New Insights on Dimethylaminoethanol (DMAE) Features as a Free Radical Scavenger

Recently, a number of synthetic drugs used in a variety of therapeutic indications have been reported to have antiaging effects. Among them, Dimethylaminoethanol (DMAE), an anologue of dietylaminoethanol, is a precursor of choline, which in turn allows the brain to optimize the production of acetylcholine that is a primary neurotransmitter involved in learning and memory. The data presented here includes new information on the ability of the compound to scavenge specific free radicals, assessed by Electron Spectroscopic Resonance (EPR), to further analyze the role of DMAE as an antioxidant. DMAE ability to directly react with hydroxyl, ascorbyl and lipid radicals was tested employing in vitro assays, and related to the supplemented dose of the compound.Fil: Malanga, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analitica y Fisicoquímica. Cátedra de Fisicoquímica; ArgentinaFil: Aguiar, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analitica y Fisicoquímica. Cátedra de Fisicoquímica; ArgentinaFil: Martinez, Hugo D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analitica y Fisicoquímica. Cátedra de Fisicoquímica; ArgentinaFil: Puntarulo, Susana Ángela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analitica y Fisicoquímica. Cátedra de Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Complete Rotator Cuff Tear: An Evidence-Based Conservative Management Approach

Rotator cuff disease accounts for 10% of all shoulder pain and major shoulder disability, with limited information concerning the natural history and treatment approaches for the disorder. Our objective is to assess the available evidence for the efficacy and morbidity of commonly used systemic medications, physiotherapy, and injections alongside evaluating any negative long-term effects. Although there is conflicting literature, there appears to be some consensus on the best indicators for choosing to treat a full-thickness tears (FTT) non-operatively to reduce pain and improve function. The risks associated with these tears include the potential of the progression of the tear, a diminished healing potential due to age or longer symptom duration, muscle atrophy, and fatty infiltration. The indications for surgery following conservative treatment are becoming more defined, and an outline regarding what scenarios warrant a transition from an initial conservative treatment plan has been developed. The developing benefits of using mesenchymal stem cells (MSCs) and other biologics have the potential to be disruptive to current treatment protocols in the approaches to healing rotator cuff tears (RCTs). With improved imaging modalities, diagnostic accuracy, and sensitivity, practitioners of the future will hopefully be able to intervene earlier in the disease pathogenesis cycle

Tinnitus and equilibrium disorders in COVID-19 patients: preliminary results

Purpose: Tinnitus and equilibrium disorders such as dizziness and vertigo have been reported by patients with COVID-19; however, they have been rarely investigated. The aim of this study was to study the prevalence of subjective tinnitus and dizziness in a sample of COVID-19 patients using an online 10-item close-ended questionnaire. Methods: A multicentric study that included 15 Italian hospitals in different regions was conducted using an online 10-item close-ended questionnaire developed to identify the presence of tinnitus and balance disorders in patients with COVID-19 between May 5 and June 10, 2020. The questionnaire was administered to 185 patients in a period of > 30 – < 60 days after diagnosis of COVID-19; responses were recorded in an online Excel spreadsheet. The questionnaire was composed of three sections: (1) demographic information; (2) presence and characteristics of tinnitus and dizziness after COVID-19 diagnosis; (3) possible association with migraine. Results: Thirty-four patients (18.4%) reported equilibrium disorders after COVID-19 diagnosis. Of these, 32 patients reported dizziness (94.1%) and 2 (5.9%) reported acute vertigo attacks. Forty-three patients (23.2%) reported tinnitus; 14 (7.6%) reported both tinnitus and equilibrium disorders. Conclusion: This study suggests that the presence of subjective otoneurological symptoms such as tinnitus and balance disorders can affect COVID-19 patients; further studies are necessary to investigate the prevalence and pathophysiological mechanisms underlying these subjective symptoms in COVID-19 patients

Hamstring stretch reflex:could it be a reproducible objective measure of functional knee stability?"

Background: The anterior cruciate ligament (ACL) plays an important role in anterior knee stability by preventing anterior translation of the tibia on the femur. Rapid translation of the tibia with respect to the femur produces an ACL-hamstring stretch reflex which may provide an object measure of neuromuscular function following ACL injury or reconstruction. The aim of this study was to determine if the ACL-hamstring stretch reflex could be reliably and consistently obtained using the KT-2000 arthrometer.  Methods: A KT-2000 arthrometer was used to translate the tibia on the femur while recording the electromyography over the biceps femoris muscle in 20 participants, all with intact ACLs. In addition, a sub-group comprising 4 patients undergoing a knee arthroscopy for meniscal pathology, were tested before and after anaesthetic and with direct traction on the ACL during arthroscopy. The remaining 16 participants underwent testing to elicit the reflex using the KT-2000 only.  Results: A total number of 182 trials were performed from which 70 trials elicited stretch reflex (38.5 %). The mean onset latency of the hamstring stretch reflexes was 58.9 ± 17.9 ms. The average pull force was 195 ± 47 N, stretch velocity 48 ± 35 mm/s and rate of force 19.7 ± 6.4 N/s. Conclusions Based on these results, we concluded that the response rate of the anterior cruciate ligament-hamstring reflex is too low for it to be reliably used in a clinical setting, and thus would have limited value in assessing the return of neuromuscular function following ACL injuries

