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Abstract Background Unhealthy alcohol use is a common public health problem in HIV care settings in Africa and it affects the HIV continuum of care. In Uganda and other low-income countries, HIV care providers are a key resource in caring for young people (15–24 years) living with HIV (YPLH) with unhealthy alcohol use. Caring for YPLH largely depends on care providers’ perceptions of the problem. However, data that explores HIV care providers’ perceptions about caring for YPLH with unhealthy drinking are lacking in Uganda. We sought to describe the perceptions of HIV care providers regarding caring for YPLH with unhealthy drinking in the Immune Suppression Syndrome (ISS) Clinic of Mbarara Regional Referral Hospital in southwestern Uganda. Methods We used semi-structured in-depth interviews (IDIs) to qualitatively explore HIV care providers’ perceptions regarding caring for YPLH with unhealthy alcohol use. The study was conducted at the adolescent immunosuppression (ISS) clinic of Mbarara Regional Referral Hospital. Interviews were tape-recorded and transcribed verbatim. Using thematic content analysis, data from 10 interviews were analyzed. Results HIV care providers were concerned and intended to care for YPLH with unhealthy alcohol use. They understood that unhealthy drinking negatively impacts HIV care outcomes and used counseling, peer support, and referrals to routinely intervene. They however, did not apply other known interventions such as health education, medications and follow-up visits because these required family and institutional support which was largely lacking. Additional barriers that HCPs faced in caring for YPLH included; gaps in knowledge and skills required to address alcohol use in young patients, heavy workloads that hindered the provision of psychosocial interventions, late payment of and low remunerations, lack of improvement in some YPLH, and inadequate support from both their families and hospital management. Conclusion HIV care providers are important stakeholders in the identification and care of YPLH with unhealthy alcohol use in Southwestern Uganda. There is a need to train and skill HCPs in unhealthy alcohol use care. Such training ought to target the attitudes, subjective norms, and perceived control of the providers.

Abstract Parkinson’s disease (PD) is a prevalent neurodegenerative disorder affecting millions of elderly individuals worldwide. Clinically, PD is diagnosed based on the presentation of motoric symptoms. Other methods such as F-DOPA PET scan or α-Synuclein detection from the cerebral spinal fluid are either too expensive or invasive for routine use. Omics platforms such as transcriptomics, proteomics, and metabolomics may identify PD biomarkers from blood, which can reduce cost and increase efficiency. However, there are many biological moieties being measured and issues with false positives/negatives. It is also unknown which omics platform offers most useful information. Therefore, it is important to assess the reliability of these omics studies. Here, we shortlisted and analysed nearly 80 published reports across transcriptomics, proteomics and metabolomics in search of overlapping blood-based biomarkers for PD. The top biomarkers were reported across 29%, 42% and 12.5% of shortlisted papers in transcriptomics, proteomics and metabolomics respectively. These percentages increased to 42%, 60% and 50% accordingly when studies were grouped by specific blood subtypes for analysis, demonstrating the need for test kits to be blood-subtype specific. Following systematic analyses, we propose six novel PD biomarkers: two mRNAs (Whole blood, WB) – Arg1 and SNCA, two proteins (Plasma EV) – SNCA and APOA1, and two metabolites (WB) – 8-OHdG and uric acid for further validation. While these proposed biomarkers are useful, they are also snapshots, representing subsets of larger pathways of origin where the different omics levels corroborate. Indeed, identifying the interconnections across different biological layers can strengthen contextual reasoning, which in turn, would give rise to better quality biomarkers. Knowledge integration across the omics spectrum revealed consistent aberrations on the same neuroinflammation pathway, showcasing the value of integrative (i)-omics agreements for increasing confidence of biomarker selection. We believe that our findings could pave the way for identifying reproducible PD biomarkers, with potential for clinical deployment. Graphical Abstract Six Proposed blood-based biomarkers. Seventy-nine publications across transcriptomics, proteomics and metabolomics were shortlisted and analysed for reported biomarkers. The proposed biomarkers are SNCA, APOA1, Arg1, 8-OHdG and Uric acid.

This report discusses a case of transient 2:1 atrioventricular block with conduction system pacing 4 hours after leadless right ventricular pacemaker implantation in a 19-year-old patient with a history of cardioinhibitory syncope and asystole cardiac arrest but without preexisting atrioventricular block. The atrioventricular block was resolved spontaneously. Pacing morphology was suggestive of right bundle branch pacing. Neither 2:1 atrioventricular block nor conduction system pacing has previously been a reported outcome of right ventricular leadless pacemaker implantation. The report demonstrates that conduction system pacing with leadless devices is achievable. Further study of techniques, limitations, and complications related to intentional right ventricular leadless conduction system pacing is warranted.

Abstract RNA plays an indispensable role in mammalian cell functions. Cas13, a class of RNA-guided ribonuclease, is a flexible tool for modifying and regulating coding and non-coding RNAs, with enormous potential for creating new cell functions. However, the lack of control over Cas13 activity has limited its cell engineering capability. Here, we present the CRISTAL (Control of RNA with Inducible SpliT CAs13 Orthologs and Exogenous Ligands) platform. CRISTAL is powered by a collection (10 total) of orthogonal split inducible Cas13 effectors that can be turned ON or OFF via small molecules in multiple cell types, providing precise temporal control. Also, we engineer Cas13 logic circuits that can respond to endogenous signaling and exogenous small molecule inputs. Furthermore, the orthogonality, low leakiness, and high dynamic range of our inducible Cas13d and Cas13b enable the design and construction of a robust incoherent feedforward loop, leading to near-perfect and tunable adaptation response. Finally, using our inducible Cas13 effectors, we achieve simultaneous multiplexed control of multiple genes in vitro and in mice. Together, our CRISTAL design represents a powerful platform for precisely regulating RNA dynamics to advance cell engineering and elucidate RNA biology.

