Comparative Effectiveness of Umeclidinium/Vilanterol versus Indacaterol/Glycopyrronium on Moderate-to-Severe Exacerbations in Patients with Chronic Obstructive Pulmonary Disease in Clinical Practice in England.

Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with significant morbidity and mortality and increased economic healthcare burden for patients with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) dual therapy is recommended for patients receiving mono-bronchodilator therapy who experience exacerbations or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), on moderate-to-severe exacerbation rates in patients with COPD in England.

Comparison of Rescue Medication Prescriptions in Patients with Chronic Obstructive Pulmonary Disease Receiving Umeclidinium/Vilanterol versus Tiotropium Bromide/Olodaterol in Routine Clinical Practice in England.

Purpose: Routinely collected healthcare data on the comparative effectiveness of the long-acting muscarinic antagonist/long-acting β-agonist combination umeclidinium/vilanterol (UMEC/VI) versus tiotropium bromide/olodaterol (TIO/OLO) for chronic obstructive pulmonary disease (COPD) is limited. This study compared rescue medication prescriptions in patients with COPD in England receiving UMEC/VI versus TIO/OLO.

Patients And Methods: This retrospective cohort study used primary care data from the Clinical Practice Research Datalink Aurum database linked with secondary care administrative data from Hospital Episode Statistics.

Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets.

COPD pathogenesis is frequently associated with endoplasmic reticulum stress (ER stress) progression. Targeting the major unfolded protein response (UPR) branches in the ER stress pathway may provide pharmacotherapeutic selection strategies for treating COPD and enable relief from its symptoms. In this study, we aimed to systematically review the potential role of the ER stress inhibitors of major UPR branches (IRE1, PERK, and ATF6) in COPD-related studies and determine the current stage of knowledge in this field.

Comparative Effectiveness of Umeclidinium/Vilanterol versus Inhaled Corticosteroid/Long-Acting β-Agonist in Patients with Chronic Obstructive Pulmonary Disease in a Primary Care Setting in England.

Purpose: To compare adherence to once-daily umeclidinium/vilanterol (UMEC/VI), a long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA), and twice-daily inhaled corticosteroids (ICS)/LABA single-inhaler dual therapy in patients with chronic obstructive pulmonary disease (COPD) in a primary care cohort in England.

Patients And Methods: Active comparator, new-user, retrospective cohort study using CPRD-Aurum primary care data and linked Hospital Episode Statistics secondary care administrative data. Patients without exacerbations in the previous year were indexed on first/earliest prescription date of once-daily UMEC/VI or twice-daily ICS/LABA as initial maintenance therapy between July 2014-September 2019.

Reducing voltage-dependent potassium channel Kv3.4 levels ameliorates synapse loss in a mouse model of Alzheimer's disease.

Synapse loss is associated with cognitive decline in Alzheimer's disease, and owing to their plastic nature, synapses are an ideal target for therapeutic intervention. Oligomeric amyloid beta around amyloid plaques is known to contribute to synapse loss in mouse models and is associated with synapse loss in human Alzheimer's disease brain tissue, but the mechanisms leading from Aβ to synapse loss remain unclear. Recent data suggest that the fast-activating and -inactivating voltage-gated potassium channel subtype 3.

The Bisindole Alkaloids Angustilongines M and A from Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization.

A new linearly fused macroline-sarpagine bisindole, angustilongine M (), was isolated from the methanolic extract of . The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (). Compounds and showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines.

Working in lockdown: the relationship between COVID-19 induced work stressors, job performance, distress, and life satisfaction.

Background & Aim: In the wake of COVID-19, organizations all over India have closed their premises and shifted to work from home policy to curb the further spread of the virus. This has led to increased stress and anxiety among employees, which explicably affects their satisfaction with life. Thus, the present study analyses the effect of COVID-19 induced stressors (role overload, lifestyle choices, family distraction, and occupational discomfort) on employees' distress levels and job performance.

Sequential habituation to space, object and stranger is differentially modulated by glutamatergic, cholinergic and dopaminergic transmission.

Novel object and social interaction tasks allow assessments of rodent cognition and social behavior. Here, we combined these tasks and defined unequivocal locations of interest. Our procedure, termed OF-NO-SI, comprised habituation to the open field (OF), novel object (NO) and social interaction (SI) stages.

Macroline, talpinine, and sarpagine alkaloids from Alstonia penangiana. An NMR-based method for differentiating between A. penangiana and A. macrophylla.

