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Background Smell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID-19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID-19 patients suggests that self-reported measures are insufficient for capturing patients with chemosensory dysfunction. Objectives The purpose of this study was to quantify the impact of recent COVID-19 infection on chemosensory function and demonstrate the use of at-home objective smell and taste testing in an at-risk population of healthcare workers. Methods Two hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self-administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one-month follow-up surveys were completed. Results Among subjects with prior SARS-CoV-2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self-reported smell and taste loss were both strong predictors of COVID-19 positivity. Subjects with evidence of recent SARS-CoV-2 infection (

Background Personal-protective equipment (PPE)-preparedness, defined as adherence to guidelines, healthcare worker (HCW) training, procuring PPE stocks and responding appropriately to suspected cases, is crucial to prevent HCW-infections. Objective To perform a follow-up survey to assess changes in PPE-preparedness across six Asia-Pacific countries during the COVID-19 pandemic. Design Prospective follow-up cross-sectional, web-based survey between 10/08/2020 to 01/09/2020, five months after the initial Phase 1 survey. Setting The same six Asia-Pacific countries (Australia, Hong Kong, India, New Zealand, Philippines, and Singapore) that participated in Phase 1. Participants Intensivists from 231 ICUs across these six countries. Main outcome measures Changes in PPE-preparedness between Phases 1 and 2. Results Phase 2 had responses from 132 ICUs (57%). Compared to Phase 1 respondents reported increased use of PPE-based practices such as powered air-purifying respirator (40.2% vs. 6.1%), N95-masks at all times (86.4% vs. 53.7%) and double-gloving (87.9% vs. 42.9%). The reported awareness of PPE stocks (85.6% vs. 51.9%), mandatory showering policies following PPE-breach (31.1% vs. 6.9%) and safety perception amongst HCWs (60.6% vs. 28.4%) improved significantly during Phase 2. Despite reported statistically similar adoption rate of the buddy system in both phases (42.4% vs. 37.2%), there was a reported reduction in donning/doffing training in Phase 2 (44.3% vs. 60.2%). There were no reported differences HCW training in other areas, such as tracheal intubation, intra-hospital transport and safe waste disposal, between the 2 phases. Conclusions Overall reported PPE-preparedness improved between the two survey periods, particularly in PPE use, PPE inventory and HCW perceptions of safety. However, the uptake of HCW training and implementation of low-cost safety measures continued to be low and the awareness of PPE breach management policies were suboptimal. Therefore, the key areas for improvement should focus on regular HCW training, implementing low-cost buddy-system and increasing awareness of PPE-breach management protocols.

Rationale: Delivery of therapeutic agents to the brain is limited by the presence of the blood-brain barrier (BBB). An emerging strategy to temporarily and locally increase the permeability of the BBB is the use of transcranial focused ultrasound (FUS) and systematically injected microbubbles (MBs). FUS+MB BBB treatments cause an acute inflammatory response, marked by a transient upregulation of pro-inflammatory genes; however, the cellular immune response remains unknown. Methods: FUS+MB BBB treatments were monitored in real-time using two-photon fluorescence microscopy and transgenic EGFP Wistar rats, which harbour several fluorescent cell types. Leukocyte identification and counts were confirmed using magnetic resonance imaging-guided FUS+MB BBB treatments. Participation of leukocytes in reducing β-amyloid pathology following repeated FUS+MB BBB treatments was investigated in the TgCRND8 mouse model of Alzheimer's disease. Results: Intravascular leukocyte activity indicative of acute inflammation were identified, including transendothelial migration, formation of cell aggregates, and cell masses capable of perturbing blood flow. Leukocyte responses were only observed after the onset of sonication. Neutrophils were identified to be a key participating leukocyte. Significantly more neutrophils were detected in the sonicated hemisphere compared to the contralateral hemisphere, and to untreated controls. Three to five biweekly FUS+MB BBB treatments did not induce significantly more neutrophil recruitment, nor neutrophil phagocytosis of β-amyloid plaques, in TgCRND8 mice compared to untreated controls. Conclusions: This study provides evidence that the cellular aspect of the peripheral immune response triggered by FUS+MB BBB treatments begins immediately after sonication, and emphasizes the importance for further investigations to be conducted to understand leukocyte dynamics and cerebral blood flow responses to FUS+MB BBB treatments.

Cancer-Testis antigens (CTA) are immunogenic molecules with normal tissue expression restricted to testes but with aberrant expression in up to 30% of non-small cell lung cancers (NSCLCs). Regulation of CTA expression is mediated in part through promoter DNA methylation. Recently, immunotherapy has altered treatment paradigms in NSCLC. Given its immunogenicity and ability to be re-expressed through demethylation, NY-ESO-1 promoter methylation, protein expression and its association with programmed death receptor ligand-1 (PD-L1) expression and clinicopathological features were investigated. Lung cancer cell line demethylation resulting from 5-Aza-2'-deoxycytidine treatment was associated with both NY-ESO-1 and PD-L1 re-expression in vitro but not increased chemosensitivity. NY-ESO-1 hypomethylation was observed in 15/94 (16%) of patient samples and associated with positive protein expression (P < 0.0001). In contrast, PD-L1 expression was observed in 50/91 (55%) but strong expression in only 12/91 (13%) cases. There was no association between NY-ESO-1 and PD-L1 expression, despite resultant re-expression of both by 5-Aza-2'-deoxycytidine. Importantly, NY-ESO-1 hypomethylation was found to be an independent marker of poor prognosis in patients not treated with chemotherapy (HR 3.59, P = 0.003) in multivariate analysis. In patients treated with chemotherapy there were no differences in survival associated with NY-ESO-1 hypomethylation. Collectively, these results provided supporting evidence for the potential use of NY-ESO-1 hypomethylation as a prognostic biomarker in stage 3 NSCLCs. In addition, these data highlight the potential to incorporate demethylating agents to enhance immune activation, in tumours currently devoid of immune infiltrates and expression of immune checkpoint genes.

Background: A clinical decision support system (CDSS) has been designed to predict the outcome (overall survival) by extracting and analyzing information from routine clinical activity as a complement to clinical guidelines in lung cancer patients. Materials and methods: Prospective multicenter data from 543 consecutive (2013–2017) lung cancer patients with 1167 variables were used for development of the CDSS. Data Mining analyses were based on the XGBoost and Generalized Linear Models algorithms. The predictions from guidelines and the CDSS proposed were compared. Results: Overall, the highest (> 0.90) areas under the receiver-operating characteristics curve AUCs for predicting survival were obtained for small cell lung cancer patients. The AUCs for predicting survival using basic items included in the guidelines were mostly below 0.70 while those obtained using the CDSS were mostly above 0.70. The vast majority of comparisons between the guideline and CDSS AUCs were statistically significant (p < 0.05). For instance, using the guidelines, the AUC for predicting survival was 0.60 while the predictive power of the CDSS enhanced the AUC up to 0.84 (p = 0.0009). In terms of histology, there was only a statistically significant difference when comparing the AUCs of small cell lung cancer patients (0.96) and all lung cancer patients with longer (≥ 18 months) follow up (0.80; p < 0.001). Conclusions: The CDSS successfully showed potential for enhancing prediction of survival. The CDSS could assist physicians in formulating evidence-based management advice in patients with lung cancer, guiding an individualized discussion according to prognosis. Instituto de Salud Carlos III PI16/02104 Junta de Andalucía PIN-0476-2017 Ministerio de Economía y Competitividad FPAP13-1E-2429

Background The outbreak of COVID-19 and the physical isolation measures taken by the governments to reduce its propagation might have negative psychological consequences on the population. In this study, we aimed to explore, for the first time, how mental health status fluctuated along the weeks of the emergency state in Portugal, and to identify which factors may shape these changes in mental health outcomes. Methods To this end, we conducted an online survey to evaluate demographic, lifestyle and mental health variables (DASS-21 and quality of life) in the Portuguese population at three different time-points. 748 participants (mean age = 39.52, % females = 79.95) provided data at all time-points. Results We observed that depression, anxiety and stress symptoms seemed to improve as the weeks passed during the state of emergency, while the perception of quality of life and sleep got worse. In particular, being female, younger, actively working, and extroverted appear to be protective factors of mental health adaptability during this particular period. On the contrary, having a psychiatric diagnosis or physical illness, and higher neuroticism seem to be risk factors for mental health worsening. Limitations The lack of a more diverse sample could limit the generalizability of our results, and other factors that were not considered in our analysis might also have a significant impact on mental health. Conclusions Our results provide relevant and novel insights about the course of mental health changes and its predictors during the outbreak of COVID-19, which may help identify potential vulnerability groups.

