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The World Journal of Biological... Dec 2023Anxiety disorders (AD) are common in the general population, leading to high emotional distress and disability. The German National Cohort (NAKO) is a population-based...
OBJECTIVES
Anxiety disorders (AD) are common in the general population, leading to high emotional distress and disability. The German National Cohort (NAKO) is a population-based mega-cohort study, examining participants in 16 German regions. The present study includes data of the first 101,667 participants and investigates the frequency and severity of generalised anxiety symptoms and panic attacks (PA).
METHODS
The Generalised Anxiety Disorder Symptoms Scale (GAD-7) and the first part of the Patient Health Questionnaire Panic Disorder (PHQ-PD) were filled out by NAKO participants (93,002). We examined the correlation of GAD-7 and PHQ-PD with demographic variables, stress (PHQ-Stress), depression (PHQ-9) and childhood trauma (CTS).
RESULTS
The total proportion of prior lifetime diagnoses of AD in the NAKO cohort reached 7.8%. Panic attacks were reported by 6.0% and possible/probable current GAD symptoms in 5.2% of the examined participants. Higher anxiety severity was associated with female sex, lower education level, German as a foreign language and younger age as well as high perceived stress and depression.
CONCLUSIONS
Clinically relevant GAD symptoms as well as panic attacks are frequent in the NAKO and are associated with sociodemographic factors, and high anxiety symptoms are accompanied by pronounced stress and depression levels.
Topics: Humans; Female; Cohort Studies; Anxiety Disorders; Panic Disorder; Anxiety
PubMed: 34842503
DOI: 10.1080/15622975.2021.2011409 -
Environment International Oct 2023Exclusive clean fuel use is essential for realizing health and other benefits but is often unaffordable. Decreasing household-level fuel needs could make exclusive clean...
BACKGROUND
Exclusive clean fuel use is essential for realizing health and other benefits but is often unaffordable. Decreasing household-level fuel needs could make exclusive clean fuel use more affordable, but there is a lack of knowledge on the amount of fuel savings that could be achieved through fuel conservation behaviors relevant to rural settings in low- and middle-income countries.
METHODS
Within a trial in Peru, we trained a random half of intervention participants, who had previously received a liquefied petroleum gas (LPG) stove and were purchasing their own fuel, on fuel conservation strategies. We measured the amount of fuel and mega joules (MJ) of energy consumed by all participants, including control participants who were receiving free fuel from the trial. We administered surveys on fuel conservation behaviors and assigned a score based on the number of behaviors performed.
RESULTS
Intervention participants with the training had a slightly higher conservation score than those without (7.2 vs. 6.6 points; p = 0.07). Across all participants, average daily energy consumption decreased by 9.5 MJ for each 1-point increase in conservation score (p < 0.001). Among households who used exclusively LPG (n = 99), each 1-point increase in conservation score was associated with a 0.04 kg decrease in LPG consumption per household per day (p = 0.03). Using pressure cookers and heating water in the sun decreased energy use, while using clay pots and forgetting to close stove knobs increased energy use.
CONCLUSION
Our findings suggest that a household could save 1.16 kg of LPG per month for each additional fuel conservation behavior, for a maximum potential savings of 8.1 kg per month. Fuel conservation messaging could be integrated into national household energy policies to increase the affordability of exclusive clean fuel use, and subsequently achieve the environmental and health benefits that could accompany such a transition.
Topics: Humans; Air Pollution, Indoor; Household Articles; Cooking; Petroleum; Public Policy; Costs and Cost Analysis
PubMed: 37748372
DOI: 10.1016/j.envint.2023.108223 -
Therapeutic Advances in... 2024Bipolar disorder (BD) is a severe mental disorder with various hypotheses regarding its pathogenesis. This article provides a summary of numerous studies on the... (Review)
Review
Bipolar disorder (BD) is a severe mental disorder with various hypotheses regarding its pathogenesis. This article provides a summary of numerous studies on the variations in inflammatory cytokine levels in patients with BD and the effects of treatment with antipsychotics, mood stabilizers, and antidepressants on these levels. In addition, patients with autoimmune diseases who use anti-inflammatory monoclonal antibodies experience symptoms, such as depression, anxiety, and insomnia. These pieces of evidence suggest a potential association between immune inflammation and BD and offer new possibilities for therapy. Building upon this relationship, the authors propose an innovative approach for treating BD through individualized and precise therapy using anti-inflammatory monoclonal antibody drugs. To support this proposal, the authors compile information on pharmacological effects and relevant studies, including trials of various anti-inflammatory therapeutic monoclonal antibody drugs (e.g. infliximab, tocilizumab, and canakinumab) for the potential treatment of BD and its associated side effects in psychiatry. The authors categorize these anti-inflammatory monoclonal antibody drugs into levels I-IV through a comprehensive analysis of their advantages and disadvantages. Their potential is examined, and the need for further exploration of their pharmaceutical effects is established.
PubMed: 38322010
DOI: 10.1177/20451253241227772 -
European Journal of Pharmaceutical... Dec 2023Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that...
Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.
Topics: Adult; Humans; Antiviral Agents; COVID-19; Enzyme Inhibitors; Healthy Volunteers; Protease Inhibitors; Ritonavir; SARS-CoV-2
PubMed: 37783378
DOI: 10.1016/j.ejps.2023.106598 -
Critical Care and Resuscitation :... Sep 2023The effect of conservative vs. liberal oxygen therapy on outcomes of intensive care unit (ICU) patients with hypoxic ischaemic encephalopathy (HIE) is uncertain and will...
BACKGROUND
The effect of conservative vs. liberal oxygen therapy on outcomes of intensive care unit (ICU) patients with hypoxic ischaemic encephalopathy (HIE) is uncertain and will be evaluated in the Low Oxygen Intervention for Cardiac Arrest injury Limitation (LOGICAL) trial.
OBJECTIVE
The objective of this study was to summarise the protocol and statistical analysis plans for the LOGICAL trial.
DESIGN SETTING AND PARTICIPANTS
LOGICAL is a randomised clinical trial in adults in the ICU who are comatose with suspected HIE (i.e., those who have not obeyed commands following return of spontaneous circulation after a cardiac arrest where there is clinical concern about possible brain damage). The LOGICAL trial will include 1400 participants and is being conducted as a substudy of the Mega Randomised registry trial comparing conservative vs. liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX).
MAIN OUTCOME MEASURES
The primary outcome is survival with favourable neurological function at 180 days after randomisation as measured with the Extended Glasgow Outcome Scale (GOS-E). A favourable neurological outcome will be defined as a GOS-E score of lower moderate disability or better (i.e. a GOS-E score of 5-8). Secondary outcomes include survival time, day 180 mortality, duration of invasive mechanical ventilation, ICU length of stay, hospital length of stay, the proportion of patients discharged home, quality of life assessed at day 180 using the EQ-5D-5L, and cognitive function assessed at day 180 using the Montreal Cognitive Assessment (MoCA-blind).
CONCLUSIONS
The LOGICAL trial will provide reliable data on the impact of conservative vs. liberal oxygen therapy in ICU patients with suspected HIE following resuscitation from a cardiac arrest. Prepublication of the LOGICAL protocol and statistical analysis plan prior to trial conclusion will reduce the potential for outcome-reporting or analysis bias.
TRIAL REGISTRATION
Australian and New Zealand Clinical Trials Registry (ACTRN12621000518864).
PubMed: 37876368
DOI: 10.1016/j.ccrj.2023.06.007 -
Molecular Therapy : the Journal of the... Mar 2024Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission....
Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.
Topics: Animals; Mice; Humans; Antibodies, Neutralizing; Immunoglobulin A, Secretory; SARS-CoV-2; COVID-19 Vaccines; COVID-19; Antibodies, Monoclonal; Immunoglobulin G; Antibodies, Viral
PubMed: 38268188
DOI: 10.1016/j.ymthe.2024.01.025 -
International Journal of Molecular... Jan 2024Hepatocellular carcinoma (HCC) is a highly detrimental cancer type and has limited therapeutic options, posing significant threats to human health. The development of...
Establishment and Validation of Novel Prognostic Subtypes in Hepatocellular Carcinoma Based on Bile Acid Metabolism Gene Signatures Using Bulk and Single-Cell RNA-Seq Data.
Hepatocellular carcinoma (HCC) is a highly detrimental cancer type and has limited therapeutic options, posing significant threats to human health. The development of HCC has been associated with a disorder in bile acid (BA) metabolism. In this study, we employed an integrative approach, combining various datasets and omics analyses, to comprehensively characterize the tumor microenvironment in HCC based on genes related to BA metabolism. Our analysis resulted in the classification of HCC samples into four subtypes (C1, C2a, C2b, and C3). Notably, subtype C2a, characterized by the highest bile acid metabolism score (BAMS), exhibited the highest survival probability. This subtype also demonstrated increased immune cell infiltration, lower cell cycle scores, reduced AFP levels, and a lower risk of metastasis compared to subtypes C1 and C3. Subtype C1 displayed poorer survival probability and elevated cell cycle scores. Importantly, the identified subtypes based on BAMS showed potential relevance to the gene expression of drug targets in currently approved drugs and those under clinical research. Genes encoding (FLT4 and KDR) and were elevated in C2, while genes such as , , , , , , , , , and were elevated in C1. Additionally, and , along with immune target genes including and , were higher in C3. This suggests that subtypes C1, C2, and C3 might represent distinct potential candidates for inhibitors, inhibitors, and immune checkpoint blockade treatments, respectively. Significantly, both bulk and single-cell transcriptome analyses unveiled a negative correlation between BA metabolism and cell cycle-related pathways. In vitro experiments further confirmed that the treatment of HCC cell lines with BA receptor agonist ursodeoxycholic acid led to the downregulation of the expression of cell cycle-related genes. Our findings suggest a plausible involvement of BA metabolism in liver carcinogenesis, potentially mediated through the regulation of tumor cell cycles and the immune microenvironment. This preliminary understanding lays the groundwork for future investigations to validate and elucidate the specific mechanisms underlying this potential association. Furthermore, this study provides a novel foundation for future precise molecular typing and the design of systemic clinical trials for HCC therapy.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Single-Cell Gene Expression Analysis; Liver Neoplasms; Bile Acids and Salts; Tumor Microenvironment
PubMed: 38255993
DOI: 10.3390/ijms25020919 -
Clinical Nutrition (Edinburgh, Scotland) May 2024Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIM
Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants.