Background:. As long-term, regular aesthetic botulinum neurotoxin A (BoNT-A) use becomes more commonplace, it is vital to understand real-world risk factors and impact of BoNT-A immunoresistance. The first Aesthetic Council on Ethical Use of Neurotoxin Delivery panel discussed issues relating to BoNT-A immunoresistance from the health care professionals’ (HCPs’) perspective. Understanding the implications of BoNT-A immunoresistance from the aesthetic patient’s viewpoint allows HCPs to better support patients throughout their aesthetic treatment journey. Methods:. A real-world consumer study surveyed 363 experienced aesthetic BoNT-A recipients across six Asia-Pacific territories. The survey mapped participants’ BoNT-A aesthetic treatment journey and characterized awareness and attitudes relating to BoNT-A immunoresistance and treatment implications. At the second Aesthetic Council on Ethical use of Neurotoxin Delivery meeting, panelists discussed survey findings and developed consensus statements relating to the impact of BoNT-A immunoresistance on the aesthetic treatment journey. Results:. Aesthetic BoNT-A patients’ depth of knowledge about BoNT-A immunoresistance remains low, and risk/benefit communications need to be more lay-friendly. The initial consultation is the most important touchpoint for HCPs to raise awareness of BoNT-A immunoresistance as a potential side effect considering increased risk with repeated high-dose treatments. HCPs should be cognizant of differences across BoNT-A formulations due to the presence of certain excipients and pharmacologically unnecessary components that can increase immunogenicity. Standardized screening for clinical signs of secondary nonresponse and a framework for diagnosing and managing immunoresistance-related secondary nonresponse were proposed. Conclusion:. These insights can help patients and HCPs make informed treatment decisions to achieve desired aesthetic outcomes while preserving future treatment options with BoNT-A.

Computational models of cardiac electrophysiology have gradually matured during the past few decades and are now being personalised to provide patient-specific therapy guidance for improving suboptimal treatment outcomes. The predictive features of these personalised electrophysiology models hold the promise of providing optimal treatment planning, which is currently limited in the clinic owing to reliance on a population-based or average patient approach. The generation of a personalised electrophysiology model entails a sequence of steps for which a range of activation mapping, calibration methods and therapy simulation pipelines have been suggested. However, the optimal methods that can potentially constitute a clinically relevant in silico treatment are still being investigated and face limitations, such as uncertainty of electroanatomical data recordings, generation and calibration of models within clinical timelines and requirements to validate or benchmark the recovered tissue parameters. This paper is aimed at reporting techniques on the personalisation of cardiac computational models, with a focus on calibrating cardiac tissue conductivity based on electroanatomical mapping data.

We present a case of anatomic repair of dextro-transposition of the great arteries (d-TGA) with ventricular septal defect (VSD) in a 55-year-old man who presented with acute heart failure. This case highlights the importance of multimodal imaging and multidisciplinary involvement in developing a comprehensive surgical and medical plan for adults with congenital heart disease. We think this is the oldest reported patient undergoing anatomic surgical repair of d-TGA with VSD.

IntroductionThe potential for deployment of Artificial Intelligence (AI) technologies in various fields of medicine is vast, yet acceptance of AI amongst clinicians has been patchy. This research therefore examines the role of antecedents, namely trust, attitude, and beliefs in driving AI acceptance in clinical practice.MethodsWe utilized online surveys to gather data from clinicians in the field of gastroenterology.ResultsA total of 164 participants responded to the survey. Participants had a mean age of 44.49 (SD = 9.65). Most participants were male (n = 116, 70.30%) and specialized in gastroenterology (n = 153, 92.73%). Based on the results collected, we proposed and tested a model of AI acceptance in medical practice. Our findings showed that while the proposed drivers had a positive impact on AI tools’ acceptance, not all effects were direct. Trust and belief were found to fully mediate the effects of attitude on AI acceptance by clinicians.DiscussionThe role of trust and beliefs as primary mediators of the acceptance of AI in medical practice suggest that these should be areas of focus in AI education, engagement and training. This has implications for how AI systems can gain greater clinician acceptance to engender greater trust and adoption amongst public health systems and professional networks which in turn would impact how populations interface with AI. Implications for policy and practice, as well as future research in this nascent field, are discussed.

The Chimeric Antigen Receptor (CAR) T Cell Safety Database Project explored the use of cross-study safety data to identify risk factors associated with severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) after CAR T cell administration. Sponsors voluntarily submitted data for 1,926 subjects from 17 phases 1 and 2 studies (six acute lymphocytic leukemia [ALL], five non-Hodgkin’s lymphoma [NHL], and six multiple myeloma [MM] studies). Subjects with ALL had a higher risk for developing sCRS and sNTX compared with subjects with NHL or MM. Subjects who received CAR T cells produced with gammaretrovirus vectors including CD28 sequences had higher rates of sNTX compared with subjects who received products produced with other vector designs included in the database. Use of cytokine-directed therapies and corticosteroids at lower toxicity grades were associated with lower rates of sCRS. Although this exploratory study was limited by unadjusted cross-study comparisons, it independently reproduced known risk factors for CAR T cell toxicity. Findings provide stakeholders in the CAR T cell clinical development community information on safety trends for consideration in early phase clinical trial design, as well as avenues for additional research.

Morphological subtypes of autism spectrum disorder (ASD) may differ in their genetic bases. Chan et al. develop a method for calculating a patient-level, genome-wide rare variant score and find significant differences in rare and common variant associations between dysmorphic and nondysmorphic ASD groups.

Abstract Background: The intersection of synthetic biology and biomaterials promises to enhance safety and efficacy in novel therapeutics. Both fields increasingly employ Boolean logic, which allows for specific therapeutic outputs (e.g., drug release, peptide synthesis) in response to inputs such as disease markers or bio‐orthogonal stimuli. Examples include stimuli‐responsive drug delivery devices and logic‐gated chimeric antigen receptor (CAR) T cells. In this review, we explore recent manuscripts highlighting the potential of synthetic biology and biomaterials with Boolean logic to create novel and efficacious living therapeutics. Main body: Collaborations in synthetic biology and biomaterials have led to significant advancements in drug delivery and cell therapy. Borrowing from synthetic biology, researchers have created Boolean‐responsive biomaterials sensitive to multiple inputs including pH, light, enzymes and more to produce functional outputs such as degradation, gel‐sol transition and conformational change. Biomaterials also enhance synthetic biology, particularly CAR T and adoptive T cell therapy, by modulating therapeutic immune cells in vivo. Nanoparticles and hydrogels also enable in situ generation of CAR T cells, which promises to drive down production costs and expand access to these therapies to a larger population. Biomaterials are also used to interface with logic‐gated CAR T cell therapies, creating controllable cellular therapies that enhance safety and efficacy. Finally, designer cells acting as living therapeutic factories benefit from biomaterials that improve biocompatibility and stability in vivo. Conclusion: By using Boolean logic in both cellular therapy and drug delivery devices, researchers have achieved better safety and efficacy outcomes. While early projects show incredible promise, coordination between these fields is ongoing and growing. We expect that these collaborations will continue to grow and realize the next generation of living biomaterial therapeutics.