Alternative splicing in Tau exon 10 generates 3 R- and 4 R-Tau proteoforms, which have equal abundance in healthy adult human brain. Aberrant alternative splicing in Tau exon 10 leads to distortion of the balanced 3 R- and 4 R-Tau expression levels, which is a causal factor to trigger toxic Tau aggregation, neuron dysfunction and patient death in a group of neurodegenerative diseases known as tauopathies. Hence, identification of regulators upstream of the Tau exon 10 splicing events are crucial to understanding pathogenic mechanisms driving tauopathies. In this study, we used RNA Antisense Purification with Mass Spectrometry (RAP-MS) analysis to identify RNA-binding proteins (RBPs) that interact with the Tau pre-mRNA near exon 10. Among the newly identified RBP candidates, we show that knockdown of hnRNPC induces Tau exon 10 skipping whereas overexpression of hnRNPC promotes Tau exon 10 inclusion. In addition, we show that hnRNPC interacts with the poly-uridine (U-tract) sequences in introns 9 and 10 of Tau pre-mRNA. Mutation of these U-tract motifs abolished binding of hnRNPC with Tau pre-mRNA fragment and blocked its impact on Tau exon 10 inclusion. These findings indicate that hnRNPC binds and utilizes these U-tract motifs located in introns 9 and 10 of Tau pre-mRNA to promote Tau exon 10 inclusion. Intriguingly, high hnRNPC expression level is associated with progressive supranuclear palsy (PSP), a sporadic tauopathy with pathological accumulation of Tau species that contain exon 10, which suggests a putative therapeutic role of hnRNPC for PSP treatment. [Figure: see text].

Neurons have highlighted the needs for decentralized gene expression and specific RNA function in somato-dendritic and axonal compartments, as well as in intercellular communication via extracellular vesicles (EVs). Despite advances in miRNA biology, the identity and regulatory capacity of other small non-coding RNAs (sncRNAs) in neuronal models and local subdomains has been largely unexplored.We identified a highly complex and differentially localized content of sncRNAs in axons and EVs during early neuronal development of cortical primary neurons and in adult axons invivo. This content goes far beyond miRNAs and includes most known sncRNAs and precisely processed fragments from tRNAs, sno/snRNAs, Y RNAs and vtRNAs. Although miRNAs are the major sncRNA biotype in whole-cell samples, their relative abundance is significantly decreased in axons and neuronal EVs, where specific tRNA fragments (tRFs and tRHs/tiRNAs) mainly derived from tRNAs Gly-GCC, Val-CAC and Val-AAC predominate. Notably, although 5'-tRHs compose the great majority of tRNA-derived fragments observed invitro, a shift to 3'-tRNAs is observed in mature axons invivo.The existence of these complex sncRNA populations that are specific to distinct neuronal subdomains and selectively incorporated into EVs, equip neurons with key molecular tools for spatiotemporal functional control and cell-to-cell communication. ispartof: RNA BIOLOGY vol:18 issue:sup2 pages:832-855 ispartof: location:United States status: published

Background after hospitalisation for cardiac disease, older patients are at high risk of readmission and death. Objective the cardiac care bridge (CCB) transitional care programme evaluated the impact of combining case management, disease management and home-based cardiac rehabilitation (CR) on hospital readmission and mortality. Design single-blind, randomised clinical trial. Setting the trial was conducted in six hospitals in the Netherlands between June 2017 and March 2020. Community-based nurses and physical therapists continued care post-discharge. Subjects cardiac patients ≥ 70 years were eligible if they were at high risk of functional loss or if they had had an unplanned hospital admission in the previous 6 months. Methods the intervention group received a comprehensive geriatric assessment-based integrated care plan, a face-to-face handover with the community nurse before discharge and follow-up home visits. The community nurse collaborated with a pharmacist and participants received home-based CR from a physical therapist. The primary composite outcome was first all-cause unplanned readmission or mortality at 6 months. Results in total, 306 participants were included. Mean age was 82.4 (standard deviation 6.3), 58% had heart failure and 92% were acutely hospitalised. 67% of the intervention key-elements were delivered. The composite outcome incidence was 54.2% (83/153) in the intervention group and 47.7% (73/153) in the control group (risk differences 6.5% [95% confidence intervals, CI −4.7 to 18%], risk ratios 1.14 [95% CI 0.91–1.42], P = 0.253). The study was discontinued prematurely due to implementation activities in usual care. Conclusion in high-risk older cardiac patients, the CCB programme did not reduce hospital readmission or mortality within 6 months. Trial registration Netherlands Trial Register 6,316, https://www.trialregister.nl/trial/6169

Summary Acute Myeloid Leukaemia (AML) is a rare but serious group of diseases that require critical decision-making for curative treatment. Over the past decade, scientific discovery has revealed dozens of prognostic gene mutations for AML while sequencing costs have plummeted. In this study, we compared the cost-effectiveness of multigene integrative analysis (genomic analysis) with the standard molecular testing currently used for diagnosis of intermediate-risk AML. We used a decision analytic model with data for costs and outcomes from British Columbia, Canada, to assess the long-term (10-year) economic impacts. Our results suggest that genomic analysis would result in a 26% increase in the use of first-remission allogeneic stem cell transplantation. The resulting treatment decisions and downstream effects would come at an additional cost of $12 556 [2013 Canadian dollars (CAD)] per person and the incremental cost-effectiveness ratio would be $49 493 per quality-adjusted life-year gained. Cost-effectiveness was dependent on quality of life during the long-term (5–10) years of survival, relapse rates following first-remission chemotherapy and the upfront cost of transplantation. Non-relapse mortality rates, short-term quality of life and the cost of genomic sequencing had only minor impacts. Further research on post-remission outcomes can lead to improvements in the cost-effectiveness of curative treatments for AML.

Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized that disruption of gut homeostasis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage of the Syrian hamster model. Our data confirmed that this model recapitulates some hallmark features of the human disease in the lungs. We further showed that SARS-CoV-2 infection associated with mild intestinal inflammation, relative alteration in intestinal barrier property and liver inflammation and altered lipid metabolism. These changes occurred concomitantly with an alteration of the gut microbiota composition over the course of infection, notably characterized by a higher relative abundance of deleterious bacterial taxa such as Enterobacteriaceae and Desulfovibrionaceae. Conversely, several members of the Ruminococcaceae and Lachnospiraceae families, including bacteria known to produce the fermentative products short-chain fatty acids (SCFAs), had a reduced relative proportion compared to non-infected controls. Accordingly, infection led to a transient decrease in systemic SCFA amounts. SCFA supplementation during infection had no effect on clinical and inflammatory parameters. Lastly, a strong correlation between some gut microbiota taxa and clinical and inflammation indices of SARS-CoV-2 infection severity was evidenced. Collectively, alteration of the gut microbiota correlates with disease severity in hamsters making this experimental model valuable for the design of interventional, gut microbiota-targeted, approaches for the control of COVID-19. Abbreviations: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; SCFAs, short-chain fatty acids; dpi, day post-infection; RT-PCR, reverse transcription polymerase chain reaction; IL, interleukin. ACE2, angiotensin converting enzyme 2; TMPRSS2, transmembrane serine protease 2.

