-
Redox Biology Jun 2024Hydrogen peroxide is a key element in redox signaling and in setting cellular redox tone. DUOX1 and DUOX2, that directly synthesize hydrogen peroxide, are the most...
Hydrogen peroxide is a key element in redox signaling and in setting cellular redox tone. DUOX1 and DUOX2, that directly synthesize hydrogen peroxide, are the most abundant NADPH oxidase transcripts in most epithelia. DUOX1 and DUOX2 hydrogen peroxide synthesis is regulated by intracellular calcium transients and thus cells can respond to signals and initiate responses by increasing cellular hydrogen peroxide synthesis. Nevertheless, many details of their enzymatic regulation are still unexplored. DUOX1 and DUOXA1 were expressed in HEK293T cells and activity was studied in homogenates and membrane fractions. When DUOX1 homogenates or membranes were pre-incubated in NADPH and started with addition of Ca, to mimic intracellular activation, progress curves were distinctly different from those pre-incubated in Ca and started with NADPH. The Ca EC for DUOX1's initial rate when pre-incubated in Ca, was three orders of magnitude lower (EC ∼ 10 M) than with preincubation in NADPH (EC ∼ 10 M). In addition, activity was several fold lower with Ca start. Identical results were obtained using homogenates and membrane fractions. The data suggested that DUOX1 Ca binding in expected physiological signaling conditions only slowly leads to maximal hydrogen peroxide synthesis and that full hydrogen peroxide synthesis activity in vivo only can occur when encountering extremely high concentration Ca signals. Thus, a complex interplay of intracellular NADPH and Ca concentrations regulate DUOX1 over a wide extent and may limit DUOX1 activity to a restricted range and spatial distribution.
PubMed: 38936256
DOI: 10.1016/j.redox.2024.103251 -
Redox Biology Jun 2024The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance...
INTRODUCTION
The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance and inflammation at rest and in response to acute exercise, and exercise performance in female athletes.
METHODS
Twelve female endurance athletes (age: 26.8 ± 3.4 yrs, maximum oxygen uptake (V˙O): 55.2 ± 5.1 mL × min × kg) were included in a randomized, single-blinded crossover study. They were allocated to begin with either 14 days of optimal energy availability diet (OEA, 52 ± 2 kcal × kg fat free mass (FFM) × day) or LEA diet (22 ± 2 kcal × kg FFM × day), followed by 3 days of refueling (OEA) with maintained training volume. Peripheral blood mononuclear cells (PBMCs) were isolated, and plasma obtained at rest before and after each dietary period. The PBMCs were used for analysis of mitochondrial respiration and HO emission and specific proteins. Exercise performance was assessed on cycle by a 20-min time trial and time to exhaustion at an intensity corresponding to ∼110 % V˙O).
RESULTS
LEA was associated with a 94 % (P = 0.003) increase in PBMC NADPH oxidase 2 protein content, and a 22 % (P = 0.013) increase in systemic cortisol. LEA also caused an alteration of several inflammatory related proteins (P < 0.05). Acute exercise augmented HO emission in PBMCs (P < 0.001) following both OEA and LEA, but to a greater extent following LEA. LEA also reduced the mobilization of white blood cells with acute exercise. After LEA, performance was reduced in both exercise tests (P < 0.001), and the reduced time trial performance remained after the 3 days of refueling (P < 0.001).
CONCLUSION
14 days of LEA in female athletes increased cortisol levels and had a pronounced effect on the immune system, including increased capacity for ROS production, altered plasma inflammatory proteome and lowered exercise induced mobilization of leukocytes. Furthermore, LEA resulted in a sustained impairment in exercise performance.
PubMed: 38936255
DOI: 10.1016/j.redox.2024.103250 -
Developmental Cognitive Neuroscience Jun 2024Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry....
Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry. Functional magnetic resonance imaging findings of increased ventral striatum (VS) recruitment by reward prospects in adolescents compared to adults support this theory. Other studies found blunted VS recruitment by reward-predictive cues in adolescents compared to adults. Task features may explain this discrepancy but have never been systematically explored. Adolescents and adults performed a novel reward task that holds constant the expected value of all rewards but varies whether rewards are dependent on vigilance-intensive responding versus making a lucky choice during a relaxed response window. We examined group by sub-task contrast differences in activation of VS and more motoric regions of striatum in response to anticipatory cues. Reward anticipation in both task conditions activated portions of striatum in both groups. In voxel-wise comparison, adults showed greater anticipatory recruitment of VS in trials involving choice during a relaxed time window, not in the more vigilance-demanding trials as hypothesized. In accord with our hypotheses, however, adults showed greater activation in dorsal striatum and putamen volumes of interest during reward anticipation under vigilance-demanding conditions. Following trial outcome notifications, adolescents showed greater activation of the VS during reward notification but lower activation during loss notification. These data extend findings of cross-sectional age-group differences in incentive-anticipatory recruitment of striatum, by demonstrating in adults relatively greater recruitment of motor effector regions of striatum by attentional and motor demands.