Abstract Background Vocal cord palsy after cervical mediastinoscopy is usually reported at less than 1%. However, its incidence might be underestimated and no follow-up studies are available. Our study aimed to evaluate the incidence of voice changes after cervical mediastinoscopy and report on long-term outcomes, including quality of life, after at least one-year follow-up. Methods A retrospective cohort study was performed, considering all patients who underwent cervical mediastinoscopy in our center between January 2011 and April 2016. Patients with pre-existing voice changes, voice changes only after pulmonary resection and patients who underwent neoadjuvant chemo(radio)therapy were excluded. Voice changes with full recovery within 14 days were attributed to intubation-related causes. Follow-up questionnaires, including the standardized Voice Handicap Index, were sent to patients with documented voice changes. Results Of 270 patients who were included for final analysis, 17 (6.3%) experienced voice changes after cervical mediastinoscopy, which persisted > 2 years in 4 patients (1.5%), causing mild to moderate disabilities in daily living. Twelve patients (out of 17, 71%) were referred for otolaryngology consultation, and paresis of the left vocal cord suggesting recurrent laryngeal nerve injury was confirmed in 10 (3.7% of our total study group). Additionally, 83% of the patients who were referred for otolaryngology consultation received voice treatment. Recovery rate after vocal exercises therapy and injection laryngoplasty was respectively 71% and 33%. Conclusions Voice changes after cervical mediastinoscopy is an underreported complication, with an incidence of at least 6.3% in our retrospective study, with persisting complaints in at least 1.5% of patients, leading to mild to moderate disabilities in daily living. These findings highlight the need for appropriate patient education for this underestimated complication, as well as the exploration of possible preventive measures.

Abstract Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p = 6.70 × 10−7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (odds ratio 6.7–58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP.

This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research.

BackgroundMental disorders are known to predict poverty, morbidity and mortality. In resource limited settings, low levels of mental health literacy (MHL) and high mental illness stigma (MIS) have been sighted as possible factors that may impede access to mental health care. However, little has been done to examine the association between mental disorders and these factors (MHL and MIS) in sub-Saharan Africa.MethodsWe assessed for the prevalence of major depressive disorders (MDD), substance use disorders (SUD), post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), documented MHL and MIS among 814 participants from 24 villages in central Uganda. We conducted regression analyses to examine the association between the prevalence of mental disorders, demographic factors as well as MIS and MHL.ResultsOver two thirds of the participants 581 (70%) were female. The mean age of the participants was 38 years (SD± 13.5). The prevalence of mental disorders ranged from 6.8-32%. Participants who were older were less likely to screen positive for GAD (OR 0.98; 0.96-0.99), female gender was protective against SUD (OR 0.46; 0.3-0.68) and those with MDD had lower education level (OR 0.23; 0.1-0.53). The mean MIS score was 11.3 (SD± 5.4) with a range of 6-30 and the mean MHL score was 21.7 (SD ±3.0) with a range of 10-30. MIS was negatively associated with GAD [β = -1.211 (-2.382 to -0.040)]. There no statistically significant association between MHL and a mental disorder.ConclusionThere was a high prevalence of mental disorders in the community that we studied. Adequate resources should be allocated to address this burden.

The study of cardiac electrophysiology is built on experimental models that span all scales, from ion channels to whole-body preparations. Novel discoveries made at each scale have contributed to our fundamental understanding of human cardiac electrophysiology, which informs clinicians as they detect, diagnose, and treat complex cardiac pathologies. This expert review describes an engineering approach to developing experimental models that is applicable across scales. The review also outlines how we applied the approach to create a set of multiscale whole-body experimental models of cardiac electrophysiology, models that are driving new insights into the response of the myocardium to acute ischemia. Specifically, we propose that researchers must address three critical requirements to develop an effective experimental model: 1) how the experimental model replicates and maintains human physiological conditions, 2) how the interventions possible with the experimental model capture human pathophysiology, and 3) what signals need to be measured, at which levels of resolution and fidelity, and what are the resulting requirements of the measurement system and the access to the organs of interest. We will discuss these requirements in the context of two examples of whole-body experimental models, a closed chest in situ model of cardiac ischemia and an isolated-heart, torso-tank preparation, both of which we have developed over decades and used to gather valuable insights from hundreds of experiments.

Abstract Investigating the determinants of the reproductive biology of fishes is an essential component of fisheries research. Tilapia breeding patterns were investigated to determine the impact of non‐native Oreochromis niloticus on the native congeneric Oreochromis macrochir in the upper Kabompo River in the Northwest of Zambia using the gonadosomatic index and the sex ratios. Oreochromis niloticus was the most abundant fish caught (221, 63.5%) than O. macrochir (127, 36.5%). Results showed that the overall gonadosomatic index means of O. macrochir in both sections were similar. Oreochromis macrochir bred in December and February–March, with no reproduction in June. However, O. niloticus in the invaded section indicated all year reproduction through reduced spawning in May–June, with increased spawning activity in February–March. The sex ratio (females: males) was 1:1.3 and 1:1.7 for O. niloticus and O. macrochir, respectively, and both significantly deviated from the sex ratio of 1:1 (ꭓ2 = 8.42 and 9.37, p

Cell-based transcriptional reporters are an invaluable part of highthroughput screening, but many such reporters have weak or transient responses. Here, the authors describe a digitizer circuit for amplifying reporter activity, increasing sensitivity, and retaining memory of pathway activation.

