Antagonistic conflict between transposon-encoded introns and guide RNAs.

TnpB nucleases represent the evolutionary precursors to CRISPR-Cas12 and are widespread in all domains of life. IS605-family TnpB homologs function as programmable RNA-guided homing endonucleases in bacteria, driving transposon maintenance through DNA double-strand break-stimulated homologous recombination. In this work, we uncovered molecular mechanisms of the transposition life cycle of IS607-family elements that, notably, also encode group I introns. We identified specific features for a candidate "IStron" from Clostridium botulinum that allow the element to carefully control the relative levels of spliced products versus functional guide RNAs. Our results suggest that IStron transcripts evolved an ability to balance competing and mutually exclusive activities that promote selfish transposon spread while limiting adverse fitness costs on the host. Collectively, this work highlights molecular innovation in the multifunctional utility of transposon-encoded noncoding RNAs.

Associations of COVID-19-related fear with kidney disease quality of life and its subscales among hemodialysis patients as modified by health literacy: a multi-hospital survey.

Background: Receiving hemodialysis treatment makes end-stage renal disease (ESRD) patients highly vulnerable amidst the COVID-19 pandemic. Hence, their kidney disease quality of life (KDQOL) is affected. We aimed to examine the association between fear of COVID-19 (FCoV-19) and KDQOL, and the effect modification of Health literacy (HL) on this association. Material and Methods: A survey was conducted at 8 hospitals from July 2020 to March 2021 on 972 patients. Data collection includes socio-demographic factors, clinical parameters, HL, digital healthy diet literacy (DDL), hemodialysis diet knowledge (HDK), FCoV-19, suspected COVID-19 symptoms (S-COVID-19-S), and KDQOL. Results: Higher HL scores B = 0.13 (95% CI = 0.06-0.21, p = 0.001) and HDK scores B = 0.58 (95% CI = 0.31-0.85, p = 0.001) were associated with higher KDQOL scores. Whereas, S-COVID-19-S B = -6.12 (95% CI = -7.66 to - 4.58, p = 0.001) and FCoV-19 B = -0.91 (95% CI = -1.03 to - 0.80, p = 0.001) were associated with lower KDQOL scores. Notably, higher HL scores significantly attenuate the negative impact of FCoV-19 on overall KDQOL and the kidney disease component summary. Conclusions: In hemodialysis patients, FCoV-19 and S-COVID-19-S were associated with a lower KDQOL. Health literacy significantly mitigates the negative impact of FCoV-19 on KDQOL. Strategic public health interventions to improve HL are suggested to protect patient's KDQOL during the pandemic.

TnpB homologues exapted from transposons are RNA-guided transcription factors.

Transposon-encoded tnpB and iscB genes encode RNA-guided DNA nucleases that promote their own selfish spread through targeted DNA cleavage and homologous recombination1-4. These widespread gene families were repeatedly domesticated over evolutionary timescales, leading to the emergence of diverse CRISPR-associated nucleases including Cas9 and Cas12 (refs. 5,6). We set out to test the hypothesis that TnpB nucleases may have also been repurposed for novel, unexpected functions other than CRISPR-Cas adaptive immunity. Here, using phylogenetics, structural predictions, comparative genomics and functional assays, we uncover multiple independent genesis events of programmable transcription factors, which we name TnpB-like nuclease-dead repressors (TldRs). These proteins use naturally occurring guide RNAs to specifically target conserved promoter regions of the genome, leading to potent gene repression in a mechanism akin to CRISPR interference technologies invented by humans7. Focusing on a TldR clade found broadly in Enterobacteriaceae, we discover that bacteriophages exploit the combined action of TldR and an adjacently encoded phage gene to alter the expression and composition of the host flagellar assembly, a transformation with the potential to impact motility8, phage susceptibility9, and host immunity10. Collectively, this work showcases the diverse molecular innovations that were enabled through repeated exaptation of transposon-encoded genes, and reveals the evolutionary trajectory of diverse RNA-guided transcription factors.

Sex Differences in Clustering Unhealthy Lifestyles Among Survivors of COVID-19: Latent Class Analysis.

BACKGROUND: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. OBJECTIVE: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences. METHODS: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group. RESULTS: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group. CONCLUSIONS: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being.

Targeting Dendritic Cell Dysfunction to Circumvent Anti-PD1 Resistance in Head and Neck Cancer.