Sudden olfactory loss as an early marker of COVID-19: a nationwide Italian survey

Purpose: The presence of many asymptomatic COVID-19 cases may increase the risks of disease dissemination, mainly for physicians. There are numerous reports on the frequent findings of sudden anosmia or hyposmia, before or at the same time of the typical COVID-19 symptoms onset. The aim of this study was to verify the association of olfactory impairment and COVID-19, providing a basis for subsequent research in the field of COVID-19 clinical heterogeneity. Methods: We developed a 15-item online questionnaire on “Sudden Olfactory Loss (SOL) and COVID-19” that was administered during March 2020 to Italian general practitioners registered to a social media group. Results: One hundred and eighty responses were received. SOL was identified as a significant sign of infection in COVID-19 patients, mainly aged between 30 and 40 years, even in the absence of other symptoms. SOL was present as an initial symptom in 46.7% of subjects, and in 16.7%, it was the only symptom. Among the COVID-19 confirmed cases, SOL occurred as the only symptom in 19.2% of patients. Conclusion: SOL could represent a possible early symptom in otherwise asymptomatic COVID-19 subjects. Subjects affected by SOL should be considered as potential COVID-19 cases. Level of evidence: 4

A Novel Mutation in the Upstream Open Reading Frame of the CDKN1B Gene Causes a MEN4 Phenotype

PubMed ID: 23555276This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1α-mediated unfolded protein response

Poly(ADP-ribose) polymerases (PARPs; also known as ADP-ribosyl transferase D proteins) modify acceptor proteins with ADP-ribose modifications of varying length (reviewed in refs 1, 2, 3). PARPs regulate key stress response pathways, including DNA damage repair and the cytoplasmic stress response. Here, we show that PARPs also regulate the unfolded protein response (UPR) of the endoplasmic reticulum (ER). Human PARP16 (also known as ARTD15) is a tail-anchored ER transmembrane protein required for activation of the functionally related ER stress sensors PERK and IRE1α during the UPR. The third identified ER stress sensor, ATF6, is not regulated by PARP16. As is the case for other PARPs that function during stress, the enzymatic activity of PARP16 is upregulated during ER stress when it ADP-ribosylates itself, PERK and IRE1α. ADP-ribosylation by PARP16 is sufficient for activating PERK and IRE1α in the absence of ER stress, and is required for PERK and IRE1α activation during the UPR. Modification of PERK and IRE1α by PARP16 increases their kinase activities and the endonuclease activity of IRE1α. Interestingly, the carboxy-terminal luminal tail of PARP16 is required for PARP16 function during ER stress, suggesting that it transduces stress signals to the cytoplasmic PARP catalytic domain.National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051)National Institutes of Health (U.S.) (Grant 5R01 GM087465-02)Kathy and Curt Marble Cancer Research FundJeptha H. and Emily V. Wade FundVirginia and D.K. Ludwig Fund for Cancer Researc

The G Protein-Biased -Opioid Receptor Agonist RB-64 Is Analgesic with a Unique Spectrum of Activities In Vivo

The hypothesis that functionally selective G protein-coupled receptor (GPCR) agonists may have enhanced therapeutic benefits has revitalized interest for many GPCR targets. In particular, although κ-opioid receptor (KOR) agonists are analgesic with a low risk of dependence and abuse, their use is limited by a propensity to induce sedation, motor incoordination, hallucinations, and dysphoria-like states. Several laboratories have produced a body of work suggesting that G protein-biased KOR agonists might be analgesic with fewer side effects. Although that has been an intriguing hypothesis, suitable KOR-selective and G protein-biased agonists have not been available to test this idea. Here we provide data using a G protein-biased agonist, RB-64 (22-thiocyanatosalvinorin A), which suggests that KOR-mediated G protein signaling induces analgesia and aversion, whereas β-arrestin-2 signaling may be associated with motor incoordination. Additionally, unlike unbiased KOR agonists, the G protein-biased ligand RB-64 does not induce sedation and does not have anhedonia-like actions, suggesting that a mechanism other than G protein signaling mediates these effects. Our findings provide the first evidence for a highly selective and G protein-biased tool compound for which many, but not all, of the negative side effects of KOR agonists can be minimized by creating G protein-biased KOR agonists