Evaluating the Patient Boarding during Omicron Surge in Hong Kong: Time Series Analysis.

The fifth wave of COVID-19 outbreaks in Hong Kong (HK) from January to March 2022 has the highest confirmed cases and deaths compared with previous waves. Severe hospital boarding (to inpatient wards) was noted in various Emergency Departments (EDs). Our objective is to identify factors associated with hospital boarding during Omicron surge in HK. We conducted a retrospective cohort study including all ED visits and inpatient (IP) ward admissions from January 1st to March 31st, 2022. Vector Autoregression model evaluated the effects of a single variable on the targeted hospital boarding variables. Admissions from elderly homes with 6 lag days held the highest positive value of statistical significance (t-stat = 2.827, P < .05) caused prolonged admission waiting time, while medical patients with 4 lag days had the highest statistical significance (t-stat = 2.530, P < .05) caused an increased number of boarding patients. Within one week after impulses, medical occupancy's influence on the waiting time varied from 0.289 on the 1st day to -0.315 on the 7th day. While occupancy of medical wards always positively affected blocked number of patients, and its response was maximized at 0.309 on the 2nd day. Number of confirmed COVID-19 cases was not the sole significant contributor, while occupancy of medical wards was still a critical factor associated with patient boarding. Increasing ward capacity and controlling occupancy were suggested during the outbreak. Moreover, streamlining elderly patients in ED could be an approach to relieve pressure on the healthcare system.

Non-invasive brain stimulation combined with psychosocial intervention for depression: a systematic review and meta-analysis.

OBJECTIVES: This review investigates the efficacy and safety of non-invasive brain stimulation (NIBS) combined with psychosocial intervention on depressive symptoms. MATERIALS AND METHODS: We systematically searched five electronic databases from their inception to June 2021: PubMed, Embase, PsycINFO, Web of Science, and Medline. Randomized or non-randomized clinical trials in which NIBS plus psychosocial intervention was compared to control conditions in people with depressive symptoms were included. RESULTS: A total of 17 eligible studies with 660 participants were included. The meta-analysis results showed that NIBS combined with psychosocial therapy had a positive effect on moderate to severe depression ([SMD = - 0.46, 95%CI (- 0.90, - 0.02), I2 = 73%, p < .01]), but did not significantly improve minimal to mild depression ([SMD = - 0.12, 95%CI (- 0.42, 0.18), I2 = 0%, p = .63]). Compared with NIBS alone, the combination treatment had a significantly greater effect in alleviating depressive symptoms ([SMD = - 0.84, 95%CI (- 1.25, - 0.42), I2 = 0%, p = .93]). However, our results suggested that the pooled effect size of ameliorating depression of NIBS plus psychosocial intervention had no significant difference compared with the combination of sham NIBS [SMD = - 0.12, 95%CI (- 0.31, 0.07), I2 = 0%, p = .60] and psychosocial intervention alone [SMD = - 0.97, 95%CI (- 2.32, 0.38), I2 = 72%, p = .01]. CONCLUSION: NIBS when combined with psychosocial intervention has a significant positive effect in alleviating moderately to severely depressive symptoms. Further well-designed studies of NIBS combined with psychosocial intervention on depression should be carried out to consolidate the conclusions and explore the in-depth underlying mechanism.

Effects of rhythmic auditory stimulation on upper-limb movement speed in patients with schizophrenia spectrum disorders.

Movement slowness, linked to dysfunctional basal ganglia and cerebellum, is prevalent but lacks effective therapy in patients with schizophrenia spectrum disorders. This study was to examine immediate effects of rhythmic auditory stimulation (RAS) on upper-limb movement speed in patients. Thirty patients and 30 psychiatrically healthy people executed the right-hand task and the both-hand task of the Purdue Pegboard Test when listening to RAS with two tempi: normal (equal to the fastest movement tempo for each participant without RAS) and fast (120% of the normal tempo). The testing order of the RAS tempi for each participant was randomized. Patients had lower scores of right-hand and both-hand tasks than did psychiatrically healthy people. Scores of right-hand and both-hand tasks were higher in the fast-RAS condition than the normal-RAS condition in participants. This is the first study to explore the possibility of applying RAS to movement therapy for patients with schizophrenia spectrum disorders. The results demonstrated that faster RAS was effective in inducing faster upper-limb movements in patients and psychiatrically healthy people, suggesting that manipulating RAS may be a feasible therapeutic strategy utilized to regulate movement speed. The RAS may involve alternative neural pathways to modulate movement speed and thus to compensate for impaired function of basal ganglia and cerebellum in patients.