PURPOSE: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed. EXPERIMENTAL DESIGN: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model. RESULTS: An aPD1-resistant mouse model showed poor priming in the tumor DLN due to type 1 conventional dendritic cell (cDC1) dysfunction, which correlated with exhausted and poorly responsive antigen-specific T cells. Tumor microenvironment analysis also showed decreased cDC1 in aPD1-resistant tumors compared with sensitive tumors. Following neoadjuvant aPD1 therapy, pathologic responses in patients also positively correlated with baseline transcriptomic cDC1 signatures. In an aPD1-resistant model, intratumoral cDC1 vaccine was sufficient to restore aPD1 response by enhancing T-cell infiltration and increasing antigen-specific responses with improved tumor control. Mechanistically, CCL5 expression significantly correlated with neoadjuvant aPD1 response and enforced expression of CCL5 in an aPD1-resistant model, enhanced cDC1 tumor infiltration, restored antigen-specific responses, and recovered sensitivity to aPD1 treatment. CONCLUSIONS: These data highlight the contribution of tumor-infiltrating cDC1 in HNSCC aPD1 response and approaches to enhance cDC1 infiltration and function that may circumvent aPD1 resistance in patients with HNSCC.

Antagonistic conflict between transposon-encoded introns and guide RNAs.

TnpB nucleases represent the evolutionary precursors to CRISPR-Cas12 and are widespread in all domains of life, presumably due to the critical roles they play in transposon proliferation. IS605family TnpB homologs function in bacteria as programmable homing endonucleases by exploiting transposon-encoded guide RNAs to cleave vacant genomic sites, thereby driving transposon maintenance through DSB-stimulated homologous recombination. Whether this pathway is conserved in other genetic contexts, and in association with other transposases, is unknown. Here we uncover molecular mechanisms of transposition and RNA-guided DNA cleavage by IS607-family elements that, remarkably, also encode catalytic, self-splicing group I introns. After reconstituting and systematically investigating each of these biochemical activities for a candidate 'IStron' derived from Clostridium botulinum, we discovered sequence and structural features of the transposon-encoded RNA that satisfy molecular requirements of a group I intron and TnpB guide RNA, while still retaining the ability to be faithfully mobilized at the DNA level by the TnpA transposase. Strikingly, intron splicing was strongly repressed not only by TnpB, but also by the secondary structure of ωRNA alone, allowing the element to carefully control the relative levels of spliced products versus functional guide RNAs. Our results suggest that IStron transcripts have evolved a sensitive equilibrium to balance competing and mutually exclusive activities that promote transposon maintenance while limiting adverse fitness costs on the host. Collectively, this work explains how diverse enzymatic activities emerged during the selfish spread of IS607-family elements and highlights molecular innovation in the multi-functional utility of transposon-encoded noncoding RNAs.

Emergence of RNA-guided transcription factors via domestication of transposon-encoded TnpB nucleases.

Transposon-encoded tnpB genes encode RNA-guided DNA nucleases that promote their own selfish spread through targeted DNA cleavage and homologous recombination1-4. This widespread gene family was repeatedly domesticated over evolutionary timescales, leading to the emergence of diverse CRISPR-associated nucleases including Cas9 and Cas125,6. We set out to test the hypothesis that TnpB nucleases may have also been repurposed for novel, unexpected functions other than CRISPR-Cas. Here, using phylogenetics, structural predictions, comparative genomics, and functional assays, we uncover multiple instances of programmable transcription factors that we name TnpB-like nuclease-dead repressors (TldR). These proteins employ naturally occurring guide RNAs to specifically target conserved promoter regions of the genome, leading to potent gene repression in a mechanism akin to CRISPRi technologies invented by humans7. Focusing on a TldR clade found broadly in Enterobacteriaceae, we discover that bacteriophages exploit the combined action of TldR and an adjacently encoded phage gene to alter the expression and composition of the host flagellar assembly, a transformation with the potential to impact motility8, phage susceptibility9, and host immunity10. Collectively, this work showcases the diverse molecular innovations that were enabled through repeated exaptation of genes encoded by transposable elements, and reveals that RNA-guided transcription factors emerged long before the development of dCas9-based editors.

Amelioration of Subglottic Stenosis by Antimicrobial Peptide Eluting Endotracheal Tubes.

