Tag: pubmed

Lancet Neurol. 2022 Oct 27:S1474-4422(22)00335-0. doi: 10.1016/S1474-4422(22)00335-0. Online ahead of print.

ABSTRACT

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide, and it is associated with a high risk of recurrent stroke with currently recommended treatments. We aimed to evaluate the effect of chronic remote ischaemic conditioning on prevention of ischaemic events in patients with symptomatic ICAS.

METHODS: The RICA trial is a multicentre, randomised, double-blind, sham-controlled trial at 84 stroke centres in China. Patients aged 40-80 years with ischaemic stroke or transient ischaemic attack attributable to angiographically verified 50-99% stenosis of a major intracranial artery were randomly assigned (1:1), via an interactive web-based system by computer-generated randomisation code, to either remote ischaemic conditioning or sham remote ischaemic conditioning once daily for 12 months and voluntarily thereafter. All investigators and patients were masked to treatment allocation. The primary efficacy endpoint was the time to first occurrence of non-fatal or fatal ischaemic stroke, with survival analysed by the Kaplan-Meier method. Primary and safety analyses were done in the intention-to-treat population. The RICA trial is registered with ClinicalTrials.gov, number NCT02534545.

FINDINGS: Between Oct 28, 2015, and Feb 28, 2019, 3033 patients were enrolled and randomly assigned to either remote ischaemic conditioning (n=1517; intervention group) or sham remote ischaemic conditioning (n=1516; sham group). Median follow-up was 3·5 years (IQR 2·7-4·4). A non-fatal or fatal ischaemic stroke occurred in 257 (16·9%) patients in the intervention group compared with 288 (19·0%) patients in sham group. There was no difference in the survival distribution for time to first occurrence of non-fatal or fatal ischaemic stroke (hazard ratio 0·87, 95% CI 0·74-1·03; p=0·12). In the intervention group, 79 (5·2%) patients died from any cause, and in the sham group, 84 (5·5%) patients died from any cause (hazard ratio 0·93, 95% CI 0·68-1·27; p=0·65). No intervention-related serious adverse events were observed.

INTERPRETATION: No evidence was found for a difference between remote ischaemic conditioning and sham remote ischaemic conditioning in lowering the risk of ischaemic stroke in patients with symptomatic ICAS. The benefit of remote ischaemic conditioning might have been diluted by poor compliance. Future studies of remote ischaemic conditioning in this population should address challenges in patients’ compliance and assess longer term treatment.

FUNDING: Ministry of Science and Technology China, Beijing Municipal Education Commission, Beijing Municipal Finance Bureau.

TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

PMID:36354026 | DOI:10.1016/S1474-4422(22)00335-0

Nucleic Acids Res. 2022 Nov 10:gkac994. doi: 10.1093/nar/gkac994. Online ahead of print.

ABSTRACT

Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR is associated with numerous human diseases including several cancers. Despite consistent reports demonstrating that intrinsic sequence features can help introns evade splicing, conflicting findings about cell type- or condition-specific IR regulation by trans-regulatory and epigenetic mechanisms demand an unbiased and systematic analysis of IR in a controlled experimental setting. We integrated matched mRNA sequencing (mRNA-Seq), whole-genome bisulfite sequencing (WGBS), nucleosome occupancy methylome sequencing (NOMe-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) data from primary human myeloid and lymphoid cells. Using these multi-omics data and machine learning, we trained two complementary models to determine the role of epigenetic factors in the regulation of IR in cells of the innate immune system. We show that increased chromatin accessibility, as revealed by nucleosome-free regions, contributes substantially to the retention of introns in a cell-specific manner. We also confirm that intrinsic characteristics of introns are key for them to evade splicing. This study suggests an important role for chromatin architecture in IR regulation. With an increasing appreciation that pathogenic alterations are linked to RNA processing, our findings may provide useful insights for the development of novel therapeutic approaches that target aberrant splicing.

PMID:36354002 | DOI:10.1093/nar/gkac994

Hypertension. 2022 Nov 10. doi: 10.1161/HYPERTENSIONAHA.122.20286. Online ahead of print.

ABSTRACT

BACKGROUND: Education, intelligence, and cognition are associated with hypertension, but which one plays the most prominent role in the pathogenesis of hypertension and which modifiable risk factors mediate the causal effects remains unknown.

