FAM69C functions as a kinase for eIF2α and promotes stress granule assembly.

Stress granules are dynamic cytoplasmic ribonucleoprotein granules that assemble in response to cellular stress. Aberrant formation of stress granules has been linked to neurodegenerative diseases. However, the molecular mechanisms underlying the initiation of stress granules remain elusive. Here we report that the brain-enriched protein kinase FAM69C promotes stress granule assembly through phosphorylation of eukaryotic translation initiation factor 2 (eIF2α). FAM69C physically interacts with eIF2α and functions as a stress-specific kinase for eIF2α, leading to stress-induced protein translation arrest and stress granule assembly. Primary microglia derived from Fam69c knockout mice exhibit aberrant stress granule assembly in response to oxidative stress and ATP. Defective stress granule assembly in microglia correlates with the formation of ASC specks and NLRP3 inflammasome activation, whereas induction of stress granule precludes inflammasome formation. Consistently, increased NLRP3 levels, caspase-1 cleavage and Il18 expression corroborate microglia-associated neuroinflammation in aged Fam69c knockout mice. Our study demonstrates that FAM69C is critical for stress granule assembly and suggests its role in the regulation of microglia function.

BREAST-Q REACT: Qualitative Assessment of the Design, Functionality, and Clinical Utility of a New Score Interpretation Tool.

BACKGROUND: The BREAST-Q real-time engagement and communication tool (REACT) was developed to aid with BREAST-Q score interpretation and guide patient-centered care. OBJECTIVE: The purpose of this qualitative study was to examine the perspectives of patients and providers on the design, functionality, and clinical utility of REACT and refine the REACT based on their recommendations. METHODS: We conducted three patient focus groups with women who were at least 6 postoperative months from their postmastectomy breast reconstruction, and two provider focus groups with plastic surgeons, breast surgeons, and advanced practice providers. Focus groups were audio-taped, transcribed verbatim, and analyzed thematically. RESULTS: A total of 18 breast reconstruction patients and 14 providers participated in the focus groups. Themes identified by thematic analysis were organized into two categories: (1) design and functionality, and (2) clinical utility. On the design and functionality of REACT, four major themes were identified: visual appeal and usefulness; contextualizing results; ability to normalize patients' experiences, noting participants' concerns; and suggested modifications. On the clinical utility of REACT, three major themes were identified: potential to empower patients to communicate with their providers; increase patient and provider motivation to engage with the BREAST-Q; and effective integration into clinical workflow. CONCLUSION: Patients and providers in this qualitative study indicated that with some modifications, REACT has a great potential to elevate the clinical utility of the BREAST-Q by enhancing patient-provider communication that can lead to patient-centered, clinically relevant action recommendations based on longitudinal BREAST-Q scores.

Antifungal efficacy of natural antiseptic products against Candida auris.

Candida auris is an emerging fungal pathogen responsible for healthcare associated infections and outbreaks with high mortality around the world. It readily colonizes the skin, nares, respiratory and urinary tract of hospitalized patients, and such colonization may lead to invasive Candida infection in susceptible patients. However, there is no recommended decolonization protocol for C. auris by international health authorities. The aim of this study is to evaluate the susceptibility of C. auris to commonly used synthetic and natural antiseptic products using an in vitro, broth microdilution assay. Synthetic antiseptics including chlorhexidine, povidone-iodine, and nystatin were shown to be fungicidal against C. auris. Among the natural antiseptics tested, tea tree oil and manuka oil were both fungicidal against C. auris at concentrations less than or equal to 1.25% (v/v). Manuka honey inhibited C. auris at 25% (v/v) concentrations. Among the commercial products tested, manuka body wash and mouthwash were fungicidal against C. auris at concentrations less than or equal to 0.39% (w/v) and 6.25% (v/v) of products as supplied for use, respectively, while tea tree body wash and MedihoneyTM wound gel demonstrated fungistatic properties. In conclusion, this study demonstrated good in vitro antifungal efficacy of tea tree oil, manuka oil, manuka honey, and commercially available antiseptic products containing these active ingredients. Future studies are warranted to evaluate the effectiveness of these antiseptic products in clinical settings.