Fourteen previously undescribed alkaloids comprising two N-1-hydroxymethylmacroline alkaloids, one talpinine-type oxindole acetal, a pair of equilibrating talpinine-type oxindole hemiacetals, eight oxidized derivatives of sarpagine- and akuammiline-type indole alkaloids, in addition to alstochalotine a diastereomer of gelsochalotine recently isolated from Gelsemium elegans, were isolated from the leaf and stem-bark extracts of Alstonia penangiana. The structures and relative configurations of these alkaloids were established using NMR, MS, and in one instance, confirmed by X-ray diffraction analysis. An NMR-based method is described as a useful chemotaxonomic tool for differentiating between A.

Macroline-Sarpagine Bisindole Alkaloids with Antiproliferative Activity from .

A methanol extract of the stem bark of the Malayan provided seven new bisindole alkaloids, comprising six macroline-sarpagine alkaloids (angustilongines E-K, -) and one macroline-pleiocarpamine bisindole alkaloid (angustilongine L, ). Analysis of the spectroscopic data (NMR and MS) of these compounds led to the proposed structures of these alkaloids. The macroline-sarpagine alkaloids (-) showed in vitro growth inhibitory activity against a panel of human cancer cell lines, inclusive of KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells (IC values: 0.

Lycopodium Alkaloids: Lycoplatyrine A, an Unusual Lycodine-Piperidine Adduct from Lycopodium platyrhizoma and the Absolute Configurations of Lycoplanine D and Lycogladine H.

Three new Lycopodium alkaloids comprising two lycodine-type alkaloids (1, 2) and one fawcettimine alkaloid (3), in addition to 16 known alkaloids, were isolated from Lycopodium platyrhizoma. The structures of these alkaloids were elucidated based on analysis of their NMR and MS data. Lycoplatyrine A (1) represents an unusual lycodine-piperidine adduct.

Histological and Behavioral Phenotypes of a Novel Mutated APP Knock-In Mouse.

Gene mutations within amyloid precursor protein (APP or AβPP) and/or presenilin 1 (PS1) genes are determinants of familial Alzheimer's disease (fAD) and remain fundamental for experimental models. Here, we generated a neuronal knock-in mouse (PLB2APP) with mutated human APPSwe/Lon and investigated histopathology and behavioral phenotypes. Additionally, PLB2APP mice were cross-bred with a presenilin (PS1A246E) line to assess the impact of this gene combination.

Of mice and motion: Behavioural-EEG phenotyping of Alzheimer's disease mouse models.

Background: Rodent electroencephalography (EEG) in preclinical research is frequently conducted in behaving animals. EEG analysis is complicated by a number of confounds, particularly 1. The close relationship between EEG power and movement speed must be controlled for prior to further analysis.

Ajmaline, Oxindole, and Cytotoxic Macroline-Akuammiline Bisindole Alkaloids from Alstonia penangiana.

Examination of the EtOH extract of the Malayan Alstonia penangiana resulted in the isolation of 10 new alkaloids, comprising two ajmaline (1, 2), four macroline oxindole (3-6), and four macroline-akuammiline bisindole alkaloids (7-10). The structures of these alkaloids were determined based on analysis of the spectroscopic data and, in the case of the oxindole 6 and the bisindole alkaloid 7, also confirmed by X-ray diffraction analysis. The bisindole alkaloids 7 and 8 showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells with IC values in the 0.

Biosynthetic Enantiodivergence in the Eburnane Alkaloids from Kopsia.

Reexamination of the absolute configuration of recently isolated eburnane alkaloids from Malaysian Kopsia and Leuconotis species by X-ray diffraction analysis and ECD/TDDFT has revealed the existence of biosynthetic enantiodivergence. Three different scenarios are discerned with respect to the composition of the enantiomeric eburnane alkaloids in these plants: first, where the new eburnane congeners possess the same C-20, C-21 absolute configurations as the common eburnane alkaloids (eburnamonine, eburnamine, isoeburnamine, eburnamenine) occurring in the same plant; second, where the new eburnane congeners possess opposite or enantiomeric C-20, C-21 absolute configurations compared to the common eburnane alkaloids found in the same plant; and, third, where the four common eburnane alkaloids were isolated as racemic or scalemic mixtures, while the new eburnane congeners were isolated as pure enantiomers with a common C-20, C-21 configuration (20α, 21α). Additionally, the same Kopsia species (K.