Objective Salivary gland tumors account for 6%–8% of head and neck neoplasms with the parotid gland as the most common primary site. Pleomorphic adenomas (PA) are considered the most common benign parotid gland neoplasms, followed by Warthin tumors (WT). The goal of this study was to investigate the distribution of parotid gland neoplasms among a United States veteran population. Design Retrospective chart review. Setting Washington DC Veterans Affairs Medical Center. Participants Veterans who underwent fine needle aspiration (FNA) for a parotid gland mass from 2000 to 2018 were included. Medical records were reviewed for gender, age, tobacco use, surgery date, and pathology results. Main outcome measures Changes in the distribution of parotid neoplasms and tobacco use over an 18-year period. Results Of 141 patients with parotid gland masses, 86.5% (n = 122) were benign, 9.9% (n = 14) were malignant, and 3.5% (n = 5) were indeterminate. Of benign tumors, WT accounted for the majority at 51.6%, followed by PA at 40.2%. When stratified by decade (2000–2009 and 2010–2018), the proportion of WT compared to all other benign and malignant neoplasms increased from 31.6% to 53.6%, whereas the proportion of PA decreased from 36.8% to 33.3%. The rate of tobacco use was unchanged at approximately 32.0% among our cohort from 2000 to 2018. Conclusion Among our cohort of veteran patients, WT was the most common benign parotid tumor and has increased in incidence over the last two decades despite an unchanged smoking rate.

Sialendoscopy is a minimally invasive technique that facilitates the diagnosis and treatment of sialolithiasis. This case series presents the novel use of sialendoscopy to treat sialodocholithiasis in six patients with a non-functional or surgically absent submandibular gland by a single surgeon at the University of Pennsylvania Health System between March 2013 and December 2019. The four female and two male patients had a median age of 56 years and mean follow-up of 16.2 months (range 1–44.5). All stones were successfully removed using sialendoscopy, and in 5 patients a combined approach was utilized. All patients remain asymptomatic at last clinical follow-up. We conclude that sialendoscopy is a viable, minimally invasive method for managing sialodocholithiasis in patients with prior submandibular gland excision or atretic gland. It is also useful as an assistive tool when approaching complex transcervical or transoral procedures in previously instrumented patients.

Objective To evaluate the necessity and effectiveness of a preplanned technique for drilling during transcanal endoscopic ear surgery. Methods Study design: Retrospective case series study from June 2011 to June 2015. Setting: Private tertiary care hospital. Patients: Eighty-five ears of 78 patients, age ranging from 9 to 57 years underwent transcanal endoscopic drilling for various types of pathology in their middle and external ear. Interventions: Application of a preplanned technique for transcanal drilling in endoscopic ear surgery that involved short timed drilling with use of intermittent irrigation and suction. Every events of the procedure were done one after another with the single hand of the surgeon. An attachment providing protecting sheath around rotating burr was used during each time of drilling. Main outcomes measure: Efficacy of such drilling technique in single handed endoscopic ear surgery. Presence of any postoperative thermal injury of facial nerve and any lacerated injury of skin of external ear. Results This preplanned technique was found suitable for transcanal endoscopic drilling with the single hand of the surgeon. Postoperative facial nerve palsy or laceration of skin of external ear was not noted in any patient. Conclusion After using the present technique, transcanal endoscopic drilling could be done easily and safely with single hand of the surgeon.

Background Analysis of fluid metabolites has the potential to provide insight into the neuropathophysiology of injury in patients with traumatic brain injury (TBI). Objective Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined (1) if urinary metabolites change during recovery in patients with mild to severe TBI; (2) whether changes in urinary metabolites correlate to injury severity; (3) whether biological pathway analysis reflects mechanisms that mediate neural damage/repair throughout TBI recovery. Methods Urine samples were collected within 7 days and at 6-months post-injury in male participants (n = 8) with mild-severe TBI. Samples were analyzed with NMR-based quantitative spectroscopy for metabolomic profiles and analyzed with multivariate statistical and machine learning-based analyses. Results Lower levels of homovanillate (R = −0.74, p ≤ 0.001), L-methionine (R = −0.78, p, Highlights • NMR-based metabolomics of urine can identify metabolic fingerprints associated with functional recovery following TBI. • Metabolic profiles in urine correlate to injury severity. • Biological pathway analysis reflects mechanisms that mediate neural damage and repair processes throughout recovery. • Metabolomics provides insight into the neuropathophysiology of injury in TBI patients.

Objective: We conducted this study to determine the associations of possible risk factors and prevalence of recurrent otitis media with effusion (OME) in a cohort of children in Upper Egypt. Methods: This was a cross-sectional study undertaken in two tertiary referral centers in Upper Egypt. Associations of possible risk factors with prevalence of recurrent OME were studied. Multi-factor logistic regression analysis was done to recognize the statistically significant risk factors associated with recurrent OME. Results: We collected the data of 2003 pediatric patients, of which 1016 were males (50.7%). A total number of 310 children have OME, including 159 males (51.3%). The prevalence rate of OME in our cohort was 15.5%. Multi-factor logistic regression analysis of the risk factors related to recurrent OME showed it was strongly associated with adenoid hypertrophy (P

Objectives: Describe the h index as a bibliometric that can be utilized to objectively evaluate scholarly impact. Identify which otolaryngology subspecialties are the most scholarly. Describe if NIH funding to one’s choice of medical school, residency, or fellowship has any impact on one’s scholarly output. Determine other factors predictive of an academic otolaryngologist’s productivity. Study design: Analysis of bibliometric data of academic otolaryngologists. Methods: Active grants from the National Institutes of Health (NIH) to otolaryngology departments were ascertained via the NIH Research Portfolio Online Reporting Tools Expenditures and Reports database. Faculty listings from these departments were gleaned from departmental websites. H index was calculated using the Scopus database. Results: Forty-seven otolaryngology programs were actively receiving NIH funding. There were 838 faculty members from those departments who had a mean h index of 9.61. Otology (h index 12.50) and head and neck (h index 11.96) were significantly (P

INTRODUCTION: There is growing concern about the effect of lockdown and social distancing on mental health. Subjective feelings related to social relationships such as detachment have shown a strong effect on mental health, whereas objective factors might have a moderating role in that association. OBJECTIVE: To investigate whether social support and living situation have a moderating effect on the association between detachment and affective disorder symptoms during the COVID-19 lockdown. METHODS: 3,305 Spanish adults were interviewed by phone at the end of the COVID-19 lockdown (May-June 2020). Detachment during confinement was assessed with a single-item frequency question. Anxiety symptoms were measured through GAD-7, depressive symptoms through PHQ-9, and social support through the Oslo Social Support Scale (OSSS). Associations with anxiety and depressive symptoms were tested through Tobit regression models. Interactions of detachment with living situation and social support were tested as independent variables. RESULTS: People living alone showed significantly lower levels of anxiety whereas people living with another (but not as a couple) showed higher levels of depression. Detachment was strongly associated with both affective disorders. Social support had a statistically significant moderating effect on that association. Those with a low level of social support and a high level of detachment reported means of depression and anxiety above major depression (10.5 CI 95% 9.6, 11.4 at OSSS=10) and generalized anxiety disorders (10.1 CI 95% 9.2, 11.0 at OSSS=9) cut offs CONCLUSION: Interventions centered on improving social support could alleviate feelings of detachment and prevent affective disorders during lockdowns.

Background The COVID-19 pandemic has brought about tremendous social and economic turmoil, which has been associated with increased levels of depression and anxiety. Methods We analyzed data from the Healthy Minds Study (Fall Semester Cohort 2020), a non-probability sample of students across multiple colleges who completed an online survey between September – December 2020. Using multivariable logistic regression, we examined the associations between COVID-19 dimensions (concern, racial/ethnic discrimination, financial distress, infection, illness of loved one, death of loved one, caregiving) and mental health outcomes (depression, anxiety), adjusting for age, gender, race/ethnicity, and international student status. Results Nearly a fifth of the sample reported moderately severe or severe depression, and nearly a third reported moderately severe or severe anxiety over the past two weeks. When accounting for all COVID-19 dimensions in the same model, COVID-19 concern, racial/ethnic discrimination, financial distress, and infection were significantly associated with moderately severe or severe depression; COVID-19 concern, financial distress, and infection were significantly associated with moderately severe or severe anxiety. Conclusions This study showed that the COVID-19 pandemic may have shaped mental health through a range of potential social and environmental dimensions. Interventions are required that consider multiple dimensions of COVID-19 to improve mental health during and after the pandemic.

