Sleep, Stress, and Symptoms Among People With Heart Failure During the COVID-19 Pandemic.
The Journal of cardiovascular nursing. 202301;38(2):E55-E60
Plain language summary
COVID-19 pandemic raised concerns about the effects of stress on mental health and sleep deficiency. Cognitive behavioural therapy for insomnia (CBT-I) has been shown to improve sleep quality and insomnia severity, as well as anxiety and depression, and may be protective during times of stress, including the COVID-19 pandemic. The aim of this study was to examine changes in sleep, sleep-related cognitions, stress, anxiety, and depression among people with heart failure (HF). This study was a randomised controlled trial of the effects of CBT-I compared with HF self-management education (attention-control condition), the “HeartSleep Study.” Results showed that improvements in insomnia severity, sleep quality, latency, and efficiency, sleep-related cognitions and stress, anxiety, and depression after participation in CBT-I or an HF self-management class were sustained during the pandemic. Authors conclude that their findings confirm the clinical benefits of CBT-I for people with HF and comorbidities and also suggest the potential benefits of HF self-management education.
BACKGROUND The COVID-19 pandemic raised concerns about the effects of stress on sleep and mental health, particularly among people with chronic conditions, including people with heart failure (HF). OBJECTIVE The aim of this study was to examine changes in sleep, sleep-related cognitions, stress, anxiety, and depression among people with HF who participated in a randomized controlled trial of cognitive behavioral therapy for insomnia before the COVID-19 pandemic. METHODS Participants self-reported sleep characteristics, symptoms, mood, and stress at baseline, 6 months after cognitive behavioral therapy for insomnia or HF self-management education (attention control), and during the pandemic. RESULTS The sample included 112 participants (mean age, 63 ± 12.9 years; 47% women; 13% Black; 68% New York Heart Association class II or III). Statistically significant improvements in sleep, stress, mood, and symptoms that occurred 6 months post treatment were sustained during the pandemic. CONCLUSIONS Improving sleep and symptoms among people with HF may improve coping during stressful events, and cognitive behavioral therapy for insomnia may be protective.
Techniques for Developing Reliable Machine Learning Classifiers Applied to Understanding and Predicting Protein:Protein Interaction Hot Spots.
Methods in molecular biology (Clifton, N.J.). 2024;:235-268
With machine learning now transforming the sciences, successful prediction of biological structure or activity is mainly limited by the extent and quality of data available for training, the astute choice of features for prediction, and thorough assessment of the robustness of prediction on a variety of new cases. In this chapter, we address these issues while developing and sharing protocols to build a robust dataset and rigorously compare several predictive classifiers using the open-source Python machine learning library, scikit-learn. We show how to evaluate whether enough data has been used for training and whether the classifier has been overfit to training data. The most telling experiment is 500-fold repartitioning of the training and test sets, followed by prediction, which gives a good indication of whether a classifier performs consistently well on different datasets. An intuitive method is used to quantify which features are most important for correct prediction.The resulting well-trained classifier, hotspotter, can robustly predict the small subset of amino acid residues on the surface of a protein that are energetically most important for binding a protein partner: the interaction hot spots. Hotspotter has been trained and tested here on a curated dataset assembled from 1046 non-redundant alanine scanning mutation sites with experimentally measured change in binding free energy values from 97 different protein complexes; this dataset is available to download. The accessible surface area of the wild-type residue at a given site and its degree of evolutionary conservation proved the most important features to identify hot spots. A variant classifier was trained and validated for proteins where only the amino acid sequence is available, augmented by secondary structure assignment. This version of hotspotter requiring fewer features is almost as robust as the structure-based classifier. Application to the ACE2 (angiotensin converting enzyme 2) receptor, which mediates COVID-19 virus entry into human cells, identified the critical hot spot triad of ACE2 residues at the center of the small interface with the CoV-2 spike protein. Hotspotter results can be used to guide the strategic design of protein interfaces and ligands and also to identify likely interfacial residues for protein:protein docking.
Systematic review and meta-analysis on the impact of COVID-19 related restrictions on air quality in low- and middle-income countries.
