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Redox imbalance driven epigenetic reprogramming and cardiovascular dysfunctions: phytocompounds for prospective epidrugs.
Jyotirmaya, SS, Rath, S, Dandapat, J
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2025;:156380
Abstract
BACKGROUND Cardiovascular diseases (CVDs) are the major contributor to global mortality and are gaining incremental attention following the COVID-19 outbreak. Epigenetic events such as DNA methylation, histone modifications, and non-coding RNAs have a significant impact on the incidence and onset of CVDs. Altered redox status is one of the major causative factors that regulate epigenetic pathways linked to CVDs. Various bioactive phytocompounds used in alternative therapies including Traditional Chinese Medicines (TCM) regulate redox balance and epigenetic phenomena linked to CVDs. Phytocompound-based medications are in the limelight for the development of cost-effective drugs with the least side effects, which will have immense therapeutic applications. PURPOSE This review comprehends certain risk factors associated with CVDs and triggered by oxidative stress-driven epigenetic remodelling. Further, it critically evaluates the pharmacological efficacy of phytocompounds as inhibitors of HAT/HDAC and DNMTs as well as miRNAs regulator that lowers the incidence of CVDs, aiming for new candidates as prospective epidrugs. METHODS PRISMA flow approach has been adopted for systematic literature review. Different Journals, computational databases, search engines such as Google Scholar, PubMed, Science Direct, Scopus, and ResearchGate were used to collect online information for literature survey. Statistical information collected from the World Health Organization (WHO) site (https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)) and the American Heart Association of Heart Disease and Stroke reported the international and national status of CVDs. RESULTS The meta-analysis of various studies is elucidated in the literature, shedding light on major risk factors such as socioeconomic parameters, which contribute highly to redox imbalance, epigenetic modulations, and CVDs. Going forward, redox imbalance driven epigenetic regulations include changes in DNA methylation status, histone modifications and non-coding RNAs expression pattern which further regulates global as well as promoter modification of various transcription factors leading to the onset of CVDs. Further, the role of various bioactive compounds used in herbal medicine, including TCM for redox regulation and epigenetic modifications are discussed. Pharmacological safety doses and different phases of clinical trials of these phytocompounds are elaborated on, which shed light on the acceptance of these phytocompounds as prospective drugs. CONCLUSION This review suggests a strong linkage between therapeutic and preventive measures against CVDs by targeting redox imbalance-driven epigenetic reprogramming using phytocompounds as prospective epidrugs. Future in-depth research is required to evaluate the possible molecular mechanisms behind the phytocompound-mediated epigenetic reprogramming and oxidative stress management during CVD progression.
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Metabolic acidosis with elevated anion gap and euglycemic ketoacidosis in pregnant and postpartum women with severe Covid-19.
Melo Mendes, IC, Martins de Oliveira, AL, Pinheiro Trindade, PM, Mendes da Silva, W, Pimentel, C, Perlingeiro, RM, Melo Guedes, C, Caminha Escosteguy, C, Galliez, RM
Annals of medicine. 2025;(1):2445189
Abstract
BACKGROUND/OBJECTIVES Pregnant and postpartum women have a higher risk for developing severe Covid-19 and other clinical and obstetric complications. This study aims to evaluate the frequency of metabolic acidosis with elevated anion gap and describe a case series of euglycemic ketoacidosis (EKA) in pregnant and postpartum women with severe confirmed or suspected Covid-19. MATERIALS AND METHODS Observational retrospective study carried in a reference intensive care unit from May 2020 to June 2022. Cases were confirmed with positive RT-PCR or rapid antigen test. Cases with compatible clinical and radiologic findings were also included. Ketoacidosis was defined as the presence of metabolic acidosis with high anion gap (bicarbonate < 15 mEq/L and AG > 10 mEq/L) and ketonuria (2+ or more in urine test). Statistical analyses were made with R software. RESULTS Of 101 admissions, 61 (60.4%) presented metabolic acidosis with high anion gap. The median age was 29 years, and most were in the third trimester. Evolution to invasive mechanical ventilation (54.0%) and obstetric complications (78.0%) were frequent. The prevalence of metabolic acidosis with high anion gap and absence of hyperlactatemia was of 43.6% (44/101). Six (5.94%) women met the criteria for EKA. Despite severity, there were no deaths. CONCLUSIONS The prevalence of metabolic acidosis and EKA in pregnant and postpartum women with severe Covid-19 was high. This condition should be routinely, so it can be promptly treated.