PubMed: 38936253
DOI: 10.1016/j.dcn.2024.101412 -
Jornal Brasileiro de Nefrologia 2024Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a...
INTRODUCTION
Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a Brazilian sample is sparce. Therefore, the aim of this study was to identify risk factors for renal outcomes and death in a Brazilian cohort of ADPKD patients.
METHODS
Patients had the first medical appointment between January 2002 and December 2014, and were followed up until December 2019. Associations between clinical and laboratory variables with the primary outcome (sustained decrease of at least 57% in the eGFR from baseline, need for dialysis or renal transplantation) and the secondary outcome (death from any cause) were analyzed using a multiple Cox regression model. Among 80 ADPKD patients, those under 18 years, with glomerular filtration rate <30 mL/min/1.73 m2, and/or those with missing data were excluded. There were 70 patients followed.
RESULTS
The factors independently associated with the renal outcomes were total kidney length - adjusted Hazard Ratio (HR) with a 95% confidence interval (95% CI): 1.137 (1.057-1.224), glomerular filtration rate - HR (95% CI): 0.970 (0.949-0.992), and serum uric acid level - HR (95% CI): 1.643 (1.118-2.415). Diabetes mellitus - HR (95% CI): 8.115 (1.985-33.180) and glomerular filtration rate - HR (95% CI): 0.957 (0.919-0.997) were associated with the secondary outcome.
CONCLUSIONS
These findings corroborate the hypothesis that total kidney length, glomerular filtration rate and serum uric acid level may be important prognostic predictors of ADPKD in a Brazilian cohort, which could help to select patients who require closer follow up.
Topics: Humans; Polycystic Kidney, Autosomal Dominant; Male; Female; Disease Progression; Brazil; Glomerular Filtration Rate; Adult; Middle Aged; Risk Factors; Cohort Studies; Uric Acid; Retrospective Studies
PubMed: 38935976
DOI: 10.1590/2175-8239-JBN-2023-0040en -
Journal of Medical Internet Research Jun 2024The US health care delivery system does not systematically engage or support family or friend care partners. Meanwhile, the uptake and familiarity of portals to personal...
The US health care delivery system does not systematically engage or support family or friend care partners. Meanwhile, the uptake and familiarity of portals to personal health information are increasing among patients. Technology innovations, such as shared access to the portal, use separate identity credentials to differentiate between patients and care partners. Although not well-known, or commonly used, shared access allows patients to identify who they do and do not want to be involved in their care. However, the processes for patients to grant shared access to portals are often limited or so onerous that interested patients and care partners often circumvent the process entirely. As a result, the vast majority of care partners resort to accessing portals using a patient's identity credentials-a "do-it-yourself" solution in conflict with a health systems' legal responsibility to protect patient privacy and autonomy. The personal narratives in this viewpoint (shared by permission) elaborate on quantitative studies and provide first-person snapshots of challenges faced by patients and families as they attempt to gain or grant shared access during crucial moments in their lives. As digital modalities increase patient roles in health care interactions, so does the importance of making shared access work for all stakeholders involved-patients, clinicians, and care partners. Electronic health record vendors must recognize that both patients and care partners are important users of their products, and health care organizations must acknowledge and support the critical contributions of care partners as distinct from patients.
Topics: Humans; Patient Portals; Electronic Health Records; Caregivers; Patient Participation
PubMed: 38935963
DOI: 10.2196/49394 -
JMIR Bioinformatics and Biotechnology Jul 2023While genomic variations can provide valuable information for health care and ancestry, the privacy of individual genomic data must be protected. Thus, a secure...
BACKGROUND
While genomic variations can provide valuable information for health care and ancestry, the privacy of individual genomic data must be protected. Thus, a secure environment is desirable for a human DNA database such that the total data are queryable but not directly accessible to involved parties (eg, data hosts and hospitals) and that the query results are learned only by the user or authorized party.
OBJECTIVE
In this study, we provide efficient and secure computations on panels of single nucleotide polymorphisms (SNPs) from genomic sequences as computed under the following set operations: union, intersection, set difference, and symmetric difference.
METHODS
Using these operations, we can compute similarity metrics, such as the Jaccard similarity, which could allow querying a DNA database to find the same person and genetic relatives securely. We analyzed various security paradigms and show metrics for the protocols under several security assumptions, such as semihonest, malicious with honest majority, and malicious with a malicious majority.
