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Nucleic Acids Research Jul 2024Fluorogenic RNA aptamer tags with high affinity enable RNA purification and imaging. The G-quadruplex (G4) based Mango (M) series of aptamers were selected to bind a...
Fluorogenic RNA aptamer tags with high affinity enable RNA purification and imaging. The G-quadruplex (G4) based Mango (M) series of aptamers were selected to bind a thiazole orange based (TO1-Biotin) ligand. Using a chemical biology and reselection approach, we have produced a MII.2 aptamer-ligand complex with a remarkable set of properties: Its unprecedented KD of 45 pM, formaldehyde resistance (8% v/v), temperature stability and ligand photo-recycling properties are all unusual to find simultaneously within a small RNA tag. Crystal structures demonstrate how MII.2, which differs from MII by a single A23U mutation, and modification of the TO1-Biotin ligand to TO1-6A-Biotin achieves these results. MII binds TO1-Biotin heterogeneously via a G4 surface that is surrounded by a stadium of five adenosines. Breaking this pseudo-rotational symmetry results in a highly cooperative and homogeneous ligand binding pocket: A22 of the G4 stadium stacks on the G4 binding surface while the TO1-6A-Biotin ligand completely fills the remaining three quadrants of the G4 ligand binding face. Similar optimization attempts with MIII.1, which already binds TO1-Biotin in a homogeneous manner, did not produce such marked improvements. We use the novel features of the MII.2 complex to demonstrate a powerful optically-based RNA purification system.
PubMed: 38945550
DOI: 10.1093/nar/gkae493 -
Chest Jun 2024Childhood asthma is a prevalent condition with potential impact on adult life.
BACKGROUND
Childhood asthma is a prevalent condition with potential impact on adult life.
RESEARCH QUESTION
In a 60-year follow-up study of adults with a history of severe childhood asthma, what are the potential differences in characteristics between individuals with persistent asthma and asthma remission in adulthood?
STUDY DESIGN AND METHODS
Danish adults with a history of childhood asthma and a 4-month stay in at an asthma care facility in Kongsberg, Norway (1950-1979) in childhood were included. Recruitment was done through social media and personal invitation letters. Participants completed questionnaires and underwent spirometry, bronchial provocation, and bronchodilator reversibility and blood tests. Asthma remission was defined as no use of asthma medication and no asthma symptoms within the past 12 months with the remaining participants being classified as having current asthma.
RESULTS
Among 1394 eligible participants, 232 completed the follow-up. Ninety percent had current asthma, of whom 26% reported exacerbations in the past year. Only 16% of all the participants were managed in secondary care. Common comorbidities were allergic rhinitis (60%), hypertension (21%), eczema (16%), and cataract (8%). Compared to participants in remission, participants with persistent asthma had higher total immunoglobulin E (p=0.03), and both lower FEV%pred (p=0.03), and FEV/FVC ratio (p<0.001), as well as numerically higher fractional exhaled nitric oxide and blood eosinophil count.
INTERPRETATION
Our 60-year follow-up study of adults with a history of severe childhood asthma revealed that nine out of ten still had current asthma. Persistent asthma was associated with lower lung function and higher levels of type 2 inflammatory biomarkers compared to those with asthma remission.
PubMed: 38945358
DOI: 10.1016/j.chest.2024.06.005 -
Toxicon : Official Journal of the... Jun 2024Morocco is one of the main countries affected in North African with the scorpion envenomations. Faced with the threat, significant morbidity and a major risk of death...
Morocco is one of the main countries affected in North African with the scorpion envenomations. Faced with the threat, significant morbidity and a major risk of death especially in children, a detailed identification of scorpionic profile of stings remains important for health authorities at national or even regional level. The current study aims to establish the epidemiological, clinical, biological and evolutionary data of the scorpionism by analyzing 383 cases of scorpion stings in children from three age groups (< 1 year, 1-5 years and > 5 years), admitted at the Regional Hospital Hassan II-Agadir in the Souss Massa region during the period of 9 years and 10 months from January 2013 to October 2022. Our results showed that patients under 1 year of age presented the most severe cases and had the highest mortality rate. However, the clinical signs and symptoms observed illustrated severe damages to vital systems, particularly the cardiovascular, neurological and pulmonary systems, although the signs associated with the latter were present only in cases admitted in grades 2 and 3 for the three age categories studied. Fluctuations in vital constants (temperature and peripheral oxygen saturation, blood pressure, heart rate and respiratory rate), biochemical parameters (ASAT, ALAT, urea and blood creatine, as well as blood sugar) and CBC results revealed major functional disturbances in vital organs, especially in envenomated cases admitted in grade 3. A positive correlation was mentioned between the state of evolution and the various epidemiological parameters, digestive symptoms, as well as signs and symptoms linked to hemodynamic state, general and neurological state. The main interest is to illustrate the seriousness of scorpion envenomations, especially in the high-risk population, for whom an improved therapeutic approach in health centers will undoubtedly be reinforced, and the admission of immunotherapy, as a fundamental part of the treatment, remains important.