Abstract Invasive alien species have been revealed to drastically alter the structure of native communities; however, there is scarce information on whether taxonomic and functional spaces occupied by native species are equally filled by exotic species. We investigated the diversity of native species to understand the impact of exotic Oreochromis niloticus in the upper Kabompo River, northwest of Zambia using taxonomic and functional diversity indices. To achieve this, two tests were performed (Test 1, compared natives in invaded and uninvaded sections; Test 2, compared natives in invaded section). A total of 17 species were collected for functional diversity computation, out of which fourteen (14) functional trait measurements linked to feeding, locomotion, and life history strategy were taken. Findings revealed that taxonomic and functional diversity values changed with invasion in both tests. Taxonomic diversity was 15% more in invaded than uninvaded sections in Test 1 and was not consistent across sampling points of invaded section in Test 2. Invaded areas were taxonomically less diverse, but functionally diverse in both tests. The analysis of similarity and nonmetric multidimensional scaling revealed no difference in Bray–Curtis similarity assemblages in both tests. Our findings revealed that exotic species more often occupy unfilled gaps in the communities often occupied by the native species; this is achieved by occupying functional spaces. Overall, changes in taxonomic and functional diversity of native species documented here partially confirmed impacts of O. niloticus invasion. Therefore, we recommend a multifaceted approach to assess cumulative impacts of invasion on native species.

BackgroundWith the rise of fragility, conflict and violence (FCV), understanding the prevalence and risk factors associated with mental disorders is beneficial to direct aid to vulnerable groups. To better understand mental disorders depending on the population and the timeframe, we performed a systematic review to investigate the aggregate prevalence of depression, anxiety and post-traumatic stress symptoms among both civilian and military population exposed to war.MethodsWe used MEDLINE (PubMed), Web of Science, PsycINFO, and Embase to identify studies published from inception or 1–Jan, 1945 (whichever earlier), to 31–May, 2022, to reporting on the prevalence of depression, anxiety and post-traumatic stress symptoms using structured clinical interviews and validated questionnaires as well as variables known to be associated with prevalence to perform meta-regression. We then used random-effects bivariate meta-analysis models to estimate the aggregate prevalence rate.ResultsThe aggregate prevalence of depression, anxiety and post-traumatic stress during times of conflict or war were 28.9, 30.7, and 23.5%, respectively. Our results indicate a significant difference in the levels of depression and anxiety, but not post-traumatic stress, between the civilian group and the military group respectively (depression 34.7 vs 21.1%, p < 0.001; anxiety 38.6 vs 16.2%, p < 0.001; post-traumatic stress: 25.7 vs 21.3%, p = 0.256). The aggregate prevalence of depression during the wars was 38.7% (95% CI: 30.0–48.3, I2 = 98.1%), while the aggregate prevalence of depression post-wars was 29.1% (95% CI: 24.7–33.9, I2 = 99.2%). The aggregate prevalence of anxiety during the wars was 43.4% (95% CI: 27.5–60.7, I2 = 98.6%), while the aggregate prevalence of anxiety post-wars was 30.3% (95% CI: 24.5–36.9, I2 = 99.2%). The subgroup analysis showed significant difference in prevalence of depression, and anxiety between the civilians and military group (p < 0.001).ConclusionThe aggregate prevalence of depression, anxiety and post-traumatic stress in populations experiencing FCV are 28.9, 30.7, and 23.5%, respectively. There is a significant difference in prevalence of depression and anxiety between civilians and the military personnels. Our results show that there is a significant difference in the prevalence of depression and anxiety among individuals in areas affected by FCV during the wars compared to after the wars. Overall, these results highlight that mental health in times of conflict is a public health issue that cannot be ignored, and that appropriate aid made available to at risk populations can reduce the prevalence of psychiatric symptoms during time of FCV.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=337486, Identifier 337486.

With increasing off-label aesthetic indications using higher botulinum neurotoxin A (BoNT-A) doses and individuals starting treatment at a younger age, particularly in Asia, there is a greater risk of developing immunoresistance to BoNT-A. This warrants more in-depth discussions by aesthetic practitioners to inform patients and guide shared decision-making. A panel comprising international experts and experienced aesthetic practitioners in Hong Kong discussed the implications and impact of immunoresistance to BoNT-A in contemporary aesthetic practice, along with practical strategies for risk management. Following discussions on a clinical case example and the results of an Asia-Pacific consumer study, the panel concurred that it is a priority to raise awareness of the possibility and long-term implications of secondary non-response due to immunoresistance to BoNT-A. Where efficacy and safety are comparable, a formulation with the lowest immunogenicity is preferred. The panel also strongly favored a thorough initial consultation to establish the patient’s treatment history, explain treatment side effects, including the causes and consequences of immunoresistance, and discuss treatment goals. Patients look to aesthetic practitioners for guidance, placing an important responsibility on practitioners to adopt risk-mitigating strategies and adequately communicate important risks to patients to support informed and prudent BoNT-A treatment decisions.

Purpose: To compare the efficacy and safety of 6-weekly and 12-weekly intravenous methylprednisolone (IVMP) regimens in moderate-to-severe, active thyroid-associated orbitopathy (TAO) patients. Basic Procedures: Retrospective comparative study of patients who received IVMP between January 2011 and July 2021 at the Thyroid Eye Clinic, the Chinese University of Hong Kong. Outcome measures included the 7-item clinical activity score (CAS), exophthalmos, extraocular muscle motility (EOMy), marginal reflex distance (MRD), best corrected visual acuity (BCVA), intraocular pressure (IOP), the requirement of additional treatment, and complications. Main findings: A total of 65 (63% (41/65) females) moderate-to-severe, active TAO patients aged 50 ± 13 (25–74) years received 6-weekly (n = 22) or 12-weekly (n = 43) IVMP. Sex, age, smoking status, and Graves’ disease status were comparable in the two groups (all p > 0.05). CAS at week 6 (p = 0.0279), 12 (p = 0.00228), and 52 (p = 0.0228) were lower at each time for the 12-weekly group. Exophthalmos improved more at week 6 (p = 0.0453) and 12 (p = 0.0347) in the 12-weekly group. The improvement of diplopia, MRD1, MRD2, and EOMy were comparable between the two groups. More patients in the 6-weekly group (p = 0.00169) required additional treatments including IVMP+/−ORT. Patients in the 6-weekly group who did not require additional treatment had a lower presenting CAS (p = 0.0193) than those who required additional treatment. The total numbers of adverse events were comparable between the two groups.