Inactivation Kinetics and Mechanism of a Human Norovirus Surrogate on Stainless Steel Coupons via Chlorine Dioxide Gas.

Acute gastroenteritis caused by human norovirus is a significant public health issue. Fresh produce and seafood are examples of high-risk foods associated with norovirus outbreaks. Food contact surfaces also have the potential to harbor noroviruses if exposed to fecal contamination, aerosolized vomitus, or infected food handlers.

Solvent-enabled nonenyzmatic sugar production from biomass for chemical and biological upgrading.

We recently reported a nonenzymatic biomass deconstruction process for producing carbohydrates using homogeneous mixtures of γ-valerolactone (GVL) and water as a solvent. A key step in this process is the separation of the GVL from the aqueous phase, enabling GVL recycling and the production of a concentrated aqueous carbohydrate solution. In this study, we demonstrate that phenolic solvents-sec-butylphenol, nonylphenol, and lignin-derived propyl guaiacol-are effective at separating GVL from the aqueous phase using only small amounts of solvent (0.

Assessing Knowledge Sharing Among Academics: A Validation of the Knowledge Sharing Behavior Scale (KSBS).

Background: There is a belief that academics tend to hold on tightly to their knowledge and intellectual resources. However, not much effort has been put into the creation of a valid and reliable instrument to measure knowledge sharing behavior among the academics.

Objectives: To apply and validate the Knowledge Sharing Behavior Scale (KSBS) as a measure of knowledge sharing behavior within the academic community.

Relationship between cervical spine injury and helmet use in motorcycle road crashes.

Motorcycle helmets have been proven to prevent head injury and reduce fatality in road crashes. However, certain studies indicate that the helmet increases the mass to the head, and thus the potential of neck injury due to the flexion/extension of the head-neck segment in a road crash may increase. This study was conducted to evaluate the effects of motorcycle helmets and the ways in which the accidents that occurred affected the incidence of cervical spine injury.

Transphyseal fracture-separation of the femoral capital epiphysis: a true SCFE of traumatic origin.

Acute traumatic transphyseal fracture of the capital femoral epiphysis is a rare but serious injury. The injury is typically inflicted by a severe trauma. Because of the vulnerability and predisposed anatomy of the femoral epiphysis in relation to its blood supply, the fracture has been designated to have poor prognosis with inevitable osteonecrosis and eventual deformity of the hip.

Screw osteosynthesis of displaced lateral humeral condyle fractures in children: a mid-term review.

Displaced humeral condyle fractures in children are traditionally fixed with smooth Kirschner wire at the expense of a risk of secondary displacement following removal of wire. Screw fixation of such fractures has recently been advocated as it provides stable fixation. We have been using screw osteosynthesis for treatment of displaced lateral humeral condyle fractures in children in our institution since the turn of this century.

Prophylactic antibiotics in orthopaedic surgery: guidelines and practice.

The national clinical practice guideline has recommended that prophylactic antibiotic be given in orthopaedic surgery involving joint replacements and internal fixation of fractures. The aim of this study is to assess the current antibiotics prophylaxis practice in a state level hospital. One hundred and three patients (68 males, 35 females; mean age 41.

Shoulder pain -- a common problem in world-class badminton players.

Badminton is a sport that requires a lot of over-shoulder motion, with the shoulder in abduction/external rotation. This questionnaire study on 188 international top-level badminton players during the World Mixed Team Championships showed that previous or present shoulder pain on the dominant side was reported by 52% of the players. Previous shoulder pain was reported by 37% of the players and on-going shoulder pain by 20% of the players.

Revision surgery for developmental dysplasia of the hip.

Revision surgery following failed open reduction for developmental dysplasia of the hip (DDH) is technically demanding. We reviewed 12 patients in our institution that required a revision surgery between January 1994 and December 2003. The aims of this study are to identify the causes of redislocation after the primary open reduction and to determine the clinical and radiological outcome after the revision surgery.

Audit on radiographs in anterior shoulder dislocations.

The radiographs of 115 anterior shoulder dislocations (100 patients; 74 males, 26 female were reviewed to assess the radiographic views used in the management of this dislocation. Eighty-eight patients (88%) had only the anteroposterior (AP) view, 10 patients had 2 radiographic views taken and only 2 patients had three radiographic views. Hill-Sachs lesions were found in 18%, and glenoid rim fractures in 3% of the patients.