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Sarcoidosis, Vasculitis, and Diffuse... Jun 2024Cardiac sarcoidosis is associated with significant morbidity and mortality. Immunosuppressive treatment focuses on suppressing myocardial inflammation, which can lead to...
Cardiac sarcoidosis is associated with significant morbidity and mortality. Immunosuppressive treatment focuses on suppressing myocardial inflammation, which can lead to major adverse events especially when progressing to fibrosis. Conventional management usually includes steroids and steroid sparing agents such as methotrexate and azathioprine. Tumour necrosis factor alpha inhibitors are often reserved for those with a worsening clinical status and/or evidence of persistent inflammatory activity despite conventional therapy. Refractory cardiac sarcoidosis (CS) can be defined as the persistence or progression of active disease, evidenced either by lack of clinical response or persistence or progression of imaging abnormalities, despite being on conventional therapy. In the United Kingdom, tumour necrosis factor alpha inhibitors are currently not licensed for cardiac sarcoidosis as there are no randomised controlled trials to assess the efficacy of infliximab in this patient cohort. In this study, we present the outcomes of six patients treated with infliximab for refractory cardiac sarcoidosis at Royal Brompton Hospital and performed a systematic review of the existing literature on use of infliximab in cardiac sarcoidosis. We searched the Cochrane Library, OVID Medline, OVID Embase, Web of Science and Pubmed to identify 7 full-text studies assessing the role of infliximab in the management of cardiac sarcoidosis. Infliximab was found to play a vital role in stabilising refractory cardiac sarcoidosis by stemming clinical deterioration, arrythmia burden and even reducing steroids requirements. Further prospective trial data is necessary to validate these findings.
PubMed: 38940716
DOI: 10.36141/svdld.v41i2.14484 -
Journal of Integrative Neuroscience May 2024Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain and the formation of intracellular protein aggregates known as Lewy bodies, of which a major component is the protein α-synuclein. Several studies have suggested that mitochondria play a central role in the pathogenesis of PD, encompassing both familial and sporadic forms of the disease. Mitochondrial dysfunction is attributed to bioenergetic impairment, increased oxidative stress, damage to mitochondrial DNA, and alteration in mitochondrial morphology. These alterations may contribute to improper functioning of the central nervous system and ultimately lead to neurodegeneration. The perturbation of mitochondrial function makes it a potential target, worthy of exploration for neuroprotective therapies and to improve mitochondrial health in PD. Thus, in the current review, we provide an update on mitochondria-based therapeutic approaches toward α-synucleinopathies in PD.
Topics: Humans; Parkinson Disease; Synucleinopathies; Mitochondria; Animals; alpha-Synuclein
PubMed: 38940084
DOI: 10.31083/j.jin2306109 -
Frontiers in Bioscience (Landmark... Jun 2024The inhibitors of mammalian target of rapapmycin (mTOR), everolimus, temsirolimus and rapamycin, have a wide range of clinical utility; however, as is inevitably the... (Review)
Review
The inhibitors of mammalian target of rapapmycin (mTOR), everolimus, temsirolimus and rapamycin, have a wide range of clinical utility; however, as is inevitably the case with other chemotherapeutic agents, resistance development constrains their effectiveness. One putative mechanism of resistance is the promotion of autophagy, which is a direct consequence of the inhibition of the mTOR signaling pathway. Autophagy is primarily considered to be a cytoprotective survival mechanism, whereby cytoplasmic components are recycled to generate energy and metabolic intermediates. The autophagy induced by everolimus and temsirolimus appears to play a largely protective function, whereas a cytotoxic function appears to predominate in the case of rapamycin. In this review we provide an overview of the autophagy induced in response to mTOR inhibitors in different tumor models in an effort to determine whether autophagy targeting could be of clinical utility as adjuvant therapy in association with mTOR inhibition.
Topics: Humans; Autophagy; TOR Serine-Threonine Kinases; MTOR Inhibitors; Animals; Neoplasms; Signal Transduction; Antineoplastic Agents; Cytoprotection; Sirolimus
PubMed: 38940039
DOI: 10.31083/j.fbl2906231 -
Frontiers in Pharmacology 2024Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play... (Review)
Review
Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play crucial roles in various cancers, including urologic malignancies. This article provides a summary of the latest research findings, suggesting that lncRNA-mediated autophagy could either suppress or promote tumors in prostate, kidney, and bladder cancers. The intricate network involving different lncRNAs, target genes, and mediated signaling pathways plays a crucial role in urological malignancies by modulating the autophagic process. Dysregulated expression of lncRNAs can disrupt autophagy, leading to tumorigenesis, progression, and enhanced resistance to therapy. Consequently, targeting particular lncRNAs that control autophagy could serve as a dependable diagnostic tool and a promising prognostic biomarker in urologic oncology, while also holding potential as an effective therapeutic approach.
PubMed: 38939836
DOI: 10.3389/fphar.2024.1405199 -
Oxidative Medicine and Cellular... 2024Spinal cord injury (SCI) is a common neurological disease worldwide, often resulting in a substantial decrease in quality of life, disability, and in severe cases, even... (Review)
Review
Spinal cord injury (SCI) is a common neurological disease worldwide, often resulting in a substantial decrease in quality of life, disability, and in severe cases, even death. Unfortunately, there is currently no effective treatment for this disease. Nevertheless, current basic and clinical evidence suggests that vitamins, with their antioxidant properties and biological functions, may play a valuable role in improving the quality of life for individuals with SCI. They can promote overall health and facilitate the healing process. In this review, we discuss the mechanisms and therapeutic potential of vitamins in the treatment of SCI.