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Emerging Evidence on Balneotherapy and Thermal Interventions in Post-COVID-19 Syndrome: A Systematic Review.
Ferrara, E, Scaramuzzino, M, Murmura, G, D'Addazio, G, Sinjari, B
Healthcare (Basel, Switzerland). 2025;(2)
Abstract
BACKGROUND Post-COVID-19 syndrome affects 10-60% of SARS-CoV-2 survivors. While conventional treatments show limited efficacy, emerging evidence suggests the potential benefits of balneotherapy in managing persistent symptoms. We aimed to systematically evaluate the efficacy and safety of balneotherapy and thermal treatment interventions in treating post-COVID-19 syndrome. METHODS We conducted a systematic review following PRISMA guidelines, searching major databases through 31 January 2024. Eligible studies included randomized controlled trials, observational studies, and pilot studies investigating thermal spa treatments for adult post-COVID-19 patients. RESULTS Analysis of six eligible studies (n = 617) demonstrated significant therapeutic benefits. The largest cohort (n = 159) showed 47% reduction in fatigue and 48% reduction in muscle pain (p < 0.01). Comprehensive spa therapy achieved complete symptom resolution in one-third of the participants. Combined spa-ubiquinol therapy improved metabolic function (p < 0.05). All interventions demonstrated favorable safety profiles. CONCLUSIONS Preliminary evidence suggests balneotherapy effectively ameliorates multiple post-COVID-19 symptoms, particularly fatigue, muscle pain, and exercise intolerance. While safety profiles appear favorable, larger randomized controlled trials with standardized protocols are needed to establish definitive therapeutic recommendations.
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Environmental, climatic, socio-economic factors and non-pharmacological interventions: A comprehensive four-domain risk assessment of COVID-19 hospitalization and death in Northern Italy.
Palandri, L, Rizzi, C, Vandelli, V, Filippini, T, Ghinoi, A, Carrozzi, G, Girolamo, G, Morlini, I, Coratza, P, Giovannetti, E, et al
International journal of hygiene and environmental health. 2025;:114471
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INTRODUCTION Up to now, studies on environmental, climatic, socio-economic factors, and non-pharmacological interventions (NPI) show diverse associations, often contrasting, with COVID-19 spread or severity. Most studies used large-scale, aggregated data, with limited adjustment for individual factors, most of them focused on viral spread than severe outcomes. Moreover, evidence simultaneously evaluating variables belonging to different exposure domains is scarce, and none analysing their collective impact on an individual level. METHODS Our population-based retrospective cohort study aimed to assess the comprehensive role played by exposure variables belonging to four different domains, environmental, climatic, socio-economic, and non-pharmacological interventions (NPI), on individual COVID-19-related risk of hospitalization and death, analysing data from all patients (no. 68472) tested positive to a SARS-CoV-2 swab in Modena Province (Northern Italy) between February 2020 and August 2021. Using adjusted Cox proportional hazard models, we estimated the risk of severe COVID-19 outcomes, investigating dose-response relationships through restricted cubic spline modelling for hazard ratios. RESULTS Several significant associations emerged: long-term exposure to air pollutants (NO2, PM10, PM2.5) was linked to hospitalization risk in a complex way and showed an increased risk for death; while humidity was inversely associated; temperature showed a U-shaped risk; wind speed showed a linear association with both outcomes. Precipitation increased hospitalization risk but decreased mortality. Socio-economic and NPI indices showed clear linear associations, respectively negative and positive, with both outcomes. CONCLUSIONS Our findings offer insights for evidence-based policy decisions, improving precision healthcare practices, and safeguarding public health in future pandemics. Refinement of pandemic response plans by healthcare authorities could benefit significantly.
