Boundaries of solidarity: a meta-ethnography of mask use during past epidemics to inform SARS-CoV-2 suppression

Background: Many countries aiming to suppress SARS-CoV-2 recommend the use of face masks by the general public. The social meanings attached to masks may influence their use, but remain underinvestigated. / Methods: We systematically searched eight databases for studies containing qualitative data on public mask use during past epidemics, and used meta-ethnography to explore their social meanings. We compared key concepts within and across studies, then jointly wrote a critical synthesis. / Results: We found nine studies from China (n=5), Japan (n=1), Mexico (n=1), South Africa (n=1) and the USA (n=1). All studies describing routine mask use during epidemics were from East Asia. Participants identified masks as symbols of solidarity, civic responsibility and an allegiance to science. This effect was amplified by heightened risk perception (eg, during SARS in 2003), and by seeing masks on political leaders and in outdoor public spaces. Masks also acted as containment devices to manage threats to identity at personal and collective levels. In China and Japan, public and corporate campaigns framed routine mask use as individual responsibility for disease prevention in return for state- or corporate-sponsored healthcare access. In most studies, mask use waned as risk perception fell. In contexts where masks were mostly worn by patients with specific diseases (eg, for patients with tuberculosis in South Africa), or when trust in government was low (eg, during H1N1 in Mexico), participants described masks as stigmatising, uncomfortable or oppressive. / Conclusion: Face masks can take on positive social meanings linked to solidarity and altruism during epidemics. Unfortunately, these positive meanings can fail to take hold when risk perception falls, rules are seen as complex or unfair, and trust in government is low. At such times, ensuring continued use is likely to require additional efforts to promote locally appropriate positive social meanings, simplifying rules for use and ensuring fair enforcement

Epstein-barr virus-encoded latent membrane protein 1 impairs G2 checkpoint in human nasopharyngeal epithelial cells through defective Chk1 activation

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, particularly in southern regions of China. EBV infection is closely associated with NPC and has long been postulated to play an etiological role in the development of NPC. However, the role of EBV in malignant transformation of nasopharyngeal epithelial cells remains enigmatic. The current hypothesis of NPC development is that premalignant nasopharyngeal epithelial cells harboring genetic alterations support EBV infection and expression of EBV genes induces further genomic instability to facilitate the development of NPC. The latent membrane protein 1 (LMP1) is a well-documented EBV-encoded oncogene. The involvement of LMP1 in human epithelial malignancies has been implicated, but the mechanisms of oncogenic actions of LMP1, particularly in nasopharyngeal cells, are unclear. Here we observed that LMP1 expression in nasopharyngeal epithelial cells impaired G2 checkpoint, leading to formation of unrepaired chromatid breaks in metaphases after γ-ray irradiation. We further found that defective Chk1 activation was involved in the induction of G2 checkpoint defect in LMP1-expressing nasopharyngeal epithelial cells. Impairment of G2 checkpoint could result in loss of the acentrically broken chromatids and propagation of broken centric chromatids in daughter cells exiting mitosis, which facilitates chromosome instability. Our findings suggest that LMP1 expression facilitates genomic instability in cells under genotoxic stress. Elucidation of the mechanisms involved in LMP1-induced genomic instability in nasopharyngeal epithelial cells will shed lights on the understanding of role of EBV infection in NPC development. © 2012 Deng et al.published_or_final_versio

Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.published_or_final_versio

A pilot controlled trial of a combination of dense cranial electroacupuncture stimulation and body acupuncture for post-stroke depression

Our previous studies have demonstrated the treatment benefits of dense cranial electroacupuncture stimulation (DCEAS), a novel brain stimulation therapy in patients with major depression, postpartum depression and obsessive-compulsive disorder. The purpose of the present study was to further evaluate the effectiveness of DCEAS combined with body acupuncture and selective serotonin reuptake inhibitors (SSRIs) in patients with post-stroke depression (PSD).published_or_final_versio

Individualized surgical strategies for left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

