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Interplay of calcium, vitamin D, and parathormone in the milieu of infections and immunity: Reassessed in the context of COVID-19.
Bandyopadhyay, U, Sen, D, Ahuja, D, Mahapatra, SP, Biswas, D, Maiti, R, Chakraborty, S, Hazra, A, Parua, S, Basak, AK, et al
The Journal of steroid biochemistry and molecular biology. 2025;:106624
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized for inducing severe respiratory symptoms like cough, and shortness of breathing. Although symptom severity varies, some individuals remain asymptomatic. This virus has sparked a global pandemic, imposing a substantial rate of mortality or morbidity, with extended periods of illness reported. People with underlying medical issues and the elderly are more likely to experience adverse results. The virus's frequent mutations pose challenges for medical professionals, necessitating adaptable therapeutic and preventive strategies. Vitamin D, a versatile regulatory molecule, not only influences physiological processes such as serum calcium regulation but also exhibits immunomodulatory functions. Calcium ions play a crucial role as secondary signal transduction molecules, impacting diverse cellular functions and maintaining homeostasis through ion channel regulation. Parathormone, another key regulator of serum calcium, often acts antagonistically to vitamin D. This review delves into the interplay of vitamin D, calcium, and parathormone, exploring their possible influence on the progression of COVID-19. The intricate signaling involving these elements contributes to adverse prognosis, emphasizing the need for comprehensive understanding. Monitoring and controlling these physiological factors and associated pathways have shown the potential to alter disease outcomes, underscoring the importance of a holistic approach.
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Do dynamic changes in haematological and biochemical parameters predict mortality in critically ill COVID-19 patients?
Jandric, M, Zlojutro, B, Momcicevic, D, Dragic, S, Kovacevic, T, Djajic, V, Stojiljkovic, MP, Loncar-Stojiljkovic, D, Skrbic, R, Djuric, DM, et al
Technology and health care : official journal of the European Society for Engineering and Medicine. 2025;(1):275-286
Abstract
BACKGROUND Critically ill COVID-19 patients are usually subjected to clinical, laboratory, and radiological diagnostic procedures resulting in numerous findings. Utilizing these findings as indicators for disease progression or outcome prediction is particularly intriguing. OBJECTIVES Exploring the significance of dynamic changes in haematological and biochemical parameters in predicting the mortality of critically ill COVID-19 patients. METHODS The present study was a prospective and observational study involving mechanically ventilated 75 critically ill adult COVID-19 patients with hypoxemic respiratory failure. The collected data included baseline patient characteristics, treatment options, outcome, and laboratory findings at admission and 7 days after. The dynamics of the obtained findings were compared between survivors and non-survivors. RESULTS The 28-day survival rate was 61.3%. In the group of non-survivors significant dynamic changes were found for C-reactive protein (p= 0.001), interleukin-6 (p< 0.001), lymphocyte (p= 0.003), neutrophil-lymphocyte ratio (p= 0.003), platelets (p< 0.001), haemoglobin (p< 0.001), iron (p= 0.012), and total iron-binding capacity (p< 0.001). Statistically significant changes over time were found for ferritin (p= 0.010), D-dimer (p< 0.001), hs-troponin T (p< 0.002), lactate dehydrogenase (p= 0.001), glucose (p= 0.023), unsaturated iron-binding capacity (p= 0.008), and vitamin D (p< 0.001). CONCLUSION The dynamic changes in inflammatory, haematological and biochemical parameters can predict disease severity, and outcome.
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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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The impact of the COVID-19 pandemic on dietary behaviors among school-age children, adolescents, and young adults: a systematic review and meta-analysis.
Na, X, Zhang, J, Xie, C, Zeng, H, Wu, L, Fan, D, Yang, H, Shi, X, Zhou, Y, Yu, H, et al
Nutrition reviews. 2025;(2):e195-e210
Abstract
CONTEXT The COVID-19 pandemic has had a global impact on food security and nutrition, both in the short and long term. The influence on school-age children, adolescents, and young adults may be particularly significant and long-lasting. OBJECTIVE This systematic review and meta-analysis aimed to quantify the impact of the COVID-19 pandemic on dietary habits among school-age children, adolescents, and young adults worldwide. DATA SOURCES PubMed, Web of Science, and Embase were searched from inception to October 5, 2023. DATA EXTRACTION We included observational studies published in English that reported dietary quality scores and dietary intake quantities during and before the COVID-19 pandemic among school-age children, adolescents, and young adults. We included a total of 22 cohort studies and 20 cross-sectional studies of high or moderate quality. DATA ANALYSIS We conducted a meta-analysis, expressing dietary quality scores and dietary intake quantities as standardized mean differences (SMD) with 95% confidence intervals (CIs). For studies with low heterogeneity, we used a fixed-effects model; otherwise, we applied a random-effects model. The Newcastle-Ottawa Scale was employed by 2 reviewers independently to evaluate methodological quality. The analysis indicated that, overall, juice intake increased (SMD = 0.12, 95% CI: 0.04 to 0.20), while alcohol consumption reduced during the COVID-19 pandemic (SMD = -0.28, 95% CI: -0.47 to -0.08). However, the age-stratified results varied. Among school-age children, intake of fruit, dairy products, sugar, and juice increased. Adolescents showed an increase in meal frequency and vegetable intake. Young adults showed reduced carbohydrate and alcohol intakes, while protein and dairy product intakes increased, based on limited included studies. CONCLUSION Dietary changes in school-age children from before to during the pandemic were mixed, while dietary behavior changes in adolescents and young adults tended to be more positive. Considering the lasting effects of negative dietary behaviors, attention should be given to addressing the increased sugar and juice intakes. It is also crucial that caregivers and researchers monitor whether positive dietary behaviors will rebound after returning to normal study and life. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42023420923.
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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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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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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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Washing Illness Away: A Systematic Review of the Impact of Nasal Irrigation and Spray on COVID-19.
Gandhi, K, Paczkowski, F, Sowerby, L
The Laryngoscope. 2025;(2):517-528
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OBJECTIVE Nasal irrigation is a common treatment for sinonasal disorders; however, it is unknown if it can reduce SARS-CoV-2 nasopharyngeal viral load (NVL). This systematic review investigated the efficacy of nasal irrigation with saline, povidone iodine (PVP-I), and intranasal corticosteroids (INCS) at reducing SARS-CoV-2 NVL and transmissibility. DATA SOURCES Databases including Embase, MEDLINE, Web of Science, and ClinicalTrials.gov. REVIEW METHODS A systematic review was completed with pre-defined search criteria using keywords related to nasal irrigation and COVID-19 from 1946 through January 2024. This review followed PRISMA reporting guidelines and was registered on PROSPERO. Only in-vivo studies testing nasal irrigation with either saline, PVP-I, or INCS for reducing NVL were included. RESULTS Nine out of ten studies on saline-based solutions reported positive effects in reducing NVL, with benefits noted in earlier time to negative nasopharyngeal PCR and a greater decline in NVL during early study time points, compared with controls. Isotonic and hypertonic saline mediums were found to be effective with three studies demonstrating enhanced efficacy with additives. Four out of seven studies on PVP-I showed a positive effect on reducing NVL, but results were heterogenous. Four studies demonstrated reduction of transmission with saline or PVP-I. No studies were found on INCS. CONCLUSION Saline nasal irrigation showed the best efficacy in reducing SARS-CoV-2 NVL. Additives to saline may have a clinical benefit, but further studies are needed to elucidate their isolated impacts on NVL. Data on PVP-I is inconclusive and further studies are warranted to determine the ideal concentration for irrigation. Laryngoscope, 135:517-528, 2025.
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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).
