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1.
Expert Opin Drug Saf ; 23(7): 845-853, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38938223

ABSTRACT

INTRODUCTION: Sugammadex, a novel selective antagonist of non-depolarizing neuromuscular blocking agents, has been shown to rapidly and effectively reverse moderate and deep paralysis in adults and pediatric patients over age 2, improving patient recovery and reducing the risk of postoperative complications. AREAS COVERED: Since the use of sugammadex in patients under age 2 is not widely studied, we aim to provide an overview on the drug's application and potential use in infants and neonates. There is a limited but growing body of evidence for the safe, efficacious use of sugammadex in children under age 2. Relevant studies were identified from the most updated data including case reports, clinical trials, systematic reviews, and meta analyses. EXPERT OPINION: The results suggest that at a dose of 2 to 4 mg/kg of sugammadex can be safely used to rapidly and effectively reverse neuromuscular blockade in neonates and infants; it is non-inferior based on incidence of adverse events compared to neostigmine. Additionally, sugammadex doses between 8 and 16 mg/kg may be used as a rescue agent for infants during 'can't intubate, can't ventilate' crisis. Overall, sugammadex offers new value in the perioperative care of patients under age 2, with further studies warranted to better understand its application and full effect in the pediatric population.


Subject(s)
Dose-Response Relationship, Drug , Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents , Sugammadex , Humans , Sugammadex/administration & dosage , Sugammadex/adverse effects , Sugammadex/pharmacology , Infant , Neuromuscular Blockade/methods , Neuromuscular Blockade/adverse effects , Infant, Newborn , Age Factors , Neuromuscular Nondepolarizing Agents/administration & dosage , Neuromuscular Nondepolarizing Agents/adverse effects , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Postoperative Complications/prevention & control , Neostigmine/administration & dosage , Neostigmine/adverse effects , Perioperative Care/methods
2.
Nat Commun ; 15(1): 3963, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38729943

ABSTRACT

Translation initiation in bacteria is frequently regulated by various structures in the 5' untranslated region (5'UTR). Previously, we demonstrated that G-quadruplex (G4) formation in non-template DNA enhances transcription. In this study, we aim to explore how G4 formation in mRNA (RG4) at 5'UTR impacts translation using a T7-based in vitro translation system and in E. coli. We show that RG4 strongly promotes translation efficiency in a size-dependent manner. Additionally, inserting a hairpin upstream of the RG4 further enhances translation efficiency, reaching up to a 12-fold increase. We find that the RG4-dependent effect is not due to increased ribosome affinity, ribosome binding site accessibility, or mRNA stability. We propose a physical barrier model in which bulky structures in 5'UTR biases ribosome movement toward the downstream start codon, thereby increasing the translation output. This study provides biophysical insights into the regulatory role of 5'UTR structures in in vitro and bacterial translation, highlighting their potential applications in tuning gene expression.


Subject(s)
5' Untranslated Regions , Escherichia coli , G-Quadruplexes , Protein Biosynthesis , RNA, Messenger , Ribosomes , 5' Untranslated Regions/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Ribosomes/metabolism , Ribosomes/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics , Nucleic Acid Conformation , RNA Stability , Binding Sites
3.
Brain Sci ; 14(4)2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38671951

ABSTRACT

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex (L-DLPFC) for enhancing cognitive flexibility based on performance on a cognitive task. First, forty healthy participants had their single target site at the L-DLPFC determined based on each individual's performance on a random letter generation task. Participants then received, in a cross-over single-blinded experimental design, a single session of intermittent theta burst stimulation (iTBS) to their individualised DLPFC target site, an active control site and sham iTBS. Following each treatment condition, participants completed the Task Switching task and Colour-Word Stroop test. There was no significant main effect of treatment condition on the primary outcome measure of switch reaction times from the Task Switching task [F = 1.16 (2, 21.6), p = 0.33] or for any of the secondary cognitive outcome measures. The current results do not support the use of our novel individualised targeting methodology for enhancing cognitive flexibility in healthy participants. Research into alternative methodological targeting approaches is required to further improve rTMS's cognitive enhancing effects.

