Diagnosis and outcome following tenoscopic surgery of the digital flexor tendon sheath in German sports and pleasure horses

Background Digital flexor tendon sheath (DFTS) pathology is an important cause of lameness in horses. The outcome after surgical treatment is variable and depends on the exact diagnosis. Objectives To (1) describe the prevalence of lesions associated with lameness caused by nonseptic DFTS tenosynovitis in a large population of German sports and pleasure horses; (2) determine the sensitivity and specificity of diagnostic imaging techniques for identifying lesions within the DFTS with tenoscopic diagnosis being the gold standard; (3) explore associations between tenoscopically diagnosed lesions and signalment, purpose, and limb affected; and (4) describe the outcome following DFTS tenoscopy with nonseptic DFTS tenosynovitis in this population. Study design Retrospective case series. Methods Medical records of horses admitted for tenoscopic surgery of nonseptic DFTS tenosynovitis between 2011 and 2020 were reviewed. Follow‐up information was obtained via telephone contact. Sensitivity and specificity of ultrasonography and contrast tenography were determined using tenoscopic diagnosis as gold standard and univariable analysis was used to explore associations between signalment, case history, and tenoscopic diagnosis. Results Medical records from 131 horses were retrieved, of which 8 horses had bilateral disease and 6 horses were presented for tenoscopy on two separate occasions (3 for tenoscopy in the same limb, 3 in a different limb), thus, making a total of 145 limbs. Lesions were most commonly diagnosed in the deep (DDFT; n = 55 limbs) and superficial (SDFT; n = 55 limbs) digital flexor tendons. Manica flexoria (MF) lesions were detected in 44 limbs and palmar/plantar annular ligament (PAL) constriction in 99 limbs. In 36 limbs, only one structure within the DFTS was injured, whereas in 109 limbs a combination of lesions was noted, the most common being the combination of a SDFT lesion with PAL constriction. All affected limbs were examined with diagnostic ultrasonography; contrast tenography was performed in 86 limbs. For diagnosis of MF and DDFT tears, tenography was more sensitive (89% [confidence interval, CI: 65.4%–95.2%]; 72% [CI: 46.4%–89.3%], respectively) than specific (64% [CI: 52.5%–77.6%]; 53% [CI: 42.2%–73.3%], respectively) whereas ultrasonography was more specific (92% [CI: 84.5%–96.3%]; 92% [CI: 83.6%–96.0%]) with lower sensitivity (64% [CI: 47.7%–77.2%]; 54% [CI: 39.5%–67.9%]). For SDFT lesions, ultrasonography was highly specific (94% [CI: 86.9%–97.9%]) with lower sensitivity (66% [CI: 51.3%–77.4%]). Follow‐up information following first surgery was obtained for 118 horses (132 limbs): 18 (15.3%) of 118 horses remained chronically lame, 40 (33.8%) performed at a reduced level and 60 (50.8%) performed at the same or higher level following rehabilitation after tenoscopy. Horses with DDFT lesions had the poorest outcomes with only 36.6% returning to the same or higher level of exercise. Main limitations Retrospective analysis of clinical records and subjective outcome assessment based on owner follow‐up with potential recall bias. Findings on diagnostic imaging are impacted by many factors including equipment quality and operator expertise and experience. Conclusion Diagnostic imaging techniques were complimentary and contrast tenography was sensitive and ultrasonography was specific for the diagnosis of MF and DDFT lesions. Following tenoscopic surgery for nonseptic tenosynovitis of the DFTS, approximately half the cases were able to return to preinjury level of exercise

Hypothesis and theory : a pathophysiological concept of stroke-induced acute phase response and increased intestinal permeability leading to secondary brain damage