PubMed: 38945218
DOI: 10.1016/j.toxicon.2024.107832 -
World Neurosurgery Jun 2024This study aimed to pinpoint independent predictors influencing overall survival (OS) and cancer-specific survival (CSS) in elderly patients with small cell lung cancer...
OBJECTIVE
This study aimed to pinpoint independent predictors influencing overall survival (OS) and cancer-specific survival (CSS) in elderly patients with small cell lung cancer (SCLC) brain metastasis (BM), and to create and validate nomograms for OS and CSS prediction.
METHODS
Data from elderly SCLC BM patients were extracted out of the SEER database, including 1200 patients identified from 2010 and 2015 who were randomly allocated into a training set and an internal validation set at a proportion of 7:3, and 666 patients diagnosed between 2018 and 2020 as a temporal external validation set. Independent predictors for OS and CSS were determined through univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis sequentially. Nomograms for OS and CSS were constructed, and validated by the internal and temporal external validation sets.
RESULTS
Age, N stage, chemotherapy, and liver metastasis were determined as independent predictors of OS and CSS, while radiotherapy and surgery were not. Nomograms were constructed based on these independent predictors. The results of the receiver operator characteristic (ROC) curves, the areas under the curve (AUC) and calibration curve demonstrated that the nomograms exhibited commendable discriminative ability and calibration. Moreover, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) also suggested that the nomograms possessed superior clinical usefulness and predictive capability relative to the TNM system.
CONCLUSIONS
Prognostic nomograms for elderly patients with SCLC BM have been developed, demonstrating good performance in terms of accuracy, reliability, and practicality.
PubMed: 38945206
DOI: 10.1016/j.wneu.2024.06.137 -
American Journal of Preventive Medicine Jun 2024
PubMed: 38945180
DOI: 10.1016/j.amepre.2024.06.021 -
The Lancet. Healthy Longevity Jul 2024Parkinson's disease is the second most common neurodegenerative disorder, exhibiting an upward trend in prevalence. We aimed to investigate the prevalence of Parkinson's... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease is the second most common neurodegenerative disorder, exhibiting an upward trend in prevalence. We aimed to investigate the prevalence of Parkinson's disease, temporal trends between 1980 and 2023, and variations in prevalence by location, age, sex, survey period, sociodemographic index (SDI), human development index (HDI), and study characteristics (sample size, diagnostic criteria, and data source).
METHODS
In this systematic review and meta-analysis we searched PubMed, Cochrane, Web of Science, Embase, Scopus, and Global Health for observational studies that reported Parkinson's disease prevalence in the general population from database inception to Nov 1, 2023. We included studies if they were original observational investigations, had participants from the general population or community-based datasets, and provided numerical data on the prevalence of Parkinson's disease either with 95% CIs or with sufficient information to calculate 95% CIs. Studies were excluded if they were conducted in a specific population, had a sample size smaller than 1000, or were review articles, case reports, protocols, meeting abstracts, letters, comments, short communications, posters, and reports. The publication characteristics (first author and publication year), study location (countries, WHO regions, SDI, and HDI), survey period, study design, diagnostic criteria, data source, participant information, and prevalence data were extracted from articles using a standard form. Two authors independently evaluated eligibility, and discrepancies were resolved through discussion with the third author. We used random effect models to pool estimates with 95% CIs. Estimated annual percentage change (EAPC) was calculated to assess the temporal trend in prevalence of Parkinson's disease. The study was registered with PROSPERO, CRD42022364417.