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Efficacy and Safety of Sodium Oxybate in Isolated Focal Laryngeal Dystonia: A Phase IIb Double-Blind Placebo-Controlled Cross-Over Randomized Clinical Trial.
Simonyan, K, O'Flynn, LC, Hamzehei Sichani, A, Frucht, SJ, Rumbach, AF, Sharma, N, Song, PC, Worthley, A
Annals of neurology. 2025;(2):329-343
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OBJECTIVE To examine the efficacy and safety of sodium oxybate versus placebo in a phase IIb randomized double-blind placebo-controlled 2-period cross-over clinical trial in patients with isolated laryngeal dystonia (LD). METHODS The study was conducted from January 2018 to December 2021, pausing during the COVID-19 pandemic, at Massachusetts Eye and Ear in 106 patients with alcohol-responsive (EtOH+) and alcohol-non-responsive (EtOH-) LD (53 to receive 1.5g of sodium oxybate first, 53 to receive matching placebo first). The primary outcome was a change from baseline in LD symptom severity 40 minutes after drug intake. Safety was based on vital signs, cognitive function, suicidality, daytime sleepiness, and adverse events. Patients, investigators, and outcome assessors were masked to study procedures. RESULTS Compared to baseline, EtOH+ but not EtOH- patients had a statistically significant improvement in LD symptoms following sodium oxybate versus placebo (EtOH+: 98.75% confidence interval [CI] = 0.6-26.9; p = 0.008; EtOH-: 98.75% CI = -6.2 to 18.7; p = 0.42). Statistically significant minimum drug efficacy in EtOH+ patients was found at ≥16% symptom improvement (OR = 2.09; 98.75% CI = 0.75-5.80; p = 0.036), with an average of 40.81% benefits (98.75% CI = 34.7-48.6). Drug efficacy waned by 300 minutes after intake without a rebound. No changes were found in cognitive function, suicidality, or vital signs. Common adverse events included mild dizziness, nausea, and daytime sleepiness. INTERPRETATION Sodium oxybate showed clinically meaningful improvement of symptoms in EtOH+ LD patients, with acceptable tolerability. Sodium oxybate offers the first pathophysiologically relevant oral treatment for laryngeal dystonia. ANN NEUROL 2025;97:329-343.
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A family-based behavioral group obesity randomized control feasibility trial across a clinical trials network: a focus on contact hours.
Davis, AM, Darden, P, Lancaster, B, Chang, D, Cushing, CC, Janicke, DM, Lim, CS, Olalde, M, Bullard, S, McCulloh, R, et al
Journal of pediatric psychology. 2025
Abstract
OBJECTIVE This ancillary study's purpose is to describe the relationship between dose of treatment and body mass index (BMI) outcomes in a tele-behavioral health program delivered in the IDeA States Pediatric Clinical Trials Network to children and their families living in rural communities. METHODS Participants randomized to the intervention were able to receive 26 contact hours (15 hr of group sessions and 11 hr of individual sessions) of material focused on nutrition, physical activity, and behavioral caregiver training delivered via interactive televideo. Dose of the intervention received by child/caregiver dyads (n = 52) from rural areas was measured as contact hours. The total doses of group, individual, and total contact hours were analyzed, and generalized linear mixed models were utilized to determine how dose received impacted BMI outcomes. RESULTS The majority (64.4%) of participants received the target of at least 80% (20.8 hr) of the total intervention dose. Older children (9-11 years) achieved significantly less intervention dose than targeted (M = 19.7; p = .031); as did males (M = 17.2; p < .001), children who identified as Black (M = 17.8; p < .001), and children from Site 3 (M = 18.0; p < .001). Dose was not significantly related to BMI outcomes in children or caregivers. CONCLUSIONS As this study is underpowered and took place during the early stages of the COVID-19 pandemic, results should be interpreted with caution, but contact hours did not predict health outcomes for families living in rural communities.
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E-cigarette, or Vaping, Product Use Associated Lung Injury: Epidemiology, Challenges, and Implications With COVID-19.