5.
Health Psychol ; 43(6): 397-417, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38330307

ABSTRACT

OBJECTIVE: A systematic review and meta-analysis was conducted to examine associations between attempts to cope with stressors through the two facets of emotional approach coping (EAC; i.e., processing and expressing stressor-related emotions) and indicators of physical and mental health. METHOD: EBSCO databases including MEDLINE, PsycINFO, and Cochrane Collections were searched from inception to November 2022. In all, 86 studies were included in a meta-analytic evaluation using a random-effects model and meta-regression analysis. RESULTS: EAC was associated with better overall health (r = .05; p = .04; 95% confidence interval = [.003, .10]). Emotional expression (EE) and emotional processing (EP) also were positively associated with better overall health, although these relationships were not statistically significant. In meta-regressions examining specific health domains, EAC was linked to better health in biological/physiological, physical, and resilience-related psychological adjustment domains, as well as to worse outcomes in the risk-related psychological adjustment and mental/emotional distress domains. Results for EE and EP mirrored this pattern; however, only EP was associated with more engagement in health-promoting behaviors. CONCLUSIONS: Coping with stressors through emotional approach appears to be associated with better mental and physical health, with some observed differences for EE and EP. The literature on EAC and health is marked by heterogeneity across study methodologies and measures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Adaptation, Psychological , Emotions , Stress, Psychological , Humans , Stress, Psychological/psychology
6.
Res Sq ; 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37790436

ABSTRACT

Translation initiation in bacteria is frequently regulated by various structures in the 5' untranslated region (5'UTR). Previously, we demonstrated that G-quadruplex (G4) formation in non-template DNA enhances transcription. In this study, we aimed to explore how G4 formation in mRNA (RG4) at 5'UTR impacts translation using a T7-based in vitro translation system and in E. coli. We showed that RG4 strongly promotes translation efficiency in a size-dependent manner. Additionally, inserting a hairpin upstream of the RG4 further enhances translation efficiency, reaching up to a 12-fold increase. We found that the RG4-dependent effect is not due to increased ribosome affinity, ribosome binding site accessibility, or mRNA stability. We proposed a physical barrier model in which bulky structures in 5'UTR prevent ribosome dislodging and thereby increase the translation output. This study provides biophysical insights into the regulatory role of 5'UTR structures in bacterial translation, highlighting their potential applications in tuning gene expression.

7.
Kidney Med ; 5(10): 100707, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37771916

ABSTRACT

Rationale & Objective: Limited data exist on patient perspectives of the implications of kidney biopsies. We explored patients' perspectives alongside those of clinicians to better understand how kidney biopsies affect patients' viewpoints and the clinical utility of biopsies. Study Design: Prospective Cohort Study. Setting & Participants: Patient participants and clinicians in the Kidney Precision Medicine Project, a prospective cohort study of patients who undergo a research protocol biopsy, at 9 recruitment sites across the United States. Surveys were completed at enrollment before biopsy and additional timepoints after biopsy (participants: 28 days, 6 months; clinicians: 2 weeks). Analytical Approach: Kappa statistics assessed prebiopsy etiology concordance between clinicians and participants. Participant perspectives after biopsy were analyzed using a thematic approach. Clinician ratings of clinical management value were compared to prebiopsy ratings with Wilcoxon matched-pairs signed-rank tests and paired t tests. Results: A total of 167 participants undergoing biopsy (124 participants with chronic kidney disease [CKD], 43 participants with acute kidney injury [AKI]) and 58 clinicians were included in this study. CKD participants and clinicians had low etiology concordance for the 2 leading causes of CKD: diabetes (k = 0.358) and hypertension (k = 0.081). At 28 days postbiopsy, 46 (84%) participants reported that the biopsy affected their understanding of their diagnosis, and 21 (38%) participants reported that the results of the biopsy affected their medications. Participants also shared biopsy impressions in free-text responses, including impacts on lifestyle and concurrent condition management. The biopsy positively shifted clinician perceptions of the procedure's clinical management benefits, while perceptions of prognostic value decreased and diagnostic ratings remained unchanged. Limitations: Our study did not have demographic data of clinicians and could not provide insight into postbiopsy experiences for participants who did not respond to follow-up surveys. Conclusions: Participant perspectives of the personal implications of kidney biopsy can be integrated into shared decision-making between clinicians and patients. Enhanced biopsy reports and interactions between nephrologists and pathologists could augment the management and prognostic value of kidney biopsies. Plain-Language Summary: The utility of kidney biopsy is debated among clinicians, and patients' perspectives are even less explored. To address these gaps, we synthesized perspectives from clinicians and patient participants of the Kidney Precision Medicine Project (KPMP). Both before and after biopsy, clinicians were surveyed on how the procedure affected their clinical management, diagnosis, and prognosis. After biopsy, participants shared how the procedure affected their diagnosis, medication, and lifestyle changes. Clinicians and patients shared an appreciation for the biopsy's impact on medical management but diverged in their takeaways on diagnosis and prognosis. These findings highlight the need for greater collaboration between patients and clinicians, particularly as they navigate shared decision-making when considering kidney biopsy.