The Science of the total environment. 2024;:168110
BACKGROUND Low- and middle-income countries (LMIC) are disproportionately affected by air pollution and its health burden, representing a global inequity. The COVID-19 pandemic provided a unique opportunity to investigate the impact of unprecedented lockdown measures on air pollutant concentrations globally. We aim to quantify air pollutant concentration changes across LMIC settings as a result of COVID-19 restrictions. METHODS Searches for this systematic review and meta-analysis were carried out across five databases on 30th March 2022; MEDLINE, Embase, Web of Science, Scopus and Transport Research Information Documentation. Modelling and observational studies were included, as long as the estimates reflected city or town level data and were taken exclusively in pre-lockdown and lockdown periods. Mean percentage changes per pollutant were calculated and meta-analyses were carried out to calculate mean difference in measured ground-level observed concentrations for each pollutant (PROSPERO CRD42022326924). FINDINGS Of the 2982 manuscripts from initial searches, 256 manuscripts were included providing 3818 percentage changes of all pollutants. No studies included any countries from Sub-Saharan Africa and 34 % and 39.4 % of studies were from China and India, respectively. There was a mean percentage change of -37.4 %, -21.7 %, -54.6 %, -39.1 %, -48.9 %, 16.9 %, -34.9 %, -30.6 % and - 14.7 % for black carbon (BC), carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), oxides of nitrogen (NOx), ozone (O3), particulate matter 10 (PM10) and 2.5 (PM2.5) and sulphur dioxide (SO2), respectively. Meta-analysis included 100 manuscripts, providing 908 mean concentration differences, which showed significant reduction in mean concentration in all study settings for BC (-0.46 μg/m3, PI -0.85; -0.08), CO (-0.25 mg/m3, PI -0.44; -0.03), NO2 (-19.41 μg/m3, PI -31.14; -7.68) and NOx (-22.32 μg/m3, PI -40.94; -3.70). INTERPRETATION The findings of this systematic review and meta-analysis quantify and confirm the trends reported across the globe in air pollutant concentration, including increases in O3. Despite the majority of global urban growth occurring in LMIC, there are distinct geographical gaps in air pollution data and, where it is available, differing approaches to analysis and reporting.
The effect of the urban exposome on COVID-19 health outcomes: A systematic review and meta-analysis.
Environmental research. 2024;(Pt 2):117351
BACKGROUND The global severity of SARS-CoV-2 illness has been associated with various urban characteristics, including exposure to ambient air pollutants. This systematic review and meta-analysis aims to synthesize findings from ecological and non-ecological studies to investigate the impact of multiple urban-related features on a variety of COVID-19 health outcomes. METHODS On December 5, 2022, PubMed was searched to identify all types of observational studies that examined one or more urban exposome characteristics in relation to various COVID-19 health outcomes such as infection severity, the need for hospitalization, ICU admission, COVID pneumonia, and mortality. RESULTS A total of 38 non-ecological and 241 ecological studies were included in this review. Non-ecological studies highlighted the significant effects of population density, urbanization, and exposure to ambient air pollutants, particularly PM2.5. The meta-analyses revealed that a 1 μg/m3 increase in PM2.5 was associated with a higher likelihood of COVID-19 hospitalization (pooled OR 1.08 (95% CI:1.02-1.14)) and death (pooled OR 1.06 (95% CI:1.03-1.09)). Ecological studies, in addition to confirming the findings of non-ecological studies, also indicated that higher exposure to nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), and carbon monoxide (CO), as well as lower ambient temperature, humidity, ultraviolet (UV) radiation, and less green and blue space exposure, were associated with increased COVID-19 morbidity and mortality. CONCLUSION This systematic review has identified several key vulnerability features related to urban areas in the context of the recent COVID-19 pandemic. The findings underscore the importance of improving policies related to urban exposures and implementing measures to protect individuals from these harmful environmental stressors.
Update on fungal lipid biosynthesis inhibitors as antifungal agents.
Microbiological research. 2024;:127517
Fungal diseases today represent a world-wide problem. Poor hygiene and decreased immunity are the main reasons behind the manifestation of this disease. After COVID-19, an increase in the rate of fungal infection has been observed in different countries. Different classes of antifungal agents, such as polyenes, azoles, echinocandins, and anti-metabolites, as well as their combinations, are currently employed to treat fungal diseases; these drugs are effective but can cause some side effects and toxicities. Therefore, the identification and development of newer antifungal agents is a current need. The fungal cell comprises many lipids, such as ergosterol, phospholipids, and sphingolipids. Ergosterol is a sterol lipid that is only found in fungal cells. Various pathways synthesize all these lipids, and the activities of multiple enzymes govern these pathways. Inhibiting these enzymes will ultimately impede the lipid synthesis pathway, and this phenomenon could be a potential antifungal therapy. This review will discuss various lipid synthesis pathways and multiple antifungal agents identified as having fungal lipid synthesis inhibition activity. This review will identify novel compounds that can inhibit fungal lipid synthesis, permitting researchers to direct further deep pharmacological investigation and help develop drug delivery systems for such compounds.