Abstract Background Literature shows a high prevalence of psychological distress (PD) as well as common mental disorders (CMD) such as major depressive disorders (MDD), generalized anxiety disorders (GAD), post-traumatic stress disorders (PTSD), and substance misuse disorders (SUD) among people exposed to disasters and pandemics like the COVID-19. Moreover, CMD are associated with increased mortality (mainly through suicide) and morbidity (loss of productivity). A number of countries have made deliberate efforts to identify and manage CMD in light of COVID-19. However, low levels of mental health literacy (MHL) manifested by the individual’s unawareness of CMD symptoms, limited human and mental health infrastructure resources, and high levels of mental illness stigma (MIS) are barriers to integration of mental health care in general health care during pandemics and epidemics such as the COVID-19. Objectives For the proposed study, we will determine effectiveness of a psycho-education intervention delivered by village health team (VHT) members. Methods We will employ a cluster randomized trial design in 24 villages in central Uganda. We will collect baseline data to and document the prevalence of MHL, PD, MDD, PTSD, GAD, and SUD. We will distribute information education and communication materials (IEC) aimed at improving MHL to 420 adult individuals in the intervention arm (n = 12 villages). In the control arm (n = 12 villages), VHTs will distribute ministry of health COVID-19 information leaflets to 420 participants. Within 7 days of distributing the materials, research assistants will conduct a follow-up interview and assess for the same parameters (MHL, PD, MDD, PTSD, GAD, and SUD). We will use an intention to treat analysis to estimate the effectiveness of the psycho-education intervention. Discussion Findings from this research will guide policy and practice regarding the integration of mental health services in the community in the context of epidemic preparedness and response. Trial registration ClinicalTrials.gov NCT04616989 . Registered on 05 November 2020

Kiwimagi & Letendre et al. present a workflow to quantitatively define recombinase-based digitizer and predict responses to different input signals. With a mechanistic/phenotypic model that can predict circuit performance, they generate a synthetic cell-cell communication device that amplifies a synNotch output signal.

Abstract The study aims to determine the prevalence of strabismus and its risk factors among school children in Hong Kong. This is a cross-sectional study involving 6–8 year old children from different districts in Hong Kong. 4273 children received comprehensive ophthalmological examination, cycloplegic auto-refraction, best corrected visual acuity (BCVA), anterior segment examination, cover/uncover test, ocular motility, and fundus examination. Demographic information, pre- and post- natal background, parental smoking status, and family history of strabismus were obtained through questionnaires. Strabismus was found among 133 children (3.11%, 95% CI 2.59–3.63%), including 117 (2.74%) exotropia and 12 (0.28%) esotropia cases (exotropia-esotropia ratio: 9.75:1). There was no significant difference in prevalence across age (6–8 years) and gender. Multivariate analysis revealed associations of strabismus with myopia (≤ − 1.00D; OR 1.61; 95% CI 1.03–2.52; P = 0.037) hyperopia (≥ + 2.00D; OR 2.49; 95% CI 1.42–4.39; P = 0.002), astigmatism (≥ + 2.00D; OR 2.32; 95% CI 1.36–3.94; P = 0.002), and anisometropia (≥ 2.00D; OR 3.21; 95% CI 1.36–7.55; P = 0.008). Other risk factors for strabismus included maternal smoking during pregnancy (OR 4.21; 95% CI 1.80–9.81; P = 0.001), family history of strabismus (OR 6.36; 95% CI 2.78–14.50, P 35 years; OR 1.65; CI 1.09–2.49, P = 0.018). The prevalence of strabismus among children aged 6—8 years in Hong Kong is 3.11%. Refractive errors, family history of strabismus and maternal smoking history during pregnancy are risk factors. Early correction of refractive errors and avoidance of maternal smoking during pregnancy are potentially helpful in preventing strabismus.

Background:. Botulinum neurotoxin A (BoNT-A) injection is the most widely performed aesthetic procedure and a first-line therapeutic option for various medical conditions. The potential for BoNT-A immunoresistance and secondary nonresponse related to neutralizing antibody (NAb) formation warrants attention as the range of BoNT-A aesthetic applications continues to expand. Methods:. An international multidisciplinary panel reviewed published evidence on BoNT-A immunoresistance in aesthetic and therapeutic applications and discussed best practices integrating clinical, ethical, and aesthetic considerations. Consensus statements relating to awareness, assessment, and management of the risk of NAb-related secondary nonresponse in aesthetic practice were developed. Results:. There was a consensus that, as doses used in aesthetic practice become like those in therapeutics, rates of NAb formation may be expected to increase. However, the true extent of NAb formation in aesthetics is likely underestimated due to limitations of published evidence and variability in treatment patterns of aesthetic patients. Since BoNT-A therapy is often lifelong, practitioners need to recognize immunogenicity as a potential complication that might affect future therapeutic use and strive to minimize modifiable risk factors. The selection and use of a BoNT-A product with the least immunogenic potential from the beginning may thus be advantageous, especially when treatment with high doses is planned. Conclusions:. In view of current trends in BoNT-A aesthetic use, it is essential for practitioners to conduct thorough clinical assessments, inform patients of treatment risks, and develop BoNT-A treatment plans to minimize immunogenicity. This can help preserve the option of continued or future BoNT-A treatment with satisfactory outcomes.