Background Anxiety sensitivity (AS) is a well-studied transdiagnostic risk construct that is believed to amplify responses to many forms of stress. The COVID-19 pandemic is a broad stressor with significant physical and social threats. In the current study, we were interested in ascertaining the degree to which AS would relate to distress and disability in the context of COVID-19. We hypothesized that AS would be associated with increased distress and disability. Moreover, we hypothesized that AS would be uniquely predictive while controlling for other relevant risk factors such as age, race, and perceived local COVID-19 infection rates. Method Participants (N = 249) were U.S. adults assessed using online data resourcing and re-assessed one month later. Results At the first time point, during the beginning phases of the COVID-19 pandemic, AS was significantly related to COVID-19 distress and disability with a moderate effect size. AS was longitudinally associated with higher COVID-19 worry and depression. Limitations Our findings are limited by the use of a relatively small online sample. Additionally, assessment of pre-pandemic and post-pandemic symptoms and functioning would be beneficial for future research. Conclusions Taken together, the current study provided evidence consistent with AS as a causal risk factor for the development of distress and depression during the COVID-19 pandemic.

International audience; Pompe disease is an inherited metabolic disorder due to the deficiency of the lysosomal acid α-glucosidase (GAA). The only approved treatment is enzyme replacement therapy with the recombinant enzyme (rhGAA). Further approaches like pharmacological chaperone therapy, based on the stabilising effect induced by small molecules on the target enzyme, could be a promising strategy. However, most known chaperones could be limited by their potential inhibitory effects on patient's enzymes. Here we report on the discovery of novel chaperones for rhGAA, L- and D-carnitine, and the related compound acetyl-D-carnitine. These drugs stabilise the enzyme at pH and temperature without inhibiting the activity and acted synergistically with active-site directed pharmacological chaperones. Remarkably, they enhanced by 4-fold the acid α-glucosidase activity in fibroblasts from three Pompe patients with added rhGAA. This synergistic effect of L-carnitine and rhGAA has the potential to be translated into improved therapeutic efficacy of ERT in Pompe disease.

Objective:To describe existing online, 24-h dietary recall (24-h DR) tools in terms of functionalities and ability to tackle challenges encountered during national dietary surveys, such as maximising response rates and collecting high-quality data from a representative sample of the population, while minimising the cost and response burden.Design:A search (from 2000 to 2019) was conducted in peer-reviewed and grey literature. For each tool, information on functionalities, validation and user usability studies, and potential adaptability for integration into a new context was collected.Setting:Not country-specificParticipants:General populationResults:Eighteen online 24-h DR tools were identified. Most were developed in Europe, for children ≥10 years old and/or for adults. Eight followed the five multiple-pass steps but used various methodologies and features. Almost all tools (except three) validated their nutrient intake estimates, but with high heterogeneity in methodologies. User usability was not always assessed, and rarely by applying real-time methods. For researchers, eight tools developed a web platform to manage the survey and five appeared to be easily adaptable to a new context.Conclusions:Among the eighteen online 24-h DR tools identified, the best candidates to be used in national dietary surveys should be those that were validated for their intake estimates, had confirmed user and researcher usability, and seemed sufficiently flexible to be adapted to new contexts. Regardless of the tool, adaptation to another context will still require time and funding, and this is probably the most challenging step.

Background Healthcare workers (HCW) are exposed to an increased risk of COVID-19 through direct contact with patients and patient environments. We calculated the; seroprevalence of SARS-CoV-2 in HCW at Eastern Health, a tertiary healthcare network in Victoria, and assessed associations with demographics, work location and role. Methods A cross-sectional cohort study of HCW at Eastern Health was conducted. Serum was analysed for the presence of antibodies to SARS-CoV-2, and all participants completed; an online survey collecting information on demographics, place of work, role, and exposures; to COVID-19. Seroprevalence was calculated as the proportion participants with SARS-CoV-2; antibodies out of all tested individuals. Results The crude seroprevalence of SARS-CoV-2 antibodies in this study was 2.17% (16/736). Thirteen of the 16 (81.2%) positive cases had previously been diagnosed with COVID-19 by PCR: the seroprevalence in the group not previously diagnosed with COVID by PCR was 0.42% (3/720). Having direct contact with COVID-19 patients did not increase the likelihood of having positive serology. A prior history of symptoms consistent with COVID-19 was associated with a higher likelihood of having positive serology (OR 17.2, p = 0.006, 95%CI: 2.25–131.55). Conclusion Our calculated seroprevalence of 2.17% is higher than estimated in the general Australian population, but lower than that reported in HCW internationally. The; majority of those with positive serology in our study had previously been diagnosed with COVID-19 by PCR based testing. Seropositivity was not associated with interaction with COVID-19 positive patients, highlighting effective infection prevention and control practices within the workplace.

The contributions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) to breast cancer are critical areas of investigation. In this study, we identified a novel lncRNA RP11-283G6.5 which was lowly expressed in breast cancer and whose low expression was correlated with poor overall survival and disease-free survival of breast cancer patients. Functional experiments revealed that ectopic expression of RP11-283G6.5 confined breast cancer cellular growth, migration, and invasion, and promoted cellular apoptosis. Conversely, RP11-283G6.5 silencing facilitated breast cancer cellular growth, migration, and invasion, and repressed cellular apoptosis. Moreover, RP11-283G6.5 was found to confine breast cancer tumour growth and metastasis in vivo. Mechanistically, RP11-283G6.5 competitively bound to ILF3, reduced the binding of ILF3to primary miR-188 (pri-miR-188), abolished the suppressive effect of ILF3 on pri-miR-188 processing, and therefore promoted pri-miR-188 processing, leading to the reduction of pri-miR-188 and the upregulation of mature miR-188-3p. The expression of RP11-283G6.5 was significantly positively correlated with that of miR-188-3p in breast cancer tissues. Through increasing miR-188-3p, RP11-283G6.5 decreased TMED3, a target of miR-188-3p. RP11-283G6.5 further suppressed Wnt/β-catenin signalling via decreasing TMED3. Rescue assays revealed that inhibition of miR-188-3p, overexpression of TMED3 or blocking Wnt/β-catenin signalling all attenuated the roles of RP11-283G6.5 in breast cancer. Collectively, these findings demonstrated that RP11-283G6.5 is a tumour suppressive lncRNA in breast cancer via modulating miR-188-3p/TMED3/Wnt/β-catenin signalling. This study indicated that RP11-283G6.5 might be a promising prognostic biomarker and therapeutic target for breast cancer.

Background Care home (CH) residents are mainly inactive, leading to increased dependency and low mood. Strategies to improve activity are required. Design and setting Cluster randomised controlled feasibility trial with embedded process and health economic evaluations. Twelve residential CHs in Yorkshire, United Kingdom, were randomised to the MoveMore intervention plus usual care (UC) (n = 5) or UC only (n = 7). Participants Permanent residents aged ≥65 years. Intervention MoveMore: a whole home intervention involving all CH staff designed to encourage and support increase in movement of residents. Objectives and measurements Feasibility objectives relating to recruitment, intervention delivery, data collection and follow-up and safety concerns informed the feasibility of progression to a definitive trial. Data collection at baseline, 3, 6 and 9 months included: participants’ physical function and mobility, perceived health, mood, quality of life, cognitive impairment questionnaires; accelerometry; safety data; intervention implementation. Results 300 residents were screened; 153 were registered (62 MoveMore; 91 UC). Average cluster size: MoveMore: 12.4 CHs; UC: 13.0 CHs. There were no CH/resident withdrawals. Forty (26.1%) participants were unavailable for follow-up: 28 died (12 MoveMore; 16 UC); 12 moved from the CH. Staff informant/proxy data collection for participants was >80%; data collection from participants was Conclusions Recruiting CHs and residents was feasible. Intervention implementation and data collection methods need refinement before a definitive trial. There were no safety concerns.