Soerianto, W, Jaspers, I
Pediatric pulmonology. 2025;(1):e27448
Abstract
BACKGROUND E-cigarette, or vaping products produce an aerosol by heating nicotine, or cannabis including tetrahydrocannabinol (THC) and cannabidiol (CBD), mixed with other chemicals that help make the aerosol. They are increasingly popular among teenagers and young adults, with a 2023 survey reporting that 2.13 million middle and high school students in the United States used e-cigarettes within the last 30 days. The use of e-cigarette, or vaping products could lead to an acute pulmonary inflammatory syndrome called e-cigarette, or vaping, product use-associated lung injury (EVALI). We review the challenges in diagnosing and treating EVALI, especially during the COVID-19 pandemic. METHODS We conducted a literature search on June 10, 2024 using the PubMed database. We searched for articles, case reports and CDC reports investigating the pathogenesis, treatment, and challenges of diagnosing EVALI during the COVID-19 pandemic. RESULTS The exact causes of EVALI are not completely understood, although it has been linked to the use of THC and vitamin E acetate. There are no specific biomarkers to diagnose EVALI and it is typically diagnosed through a process of eliminating other possible conditions. Eight studies detailed cases where pediatric patients were initially diagnosed with COVID-19 or community-acquired pneumonia, despite multiple negative COVID-19 tests, and were later found to have EVALI. CONCLUSIONS After alerting the public about the removal of vitamin E acetate from vape liquids in 2020, there has been a decline in cases of EVALI, although they are still detected. Therefore, it is necessary to continue looking for diagnostic markers of EVALI and further investigate the toxicity of vapes and e-cigarettes to prevent the recurrence of another EVALI epidemic, especially among teenagers and young adults.
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Physicochemical Evaluation of Remote Homology in the Twilight Zone.
Dixson, JD, Azad, RK
Proteins. 2025;(2):452-464
Abstract
A fundamental problem in the field of protein evolutionary biology is determining the degree and nature of evolutionary relatedness among homologous proteins that have diverged to a point where they share less than 30% amino acid identity yet retain similar structures and/or functions. Such proteins are said to lie within the "Twilight Zone" of amino acid identity. Many researchers have leveraged experimentally determined structures in the quest to classify proteins in the Twilight Zone. Such endeavors can be highly time consuming and prohibitively expensive for large-scale analyses. Motivated by this problem, here we use molecular weight-hydrophobicity physicochemical dynamic time warping (MWHP DTW) to quantify similarity of simulated and real-world homologous protein domains. MWHP DTW is a physicochemical method requiring only the amino acid sequence to quantify similarity of related proteins and is particularly useful in determining similarity within the Twilight Zone due to its resilience to primary sequence substitution saturation. This is a step forward in determination of the relatedness among Twilight Zone proteins and most notably allows for the discrimination of random similarity and true homology in the 0%-20% identity range. This method was previously presented expeditiously just after the outbreak of COVID-19 because it was able to functionally cluster ACE2-binding betacoronavirus receptor binding domains (RBDs), a task that has been elusive using standard techniques. Here we show that one reason that MWHP DTW is an effective technique for comparisons within the Twilight Zone is because it can uncover hidden homology by exploiting physicochemical conservation, a problem that protein sequence alignment algorithms are inherently incapable of addressing within the Twilight Zone. Further, we present an extended definition of the Twilight Zone that incorporates the dynamic relationship between structural, physicochemical, and sequence-based metrics.
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Reliability and Validity of Diabetes Nutrition Self-Efficacy and Behavior Measures for the "What Can I Eat" Diabetes Nutrition Education Program for American Indian and Alaska Native Adults With Type 2 Diabetes.
