51886 research outputs found
Sort by
Impact of Preoperative Education on Clinical Outcomes Following Major Head & Neck Surgery: A Systematic Review
No full textObjective:
To perform a systematic review of the effect of preoperative teaching methods on outcomes for adult patients undergoing major head and neck surgery.
Data Sources:
OVID Medline, CINAHL, Cochrane, Pubmed, and Embase databases were queried.
Review Methods:
A comprehensive literature search was conducted in January 2024 using Medline (Ovid), Embase (Ovid), CINAHL Complete (EBSCOhost), and Cochrane Central Register of Controlled Trials (CENTRAL). Following PRISMA methodology, primary literature published between January 2000 and January 2024 was queried. The search focused on studies examining preoperative patient education for major head and neck cancer surgeries. The Methodological Index for Non‐Randomized Studies (MINORS) criteria were employed to assess the risk of bias in the included studies.
Results:
Our initial search strategy yielded 1140 titles with 54 meeting criteria for full‐text review. Four publications were included in the final study, all of which were published within the last 8 years. Thematic analysis revealed that most teaching interventions included multidisciplinary sessions or days, educational material, and support to caregivers. The most common finding from teaching interventions was decreased hospital length of stay, while some authors also found decreased readmission rates and fewer post operative complications in intervention cohorts.
Conclusion:
Preoperative education utilizing multidisciplinary teams has demonstrated an improvement in length of stay and in some cases, fewer complications and readmissions in adult patients following major head and neck surgery. More robust research is needed to draw further conclusions on impact to patient outcomes and cost
Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups
No full textBackground: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) pathology. Recently, plasma biomarkers, particularly p-tau217, have emerged as promising tools for early diagnosis and risk stratification. In this retrospective study, we evaluated the diagnostic performance of p-tau217 combined with other plasma biomarkers in distinguishing Aβ Positron emission tomography (PET) positivity in cognitively unimpaired (CU) and cognitively impaired (CI) individuals across diverse clinical subgroups.
Methods: We analyzed 2,497 participants from the Korea-Registries to Overcome dementia and Accelerate Dementia (K-ROAD) cohort, including 636 CU and 1,971 CI individuals. Plasma p-tau217 was measured using both SIngle MOlecule Array (SIMOA) and Meso Scale Discovery (MSD) assays, alongside Aβ42/40, Glial fibrillary acidic protein (GFAP), and Neurofilament light chain (NfL). We assessed the diagnostic performance of biomarker combinations for Aβ PET positivity through the area under the receiver operating characteristic curve (AUC), Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), and performed subgroup analyses based on age, sex, body mass index (BMI), and Apolipoprotein E (APOE) ε4 status. To assess applicability, we stratified the cohort by recruitment site into a development set (Samsung Medical Center, n = 1,545) and a validation set (other centers, n = 952).
Results: In CU individuals from the development cohort, the combination of p-tau217 and Aβ42/40 significantly improved diagnostic accuracy (AUC: ALZpath 0.937 vs. 0.905, MSD 0.901 vs. 0.861; p < 0.05, DeLong test; 95% CIs) and model fit (AIC /BIC, p < 0.001) compared to p-tau217 alone. In contrast, in CI individuals, the combination provided only modest improvements in model fit without significantly enhancing AUC. GFAP and NfL did not contribute significantly to amyloid detection in either group. These findings were successfully validated in an independent cohort from other centers. Subgroup analyses in CU individuals showed the greatest improvements in older adults, females, and APOE4 non-carriers, regardless of obesity status. In CI individuals, the combination had no significant impact on AUC except in males, where a small but significant increase was observed (p = 0.002).
Conclusion: Combining p-tau217 with Aβ42/40 enhances amyloid detection in CU individuals, improving both diagnostic accuracy and model fit, whereas its impact in CI individuals is limited. These results highlight the potential of plasma biomarker combinations for refining early AD diagnostics and individualized risk assessment
A three-stage assembly program governing pancreatic, plasma, pituitary, and bone secretory cell differentiation: A strategy to augment protein delivery
No full textDefective secretory cell function underlies many diseases, and recent therapeutic strategies have focused on enhancing protein synthesis and delivery by targeting the secretory machinery of mature cells. However, mature differentiated cells appear to have intrinsic limits to their secretory capacity. In this review, we propose new strategies for engineering these cells to overcome these limits on secretion. The integrated stress response (ISR) and the related unfolded protein response (UPR) are stress adaptation systems that modulate transcriptional and translational programs of gene expression. These programs drive remodeling of cellular architecture to boost protein production and trafficking but also play critical roles in the differentiation of secretory cells. This dual function suggests that the limits of the secretory capacity of mature cells are pre-programmed during development. A potentially more effective therapeutic approach to expand protein secretion may lie in reprogramming the secretory capacity early in differentiation. Two additional transcriptional programs work in concert with the ISR and UPR to shape differentiated cell identities, their secretory outputs, and production capacity. The first involves lineage-determining transcription factors that define both cell type and secretory products. The second involves "scaling factors" that set the magnitude of the cell's protein synthesis and secretion capacity. We explore the mechanisms by which these three programs-lineage specification, scaling, and stress adaptation-interact to define and potentially enhance secretory capacity. We will illustrate this integrated model across several secretory cell types, including pancreatic, plasma, pituitary, and bone secretory cells, with a focus on applications to enhance therapeutic outcomes in osteoporosis