Life satisfaction of 511 elderly Chinese stroke survivors: moderating roles of social functioning and depression in a quality of life model.

OBJECTIVE: Using a published quality of life model, to investigate the moderating roles played by social functioning and post-stroke depression in buffering the relationship between physical functioning and life satisfaction among elderly Chinese stroke survivors. DESIGN: Cross-sectional survey through face-to-face interviews. SETTING: Fangshan district of the Beijing Municipality in China. PARTICIPANTS: A representative random sample of 511 community-dwelling elderly Chinese stroke survivors aged 60 years or above. In total, 127 participants were categorized as stroke survivors with clinical depression and 384 without. MEASURES: Satisfaction With Life Scale, Center for Epidemiologic Studies Depression Scale, International Residential Assessment Instrument Activities of Daily Living Hierarchy scale, International Residential Assessment Instrument Instrumental Activities of Daily Living Performance scale, De Jong Gierveld Loneliness Scale, and Lubben Social Network Scale. RESULTS: Analyses revealed that the unique variance shown by social functioning (16%) is more important than physical functioning (5%) or depressive symptoms (12%) in promoting life satisfaction among all elderly stroke survivors. The moderation model denotes the interaction effect between depressed mood and physical functioning (ß = .152 to .176, p < .001) for all stroke survivors. For stroke survivors without clinical depression, loneliness (ß = .264 to .287, p < .001) and social support (ß = .115 to .151, p < .05) buffered the relationship between physical functioning and life satisfaction; whereas for those with clinical depression, only loneliness (ß = -.264 to .236, p < .05) moderated the corresponding relationship. CONCLUSIONS: Social functioning and post-stroke depression buffered the relationship between physical dependence and life satisfaction among elderly Chinese stroke survivors.

Evolutionarily conserved Tbx5-Wnt2/2b pathway orchestrates cardiopulmonary development.

Codevelopment of the lungs and heart underlies key evolutionary innovations in the transition to terrestrial life. Cardiac specializations that support pulmonary circulation, including the atrial septum, are generated by second heart field (SHF) cardiopulmonary progenitors (CPPs). It has been presumed that transcription factors required in the SHF for cardiac septation, e.g., Tbx5, directly drive a cardiac morphogenesis gene-regulatory network. Here, we report instead that TBX5 directly drives Wnt ligands to initiate a bidirectional signaling loop between cardiopulmonary mesoderm and the foregut endoderm for endodermal pulmonary specification and, subsequently, atrial septation. We show that Tbx5 is required for pulmonary specification in mice and amphibians but not for swim bladder development in zebrafish. TBX5 is non-cell-autonomously required for pulmonary endoderm specification by directly driving Wnt2 and Wnt2b expression in cardiopulmonary mesoderm. TBX5 ChIP-sequencing identified cis-regulatory elements at Wnt2 sufficient for endogenous Wnt2 expression domains in vivo and required for Wnt2 expression in precardiac mesoderm in vitro. Tbx5 cooperated with Shh signaling to drive Wnt2b expression for lung morphogenesis. Tbx5 haploinsufficiency in mice, a model of Holt-Oram syndrome, caused a quantitative decrement of mesodermal-to-endodermal Wnt signaling and subsequent endodermal-to-mesodermal Shh signaling required for cardiac morphogenesis. Thus, Tbx5 initiates a mesoderm-endoderm-mesoderm signaling loop in lunged vertebrates that provides a molecular basis for the coevolution of pulmonary and cardiac structures required for terrestrial life.

Dual TGFß and Wnt inhibition promotes Mesp1-mediated mouse pluripotent stem cell differentiation into functional cardiomyocytes.