FINDINGS
83 studies from 37 countries were eligible for analysis, with 56 studies providing all-age prevalence, 53 studies reporting age-specific prevalence, and 26 studies providing both all-age and age-specific prevalence. Global pooled prevalence of Parkinson's disease was 1·51 cases per 1000 (95% CI 1·19-1·88), which was higher in males (1·54 cases per 1000 [1·17-1·96]) than in females (1·49 cases per 1000 [1·12-1·92], p=0·030). During different survey periods, the prevalence of Parkinson's disease was 0·90 cases per 1000 (0·48-1·44; 1980-89), 1·38 cases per 1000 (1·17-1·61; 1990-99), 1·18 cases per 1000 (0·77-1·67; 2000-09), and 3·81 cases per 1000 (2·67-5·14; 2010-23). The EAPC of Parkinson's disease prevalence was significantly higher in the period of 2004-23 (EAPC 16·32% [95% CI 6·07-26·58], p=0·0040) than in the period of 1980-2003 (5·30% [0·82-9·79], p=0·022). Statistically significant disparities in prevalence were observed across six WHO regions. Prevalence increased with HDI or SDI. Considerable variations were observed in the pooled prevalence of Parkinson's disease based on different sample sizes or diagnostic criteria. Prevalence also increased with age, reaching 9·34 cases per 1000 (7·26-11·67) among individuals older than 60 years.
INTERPRETATION
The global prevalence of Parkinson's disease has been increasing since the 1980s, with a more pronounced rise in the past two decades. The prevalence of Parkinson's disease is higher in countries with higher HDI or SDI. It is necessary to conduct more high-quality epidemiological studies on Parkinson's disease, especially in low SDI countries.
FUNDING
National Nature Science Foundation of China.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Parkinson Disease; Humans; Prevalence; Female; Male; Global Health
PubMed: 38945129
DOI: 10.1016/S2666-7568(24)00094-1 -
International Immunopharmacology Jun 2024Acute lung injury (ALI) is manifested by increased blood vessel permeability within the lungs and subsequent impairment of alveolar gas exchange. Methylprednisolone (MP)...
BACKGROUND
Acute lung injury (ALI) is manifested by increased blood vessel permeability within the lungs and subsequent impairment of alveolar gas exchange. Methylprednisolone (MP) is commonly used as a treatment for ALI to reduce inflammation, yet its molecular mechanism remains unclear. This study aims to explore the underlying mechanisms of MP on ALI in a model induced by lipopolysaccharide (LPS).
MATERIAL AND METHODS
The proliferation, viability, apoptosis, and miR-151-5p expression of alveolar type II epithelial cells (AECII) were detected using the cell EdU assay, Annexin V/PI Apoptosis Kit, counting kit-8 (CCK-8) assay, and RT-qPCR. Western blot analysis was used to detect the Usp38 protein level. IL-6 and TNF-α were measured by ELISA. The combination of miR-151-5p and USP38 was determined by chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay.
RESULTS
MP greatly improved pulmonary function in vivo, reduced inflammation, and promoted the proliferation of the alveolar type II epithelial cells (AECII) in vitro. By comparing the alterations of microRNAs in lung tissues between MP treatment and control groups, we found that miR-151-5p exhibited a significant increase after LPS-treated AECII, but decreased after MP treatment. Confirmed by a luciferase reporter assay, USP38, identified as a downstream target of miR-151-5p, was found to increase after MP administration. Inhibition of miR-151-5p or overexpression of USP38 in AECII significantly improved the anti-inflammatory, anti-apoptotic, and proliferation-promotive effects of MP.
CONCLUSION
In summary, our data demonstrated that MP alleviates the inflammation and apoptosis of AECII induced by LPS, and promotes the proliferation of AECII partially via miR-151-5p suppression and subsequent USP38 activation.
PubMed: 38944949
DOI: 10.1016/j.intimp.2024.112548 -
JAMA Health Forum Jun 2024In the US, the COVID-19 pandemic led to a significant rise in unemployment and economic loss that disproportionately impacted low-income individuals. It is unknown how...
IMPORTANCE
In the US, the COVID-19 pandemic led to a significant rise in unemployment and economic loss that disproportionately impacted low-income individuals. It is unknown how health care and prescription medication affordability changed among low-income adults during the COVID-19 pandemic overall and compared with their higher-income counterparts.
