Mcconnelldunlap6610
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has afflicted many lives and led to approvals of drugs and vaccines for emergency use. Even though vaccines have emerged, the high mortality of COVID-19 and its insurgent proliferation throughout the masses commands an innovative therapeutic proposition for the treatment. Targeted protein degradation has been applied to various disease domains and we propose that it could be incredibly beneficial to tackle the current pandemic. In this study, we have attempted to furnish insights on the design of suitable PROTACs for the main protease (Mpro) of SARS-CoV-2, a protein that is considered to be an essential target for viral replication. We have employed protein-protein docking to predict the possible complementarity between a cereblon E3 ligase and Mpro of SARS-CoV-2, and estimate possible linker length. Molecular Dynamic simulation and analysis on generated ternary complexes demonstrated stable interactions that suggested that designed PROTAC has a potential to cause degradation. The superior characteristics rendered by PROTACS led us to propose them as possibly the next-generation antiviral drugs for SARS-CoV-2.
There is a lack of knowledge on coping with pain and sub-group specific pain-coping profiles among older home care receivers with chronic pain. To describe pain-coping strategies, identify subgroups based on cognitive and behavioral pain-coping strategies and pain-related psychological impairment and to compare these groups with regard to socio-demographic, medical, pharmacological and psychological characteristics.
Data of 212 care receivers were examined using the German pain-coping questionnaire (FESV) to determine how they cope with pain. Subgroups were identified using hierarchic agglomerative cluster analysis, using Ward's algorithm and squared Euclidean distance, and characterized using socio-demographic, medical, pharmacological and psychological parameters. Multinomial logistic regression was used to identify variables associated with the subgroups.
Older care receivers apply cognitive and behavioral strategies to manage pain. Three subgroups were identified Cluster 1 (25.9%) with good coping cfic pain-oriented psychotherapeutic interventions, which can result in improved pain management.
Eosinophils play a central role in the inflammation of asthma and are the target of new biologic treatments for patients with severe asthma. Biologics targeting the IL-5 pathway have been shown to reduce asthma exacerbations, improve lung function, reduce oral corticosteroid use, and improve quality of life, accompanied by reduced or even eliminated blood eosinophils. Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of these long-term therapies that reduce or eliminate them.
In this review, we explore the current safety profile of biologics regarding the impact they may have on blood eosinophils, trying to answer the question about any safety consideration.
Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of long-term therapies that reduce or eliminate these blood cells.
Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of long-term therapies that reduce or eliminate these blood cells.In this work, we investigated the simultaneous binding of curcumin (CUR) to human serum albumin (HSA) and human-holo transferrin (HTF) in the roles of binary and ternary systems. 3-Amino-9-ethylcarbazole chemical structure The binding affinity and binding site of protein-protein interaction were studied by the methods of multiple spectroscopic and molecular dynamics (MD) simulation. According to the results, the measurements for binding constant of HSA-CUR, HTF-CUR and (HSA-HTF) CUR complexes were observed to be 1.51 × 105, 7.93 × 104 and 1.44 × 105 M-1 respectively. Thermodynamic parameters were considered to be set at three varying temperatures including 298, 303, and 308 K. In conformity to the negative values of ΔH0 and ΔS0 the significant roles of hydrogen binding and van der-Waals forces in the formation of complexes are quiet evident. The binding distance between Trp residues of HSA, HTF and HSA-HTF upon interaction with CUR, were acquired by applying the Förster's theory of non-radioactive energy transfer and reported to be 2.04 nm, 1.78 nm, and 1.86 nm, respectively. In accordance with the conductometry and Resonance light scattering (RLS) results, there were different interaction behaviors among the HSA-HTF complex and CUR in ternary system when being compared to the outcomes of binary system. The secondary structure of all three cases increased as the CUR concentration was intensified, which confirmed the inducement of proteins conformational changes through the application of circular dichroism (CD) technique. The experimental results that were acquired throughout the binding of HSA-CUR, HTF-CUR, and (HSA-HTF) CUR complexes were approved by molecular modeling.Communicated by Ramaswamy H. Sarma.
Hydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome
oxidase. Cyanide is generated in structural fires and methanethiol is released by decaying organic matter. Current treatments for cyanide exposure do not lend themselves to treatment in the field and no treatment exists for methanethiol poisoning. Sodium tetrathionate (tetrathionate), a product of thiosulfate oxidation, could potentially serve as a cyanide antidote, and, based on its chemical structure, we hypothesized it could react with methanethiol.