The complex interactions between cells of the tumor microenvironment and cancer cells are considered a major determinant of cancer progression and metastasis. Yet, our understanding of the mechanisms of metastatic disease is not sufficient to successfully treat patients with advanced-stage cancer. JUNB is a member of the AP-1 transcription factor family shown to be frequently deregulated in human cancer and associated with invasion and metastasis. A strikingly high stromal JUNB expression in human breast cancer samples prompted us to functionally investigate the consequences of JUNB loss in cells of the tumor microenvironment on cancer progression and metastasis in mice. To adequately mimic the clinical situation, we applied a syngeneic spontaneous breast cancer metastasis model followed by primary tumor resection and identified stromal JUNB as a potent suppressor of distant metastasis. Comprehensive characterization of the JUNB-deficient tumor microenvironment revealed a strong influx of myeloid cells into primary breast tumors and lungs at early metastatic stage. In these infiltrating neutrophils, BV8 and MMP9, proteins promoting angiogenesis and tissue remodeling, were specifically upregulated in a JUNB-dependent manner. Taken together, we established stromal JUNB as a strong suppressor of distant metastasis. Consequently, therapeutic strategies targeting AP-1 should be carefully designed not to interfere with stromal JUNB expression as this may be detrimental for cancer patients. Supplementary Information The online version contains supplementary material available at 10.1007/s10585-021-10108-9.

Key Summary Points Aim To examine changing trends in presentation of older people to the emergency department during the COVID-19 pandemic compared to 2018/2019. Findings On average 4 fewer people aged ≥70 years presented to the ED in the first 6 months of the COVID-19 pandemic (March-August 2020). There was a 20% reduction in presentations of stroke and cardiac complaints but a 25% increase in falls/injuries following easing of lockdown restrictions. Message It is imperative that we consider enabling strategies to ensure older people access unscheduled care in a timely manner when necessary., Purpose Reports suggest that many older people deferred seeking healthcare during the COVID-19 pandemic due to fear of contracting COVID-19. The aim of this study was to examine trends of emergency department (ED) use by older people during the first wave of the COVID-19 pandemic compared to previous years. Methods The study site is a 1000-bed university teaching hospital with annual ED new-patient attendance of > 50,000. All ED presentations of patients aged ≥ 70 years from March to August 2020, 2019 and 2018 inclusive (n = 13,989) were reviewed and compared for presenting complaint, Manchester Triage Score, and admission/discharge decision. Results There was a 16% reduction in presentations across the 6 months in 2020 compared to the average of 2018/2019. On average, 4 fewer people aged ≥ 70 years presented to the ED per day in 2020. Much of this was concentrated in March (33% fewer presentations) and April (31% fewer presentations), when the country was in ‘lockdown’, i.e. non-essential journeys were banned. There was a 20% reduction in patients presenting with stroke and cardiac complaints. In the 3 months following easing of restrictions, there was a 25% increase in falls and orthopaedic injuries when compared to 2018/2019. Conclusion This study demonstrates a significant decline in the number of older people presenting to the ED for unscheduled care, including for potentially time-dependent illnesses such as stroke or cardiac complaints. Given the possibility of further lockdowns, it is imperative that we consider enabling strategies to ensure older people access unscheduled care in a timely manner when necessary.

Purpose Prisoners have poorer oral health than the general population. Good oral health is essential for both social and physical well-being. For prisoners, poor oral health is also related to drug use after release, whereas good oral health is related to successful reintegration into society. The purpose of this study was twofold: to examine the effect of an intervention based on motivational interviewing (MI) on prisoners’ oral health-related behavior and to assess if the intervention is a good fit for this population. Design/methodology/approach In total, 16 prisoners in a Norwegian prison were offered a brief MI-based intervention focusing on changing their oral health-related behavior. An oral examination was also performed and the prisoners received a small package containing oral hygiene aids. Two weeks later, a second oral examination and a semi-structured interview were conducted to explore the effect of the intervention and examine the prisoners’ responses to the intervention. Qualitative data analyzes were guided by thematic analysis. Findings The findings indicate that the intervention had positive effects on both the prisoners’ motivation to use oral health-related behavior and their performance of oral health-related behavior. The findings also indicate that the intervention was well adapted to the target population. Originality/value This is one of the first studies that explore the effect of an intervention in improving prisoners’ oral health and bridges a knowledge gap in the literature. The findings may increase the understanding of how dental services should be organized and offered to provide dental health care to this vulnerable group.

Key summary points Aim The aim of the study is to assess the association of chronic conditions and multimorbidity with institutionalization in older people. Findings Having dementia, mood or neurological disorder and/or five or more chronic conditions were associated with a higher risk of institutionalization. Message These risk factors should be recognized in primary care when providing and targeting care and support for home-dwelling older people. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00535-y., Purpose The ageing population is increasingly multimorbid. This challenges health care and elderly services as multimorbidity is associated with institutionalization. Especially dementia increases with age and is the main risk factor for institutionalization. The aim of this study was to assess the association of chronic conditions and multimorbidity with institutionalization in home-dwelling older people, with and without dementia. Methods In this prospective study with 18-year follow-up, the data on participants’ chronic conditions were gathered at the baseline examination, and of conditions acquired during the follow-up period from the municipality’s electronic patient record system and national registers. Only participants institutionalized or deceased by the end of the follow-up period were included in this study. Different cut-off-points for multimorbidity were analyzed. Cox regression model was used in the analyses. Death was used as a competing factor. Results The mean age of the participants (n = 820) was 74.7 years (64.0‒97.0). During the follow-up, 328 (40%) were institutionalized. Dementia, mood disorders, neurological disorders, and multimorbidity defined as five or more chronic conditions were associated with a higher risk of institutionalization in all the participants. In people without dementia, mood disorders and neurological disorders increased the risk of institutionalization. Conclusion Having dementia, mood or neurological disorder and/or five or more chronic conditions were associated with a higher risk of institutionalization. These risk factors should be recognized when providing and targeting care and support for older people still living at home. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00535-y.

Introduction We studied the costs of formal and informal care in relation to Alzheimer’s disease (AD) progression. Methods 231 persons with AD with a family caregiver were followed up for 5 years. The Clinical Dementia Rating Scale—Sum of Boxes (CDR-SB) was used to measure AD progression. Health and social care unit costs were used for formal care costs. An opportunity cost method for lost leisure time was applied to analyse the cost of informal care. Results Total cost of care in early stage AD (CDR-SB ≤ 4) was 16,448€ (95% CI 13,722–19,716) annually. In mild (CDR-SB 4.5–9), moderate (CDR-SB 9.5–15.5) and severe (CDR-SB ≥ 16) AD, the total costs were 2.3, 3.4 and 4.4 times higher, respectively. A one-unit increase in CDR-SB increased the total, formal and informal costs by 15, 11 and 18%, respectively. Conclusions Compared to early AD, the costs of total, formal and informal care are remarkably higher already in mild AD. This finding emphasises early diagnosis, interventions and family support for persons with AD and their caregivers.

AimsIndividuals with mental disorders, on average, die prematurely, have higher levels of physical comorbidities and may experience accelerated ageing. In individuals with lifetime depression and healthy controls, we examined associations between age and multiple physiological measures.MethodThe UK Biobank study recruited >500,000 participants, aged 37–73 years, between 2006–2010. Generalised additive models were used to examine associations between age and grip strength, cardiovascular function, body composition, lung function and bone mineral density. Analyses were conducted separately in males and females with depression compared to healthy controls.ResultAnalytical samples included up to 342,393 adults (mean age = 55.87 years; 52.61% females). We found statistically significant differences between individuals with depression and healthy controls for most physiological measures, with standardised mean differences between -0.145 and 0.156. There was some evidence that age-related changes in body composition, cardiovascular function, lung function and heel bone mineral density followed different trajectories in individuals with depression. These differences did not uniformly narrow or widen with age. For example, BMI in female cases was 1.1 kg/m2 higher at age 40 and this difference narrowed to 0.4 kg/m2 at age 70. In males, systolic blood pressure was 1 mmHg lower in cases at age 45 and this difference widened to 2.5 mmHg at age 65.ConclusionIndividuals with depression differed from healthy controls across a broad range of physiological measures. Differences in ageing trajectories differed by sex and were not uniform across physiological measures, with evidence of both age-related narrowing and widening of case-control differences.