Candida auris is an emerging superbug fungus that poses a serious threat to global public health. The excellent antifungal efficacy of natural antiseptics and their commercial hygiene products provide new insights into development of an alternative decolonization regimen against Candida auris.

Adaptive designs were primarily used but inadequately reported in early phase drug trials.

BACKGROUND: Faced with the high cost and limited efficiency of classical randomized controlled trials, researchers are increasingly applying adaptive designs to speed up the development of new drugs. However, the application of adaptive design to drug randomized controlled trials (RCTs) and whether the reporting is adequate are unclear. Thus, this study aimed to summarize the epidemiological characteristics of the relevant trials and assess their reporting quality by the Adaptive designs CONSORT Extension (ACE) checklist. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to January 2020. We included drug RCTs that explicitly claimed to be adaptive trials or used any type of adaptative design. We extracted the epidemiological characteristics of included studies to summarize their adaptive design application. We assessed the reporting quality of the trials by Adaptive designs CONSORT Extension (ACE) checklist. Univariable and multivariable linear regression models were used to the association of four prespecified factors with the quality of reporting. RESULTS: Our survey included 108 adaptive trials. We found that adaptive design has been increasingly applied over the years, and was commonly used in phase II trials (n = 45, 41.7%). The primary reasons for using adaptive design were to speed the trial and facilitate decision-making (n = 24, 22.2%), maximize the benefit of participants (n = 21, 19.4%), and reduce the total sample size (n = 15, 13.9%). Group sequential design (n = 63, 58.3%) was the most frequently applied method, followed by adaptive randomization design (n = 26, 24.1%), and adaptive dose-finding design (n = 24, 22.2%). The proportion of adherence to the ACE checklist of 26 topics ranged from 7.4 to 99.1%, with eight topics being adequately reported (i.e., level of adherence ≥ 80%), and eight others being poorly reported (i.e., level of adherence ≤ 30%). In addition, among the seven items specific for adaptive trials, three were poorly reported: accessibility to statistical analysis plan (n = 8, 7.4%), measures for confidentiality (n = 14, 13.0%), and assessments of similarity between interim stages (n = 25, 23.1%). The mean score of the ACE checklist was 13.9 (standard deviation [SD], 3.5) out of 26. According to our multivariable regression analysis, later published trials (estimated ß = 0.14, p < 0.01) and the multicenter trials (estimated ß = 2.22, p < 0.01) were associated with better reporting. CONCLUSION: Adaptive design has shown an increasing use over the years, and was primarily applied to early phase drug trials. However, the reporting quality of adaptive trials is suboptimal, and substantial efforts are needed to improve the reporting.

Design and statistical analysis reporting among interrupted time series studies in drug utilization research: a cross-sectional survey.

INTRODUCTION: Interrupted time series (ITS) design is a commonly used method for evaluating large-scale interventions in clinical practice or public health. However, improperly using this method can lead to biased results. OBJECTIVE: To investigate design and statistical analysis characteristics of drug utilization studies using ITS design, and give recommendations for improvements. METHODS: A literature search was conducted based on PubMed from January 2021 to December 2021. We included original articles that used ITS design to investigate drug utilization without restriction on study population or outcome types. A structured, pilot-tested questionnaire was developed to extract information regarding study characteristics and details about design and statistical analysis. RESULTS: We included 153 eligible studies. Among those, 28.1% (43/153) clearly explained the rationale for using the ITS design and 13.7% (21/153) clarified the rationale of using the specified ITS model structure. One hundred and forty-nine studies used aggregated data to do ITS analysis, and 20.8% (31/149) clarified the rationale for the number of time points. The consideration of autocorrelation, non-stationary and seasonality was often lacking among those studies, and only 14 studies mentioned all of three methodological issues. Missing data was mentioned in 31 studies. Only 39.22% (60/153) reported the regression models, while 15 studies gave the incorrect interpretation of level change due to time parameterization. Time-varying participant characteristics were considered in 24 studies. In 97 studies containing hierarchical data, 23 studies clarified the heterogeneity among clusters and used statistical methods to address this issue. CONCLUSION: The quality of design and statistical analyses in ITS studies for drug utilization remains unsatisfactory. Three emerging methodological issues warranted particular attention, including incorrect interpretation of level change due to time parameterization, time-varying participant characteristics and hierarchical data analysis. We offered specific recommendations about the design, analysis and reporting of the ITS study.

