Complications/diagnostic imaging , Preoperative Care/instrumentation , Retrospective Studies , Surgery, Computer-Assisted/instrumentation
19.
Curr Mol Med ; 13(5): 707-22, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23642053

ABSTRACT

The in vitro differentiation of human pluripotent stem cells represents a convenient approach to generate large numbers of neural cells for basic and translational research. We recently described the derivation of homogeneous populations of long-term self-renewing neuroepithelial-like stem cells from human pluripotent stem cells (lt-NES® cells). These cells constitute a suitable source of neural stem cells for in vitro modelling of early human neural development. Recent evidence demonstrates that microRNAs are important regulators of stem cells and nervous system development. Studies in several model organisms suggest that microRNAs contribute to different stages of neurogenesis - from progenitor self-renewal to survival and function of differentiated neurons. However, the understanding of the impact of microRNA-based regulation in human neural development is still at its dawn. Here, we give an overview on the current state of microRNA biology in stem cells and neural development and examine the role of the neural-associated miR-124, miR- 125b and miR-9/9* in human lt-NES® cells. We show that overexpression of miR-124, as well as overexpression of miR-125b, impair lt-NES® cell self-renewal and induce differentiation into neurons. Overexpression of the miR-9/9* locus also impairs self-renewal of lt-NES® cells and supports their commitment to neuronal differentiation. A detailed examination revealed that overexpression of miR-9 promotes differentiation, while overexpression of miR-9* affects both proliferation and differentiation of lt-NES® cells. This work provides insights into the regulation of early human neuroepithelial cells by microRNAs and highlights the potential of controlling differentiation of human stem cells by modulating the expression of selected microRNAs.


Subject(s)
MicroRNAs/physiology , Neurogenesis/genetics , Pluripotent Stem Cells/physiology , Animals , Brain/cytology , Brain/growth & development , Brain/metabolism , Cell Proliferation , Cells, Cultured , Gene Expression , Humans , Neural Stem Cells/physiology , RNA Interference
20.
Sportverletz Sportschaden ; 27(1): 21-7, 2013 Mar.
Article in German | MEDLINE | ID: mdl-23413019

ABSTRACT

BACKGROUND: The aim of this study is to provide a valid and reliable German version of the Tegner activity scale (Tegner-G). The Tegner activity scale assesses on 11 levels the activity in sports (competitive and recreational) and work of patients with anterior cruciate ligament injuries. The English original version was elaborated in Sweden and contains sports that are unknown in German-speaking countries. METHODS: The translation and adaptation was conducted in several steps according to the guidelines in the literature. The validity (discriminative validity and content validity) and (absolute and relative) reliability were determined in 46 patients after reconstruction of the anterior cruciate ligament and in 20 healthy subjects. The patients were divided into an acute group (< 3 months after operation; 11 men; 30.9 ± 8.3 years) and a chronic group (3 - 12 months after operation; 18 men; 31.3 ± 11.6 years). All subjects filled in the scale two times within 3 - 7 days. For the additional determination of the relation between activity and function, they also filled in the German version of the Lysholm score (Lysholm-G). RESULTS: The three groups differed significantly from each other (Kruskal-Wallis test: χ2 = 27.95, p < 0.001; post hoc Mann-Whitney U tests: acute-chronic p < 0.001; acute-control p < 0.001; chronic-control p = 0.003). There was a floor effect in the acute patient group. The intraclass correlation coefficients indicated a high relative reliability (ICC2,1 > 0.9). The minimal detectable change was 1.4 points. The relation between activity (Tegner-G) and function (Lysholm-G) was stronger in the acute than in the chronic patient group (ρ = 0.77 and ρ = 0.60, respectively). CONCLUSION: The psychometric properties of the Tegner-G are comparable to those of the English original version. The Tegner-G is thus valid and reliable for the German-speaking part of Switzerland. The application in other German-speaking countries probably requires adaptations for some of the sports included. The relation between activity and function changes depending on time since operation. This confirms that a comprehensive assessment of the outcome after an anterior cruciate ligament injury requires the separate assessment of both parameters.


Subject(s)
Activities of Daily Living , Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament/surgery , Knee Injuries/diagnosis , Knee Injuries/surgery , Outcome Assessment, Health Care/methods , Trauma Severity Indices , Adult , Germany , Humans , Male , Recovery of Function , Reproducibility of Results , Sensitivity and Specificity , Treatment Outcome
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