8.
Support Care Cancer ; 31(9): 538, 2023 Aug 26.
Article in English | MEDLINE | ID: mdl-37632538

ABSTRACT

OBJECTIVE: Systematic understanding of patients' unmet needs is essential for providing effective supportive care. This study sought to compare the unmet needs of patients with cancer identified by health care providers (HCPs) among four major healthcare systems. METHODS: HCPs (n = 247) participated in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey, evaluating their patients' unmet needs. The country of HCPs was grouped into four major healthcare systems: Beveridge model, Bismarck model, National Health Insurance model, and out-of-pocket model. RESULTS: Most HCPs were from countries with the Bismarck model. Substantial levels (> 50%) of unmet needs in all domains are reported across the four healthcare systems. Pediatric patients/survivors living in countries under out-of-pocket healthcare model were evaluated to have less unmet needs for managing decline in physical or cognitive functioning and insomnia/sleep difficulty/fatigue, than those in countries under Beveridge, Bismarck, and National Health Insurance models. Moreover, middle-aged patients/survivors under Beveridge and National Health Insurance models were likely to have greater unmet needs for dealing with cancer-related financial concerns than those under Bismarck model. CONCLUSION: This study provides valuable insights into the unmet needs of patients with cancer in different healthcare systems, highlighting the significance of targeted interventions to address the unique needs of patients across diverse healthcare systems. Further investigation is warranted to identify the system factors associated with patients' unmet needs, enabling the development of effective healthcare policies and interventions to comprehensively address the multifaceted needs of patients with cancer.


Subject(s)
Neoplasms , Survivorship , Middle Aged , Humans , Child , Psycho-Oncology , Survival , Neoplasms/therapy , Health Personnel
9.
Front Neurol ; 14: 1150135, 2023.
Article in English | MEDLINE | ID: mdl-37351266

ABSTRACT

Anesthesia-induced neurotoxicity is a set of unfavorable adverse effects on central or peripheral nervous systems associated with administration of anesthesia. Several animal model studies from the early 2000's, from rodents to non-human primates, have shown that general anesthetics cause neuroapoptosis and impairment in neurodevelopment. It has been difficult to translate this evidence to clinical practice. However, some studies suggest lasting behavioral effects in humans due to early anesthesia exposure. Dexmedetomidine is a sedative and analgesic with agonist activities on the alpha-2 (ɑ2) adrenoceptors as well as imidazoline type 2 (I2) receptors, allowing it to affect intracellular signaling and modulate cellular processes. In addition to being easily delivered, distributed, and eliminated from the body, dexmedetomidine stands out for its ability to offer neuroprotection against apoptosis, ischemia, and inflammation while preserving neuroplasticity, as demonstrated through many animal studies. This property puts dexmedetomidine in the unique position as an anesthetic that may circumvent the neurotoxicity potentially associated with anesthesia.