Gut integrity impairment leading to increased intestinal permeability (IP) is hypothesized to be a trigger of critically illness. Approximately 15–20% of human ischemic stroke (IS) victims require intensive care, including patients with impaired level of consciousness or a high risk for developing life-threatening cerebral edema. Local and systemic inflammatory reactions are a major component of the IS pathophysiology and can significantly aggravate brain tissue damage. Intracerebral inflammatory processes following IS have been well studied. Until now, less is known about systemic inflammatory responses and IS consequences apart from a frequently observed post-IS immunosuppression. Here, we provide a hypothesis of a crosstalk between systemic acute phase response (APR), IP and potential secondary brain damage during acute and subacute IS stages supported by preliminary experimental data. Alterations of the acute phase proteins (APPs) C-reactive protein and lipopolysaccharide-binding protein and serum level changes of antibodies directed against Escherichia coli-cell extract antigen (IgA-, IgM-, and IgG-anti-E. coli) were investigated at 1, 2, and 7 days following IS in ten male sheep. We found an increase of both APPs as well as a decrease of all anti-E. coli antibodies within 48 h following IS. This may indicate an early systemic APR and increased IP, and underlines the importance of the increasingly recognized gut-brain axis and of intestinal antigen release for systemic immune responses in acute and subacute stroke stages

Hypothesis and Theory: A Pathophysiological Concept of Stroke-Induced Acute Phase Response and Increased Intestinal Permeability Leading to Secondary Brain Damage

Gut integrity impairment leading to increased intestinal permeability (IP) is hypothesized to be a trigger of critically illness. Approximately 15–20% of human ischemic stroke (IS) victims require intensive care, including patients with impaired level of consciousness or a high risk for developing life-threatening cerebral edema. Local and systemic inflammatory reactions are a major component of the IS pathophysiology and can significantly aggravate brain tissue damage. Intracerebral inflammatory processes following IS have been well studied. Until now, less is known about systemic inflammatory responses and IS consequences apart from a frequently observed post- IS immunosuppression. Here, we provide a hypothesis of a crosstalk between systemic acute phase response (APR), IP and potential secondary brain damage during acute and subacute IS stages supported by preliminary experimental data. Alterations of the acute phase proteins (APPs) C-reactive protein and lipopolysaccharide-binding protein and serum level changes of antibodies directed against Escherichia coli-cell extract antigen (IgA-, IgM-, and IgG-anti-E. coli) were investigated at 1, 2, and 7 days following IS in ten male sheep. We found an increase of both APPs as well as a decrease of all anti- E. coli antibodies within 48 h following IS. This may indicate an early systemic APR and increased IP, and underlines the importance of the increasingly recognized gut-brain axis and of intestinal antigen release for systemic immune responses in acute and subacute stroke stages

Somatic Mutation Profiles of MSI and MSS Colorectal Cancer Identified by Whole Exome Next Generation Sequencing and Bioinformatics Analysis

BACKGROUND: Colorectal cancer (CRC) is with approximately 1 million cases the third most common cancer worldwide. Extensive research is ongoing to decipher the underlying genetic patterns with the hope to improve early cancer diagnosis and treatment. In this direction, the recent progress in next generation sequencing technologies has revolutionized the field of cancer genomics. However, one caveat of these studies remains the large amount of genetic variations identified and their interpretation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the first work on whole exome NGS of primary colon cancers. We performed 454 whole exome pyrosequencing of tumor as well as adjacent not affected normal colonic tissue from microsatellite stable (MSS) and microsatellite instable (MSI) colon cancer patients and identified more than 50,000 small nucleotide variations for each tissue. According to predictions based on MSS and MSI pathomechanisms we identified eight times more somatic non-synonymous variations in MSI cancers than in MSS and we were able to reproduce the result in four additional CRCs. Our bioinformatics filtering approach narrowed down the rate of most significant mutations to 359 for MSI and 45 for MSS CRCs with predicted altered protein functions. In both CRCs, MSI and MSS, we found somatic mutations in the intracellular kinase domain of bone morphogenetic protein receptor 1A, BMPR1A, a gene where so far germline mutations are associated with juvenile polyposis syndrome, and show that the mutations functionally impair the protein function. CONCLUSIONS/SIGNIFICANCE: We conclude that with deep sequencing of tumor exomes one may be able to predict the microsatellite status of CRC and in addition identify potentially clinically relevant mutations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Was reflektieren wir und wie reflektieren wir? – Reflexionsgegenstände und -zugänge in der multiparadigmatischen Lehrer*innenbildung

