RepoMed (Medizinische Hochschule Hannover)
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Diagnostic Accuracy for Periprosthetic Joint Infection Does Not Improve by a Combined Use of Glucose and Leukocyte Esterase Strip Reading as Diagnostic Parameters.
No full textThe diagnosis of periprosthetic infections (PJI) can be challenging in clinical practice because the clinical presentations of aseptic loosening and low-grade infections are similar. Semiquantitative evaluation of leukocyte esterase (LE) in synovial fluid using a urine strip test has already established itself as a diagnostic method over the past decade. The analysis of LE in synovial fluid leads to a high number of false-positive test results. In the present study, the value of a combined semiquantitative determination of glucose and LE in synovial fluid to improve the diagnosis of PJI was investigated. Over a 4-year period, 145 synovial samples were collected from patients who developed joint effusion after arthroplasty. LE and glucose test strips were considered as an index test for the diagnosis of PJI. A ++ or +++ LE and a negative glucose test strip reading were considered as positive test results. Modified diagnostic criteria for PJI as recommended by the Musculoskeletal Infection Society (MSIS) served as the reference test, except that intraoperative findings were excluded. Forty-six out of 145 samples were classified as septic complication according to the reference test. In regard to PJI, our data showed that combined use of LE and glucose strip test reading displayed a 98.0% specificity (95% confidence interval (CI): 95.2% to 100%), a 50% sensitivity (95% CI: 35.6% to 64.4%), a 92% positive predictive value (95% CI: 81.4% to 100.0%), and an 80.3% negative predictive value (95% CI: 73.2% to 87.4%). In contrast, the exclusive analysis of LE on the urine strip to diagnose PJI demonstrated a 90.9% specificity (95% CI: 85.2% to 96.6%), a 67.4% sensitivity (95% CI: 53.8% to 80.9%), a 77.5% positive predictive value (95% CI: 64.6% to 90.4%), and an 85.7% negative predictive value (5% CI: 79.0% to 92.4%). A combination of LE and glucose test pad reading is considered superior as a potential "rule-in" method for the diagnosis of PJI compared with LE test pad analysis alone. However, combined LE and glucose synovial fluid testing also demonstrated lower test sensitivity and thus diagnostic accuracy compared with LE analysis alone. Therefore, combined glucose and LE test pad analysis does not represent a sufficient diagnostic standard to exclude PJI with certainty
Wirkung proinflammatorischer Zytokine auf Betazellen generiert aus humanen pluripotenten Stammzellen
No full textEinfluss von Nabelschnurumschlingungen auf das neonatale Outcome und das Meinungsbild bei medizinischem Fachpersonal und schwangeren und nichtschwangeren Frauen
No full textPsychological and Psychopharmacological Interventions in Psychocardiology.
No full textPatients with mental disorders have an increased risk to develop cardiovascular disease (CVD), and CVD are frequently comorbid with especially adjustment, anxiety and depressive disorders. Therefore, clinicians need to be aware of effective and safe psychological and pharmacological treatment strategies for patients with comorbid CVD and mental disorders. Cognitive behavioral therapy and third-wave of cognitive-behavioral therapy are effective for patients with CVD and mental disorders. Internet-based psychological treatments may also be considered. In more severe cases, psychopharmacological drugs are frequently used. Although generally well tolerated and efficacious, drug- and dose-dependent side effects require consideration. Among antidepressants, selective serotonin reuptake inhibitors, selective serotonin and noradrenalin reuptake inhibitors, and newer antidepressants, such as mirtazapine, bupropion, agomelatine, and vortioxetine, can be considered, while tricyclic antidepressants should be avoided due to their cardiac side effects. Mood stabilizers have been associated with arrhythmias, and some first- and second-generation antipsychotics can increase QTc and metabolic side effects, although substantial differences exist between drugs. Benzodiazepines are generally safe in patients with CVD when administered short-term, and may mitigate symptoms of acute coronary syndrome. Laboratory and ECG monitoring is always recommended in psychopharmacological drug-treated patients with CVD. Presence of a heart disease should not exclude patients from necessary interventions, but may require careful risk-benefit evaluations. Effectively and safely addressing mental disorders in patients with CVD helps to improve both conditions. Since CVD increase the risk for mental disorders and vice versa, care providers need to screen for these common comorbidities to comprehensively address the patients' needs
Free L-Lysine and Its Methyl Ester React with Glyoxal and Methylglyoxal in Phosphate Buffer (100 mM, pH 7.4) to Form Nε-Carboxymethyl-Lysine, Nε-Carboxyethyl-Lysine and Nε-Hydroxymethyl-Lysine.