International audience; We previously demonstrated that F4 peptide (CNPEDCLYPVSHAHQR) from collagen XIX was able to inhibit melanoma cell migrationin vitro and cancer progression in a mouse melanoma model. The aim of the present work was to study the anti-angiogenic properties of F4 peptide. We demonstrated that F4 peptide inhibited VEGF-induced pseudo-tube formation on Matrigel by endothelial cells and endothelial sprouting in a rat aortic ring assay. By affinity chromatography, we identified αvβ3 and α5β1 integrins as potential receptors for F4 peptide on endothelial cell surface. Using solid phase assays, we proved the direct interaction between F4 and both integrins. Taken together, our results demonstrate that F4 peptide is a potent antitumor agent inhibiting both angiogenesis and tumor cell migration.

Summary Glucocorticoids form the backbone of paediatric acute lymphoblastic leukaemia (ALL) treatment. Many studies have been performed on steroid resistance; however, few studies have addressed the relationship between dose, concentration and clinical response. The aim of the present study was to evaluate the pharmacokinetics of prednisolone in the treatment of paediatric ALL and the correlation with clinical parameters. A total of 1028 bound and unbound prednisolone plasma concentrations were available from 124 children (aged 0–18 years) with newly diagnosed ALL enrolled in the Dutch Childhood Oncology Group studies. A population pharmacokinetic model was developed and post hoc area under the curve (AUC) was tested against treatment outcome parameters. The pharmacokinetics of unbound prednisolone in plasma was best described with allometric scaling and saturable binding to proteins. Plasma protein binding decreased with age. The AUC of unbound prednisolone was not associated with any of the disease parameters or treatment outcomes. Unbound prednisolone plasma concentrations correlated with age. No effect of exposure on clinical treatment outcome parameters was observed and does not substantiate individualised dosing. Poor responders, high‐risk and relapsed patients showed a trend towards lower exposure compared to good responders. However, the group of poor responders was small and requires further research.

No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery.In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor.First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity.Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value.Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment.Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.

Objective The aim of this study is to develop and evaluate a set of psychometrically equivalent disyllabic wordlist (SC-10) in Singapore Mandarin for clinical use. Study design A preliminary set of 1000 words were obtained from a dictionary of frequently used words by Singapore students. Ten native judges rate the familiarity level of each word. This is followed by a face-to-face public survey to rank the shortlisted word set from most to least familiar. The final 108 disyllabic words were recorded by a native female talker. 20 normal hearing subjects were used to obtain the percentage of correct word recognition at 24 intensity levels (−10 dB HL to 26 dB HL in 2 dB increment). Psychometric function slopes were calculated for each word. 100 words were eventually chosen and assigned into ten 10-word lists based on a psychometric balancing protocol. Minor digital adjustments were made to the intensity of each wordlist to improve their auditory homogeneity. The developed SC-10 wordlists were validated by a separate group of 25 normal hearing subjects. Test-retest reliability was carried out on 20 out of 25 participants at the selected intensity levels (SRT-5, SRT, SRT+5). Results The calculated regression slopes in the psychometric functions for the ten lists are between 8.0 and 9.8%/dB. Single factor ANOVA analysis showed no significant difference in both the mean intensity required to obtain 50% recognition score (f = 0.109, df = 9, p = 0.999) and the slopes of the psychometric functions (f = 0.078, df = 9, p = 0.999) between the ten word lists. List validation on 25 normal hearing participants (PTA = 11.0 dB HL, SD = 4.3) showed a mean speech recognition threshold (SRT) of 9.3 dB HL (SD = 3.5)and regression slope of 8.395%/dB. Quadratic regression analysis showed a positive correlation (r2 = 0.923) between presentation level and word recognition score (WRS). The difference between PTA and SRT of each subject all fall within the clinically acceptable difference of 10 dB HL. Test-retest reliability, carried out on 20 subjects at three levels (SRT-5, SRT, and SRT+5 dB), showed no significance difference between word recognition score when the same participant is tested again at the same intensity level using a different wordlist. Conclusion All in all, it shows that the SC-10 speech materials are valid for clinical use for Mandarin speech audiometry in Singapore.

Background the aim of this study was to examine the cross-sectional and longitudinal associations of different multimorbidity patterns with physical frailty in older adults. Methods we used data from the Swedish National study on Aging and Care in Kungsholmen to generate a physical frailty measure, and clusters of participants with similar multimorbidity patterns were identified through fuzzy c-means cluster analyses. The cross-sectional association (n = 2,534) between multimorbidity clusters and physical frailty was measured through logistic regression analyses. Six- (n = 2,122) and 12-year (n = 2,140) longitudinal associations were determined through multinomial logistic regression analyses. Results six multimorbidity patterns were identified at baseline: psychiatric diseases; cardiovascular diseases, anaemia and dementia; sensory impairments and cancer; metabolic and sleep disorders; musculoskeletal, respiratory and gastrointestinal diseases; and an unspecific pattern lacking any overrepresented diseases. Cross-sectionally, each pattern was associated with physical frailty compared with the unspecific pattern. Over 6 years, the psychiatric diseases (relative risk ratio [RRR]: 3.04; 95% confidence intervals [CI]: 1.59–5.79); cardiovascular diseases, anaemia and dementia (RRR 2.25; 95% CI: 1.13–4.49) and metabolic and sleep disorders (RRR 1.99; 95% CI: 1.25–3.16) patterns were associated with incident physical frailty. The cardiovascular diseases, anaemia and dementia (RRR: 4.81; 95% CI: 1.59–14.60); psychiatric diseases (RRR 2.62; 95% CI: 1.45–4.72) and sensory impairments and cancer (RRR 1.87; 95% CI: 1.05–3.35) patterns were more associated with physical frailty, compared with the unspecific pattern, over 12 years. Conclusions we found that older adults with multimorbidity characterised by cardiovascular and neuropsychiatric disease patterns are most susceptible to developing physical frailty.

The role of lncRNA HCP5 in esophageal squamous cell carcinoma (ESCC) remains unknown despite its involvement in different malignancies. MTT assay, EdU assay, TUNEL assay, transwell assay, and sphere formation assay were conducted to reveal ESCC cell viability, proliferation, apoptosis, migration, invasion, and stemness characteristics. FISH and subcellular fraction assays were performed to reveal the subcellular location of HCP5 in ESCC cells. Luciferase reporter assay and RIP assay were conducted to explore the downstream axis of HCP5. Our findings revealed that HCP5 expression was at a higher level in ESCC tissues and cells compared to that in control tissues and cells. Additionally, HCP5 promoted ESCC cellular activities by promoting proliferation, migration, invasion ability and stemness characteristics of ESCC cells as well as suppressing cell apoptosis. Furthermore, we found that HCP5 bound with miR-139-5p to upregulate PDE4A via the competing endogenous RNA network in ESCC cells. Importantly, HCP5 was discovered to stimulate the PI3K/AKT/mTOR signaling by regulating the downstream target genes. Finally, rescue assays indicated that HCP5 promoted ESCC cell growth by activating the PDE4A-medaited PI3K/AKT/mTOR pathway. HCP5 promotes ESCC cellular development by modulating the miR-139-5p/PDE4A pathway and stimulating the PI3K/AKT/mTOR signaling pathway, which may be conducive for the improvement of ESCC treatment.