Tethered balloon system and High-Resolution Mass Spectrometry Reveal Increased Organonitrates Aloft Compared to the Ground Level.

Atmospheric particles play critical roles in climate. However, significant knowledge gaps remain regarding the vertically resolved organic molecular-level composition of atmospheric particles due to aloft sampling challenges. To address this, we use a tethered balloon system at the Southern Great Plains Observatory and high-resolution mass spectrometry to, respectively, collect and characterize organic molecular formulas (MF) in the ground level and aloft (up to 750 m) samples. We show that organic MF uniquely detected aloft were dominated by organonitrates (139 MF; 54% of all uniquely detected aloft MF). Organonitrates that were uniquely detected aloft featured elevated O/C ratios (0.73 ± 0.23) compared to aloft organonitrates that were commonly observed at the ground level (0.63 ± 0.22). Unique aloft organic molecular composition was positively associated with increased cloud coverage, increased aloft relative humidity (∼40% increase compared to ground level), and decreased vertical wind variance. Furthermore, 29% of extremely low volatility organic compounds in the aloft sample were truly unique to the aloft sample compared to the ground level, emphasizing potential oligomer formation at higher altitudes. Overall, this study highlights the importance of considering vertically resolved organic molecular composition (particularly for organonitrates) and hypothesizes that aqueous phase transformations and vertical wind variance may be key variables affecting the molecular composition of aloft organic aerosol.

Adoption of the cardiopulmonary exercise test in the exercise ability and cardiopulmonary function rehabilitation of coronary artery disease (CAD) patients.

BACKGROUND: This study aimed to explore the application of cardiopulmonary exercise testing in coronary artery disease (CAD) patients, evaluate its impact on exercise ability and cardiopulmonary function in patients with coronary heart disease (CHD), and promote the application of cardiopulmonary exercise testing in CAD management. METHODS: Fifty CHD patients after percutaneous coronary intervention (PCI) were recruited and randomly enrolled into the control (Ctrl) group and intervention (Int) group. Routine health education and health education combined with RT training were carried out for the two groups. Blood lipid levels and lung function were compared between the two groups after intervention. Cardiac function was evaluated by Doppler ultrasonography, and cardiopulmonary fitness and exercise ability were evaluated by a cardiopulmonary exercise test (CPET). The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were employed to evaluate negative emotions. The 36-item short-form (SF-36) was adopted to evaluate quality of life. RESULT: Compared with those in the Ctrl group, the levels of serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) decreased in the Int group, while the levels of high-density lipoprotein increased (P < 0.05). The quantitative load results showed that compared with the Ctrl group, the heart rate (HR) and self-perceived fatigue degree of the Int group decreased, and the ST segment increased (P < 0.05). Compared with the Ctrl group, the left ventricular ejection fraction (LVEF), forced expiratory volume at 1 s (FEV1), ratio of forced expiratory volume to forced vital volume (FEV1/FVC%), and maximum chase volume (MVV) increased in the Int group, while the left ventricular end diastolic diameter and left ventricular end contractile diameter decreased (P < 0.05). The results of the CPET showed that compared with the Ctrl group, minute ventilation/carbon dioxide production slope, VE/VCO2 - Peak, anaerobic threshold (AT), peak oxygen pulse (VO2/HR peak), oxygen uptake efficiency platform (OUEP), increasing power exercise time (IPEt), HR recovery 1 min after exercise, peak load power (Watt peak), and value metabolic equivalent (Watt peak) increased in the Int group (P < 0.05). Compared with the Ctrl group, the SAS and SDS scores in the Int group decreased (P < 0.05). The results of the quality of life evaluation showed that compared with the Ctrl group, the score of the SF-36 dimensions increased in the Int group (P < 0.05). CONCLUSION: RT training can reduce postoperative blood lipid and quantitative load levels in CAD patients and improve adverse mood. Furthermore, it can improve patients' cardiopulmonary function, cardiopulmonary fitness, exercise ability, and quality of life.