METHODS: Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted 2-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, or cognition on hypertension (FinnGen study, 70 651 cases/223 663 controls; UK Biobank, 77 723 cases/330 366 controls) and blood pressure (International Consortium of Blood Pressure, 757 601 participants), and used 2-step Mendelian randomization to evaluate 25 potential mediators of the association and calculate the mediated proportions.

RESULTS: Meta-analysis of inverse variance weighted Mendelian randomization results from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.2 years) higher education was associated with 44% (95% CI: 0.40-0.79) decreased hypertension risk and 1.682 mm Hg lower systolic and 0.898 mm Hg lower diastolic blood pressure, independently of intelligence and cognition. While the causal effects of intelligence and cognition on hypertension were not independent of education, 6 out of 25 cardiometabolic risk factors were identified as mediators of the association between education and hypertension, ranked by mediated proportions, including body mass index (mediated proportion: 30.1%), waist-to-hip ratio (22.8%), body fat percentage (14.1%), major depression (7.0%), high-density lipoprotein cholesterol (4.7%), and triglycerides (3.4%). These results were robust to sensitivity analyses.

CONCLUSIONS: Our findings illustrated the causal, independent impact of education on hypertension and blood pressure and outlined cardiometabolic mediators as priority targets for prevention of hypertension attributable to low education.

PMID:36353998 | DOI:10.1161/HYPERTENSIONAHA.122.20286

Rev Esp Enferm Dig. 2022 Nov 10;114. doi: 10.17235/reed.2022.9289/2022. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic Fibrosis Liver Disease is a poorly understood entity, especially in adults, in terms of its real prevalence, natural history and diagnostic criteria, despite being the most important extrapulmonary cause of mortality. The aim was to evaluate the prevalence, characteristics and potential risk factors of liver disease in adults with cystic fibrosis, according to two diagnostic criteria accepted in the scientific literature.

METHODS: Patients were recruited in a tertiary referral hospital, and laboratory, ultrasound, non-invasive liver fibrosis tests (AST to Platelet Ratio Index; Fibrosis-4 Index) and transient elastography (Fibroscan) were performed. The proportion of patients with liver disease according to the Debray and Koh criteria were evaluated.

RESULTS: 95 patients were included, 48 (50.5%) females, with a mean age of 30.4 (28.6-32.2) years. According to the Debray criteria, 6 (6.3%) patients presented liver disease. According to the Koh criteria, prevalence increased up to 8.4%, being statistically different from the 25% value described in other published series (p = 0.005). Seven (7.5%) presented ultrasonographic chronic liver disease. Eleven (13%) presented liver fibrosis according to the APRI score; 95 (100%) had a normal FIB-4 value. Mean liver stiffness value was 4.4 (4.1-4.7) kPa. FEV1 (OR=0.16, p 0.05), meconium ileus (OR=14.16, p 0.002), platelets (Pearson coefficient -0.25, p 0.05) and younger age (Pearson coefficient -0.19, p 0.05) were risk factors.

CONCLUSIONS: Prevalence and severity of liver disease in adult cystic fibrosis patients were lower than expected. Meconium ileus, platelets, age and respiratory function were confirmed as risk factors associated to cystic fibrosis liver disease.

PMID:36353964 | DOI:10.17235/reed.2022.9289/2022

Rev Esp Enferm Dig. 2022 Nov 10. doi: 10.17235/reed.2022.9228/2022. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Vonoprazan, a novel potassium-competitive acid blocking agent, has better clinical outcomes in the treatment of acid-related diseases. However, some adverse events have been associated with Vonoprazan for the treatment of acid-associated diseases. Therefore, this systematic review and meta-analysis aimed to explore the safety and tolerability of Vonoprazan for acid-associated diseases.

METHODS: Electronic databases were retrieved to determine random control trials (RCTs) of Vonoprazan for acid-associated diseases with any adverse effects and discontinuation.