Efficient derivation of cardiomyocytes from mouse pluripotent stem cells has proven challenging, and existing approaches rely on expensive supplementation or extensive manipulation. Mesp1 is a transcription factor that regulates cardiovascular specification during embryo development, and its overexpression has been shown to promote cardiogenesis. Here, we utilize a doxycycline-inducible Mesp1-expressing mouse embryonic stem cell system to develop an efficient differentiation protocol to generate functional cardiomyocytes. Our cardiac differentiation method involves transient Mesp1 induction following by subsequent dual inhibition of TGFß and Wnt signaling pathways using small molecules. We discovered that whereas TGFß inhibition promoted Mesp1-induced cardiac differentiation, Wnt inhibition was ineffective. Nevertheless, a combined inhibition of both pathways was superior to either inhibition alone in generating cardiomyocytes. These observations suggested a potential interaction between TGFß and Wnt signaling pathways in the context of Mesp1-induced cardiac differentiation. Using a step-by-step approach, we have further optimized the windows of Mesp1 induction, TGFß inhibition and Wnt inhibition to yield a maximal cardiomyocyte output - Mesp1 was induced first, followed by dual inhibition of TGFß and Wnt signaling. Our protocol is capable of producing approximately 50% of cardiomyocytes in 12 days, which is comparable to existing methods, and have the advantages of being technically simple and inexpensive. Moreover, cardiomyocytes thus derived are functional, displaying intrinsic contractile capacity and contraction in response to electric stimulus. Derivation of mouse cardiomyocytes without the use of growth factors or other costly supplementation provides an accessible cell source for future applications.

A randomized controlled trial on the comparative effectiveness of mindfulness-based cognitive therapy and health qigong-based cognitive therapy among Chinese people with depression and anxiety disorders.

BACKGROUND: The goal of this study was to investigate treatment outcome and related intervention processes of mindfulness-based cognitive therapy versus health qigong-based cognitive therapy versus waitlist control among individuals with mood disorders. METHODS: A total of 187 individuals with mood disorders were randomized and allocated into mindfulness-based cognitive therapy, health qigong-based cognitive therapy, or waitlist control groups. All participants were assessed at three time points with regard to depressive and anxiety symptoms, physical and mental health status, perceived stress, sleep quality, and self-efficacy. Linear mixed models analysis was used to test the individual growth model by studying the longitudinal data. RESULTS: Mindfulness-based cognitive therapy and health qigong-based cognitive therapy both produced greater improvements on all outcome measures as compared with waitlist control. Relatively, more reductions of mood symptoms were observed in the health qigong-based cognitive therapy group as compared with the mindfulness-based cognitive therapy group. Health qigong-based cognitive therapy is more conducive to physical health status whereas mindfulness-based cognitive therapy has more favorable mental health outcomes. Individual growth curve models indicated that alterations in perceived stress was the common predictor of mood changes in both intervention groups. CONCLUSIONS: The predominant emphasis on physical health in health qigong-based cognitive therapy makes it more acceptable and effective than mindfulness-based cognitive therapy as applied in Chinese individuals with mood disorders. The influence of Chinese culture is discussed. TRIAL REGISTRATION: HKU Clinical Trials Registry. Identifier: HKUCTR-2558 . Registered 21st Nov 2018.

Single-cell RNA-seq analysis of Mesp1-induced skeletal myogenic development.

The Mesp1 lineage contributes to cardiac, hematopoietic and skeletal myogenic development. Interestingly, muscle stem cells residing in craniofacial skeletal muscles primarily arise from Mesp1+ progenitors, but those in trunk and limb skeletal muscles do not. To gain insights into the difference between the head and trunk/limb muscle developmental processes, we studied Mesp1+ skeletal myogenic derivatives via single-cell RNA-seq and other strategies. Using a doxycycline-inducible Mesp1-expressing mouse embryonic stem cell line, we found that the development of Mesp1-induced skeletal myogenic progenitors can be characterized by dynamic expression of PDGFRα and VCAM1. Single-cell RNA-seq analysis further revealed the heterogeneous nature of these Mesp1+ derivatives, spanning pluripotent and mesodermal to mesenchymal and skeletal myogenic. We subsequently reconstructed the single-cell trajectories of these subpopulations. Our data thereby provide a cell fate projection of Mesp1-induced skeletal myogenesis.

The effect of a brief mindfulness-based intervention on personal recovery in people with bipolar disorder: a randomized controlled trial (study protocol).