OBJECTIVE
To evaluate changes in health care affordability and prescription medication affordability during the COVID-19 pandemic (2021 and 2022) compared with pre-COVID-19 pandemic levels (2019) and whether income-based inequities changed.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cross-sectional study included adults 18 years and older participating in the National Health Interview Survey (NHIS) in 2019, 2021, and 2022. Low-income adults were defined as having a household income of 200% or less of the federal poverty level (FPL); middle-income adults, 201% to 400% of the FPL; and high-income adults, more than 400% of the FPL. Data were analyzed from June to November 2023.
MAIN OUTCOMES AND MEASURES
Measures of health care affordability and prescription medication affordability.
RESULTS
The study population included 89 130 US adults. Among the weighted population, 51.6% (95% CI, 51.2-52.0) were female, and the mean (SD) age was 48.0 (0.12) years. Compared with prepandemic levels, during the COVID-19 pandemic, low-income adults were less likely to delay medical care (2022: 11.2%; 95% CI, 10.3-12.1; 2019: 15.4%; 95% CI, 14.3-16.4; adjusted relative risk [aRR], 0.73; 95% CI, 0.66-0.81) or avoid care (2022: 10.7%; 95% CI, 9.7-11.6; 2019: 14.9%; 95% CI, 13.8-15.9; aRR, 0.72; 95% CI, 0.64-0.80) due to cost, while high-income adults experienced no change, resulting in a significant improvement in income-based disparities. Low-income and high-income adults were less likely to experience problems paying medical bills but experienced no change in worrying about medical bills during the COVID-19 pandemic compared with prepandemic levels. Across measures of prescription medication affordability, low-income adults were less likely to delay medications (2022: 9.4%; 95% CI, 8.4-10.4; 2019: 12.7%; 95% CI, 11.6-13.9; aRR, 0.74; 95% CI, 0.65-0.84), not fill medications (2022: 8.9%; 95% CI, 8.1-9.8; 2019: 12.0%; 95% CI, 11.1-12.9; aRR, 0.75; 95% CI, 0.66-0.83), skip medications (2022: 6.7%; 95% CI, 5.9-7.6; 2019: 10.1%; 95% CI, 9.1-11.1; aRR, 0.67; 95% CI, 0.57-0.77), or take less medications (2022: 7.3%; 95% CI, 6.4-8.1; 2019: 11.2%; 95% CI, 10.%-12.2; aRR, 0.65; 95% CI, 0.56-0.74) due to costs, and these patterns were largely similar among high-income adults. Improvements in measures of health care and prescription medication affordability persisted even after accounting for changes in health insurance coverage and health care use. These patterns were similar when comparing measures of affordability in 2021 with 2019.
CONCLUSIONS AND RELEVANCE
Health care affordability improved for low-income adults during the COVID-19 pandemic, resulting in a narrowing of income-based disparities, while prescription medication affordability improved for all income groups. These findings suggest that the recent unwinding of COVID-19 pandemic-related safety-net policies may worsen health care affordability and widen existing income-based inequities.
Topics: Humans; COVID-19; Cross-Sectional Studies; United States; Male; Female; Middle Aged; Retrospective Studies; Adult; Prescription Drugs; Poverty; Income; Aged; Health Services Accessibility; Young Adult; Adolescent; Pandemics
PubMed: 38944763
DOI: 10.1001/jamahealthforum.2024.1939 -
Mymensingh Medical Journal : MMJ Jul 2024Physical activity and mindfulness techniques, such as exercise and Kapalbhati Pranayama, are known to have positive effects on health and well-being. However, limited... (Comparative Study)
Comparative Study
Comparative Analysis of the Effects of Exercise and Kapalbhati Pranayama on Heart Rate Variability and Electroencephalogram Activity: Unveiling Physiological and Cognitive Insights.