RESULTS
We show that our methods can be used practically on realistically sized data. Specifically, we can compute the Jaccard similarity of two genomes when considering sets of SNPs, each with 400,000 SNPs, in 2.16 seconds with the assumption of a malicious adversary in an honest majority and 0.36 seconds under a semihonest model.
CONCLUSIONS
Our methods may help adopt trusted environments for hosting individual genomic data with end-to-end data security.
PubMed: 38935952
DOI: 10.2196/44700 -
JMIR MHealth and UHealth Jun 2024Rising rates of psychological distress (symptoms of depression, anxiety, and stress) among adults in the United States necessitate effective mental wellness...
BACKGROUND
Rising rates of psychological distress (symptoms of depression, anxiety, and stress) among adults in the United States necessitate effective mental wellness interventions. Despite the prevalence of smartphone app-based programs, research on their efficacy is limited, with only 14% showing clinically validated evidence. Our study evaluates Noom Mood, a commercially available smartphone-based app that uses cognitive behavioral therapy and mindfulness-based programming. In this study, we address gaps in the existing literature by examining postintervention outcomes and the broader impact on mental wellness.
OBJECTIVE
Noom Mood is a smartphone-based mental wellness program designed to be used by the general population. This prospective study evaluates the efficacy and postintervention outcomes of Noom Mood. We aim to address the rising psychological distress among adults in the United States.
METHODS
A 1-arm study design was used, with participants having access to the Noom Mood program for 16 weeks (N=273). Surveys were conducted at baseline, week 4, week 8, week 12, week 16, and week 32 (16 weeks' postprogram follow-up). This study assessed a range of mental health outcomes, including anxiety symptoms, depressive symptoms, perceived stress, well-being, quality of life, coping, emotion regulation, sleep, and workplace productivity (absenteeism or presenteeism).
RESULTS
The mean age of participants was 40.5 (SD 11.7) years. Statistically significant improvements in anxiety symptoms, depressive symptoms, and perceived stress were observed by week 4 and maintained through the 16-week intervention and the 32-week follow-up. The largest changes were observed in the first 4 weeks (29% lower, 25% lower, and 15% lower for anxiety symptoms, depressive symptoms, and perceived stress, respectively), and only small improvements were observed afterward. Reductions in clinically relevant anxiety (7-item generalized anxiety disorder scale) and depression (8-item Patient Health Questionnaire depression scale) criteria were also maintained from program initiation through the 16-week intervention and the 32-week follow-up. Work productivity also showed statistically significant results, with participants gaining 2.57 productive work days from baseline at 16 weeks, and remaining relatively stable (2.23 productive work days gained) at follow-up (32 weeks). Additionally, effects across all coping, sleep disturbance (23% lower at 32 weeks), and emotion dysregulation variables exhibited positive and significant trends at all time points (15% higher, 23% lower, and 25% higher respectively at 32 weeks).
CONCLUSIONS
This study contributes insights into the promising positive impact of Noom Mood on mental health and well-being outcomes, extending beyond the intervention phase. Though more rigorous studies are necessary to understand the mechanism of action at play, this exploratory study addresses critical gaps in the literature, highlighting the potential of smartphone-based mental wellness programs to lessen barriers to mental health support and improve diverse dimensions of well-being. Future research should explore the scalability, feasibility, and long-term adherence of such interventions across diverse populations.
Topics: Humans; Prospective Studies; Male; Female; Adult; Middle Aged; Surveys and Questionnaires; Mobile Applications; Health Promotion; Cognitive Behavioral Therapy; Program Evaluation; United States; Mindfulness; Quality of Life
PubMed: 38935946
DOI: 10.2196/54634 -
JMIR Research Protocols Jun 2024Sound therapy methods have seen a surge in popularity, with a predominant focus on music among all types of sound stimulation. There is substantial evidence documenting... (Review)
Review
BACKGROUND
Sound therapy methods have seen a surge in popularity, with a predominant focus on music among all types of sound stimulation. There is substantial evidence documenting the integrative impact of music therapy on psycho-emotional and physiological outcomes, rendering it beneficial for addressing stress-related conditions such as pain syndromes, depression, and anxiety. Despite these advancements, the therapeutic aspects of sound, as well as the mechanisms underlying its efficacy, remain incompletely understood. Existing research on music as a holistic cultural phenomenon often overlooks crucial aspects of sound therapy mechanisms, particularly those related to speech acoustics or the so-called "music of speech."