Introduction: Pediatric subglottic stenosis (SGS) results from prolonged intubation where scar tissue leads to airway narrowing that requires invasive surgery. We have recently discovered that modulating the laryngotracheal microbiome can prevent SGS. Herein, we show how our patent-pending antimicrobial peptide-eluting endotracheal tube (AMP-ET) effectively modulates the local airway microbiota resulting in reduced inflammation and stenosis resolution. Materials and Methods: We fabricated mouse-sized ETs coated with a polymeric AMP-eluting layer, quantified AMP release over 10 days, and validated bactericidal activity for both planktonic and biofilm-resident bacteria against Staphylococcus aureus and Pseudomonas aeruginosa. Ex vivo testing: we inserted AMP-ETs and ET controls into excised laryngotracheal complexes (LTCs) of C57BL/6 mice and assessed biofilm formation after 24 h. In vivo testing: AMP-ETs and ET controls were inserted in sham or SGS-induced LTCs, which were then implanted subcutaneously in receptor mice, and assessed for immune response and SGS severity after 7 days. Results: We achieved reproducible, linear AMP release at 1.16 µg/day resulting in strong bacterial inhibition in vitro and ex vivo. In vivo, SGS-induced LTCs exhibited a thickened scar tissue typical of stenosis, while the use of AMP-ETs abrogated stenosis. Notably, SGS airways exhibited high infiltration of T cells and macrophages, which was reversed with AMP-ET treatment. This suggests that by modulating the microbiome, AMP-ETs reduce macrophage activation and antigen specific T cell responses resolving stenosis progression. Conclusion: We developed an AMP-ET platform that reduces T cell and macrophage responses and reduces SGS in vivo via airway microbiome modulation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00769-9.

Transposon-encoded nucleases use guide RNAs to promote their selfish spread.

Insertion sequences are compact and pervasive transposable elements found in bacteria, which encode only the genes necessary for their mobilization and maintenance1. IS200- and IS605-family transposons undergo 'peel-and-paste' transposition catalysed by a TnpA transposase2, but they also encode diverse, TnpB- and IscB-family proteins that are evolutionarily related to the CRISPR-associated effectors Cas12 and Cas9, respectively3,4. Recent studies have demonstrated that TnpB and IscB function as RNA-guided DNA endonucleases5,6, but the broader biological role of this activity has remained enigmatic. Here we show that TnpB and IscB are essential to prevent permanent transposon loss as a consequence of the TnpA transposition mechanism. We selected a family of related insertion sequences from Geobacillus stearothermophilus that encode several TnpB and IscB orthologues, and showed that a single TnpA transposase was broadly active for transposon mobilization. The donor joints formed upon religation of transposon-flanking sequences were efficiently targeted for cleavage by RNA-guided TnpB and IscB nucleases, and co-expression of TnpB and TnpA led to substantially greater transposon retention relative to conditions in which TnpA was expressed alone. Notably, TnpA and TnpB also stimulated recombination frequencies, surpassing rates observed with TnpB alone. Collectively, this study reveals that RNA-guided DNA cleavage arose as a primal biochemical activity to bias the selfish inheritance and spread of transposable elements, which was later co-opted during the evolution of CRISPR-Cas adaptive immunity for antiviral defence.

Solitary fibrous tumor of the tympanic membrane a case report and systematic review.

PURPOSE: Otological solitary fibrous tumors (SFT) are exceedingly rare. There has been no report of SFT localized to the tympanic membrane. To report on a rare case of solitary fibrous tumor of the tympanic membrane and provide systematic review of the literature pertaining the demographics and pathophysiology of otological SFTs. MATERIALS AND METHODS: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. A search of PubMed, Google Scholar, and Cochrane Library databases was conducted to identify English-language articles on solitary fibrous tumor of the ear, with emphasis on the tympanic membrane, published through 2022. A combination of Boolean operators and the following keywords were included in the search strategy: "solitary fibrous tumor", "tympanic membrane", and "ear". RESULTS: We found 12 previous reports of solitary fibrous tumors of the ears, none of which were in the tympanic membrane. All cases underwent surgical resection, with or without perioperative embolization, or radiation. There was no evidence of distant diseases in any cases. CONCLUSIONS: In the context of a tympanic membrane mass with associated pain and hearing loss, our findings suggest that solitary fibrous tumor should be included in the differential diagnosis.

