Abstract
Study Objectives
Mobility restrictions imposed to suppress transmission of COVID-19 can alter physical activity (PA) and sleep patterns that are important for health and well-being. ...Characterization of response heterogeneity and their underlying associations may assist in stratifying the health impact of the pandemic.
Methods
We obtained wearable data covering baseline, incremental mobility restriction, and lockdown periods from 1,824 city-dwelling, working adults aged 21–40 years, incorporating 206,381 nights of sleep and 334,038 days of PA. Distinct rest-activity rhythm (RAR) profiles were identified using k-means clustering, indicating participants’ temporal distribution of step counts over the day. Hierarchical clustering of the proportion of days spent in each of these RAR profiles revealed four groups who expressed different mixtures of RAR profiles before and during the lockdown.
Results
Time in bed increased by 20 min during the lockdown without loss of sleep efficiency, while social jetlag measures decreased by 15 min. Resting heart rate declined by ~2 bpm. PA dropped an average of 42%. Four groups with different compositions of RAR profiles were found. Three were better able to maintain PA and weekday/weekend differentiation during lockdown. The least active group comprising ~51% of the sample, were younger and predominantly singles. Habitually less active already, this group showed the greatest reduction in PA during lockdown with little weekday/weekend differences.
Conclusion
In the early aftermath of COVID-19 mobility restriction, PA appears to be more severely affected than sleep. RAR evaluation uncovered heterogeneity of responses to lockdown that could associate with different outcomes should the resolution of COVID-19 be protracted.
The pharmacological activity and constituents of the sanchi ginseng Panax notoginseng have been reviewed. The bulk of pharmacological findings have been based on the saponins or steryl glycosides, ...although polysaccharides with immunopotentiating activity, proteins with antifungal, ribonuclease and xylanase activity, and a triacylglycerol (trilinolein) with antioxidant activity have been reported. Protective actions against cerebral ischaemia, beneficial effects on the cardiovascular system, and haemostatic, antioxidant, hypolipidaemic, hepatoprotective, renoprotective and estrogen‐like activities have been described. Various methods for authentication of P. notoginseng are available.
We present a new instrument, the Aerosol Chemical Speciation Monitor (ACSM), which routinely characterizes and monitors the mass and chemical composition of non-refractory submicron particulate ...matter in real time. Under ambient conditions, mass concentrations of particulate organics, sulfate, nitrate, ammonium, and chloride are obtained with a detection limit <0.2 μg/m
3
for 30 min of signal averaging. The ACSM is built upon the same technology as the widely used Aerodyne Aerosol Mass Spectrometer (AMS), in which an aerodynamic particle focusing lens is combined with high vacuum thermal particle vaporization, electron impact ionization, and mass spectrometry. Modifications in the ACSM design, however, allow it to be smaller, lower cost, and simpler to operate than the AMS. The ACSM is also capable of routine stable operation for long periods of time (months). Results from a field measurement campaign in Queens, NY where the ACSM operated unattended and continuously for 8 weeks, are presented. ACSM data is analyzed with the same well-developed techniques that are used for the AMS. Trends in the ACSM mass concentrations observed during the Queens, NY study compare well with those from co-located instruments. Positive Matrix Factorization (PMF) of the ACSM organic aerosol spectra extracts two components: hydrocarbon-like organic aerosol (HOA) and oxygenated organic aerosol (OOA). The mass spectra and time trends of both components correlate well with PMF results obtained from a co-located high resolution time-of-flight AMS instrument.
A 15-kDa antifungal protein, designated ganodermin, was isolated from the medical mushroom
Ganoderma lucidum. The isolation procedure utilized chromatography on DEAE-cellulose, Affi-gel blue gel, ...CM-Sepharose and Superdex 75. Ganodermin was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and CM-Sepharose. Ganodermin inhibited the mycelial growth of
Botrytis cinerea,
Fusarium oxysporum and
Physalospora piricola with an IC
50 value of 15.2
μM, 12.4
μM and 18.1
μM, respectively. It was devoid of hemagglutinating, deoxyribonuclease, ribonuclease and protease inhibitory activities.