Physical activity and mindfulness techniques, such as exercise and Kapalbhati Pranayama, are known to have positive effects on health and well-being. However, limited research has directly compared their impact on physiological and psychological parameters. This study aimed to investigate and compare the effects of exercise and Kapalbhati Pranayama on Heart Rate Variability (HRV) and Electroencephalogram (EEG) activity, shedding light on their contributions to overall health and mental well-being. The study was conducted at All India Institute of Medical Sciences (AIIMS) in Bhopal, India, from 2018 to 2022. A prospective interventional design was employed over two months, involving 20 participants with normal BMI and no respiratory or cardiac conditions. Exclusion criteria included lung or cardiac diseases, smoking history, dyspnoea during physical activity, pedal edema, and high blood pressure. The Kapalbhati Pranayama intervention was supervised and limited to 5 minutes. HRV was assessed using the HRV Brain Tap Neuralchek Machine before, during, and after Kapalbhati. For exercise, a mild-intensity cycling protocol was performed on healthy volunteers aged 20 to 50. HRV was recorded before, during, and after exercise. The EEG analysis revealed notable changes in brain wave patterns. At baseline, participants exhibited higher levels of delta, theta, and alpha waves, indicating a state of relaxation and calmness. During exercise, there was a significant increase in beta waves and a decrease in delta, theta, and alpha waves, reflecting heightened brain activity and alertness. After Kapalbhati, beta wave levels remained elevated, while delta and theta wave suppression was more pronounced, suggesting a stimulating effect on the brain similar to exercise. The changes in beta and gamma EEG waves could be attributed to factors such as exercise intensity, duration, frequency, and the release of endorphins during both exercise and Kapalbhati. The HRV analysis demonstrated distinct responses to exercise and Kapalbhati. Exercise led to a significant reduction in HRV parameters, characterized by increased heart rate and decreased time-domain HRV measures, aligning with the typical sympathetic nervous system dominance during physical activity. In contrast, Kapalbhati's impact on HRV parameters was milder, with minor changes in heart rate and subtle alterations in time-domain HRV measures. The high LF/HF ratio during Kapalbhati suggested a potential stimulation of the sympathetic nervous system. More comprehensive research is required to confirm these findings and understand the long-term effects of Kapalbhati on HRV and cardiovascular health. This study contributes to the understanding of how exercise and Kapalbhati Pranayama affect both cognitive and cardiovascular aspects of health. It highlights that both interventions increase brain activity and alertness, but Kapalbhati may have a more potent effect. Exercise significantly reduces HRV parameters, indicating sympathetic nervous system dominance, while Kapalbhati has milder HRV effects. Further research with larger and more diverse populations is essential to confirm and expand on these findings, providing insights into optimizing cognitive function and cardiovascular health through tailored approaches of exercise and Kapalbhati Pranayama.
Topics: Humans; Heart Rate; Electroencephalography; Adult; Male; Exercise; Female; Prospective Studies; Middle Aged; India; Young Adult; Mindfulness; Yoga; Cognition
PubMed: 38944738
DOI: No ID Found -
Mymensingh Medical Journal : MMJ Jul 2024Now a days, chronic obstructive pulmonary disease (COPD) is a global health problem. This study was done to evaluate the changes of body mass index (BMI) and blood...
Now a days, chronic obstructive pulmonary disease (COPD) is a global health problem. This study was done to evaluate the changes of body mass index (BMI) and blood pressure (BP) in COPD patients in comparison to healthy person. This analytical type of cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh between the periods from July 2018 to June 2019. Total 160 male subjects, age ranged from 30-70 years was included in this study. Among them, in study group (Group II) eighty (80) male COPD subjects and eighty (80) age matched male healthy subjects were taken as control group (Group I). BMI was calculated as weight in kilogram divided by the height in meter square. Blood pressure was measured with an aneroid sphygmomanometer. Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test. The mean±SD of BMI of Group I and Group II were 24.52±1.35kg/m² and 21.22±1.30kg/m² respectively. The mean±SD of systolic blood pressure of Group I and Group II were 118.75±7.73 mm of Hg and 134.56±15.24 mm of Hg respectively. The mean±SD diastolic blood pressure of Group I and Group II were 77.63±6.70 mm of Hg and 84.69±8.05 mm of Hg respectively. The mean±SD of BMI was significantly lower in study group and the mean±SD of systolic and diastolic blood pressure was significantly higher in study group than control group. Low BMI and hypertension in subjects with COPD are associated with a high risk of exacerbations and mortality. So assessment of this parameter is important for prevention of complication related to COPD for leading a healthy life.
Topics: Humans; Male; Middle Aged; Body Mass Index; Pulmonary Disease, Chronic Obstructive; Cross-Sectional Studies; Blood Pressure; Adult; Aged; Case-Control Studies; Hypertension
PubMed: 38944707
DOI: No ID Found