OBJECTIVES: Surgical strategies to treat drug refractory left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy include septal myectomy (SM) and, less frequently, mitral valve (MV) repair or replacement. The primary aim of this study was to report the surgical technique and management outcomes in a consecutive group of patients with variable phenotypes of hypertrophic cardiomyopathy in a broad national specialist practice. METHODS: A total of 203 consecutive patients, 132 men (mean age 48.6 ± 14.6 years) underwent surgery for the management of LVOTO. Surgical approaches included SM (n = 159), SM with MV repair (n = 25), SM with MV replacement (n = 9) and MV replacement alone (n = 10). Specific surgical approaches were performed based on the underlying mechanism of obstruction. Eleven (5.4%) patients had previous alcohol septal ablation for the management of LVOTO. Concomitant non-mitral cardiac procedures were carried out in 22 (10.8%) patients. RESULTS: Operative survival rate was 99.0% with 2 deaths within 30 days. The mean bypass time was 92.9 ± 47.8 min, with a mean length of hospital stay of 10.5 ± 7.8 days. Surgical complications included 3 ventricular septal defects requiring repair (1.5%), 1 Gerbode defect surgically repaired, 2 aortic valve repairs (1.0%), 2 transient ischaemic attacks (1.0%) and 4 strokes (2.0%). Thirty-nine (19.2%) patients had perioperative new-onset atrial fibrillation and 8 (3.9%) patients had unexpected atrioventricular block requiring a permanent pacemaker. Mean resting left ventricular outflow tract gradient improved from 70.6 ± 40.3 mmHg preoperatively to 11.0 ± 10.5 mmHg at 1 year postoperatively (P < 0.001). Mean New York Heart Association class improved from 2.6 ± 0.5 preoperatively to 1.6 ± 0.6 at 1 year after the procedure. CONCLUSIONS: In variable phenotypes of LVOTO in hypertrophic cardiomyopathy, an individualized surgical approach provided effective reductions in left ventricular outflow tract gradients and good symptomatic relief with acceptable mortality and morbidity

Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells

Undifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1. Furthermore, overexpression of cyclin D1 is closely associated with EBV infection. Therefore we investigated the potential role of cyclin D1 overexpression in dysplastic NPE cells in vitro. In human telomerase reverse transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16-resistant form of CDK4 (CDK4(R24C)) suppressed differentiation. This suppression may have implications for the close association of EBV infection with undifferentiated NPC. In these in vitro models, we found that cellular growth arrest and senescence occurred in EBV-infected cell populations immediately after infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of CDK4 or knockdown of p16 in the human telomerase reverse transcriptase-immortalized NPE cell lines could counteract the EBV-induced growth arrest and senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells may contribute to NPC pathogenesis by enabling persistent infection of EBV.published_or_final_versio

Enhanced IL-6/IL-6R Signaling Promotes Growth and Malignant Properties in EBV-Infected Premalignant and Cancerous Nasopharyngeal Epithelial Cells

Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein-Barr virus (EBV) infection. However, the exact role of EBV in NPC pathogenesis remains elusive. Activation of signal transducer and activator of transcription 3 (STAT3) is common in human cancers including NPC and plays an important role in the pathogenesis and progression of human cancers. Interleukin-6 (IL-6), a major inflammatory cytokine, is a potent activator of STAT3. In this study, we report that EBV-infected immortalized nasopharyngeal epithelial (NPE) cells often acquire an enhanced response to IL-6-induced STAT3 activation to promote their growth and invasive properties. Interestingly, this enhanced IL-6/STAT3 response was mediated by overexpression of IL-6 receptor (IL-6R). Furthermore, IL-6R overexpression enhanced IL-6-induced STAT3 activation in uninfected immortalized NPE cells in vitro, and promoted growth and tumorigenicity of EBV-positive NPC cell line (C666-1) in vivo. Moreover, it is shown for the first time that IL-6R was overexpressed in clinical specimens of NPC. IL-6 expression could also be strongly detected in the stromal cells of NPC and a higher circulating level of IL-6 was found in the sera of advance-staged NPC patients compared to the control subjects. Therefore, IL-6R overexpression, coupled with enhanced IL-6/STAT3 signaling may facilitate the malignant transformation of EBV-infected premalignant NPE cells into cancer cells, and enhance malignant properties of NPC cells. © 2013 Zhang et al.published_or_final_versio