Abstract Background Functional near-infrared spectroscopy (fNIRS) is an emerging neuroimaging modality that provides a direct and quantitative assessment of cortical haemodynamic response during a cognitive task. It may be used to identify neurophysiological differences between psychiatric disorders with overlapping symptoms, such as bipolar disorder (BD) and borderline personality disorder (BPD). Hence, this preliminary study aimed to compare the cerebral haemodynamic function of healthy controls (HC), patients with BD and patients with BPD. Methods Twenty-seven participants (9 HCs, 9 patients with BD and 9 patients with BPD) matched for age, gender, ethnicity and education were recruited. Relative oxy-haemoglobin and deoxy-haemoglobin changes in the frontotemporal cortex was monitored with a 52-channel fNIRS system during a verbal fluency task (VFT). VFT performance, clinical history and symptom severity were also noted. Results Compared to HCs, both patient groups had lower mean oxy-haemoglobin in the frontotemporal cortex during the VFT. Moreover, mean oxy-haemoglobin in the left inferior frontal region is markedly lower in patients with BPD compared to patients with BD. Task performance, clinical history and symptom severity were not associated with mean oxy-haemoglobin levels. Conclusions Prefrontal cortex activity is disrupted in patients with BD and BPD, but it is more extensive in BPD. These results provide further neurophysiological evidence for the separation of BPD from the bipolar spectrum. fNIRS could be a potential tool for assessing the frontal lobe function of patients who present with symptoms that are common to BD and BPD.

Most CAR designs lack control and computation features, limiting the sophistication of the engineered immune response. Here the authors leverage a split CAR design for engineering coordinated immune responses.

Abstract The relative and combined effects of sleep apnea with diabetes mellitus (DM) on cardiovascular outcomes in patients undergoing coronary artery bypass grafting (CABG) remain unknown. In this secondary analysis of data from the SABOT study, 1007 patients were reclassified into four groups based on their sleep apnea and DM statuses, yielding 295, 218, 278, and 216 patients in the sleep apnea (+) DM (+), sleep apnea (+) DM (−), sleep apnea (−) DM (+), and sleep apnea (−) DM (−) groups, respectively. After a mean follow-up period of 2.1 years, the crude incidence of major adverse cardiac and cerebrovascular event was 18% in the sleep apnea (+) DM (+), 11% in the sleep apnea (+) DM (−), 13% in the sleep apnea (−) DM (+), and 5% in the sleep apnea (−) DM (−) groups. Using sleep apnea (−) DM (−) as the reference group, a Cox regression analysis indicated that sleep apnea (+) and DM (+) independently predicted MACCEs (adjusted hazard ratio, 3.2; 95% confidence interval, 1.7–6.2; p = 0.005) and hospitalization for heart failure (adjusted hazard ratio, 12.6; 95% confidence interval, 3.0–52.3; p

PURPOSE Despite being the most common pediatric solid tumors, incidence and outcome of CNS tumors in Chinese children have not been systematically reported. We addressed this knowledge gap by comparing the epidemiology of pediatric CNS tumors in Hong Kong and the United States. PATIENTS AND METHODS Data between 1999 and 2016 from a population-based cancer registry in Hong Kong, China, on patients < 18 years old with CNS tumors (Hong Kong cohort) and from the US SEER Program (Asian/Pacific Islander and all ethnicities) were compared. Incidence and overall survival (OS) by histology were evaluated. RESULTS During the study period, 526 children were newly diagnosed with CNS tumors in Hong Kong (crude incidence rate, 2.47 per 100,000; 95% CI, 2.26 to 2.69). Adjusted incidences were significantly lower in the Hong Kong (2.51; 95% CI, 2.30 to 2.74) than in the SEER (Asian/Pacific Islander: 3.26; 95% CI, 2.97 to 3.57; P < .001; all ethnicities: 4.10 per 100,000; 95% CI, 3.99 to 4.22; P < .001) cohorts. Incidences of germ cell tumors (0.57 v 0.24; P < .001) were significantly higher, but those of glial and neuronal tumors (0.94 v 2.61; P < .001), ependymomas (0.18 v 0.31; P = .005), and choroid plexus tumors (0.08 v 0.16; P = .045) were significantly lower in Hong Kong compared with SEER (all ethnicities) cohorts. Compared with the SEER (Asian/Pacific Islander) cohort, histology-specific incidences were similar except for a lower incidence of glial and neuronal tumors in Hong Kong (0.94 v 1.74; P < .001). Among cohorts, OS differed only for patients with glial and neuronal tumors (5-year OS: Hong Kong, 52.5%; SEER [Asian/Pacific Islander], 73.6%; SEER [all ethnicities], 79.9%; P < .001). CONCLUSION We identified important ethnic differences in the epidemiology of CNS tumors in Chinese children. These results will inform the development of pediatric neuro-oncology services in China and aid further etiologic studies.

Catecholaminergic polymorphic ventricular tachycardia is a genetic disorder that causes ventricular tachyarrhythmias via increased release of intracellular calcium. The standard diagnostic measure is an exercise stress test that reveals ventricular ectopy. We present an extraordinary case marked by a normal stress test and no relation to exertion. (Level of Difficulty: Intermediate.)

A 45-year-old man with history of Mustard repair for transposition of the great arteries, cirrhosis, and chronic hypoxemic respiratory failure presented for subacute worsening of his chronic symptoms, which were found to be secondary to a previously unrecognized baffle stenosis and leak. Percutaneous intervention resolved his ascites and hypoxia. (Level of Difficulty: Intermediate.)

Abstract Background The severity and frequency of drought has increased around the globe, creating challenges in ensuring food security for a growing world population. As a consequence, improving water use efficiency by crops has become an important objective for crop improvement. Some wild crop relatives have adapted to extreme osmotic stresses and can provide valuable insights into traits and genetic signatures that can guide efforts to improve crop tolerance to water deficits. Eutrema salsugineum, a close relative of many cruciferous crops, is a halophytic plant and extremophyte model for abiotic stress research. Results Using comparative transcriptomics, we show that two E. salsugineum ecotypes display significantly different transcriptional responses towards a two-stage drought treatment. Even before visibly wilting, water deficit led to the differential expression of almost 1,100 genes for an ecotype from the semi-arid, sub-arctic Yukon, Canada, but only 63 genes for an ecotype from the semi-tropical, monsoonal, Shandong, China. After recovery and a second drought treatment, about 5,000 differentially expressed genes were detected in Shandong plants versus 1,900 genes in Yukon plants. Only 13 genes displayed similar drought-responsive patterns for both ecotypes. We detected 1,007 long non-protein coding RNAs (lncRNAs), 8% were only expressed in stress-treated plants, a surprising outcome given the documented association between lncRNA expression and stress. Co-expression network analysis of the transcriptomes identified eight gene clusters where at least half of the genes in each cluster were differentially expressed. While many gene clusters were correlated to drought treatments, only a single cluster significantly correlated to drought exposure in both ecotypes. Conclusion Extensive, ecotype-specific transcriptional reprogramming with drought was unexpected given that both ecotypes are adapted to saline habitats providing persistent exposure to osmotic stress. This ecotype-specific response would have escaped notice had we used a single exposure to water deficit. Finally, the apparent capacity to improve tolerance and growth after a drought episode represents an important adaptive trait for a plant that thrives under semi-arid Yukon conditions, and may be similarly advantageous for crop species experiencing stresses attributed to climate change.