No full textGlyoxal (GO) and methylglyoxal (MGO) are highly reactive species formed in carbohydrate metabolism. Nε-Carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL) are considered to be the advanced glycation end-products (AGEs) of L-lysine (Lys) with GO and MGO, respectively. Here, we investigated the reaction of free L-lysine (Lys) with GO and MGO in phosphate buffer (pH 7.4) at 37 °C and 80 °C in detail in the absence of any other chemicals which are widely used to reduce Schiff bases. The concentrations of Lys, GO and MGO used in the experiments were 0.5, 2.5, 5.0, 7.5 and 10 mM. The reaction time ranged between 0 and 240 min. Experiments were performed in triplicate. The concentrations of remaining Lys and of CML and CEL formed in the reaction mixtures were measured by stable-isotope dilution gas chromatography-mass spectrometry (GC-MS). Our experiments showed that CML and CEL were formed at higher concentrations at 80 °C compared to 37 °C. CML was found to be the major reaction product. In mixtures of GO and MGO, MGO inhibited the formation of CML from Lys (5 mM) in a concentration-dependent manner. The highest CML concentration was about 300 µM corresponding to a reaction yield of 6% with respect to Lys. An addition of Lys to GO, MGO and their mixtures resulted in strong reversible decreases in the Lys concentration up to 50%. It is assumed that free Lys reacts rapidly with GO and MGO to form many not yet identified reaction products. Reaction mixtures of Lys and MGO were stronger colored than those of Lys and GO, notably at 80 °C, indicating higher reactivity of MGO towards Lys that leads to polymeric colored MGO species. We have a strong indication of the formation of Nε-(hydroxymethyl)-lysine (HML) as a novel reaction product of Lys methyl ester with MGO. A mechanism is proposed for the formation of HML from Lys and MGO. This mechanism may explain why Lys and GO do not react to form a related product. Preliminary analyses show that HML is formed at higher concentrations than CEL from Lys methyl ester and MGO. No Schiff bases or their hydroxylic precursors were identified as reaction products. In their reactions with Lys, GO and MGO are likely to act both as chemical oxidants on the terminal aldehyde group to a carboxylic group (i.e., R-CHO to R-COOH) and as chemical reductors on labile Schiff bases (R-CH=N-R to R-CH2-NH-R) presumably via disproportionation and hydride transfer. Our study shows that free non-proteinic Lys reacts with GO and MGO to form CML, CEL and HML in very low yield. Whether proteinic Lys also reacts with MGO to form HML residues in proteins remains to be investigated. The physiological occurrence and concentration of HML in biological fluids and tissues and its relation to CML and CEL are elusive and warrant further investigations in health and disease. Chemical synthesis and structural characterization of HML are expected to advance and accelerate the scientific research in this topic
From Macroscopy to Ultrastructure: an Integrative Approach to Pulmonary Pathology
No full textPathology and radiology are complimentary tools, and their joint application is often crucial in obtaining an accurate diagnosis in non-neoplastic pulmonary diseases. However, both come with significant limitations of their own: Computed Tomography (CT) can only visualize larger structures due to its inherent-relatively-poor resolution, while (histo) pathology is often limited due to small sample size and sampling error and only allows for a 2D investigation. An innovative approach of inflating whole lung specimens and subjecting these subsequently to CT and whole lung microCT allows for an accurate matching of CT-imaging and histopathology data of exactly the same areas. Systematic application of this approach allows for a more targeted assessment of localized disease extent and more specifically can be used to investigate early mechanisms of lung diseases on a morphological and molecular level. Therefore, this technique is suitable to selectively investigate changes in the large and small airways, as well as the pulmonary arteries, veins and capillaries in relation to the disease extent in the same lung specimen. In this perspective we provide an overview of the different strategies that are currently being used, as well as how this growing field could further evolve
Implementation of Mobile Psychological Testing on Smart Devices: Evaluation of a ResearchKit-Based Design Approach for the Implicit Association Test.
