In‐situ characterization of deposits in ceramic hollow fiber membranes by compressed sensing RARE‐MRI

Ultrafiltration with ceramic hollow fiber membranes was investigated by compressed sensing rapid acquisition relaxation enhancement (CS-RARE) magnetic resonance imaging (MRI) to characterize filtration mechanisms. Sodium alginate was used as a model substance for extracellular polymeric substances. Dependent on the concentration of divalent ions like Ca21 in an aqueous alginate solution, the characteristics of the filtration change from concentration polarization to a gel layer. The fouling inside the membrane lumen could be measured by MRI with a CS-RARE pulse sequence. Contrast agents have been used to get an appropriate contrast between deposit and feed. The lumen was analyzed quantitatively by exploring the membrane’s radial symmetry, and the resulting intensity could be modeled. Thus, different fouling mechanisms could be distinguished. CS-RARE-MRI was proven to be an appropriate in situ tool to quantitatively characterize the deposit formation during in-out filtration processes. The results were underlined by flux interruption experiments and length dependent studies, which make it possible to differentiate between gel layer or cake filtration and concentration polarization filtration processes

Corticosteroid injection for tennis elbow or lateral epicondylitis: a review of the literature

Lateral epicondylitis or tennis elbow is a painful and functionally limiting entity affecting the upperextremity and is frequently treated by hand surgeons. Corticosteroid injection is one of the most common interventions for lateral epicondylitis or tennis elbow. Here, a review of the medical literature on this treatment is presented

Common extensor origin release in recalcitrant lateral epicondylitis - role justified?

The aim of our study was to analyse the efficacy of operative management in recalcitrant lateral epicondylitis of elbow. Forty patients included in this study were referred by general practitioners with a diagnosis of tennis elbow to the orthopaedic department at a district general hospital over a five year period. All had two or more steroid injections at the tender spot, without permanent relief of pain. All subsequently underwent simple fasciotomy of the extensor origin. Of forty patients thirty five had improvement in pain and function, two had persistent symptoms and three did not perceive any improvement. Twenty five had excellent, ten had well, two had fair and three had poor outcomes (recurrent problem; pain at rest and night). Two patients underwent revision surgery. Majority of the patients had improvement in pain and function following operative treatment. In this study, an extensor fasciotomy was demonstrated to be an effective treatment for refractory chronic lateral epicondylitis; however, further studies are warranted

Immunogenicity of prostate cancer is augmented by BET bromodomain inhibition

Abstract Background Prostate cancer responds poorly to current immunotherapies. Epigenetic therapies such as BET Bromodomain inhibition can change the transcriptome of tumor cells, possibly making them more immunogenic and thus susceptible to immune targeting. Methods We characterized the effects of BET bromodomain inhibition using JQ1 on PD-L1 and HLA-ABC expression in two human prostate cell lines, DU145 and PC3. RNA-Seq was performed to assess changes on a genome-wide level. A cytotoxic T cell killing assay was performed in MC38-OVA cells treated with JQ1 to demonstrate increased immunogenicity. In vivo experiments in the Myc-Cap model were conducted to show the effects of JQ1 administration in concert with anti-CTLA-4 checkpoint blockade. Results Here, we show that targeting BET bromodomains using the small molecule inhibitor JQ1 decreased PD-L1 expression and mitigated tumor progression in prostate cancer models. Mechanistically, BET bromodomain inhibition increased MHC I expression and increased the immunogenicity of tumor cells. Transcriptional profiling showed that BET bromodomain inhibition regulates distinct networks of antigen processing and immune checkpoint molecules. In murine models, treatment with JQ1 was additive with anti-CTLA-4 immunotherapy, resulting in an increased CD8/Treg ratio. Conclusions BET Bromodomain inhibition can mediate changes in expression at a genome wide level in prostate cancer cells, resulting in an increased susceptibility to CD8 T cell targeting. These data suggest that combining BET bromodomain inhibition with immune checkpoint blockade may have clinical activity in prostate cancer patients.https://deepblue.lib.umich.edu/bitstream/2027.42/152251/1/40425_2019_Article_758.pd

Extensor tendon release in tennis elbow: results and prognostic factors in 80 elbows