Nocardia is a genus of Gram-positive, partially acid-fast bacteria consisting of over 120 species, of which 50 are recognized as human pathogens. Nocardia spp. are common colonizers in the environment, particularly in soil and water. Nocardia spp. typically cause opportunistic infections in the immunocompetent host, although cases of nocardiosis have been described in those with a normal immune system. Nocardiosis can be localized, most often in the skin or lung, or be disseminated, with involvement of the brain, bone, and visceral organs. Treatment of nocardiosis is complex, as multiple culture-directed antibacterials with appropriate tissue penetration may need to be used for a prolonged duration. To our knowledge, we describe the first successfully treated case of disseminated Nocardia beijingensis infection in an immunocompetent host with doxycycline and trimethoprim-sulfamethoxazole and hypothesize that his occupational exposure to ubiquitous saprophytes may have led to his infection.

Objectives: This meta-analysis aims to evaluate the treatment outcomes of patients treated with Group cognitive behavioural therapy (GCBT) or group psychoeducation (GPE) as an adjunct to pharmacotherapy. Methods: Systematic search of PubMed, EMBASE, PsycINFO, and CENTRAL from inception till 1 March 2022 was conducted. Randomized-controlled-trials (RCTs) comparing GCBT/GPE with controls (treatment-as-usual/individualized therapy) in adults with bipolar disorder were eligible. The outcomes were relapse rates of any depressive or manic episodes and control of depressive and manic symptoms post-intervention. Overall odds-ratio was used to evaluate the relapse rates. Standard Mean Differences were pooled using a random-effects model for the control of depressive and manic symptoms. Results: 25 articles were assessed full-text independently by two members, and 11 studies were included in this meta-analysis. 601 and 590 participants were randomized into group-therapy (GCBT/GPE) and control, respectively. GPE significantly reduces relapse rates at post-intervention with Odds ratio of 0.43 (95% CI = 0.28-to-0.62, p < 0.0001) (I² = 41%) compared to control, however, no significant results were found for GPE on control of depressive or manic symptoms. No significant results were found for GCBT in all outcomes. Conclusion: This meta-analysis provides some evidence that GPE could be an efficacious treatment as an adjunct to treatment-as-usual in reducing the relapse rates of patients with bipolar disorder.

The availability of high performance recombinases with low basal activity and high dynamic range is limited. Here the authors present a library of over 20 orthogonal split recombinases that can be induced by small molecules, light and temperature in vivo.

Antigenic imprinting, which describes the bias of the antibody response due to previous immune history, can influence vaccine effectiveness. While this phenomenon has been reported for viruses such as influenza, there is little understanding of how prior immune history affects the antibody response to SARS-CoV-2. This study provides evidence for antigenic imprinting through immunization with two Sarbecoviruses, the subgenus that includes SARS-CoV-2. Mice were immunized subsequently with two antigenically distinct Sarbecovirus strains, namely SARS-CoV-1 and SARS-CoV-2. We found that sequential heterologous immunization induced cross-reactive binding antibodies for both viruses and delayed the emergence of neutralizing antibody responses against the booster strain. Our results provide fundamental knowledge about the immune response to Sarbecovirus and important insights into the development of pan-sarbecovirus vaccines and guiding therapeutic interventions.

Boolean logic and arithmetic through DNA excision (BLADE) is a recently developed platform for implementing inducible and logical control over gene expression in mammalian cells, which has the potential to revolutionise cell engineering for therapeutic applications. This 2-input 2-output platform can implement 256 different logical circuits that exploit the specificity and stability of DNA recombination. Here, we develop the first mechanistic mathematical model of the 2-input BLADE platform based on Cre- and Flp-mediated DNA excision. After calibrating the model on experimental data from two circuits, we demonstrate close agreement between model outputs and data on the other 111 circuits that have so far been experimentally constructed using the 2-input BLADE platform. Model simulations of the remaining 143 circuits that have yet to be tested experimentally predict excellent performance of the 2-input BLADE platform across the range of possible circuits. Circuits from both the tested and untested subsets that perform less well consist of a disproportionally high number of STOP sequences. Model predictions suggested that circuit performance declines with a decrease in recombinase expression and new experimental data was generated that confirms this relationship.

Summary: The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, a pandemic. There is currently a lack of knowledge about the antibody response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. Our results show that, although cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of a non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV but also has implications for immunogen design and vaccine development.

Inducible genetic switches based on tyrosine recombinase-based DNA excision are a promising platform for the regulation and control of chimeric antigen receptor (CAR) T cell activity in cancer immunotherapy. These switches exploit the increased stability of DNA excision in tyrosine recombinases through an inversion–excision circuit design. Here, the authors develop the first mechanistic mathematical model of switching dynamics in tyrosine recombinases and validate it against experimental data through both global optimisation and statistical approximation approaches. Analysis of this model provides guidelines regarding which system parameters are best suited to experimental tuning in order to establish optimal switch performance in vivo. In particular, they find that the switching response can be made significantly faster by increasing the concentration of the inducer drug 4-OHT and/or by using promoters generating higher expression levels of the FlpO recombinase.