Digital Healthy Diet Literacy and Fear of COVID-19 as Associated with Treatment Adherence and Its Subscales among Hemodialysis Patients: A Multi-Hospital Study.

Treatment adherence (TA) is a critical issue and is under-investigated in hemodialysis patients. A multi-center study was conducted from July 2020 to March 2021 on 972 hemodialysis patients in eight hospitals in Vietnam to explore the factors associated with TA during the COVID-19 pandemic. Data were collected, including socio-demographics, an End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ), 12-item short-form health literacy questionnaire (HLS-SF12), 4-item digital healthy diet literacy scale (DDL), 10-item hemodialysis dietary knowledge scale (HDK), 7-item fear of COVID-19 scale (FCoV-19S), and suspected COVID-19 symptoms (S-COVID19-S). Bivariate and multivariate linear regression models were used to explore the associations. Higher DDL scores were associated with higher TA scores (regression coefficient, B, 1.35; 95% confidence interval, 95%CI, 0.59, 2.12; p = 0.001). Higher FCoV-19S scores were associated with lower TA scores (B, -1.78; 95%CI, -3.33, -0.24; p = 0.023). In addition, patients aged 60-85 (B, 24.85; 95%CI, 6.61, 43.11; p = 0.008) with "very or fairly easy" medication payment ability (B, 27.92; 95%CI, 5.89, 44.95; p = 0.013) had higher TA scores. Patients who underwent hemodialysis for ≥5 years had a lower TA score than those who received <5 years of hemodialysis (B, -52.87; 95%CI, -70.46, -35.28; p < 0.001). These findings suggested that DDL and FCoV-19S, among other factors, should be considered in future interventions to improve TA in hemodialysis patients.

Osteoporosis Risk in Hemodialysis Patients: The Roles of Gender, Comorbidities, Biochemical Parameters, Health and Diet Literacy.

Osteoporosis is a common bone health disorder in hemodialysis patients that is linked with a higher morbidity and mortality rate. While previous studies have explored the associated factors of osteoporosis, there is a lack of studies investigating the impacts of health literacy (HL) and digital healthy diet literacy (DDL) on osteoporosis. Therefore, we aimed to investigate the associations of HL, DDL, and other factors with osteoporosis among hemodialysis patients. From July 2020 to March 2021, a cross-sectional study was conducted on 675 hemodialysis patients in eight hospitals in Vietnam. The data were collected by using the osteoporosis self-assessment tool for Asians (OSTA) and the 12-item short form of the health literacy questionnaire (HLS-SF12) on digital healthy diet literacy (DDL) and hemodialysis dietary knowledge (HDK). In addition, we also collected information about the socio-demographics, the clinical parameters, the biochemical parameters, and physical activity. Unadjusted and adjusted multinomial logistic regression models were utilized in order to investigate the associations. The proportion of patients at low, medium, and high levels of osteoporosis risk was 39.6%, 40.6%, and 19.8%, respectively. In the adjusted models, women had a higher likelihood of osteoporosis risk than men (odds ratio, OR, 3.46; 95% confidence interval, 95% CI, 1.86, 6.44; p < 0.001; and OR, 6.86; 95% CI, 2.96, 15.88; p < 0.001). The patients with rheumatoid arthritis (OR, 4.37; 95% CI, 1.67, 11.52; p = 0.003) and stomach ulcers (OR, 1.95; 95% CI, 1.01, 3.77; p = 0.048) were more likely to have a higher likelihood of osteoporosis risk than those without. The patients who had a higher waist circumference (WC), HL, and DDL were less likely to have a medium level of osteoporosis risk (OR, 0.95; 95% CI, 0.92, 0.98; p = 0.004; OR, 0.92; 95% CI, 0.88, 0.96; p < 0.001; OR, 0.96; 95% CI, 0.93, 0.99; p = 0.017, respectively) and a high level of osteoporosis risk (OR, 0.93; 95% CI, 0.89, 0.97; p = 0.001; OR, 0.89; 95% CI, 0.84, 0.94; p < 0.001; OR, 0.95; 95% CI, 0.91, 0.99; p = 0.008, respectively) compared with a low level of osteoporosis risk and to those with a lower WC, HL, and DDL. In addition, higher levels of hemoglobin (Hb) (OR, 0.79; 95% CI, 0.66, 0.95; p = 0.014), hematocrit (Hct) (OR, 0.95; 95% CI, 0.92, 0.99; p = 0.041), albumin (OR, 0.91; 95% CI, 0.83, 0.99; p = 0.030), and education (OR, 0.37; 95% CI, 0.16, 0.88; p = 0.025) were associated with a lower likelihood of a high level of osteoporosis risk. In conclusion, osteoporosis risk is highly prevalent in hemodialysis patients. Improved HL, DDL, education, WC, albumin, Hb, and Hct levels should be considered in preventing hemodialysis patients from developing osteoporosis.