Faix A-C, te Poel K, Pieper M, Wahbe N. Was reflektieren wir und wie reflektieren wir? – Reflexionsgegenstände und -zugänge in der multiparadigmatischen Lehrer*innenbildung. Presented at the Reflexion in der Lehrkräftebildung. Empirisch - phasenübergreifend - interdisziplinär

Was reflektieren wir und wie reflektieren wir? Reflexion in der multiparadigmatischen Lehrkräftebildung

Faix A-C, te Poel K, Wahbe N, Pieper M. Was reflektieren wir und wie reflektieren wir? Reflexion in der multiparadigmatischen Lehrkräftebildung. In: Mientus L, Klempin C, Nowak A, eds. Reflexion in der Lehrkräftebildung: Empirisch - Phasenübergreifend - Interdisziplinär . Potsdamer Beiträge zur Lehrkräftebildung und Bildungsforschung. Vol 4. Potsdam: Universitätsverlag Potsdam; 2023: 47-52.In diesem Beitrag werden aus einer Metaperspektive vier verschiedene Reflexionsformate aus dem Bielefelder Projekt „BiProfessional“ der Qualitätsoffensive Lehrerbildung gegenübergestellt. Gemeinsamkeiten und Unterschiede werden mit Blick auf das Reflexionsverständnis, den Reflexionsgegenstand und den jeweiligen Zugang beschrieben. Am Ende des Beitrags werden Konsequenzen für eine multiparadigmatische Lehrkräftebildung aufgezeigt

Urinary Dickkopf-3 (DKK3) Is Associated with Greater eGFR Loss in Patients with Resistant Hypertension

Patients with resistant hypertension (HTN) demonstrate an increased risk of chronic kidney disease and progression to end-stage renal disease; however, the individual course of progression is hard to predict. Assessing the stress-induced, urinary glycoprotein Dickkopf-3 (uDKK3) may indicate ongoing renal damage and consecutive estimated glomerular filtration rate (eGFR) decline. The present study aimed to determine the association between uDKK3 levels and further eGFR changes in patients with resistant HTN. In total, 31 patients with resistant HTN were included. Blood pressure and renal function were measured at baseline and up to 24 months after (at months 12 and 24). uDKK3 levels were determined exclusively from the first available spot urine sample at baseline or up to a period of 6 months after, using a commercial ELISA kit. Distinctions between different patient groups were analyzed using the unpaired t-test or Mann–Whitney test. Correlation analysis was performed using Spearman’s correlation. The median uDKK3 level was 303 (interquartile range (IQR) 150–865) pg/mg creatinine. Patients were divided into those with high and low eGFR loss (≥3 vs. <3 mL/min/1.73 m²/year). Patients with high eGFR loss showed a significantly higher median baseline uDKK3 level (646 (IQR 249–2555) (n = 13) vs. 180 (IQR 123–365) pg/mg creatinine (n = 18), p = 0.0412 (Mann–Whitney U)). Alternatively, patients could be classified into those with high and low uDKK3 levels (≥400 vs. <400 pg/mg creatinine). Patients with high uDKK3 levels showed significantly higher eGFR loss (−6.4 ± 4.7 (n = 11) vs. 0.0 ± 7.6 mL/min/1.73 m2/year (n = 20), p = 0.0172 (2-sided, independent t-test)). Within the entire cohort, there was a significant correlation between the uDKK3 levels and change in eGFR at the latest follow-up (Spearman’s r = −0.3714, p = 0.0397). In patients with resistant HTN, high levels of uDKK3 are associated with higher eGFR loss up to 24 months later