Comparing various Bayesian random-effects models for pooling randomized controlled trials with rare events.

The meta-analysis of rare events presents unique methodological challenges owing to the small number of events. Bayesian methods are often used to combine rare events data to inform decision-making, as they can incorporate prior information and handle studies with zero events without the need for continuity corrections. However, the comparative performances of different Bayesian models in pooling rare events data are not well understood. We conducted a simulation to compare the statistical properties of four parameterizations based on the binomial-normal hierarchical model, using two different priors for the treatment effect: weakly informative prior (WIP) and non-informative prior (NIP), pooling randomized controlled trials with rare events using the odds ratio metric. We also considered the beta-binomial model proposed by Kuss and the random intercept and slope generalized linear mixed models. The simulation scenarios varied based on the treatment effect, sample size ratio between the treatment and control arms, and level of heterogeneity. Performance was evaluated using median bias, root mean square error, median width of 95% credible or confidence intervals, coverage, Type I error, and empirical power. Two reviews are used to illustrate these methods. The results demonstrate that the WIP outperforms the NIP within the same model structure. Among the compared models, the model that included the treatment effect parameter in the risk model for the control arm did not perform well. Our findings confirm that rare events meta-analysis faces the challenge of being underpowered, highlighting the importance of reporting the power of results in empirical studies.

Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer's disease.

BACKGROUND: The identification of pathogenic mutations in Alzheimer's disease (AD) causal genes led to a better understanding of the pathobiology of AD. Familial Alzheimer's disease (FAD) is known to be associated with mutations in the APP, PSEN1, and PSEN2 genes involved in Aß production; however, these genetic defects occur in only about 10-20% of FAD cases, and more genes and new mechanism causing FAD remain largely obscure. METHODS: We performed exome sequencing on family members with a FAD pedigree and identified gene variant ZDHHC21 p.T209S. A ZDHHC21T209S/T209S knock-in mouse model was then generated using CRISPR/Cas9. The Morris water navigation task was then used to examine spatial learning and memory. The involvement of aberrant palmitoylation of FYN tyrosine kinase and APP in AD pathology was evaluated using biochemical methods and immunostaining. Aß and tau pathophysiology was evaluated using ELISA, biochemical methods, and immunostaining. Field recordings of synaptic long-term potentiation were obtained to examine synaptic plasticity. The density of synapses and dendritic branches was quantified using electron microscopy and Golgi staining. RESULTS: We identified a variant (c.999A > T, p.T209S) of ZDHHC21 gene in a Han Chinese family. The proband presented marked cognitive impairment at 55 years of age (Mini-Mental State Examination score = 5, Clinical Dementia Rating = 3). Considerable Aß retention was observed in the bilateral frontal, parietal, and lateral temporal cortices. The novel heterozygous missense mutation (p.T209S) was detected in all family members with AD and was not present in those unaffected, indicating cosegregation. ZDHHC21T209S/T209S mice exhibited cognitive impairment and synaptic dysfunction, suggesting the strong pathogenicity of the mutation. The ZDHHC21 p.T209S mutation significantly enhanced FYN palmitoylation, causing overactivation of NMDAR2B, inducing increased neuronal sensitivity to excitotoxicity leading to further synaptic dysfunction and neuronal loss. The palmitoylation of APP was also increased in ZDHHC21T209S/T209S mice, possibly contributing to Aß production. Palmitoyltransferase inhibitors reversed synaptic function impairment. CONCLUSIONS: ZDHHC21 p.T209S is a novel, candidate causal gene mutation in a Chinese FAD pedigree. Our discoveries strongly suggest that aberrant protein palmitoylation mediated by ZDHHC21 mutations is a new pathogenic mechanism of AD, warranting further investigations for the development of therapeutic interventions.

