Do Mast Cells Have a Role in Tendon Healing and Inflammation?

Understanding the links between the tendon healing process, inflammatory mechanisms, and tendon homeostasis/pain after tissue damage is crucial in developing novel therapeutics for human tendon disorders. The inflammatory mechanisms that are operative in response to tendon injury are not fully understood, but it has been suggested that inflammation occurring in response to nerve signaling, i.e., neurogenic inflammation, has a pathogenic role. The mechanisms driving such neurogenic inflammation are presently not clear. However, it has recently been demonstrated that mast cells present within the injured tendon can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling and thereby modulate neurogenic inflammation following tissue injury. In this review, we discuss the role of mast cells in the communication with peripheral nerves, and their emerging role in tendon healing and inflammation after injury

Chronic conditions in adults with cerebral palsy

Adults with cerebral palsy (CP) represent a growing population whose health status and healthcare needs are poorly understood.1 Mortality records reveal that death due to ischemic heart disease and cancer is higher among adults with CP;2 however, there have been no national surveillance efforts to track disease risk in this population. We examined estimates of chronic conditions in a population-representative sample of adults with CP

Microangiopathic Occlusion of a Perforating Prepontine Long Circumferential Artery Presenting with Lower Motor Neuron Facial Weakness: Clinical and Radiological Correlation

Case Description: A 79-year old male patient with myelodysplastic syndrome associated with severe neutropenia, thrombocytopenia, anemia, hypertension, and hyperlipidemia was admitted for pneumonia secondary to influenza A. Two weeks later he presented with new symptoms of acute dysarthria, and left facial weakness involving his upper and lower face; the following day he developed left arm weakness. Admission computed tomography (CT) and MRI scans revealed an acute ischemic stroke (AIS) in the right posterior frontal cortex. The initial MRI was reported negative for pontine lesions. Anatomically, the cortical infarct could not explain his left lower motor neuron cranial nerve VII (LMN CN VII) facial weakness distribution because in a cortical lesion the upper half of the face would be expected spared due to contralateral cortical innervation. Upon review of the MRI, the initial hyperintensity seen on Fluid-Attenuated Inversion Recovery (FLAIR) was overlooked and later identified as an acute stroke in the vicinity of the perforating prepontine long circumferential artery affecting the CN VII nucleus. Conclusion: In the absence of earache, active infection, and/or inflammation, a sudden onset facial palsy, lower motor neuron distribution, must poin

Reduced Cost and Decreased Length of Stay Associated with Acute Ischemic Stroke Care Provided by Nurse Practitioners: A Single Primary Stroke Center Experience

Nurse practitioner (NP) have a wider role in modern stroke centers providing quality evidence based care to patients with both in and outpatient settings for acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients. We studies the outcome measures, length of stay (LOS) and cost before and after implementation of nurse practitioners as the primary medical provider in a community based stroke center.https://digitalcommons.centracare.com/nursing_posters/1075/thumbnail.jp

Development and Evaluation of an Online, Patient-Driven, Family Outreach Intervention to Facilitate Sharing of Genetic Risk Information in Families with Lynch Syndrome

Departments of Gastroenterology Research, Behavioral Science, and Gastroenterology, Hepatology, and Nutrition This article has been accepted for publication in the Journal of Medical Genetics, 2021 following peer review, and the Version of Record can be accessed online at https://doi.org/10.1136/jmedgenet-2020-107615https://openworks.mdanderson.org/mdacc_ghn_pubs/1000/thumbnail.jp