BACKGROUND: With the advent of the recovery movement in mental health, a humanistic paradigm shift has occurred, placing the focus on personal recovery (i.e., hope, identity, and life meaning) instead of functional or clinical recovery only (i.e., symptom reduction or increases in physical function). Along the journey of recovery, people with bipolar disorder (BD) struggle to cope with recurring mood fluctuations between depression and mania. Mindfulness-based interventions (MBIs) have the potential to result in improvements in personal recovery outcomes. Thus, this protocol will evaluate the efficacy and mechanisms of a brief MBI for helping individuals with BD with their personal recovery. It is hypothesized that adults with BD randomly assigned to a brief MBI intervention will report greater improvements in personal recovery than those in a waiting list control condition. In addition, it is hypothesized that such benefits will be mediated by improvements in emotion awareness, emotion regulation, and illness acceptance. Moreover, the specific stage of BD is hypothesized to moderate the beneficial effects of the brief MBI, such that those in the early stage of BD will report more benefits regarding emotion awareness and emotion regulation, whereas those in the late stage of BD will report more advantages concerning illness acceptance. METHOD: One hundred and fifty-four adults with BD will be recruited from hospitals and community settings for this research project. This study will use a mixed methods design. A randomized-controlled trial will be conducted to compare a brief MBI (four sessions in total) group and a waiting list control group. Assessments will be made at baseline, after intervention, and at six-month follow-up. In addition, a qualitative and participatory research method called Photovoice will be employed to further understand the experiences of the participants who receive the brief MBI along their personal recovery journey. DISCUSSION: If the study hypotheses are supported, the findings from this research project will provide empirical support for an alternative treatment. Moreover, by identifying the mechanisms of the beneficial effects of the brief MBI, the findings will highlight process variables that could be specifically targeted to make MBI treatment even more effective in this population. TRIAL REGISTRATION: This study is registered with the Chinese Clinical Trial Registry ( ChiCTR- 1900024658 ). Registered 20th July 2019.

A moderate oestradiol level enhances neutrophil number and activity in muscle after traumatic injury but strength recovery is accelerated.

KEY POINTS: The female hormone oestrogen may protect muscle from injury by reducing inflammation but this is debatable. In this study, the inflammatory response of injured muscle from oestrogen-replete mice was comprehensively compared to that from oestrogen-deficient mice. We show that oestrogen markedly promotes movement of neutrophils, an inflammatory white blood cell type, into muscle over the first few days after injury but has only a minor effect on the movement of macrophages, another inflammatory cell type. Despite the enhancement of inflammation by oestrogen in injured muscle, we found strength in oestrogen-replete mice to recover faster and to a greater extent than it does in oestrogen-deficient mice. Our study and others indicate that lower doses of oestrogen, such as that used in our study, may affect muscle inflammation and injury differently from higher doses. ABSTRACT: Oestrogen has been shown to protect against skeletal muscle injury and a reduced inflammatory response has been suggested as a possible protective mechanism. There are, however, dissenting reports. Our objective was to conduct an unbiased, comprehensive study of the effect of oestradiol on the inflammatory response following muscle injury. Female C57BL6/J mice were ovariectomized and supplemented with and without oestradiol. Tibialis anterior muscles were freeze injured and studied primarily at 1-4 days post-injury. Oestradiol supplementation increased injured muscle gene expression of neutrophil chemoattractants (Cxcl1 and Cxcl5) and to a lesser extent that of monocyte/macrophage chemoattractants (Ccl2 and Spp1). Oestradiol markedly increased gene expression of the neutrophil cell surface marker (Ly6g) but had less consistent effects on the monocyte/macrophage cell surface markers (Cd68, Cd163 and Cd206). These results were confirmed at the protein level by immunoblot with oestradiol increasing LY6G/C content and having no significant effect on CD163 content. These findings were confirmed with fluorescence-activated cell sorting counts of neutrophils and macrophages in injured muscles; oestradiol increased the proportion of CD45+ cells that were neutrophils (LY6G+ ) but not the proportion that were macrophages (CD68+ or CD206+ ). Physiological impact of the oestradiol-enhanced neutrophil response was assessed by strength measurements. There was no significant difference in strength between oestradiol-supplemented and -unsupplemented mice until 2 weeks post-injury; strength was 13-24% greater in supplemented mice at 2-6 weeks post-injury. In conclusion, a moderate level of oestradiol supplementation enhances neutrophil infiltration in injured muscle and this is associated with a beneficial effect on strength recovery.

Heterogeneity of Mesp1+ mesoderm revealed by single-cell RNA-seq.