Vertical Gradient of Size-Resolved Aerosol Compositions over the Arctic Reveals Cloud Processed Aerosol in-Cloud and above Cloud.

Arctic aerosols play a significant role in aerosol-radiation and aerosol-cloud interactions, but ground-based measurements are insufficient to explain the interaction of aerosols and clouds in a vertically stratified Arctic atmosphere. This study shows the vertical variability of a size resolved aerosol composition via a tethered balloon system at Oliktok Point, Alaska, at different cloud layers for two representative case studies (background aerosol and polluted conditions). Multimodal microspectroscopy analysis during the background case reveals a broadening of chemically specific size distribution above the cloud top with a high abundance of sulfate particles and core-shell morphology, suggesting possible cloud processing of aerosols. The polluted case also indicates broadening of aerosol size distribution at the upper layer within the clouds with the dominance of carbonaceous particles, which suggests that the carbonaceous particles play a potential role in modulating Arctic cloud properties.

Molecular Imaging Reveals Two Distinct Mixing States of PM2.5 Particles Sampled in a Typical Beijing Winter Pollution Case.

Mixing states of aerosol particles are crucial for understanding the role of aerosols in influencing air quality and climate. However, a fundamental understanding of the complex mixing states is still lacking because most traditional analysis techniques only reveal bulk chemical and physical properties with limited surface and 3-D information. In this research, 3-D molecular imaging enabled by ToF-SIMS was used to elucidate the mixing states of PM2.5 samples obtained from a typical Beijing winter haze event. In light pollution cases, a thin organic layer covers separated inorganic particles; while in serious pollution cases, ion exchange and an organic-inorganic mixing surface on large-area particles were observed. The new results provide key 3-D molecular information of mixing states, which is highly potential for reducing uncertainty and bias in representing aerosol-cloud interactions in current Earth System Models and improving the understanding of aerosols on air quality and human health.

Negative pressure wound therapy for treating pressure ulcers.

BACKGROUND: Pressure ulcers, also known as bedsores, pressure sores, or pressure injuries, are localised damage to the skin and underlying soft tissue, usually caused by intense or long-term pressure, shear, or friction. Negative pressure wound therapy (NPWT) has been widely used in the treatment of pressure ulcers, but its effect needs to be further clarified. This is an update of a Cochrane Review first published in 2015. OBJECTIVES: To evaluate the effectiveness of NPWT for treating adult with pressure ulcers in any care setting. SEARCH METHODS: On 13 January 2022, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase, and EBSCO CINAHL Plus. We also searched ClinicalTrials.gov and the WHO ICTRP Search Portal for ongoing and unpublished studies and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: We included published and unpublished randomised controlled trials (RCTs) comparing the effects of NPWT with alternative treatments or different types of NPWT in the treatment of adults with pressure ulcers (stage II or above). DATA COLLECTION AND ANALYSIS: Two review authors independently conducted study selection, data extraction, risk of bias assessment using the Cochrane risk of bias tool, and the certainty of the evidence assessment using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. Any disagreement was resolved by discussion with a third review author. MAIN RESULTS: This review included eight RCTs with a total of 327 randomised participants. Six of the eight included studies were deemed to be at a high risk of bias in one or more risk of bias domains, and evidence for all outcomes of interest was deemed to be of very low certainty. Most studies had small sample sizes (range: 12 to 96, median: 37 participants). Five studies compared NPWT with dressings, but only one study reported usable primary outcome data (complete wound healing and adverse events). This study had only 12 participants and there were very few events; only one participant was healed in the study (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.15 to 61.74, very low-certainly evidence). There was no evidence of a difference in the number of participants with adverse events in the NPWT group and the dressing group, but the evidence for this outcome was also assessed as very low certainty (RR 1.25, 95% CI 0.64 to 2.44, very low-certainty evidence). Changes in ulcer size, pressure ulcer severity, cost, and pressure ulcer scale for healing (PUSH) sores were also reported, but we were unable to draw conclusions due to the low certainly of the evidence. One study compared NPWT with a series of gel treatments, but this study provided no usable data. Another study compared NPWT with 'moist wound healing',  which did not report primary outcome data. Changes in ulcer size and cost were reported in this study, but we assessed the evidence as being of very low certainty; One study compared NPWT combined with internet-plus home care with standard care, but no primary outcome data were reported. Changes in ulcer size, pain, and dressing change times were reported, but we also assessed the evidence as being of very low certainty. None of the included studies reported time to complete healing, health-related quality of life, wound infection, or wound recurrence. AUTHORS' CONCLUSIONS: The efficacy, safety, and acceptability of NPWT in treating pressure ulcers compared to usual care are uncertain due to the lack of key data on complete wound healing, adverse events, time to complete healing, and cost-effectiveness.  Compared with usual care, using NPWT may speed up the reduction of pressure ulcer size and severity of pressure ulcer, reduce pain, and dressing change times. Still, trials were small, poorly described, had short follow-up times, and with a high risk of bias; any conclusions drawn from the current evidence should be interpreted with considerable caution. In the future, high-quality research with large sample sizes and low risk of bias is still needed to further verify the efficacy, safety, and cost-effectiveness of NPWT in the treatment of pressure ulcers. Future researchers need to recognise the importance of complete and accurate reporting of clinically important outcomes such as the complete healing rate, healing time, and adverse events.