An Anti-Glitch in a Magnetar

Magnetars are neutron stars showing dramatic X-ray and soft $\gamma$-ray outbursting behaviour that is thought to be powered by intense internal magnetic fields. Like conventional young neutron stars in the form of radio pulsars, magnetars exhibit "glitches" during which angular momentum is believed to be transferred between the solid outer crust and the superfluid component of the inner crust. Hitherto, the several hundred observed glitches in radio pulsars and magnetars have involved a sudden spin-up of the star, due presumably to the interior superfluid rotating faster than the crust. Here we report on X-ray timing observations of the magnetar 1E 2259+586 which we show exhibited a clear "anti-glitch" -- a sudden spin down. We show that this event, like some previous magnetar spin-up glitches, was accompanied by multiple X-ray radiative changes and a significant spin-down rate change. This event, if of origin internal to the star, is unpredicted in models of neutron star spin-down and is suggestive of differential rotation in the neutron star, further supporting the need for a rethinking of glitch theory for all neutron stars

Checkpoints are blind to replication restart and recombination intermediates that result in gross chromosomal rearrangements

Replication fork inactivation can be overcome by homologous recombination, but this can cause gross chromosomal rearrangements that subsequently missegregate at mitosis, driving further chromosome instability. It is unclear when the chromosome rearrangements are generated and whether individual replication problems or the resulting recombination intermediates delay the cell cycle. Here we have investigated checkpoint activation during HR-dependent replication restart using a site-specific replication fork-arrest system. Analysis during a single cell cycle shows that HR-dependent replication intermediates arise in S phase, shortly after replication arrest, and are resolved into acentric and dicentric chromosomes in G2. Despite this, cells progress into mitosis without delay. Neither the DNA damage nor the intra-S phase checkpoints are activated in the first cell cycle, demonstrating that these checkpoints are blind to replication and recombination intermediates as well as to rearranged chromosomes. The dicentrics form anaphase bridges that subsequently break, inducing checkpoint activation in the second cell cycle

Endemicity of Zoonotic Diseases in Pigs and Humans in Lowland and Upland Lao PDR: Identification of Socio-cultural Risk Factors

In Lao People's Democratic Republic pigs are kept in close contact with families. Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products. This cross-sectional study was conducted in Luang Prabang (north) and Savannakhet (central-south) Provinces. A total of 59 villages, 895 humans and 647 pigs were sampled and serologically tested for zoonotic pathogens including: hepatitis E virus (HEV), Japanese encephalitis virus (JEV) and Trichinella spiralis; In addition, human sera were tested for Taenia spp. and cysticercosis. Seroprevalence of zoonotic pathogens in humans was high for HEV (Luang Prabang: 48.6%, Savannakhet: 77.7%) and T. spiralis (Luang Prabang: 59.0%, Savannakhet: 40.5%), and lower for JEV (around 5%), Taenia spp. (around 3%) and cysticercosis (Luang Prabang: 6.1, Savannakhet 1.5%). Multiple correspondence analysis and hierarchical clustering of principal components was performed on descriptive data of human hygiene practices, contact with pigs and consumption of pork products. Three clusters were identified: Cluster 1 had low pig contact and good hygiene practices, but had higher risk of T. spiralis. Most people in cluster 2 were involved in pig slaughter (83.7%), handled raw meat or offal (99.4%) and consumed raw pigs' blood (76.4%). Compared to cluster 1, cluster 2 had increased odds of testing seropositive for HEV and JEV. Cluster 3 had the lowest sanitation access and had the highest risk of HEV, cysticercosis and Taenia spp. Farmers which kept their pigs tethered (as opposed to penned) and disposed of manure in water sources had 0.85 (95% CI: 0.18 to 0.91) and 2.39 (95% CI: 1.07 to 5.34) times the odds of having pigs test seropositive for HEV, respectively. The results have been used to identify entry-points for intervention and management strategies to reduce disease exposure in humans and pigs, informing control activities in a cysticercosis hyper-endemic village