Values of sleep/wake, activity/rest, circadian rhythms, and fatigue prior to adjuvant breast cancer chemotherapy.

Fatigue is the most prevalent and distressing symptom experienced by patients receiving adjuvant chemotherapy for early stage breast cancer. Higher fatigue levels have been related to sleep maintenance problems and low daytime activity in patients who have received chemotherapy, but knowledge describing these relationships prior to chemotherapy is sparse. The Piper Integrated Fatigue Model guided this study, which describes sleep/wake, activity/rest, circadian rhythms, and fatigue and how they interrelate in women with Stage I, II, or IIIA breast cancer during the 48 hours prior to the first adjuvant chemotherapy treatment. The present report describes these variables in 130 females, mean age=51.4 years; the majority were married and employed. Subjective sleep was measured by the Pittsburgh Sleep Quality Index and fatigue was measured by the Piper Fatigue Scale. Wrist actigraphy was used to objectively measure sleep/wake, activity/rest, and circadian rhythms. Mean Pittsburgh Sleep Quality Index score was 6.73+/-3.4, indicating poor sleep. Objective sleep/wake results were within normal limits established for healthy individuals, except for the number and length of night awakenings. Objective activity/rest results were within normal limits except for low mean daytime activity. Circadian rhythm mesor was 132.3 (24.6) and amplitude was 97.2 (22.8). Mean Piper Fatigue Scale score was 2.56+/-2, with 72% reporting mild fatigue. There were significant relationships between subjective and objective sleep, but no consistent patterns. Higher total and subscale fatigue scores were correlated with most components of poorer subjective sleep quality (r=0.25-0.42, P\u3c or =0.005)

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1- hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist

The optimisation of two series of 4-hydroxybenzothiazolone derived β2-adrenoceptor agonists, bearing α-substituted cyclopentyl and β-phenethyl amino-substituents, as inhaled long-acting bronchodilators is described. Analogues were selected for synthesis using a lipophilicity based hypothesis to achieve the targeted rapid onset of action in combination with a long duration of action. The profiling of the two series led to identification of the α-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting β2-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the backup development candidate to indacaterol from the Novartis LABA project. © 2014 Elsevier Ltd. All rights reserved