Topics: Spinal Cord Injuries; Humans; Vitamins; Animals; Antioxidants
PubMed: 38938696
DOI: 10.1155/2024/4293391 -
Hemodialysis International.... Jun 2024Continuous renal replacement therapy (CKRT) is delivered to some of the most critically ill patients in hospitals. This therapy is expensive and requires coordination of...
BACKGROUND
Continuous renal replacement therapy (CKRT) is delivered to some of the most critically ill patients in hospitals. This therapy is expensive and requires coordination of multidisciplinary teams to ensure the prescribed dose is delivered. With increased demands on the critical care nursing staff and increased complexities of patients admitted to critical care units, we evaluated the role of specialized renal technologists in ensuring the prescribed dose is delivered. Therefore, the aim of this study is to investigate the impact of supporting intensive care unit nurses with specialized renal technologists on optimizing efficiency of CKRT sessions in the United Arab Emirates.
METHODS
This is a retrospective study that compared critically ill patients on CKRT overseen by specialized renal technologists versus who are non-covered in the year 2021.
RESULTS
A total of 331 sessions on 158 patients were included in the study. The mean filter life was longer in specialized renal technologists-covered patients compared to the non-covered group (66 vs. 59 h, p = 0.019). After adjustment by multiple regression analysis for risk factors (i.e., age, gender, mechanical ventilation, sepsis, mean arterial pressure, vasopressors, and SOFA) that may affect CKRT machines' filter life, presence of a specialized renal technologists resulted in significantly longer filter life (co-efficient 0.129; CI 95% 1.080, 11.970; p-value: 0.019).
CONCLUSION
Our study suggests that specialized renal technologists play a vital role in prolonging CKRT machine's filter life span and optimizing CKRT machine's efficiency. Further research should focus on other potential benefits of having specialized renal technologists performing CKRT sessions, and to confirm the finding of this study. Additionally, a cost-benefit analysis could be conducted to determine the economic impact of having specialized teams performing CKRT.
PubMed: 38937144
DOI: 10.1111/hdi.13167 -
Neurologic Clinics Aug 2024This article provides a comprehensive review of widely utilized stroke scales in both routine clinical settings and research. These scales are crucial for planning... (Review)
Review
This article provides a comprehensive review of widely utilized stroke scales in both routine clinical settings and research. These scales are crucial for planning treatment, predicting outcomes, and helping stroke patients recover. They also play a pivotal role in planning, executing, and comprehending stroke clinical trials. Each scale presents distinct advantages and limitations, and the authors explore these aspects within the article. The authors' intention is to provide the reader with practical insights for a clear understanding of these scales, and their effective use in their clinical practice.
Topics: Humans; Stroke; Cerebrovascular Disorders; Severity of Illness Index
PubMed: 38937040
DOI: 10.1016/j.ncl.2024.03.008 -
Pharmacological Research Jun 2024The Frizzleds (FZDs) receptors on the cell surface belong to the class F of G protein-coupled receptors (GPCRs) which are the major receptors of WNT protein that... (Review)
Review
The Frizzleds (FZDs) receptors on the cell surface belong to the class F of G protein-coupled receptors (GPCRs) which are the major receptors of WNT protein that mediates the classical WNT signaling pathway and other non-classical pathways. Besides, the FZDs also play a core role in tissue regeneration and tumor occurrence. With the structure and mechanism of FZDs activation becoming clearer, a series of FZDs modulators (inhibitors and agonists) have been developed, with the hope of bringing benefits to the treatment of cancer and degenerative diseases. Most of the FZDs inhibitors (small molecules, antibodies or designed protein inhibitors) block WNT signaling through binding to the cysteine-rich domain (CRD) of FZDs. Several small molecules impede FZDs activation by targeting to the third intracellular domain or the transmembrane domain of FZDs. However, three small molecules (FZM1.8, SAG1.3 and purmorphamine) activate the FZDs through direct interaction with the transmembrane domain. Another type of FZDs agonists are bivalent or tetravalent antibodies which activate the WNT signaling via inducing FZD-LRP5/6 heterodimerization. In this article, we reviewed the FZDs modulators reported in recent years, summarized the critical molecules' discovery processes and the elucidated relevant structural and pharmacological mechanisms. We believe the summaried molecular mechanisms of the relevant modulators could provide important guidance and reference for the future development of FZD modulators.
PubMed: 38936522
DOI: 10.1016/j.phrs.2024.107286 -
Biochimica Et Biophysica Acta. Reviews... Jun 2024Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as "genomic junk" to key players in cancer progression.... (Review)
Review
Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as "genomic junk" to key players in cancer progression. Contemporary research links TE regulatory disruptions with cancer development, underscoring their therapeutic potential. Advances in long-read sequencing, computational analytics, single-cell sequencing, proteomics, and CRISPR-Cas9 technologies have enriched our understanding of TEs' clinical implications, notably their impact on genome architecture, gene regulation, and evolutionary processes. In cancer, TEs, including LINE-1, Alus, and LTRs, demonstrate altered patterns, influencing both tumorigenic and tumor-suppressive mechanisms. TE-derived nucleic acids and tumor antigens play critical roles in tumor immunity, bridging innate and adaptive responses. Given their central role in oncology, TE-targeted therapies, particularly through reverse transcriptase inhibitors and epigenetic modulators, represent a novel avenue in cancer treatment. Combining these TE-focused strategies with existing chemotherapy or immunotherapy regimens could enhance efficacy and offer a new dimension in cancer treatment. This review delves into recent TE detection advancements, explores their multifaceted roles in tumorigenesis and immune regulation, discusses emerging diagnostic and therapeutic approaches centered on TEs, and anticipates future directions in cancer research.
PubMed: 38936517
DOI: 10.1016/j.bbcan.2024.189143 -
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