10.
Qual Life Res ; 32(11): 3185-3193, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37344728

ABSTRACT

PURPOSE: Do cancer survivors experience positive changes (i.e., posttraumatic growth; PTG) resulting in better quality of life? The issue has yet to yield consistent notions. This longitudinal study extends the literature on the role of PTG by examining the curvilinear relationship between PTG and Health-Related Quality of Life (HRQoL), and explored whether PTG predicts subsequent HRQoL in a quadratic relationship across 2 years following surgery. METHODS: Women with breast cancer (N = 359; Mage = 47.5) were assessed at five waves over two years. On every measurement occasion, PTG measured by the posttraumatic growth inventory and HRQoL measured by SF-36 were assessed. The five waves reflect major medical demands and related challenges in the breast cancer trajectory, in which 1-day, 3 months, 6 months, 12 months, and 24 months after surgery were adopted as the survey timing. In a series of hierarchical linear modeling (HLM) analyses, the time-lagged predictions of PTG (i.e., linear, quadratic) on HRQoL were examined, controlling demographic and medical covariates. RESULTS: The results revealed that the quadratic term of PTG consistently significantly predicted physical and mental health quality of life (PCS and MCS), while the linear term of PTG did not significantly predict PCS or MCS. CONCLUSION: With multi-wave longitudinal data, this study demonstrated that the relationship between PTG and HRQoL is curvilinear, and this finding extends to PTG's prediction of subsequent HRQoL. The quadratic relationship has critical implications for clinical assessment and intervention. Details are discussed.


Subject(s)
Breast Neoplasms , Cancer Survivors , Posttraumatic Growth, Psychological , Stress Disorders, Post-Traumatic , Humans , Female , Breast Neoplasms/surgery , Breast Neoplasms/psychology , Quality of Life/psychology , Cancer Survivors/psychology , Longitudinal Studies , Adaptation, Psychological , Stress Disorders, Post-Traumatic/psychology
11.
Eur Radiol ; 33(10): 6883-6891, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37083741

ABSTRACT

OBJECTIVES: To perform a systematic review comparing the diagnostic accuracy of MRI vs. CT for assessing pancreatic ductal adenocarcinoma (PDAC) vascular invasion. METHODS: MEDLINE, EMBASE, Cochrane Central, and Scopus were searched until December 2021 for diagnostic accuracy studies comparing MRI vs. CT to evaluate vascular invasion of pathologically confirmed PDAC in the same patients. Findings on resection or exploratory laparotomy were the preferred reference standard. Data extraction, risk of bias, and applicability assessment were performed by two authors using the Quality Assessment of Diagnostic Accuracy Studies-Comparative Tool. Bivariate random-effects meta-analysis and meta-regression were performed with 95% confidence intervals (95% CI). RESULTS: Three studies were included assessing 474 vessels without vascular invasion and 65 with vascular invasion in 107 patients. All patients were imaged using MRI at ≥ 1.5 T and a pancreatic protocol CT. No difference was shown between MRI and CT for diagnosing PDAC vascular invasion: MRI/CT sensitivity (95% CI) were 71% (47-87%)/74% (56-86%), and specificity were 97% (94-99%)/97% (94-98%). Sources of bias included selection bias from only a subset of CT patients undergoing MRI and verification bias from patients with unresectable disease not confirmed on surgery. No patients received neoadjuvant therapy prior to staging. CONCLUSIONS: Based on limited data, no difference was observed between MRI and pancreatic protocol CT for PDAC vascular invasion assessment. MRI may be an adequate substitute for pancreatic protocol CT in some patients, particularly those who have already had a single-phase CT. Larger and more recent cohort studies at low risk of bias, including patients who have received neoadjuvant therapy, are needed. CLINICAL RELEVANCE STATEMENT: Abdominal MRI performed similarly to pancreatic protocol CT at assessing pancreatic ductal adenocarcinoma vascular invasion, suggesting local staging is adequate in some patients using MRI. More data are needed using larger, more recent cohorts including patients with neoadjuvant treatment. KEY POINTS: • Based on limited data, no difference was found between MRI and pancreatic protocol CT sensitivity and specificity for diagnosing PDAC vascular invasion (p = 0.81, 0.73 respectively). • Risk of bias could be reduced in future PDAC MRI vs CT comparative diagnostic test accuracy research by ensuring all enrolled patients undergo both imaging modalities being compared in random order and regardless of the findings on either modality. • More studies are needed that directly compare the diagnostic performance of MRI and CT for PDAC staging after neoadjuvant therapy.


Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Tomography, X-Ray Computed/methods , Magnetic Resonance Imaging , Carcinoma, Pancreatic Ductal/diagnostic imaging , Sensitivity and Specificity , Diagnostic Tests, Routine , Pancreatic Neoplasms
12.
Ann Behav Med ; 57(9): 777-786, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37078969

ABSTRACT

BACKGROUND: Young adult testicular cancer survivors experience adverse impacts after treatment. We developed Goal-focused Emotion-regulation Therapy (GET) to improve distress symptoms, emotion regulation, and goal navigation skills. PURPOSE: This pilot study examined GET versus an active control intervention in young adult survivors of testicular cancer. METHODS: Seventy-five eligible survivors treated with chemotherapy were randomized to receive GET or Individual Supportive Listening (ISL). Study acceptability, engagement, and tolerability were examined, and intervention fidelity and therapeutic alliance were compared between arms. Preliminary efficacy was evaluated by effect sizes for between-group changes in primary (anxiety and depressive symptoms) and secondary (career confusion, goal navigation, and emotion regulation) outcomes from baseline to immediately and 3-month post-intervention. RESULTS: Among the 38 men randomized to GET, 81.1% completed all study sessions compared with 82.4% of the 37 men assigned to ISL. Fidelity to the intervention was 87% in GET. Therapeutic alliance wassignificantly higher among those receiving GET versus ISL. Participants exhibited a medium group-by-time effect size with greater reductions in depressive (d = 0.45) and anxiety (d = 0.29) symptoms for those in GET versus ISL, with a similar pattern at 3 months for depressive (d = 0.46) and anxiety (d = 0.46) symptoms. CONCLUSIONS: GET is a feasible and acceptable intervention for reducing adverse outcomes after testicular cancer for young adults. Observed effect sizes preliminarily suggest meaningful change, though should be interpreted with caution in small samples. GET may be a developmentally-matched behavioral approach to improve psychosocial function in this cancer group. CLINICAL TRIAL INFORMATION: Clinicaltrials.gov, NCT04150848. Registered on October 28, 2019.


Young adult testicular cancer survivors experience adverse impacts after treatment. Goal-focused Emotion-regulation Therapy (GET) was developed to improve distress symptoms, emotion regulation, and goal navigation skills. The aim of this pilot study was to examine GET versus a control intervention in young adult survivors of testicular cancer. Seventy-five survivors were randomly assigned to GET or Individual Supportive Listening (ISL). Indictors of acceptability, engagement, and tolerability were examined, and intervention fidelity and therapeutic alliance were compared between groups. Between-group changes in primary (anxiety and depressive symptoms) and secondary (career confusion, goal navigation, and emotion regulation) outcomes from baseline to immediately and 3-month post-intervention were examined. Among GET participants, 81.1% completed all study sessions compared with 82.4% of those receiving ISL. Fidelity to the intervention was 87% in GET. Therapeutic alliance scores were significantly higher among those receiving GET. Participants exhibited greater reductions in depressive and anxiety symptoms for those in the GET versus ISL, with a similar pattern observed for changes at 3 months for depressive and anxiety symptoms. GET is a feasible and acceptable intervention for reducing adverse outcomes after testicular cancer for young adults.


Subject(s)
Emotional Regulation , Testicular Neoplasms , Male , Humans , Young Adult , Testicular Neoplasms/therapy , Pilot Projects , Goals , Survivors/psychology
13.
Drug Des Devel Ther ; 17: 875-886, 2023.
Article in English | MEDLINE | ID: mdl-36987403