Objective:To explore how some of the largest food companies involved in producing alternative proteins (AP) use health and nutrition claims to market their products.Design:We identified the largest food manufacturers, meat processors and AP companies selling plant-based AP products in the USA. Using publicly available data, we analysed the voluntary health and nutrition claims made on front-of-pack labels (FOPL) and company webpages. We also analysed company websites for further nutrition and health-related statements about their products or AP more generally. Claim classification was guided by the INFORMAS (International Network for Food and Obesity/Non-Communicable Diseases Research, Monitoring, and Action Support) taxonomy for health-related food labelling.Setting:USA.Participants:Not applicable.Results:1394 health and nutrition-related FOPL claims were identified on 216 products, including 685 nutrition claims and 709 ‘other health-related’ claims. No FOPL health claims were identified. Most nutrient claims were for nutrients associated with meat, with 94 % of products carrying a protein claim and 30 % carrying a cholesterol claim. 74 % of products carried a GMO-free claim, and 63 % carried a plant-based claim. On their websites, some companies expanded on these claims or discussed the health benefits of specific ingredients.Conclusions:Companies involved in this category appear to be using nutritional marketing primarily to position their products in relation to meat. There is a focus on nutrient and ingredient claims, with discussion of processing largely avoided. The findings highlight the challenges companies face in positioning AP products as healthy against the backdrop of debates about ultra-processed foods.

We recently identified a CD63-interacting protein to understand the role of CD63 in virion production of the human immunodeficiency virus type 1, and we have found that Rab3a forms a complex with CD63. In this study, we analysed the effect of Rab3a on virion production of the murine leukaemia virus (MLV), which is another member of the retrovirus family. We found that Rab3a silencing induced lysosomal degradation of the MLV Gag protein, and recovery of the Rab3a expression restored the level of the Gag protein through a complex formation of MLV Gag and Rab3a, indicating that Rab3a is required for MLV Gag protein expression. In contrast, CD63 silencing decreased the infectivity of released virions but had no effect on virion production, indicating that CD63 facilitates the infectivity of released MLV particles. Although Rab3a induced CD63 degradation in uninfected cells, the complex of MLV Gag and Rab3a suppressed the Rab3a-mediated CD63 degradation in MLV-infected cells. Finally, we found that the MLV Gag protein interacts with Rab3a to stabilize its own protein and CD63 that facilitates the infectivity of released MLV particles. Considering the involvement of Rab3a in lysosome trafficking to the plasma membrane, it may also induce cell surface transport of the MLV Gag protein., Small GTPases, 13(1), pp.162-182; 2022

Animal studies have reported the use of different opioid-vaccine formulations with relative success These studies have suggested that new opioid-vaccine formulations are required, which are capable of triggering a robust humoral response. One strategy that has been used is the co-administration of two or more vaccines with different but complementary properties, which are capable of generating a robust immune response. We have developed two formulations of opioid-vaccine, the M(6)-TT, and M(3)-TT, which generate a robust immune response capable of recognizing heroin and morphine. In this work, we evaluate the combination of two vaccine formulations, which we call the M(3/6)-TT vaccine, to elicit a robust immune response and protection against heroin and morphine. Balb/c mice were immunized simultaneously with M(6)-TT vaccine and with M(3)-TT vaccine. A solid-phase antibody-capture ELISA was used for monitoring antibody titer responses after each booster dose in vaccinated animals. The study used tail-flick and hot-plate testing to evaluate the antinociceptive effects induced by heroin or morphine. Immunization with M(3)-TT and M(6)-TT vaccine elicits a robust immune response with an antibody titer of 1: 590 000 able to recognize heroin and morphine. These antibodies are capable of reducing the antinociceptive effects induced by doses of up to 40 mg/Kg. of morphine or 10 mg/kg of heroin. This suggests that the combination of two vaccine formulations that generate antibodies with different but complementary characteristics would be a new therapeutic strategy aimed at reducing drug relapses.

Objective:To explore the promotion of discretionary foods/beverages and marketing strategies employed by the top three online food delivery services’ (OFDS) Instagram accounts in three countries before and during the coronavirus disease 2019 (COVID-19) pandemic.Design:Publicly available data were extracted for the top three OFDS Instagram accounts for Australia, United Kingdom (UK) and the United States of America (USA) from March to May 2019 and 2020. Food/beverage items from posts were classified as ‘discretionary’ or from the five food groups (FFG) according to the Australian Dietary Guidelines. Marketing strategies were coded using an existing framework. Posts referring to COVID-19 were coded under four marketing strategies: (i) appropriating frontline workers; (ii) combatting the pandemic; (iii) selling social distancing; and (iv) accelerating digitalisation.Results:From 581 posts, 618 food/beverage items were shown, of which 69 % (427/618) were classified as discretionary. In 2019, the most used marketing strategies were product imagery (unbranded) (137/195, 70 %), links (111/195, 57 %) and sponsorships/partnerships (58/195, 30 %). In 2020, the most used were links (252/386, 68 %), product imagery (unbranded) (179/386, 49 %) and branding elements (175/386, 45 %). The most common COVID-19 marketing strategy was combatting the pandemic (76/123, 62 %) followed by selling social distancing (53/123, 43 %), appropriating frontline workers (34/123, 28 %) and accelerating digitalisation (32/123, 26 %).Conclusions:Following the COVID-19 pandemic, OFDS adapted their marketing, creating content with the theme of ‘combatting the pandemic’. Due to the growing number of discretionary foods/beverages promoted on Instagram, this highlights the need for policy action to counter the potential influence social media platforms have on dietary behaviours.

Key summary points Aim To investigate performance of the Months of the Year Backwards (MOTYB) test in older hospitalised patients with delirium, dementia, and no cognitive impairment. Findings Half of the patients with delirium (46%) could not engage with MOTYB compared to only 11% of patients with dementia without delirium. In patients able to give responses, those with delirium or dementia performed significantly worse than those without cognitive impairment. Message Our findings show the potential value of analysing response patterns, especially initial engagement, self-correction, and ability to continue to do the task in addition to considering exclusively the capacity to correctly recite the months until July, June or January. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00521-4., Purpose To investigate performance of the Months of the Year Backwards (MOTYB) test in older hospitalised patients with delirium, dementia, and no cognitive impairment. Methods Secondary analysis of data from a case–control study of 149 hospitalised patients aged ≥ 65 years with delirium [with or without dementia (N = 50)], dementia [without delirium (N = 46)], and no cognitive impairment (N = 53). Verbatim transcripts of MOTYB audio recordings were analysed to determine group differences in response patterns. Results In the total sample [median age 85y (IQR 80–88), 82% female], patients with delirium were more often unable to recite months backward to November (36/50 = 72%) than patients with dementia (21/46 = 46%; p

Human papillomavirus (HPV) vaccination could prevent most of the ~34,000 HPV-attributable cancers diagnosed annually in the US, but uptake remains suboptimal. Healthcare systems are key partners in implementing HPV vaccination quality improvement (QI) programs. To inform future system-level HPV vaccine initiatives, we sought to understand HPV vaccine QI from the perspective of QI program leaders in healthcare systems. We conducted telephone interviews with a multi-state sample of 17 QI leaders in 15 systems. We analyzed data qualitatively via thematic analysis to describe QI leaders' perspectives on prioritizing and implementing HPV vaccine QI. All QI leaders endorsed HPV vaccination as beneficial, and some had already prioritized increasing uptake to improve adolescent health and meet payor reimbursement standards. Those not prioritizing HPV vaccination cited concerns including the relatively small size of adolescent patient populations, lack of buy-in among providers, and the need to focus on health services perceived as more profitable or urgent. When implementing HPV vaccine QI programs, QI leaders reported key barriers to be the lack of robust data systems and acceptable QI metrics, limited time, and pressures of a fee-for-service clinical environment. Facilitators included automation and standardization in QI efforts and passionate vaccine champions. Almost all QI leaders reported future plans to implement HPV vaccine QI projects. Findings suggest that many healthcare systems are motivated to improve HPV vaccination. However, resistance to guideline-consistent quality metrics, the narrow target of one vaccine in the adolescent patient population, payment structures, and constrained time of providers are key barriers to practice improvements.