Brega, AG, Stotz, SA, Moore, KR, McNulty, MC, Jiang, L
Journal of the Academy of Nutrition and Dietetics. 2025;(1):78-89.e1
Abstract
BACKGROUND American Indian and Alaska Native (AI/AN) people have high rates of diabetes and limited access to nutrition education. The "What Can I Eat? Healthy Choices for People With Type 2 Diabetes" (WCIE) diabetes nutrition education program was culturally adapted for AI/AN adults. OBJECTIVE This analysis was designed to evaluate the reliability and validity of items developed to measure diabetes nutrition self-efficacy (ie, confidence one can engage in specific behaviors) and diabetes nutrition behavior among participants in the WCIE program for AI/AN adults. DESIGN This study was a secondary analysis of data from a randomized controlled trial designed to evaluate the WCIE program for AI/AN adults. Baseline data were used to assess the reliability and validity of the self-efficacy and behavior items, which were collected via survey. Due to COVID-19 safety protocols, the intervention was conducted via Zoom (Zoom Video Communications), and both survey and clinical data were collected at home by participants. PARTICIPANTS/SETTING The study was conducted from January to December 2021 with 5 AI/AN-serving health care programs in Oklahoma, Illinois, North Carolina, California, and New York. AI/AN adults with type 2 diabetes who spoke English and had internet access were eligible. Sixty people participated. MAIN OUTCOME MEASURES Analyses examined validity and reliability of diabetes nutrition self-efficacy and behavior items. STATISTICAL ANALYSIS PERFORMED To test reliability, internal consistency and factor structures of the scales were examined. To evaluate convergent validity, Pearson correlations were computed to examine the association of the self-efficacy and behavior measures with each other and with clinical indicators (ie, body mass index, blood pressure, and hemoglobin A1c). RESULTS Two self-efficacy factors were identified. Each showed strong internal consistency (Cronbach α ≥ 0.85; McDonald ω ≥ 0.88) and was directly associated with diabetes nutrition behavior (P < .001). The factor assessing Confidence in Using the Diabetes Plate was inversely associated with hemoglobin A1c (Pearson correlation = -0.32, P = .0243). The behavior measure capturing Healthy Nutrition Behavior showed strong internal consistency (α = 0.89; ω = 0.92) and was inversely associated with hemoglobin A1c (Pearson correlation = -0.38, P = .0057). CONCLUSIONS Diabetes nutrition self-efficacy and behavior items developed for the WCIE program for AI/AN adults are valid and reliable. These items can facilitate rigorous and consistent evaluation of the AI/AN WCIE program.
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Effectiveness of Mobile Health Applications for Cardiometabolic Risk Reduction in Urban and Rural India: A Pilot, Randomized Controlled Study.
Ranjani, H, Avari, P, Nitika, S, Jagannathan, N, Oliver, N, Valabhji, J, Mohan, V, Chambers, JC, Anjana, RM
Journal of diabetes science and technology. 2025;:19322968241310861
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INTRODUCTION mHealth technology has the potential to deliver personalized health care; however, data on cardiometabolic risk factors are limited. This study aims to assess the effectiveness of mobile health applications (apps) on cardiometabolic risk factor reduction in adults aged 25 to 60 years in urban and rural India. METHODS The study design was a pilot randomized controlled trial conducted in Tamil Nadu, India. Smartphone users (25-60 years) with basic literacy and at high risk of developing diabetes (Indian Diabetes Risk Score ≥30 and/or fasting blood sugar [FBS] 100-125 mg/dL) were recruited. Four mobile apps (two commercially available, two novel) for cardiometabolic risk reduction were evaluated. Primary outcome (weight loss) was analyzed using intention-to-treat analysis with post hoc analysis and logistic regression models adjusted for confounders. RESULTS A total of 5264 participants were screened, and 610 were recruited into the study. Participants (7%) dropped out largely due to the COVID-19 pandemic. Data from 567 participants were used for the final analysis. In the intention-to-treat analysis, a significant reduction in body weight was observed in the intervention group as compared with control, more so in the urban (-2.40 kg, 95% confidence interval [CI] = [-3.10, -1.69], P < .001) compared with rural population (-1.19 kg, 95% CI = [-1.55, -0.82], P < .001). Intervention group participants showed significant reductions in body mass index, waist circumference, blood pressure, FBS, total serum cholesterol, and a positive effect on dietary and physical activity behaviors compared with controls. CONCLUSIONS mHealth interventions can reduce diabetes risk, improve cardiometabolic health, and improve lifestyle behaviors in South Asian populations. TRIAL REGISTRATION The trial is registered with the Central Trials Registry, India (CTRI/2020/03/024327).