OBJECTIVE
This study aims to provide an overview of empirical research on sound interventions to elucidate the mechanism underlying their positive effects. Specifically, we will focus on identifying therapeutic factors and mechanisms of change associated with sound interventions. Our analysis will compare the most prevalent types of sound interventions reported in clinical studies and experiments. Moreover, we will explore the therapeutic effects of sound beyond music, encompassing natural human speech and intermediate forms such as traditional poetry performances.
METHODS
This review adheres to the methodological guidance of the Joanna Briggs Institute and follows the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist for reporting review studies, which is adapted from the Arksey and O'Malley framework. Our search strategy encompasses PubMed, Web of Science, Scopus, and PsycINFO or EBSCOhost, covering literature from 1990 to the present. Among the different study types, randomized controlled trials, clinical trials, laboratory experiments, and field experiments were included.
RESULTS
Data collection began in October 2022. We found a total of 2027 items. Our initial search uncovered an asymmetry in the distribution of studies, with a larger number focused on music therapy compared with those exploring prosody in spoken interventions such as guided meditation or hypnosis. We extracted and selected papers using Rayyan software (Rayyan) and identified 41 eligible papers after title and abstract screening. The completion of the scoping review is anticipated by October 2024, with key steps comprising the analysis of findings by May 2024, drafting and revising the study by July 2024, and submitting the paper for publication in October 2024.
CONCLUSIONS
In the next step, we will conduct a quality evaluation of the papers and then chart and group the therapeutic factors extracted from them. This process aims to unveil conceptual gaps in existing studies. Gray literature sources, such as Google Scholar, ClinicalTrials.gov, nonindexed conferences, and reference list searches of retrieved studies, will be added to our search strategy to increase the number of relevant papers that we cover.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/54030.
Topics: Humans; Stress, Psychological; Music Therapy; Adult
PubMed: 38935945
DOI: 10.2196/54030 -
Aging Jun 2024The primary objective of this study was to assess the diagnostic potential of galectin-3 (Gal-3), fractalkine (FKN), interleukin (IL)-6, microRNA(miR)-21, and cardiac...
OBJECTIVE
The primary objective of this study was to assess the diagnostic potential of galectin-3 (Gal-3), fractalkine (FKN), interleukin (IL)-6, microRNA(miR)-21, and cardiac troponin I (cTnI) in patients with ischemic cardiomyopathy (ICM).
METHOD
A total of 78 ICM patients (Case group) and 80 healthy volunteers (Control group) admitted to our hospital for treatment or physical examination from Aug. 2018 to Feb. 2020 were included in the current study. The serum concentration of Gal-3, FKN, IL-6, miR-21, and plasma expression of cTnI of both groups were determined. The severity of ICM was classified using New York Heart Association (NYHA) scale.
RESULTS
When compared with the control group, the case group had a significantly high blood concentration of Gal-3, FKN, IL-6, miR-21, and cTnI ( < 0.001). NYHA class II patients had lower blood levels of Gal-3, FKN, IL-6, miR-21, and cTnI than that in patients of NYHA class III and IV without statistical significance ( > 0.05). However, statistical significance could be achieved when comparing the above-analyzed markers in patients classified between class III and IV. Correlation analysis also revealed that serum levels of Gal-3, FKN, IL-6, miR-21, and cTnI were positively correlated with NYHA classification (R = 0.564, 0.621, 0.792, 0.981, < 0.05).
CONCLUSION
Our study revealed that up-regulated serum Gal-3, FKN, IL-6, miR-21, and cTnI levels were closely related to the progression of ICM. This association implies that these biomarkers have diagnostic potential, offering a promising avenue for early detection and monitoring of ICM progression.
Topics: Humans; Female; Male; Troponin I; Interleukin-6; MicroRNAs; Chemokine CX3CL1; Middle Aged; Galectin 3; Biomarkers; Aged; Myocardial Ischemia; Cardiomyopathies; Case-Control Studies; Galectins; Blood Proteins
PubMed: 38935941
DOI: 10.18632/aging.205953 -
Emerging Microbes & Infections Dec 2024Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral...
Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (= 0.048) and 96 (= 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010-37.377; = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770). ClinicalTrials.gov identifier: NCT04098770. ClinicalTrials.gov identifier: NCT02651376.
Topics: Humans; Male; Female; Adult; Middle Aged; Immunotherapy, Adoptive; Immunocompromised Host; HLA Antigens; Acquired Immunodeficiency Syndrome; Treatment Outcome; AIDS-Related Opportunistic Infections; Transplantation, Homologous; CD4-Positive T-Lymphocytes; CD4 Lymphocyte Count
PubMed: 38935839
DOI: 10.1080/22221751.2024.2364744