RESULTS: This systematic review and meta-analysis conforming to the selection criteria included 18 RCTs with a total of 7,932 participants. Compared with proton pump inhibitors, oral Vonoprazan treatment showed no significant increase in the incidence of adverse effects (95% CI = 0.987-1.095, p = 0.141). Diarrhoea or loose stools analysis showed that there was a statistically significant difference between Vonoprazan and PPIs treatment (95% CI = 0.661-0.966, p = 0.021). While there was no significant difference in constipation, rash or eruption, nausea or vomiting, bloating or abdominal pain, dysgeusia, nasopharyngitis, neurological disorders, upper respiratory tract infection and abnormal investigations between Vonoprazan and PPIs treatment.

CONCLUSION: Vonoprazan, which has better tolerability and safety, may significantly decrease diarrhoea and loose stools in acid-related patients compared with PPIs. Our meta-analysis led to safer strategies for treating acid-related diseases. More high-quality studies with larger sample sizes are needed to further identify its efficacy and safety.

PMID:36353962 | DOI:10.17235/reed.2022.9228/2022

Glob Chang Biol. 2022 Nov 10. doi: 10.1111/gcb.16487. Online ahead of print.

ABSTRACT

Long-term atmospheric CO₂ concentration records have suggested a reduction in the positive effect of warming on high-latitude carbon uptake since the 1990s. A variety of mechanisms have been proposed to explain the reduced net carbon sink of northern ecosystems with increased air temperature, including water stress on vegetation and increased respiration over recent decades. However, the lack of consistent long-term carbon flux and in situ soil moisture data has severely limited our ability to identify the mechanisms responsible for the recent reduced carbon sink strength. In this study, we used a record of nearly 100 site-years of eddy covariance data from 11 continuous permafrost tundra sites distributed across the circumpolar Arctic to test the temperature (expressed as growing degree days, GDD) responses of gross primary production (GPP), net ecosystem exchange (NEE), and ecosystem respiration (ER) at different periods of the summer (early, peak, and late summer) including dominant tundra vegetation classes (graminoids and mosses, and shrubs). We further tested GPP, NEE, and ER relationships with soil moisture and vapor pressure deficit to identify potential moisture limitations on plant productivity and net carbon exchange. Our results show a decrease in GPP with rising GDD during the peak summer (July) for both vegetation classes, and a significant relationship between the peak summer GPP and soil moisture after statistically controlling for GDD in a partial correlation analysis. These results suggest that tundra ecosystems might not benefit from increased temperature as much as suggested by several terrestrial biosphere models, if decreased soil moisture limits the peak summer plant productivity, reducing the ability of these ecosystems to sequester carbon during the summer.

PMID:36353841 | DOI:10.1111/gcb.16487

Ann Rehabil Med. 2022 Oct;46(5):256-262. doi: 10.5535/arm.22045. Epub 2022 Oct 31.

ABSTRACT

OBJECTIVE: To analyze the correlation between standardized language assessment batteries of toddlers and developmental language delays.

METHODS: A total of 319 children with suspected language developmental delays were enrolled in this study retrospectively. They underwent the Receptive and Expressive Vocabulary Test (REVT) for vocabulary development assessment and at least one of two language assessment batteries: The Sequenced Language Scale for Infants (SELSI) or the Preschool Receptive-Expressive Language Scale (PRES) for language development assessment. The correlation of the results for receptive and expressive language between the scales were analyzed.

RESULTS: The participants were divided into two groups: SELSI and REVT (n=45) and PRES and REVT (n=273). When the children’s results were classified into groups (average, mild delay, and delay), receptive and expressive scores were significantly correlated with each other in both SELSI-REVT and PRES-REVT groups. In addition, the correlation of mean developmental age between tests are analyzed. In the SELSI-REVT group, there was weak correlation of mean developmental age between tests for receptive and expressive language. In the PRES-REVT group, there was a strong positive correlation of mean developmental age for receptive and expressive language in children aged >36 months. Attention deficits during the test was found to be the statistically significant factor affecting the differences between the tests. The odds ratios for receptive and expressive language were 2.60 (95% confidence interval,1.15-5.84) and 1.94 (95% confidence interval, 1.15-3.27), respectively.

CONCLUSION: This study examined the correlations and influencing factors between language development evaluation tools for toddlers. An integrated interpretation of comprehensive language and vocabulary evaluation tools may be possible in children older than 3 years of language developmental age.

PMID:36353838 | DOI:10.5535/arm.22045

Ann Rehabil Med. 2022 Oct;46(5):248-255. doi: 10.5535/arm.22062. Epub 2022 Oct 31.