Electrochemical degradation of key drugs to treat COVID-19: Experimental analysis of the toxic by-products formation (PCDD/Fs).
The Science of the total environment. 2024;:167660
Drug consumption has grown exponentially in recent decades, particularly during the COVID-19 pandemic, leading to their presence in various water sources. In this way, degradation technologies for pollutants, such as electrochemical oxidation (ELOX), have become crucial to safeguard the quality of natural resources. This study has as its starting point a previous research, which demonstrated the efficacy of ELOX in the removal of COVID-19 related-drugs, such as dexamethasone (DEX), paracetamol (PAR), amoxicillin (AMX), and sertraline (STR), using the electrolytes NaCl and Na2SO4. The present research aims to study the potential risks associated with the generation of toxic by-products, during the ELOX of cited drugs, specifically focusing on the highly chlorinated persistent organic pollutants (POPs), such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Dioxins and furans can be formed potentially in electrochemical systems from precursor molecules or non-precursor molecules in chloride medium. First, the degradation of the parent compounds was found to be complete. At this point, a comprehensive investigation was conducted to identify and analyse the by-products formed during the degradation process; precursors of PCDD/Fs, such as chlorophenols or hydroquinones were identified. Additionally, in continuation of the previous study, PCDD/Fs congeners were investigated, revealing elevated concentrations; the highest concentration obtained was for the congener 1,2,3,4,6,7,8-HpCDF (234.6 pg L-1 in NaCl) during degradation of the AMX. Finally, an assessment of the toxicity based on TEQ values was conducted, with DEX exhibiting the highest concentration among all compounds: 30.1 pg L-1 for NaCl medium. Therefore, the formation of minor by-products should not be underestimated, as they can significantly enhance the toxicity of the final sample, so the selection of the appropriate remediation technology, as well as the optimization of experimental operating variables, is determining in the treatment of pharmaceutical-contaminated waters.
Naturally Occurring Xanthones; Biological Activities, Chemical Profiles and In Silico Drug Discovery.
Current medicinal chemistry. 2024;(1):62-101
Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon´s isolated compounds from 2017-2020. We found that only α-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 Mpro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 Mpro with docking scores of -11.2 and -11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the Mpro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.
BBIBP-CorV vaccination accelerates anti-viral antibody responses in heterologous Omicron infection: A retrospective observation study in Shanghai.
OBJECTIVES To investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection. METHODS 440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed. RESULTS BBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients. CONCLUSIONS BBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.
Staging of COVID-19 disease; using selected laboratory profiles for prediction, prevention and management of severe SARS-CoV-2 infection in Africa-review.
African health sciences. 2023;(1):1-15
There are many uncertainties on the future management of the coronavirus disease 19 (COVID-19) in Africa. By July 2021, Africa had lagged behind the rest of the world in Covid-19 vaccines uptake, accounting for just 1.6% of doses administered globally. During that time COVID 19 was causing an average death rate of 2.6% in Africa, surpassing the then global average of 2.2%. There were no clear therapeutic guidelines, yet inappropriate and unnecessary treatments may have led to unwanted adverse events such as worsening of hyperglycemia and precipitating of ketoacidosis in administration of steroid therapy. in order to provide evidence-based policy guidelines, we examined peer-reviewed published articles in PubMed on COVID 19, or up-to date data, we focused our search on publications from 1st May 2020 to 15th July, 2021. For each of the studies, we extracted data on pathophysiology, selected clinical chemistry and immunological tests, clinical staging and treatment. Our review reports a gross unmet need for vaccination, inadequate laboratory capacity for immunological tests and the assessment of individual immune status, clinical staging and prediction of disease severity. We recommend selected laboratory tools in the assessment of individual immune status, prediction of disease severity and determination of the exact timing for suitable therapy, especially in individuals with co-morbidities.
Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2023;(1):13-21
BACKGROUND Randomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids. OBJECTIVES To estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids. DATA SOURCES PubMed, Embase, Cochrane Library, and MedRxiv. STUDY ELIGIBILITY CRITERIA Eligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control). METHODS Reviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days. PARTICIPANTS Twenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively. RESULTS All but two studies included data with only indirect evidence for the comparison of interest. CONCLUSIONS Among hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.