Intraoperative PTH Monitoring in Normohormonal Primary Hyperparathyroidism

Background: A subset of patients with primary hyperparathyroidism present with inappropriately normal PTH levels despite elevated serum calcium, called normohormonal primary hyperparathyroidism (NHPHP). This disease variant presents a clinical dilemma regarding intraoperative parathyroid hormone (IOPTH) monitoring during parathyroidectomy when using the standard criteria of a ≥ 50% reduction in IOPTH from baseline to determine surgical success. This study aimed to determine what percent reduction in post-excision IOPTH from baseline in NHPHP patients would yield a high cure rate similar to that of classic primary hyperparathyroidism. Methods: This was a single surgeon, single institution retrospective cohort study of patients that underwent parathyroidectomy between July 2013 and February 2020. Demographic, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHPHP were compared to those with classic primary hyperparathyroidism. Results: 496 patients were included in the study. 66 (13.3%) were of the normohormonal variant based on preoperative intact PTH levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the normohormonal groups were not significantly different from their classic counterparts: 98.4% and 100.0% vs 97.1% and 97.1%, p = 1.000. The median percent decline in post-excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.8% and 80.4% compared to their respective controls of 87.3% and 87.1%, p = 0.017 and p=0.001. Conclusion: A ≥ 75% decline in 15-minute post-excision IOPTH level from baseline can be used as a more stringent criterion for achieving high rates of cure in patients with NHPHP that undergo parathyroidectomy

Fifty years of spellchecking

A short history of spellchecking from the late 1950s to the present day, describing its development through dictionary lookup, affix stripping, correction, confusion sets, and edit distance to the use of gigantic databases

The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome: a potential therapeutic target for inflammatory disorders.

Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome-induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress- and inflammasome-related inflammatory disorders

Role of oxidative stress in the pathology and management of human tuberculosis

Copyright © 2018 Madhur D. Shastri et al. Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR-TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first-/second-line antitubercle antibiotics are administered in an inactive form and subsequently transformed into their active form by components of the OS responses of both host (nitric oxide, S-oxidation) and pathogen (catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in the host, including the increased bacterial NADH/NAD+ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin, superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug-susceptible and drug-resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host's OS response

Development and validation of a novel high performance liquid chromatography-coupled with Corona charged aerosol detector method for quantification of glucosamine in dietary supplements

Introduction: Glucosamine dietary supplements are commonly used for the management of osteoarthritis (OA). However, clinical trials have reported varying outcomes with regard to joint function and disease progression. One of the possible reasons for variability in observed effects of glucosamine could be that, unlike prescription drugs, the quality of manufactured dietary supplements is not closely monitored in many countries. Therefore, there is the possibility that the actual amount of glucosamine present in a dietary supplement is different from that claimed on the label. The quality control of glucosamine supplements is further complicated by the unavailability of a simple and effective analytical method for the analysis of glucosamine. Therefore, the aim of this study was to develop a simple analytical method that could be easily adapted by the pharmaceutical industry for routine analysis of glucosamine.Aims: To develop a novel high-performance liquid chromatography (HPLC) method for the quantification of glucosamine, and determine the amount of glucosamine present in a sample of dietary supplements commercially available in Australia and India.Methods: Chromatographic separation of glucosamine was achieved using a zwitter-ionic hydrophilic interaction liquid chromatography column with a mobile phase consisting of 60% acetonitrile and 40% of 85 mM ammonium acetate, at a flow rate of 0.3 mL/min and column temperature 40°C. The developed method was validated for intra- and inter-day linearity, accuracy, precision, and reproducibility. The newly-developed method was subsequently used to analyse 12 glucosamine supplements.Results: The developed method was selective for glucosamine, which had a retention time of 5.9 min. The standard curve was linear with a correlation coefficient (r2) exceeding 0.99, over the range of 10–200 μg/mL for glucosamine. The relative standard deviations for intra- and inter-day accuracy, precision and reproducibility were all less than 4%. The amount of glucosamine determined in six Australian and six Indian glucosamine supplements ranged between 98.7–101.7% and 85.9–101.8% of the labelled values, respectively.Discussion: Unlike previous HPLC methods, this newly-developed HPLC technique does not require pre-derivatisation and can separate glucosamine from both hydrochloride and sulphate salts, and from other amino sugars, such as chondroitin sulphate present in dietary supplements. This simple and effective technique can be employed by analytical laboratories for the quality control of glucosamine dietary supplements.Conclusion: The current study has developed a new analytical technique using HPLC-Corona CAD, which can analyse underivatised glucosamine hydrochloride and sulphate within 6 minutes. Using the novel assay, we confirmed that unlike the tested Australian dietary supplements, only half of the tested Indian products had a glucosamine content within ±10% of what was claimed on the label