ABSTRACT

Despite current advances in acute postoperative pain management, prevalence remains high. Inadequate treatment could lead to poor outcomes and even progression to chronic pain. Opioids have traditionally been the mainstay for treatment of moderate to severe acute pain. However, their use has been associated with opioid-related adverse events (ORAEs), such as respiratory depression, sedation, nausea, vomiting, pruritus, and decreased bowel motility. In addition, their liberal use has been implicated in the current opioid epidemic. As a result, there has been renewed interest in multimodal analgesia to target different mechanisms of action in order to achieve a synergistic effect and minimize opioid usage. Oliceridine is a novel mu-opioid receptor agonist that is part of a new class of biased ligands that selectively activate G-protein signaling and downregulate ß-arrestin recruitment. Since G-protein signaling has been associated with analgesia while ß-arrestin recruitment has been associated with ORAEs, there is potential for a wider therapeutic window. In this review, we will discuss the clinical evidence behind oliceridine and its potential role in acute postoperative pain management. We have systematically searched the PubMed database using the keywords oliceridine, olinvyk, and trv130. All articles identified were reviewed and evaluated, and all clinical trials were included.


Subject(s)
Analgesics, Opioid , Morphine , Humans , Analgesics, Opioid/adverse effects , Pain, Postoperative/drug therapy , GTP-Binding Proteins/therapeutic use
14.
medRxiv ; 2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36865094

ABSTRACT

Background: Acute decompensation is associated with increased mortality in heart failure (HF) patients, though the underlying etiology remains unclear. Extracellular vesicles (EVs) and their cargo may mark specific cardiovascular physiologic states. We hypothesized that EV transcriptomic cargo, including long non-coding RNAs (lncRNAs) and mRNAs, is dynamic from the decompensated to recompensated HF state, reflecting molecular pathways relevant to adverse remodeling. Methods: We examined differential RNA expression from circulating plasma extracellular RNA in acute HF patients at hospital admission and discharge alongside healthy controls. We leveraged different exRNA carrier isolation methods, publicly available tissue banks, and single nuclear deconvolution of human cardiac tissue to identify cell and compartment specificity of the topmost significantly differentially expressed targets. EV-derived transcript fragments were prioritized by fold change (-1.5 to + 1.5) and significance (<5% false discovery rate), and their expression in EVs was subsequently validated in 182 additional patients (24 control; 86 HFpEF; 72 HFrEF) by qRT-PCR. We finally examined the regulation of EV-derived lncRNA transcripts in human cardiac cellular stress models. Results: We identified 138 lncRNAs and 147 mRNAs (present mostly as fragments in EVs) differentially expressed between HF and control. Differentially expressed transcripts between HFrEF vs. control were primarily cardiomyocyte derived, while those between HFpEF vs. control originated from multiple organs and different (non-cardiomyocyte) cell types within the myocardium. We validated 5 lncRNAs and 6 mRNAs to differentiate between HF and control. Of those, 4 lncRNAs (AC092656.1, lnc-CALML5-7, LINC00989, RMRP) were altered by decongestion, with their levels independent of weight changes during hospitalization. Further, these 4 lncRNAs dynamically responded to stress in cardiomyocytes and pericytes in vitro , with a directionality mirroring the acute congested state. Conclusion: Circulating EV transcriptome is significantly altered during acute HF, with distinct cell and organ specificity in HFpEF vs. HFrEF consistent with a multi-organ vs. cardiac origin, respectively. Plasma EV-derived lncRNA fragments were more dynamically regulated with acute HF therapy independent of weight change (relative to mRNAs). This dynamicity was further demonstrated with cellular stress in vitro . Prioritizing transcriptional changes in plasma circulating EVs with HF therapy may be a fruitful approach to HF subtype-specific mechanistic discovery. CLINICAL PERSPECTIVE: What is new?: We performed extracellular transcriptomic analysis on the plasma of patients with acute decompensated heart failure (HFrEF and HFpEF) before and after decongestive efforts.Long non-coding RNAs (lncRNAs) within extracellular vesicles (EVs) changed dynamically upon decongestion in concordance with changes within human iPSC-derived cardiomyocytes under stress.In acute decompensated HFrEF, EV RNAs are mainly derived from cardiomyocytes, whereas in HFpEF, EV RNAs appear to have broader, non-cardiomyocyte origins.What are the clinical implications?: Given their concordance between human expression profiles and dynamic in vitro responses, lncRNAs within EVs during acute HF may provide insight into potential therapeutic targets and mechanistically relevant pathways. These findings provide a "liquid biopsy" support for the burgeoning concept of HFpEF as a systemic disorder extending beyond the heart, as opposed to a more cardiac-focused physiology in HFrEF.