Mesp1 is a transcription factor that promotes differentiation of pluripotent cells into different mesoderm lineages including hematopoietic, cardiac and skeletal myogenic. This occurs via at least two transient cell populations: a common hematopoietic/cardiac progenitor population and a common cardiac/skeletal myogenic progenitor population. It is not established whether Mesp1-induced mesoderm cells are intrinsically heterogeneous, or are simply capable of multiple lineage decisions. In the current study, we applied single-cell RNA-seq to analyze Mesp1+ mesoderm. Initial whole transcriptome analysis showed a surprising homogeneity among Mesp1-induced mesoderm cells. However, this apparent global homogeneity masked an intrinsic heterogeneity revealed by interrogating a panel of early mesoderm patterning factors. This approach enabled discovery of subpopulations primed for hematopoietic or cardiac development. These studies demonstrate the heterogeneic nature of Mesp1+ mesoderm.

Meta-analysis of predictors of favorable employment outcomes among individuals with bipolar disorder.

OBJECTIVES: Although several studies have reported on predictors of employment in individuals with bipolar disorder (BD), the magnitude of the impact of these variables is unclear as no previous studies have estimated the collective effect sizes (ESs). The present meta-analysis estimated ESs and explored which of these variables are associated with positive employment outcomes. METHODS: We searched for articles published between 2000 and 2011 that reported associations between sociodemographic, clinical, psychosocial, and/or cognitive variables with employment outcomes in BD. Of the 781 articles identified, 22 met the inclusion criteria and were included in the final analysis (n = 6,301). Weighted correlation coefficients (r-index) were computed as ESs for each of the predictor variables, which were grouped into six categories: cognitive performance, symptomatology, sociodemographic factors, course of illness, clinical variables, and other personal factors. The overall ES (Rw) was estimated by assuming random-effect models. Sensitivity analyses were also performed to determine the robustness of the findings. RESULTS: Significant predictors of favorable employment outcomes included: cognitive performance (e.g., verbal memory, Rw = 0.33; executive function, Rw = 0.26), sociodemographic factors (e.g., years of education, Rw = 0.23), course of illness (e.g., number of lifetime psychiatric hospitalizations, Rw = -0.35), symptomatology (e.g., depression, Rw = -0.25), and other personal factors (e.g., personality disorder, Rw = -0.49). CONCLUSIONS: Overall, the cognitive performance and course of illness had larger average ESs than symptomatology or sociodemographic factors on favorable employment outcomes. These findings may help to guide the design of more effective work interventions for people with BD.

In vivo PSC differentiation as a platform to identify factors for improving the engraftability of cultured muscle stem cells.

Producing an adequate number of muscle stem cells (MuSCs) with robust regenerative potential is essential for the successful cell therapy of muscle-wasting disorders. We have recently developed a method to produce skeletal myogenic cells with exceptional engraftability and expandability through an in vivo pluripotent stem cell (PSC) differentiation approach. We have subsequently mapped engraftment and gene expression and found that leukemia inhibitory factor receptor (Lifr) expression is positively correlated with engraftability. We therefore investigated the effect of LIF, the endogenous ligand of LIFR, on cultured MuSCs and examined their engraftment potential. We found that LIF-treated MuSCs exhibited elevated expression of PAX7, formed larger colonies from single cells, and favored the retention of PAX7+ "reserve cells" upon myogenic differentiation. This suggested that LIF promoted the maintenance of cultured MuSCs at a stem cell stage. Moreover, LIF enhanced the engraftment capability of MuSCs that had been expanded in vitro for 12 days by 5-fold and increased the number of MuSCs that repopulated the stem cell pool post-transplantation. These results thereby demonstrated the effectiveness of our in vivo PSC differentiation platform to identify positive regulators of the engraftability of cultured MuSCs.

Inducing positive inotropy in human iPSC-derived cardiac muscle by gene editing-based activation of the cardiac α-myosin heavy chain.