We show that tetrathionate, unlike thiosulfate, reacts directly with cyanide
under physiological conditions, and based on rabbit studies where we monitor cyanide poisoning in real-time, tetrathionate likely reacts directly with cyanide
. We found that tetrathionate administered by intramuscular injection rescues >80% of juvenile, young adult, and old adult mice from exposure to inhaled hydrogen cyanide gas that is >80% lethal. Tetrathionate also rescued young adult rabbits from intravenously administered sodium cyanide. Tetrathionate was reasonably well-tolerated by mice and rats, yielding a therapeutic index of ∼5 in juvenile and young adult mice, and ∼3.3 in old adult mice; it was non-mutagenic in Chinese Hamster ovary cells and by the Ames bacterial test. We found by gas chromatography-mass spectrometry that both tetrathionate and thiosulfate react with methanethiol to generate dimethyldisulfide, but that tetrathionate was much more effective than thiosulfate at recovering intracellular ATP in COS-7 cells and rescuing mice from a lethal exposure to methanethiol gas.
We conclude that tetrathionate has the potential to be an effective antidote against cyanide and methanethiol poisoning.
We conclude that tetrathionate has the potential to be an effective antidote against cyanide and methanethiol poisoning.
Soft tissue filler augmentation has become increasingly popular due to its perceived ease and impressive results. Unfortunately, although the results are impressive, so are the reported complications. This article describes complications specific to peri-oral soft tissue filler injection and then discusses evidence-based, anatomic prevention and treatment guidelines.
The authors aimed at providing an overview of the complications associated with peri-oral soft tissue filler. Hyaluronic Acid (H.A) fillers may have devastating complications which are oft undisclosed or published. This narrative review aims to describe the various complications and provide preventative strategies.
Given the paucity of prospective, randomized clinical trials on the subject and in light of complication underreporting, the authors believe that efficacy and safety literature on the subject is lacking. Injectors must rely on the one strength which exists in the lip literature to date, that is anatomy. The basis of all successful injections is a mandatory understanding of normal as well as variations of vital structures in an area, combined with meticulous injection techniques, deposition of small aliquots of product and the ability to recognize unwanted adverse events early enough to act on them.
Given the paucity of prospective, randomized clinical trials on the subject and in light of complication underreporting, the authors believe that efficacy and safety literature on the subject is lacking. Injectors must rely on the one strength which exists in the lip literature to date, that is anatomy. The basis of all successful injections is a mandatory understanding of normal as well as variations of vital structures in an area, combined with meticulous injection techniques, deposition of small aliquots of product and the ability to recognize unwanted adverse events early enough to act on them.
Healthcare professionals (HCPs) in family medicine (FM) in Croatia work in a demanding environment caused by the SARS-CoV-2 pandemic. Besides particular circumstances in healthcare, an unknown virus, social distancing, and homeschooling, the capital was hit with the earthquake during the lockdown.
To assess the prevalence of stress, anxiety, depression, posttraumatic stress disorder (PTSD) and the influence of demographic characteristics, professional differences, medical history, and specific stressors on the psychological outcomes.
A cross-sectional study with the online questionnaire containing the Depression, Anxiety and Stress Scale (DASS-21) and the Impact of Event Scale-Revised (IES-R) was conducted from 1st to 15 May 2020 in FM.
HCPs (534, 35% response rate), predominantly female (84.5%), participated in the research. High prevalence of stress (30.9%), anxiety (33.1%), depression (30.7%), and PTSD (33.0%) were found. Female participants had higher results in the anxiety subscale of DASS-21 and IES-R scores. Pre-existing conditions were associated with higher levels of stress, anxiety, depression, and PTSD. The IES-R score for PTSD showed borderline correlation (
= 0.053) with working in regions with the highest incidence of COVID-19. Having schoolchildren made a difference on a stress subscale in DASS-21 (
< 0.043), but the earthquake did not have an impact.
Family physicians and nurses in FM in Croatia are under a great mental load during the COVID-19 outbreak. Results suggest that HCPs of the female sex, with pre-existing chronic conditions, work in regions with a high incidence of SARS-CoV-2 or have schoolchildren at greater risk of the poor psychological outcome.
Family physicians and nurses in FM in Croatia are under a great mental load during the COVID-19 outbreak. Results suggest that HCPs of the female sex, with pre-existing chronic conditions, work in regions with a high incidence of SARS-CoV-2 or have schoolchildren at greater risk of the poor psychological outcome.
Technology to enhance hypertension management is increasingly used in primary care; however, it has not been evaluated in an Asian primary care setting. We aimed to understand the clinical impact and cost-effectiveness of a technology-enabled home blood pressure monitor when deployed in primary care, and patients' perspectives about the technology.
A quasi-experimental cohort study was conducted in a polyclinic in Singapore. In total, 120 patients with hypertension were assigned to the telemonitoring intervention group. Patients received a home blood pressure device connected to the clinical care team's dashboard through a mobile gateway. Tele-consultations and nurse-led tele-support were carried out using established clinical protocols. In total, 120 patients assigned to the control group continued to receive usual care in the polyclinic. Clinical outcomes, cost-effectiveness, and patient satisfaction were measured 6 months after recruitment.
In total, 217 patients completed 6 months of follow-up. Telemonitoring intervention patients had significantly increased odds of having controlled blood pressure by a factor of 2.