15.
J Cell Biol ; 222(5)2023 05 01.
Article in English | MEDLINE | ID: mdl-36828364

ABSTRACT

Dendritic spines are the postsynaptic compartment of a neuronal synapse and are critical for synaptic connectivity and plasticity. A developmental precursor to dendritic spines, dendritic filopodia (DF), facilitate synapse formation by sampling the environment for suitable axon partners during neurodevelopment and learning. Despite the significance of the actin cytoskeleton in driving these dynamic protrusions, the actin elongation factors involved are not well characterized. We identified the Ena/VASP protein EVL as uniquely required for the morphogenesis and dynamics of DF. Using a combination of genetic and optogenetic manipulations, we demonstrated that EVL promotes protrusive motility through membrane-direct actin polymerization at DF tips. EVL forms a complex at nascent protrusions and DF tips with MIM/MTSS1, an I-BAR protein important for the initiation of DF. We proposed a model in which EVL cooperates with MIM to coalesce and elongate branched actin filaments, establishing the dynamic lamellipodia-like architecture of DF.


Subject(s)
Actins , Cell Adhesion Molecules , Microfilament Proteins , Pseudopodia , Actin Cytoskeleton/metabolism , Actins/metabolism , Dendritic Spines/metabolism , Neurons/metabolism , Pseudopodia/metabolism , Synapses/metabolism , Cell Adhesion Molecules/metabolism , Microfilament Proteins/metabolism
16.
Cancer Invest ; : 1-8, 2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36621937

ABSTRACT

We sought to determine differences by low- and middle- income countries (Brazil, Romania, and Turkiye) on the degree to which health care providers (HCPs) note unmet needs among patients with cancer (N = 741). HCPs endorsed sexuality/intimacy and financial concerns as the most common. Investigating age differences in unmet needs between Brazil and Turkiye, were that should be targeted by. Results revealed that unmet needs to manage emotional distress were higher among older patients in Turkiye, whereas unmet needs to manage insomnia/fatigue were higher among pediatric patients in Brazil. Findings may guide the development of programs to address unmet needs among patients.

17.
Psychooncology ; 32(1): 77-85, 2023 01.
Article in English | MEDLINE | ID: mdl-36251612

ABSTRACT

OBJECTIVE: Cancer patients and their family caregivers have reported various needs that are not met. Recognition of the unmet needs by healthcare professionals may be a first step to adequately and systematically addressing them. Thus, the International Psycho-Oncology Society Survivorship Online Survey was developed to measure healthcare professionals' evaluation about the unmet needs of their patients and family caregivers around the globe. METHODS: The survey was developed in English and translated to additional 14 different languages. The survey was distributed on the web-based REDCap application to over 50 psycho-oncology societies and their networking platforms as well as social media and to authors who have published in psycho-oncology journals globally. RESULTS: A total of 1472 participants from 36 countries at least partially completed the survey. Healthcare professionals evaluated needs for managing one's emotional distress and patients' medical care and symptoms as the most common concerns for both patients and their family caregivers across all patient age groups. Less than two-thirds of the participating healthcare professionals reported that their institution had services or programs to address the needs of the patients or caregivers. CONCLUSIONS: Findings suggest several directions for further analyses to provide more specific information that would be readily translated into clinical practices, research, and policy aimed to enhance the quality of life of cancer patients, survivors, and family caregivers around the globe. In addition, this collaborative effort also hints at the importance of establishing international networks to promote equity in care for people touched by cancer worldwide.


