COVID-19 revisiting inflammatory pathways of arthritis

Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2, which predominantly affects the lungs and, under certain circumstances, leads to an excessive or uncontrolled immune activation and cytokine response in alveolar structures. The pattern of pro-inflammatory cytokines induced in COVID-19 has similarities to those targeted in the treatment of rheumatoid arthritis. Several clinical studies are underway that test the effects of inhibiting IL-6, IL-1\u3b2 or TNF or targeting cytokine signalling via Janus kinase inhibition in the treatment of COVID-19. Despite these similarities, COVID-19 and other zoonotic coronavirus-mediated diseases do not induce clinical arthritis, suggesting that a local inflammatory niche develops in alveolar structures and drives the disease process. COVID-19 constitutes a challenge for patients with inflammatory arthritis for several reasons, in particular, the safety of immune interventions during the pandemic. Preliminary data, however, do not suggest that patients with inflammatory arthritis are at increased risk of COVID-19

Synthetic Studies in the Chloramphenicol Series. III. Synthesis of threo-DL-Chloramphenicol from DL-Serine Ethyl Ether

A synthesis of threo-DL-chloramphenicol (I) from a-phthalimido-~-ethoxy-DL-propiophenone (II) is described. The crude ketone II obtained from a-phthalimido-~-ethoxy-DL-propionyl chloride via Friedel-Crafts reaction was reduced with aluminium isopropoxide to give a yield of 17.2 % of the corresponding carbinol III. This carbinol gave in a series of reactions threo -DL-chloramphenicol in an overall yield of 2.4 %

Immunological and Functional Properties of the Acetylcholine Receptor Expressed on the Human Cell Line TE671

Peer Reviewe

Male blue wildebeest increase activity during the rut, but not at the expense of rest

Rest is a state of adaptive inactivity that increases the efficiency of activity by regulating its timing and reducing energy use when activity is not beneficial. Thus, animals can go without rest when specific demands, such as mating, favour being awake. Sexually active male blue wildebeest (bulls) are typically territorial, and it has been reported that when a bull is protecting a harem during the mating season (rut), he neither eats nor rests. We examined the daily activity and inactivity patterns of dominant bulls by means of actigraphy for 3 months, which included the rut. We also measured faecal androgen metabolite (fAM) levels and subcutaneous temperature, both of which have variances known to delineate the rut. During the rut, wildebeest bulls experienced higher levels of activity, fAM, and a greater daily range of subcutaneous temperature. Despite previous reports, the male blue wildebeest rested daily during the rut, and while the amount of rest was low, it was not substantially lower than prior to the rut. The amount of time spent inactive increased substantially after the rut. The timing of daily activity and inactivity patterns did not vary substantially across the recording period. Across the recording period, the average daily ambient temperatures decreased (seasonality), and the subcutaneous temperature followed this pattern, although it was not as marked. It appears that in the post-rut period a substantive increase in time spent at rest occurs, potentially allowing the wildebeest bulls time to recover following a period of intense activity.Grant Sponsors: South African National Research Foundation. Open access funding provided by University of the Witwatersrand.Open access funding provided by University of the Witwatersrand.https://link.springer.com/journal/360hj2023Anatomy and PhysiologyMammal Research InstituteZoology and Entomolog

Measurement of fractionated plasma metanephrines for exclusion of pheochromocytoma: Can specificity be improved by adjustment for age?

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging

Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions

International audienceObjectives: To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions. Methods: Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: >= 50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a >= 3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a >= 50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%). Results: Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of "clear/almost clear'' increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria. Conclusions: Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response

High-Z radiation shields for x-ray free electron laser detectors

Abstract Not Provide

The evolution of mammalian brain size

Relative brain size has long been considered a reflection of cognitive capacities and has played a fundamental role in developing core theories in the life sciences. Yet, the notion that relative brain size validly represents selection on brain size relies on the untested assumptions that brain-body allometry is restrained to a stable scaling relationship across species and that any deviation from this slope is due to selection on brain size. Using the largest fossil and extant dataset yet assembled, we find that shifts in allometric slope underpin major transitions in mammalian evolution and are often primarily characterized by marked changes in body size. Our results reveal that the largest-brained mammals achieved large relative brain sizes by highly divergent paths. These findings prompt a reevaluation of the traditional paradigm of relative brain size and open new opportunities to improve our understanding of the genetic and developmental mechanisms that influence brain size

Joint contractures in the absence of inflammation may indicate mucopolysaccharidosis

<p>Abstract</p> <p>Background</p> <p>Undiagnosed patients with the attenuated form of mucopolysaccharidosis (MPS) type I often have joint symptoms in childhood that prompt referral to a rheumatologist. A survey conducted by Genzyme Corporation of 60 European and Canadian rheumatologists and pediatric rheumatologists demonstrated that < 20% recognized signs and symptoms of MPS I or could identify appropriate diagnosis tests. These results prompted formation of an international working group of rheumatologists, pediatric rheumatologists, and experts on MPS I to formulate a rheumatology-based diagnostic algorithm. The resulting algorithm applies to all MPS disorders with musculoskeletal manifestations.</p> <p>Bone and joint manifestations are prominent among most patients with MPS disorders. These life-threatening lysosomal storage diseases are caused by deficient activity of specific enzymes involved in the degradation of glycosaminoglycans. Patients with attenuated MPS disease often experience diagnostic delays. Enzyme replacement therapy is now commercially available for MPS I (laronidase), MPS II (idursulfase), and MPS VI (galsulfase).</p> <p>Presentation of the hypothesis</p> <p>Evolving joint pain and joint contractures in the absence of inflammation should always raise the suspicion of an MPS disorder. All such patients should undergo urinary glycosaminoglycan (uGAG) analysis (not spot tests for screening) in a reputable laboratory. Elevated uGAG levels and/or an abnormal uGAG pattern confirms an MPS disorder and specific enzyme testing will determine the MPS type. If uGAG analysis is unavailable and the patient exhibits any other common sign or symptom of an MPS disorder, such as corneal clouding, history of hernia surgery, frequent respiratory and/or ear, nose and throat infections; carpal tunnel syndrome, or heart murmur, proceed directly to enzymatic testing. Refer patients with confirmed MPS to a geneticist or metabolic specialist for further evaluation and treatment.</p> <p>Testing of the hypothesis</p> <p>We propose that rheumatologists, pediatric rheumatologists, and orthopedists consider our diagnostic algorithm when evaluating patients with joint pain and joint contractures.</p> <p>Implications of the hypothesis</p> <p>Children and young adults can suffer for years and sometimes even decades with unrecognized MPS. Rheumatologists may facilitate early diagnosis of MPS based on the presenting signs and symptoms, followed by appropriate testing. Early diagnosis helps ensure prompt and appropriate treatment for these progressive and debilitating diseases.</p