Objective:To investigate the association between family, teachers and peer support patterns on gaps in adolescent’s weight perceptions.Design:A cross-sectional, school-based survey collected information on weight and height, weight perception, socio-economic and family characteristics and social support. Principal component analysis (PCA) was performed to capture social support patterns (SSP). Multivariable logistic regression was used to model adolescent weight perception, including SSP adjusted for demographic variables.Setting:The 2014 Israeli Health Behaviours in School-Aged Children (HBSC) survey.Participants:Adolescents aged 11–18 years (n 7563).Results:In total, 16·1 % of the boys and 10·7 % of the girls were overweight or obese. Most participants perceived their size accurately. Body size was underestimated by 25·6 % of the boys and 15·1 % of the girls, while 15·2 % of the boys and 27·7 % of the girls overestimated their body size. PCA generated three SSP accounting for 81·9 % of the variance in social support. Female sex and higher SES increased odds of overestimating body size. Students in the top quartile (Q4 v. Q1–Q3) of family support and teacher support were less likely to overestimate their body size. Good parental communication reduced the odds of body size overestimation in middle school students. Male sex and higher family support increased odds of underestimation.Conclusions:Significant support from parents and teachers was associated with accurate weight perceptions; thus, support skills may be amenable to intervention. Efforts should be made to educate adolescents on healthy weight.

Background: This study investigated the potential molecular mechanism of circular RNA HIPK3 (circHIPK3) in breast cancer (BCa). Methods: BCa cells were transfected with miR-326 mimic, miR-326 inhibitor, circHIPK3, sicircHIPK3. The expressions of circHIPK3 and miR-326 in BCa tissues and BCa cell lines were determined by RT-qPCR. Cell viability, colony formation, migration, invasion, and apoptosis of the cells were detected by CCK-8 and colony formation, wound-healing, transwell and flow cytometric assays, respectively. The relationship between circHIPK3 and miR-326 was analyzed and confirmed by circInteractome, dual-luciferase reporter, RT-qPCR, Pearson’s correlation assays. Western blot and RT-qPCR were performed to determine the expressions of apoptosis-related molecules (Bcl-2, Bax, and cleaved Caspase-3) and EMT-related molecules (E-cadherin, N-cadherin, and Vimentin) in the BCa cells and tumor tissues. The tumor growth in mice was examined in a xenograft tumor model in which Ki-67 expression was determined by immunohistochemistry (IHC). Results: In BCa, the expression of circHIPK3 was up-regulated and that of miR-326 was down-regulated. CircHIPK3 knockdown inhibited the cell proliferation, invasion, and migration. MiR-326 was the direct target of circHIPK3, and was inversely correlated with circHIPK3 expression. CircHIPK3 overexpression promoted proliferation, migration, invasion, apoptosis resistance, and tumor growth and up-regulated Ki-67 expression, at the same time, the expressions of Bcl-2, N-cadherin, Vimentin were up-regulated, and those of Bax, cleaved Caspase-3 and E-cadherin were inhibited. These above expressions were partially reversed by miR-326 overexpression. Conclusion: CircHIPK3 sponges miR-326 to promote BCa growth and metastasis. The current findings provide a novel therapeutic target for treating BCa.

The purpose of this study is to evaluate the attitudes of healthcare professionals toward the COVID −19 vaccine, which has been introduced to healthcare professionals at the beginning of 2021 and give information to them on the disease and vaccine. This cross-sectional analytical study has been performed by conducting an online survey to the healthcare professionals who work at the healthcare institutions in the province of Samsun in Turkey between December 2020 and January 2021. In addition to sixteen questions about the demographic characteristics, the “Attitudes towards the COVID −19 vaccine” scale has been used. MANOVA test and Spearman rho correlation coefficient were used in analytical examinations. A total of 1426 healthcare professional have been reached. 64.3% of participants were female, 44.1% were nurse/midwife and 66.6% were public employees. Regarding the questions in the sub-dimension of positive attitude, the rate of response of “I agree/I strongly agree” was between 40.6% and 54.6%. Positive attitude mean values differ according to gender, age, institution, presence of children, smoking status, being a relative who died due to COVID −19, and profession (respectively p

This study investigated parental acceptability of COVID-19 vaccination for children under the age of 18 years among Chinese parents who are healthcare workers. A closed online survey among full-time doctors or nurses employed by the five collaborative hospitals who had access to smartphones was conducted. Facilitated by the hospital administrators, prospective participants received an invitation sent by the research team via the existing WeChat/QQ groups to complete an online questionnaire. A total of 2,281 participants completed the survey. This study was a sub-analysis of 1332 participants who had at least one child under the age of 18 years. Among the participants, 44.5% reported that they would likely or very likely to have their children under the age of 18 years take up COVID-19 vaccination in the next six months. After adjusting for significant background characteristics, perceived higher vaccine efficacy, longer protection duration, perceived high/very high chance for China to prevent another wave of COVID-19 outbreak with vaccines in place and willingness to receive a COVID-19 vaccination for themselves were associated with higher parental acceptability of COVID-19 vaccination. At interpersonal level, higher frequency of information exposure through social media and direct interpersonal communication were associated with higher parental acceptability of COVID-19 vaccination, while knowing some people who experienced serious side effects following COVID-19 vaccination were associated with lower parental acceptability of COVID-19 vaccination. Despite their important roles in vaccination promotion, Chinese doctors and nurses showed low parental acceptability of COVID-19 vaccination. Effective health promotion is needed when COVID-19 vaccination become available.

Purpose GSK2982772 is a selective inhibitor of receptor-interacting protein kinase-1, with a 2–3 h half-life. This study evaluated if a once-daily modified-release formulation of GSK2982772 could be developed with no significant food effect. Methods Part A evaluated the pharmacokinetics of GSK2982772 following fasted single-dose (120 mg) administration of two matrix minitab formulations (MT-8 h and MT-12 h) vs 120 mg immediate release (IR) and MT-12 h with a high-fat meal. Part B evaluated once-daily MT-12 h for 3 days at three dose levels. Part C evaluated a matrix monolithic (MM-12 h) formulation at two dose levels in different prandial states. Results All modified-release formulations dosed in the fasted state reduced maximum plasma concentration (Cmax), delayed time to Cmax, and decreased area under the curve (AUC) vs IR. When MT-12 h or MM-12 h were co-administered with a meal (standard or high-fat) Cmax and AUC increased. Dosing MM-12 h 1 h before a standard or high-fat meal had minimal impact on exposure vs fasted. Conclusions MT-12 h and MM-12 h provided a QD pharmacokinetic profile in the fasted state, however when MT-12 h was dosed with a high-fat meal a QD profile was not maintained. (ClinicalTrials.gov Identifier: NCT03266172).

Background and objectives: Influenza vaccination rates among medical students (MSs) are below the standards recommended in hospitals where influenza vaccination is not mandatory. We carried out a comparative study in two Spanish university hospitals to reassert this fact and evaluated the impact on vaccination rates of a specific program aimed at promoting influenza vaccination among MSs. Methods: A descriptive cross-sectional study was performed describing influenza vaccination rates and motivations for vaccination during the 2017/18 campaign among MSs in two hospitals affiliated to the same university. We subsequently performed a community-based intervention study during the 2018/19 campaign evaluating the impact of a strategy for promoting influenza vaccination, comparing the hospital where the intervention took place (hospital A) with the one where it did not take place (hospital B). Results: During de 2017/18 campaign the overall influenza vaccination rate was 44.8%, with no differences between hospitals A and B (difference: 3.9%; 95% CI: −4.36–12.16; p-value = .4). During the 2018/19 campaign, vaccination rate increased to 76.4% in hospital A, with significant differences compared with the previous campaign in the same hospital (29.8%; OR 5.00; 95% CI: 3.14–8.3; p-value = .0001) and with that observed in hospital B in the same campaign (21.1%; 95% CI: 13.38–28.82; p-value

Currently, most licensed vaccines against SARS-CoV-2 infection are approved for adults and not for children. We conducted a test negative case-control study to assess the effectiveness of Measles Containing Vaccines (MCVs) against SARS-CoV-2 infection in Pune, India, in children who were ≥1 year and