Human induced pluripotent stem cells and their differentiation into cardiac myocytes (hiPSC-CMs) provides a unique and valuable platform for studies of cardiac muscle structure-function. This includes studies centered on disease etiology, drug development, and for potential clinical applications in heart regeneration/repair. Ultimately, for these applications to achieve success, a thorough assessment and physiological advancement of the structure and function of hiPSC-CMs is required. HiPSC-CMs are well noted for their immature and sub-physiological cardiac muscle state, and this represents a major hurdle for the field. To address this roadblock, we have developed a hiPSC-CMs (ß-MHC dominant) experimental platform focused on directed physiological enhancement of the sarcomere, the functional unit of cardiac muscle. We focus here on the myosin heavy chain (MyHC) protein isoform profile, the molecular motor of the heart, which is essential to cardiac physiological performance. We hypothesized that inducing increased expression of α-MyHC in ß-MyHC dominant hiPSC-CMs would enhance contractile performance of hiPSC-CMs. To test this hypothesis, we used gene editing with an inducible α-MyHC expression cassette into isogeneic hiPSC-CMs, and separately by gene transfer, and then investigated the direct effects of increased α-MyHC expression on hiPSC-CMs contractility and relaxation function. Data show improved cardiac functional parameters in hiPSC-CMs induced with α-MyHC. Positive inotropy and relaxation was evident in comparison to ß-MyHC dominant isogenic controls both at baseline and during pacing induced stress. This approach should facilitate studies of hiPSC-CMs disease modeling and drug screening, as well as advancing fundamental aspects of cardiac function parameters for the optimization of future cardiac regeneration, repair and re-muscularization applications.

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study.

IMPORTANCE: The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. DESIGN: Population-based retrospective cohort study. PARTICIPANTS: Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. EXPOSURE: Warfarin use within 14 days of IE diagnosis. MAIN OUTCOMES AND MEASURES: Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. RESULTS: The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70-1.53]), intracranial hemorrhage (HR:1.25 [0.77-2.04]), and gastrointestinal bleeding (HR:1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34-8.31]), but not at 90-day (sub-HR:1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. CONCLUSIONS AND RELEVANCE: Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. KEY POINTS: Question: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe? FINDINGS: In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage.

Cardiac Development Long Non-Coding RNA (CARDEL) Is Activated during Human Heart Development and Contributes to Cardiac Specification and Homeostasis.

Successful heart development depends on the careful orchestration of a network of transcription factors and signaling pathways. In recent years, in vitro cardiac differentiation using human pluripotent stem cells (hPSCs) has been used to uncover the intricate gene-network regulation involved in the proper formation and function of the human heart. Here, we searched for uncharacterized cardiac-development genes by combining a temporal evaluation of human cardiac specification in vitro with an analysis of gene expression in fetal and adult heart tissue. We discovered that CARDEL (CARdiac DEvelopment Long non-coding RNA; LINC00890; SERTM2) expression coincides with the commitment to the cardiac lineage. CARDEL knockout hPSCs differentiated poorly into cardiac cells, and hPSC-derived cardiomyocytes showed faster beating rates after controlled overexpression of CARDEL during differentiation. Altogether, we provide physiological and molecular evidence that CARDEL expression contributes to sculpting the cardiac program during cell-fate commitment.

Producing Engraftable Skeletal Myogenic Progenitors from Pluripotent Stem Cells via Teratoma Formation.

Generating engraftable skeletal muscle progenitor cells is a promising cell therapy approach to treating degenerating muscle diseases. Pluripotent stem cell (PSC) is an ideal cell source for cell therapy because of its unlimited proliferative capability and potential to differentiate into multiple lineages. Approaches such as ectopic overexpression of myogenic transcription factors and growth factors-directed monolayer differentiation, while able to differentiate PSCs into the skeletal myogenic lineage in vitro, are limited in producing muscle cells that reliably engraft upon transplantation. Here we present a novel method to differentiate mouse PSCs into skeletal myogenic progenitors without genetic modification or monolayer culture. We make use of forming a teratoma, in which skeletal myogenic progenitors can be routinely obtained. We first inject mouse PSCs into the limb muscle of an immuno-compromised mouse. Within 3-4 weeks, α7-integrin+ VCAM-1+ skeletal myogenic progenitors are purified by fluorescent-activated cell sorting. We further transplant these teratoma-derived skeletal myogenic progenitors into dystrophin-deficient mice to assess engraftment efficiency. This teratoma formation strategy is capable of generating skeletal myogenic progenitors with high regenerative potency from PSCs without genetic modifications or growth factors supplementation.

Efficient Muscle Regeneration by Human PSC-Derived CD82+ ERBB3+ NGFR+ Skeletal Myogenic Progenitors.