METHODS
A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center.
RESULTS
On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period.
CONCLUSIONS
This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population.
CLINICAL REGISTRATION NUMBER
ClinicalTrials.gov (NCT03201588).
Topics: Humans; Docosahexaenoic Acids; Arachidonic Acid; Infant, Extremely Premature; Infant, Newborn; Female; Retrospective Studies; Male; Inflammation; Proteome
PubMed: 38603973
DOI: 10.1016/j.clnu.2024.03.031 -
Blood Advances Aug 2023Most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and... (Clinical Trial)
Clinical Trial
Most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Patients with progression or relapse in the central nervous system (CNS) face dismal outcomes. The impact of more aggressive regimens used in frontline therapy has not been systematically investigated in this context. To this end, we analyzed a large cohort of 2203 younger patients with DLBCL treated on 10 German (German Lymphoma Alliance [GLA]/The German High Grade Non-Hodgkin's Lymphoma Study Group [DSHNHL]) and French (The Lymphoma Study Association [LYSA]) prospective phase 2 and 3 trials after first-line therapy with R-CHOP, R-CHOEP (R-CHOP + etoposide), dose-escalated R-CHOEP followed by repetitive stem cell transplantation (R-MegaCHOEP), or R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, and prednisone) followed by consolidation including multiple drugs crossing the blood-brain barrier (BBB). Patients with DLBCL with an age-adjusted International Prognostic Index (aaIPI) of 0 to 1 showed very low cumulative incidence rates of CNS relapse regardless of first-line therapy and CNS prophylaxis (3-year cumulative incidences 0%-1%). Younger high-risk patients with aaIPI of 2 to 3 had 3-year cumulative incidence rates of 1.6% and 4% after R-ACVBP plus consolidation or R-(Mega)CHO(E)P, respectively (hazard ratio 2.4; 95% confidence interval: 0.8-7.4; P = .118). Thus, for younger high-risk patients, frontline regimens incorporating agents crossing the BBB may reduce often fatal CNS relapse.
Topics: Humans; Rituximab; Prednisone; Prospective Studies; Antibodies, Monoclonal, Murine-Derived; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Vincristine; Chronic Disease; Central Nervous System; Cyclophosphamide; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36716220
DOI: 10.1182/bloodadvances.2022008888 -
Heliyon Feb 2024Sorghum grain is a vital staple cereal crop for food and nutritional security for rural households in Burkina Faso. However, its yields are regularly affected by... (Review)
Review
Assessing yield performance and stability of local sorghum genotypes: A methodological framework combining multi-environment trials and participatory multi-trait evaluation.
Sorghum grain is a vital staple cereal crop for food and nutritional security for rural households in Burkina Faso. However, its yields are regularly affected by environmental and socio-economic constraints. Here, we aim to assess the performance and grain yield stability of local sorghum genotypes, as well as their acceptability by smallholder farmers. Nine genotypes were assessed across five environments in the North-Sudanian zone (700-900 mm) in Burkina Faso during the 2019, 2020, and 2021 rainy seasons. A randomized complete block with three replications was used to establish the experiments, from which data were collected on five quantitative traits as well as five participatory assessment criteria chosen by sorghum farmers and users. Grain yield analysis for each environment revealed significant differences between genotypes. The combined analysis showed highly significant differences between genotypes, environments and years, as well as their interactions. Most of the variation in grain yield was hexplained by the environment effect (29.0%), followed by the environment-by-year interaction (20.3%). The GGE biplot analysis identified two mega-environments (ME) with ME1 consisting of one environment (E1) and ME2, represented by four environments (E2, E3, E4, and E5). The E1 is a non-discriminating and poor environment with the lowest grain yield (1506 kg ha). The E5 and E2 were respectively, the most discriminating and representative environments, with also the highest grain yields (2406 and 2102 kg ha). In terms of stability, genotypes G6, G3, G5, and G9 exhibited the highest stability but lower performance, while G4 was the most unstable. G2 and G8, which produced respectively 2240 and 2072 kg ha, were better adapted to ME2. G2 was identified as the closest to the "ideal genotype". The principal component analysis showed that genotypes G2, G8, G7, G4, and G9 were the most selected in both individual and group assessments, owing to the panicle productivity, the good grain quality for storability, the grain attractiveness, and grain heaviness. This study highlighted the potential of genotypes G2 and G8 as promising varieties that could broaden the range of improved varieties and offer income opportunities for sorghum smallholder farmers in Burkina Faso.
PubMed: 38370242
DOI: 10.1016/j.heliyon.2024.e25114