ABSTRACT

OBJECTIVE: To determine the characteristics of pediatric spinal cord injury (SCI) in South Korea from 1990 to 2019.

METHODS: This single-centered retrospective study included pediatric SCIs. Individuals were divided into the following five groups according to onset age: ≤5, 6-12, 13-14, 15-17, and 18-19 years. The severity of complete injury was graded according to the American Spinal Injury Association impairment scale A (AIS A). Incomplete injury was graded according to AIS B, C, and D. Pearson chi-square test was used for statistical analysis.

RESULTS: Of the 267 individuals included, 216 (80.9%) had traumatic SCIs (male-to-female ratio of 3.2:1), and 51 (19.1%) had non-traumatic SCIs (male-to-female ratio of 0.7:1). In the traumatic SCI group, 192 (88.9%) individuals were ≥15 years at the time of injury (males, 78.6%). The most common etiologies of traumatic SCIs, ranging from most to least common, were accidents related to motorcycles, falls, cars, and diving. In the non-traumatic SCI group, inflammatory (33.3%) and neoplastic (25.5%) etiologies were found to be the most common ones.

CONCLUSION: We found that traumatic SCIs incidence in the pediatric population was high, particularly in male individuals aged 15-19 years. The non-traumatic SCIs mostly cause paraplegia and incomplete injury. Therefore, it can be used as a basic data for the evaluation, treatment and prevention strategy of pediatric patients with SCI.

PMID:36353837 | DOI:10.5535/arm.22062

Ann Rehabil Med. 2022 Oct;46(5):221-227. doi: 10.5535/arm.22121. Epub 2022 Oct 31.

ABSTRACT

This fact sheet was used to analyze the trends in the number of amputees within the population and changes in their health-related behaviors since 2011. Data from the National Survey of Disabled Persons in Korea from 2011 to 2020 were used in this study. The cases of amputation among people with disabilities have increased. Although there were more upper extremity amputations than lower extremity amputations, as amputations below the wrist account for a greater proportion in South Korea than in other countries, the number of upper extremity amputations decreased and lower extremity amputations increased. The most common cause of amputation is accidents, followed by diseases and congenital anomalies. The majority of the amputees were male; however, the number of females showed a gradual increase, and the average age also increased. The proportion of amputated patients with chronic diseases, such as diabetes and hypertension, is increasing, and medical services are relatively limited. In this review study, through the 10-year trend change in the prevalence of amputee, it was possible to infer the impact of personal, social, and environmental changes. Based on these amputee statistics, it is expected that they can be used to plan health and medical policies for the disabled.

PMID:36353834 | DOI:10.5535/arm.22121

Ann Coloproctol. 2022 Oct;38(5):343-352. doi: 10.3393/ac.2022.00535.0076. Epub 2022 Oct 28.

ABSTRACT

PURPOSE: Korea has implemented an early screening for colorectal cancer since 2004. However, it is not known whether this has translated into improved survival over the years.

METHODS: We acquired colorectal cancer mortality data from the Cause of Death Statistics in Korea from 2000 to 2020. We characterized the data into year of death, cancer-specific loci, and age group. We analyzed age-standardized mortality rates (ASMR) according to year of death, age group, and primary location to find trends in colorectal cancer mortality over a 20-year period.

RESULTS: The crude mortality rate of colorectal cancer increased from 8.78 per 100,000 in 2000 to 17.27 per 100,000 in 2020. The second decade was slower in increments compared to the first decade. ASMR showed a decrease over the second decade after an initial increase in the first decade. The decrease was primarily from the lowering of ASMR for rectosigmoid cancers. Age group analysis showed a lowering of ASMR mainly in the 45-59-year, 60-74-year, and ≥ 75-year age groups; however, 0-29-year and 30-44-year age groups showed generally unchanged ASMR over the total period.

CONCLUSION: After a brief incline of age-specific mortality of colorectal cancers during the early 2000s, colorectal cancer mortality has gradually been decreasing in the past decade. This was mainly due to decreased mortalities in rectosigmoid colon cancers especially in the age groups that were the target of early screening.

PMID:36353833 | DOI:10.3393/ac.2022.00535.0076