Differentiation of pluripotent stem cells (PSCs) is a promising approach to obtaining large quantities of skeletal myogenic progenitors for disease modeling and cell-based therapy. However, generating skeletal myogenic cells with high regenerative potential is still challenging. We recently reported that skeletal myogenic progenitors generated from mouse PSC-derived teratomas possess robust regenerative potency. We have also found that teratomas derived from human PSCs contain a skeletal myogenic population. Here, we showed that these human PSC-derived skeletal myogenic progenitors had exceptional engraftability. A combination of cell surface markers, CD82, ERBB3, and NGFR enabled efficient purification of skeletal myogenic progenitors. These cells expressed PAX7 and were able to differentiate into MHC+ multinucleated myotubes. We further discovered that these cells are expandable in vitro. Upon transplantation, the expanded cells formed new dystrophin+ fibers that reconstituted almost ¾ of the total muscle volume, and repopulated the muscle stem cell pool. Our study, therefore, demonstrates the possibility of producing large quantities of engraftable skeletal myogenic cells from human PSCs.

The effects of psychosocial and behavioral interventions on depressive and anxiety symptoms during the COVID-19 pandemic: a systematic review and meta-analysis.

Psychosocial and behavioral interventions have been shown to significantly reduce depressive and anxiety symptoms in different populations. Recent evidence suggests that the mental health of the general population has deteriorated significantly since the start of Coronavirus Disease 2019 (COVID-19) pandemic. We conducted a systematic review and meta-analysis of studies on the therapeutic effects of psychosocial and behavioral interventions on depression and anxiety during the COVID-19 pandemic. We systematically searched six electronic databases between December 2019 and February 2022 including PubMed, PsycINFO, Scopus, Web of Science, CNKI, and Wanfang Data. We included randomized clinical trials of psychosocial and behavioral interventions in individuals with depressive or anxiety symptoms during the COVID-19 outbreak compared to various control conditions. A total of 35 eligible studies with 5457 participants were included. The meta-analysis results showed that psychosocial and behavioral interventions had statistically significant moderate effects on depression [SMD = - 0.73, 95% CI (- 1.01, - 0.45), I2 = 90%] and large effects on anxiety [SMD = - 0.90, 95% CI (- 1.19, - 0.60), I2 = 92%], especially in the general population and COVID-19 survivors. Exercise and cognitive behavioral therapy were found to be the most effective treatments with moderate-to-large effect size for depression and anxiety during the outbreak of COVID-19. We also found the internet-based approach could also achieve almost equally significant effects on depression and anxiety compared with face-to-face traditional approach. Our findings suggest that cognitive behavioral therapy and physical exercise intervention are significantly effective for depression and anxiety related to the COVID-19 pandemic regardless of the delivery modes, and gender differences should be taken into consideration for better implementation of interventions in clinical and community practice.

Clinical effectiveness of mindfulness-based music therapy on improving emotional regulation in blind older women: A randomized controlled trial.

Background: This study aimed to investigate clinical effectiveness of a structured eight-week mindfulness-based music therapy (MBMT) program on improving mood regulation in older women with blindness. This investigation compared a MBMT group with a mindfulness intervention (MI) group and a control group. Methods: Ninety-two older females with blindness from a residential setting in Hong Kong were recruited and randomly allocated to a MBMT (n = 31), MI (n = 30), or control (n = 31) group. Psychological measurements regarding mood regulation and general mood states (namely, Difficulties in Emotion Regulation Scale [DERS], Geriatric Depression Scale [GDS], and Depression Anxiety Stress Scales-21), were taken at pretest and posttest. Outcome assessors were blinded to group assignment. Results: Data was analyzed based on intention-to-treat basis. At posttest, DERS scores in the MBMT group (mean differences and 95% confidence interval: 12.1, 5.5 to 18.8) and the MI group (7.2, 0.5 to 13.8) were lower than that in the control group. GDS scores in the MBMT group (2.9, 1.7 to 4.0) and the MI group (1.7, 0.6 to 2.9) were lower than those in the control group. Compared with the MI group, the MBMT group improved emotional awareness sub-scores in DERS (2.1, 0.2 to 4.1) and appeared to lower depression in GDS scores (1.1, -0.0 to 2.3; p = 0.053). Conclusion: MBMT seems more beneficial than MI alone for improving emotional regulation in older women with blindness. The combination of mindfulness and music can generate a synergetic effect by enhancing both attention and appraisal components within the emotional-regulation process. Trial registration: ClinicalTrials.gov, NCT05583695.