The Associations of Suspected COVID-19 Symptoms with Anxiety and Depression as Modified by Hemodialysis Dietary Knowledge: A Multi-Dialysis Center Study.

During the COVID-19 pandemic, it is essential to evaluate hemodialysis patients' dietary knowledge, especially among those with COVID-19 related symptoms, in order to identify appropriate strategies in managing their mental health. The study's purposes were to test the psychometric properties of the hemodialysis dietary knowledge (HDK) scale, and to investigate the modifying impact of HDK on the associations of suspected COVID-19 symptoms (S-COVID-19-S) with anxiety and depression among hemodialysis patients. A cross-sectional study was conducted from July 2020 to March 2021 at eight hospitals across Vietnam. Data of 875 hemodialysis patients were analyzed, including socio-demographic, anxiety (the generalized anxiety disorder scale, GAD-7), depression (the patient health questionnaire, PHQ-9), S-COVID-19-S, HDK, health literacy, and digital healthy diet literacy. Confirmatory factor analysis (CFA) and logistic regression models were used to analyze the data. The HDK scale demonstrates the satisfactory construct validity with good model fit (Goodness of Fit Index, GFI = 0.96; Adjusted Goodness of Fit Index, AGFI = 0.90; Standardized Root Mean Square Residual, SRMR = 0.05; Root Mean Square Error of Approximation, RMSEA = 0.09; Normed Fit Index, NFI = 0.96; Comparative Fit Index, CFI = 0.96, and Parsimony goodness of Fit Index, PGFI = 0.43), criterion validity (as correlated with HL (r = 0.22, p < 0.01) and DDL (r = 0.19, p < 0.01), and reliability (Cronbach alpha = 0.70)). In the multivariate analysis, S-COVID-19-S was associated with a higher likelihood of anxiety (odds ratio, OR, 20.76; 95% confidence interval, 95%CI, 8.85, 48.70; p < 0.001) and depression (OR, 12.95; 95%CI, 6.67, 25.14, p < 0.001). A higher HDK score was associated with a lower likelihood of anxiety (OR, 0.70; 95%CI, 0.64, 0.77; p < 0.001) and depression (OR, 0.72; 95%CI, 0.66, 0.79; p < 0.001). In the interaction analysis, the negative impacts of S-COVID-19-S on anxiety and depression were mitigated by higher HDK scores (p < 0.001). In conclusion, HDK is a valid and reliable tool to measure dietary knowledge in hemodialysis patients. Higher HDK scores potentially protect patients with S-COVID-19-S from anxiety and depression during the pandemic.

Negative Impact of Comorbidity on Health-Related Quality of Life Among Patients With Stroke as Modified by Good Diet Quality.

Background: Comorbidity, along with aging, affects stroke-induced health-related quality of life (HRQoL). We examined the potential role of diet quality in modifying the association between comorbidity and HRQoL in patients with stroke. Methods: A cross-sectional study was conducted on 951 patients with stroke from December 2019 to December 2020 across Vietnam. Comorbidity was assessed using the Charlson Comorbidity Index (CCI) items and classified into two groups (none vs. one or more). Diet quality was evaluated using the Dietary Approaches to Stop Hypertension Quality (DASH-Q) questionnaire, and HRQoL was measured using the RAND-36, with a higher score indicating better diet quality or HRQoL, respectively. Besides, socio-demographics, health-related behaviors (e.g., physical activity, smoking, and drinking), disability (using WHODAS 2.0), and health literacy were also assessed. Linear regression analysis was utilized to explore the associations and interactions. Results: The proportion of patients with stroke aged ≥65 years and having comorbidity were 53.7 and 49.9%, respectively. The HRQoL scores were 44.4 ± 17.4. The diet quality was associated with higher HRQoL score (regression coefficient, B, 0.14; (95% confidence interval, 95% CI, 0.04, 0.23; p = 0.004), whereas comorbidity was associated with lower HRQoL score (B, -7.36; 95% CI, -9.50, -5.23; p < 0.001). In interaction analysis, compared to patients without comorbidity and having the lowest DASH-Q score, those with comorbidity and higher DASH-Q score had a higher HRQoL score (B, 0.21; 95% CI, 0.03, 0.39; p = 0.021). Conclusion: The findings showed that good diet quality could modify the adverse impact of comorbidity on HRQoL in patients with stroke. Diet quality should be considered as a strategic intervention to improve the HRQoL of patients with stroke, especially those with comorbidity, and to promote healthier aging.