Introduction. Abnormal pacemaker behavior can occur during radiofrequency ablation. The behaviors are varied and include loss of capture. The mechanisms in this context have not been well described in the literature. We describe a case of epicardial unipolar lead loss of ventricular capture during pulmonary vein isolation. Case History. A 48-year-old man with an epicardial dual chamber pacemaker and persistent atrial fibrillation presented for radiofrequency ablation (RFA) of his abnormal rhythm. During RFA, intermittent loss of ventricular capture was witnessed. Review of the device settings prior to and after the procedure showed an increase in ventricular threshold after the procedure. Loss of capture was shown to be dependent on location and RF energy delivered. It was independent of QTc and independent of local cellular changes that would increase threshold. Conclusion. We hypothesize the mechanism of loss of ventricular capture in this patient with an epicardial pacemaker with unipolar leads is related to intermittent shunt of voltage from the pulse generator to the grounding pad rather than the unipolar lead.

Background: Functional near infrared spectroscopy (fNIRS) provides a direct and quantitative assessment of cortical haemodynamic function during a cognitive task. This functional neuroimaging modality may be used to elucidate the pathophysiology of psychiatric disorders, and identify neurophysiological differences between co-occurring psychiatric disorders. However, fNIRS research on borderline personality disorder (BPD) has been limited. Hence, this study aimed to compare cerebral haemodynamic function in healthy controls (HC), patients with major depressive disorder (MDD) and patients with BPD. Methods: fNIRS signals during a verbal fluency task designed for clinical assessment was recorded for all participants. Demographics, clinical history and symptom severity were also noted. Findings: Compared to HCs (n = 31), both patient groups (MDD, n = 31; BPD, n = 31) displayed diminished haemodynamic response in the frontal, temporal and parietal cortices. Moreover, haemodynamic response in the right frontal cortex is markedly lower in patients with MDD compared to patients with BPD. Interpretation: Normal cortical function in patients with BPD is disrupted, but not as extensively as in patients with MDD. These results provide further neurophysiological evidence for the distinction of patients with MDD from patients with BPD. Keywords: Near-infrared spectroscopy, Verbal fluency task, Prefrontal cortex, Haemodynamic response, Borderline personality disorder, Major depressive disorder

Abstract The prevalence of depression may be affected by changes in psychiatric practices and the availability of online mental health information in the past two decades. This study aimed to evaluate the aggregate prevalence of depression in communities from different countries between 1994 and 2014 and to explore the variations in prevalence stratified by geographical, methodological and socio-economic factors. A total of 90 studies were identified and met the inclusion criteria (n = 1,112,573 adults) with 68 studies on single point prevalence, 9 studies on one-year prevalence, and 13 studies on lifetime prevalence of depression. A random-effects model meta-analysis that was performed to calculate the aggregate point, one-year and lifetime prevalence of depression calculated prevalences of 12.9%, 7.2% and 10.8% respectively. Point prevalence of depression was significantly higher in women (14.4%), countries with a medium human development index (HDI) (29.2%), studies published from 2004 to 2014 (15.4%) and when using self-reporting instruments (17.3%) to assess depression. Heterogeneity was identified by meta-regression and subgroup analysis, and response rate, percentage of women and year of publication, respectively, were determined contribute to depression prevalence. This meta-analysis allows benchmarking of the prevalence of depression during the era when online health information emerged, facilitating future comparisons.

Abstract Background Many clinical practice guidelines encourage diagnosis and empiric treatment of lower urinary tract infection without laboratory investigation; however, urine culture testing remains one of the largest volume tests in the clinical microbiology laboratory. In this study, we sought to determine if there were specific patient groups to which increased testing was directed. To do so, we combined laboratory data on testing rates with Census Canada sociodemographic data. Methods Urine culture testing data was obtained from the Calgary Laboratory Services information system for 2011. We examined all census dissemination areas within the city of Calgary and, for each area, testing rates were determined for age and gender cohorts. We then compared these testing rates to sociodemographic factors obtained from Census Canada and used Poisson regression and generalized estimating equations to test associations between testing rates and sociodemographic variables. Results Per capita urine culture testing is increasing in Calgary. For 2011, 100,901 individuals (9.2% of all people) received urine cultures and were included in this analysis. The majority of cultures were received from the community (67.9%). Substantial differences in rate of testing were observed across the city. Most notably, urine culture testing was drastically lower in areas of high (≥ $100000) household income (RR = 0.07, p

Abstract Background An up-to-date systematic review is important for researchers to decide whether to embark on new research or continue supporting ongoing studies. The aim of this study is to examine the time taken between the last search, submission, acceptance and publication dates of systematic reviews published in nursing journals. Methods Nursing journals indexed in Journal Citation Reports were first identified. Thereafter, systematic reviews published in these journals in 2014 were extracted from three databases. The quality of the systematic reviews were evaluated by the AMSTAR. The last search, submission, acceptance, online publication, full publication dates and other characteristics of the systematic reviews were recorded. The time taken between the five dates was then computed. Descriptive statistics were used to summarize the time differences; non-parametric statistics were used to examine the association between the time taken from the last search and full publication alongside other potential factors, including the funding support, submission during holiday periods, number of records retrieved from database, inclusion of meta-analysis, and quality of the review. Results A total of 107 nursing journals were included in this study, from which 1070 articles were identified through the database search. After screening for eligibility, 202 systematic reviews were included in the analysis. The quality of these reviews was low with the median score of 3 out of 11. A total of 172 (85.1%), 72 (35.6%), 153 (75.7%) and 149 (73.8%) systematic reviews provided their last search, submission, acceptance and online published dates respectively. The median numbers of days taken from the last search to acceptance and to full publication were, respectively, 393 (IQR: 212–609) and 669 (427–915) whereas that from submission to full publication was 365 (243–486). Moreover, the median number of days from the last search to submission and from submission to online publication were 167.5 (53.5–427) and 153 (92–212), respectively. No significant association were revealed between the time lag and those potential factors. Conclusion The median time from the last search to acceptance for systematic reviews published in nursing journals was 393 days. Readers for systematic reviews are advised to check the time taken from the last search date of the reviews in order to ensure that up-to-date evidence is consulted for effective clinical decision-making.