Performance of optical sensors for cloud measurements deployed by the ARM Aerial Facility during ACE-ENA.

During the Aerosol and Cloud Experiment in the Eastern North Atlantic (ACE-ENA), a variety of in situ optical sensors using shadow imaging, scattering and holography were deployed by the Atmospheric Radiation Measurement (ARM) Aerial Facility to determine cloud properties. Taking advantage of the wide, overlapping range of instrumentation, we compare in situ cloud data from several different measurement methods for droplets up to 100 µm. Data processing was tailored to the encountered conditions, leading to good agreement. Improvements include noise reduction for holography and better out-of-focus correction for shadow imaging. Comparison between direct liquid water content measurements and optical sensors showed better agreement at higher droplet number concentrations (>120/c m 3).

Global output on artificial intelligence in the field of nursing: A bibliometric analysis and science mapping.

PURPOSE: To analyze the AI research in the field of nursing, to explore the current situation, hot topics, and prospects of AI research in the field of nursing, and to provide a reference for researchers to carry out related studies. METHODS: We used the VOSviewer 1.6.17, SciMAT, and CiteSpace 5.8.R3 to generate visual cooperation network maps for the country, organizations, authors, citations, and keywords and perform burst detection, theme evolution, and so forth. FINDINGS: A total of 9318 articles were obtained from the Web of Science Core Collection database. Four hundred and thirty-one AI research related to the field of nursing was published by 855 institutions from 54 countries. CIN-Computers Informatics Nursing was the top productive journal. The United States was the dominant country. The transnational cooperation between authors from developed countries was closer than that between authors from developing countries. The main hot topics included nurse rostering, nursing diagnosis, nursing decision support, disease risk factor prediction, nursing big data management, expert system, support vector machine, decision tree, deep learning, natural language processing, and nursing education. Machine learning represented one of the cutting-edge and most applicable branches of artificial intelligence in the field of nursing, and deep learning was the hottest technology among many machine learning methods in recent years. One of the most cited papers was published by Burke in 2004 and cited 500 times, which critically evaluated AI methods to deal with nurse scheduling problems. CONCLUSIONS: Although AI has been paid more and more attention to the field of nursing, there is still a lack of high-yielding authors who have been engaged in this field for a long time. Most of the high contribution authors and institutions came from developed countries; therefore, more transnational and multi-disciplinary cooperation is needed to promote the development of AI in the nursing field. This bibliometric analysis not only provided a comprehensive overview to help researchers to understand the important articles, journals, potential collaborators, and institutions in this field but also analyzed the history, hot spots, and future trends of the research topic to provide inspiration for researchers to choose research directions.

Registration and Reporting Quality of Systematic Reviews on Surgical Intervention: A Meta-epidemiological Study.