Metastatic Meningioma of the Neck: A Case Report and Systematic Review.

BACKGROUND: Although meningiomas are the most common central nervous system neoplasms, extracranial metastases are exceedingly rare. There are even fewer reports of metastatic meningiomas to the neck. METHODS: We described a patient with multiply recurrent orbital meningioma with metastasis to the neck found incidentally during neck exploration for composite resection and free tissue reconstruction. We performed a systematic review for all records pertaining to metastatic meningiomas to the cervical regions. RESULTS: We found 9 previous reports of cervical metastatic meningiomas. Almost all cases underwent extensive local resection. There was no evidence of an association between the histological grade of the tumor and risk of metastasis to the neck. Cervical lymph node dissemination is more common in patients presenting after previous primary tumor resection. CONCLUSIONS: In the context of a neck mass, our findings suggest that metastatic meningioma should be included in the differential diagnosis, especially in patients with previous resections.

Circadian REV-ERBs repress E4bp4 to activate NAMPT-dependent NAD+ biosynthesis and sustain cardiac function.

The heart is a highly metabolic organ that uses multiple energy sources to meet its demand for ATP production. Diurnal feeding-fasting cycles result in substrate availability fluctuations which, together with increased energetic demand during the active period, impose a need for rhythmic cardiac metabolism. The nuclear receptors REV-ERBα and ß are essential repressive components of the molecular circadian clock and major regulators of metabolism. To investigate their role in the heart, here we generated mice with cardiomyocyte (CM)-specific deletion of both Rev-erbs, which died prematurely due to dilated cardiomyopathy. Loss of Rev-erbs markedly downregulated fatty acid oxidation genes prior to overt pathology, which was mediated by induction of the transcriptional repressor E4BP4, a direct target of cardiac REV-ERBs. E4BP4 directly controls circadian expression of Nampt and its biosynthetic product NAD+ via distal cis-regulatory elements. Thus, REV-ERB-mediated E4BP4 repression is required for Nampt expression and NAD+ production by the salvage pathway. Together, these results highlight the indispensable role of circadian REV-ERBs in cardiac gene expression, metabolic homeostasis and function.

Fear, anxiety and depression among pregnant women during COVID-19 pandemic: impacts of healthy eating behaviour and health literacy.

INTRODUCTION: The COVID-19 pandemic has been influencing people's psychological health, especially in pregnant women. We aimed to examine associated factors of fear of COVID-19, anxiety and depression among pregnant women during the pandemic where the impacts of healthy eating behaviour (HES) and health literacy (HL) were emphasized. METHODS: A cross-sectional study was conducted between 14 February 2020 and 31 May 2020 in 18 health centres and hospitals across Vietnam. Data of 518 pregnant women were analysed, including socio-demographics, pregnant-related factors, HES, HL, health-related behaviours, fear of COVID-19 scale (FCoV-19S), anxiety (using the generalized anxiety disorder (GAD-7)) and depression (using the patient health questionnaire with 9 items (PHQ-9)). Regression analysis was utilized to explore the associations. RESULTS: Pregnant women with higher scores of HES and HL had lower likelihood of anxiety (odds ratio, OR, 0.79; 95% confidence interval (95%CI), 0.73, 0.87; p < .001; and OR, 0.94; 95%CI, 0.90, 0.99; p = .018) and depression (OR, 0.84; 95%CI, 0.78, 0.91; p < .001; and OR, 0.96; 95%CI, 0.91, 0.99; p = .044), respectively. Pregnant women being employed had a lower FCoV-19S score (regression coefficient, B, -1.46; 95%CI, -2.51, -0.40; p = .007). Besides, other significant predictors of anxiety were eating healthier during the pandemic, unchanged or more physical activity, elevated gestational age and smoking. Other significant predictors of depression were eating healthier during the pandemic, elevated gestational age and smoking. CONCLUSIONS: Among others, HES and HL had positive impacts on protecting pregnant women against anxiety and depression. Improving HES and HL should be addressed as a strategic approach to improve reproductive health during the pandemic.KEY MESSAGEThe COVID-19 pandemic influences antenatal mental disorders with the higher level as opposed to that before the pandemic.Healthy eating behaviour and better health literacy (HL) had critical roles in lowering prenatal anxiety and depression during the COVID-19 crisis.Strategic approaches for improving healthy eating and HL should be recommended for protecting pregnant women from mental health problems during the pandemic.