In this multicentre study, we examined 60 cases of Type II enteropathy-associated T-cell lymphoma (EATL) from the Asia-Pacific region by histological review, immunohistochemistry and molecular ...techniques. Patients were mostly adult males (median age: 58 years, male:female 2.6:1), presenting with abdominal pain (60%), intestinal perforation (40%) and weight loss (28%). None had a history of coeliac disease and the median survival was only 7 months. Histologically, these tumours could be divided into (i) central tumour zone comprising a monotonous population of neoplastic lymphocytes, (ii) peripheral zone featuring stunted villi and morphologically atypical lymphocytes showing epitheliotropism, and (iii) distant mucosa with normal villous architecture and cytologically normal intra-epithelial lymphocytes (IELs). Characterized by extensive nuclear expression of Megakaryocyte-associated tyrosine kinase (MATK) (87%) and usually a CD8(+)CD56(+) (88%) cytotoxic phenotype, there was frequent aberrant expression of CD20 (24%). T-cell receptor (TCR) expression was silent or not evaluable in 40% but of the remainder, there was predominant expression of TCRαβ over TCRγδ (1.6:1). In keeping with the normal ratio of IEL subsets, CD8(+) cases showed predominant CD8αα homodimer expression (77%), regardless of TCR lineage. These tumours constitute a distinct entity from classical EATL, and the pathology may reflect tumour progression from IEL precursors, remnants of which are often seen in the distant mucosa.
Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations ...have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
Currently available combination chemotherapy for acute myeloid leukemia (AML) often fails to result in long-term remissions, emphasizing the need for novel therapeutic strategies. We reasoned that ...targeted inhibition of a prominent nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating cells (LICs) whose survival depends on timely XPO1-mediated transport of specific protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is currently in clinical trials, has strong activity against primary AML cells while sparing normal stem and progenitor cells. Importantly, limiting dilution transplantation assays showed that this cytotoxic activity is not limited to the rapidly proliferating bulk population of leukemic cells but extends to the LICs, whose inherent drug resistance and unrestricted self-renewal capacity has been implicated in the difficulty of curing AML patients with conventional chemotherapy alone.
Cordyceps species, including C. sinensis, C. militaris, C. pruinosa and C. ophioglossoides, are prized traditional medicinal materials. The aim of this article is to review the chemical constituents ...and pharmacological actions of Cordyceps species. The chemical constituents include cordycepin (3′‐deoxyadenosine) and its derivatives, ergosterol, polysaccharides, a glycoprotein and peptides containing α‐aminoisobutyric acid. They include anti‐tumour, anti‐metastatic, immunomodulatory, antioxidant, anti‐inflammatory, insecticidal, antimicrobial, hypolipidaemic, hypoglycaemic, anti‐ageing, neuroprotective and renoprotective effects. Polysaccharide accounts for the anti‐inflammatory, antioxidant, anti‐tumour, anti‐metastatic, immunomodulatory, hypoglycaemic, steroidogenic and hypolipidaemic effects. Cordycepin contributes to the anti‐tumour, insecticidal and antibacterial activity. Ergosterol exhibits anti‐tumour and immunomodulatory activity. A DNase has been characterized.
Chikungunya fever swept across many South and South-east Asian countries, following extensive outbreaks in the Indian Ocean Islands in 2005. However, molecular epidemiological data to explain the ...recent spread and evolution of Chikungunya virus (CHIKV) in the Asian region are still limited. This study describes the genetic Characteristics and evolutionary relationships of CHIKV strains that emerged in Sri Lanka and Singapore during 2006-2008. The viruses isolated in Singapore also included those imported from the Maldives (n=1), India (n=2) and Malaysia (n=31). All analysed strains belonged to the East, Central and South African (ECSA) lineage and were evolutionarily more related to Indian than to Indian Ocean Islands strains. Unique genetic characteristics revealed five genetically distinct subpopulations of CHIKV in Sri Lanka and Singapore, which were likely to have emerged through multiple, independent introductions. The evolutionary network based on E1 gene sequences indicated the acquisition of an alanine to valine 226 substitution (E1-A226V) by virus strains of the Indian sublineage as a key evolutionary event that contributed to the transmission and spatial distribution of CHIKV in the region. The E1-A226V substitution was found in 95.7 % (133/139) of analysed isolates in 2008, highlighting the widespread establishment of mutated CHIKV strains in Sri Lanka, Singapore and Malaysia. As the E1-A226V substitution is known to enhance the transmissibility of CHIKV by Aedes albopictus mosquitoes, this observation has important implications for the design of vector control strategies to fight the virus in regions at risk of chikungunya fever.
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