Purpose The objectives of this study were to evaluate the results in the outpatient treatment of recalcitrant lateral epicondylitis with release of the common extensor origin according to Hohmann and to determine any prognostic factors. Methods Eighty tennis elbows in 77 patients with a characteristic history of activity-related pain at the lateral epicondyle interfering with the activities of daily living refractory to conservative care for at least 6 months and a confirmatory physical examination were included. Clinical outcome was evaluated using the QuickDASH score system. Data were collected before the operation and at the medians of 18 months (range 6–36 months; short term) and 4 years (range 3–6 years; medium term) postoperatively. Results The mean QuickDASH was improved both at the short- and the medium-term follow-ups and did not change significantly between the follow-ups. At the final followup, the QuickDASH was improved in 78 out of 80 elbows and 81% was rated as excellent or good (QuickDASH\40 points). We found a weak correlation between residual symptoms (a high QuickDASH score) at the final follow-up and high level of baseline symptoms (r = 0.388), acute occurrence of symptoms (r = 0.362), long duration of symptoms (r = 0.276), female gender (r = 0.269) and young age (r = 0.203), whereas occurrence in dominant arm, a work-related cause or strenuous work did not correlate significantly with the outcome. Conclusion Open lateral extensor release performed as outpatient surgery results in improved clinical outcome at both short- and medium-term follow-ups with few complications. High baseline disability, sudden occurrence of symptoms, long duration of symptoms, female gender and young age were found to be weak predictors of poor outcome

Phenotypic and Functional Properties of Helios+ Regulatory T Cells

Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios+ and Helios− Treg, we profiled cell-surface markers of FoxP3+ Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios+ Treg and that a Helios+ Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios+ Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios+ Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios+ Treg proliferated more than Helios− Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios+ cells in culture. Taken together, these data show that Helios+ Treg represent a functional subset with associated CD103 and GITR expression

Retro-trochanteric sciatica-like pain: current concept

The aim of this manuscript is to review the current knowledge in terms of retro-trochanteric pain syndrome, make recommendations for diagnosis and differential diagnosis and offer suggestions for treatment options. The terminology in the literature is confusing and these symptoms can be referred to as ‘greater trochanteric pain syndrome’, ‘trochanteric bursitis’ and ‘trochanteritis’, among other denominations. The authors focus on a special type of sciatica, i.e. retro-trochanteric pain radiating down to the lower extremity. The impact of different radiographic assessments is discussed. The authors recommend excluding pathology in the spine and pelvic area before following their suggested treatment algorithm for sciatica-like retro-trochanteric pain. Level of evidence II

Deciphering the pathogenesis of tendinopathy: a three-stages process

Our understanding of the pathogenesis of "tendinopathy" is based on fragmented evidences like pieces of a jigsaw puzzle. We propose a "failed healing theory" to knit these fragments together, which can explain previous observations. We also propose that albeit "overuse injury" and other insidious "micro trauma" may well be primary triggers of the process, "tendinopathy" is not an "overuse injury" per se. The typical clinical, histological and biochemical presentation relates to a localized chronic pain condition which may lead to tendon rupture, the latter attributed to mechanical weakness. Characterization of pathological "tendinotic" tissues revealed coexistence of collagenolytic injuries and an active healing process, focal hypervascularity and tissue metaplasia. These observations suggest a failed healing process as response to a triggering injury. The pathogenesis of tendinopathy can be described as a three stage process: injury, failed healing and clinical presentation. It is likely that some of these "initial injuries" heal well and we speculate that predisposing intrinsic or extrinsic factors may be involved. The injury stage involves a progressive collagenolytic tendon injury. The failed healing stage mainly refers to prolonged activation and failed resolution of the normal healing process. Finally, the matrix disturbances, increased focal vascularity and abnormal cytokine profiles contribute to the clinical presentations of chronic tendon pain or rupture. With this integrative pathogenesis theory, we can relate the known manifestations of tendinopathy and point to the "missing links". This model may guide future research on tendinopathy, until we could ultimately decipher the complete pathogenesis process and provide better treatments

Characters of the Positive Energy UIRs of D=4 Conformal Supersymmetry

We give character formulae for the positive energy unitary irreducible representations of the N-extended D=4 conformal superalgebras su(2,2/N). Using these we also derive decompositions of long superfields as they descend to the unitarity threshold. These results are also applicable to irreps of the complex Lie superalgebras sl(4/N). Our derivations use results from the representation theory of su(2,2/N) developed already in the 80s.Comment: 81 pages, input files: harvmac, amssym.def, amssym.tex; corrected presentation on odd reflection