REV-ERB nuclear receptors in the suprachiasmatic nucleus control circadian period and restrict diet-induced obesity.

Circadian disruption, as occurs in shift work, is associated with metabolic diseases often attributed to a discordance between internal clocks and environmental timekeepers. REV-ERB nuclear receptors are key components of the molecular clock, but their specific role in the SCN master clock is unknown. We report here that mice lacking circadian REV-ERB nuclear receptors in the SCN maintain free-running locomotor and metabolic rhythms, but these rhythms are notably shortened by 3 hours. When housed under a 24-hour light:dark cycle and fed an obesogenic diet, these mice gained excess weight and accrued more liver fat than controls. These metabolic disturbances were corrected by matching environmental lighting to the shortened endogenous 21-hour clock period, which decreased food consumption. Thus, SCN REV-ERBs are not required for rhythmicity but determine the free-running period length. Moreover, these results support the concept that dissonance between environmental conditions and endogenous time periods causes metabolic disruption.

Single and Combinative Impacts of Healthy Eating Behavior and Physical Activity on COVID-19-like Symptoms among Outpatients: A Multi-Hospital and Health Center Survey.

BACKGROUND: Healthy eating and physical activity are effective non-pharmacological approaches to boost immune function and contain the pandemic. We aimed to explore the associations and interactions between physical activity and healthy eating behavior with COVID-19-like symptoms (Slike-CV19S). METHODS: A cross-sectional study was conducted on 3947 outpatients, from 14 February to 2 March 2020, at nine health facilities in Vietnam. Data collection included sociodemographic characteristics, healthy eating behavior (using the healthy eating score (HES) questionnaire), physical activity (using the short form international physical activity questionnaire), and Slike-CV19S. The associations and interactions were tested using logistic regression models. RESULTS: Frequent intake of fruits (OR = 0.84; p = 0.016), vegetables (OR = 0.72; p = 0.036), and fish (OR = 0.43; p < 0.001) were associated with a lower Slike-CV19S likelihood, as compared with infrequent intake. Patients with higher HES levels (OR = 0.84; p = 0.033 for medium HES; OR = 0.77; p = 0.006 for high HES) or being physically active (OR = 0.69; p < 0.001) had a lower Slike-CV19S likelihood, as compared to those with low HES or physical inactivity, respectively. Patients with medium HES who were physically active (OR = 0.69; p = 0.005), or with high HES and physically active (OR = 0.58; p < 0.001), had a lower Slike-CV19S likelihood, as compared to those with low HES and physical inactivity. CONCLUSIONS: Healthy eating behavior and physical activity showed single and combinative impacts on protecting people from Slike-CV19S. Strategic approaches are encouraged to improve healthy behaviors, which may further contribute to containing the pandemic.

Associations of Underlying Health Conditions With Anxiety and Depression Among Outpatients: Modification Effects of Suspected COVID-19 Symptoms, Health-Related and Preventive Behaviors.

Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB). Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18-85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety. Results: People with UHC had higher odds of depression (OR = 2.11; p < 0.001) and anxiety (OR = 2.86; p < 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p < 0.001); and were significantly lower for those had UHC and interacted with "unchanged/more" physical activity (p < 0.001), or "unchanged/more" drinking (p < 0.001 for only anxiety), or "unchanged/healthier" eating (p < 0.001), and high PB score (p < 0.001), as compared to those without UHC and without S-COVID-19-S, "never/stopped/less" physical activity, drinking, "less healthy" eating, and low PB score, respectively. Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors.