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Glenohumeral joint Pain in COVID-19 Heirs Following Physical Venting.
Nucleic acid-based diagnostic tests often require isolation and concentration of nucleic acids from biological samples. Commercial purification kits are difficult to use in low-resource settings because of their cost and insufficient laboratory infrastructure. Several recent approaches based on the use of magnetic beads offer a potential solution but remain limited to small volume samples. We have developed a simple and low-cost nucleic acid extraction method suitable for isolation and concentration of nucleic acids from small or large sample volumes. The method uses magnetic beads, a transfer pipette, steel wool, and an external magnet to implement high-gradient magnetic separation (HGMS) to retain nucleic acid-magnetic bead complexes within the device's steel wool matrix for subsequent processing steps. We demonstrate the method's utility by extracting tuberculosis DNA from both sputum and urine, two typical large volume sample matrices (5-200 mL), using guanidine-based extraction chemistry. Our HGMS-enabled extraction method is statistically indistinguishable from commercial extraction kits when detecting a spiked 123-base DNA sequence. For our HGMS-enabled extraction method, we obtained extraction efficiencies for sputum and urine of approximately 10 and 90%, whereas commercial kits obtained 10-17 and 70-96%, respectively. We also used this method previously in a blinded sample preparation comparison study published by Beall et al., 2019. Our manual extraction method is insensitive to high flow rates and sample viscosity, with capture of ∼100% for flow rates up to 45 mL/min and viscosities up to 55 cP, possibly making it suitable for a wide variety of sample volumes and types and point-of-care users. This HGMS-enabled extraction method provides a robust instrument-free method for magnetic bead-based nucleic acid extraction, potentially suitable for field implementation of nucleic acid testing.BACKGROUND Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease so that effective therapies can be developed. The majority of pre-clinical studies evaluating skeletal muscle's response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. METHODS To create four cohorts of PDX mice evaluated in this study, tumours resected from four pancreatic ductal adenocarcinoma patients were portioned and attached to the pancreas of immunodeficient NSG mice. RESULTS Body weight, muscle mass, and fat mass were significantly decreased in eacical strategies to counter cancer cachexia. © 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.OBJECTIVE Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated through complex immunologic pathways. Approximately half of RA patients exhibit meaningful clinical response within the first 6 months of starting low-dose methotrexate (MTX) monotherapy. Whether baseline immune phenotypes differ between subsequent MTX-responders and non-responders is unknown. We employed comprehensive T cell immune phenotyping to identify specific immunologic pathways associated with MTX-non-responsive joint inflammation. METHODS 32 patients with recent-onset RA were treated with MTX therapy. After 6 months, 15 patients were categorized as responders and 17 as non-responders. Comprehensive blood T cell immunophenotyping using multi-parameter immunofluorescent flow cytometry was performed at baseline and following 6 months of treatment. RESULTS Baseline measures of disease activity (DAS28, CRP, ESR) did not differ between MTX-responders and non-responders identified following MTX treatment. Frequencies of CD4+ and CD8+ T cells were skewed to favor higher CD4CD8 ratios in MTX-responders compared to non-responders (p less then 0.05). The proportion of ICOS-expressing Tregs was significantly greater among non-responders. IL-13-producers, not IFN-γ or IL-17-producing CD4+ T effector memory (TEM ) cells, were significantly more frequent in MTX-non-responders (p less then 0.05). IL-13+ IL-17+ CD4+ TEM cell ratio was 1.9-fold higher in MTX-non-responders (p less then 0.05). Both CD4CD8 ratio and IL-13+ CD4+ TEM cell frequency correlated with changes in DAS28 following treatment, while T cell expression of immune checkpoint inhibitor markers (CTLA-4, PD-1, Tim-3) did not differ between responders and non-responders. CONCLUSION MTX-non-responsive RA patients exhibit a bias towards type 2-polarized T cell inflammatory responses. Targeting the IL-13+ CD4+ T cell pathway could be a new strategy in MTX-resistant RA patients. This article is protected by copyright. click here All rights reserved.BACKGROUND Clinical practice guidelines (CPGs) underpin patient care, thus authors of these guidelines would ideally be free from outside influence. However, it has been shown many times that authors of professional society CPGs receive large sums of money from industry drug companies, creating financial conflicts of interest. We investigated industry payments catalogued in Open Payments Database (OPD) received by authors of the American College of Rheumatology (ACR) CPGs. METHODS We used guidelines on the ACR website that were published during or after 2014 to retrieve our list of authors. We extracted all general, research, associated research, and ownership payments reported on OPD between the date of publication of the CPG and 12 months prior in parallel and blinded fashion by two investigators. RESULTS Of the total 89 US-based physician authors from the five included guidelines, 56 (62.9%) received at least one payment according to OPD records. These 56 authors received a median of $522 (IQR $119 - $2,500) and a total of $9,728,751. Nineteen authors received at least one industry payment relevant to the CPG recommendations for a median amount of $748 and a total of $1,961,362 in relevant payments. Of the total relevant payments received, a significant portion was undisclosed ($699,561, 35.7%). CONCLUSIONS Less than half the US-based physician CPG authors received relevant payments. Nonetheless, a substantial proportion of money received was not disclosed. Conflict of interest disclosure is a bare minimum requirement, and more permanent solutions may include divestiture or inclusion of more non-conflicted authors. This article is protected by copyright. All rights reserved.m6A modification is the most prevalent RNA modification in eukaryotes. As the critical N6-methyladenosine (m6A) methyltransferase, the roles of methyltransferase like 3 (METTL3) in colorectal cancer (CRC) are controversial. Here, we confirmed that METTL3, a critical m6A methyltransferase, could facilitate CRC progression in vitro and in vivo. Further, we found METTL3 promoted CRC cell proliferation by methylating the m6A site in 3'-untranslated region (UTR) of CCNE1 mRNA to stabilize it. Moreover, we found butyrate, a classical intestinal microbial metabolite, could down-regulate the expression of METTL3 and related cyclin E1 to inhibit CRC development. METTL3 promotes CRC proliferation by stabilizing CCNE1 mRNA in an m6A-dependent manner, representing a promising therapeutic strategy for the treatment of CRC. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.In recent years, Lynn Margulis has been credited in various articles as the person who introduced the concept of holobiont into biology in the early 1990s. Today, the origin of evolutionary studies on holobionts is closely linked to her name. However, Margulis was not the first person to use this concept in its current context. That honor goes to the German theoretical biologist Adolf Meyer-Abich, who introduced the holobiont concept nearly 50 years before her (in 1943). Although nearly completely forgotten today, in the 1940-60s he developed a comprehensive theory of evolutionary change through "holobiosis." It had a surprisingly modern outlook, as it not only addressed tenets of today's evolutionary developmental biology (evo-devo), like the origin of form and production of variation, but also anticipated key elements of Margulis' later endosymbiotic theory. As the holobiont concept has become an important guiding concept for organizing research, labeling conferences, and publishing articles on host-microbiota collectives and hologenomes, the field should become aware of the independent origin of this concept in the context of holistic biology of the 1940s. © 2020 The Authors. Journal of Experimental Zoology Part B Molecular and Developmental Evolution published by Wiley Periodicals, Inc.BACKGROUND Administrative data provide a unique opportunity to examine whole-of-state colorectal cancer (CRC) data. The purpose of this study was to compare types of CRC resection across Victorian geographical zones, using hospital volume and accredited training-post status. METHODS All CRC resections in Victorian public hospitals between 2008 and 2013 were analysed using validated algorithms of administrative data from the Victorian Admitted Episodes Dataset. Hospitals were grouped according to Colorectal Surgical Society of Australia and New Zealand (CSSANZ) training-post status, case-volume (high >200 in 5 years) and remoteness of location. Resection frequency and type were compared. RESULTS In 44 public hospitals over 6 years, 7596 CRC resections were performed. Patient age, American Society of Anesthesiologists Physical Status Classification System score and tumour stage were similar among groups. CSSANZ accounted for nearly 50% of cases but the lowest percentage of emergencies (16.8%). The ratio of right-sided to left-sided plus rectal resections was greater for low-volume than high-volume centres (56.8% versus 40.4%), while left colon and rectal resections comprised a larger proportion of high-volume workload. High- compared with low-volume favoured ultra-low anterior resections (62% versus 33%) over abdominoperineal resections (38% versus 67%). Work patterns among high-volume hospitals were similar regardless of remoteness or CSSANZ status. CONCLUSION This study demonstrated that administrative data can provide granular, clinically relevant information with population-wide coverage. Most public CRC resections in Victoria were performed in metropolitan hospitals. The majority of rectal cancer resections were performed in high-volume metropolitan centres but 15% were performed by low-volume regional hospitals. © 2020 Royal Australasian College of Surgeons.OBJECTIVES Osteoarthritis (OA) and pain are both made more severe by low-grade inflammation. We examined whether visceral fat, a major source of inflammatory cytokines and adipokines, was associated with an increased risk of knee OA or of musculoskeletal pain. METHODS Member of the Multicenter Osteoarthritis Study cohort, age 50-79 with or at high risk of knee osteoarthritis had whole body DEXA scans at baseline. At baseline, 30, and 60 months they obtained knee radiographs and MRIs, were asked to score the severity of their knee pain and using a body homunculus, to identify sites of joint pain. We used DEXA scans to measure total body fat and in the torso, visceral fat and subcutaneous fat. We assessed the association of fat depot size with structural outcomes (incident radiographic OA, MRI cartilage loss and synovitis) and with pain outcomes (worsening knee pain, the number of painful joints and widespread pain). Regression analyses were adjusted for age, sex, race, education, smoking, physical activity, BMI and depressive symptoms.
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