No full textObjective To determine whether a framework-based approach for mobile apps is appropriate for the implementation of psychological testing, and equivalent to established methods. Methods Apple's ResearchKit was used for implementing native implicit association test methods (IAT), and an exemplary app was developed to examine users' implicit attitudes toward overweight or thin individuals. For comparison, a web-based IAT app, based on code provided by Project Implicit, was used. Adult volunteers were asked to test both versions on an iPad with touch as well as keyboard input (altogether four tests per participant, random order). Latency values were recorded and used to calculate parameters relevant to the implicit setting. Measurements were analyzed with respect to app type and input method, as well as test order (ANOVA and χ2 tests). Results Fifty-one datasets were acquired (female, n = 21; male, n = 30, average age 35 ± 4.66 years). Test order and combination of app type and input method influenced the latency values significantly (both P<0.001). This was not mirrored for the D scores or average number of errors vs. app type combined with input method (D scores: P = 0.66; number of errors: P = 0.733) or test order (D scores: P = 0.096; number of errors: P = 0.85). Post-hoc power analysis of the linear ANOVA showed 0.8 by f 2=0.25, with α = 0.05 and 4 predictors. Conclusions The results suggest that a native mobile implementation of the IAT may be comparable to established implementations. The validity of the acquired measurements seems to depend on the properties of the chosen test rather than the specifics of the chosen platform or input method
Intraneural Ganglion of the Peroneal Nerve—A Rare Cause of Pediatric Peroneal Nerve Palsy: a case report
No full textIntraneural ganglia are benign mucinous cysts located within the epineurium of a peripheral nerve. The pathogenesis and formation of intraneural ganglia are controversial. Themain theories described in the literature are of degenerative, synovial or de novo occurrence. We present the case of a 14-year-old boy who presented in our outpatient clinic with a complaint of interdigital neuralgia between hallux and second toe, as well as left foot drop. MRI examination showed a hyperintense cystic distension of the common peroneal nerve measuring 130mm5mm extending from the poplitea to the anterior compartment of the leg. We performed microscopic decompression and neurolysis surgery. The cyst showed a sac-like distension at its distal end with connection to the tibiofibular joint and was resected. After 8 weeks, postoperatively, the boy claimed to be pain-free and slight recovery of the superficial peroneal nerve was noticed. At 6 months postoperative, the patient showed a continuous improvement of motor function, demonstrating foot eversion with 3/5 muscle strength foot extension with 2/5 muscle strength. Intraneural ganglia reported for pediatric patients represent a very rare entity. To the best of our knowledge, less than 15 cases have been described within the English-speaking literature. receive
Challenges of CRISPR-Based Gene Editing in Primary T Cells.
No full textAdaptive T-cell immunotherapy holds great promise for the successful treatment of leukemia, as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T-cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system, allowing for the deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs that were important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches
To Be or Not to Be: the Divergent Action and Metabolism of Sphingosine-1 Phosphate in Pancreatic Beta-Cells in Response to Cytokines and Fatty Acids.
No full textSphingosine-1 phosphate (S1P) is a bioactive sphingolipid with multiple functions conveyed by the activation of cell surface receptors and/or intracellular mediators. A growing body of evidence indicates its important role in pancreatic insulin-secreting beta-cells that are necessary for maintenance of glucose homeostasis. The dysfunction and/or death of beta-cells lead to diabetes development. Diabetes is a serious public health burden with incidence growing rapidly in recent decades. The two major types of diabetes are the autoimmune-mediated type 1 diabetes (T1DM) and the metabolic stress-related type 2 diabetes (T2DM). Despite many differences in the development, both types of diabetes are characterized by chronic hyperglycemia and inflammation. The inflammatory component of diabetes remains under-characterized. Recent years have brought new insights into the possible mechanism involved in the increased inflammatory response, suggesting that environmental factors such as a westernized diet may participate in this process. Dietary lipids, particularly palmitate, are substrates for the biosynthesis of bioactive sphingolipids. Disturbed serum sphingolipid profiles were observed in both T1DM and T2DM patients. Many polymorphisms were identified in genes encoding enzymes of the sphingolipid pathway, including sphingosine kinase 2 (SK2), the S1P generating enzyme which is highly expressed in beta-cells. Proinflammatory cytokines and free fatty acids have been shown to modulate the expression and activity of S1P-generating and S1P-catabolizing enzymes. In this review, the similarities and differences in the action of extracellular and intracellular S1P in beta-cells exposed to cytokines or free fatty acids will be identified and the outlook for future research will be discussed