Subject(s)
Cancer Survivors , Neoplasms , Humans , Caregivers/psychology , Cancer Survivors/psychology , Quality of Life/psychology , Neoplasms/psychology , Health Services Needs and Demand
18.
Pharmaceuticals (Basel) ; 17(1)2023 Dec 25.
Article in English | MEDLINE | ID: mdl-38256863

ABSTRACT

Although traditional opioids such as morphine and oxycodone are commonly used in the management of acute postoperative pain, novel opioids may play a role as alternatives that provide potent pain relief while minimizing adverse effects. In this review, we discuss the mechanisms of action, findings from preclinical studies and clinical trials, and potential advantages of several novel opioids. The more established include oliceridine (biased ligand activity to activate analgesia and downregulate opioid-related adverse events), tapentadol (mu-opioid agonist and norepinephrine reuptake inhibitor), and cebranopadol (mu-opioid agonist with nociceptin opioid peptide activity)-all of which have demonstrated success in the clinical setting when compared to traditional opioids. On the other hand, dinalbuphine sebacate (DNS; semi-synthetic mu partial antagonist and kappa agonist), dual enkephalinase inhibitors (STR-324, PL37, and PL265), and endomorphin-1 analog (CYT-1010) have shown good efficacy in preclinical studies with future plans for clinical trials. Rather than relying solely on mu-opioid receptor agonism to relieve pain and risk opioid-related adverse events (ORAEs), novel opioids make use of alternative mechanisms of action to treat pain while maintaining a safer side-effect profile, such as lower incidence of nausea, vomiting, sedation, and respiratory depression as well as reduced abuse potential.

19.
Support Care Cancer ; 31(1): 36, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36520223

ABSTRACT

PURPOSE: This international study aimed to compare healthcare professionals' perspectives on the unmet needs of their cancer patients with those of family caregivers and to investigate the degree to which patients' age group moderates the associations. METHODS: Healthcare professionals involved in the care for cancer patients and their family caregivers were invited to participate in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey. A total of 397 healthcare professionals from 34 countries provided valid study data. The participants evaluated whether the unmet need was the same for all age groups of patients and the degree of their patients' needs not being met per patients' age group. They evaluated the same questions for family caregivers. RESULTS: Patients' unmet needs in medical care were evaluated as greater than those of caregivers across all age groups. On the other hand, pediatric patients' unmet needs for spiritual concerns, sexuality/intimacy, and insomnia/fatigue were evaluated as greater than those of caregivers, whereas adolescent and young adult patients' unmet needs for symptom management were greater than those of caregivers. Patients' other unmet needs were evaluated as comparable with those of caregivers regardless of age groups. CONCLUSION: The findings provide insights how best healthcare providers stratify resources to address the unmet needs of patients and caregivers by the patients' age. Development of systematic assessment of unmet needs and provision of interventions tailored for patients' lifespan to address the unmet needs of cancer patients, and caregivers are warranted.


Subject(s)
Caregivers , Neoplasms , Adolescent , Young Adult , Humans , Child , Psycho-Oncology , Health Personnel , Neoplasms/therapy , Neoplasms/diagnosis , Delivery of Health Care , Health Services Needs and Demand
20.
Sci Data ; 9(1): 717, 2022 11 21.
Article in English | MEDLINE | ID: mdl-36414684

ABSTRACT

Theta burst stimulation (TBS) is a new form of repetitive transcranial magnetic stimulation (TMS) capable of non-invasively modulating cortical excitability. In recent years TBS has been increasingly used as a neuroscientific investigative tool and therapeutic intervention for psychiatric disorders, in which the dorsolateral prefrontal cortex (DLPFC) is often the primary target. However, the neuromodulatory effects of TBS on prefrontal regions remain unclear. Here we share EEG and ECG recordings and structural MRI scans, including high-resolution DTI, from twenty-four healthy participants who received intermittent TBS (two sessions), continuous TBS (two sessions), and sham stimulation (one session) applied to the left DLPFC using a single-blinded crossover design. Each session includes eyes-open resting-state EEG and single-pulse TMS-EEG obtained before TBS and 2-, 15-, and 30-minutes post-stimulation. This dataset enables foundational basic science investigations into the neuromodulatory effects of TBS on the DLPFC.


Subject(s)
Prefrontal Cortex , Transcranial Magnetic Stimulation , Humans , Healthy Volunteers , Magnetic Resonance Imaging
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