INTRODUCTION: The prospective registration of systematic reviews represent an effective strategy for reducing the selective reporting of outcomes. However, the relationship between registration and the reporting quality of systematic reviews on surgical interventions remains unclear. METHODS: MEDLINE was searched for relevant systematic reviews of randomized controlled trials investigating surgical interventions published in 2020. Data concerning general characteristics and registration information were independently extracted. The reporting quality was evaluated in accordance with pre-established evaluation criteria. Univariate and multivariate linear regression were performed to identify factors associated with improved reporting quality. RESULTS: A total of 135 systematic reviews were analyzed, of which 50 (37%) were registered. Registered systematic reviews achieved a significantly higher compliance rate on all items compared with non-registered reviews. Registered reviews also demonstrated significantly higher proportions of the reporting of seven items. Multivariate regression analysis showed that registration status and funding support were associated with better reporting quality. CONCLUSIONS: Although prospective registration associates with higher reporting quality in systematic reviews, the number of prospective registrations remains low. Therefore, prospective registration should be encouraged among authors, peer reviewers, and journal editors, as well as institutions, to enhance the value of systematic reviews in evidence-based surgical practice.

Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall.

The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere. Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions, but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear. Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.

Probiotics for the prevention of Hirschsprung-associated enterocolitis.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is a leading cause of serious morbidity and potential mortality in children with Hirschsprung's disease (HD). People with HAEC suffer from intestinal inflammation, and present with diarrhoea, explosive stools, and abdominal distension. Probiotics are live microorganisms with beneficial health effects, which can optimise gastrointestinal function and gut flora. However, the efficacy and safety of probiotic supplementation in the prevention of HAEC remains unclear. OBJECTIVES: To assess the effects of probiotic supplements used either alone or in combination with pharmacological interventions on the prevention of Hirschsprung-associated enterocolitis. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, the China BioMedical Literature database (CBM), the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, the Chinese Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, and Clinical Trials Registry-India, from database inception to 27 February 2022. We also searched the reference lists of relevant articles and reviews for any additional trails. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics and placebo, or any other non-probiotic intervention, for the prevention of HAEC were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of the included studies; disagreements were resolved by discussion with a third review author. We assessed the certainty of evidence using the GRADE approach. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes. MAIN RESULTS: We included two RCTs, with a total of 122 participants. We judged the overall risk of bias as high. We downgraded the evidence due to risk of bias (random sequence generation, allocation concealment, and blinding) and small sample size. The evidence is very uncertain about the effect of probiotics on the occurrence of HAEC (OR 0.58, 95% CI 0.10 to 3.43; I² = 74%; 2 studies, 120 participants; very low-certainty evidence). We found one included study that did not measure serious adverse events and one included study that reported no serious adverse events related to probiotics. Probiotics may result in little to no difference between probiotics and placebo in relation to the severity of children with HAEC at Grade I (OR 0.66, 95% CI 0.14 to 3.16; I² = 25%; 2 studies, 120 participants; low-certainty evidence). The effects of probiotics on the severity of HAEC at Grade II are very uncertain (OR 1.14, 95% CI 0.01 to 136.58; I² = 86%; 2 studies, 120 participants; very low-certainty evidence). Similarly, the evidence suggests that probiotics results in little to no difference in relation to the severity of HAEC at Grade III (OR 0.43, 95% CI 0.05 to 3.45; I² = 0%; 2 studies, 120 participants; low-certainty evidence). No overall mortality or withdrawals due to adverse events were reported. Probiotics may result in little to no difference in the recurrence of episodes of HAEC compared to placebo (OR 0.85, 95% CI 0.24 to 3.00; 1 study, 60 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of Hirschsprung-associated enterocolitis when compared with placebo. The presence of low- to very-low certainty evidence suggests that further well-designed and sufficiently powered RCTs are needed to clarify the true efficacy of probiotics.

Impact of preoperative sarcopenia on postoperative complications and survival outcomes of patients with esophageal cancer: a meta-analysis of cohort studies.

The effects of preoperative sarcopenia on postoperative complications and survival outcomes of patients undergoing esophageal cancer resection are controversial. From database establishment to 16 May 2021, we systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and Chinese Biomedical Literature Database to collect relevant studies investigating the effects of preoperative sarcopenia on postoperative complications, survival outcomes, and the risk of a poor prognosis of patients undergoing esophagectomy. The Newcastle-Ottawa scale was used to evaluate the quality of the included literature, and RevMan 5.3 software was used for the meta-analysis. A total of 26 studies (3 prospective cohort studies and 23 retrospective cohort studies), involving 4,515 patients, were included. The meta-analysis showed that preoperative sarcopenia significantly increased the risk of overall complications (risk ratio [RR]: 1.15; 95% confidence interval [CI]: 1.08-1.22), pulmonary complications (RR: 1.78; 95% CI: 1.48-2.14), and anastomotic leakage (RR: 1.29; 95% CI: 1.04-1.59) and reduced the overall survival rate (hazard ratio: 1.12; 95% CI: 1.04-1.20) following esophageal cancer resection. Preoperative sarcopenia increased the risks of overall postoperative and pulmonary complications in patients undergoing esophageal cancer resection. For patients with esophageal cancer, assessing the preoperative risk of preoperative sarcopenia is necessary.

Case Report of a pathologically confirmed vascular parkinsonism with early cognitive impairment and Behavioral disturbance.

BACKGROUND: Vascular Parkinsonism(VaP) is defined as parkinsonism resulting from cerebral vascular disease(CVD), with presence of variable motor and non-motor signs that are corroborated by clinical, anatomic or imaging findings of cerebrovascular disease. Overlapping syndromes with mixed pathologies make VaP difficult to distinguish from primary neurodegenerative parkinsonism.To understand the clinical and pathological features of VaP,we report a case of autopsy confirmed vascular Parkinsonism that was clinical misdiagnosed as idiopathic Parkinson's disease.Clinical features include early mixed symptoms of dementia,behavioral disturbance and parkinsonism that were similar to Dementia with lewy Body(DLB) and Parkinson disease Dementia(PDD). CASE PRESENTATION: A 84-year-old man presented progressive parkinsonism with prominent postural instability, gait impairment, pseudobulbar, early cognitive impairment, irritability, hallucination, urinary symptoms and poor responsiveness to dopaminergic drugs. He was clinically diagnosed as Parkinson disease(PD). In the post-mortem study, we examined Aß and phospho-tau as pathological biomarker for Alzheimer's disease(AD), α-synucleing in medulla, pons and midbrain for PD and DLB. Hematoxylin and eosin staining in cerebral cortex, cerebellum and brainstem examines vascular pathological changes and microvascular lesion.Neither Lewy bodies in the substantia nigra ,locus ceruleus and cerebrumnor accumulation of Aß, neurofibrillary tangles were noted. Instead, there were many cerebral infarctions and widespread arteriosclerosis in the brain. The final brain autopsy supported a diagnosis of VaP not PD. CONCLUSIONS: This case of pathologically confirmed VaP misdiagnosed as idiopathic PD suggested that we must be vigilant about the possibility of VaP for patients with parkinsonisms, cognitive impairments, early behavioral and psychological symptoms,imaging performances of cerebral small vessel disease and other vascular damages.

Observational Constraints on Warm Cloud Microphysical Processes Using Machine Learning and Optimization Techniques.

We introduce new parameterizations for autoconversion and accretion rates that greatly improve representation of the growth processes of warm rain. The new parameterizations capitalize on machine-learning and optimization techniques and are constrained by in situ cloud probe measurements from the recent Atmospheric Radiation Measurement Program field campaign at Azores. The uncertainty in the new estimates of autoconversion and accretion rates is about 15% and 5%, respectively, outperforming existing parameterizations. Our results confirm that cloud and drizzle water content are the most important factors for determining accretion rates. However, for autoconversion, in addition to cloud water content and droplet number concentration, we discovered a key role of drizzle number concentration that is missing in current parameterizations. The robust relation between autoconversion rate and drizzle number concentration is surprising but real, and furthermore supported by theory. Thus, drizzle number concentration should be considered in parameterizations for improved representation of the autoconversion process.