Investigation of GSDME results in the identification of the first pathogenic synonymous variants and genotype-phenotype correlations
No full textDespite advances in the genetic diagnosis of hearing loss, there remains room for improvement. One way to improve the genetic diagnostic rate is the proper assessment of synonymous variants that are often bioinformatically filtered out. We used GSDME as a model to demonstrate the importance of assessing synonymous variants. Variants in the gene GSDME (also known as DFNA5) are associated with autosomal dominant nonsyndromic hearing loss. The hearing loss is typically progressive and downsloping. All reported causative variants of GSDME-related hearing loss involve the skipping of exon 8, which results in the expression of a constitutively active, but truncated protein that induces apoptosis of cochlear hair cells. A retrospective search of previously tested patients identified 3 novel pathogenic synonymous GSDME variants. The functional impact of these variants was confirmed in vitro via a minigene splicing assay. We also observed variant-dependent differences in the levels of aberrant splicing, leading us to hypothesize that partial loss of splicing will result in a less severe hearing loss phenotype as compared to complete loss of splicing. Audiometric analysis found an association between complete loss of splicing and greater initial and/or more quickly progressing hearing loss as compared to partial loss of splicing. Over the course of the study, we also found limited correlation between in silico prediction and in vitro observed effects of a variant on splicing, indicating the need to cautiously apply in silico prediction tools in the context of genetic diagnosis
Mpox in the Gulf Cooperation Council Countries: Addressing a new challenge to regional health security
No full textPlasma proteomic analysis identifies proteins and pathways related to Alzheimer's risk
No full textIntroduction: We investigated associations of plasma proteins with blood-based amyloid/tau/neurodegeneration/inflammation (A/T/N/I) biomarkers for Alzheimer's disease (AD).
Methods: Plasma proteomics and clinical data from the Indiana AD Research Center (N = 498) were used. Association analysis of plasma proteins with blood A/T/N/I biomarkers as well as diagnosis was performed, followed by replication in an independent cohort (N = 323), network analysis, pathway enrichment, and machine learning classification to identify proteins and pathways related to AD risk.
Results: We identified 35 proteins associated with AD, 20 of which were replicated in the independent cohort. We identified 150, 448, and 219 proteins associated with T/N/I biomarkers, respectively, revealing biomarker-specific pathways. Network analysis identified two modules associated with T/N/I biomarkers, preserved in cerebrospinal fluid (CSF), and their enriched pathways. The classification model of proteins effectively differentiated AD (area under the curve [AUC] = 0.930).
Conclusion: Our findings suggest dysregulated plasma proteins and pathways in AD, enhancing our understanding of molecular mechanisms and diagnostic strategies for AD.
Highlights: Plasma proteins were identified as being associated with Alzheimer's disease (AD) and plasma biomarkers. The identified proteins were replicated in both plasma and cerebrospinal fluid (CSF) proteomics. The identified proteins were associated with AD biomarker-specific pathways. The identified proteins improved the performance of the AD classification. Protein network analysis identified network modules and their enriched pathways
Cracking PRMT5: Mechanistic Insights, Clinical Advances, and AI-Driven Strategies
No full textProtein arginine methyltransferase 5 (PRMT5) is a type II methyltransferase that catalyzes symmetric arginine dimethylation on histone and non-histone proteins, thereby modulating transcription, RNA splicing, and diverse signaling pathways. Dysregulated PRMT5 activity contributes to tumorigenesis and multiple pathological conditions, positioning it as a high-priority therapeutic target with strong translational relevance. Current inhibitor strategies encompass S-adenosylmethionine (SAM)-competitive agents, substrate-competitive and substrate-dependent modulators, dual-binding and methylthioadenosine (MTA)-cooperative inhibitors, PROTAC-based degraders, repurposed FDA-approved drugs, and rational combination regimens designed to improve efficacy or overcome resistance. These approaches differ in mechanism of action, tumor specificity, and toxicity profiles. This review highlights their mechanistic underpinnings, clinical development, and inherent limitations, while also examining the potential application of PRMT5 inhibitors in non-oncologic indications, including ocular and cardiovascular diseases. Finally, it explores the role of biomedical informatics and artificial intelligence (AI) in drug repurposing and outlines future directions for advancing PRMT5-targeted therapeutics
Combining Pirfenidone With Mycophenolate Mofetil for Systemic Sclerosis–Related Interstitial Lung Disease (Scleroderma Lung Study III): An Investigator‐Initiated, Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Phase 2 Trial
No full textObjective: Mycophenolate mofetil (MMF) can stabilize or improve lung function in systemic sclerosis-related interstitial lung disease (SSc-ILD). We hypothesized that combining MMF with pirfenidone (PFD) would produce a significantly more rapid and/or greater improvement in lung function.
Methods: A randomized (1:1), double-blind, placebo (PLA)-controlled phase 2 trial was conducted in SSc-ILD in which patients received PFD or PLA (801 mg three times daily) along with MMF (1,500 mg twice daily) for 18 months. The primary outcome was change in percent predicted forced vital capacity (FVC-%). Linear mixed-effects models assessed treatment differences in a modified intention-to-treat population.
Results: Only fifty-one of 150 intended subjects (34%) were randomized (MMF+PLA, n = 24; MMF+PFD, n = 27). The FVC-% improved from baseline to 18 months by 2.24 ± 1.35 (least-squares mean [LSM] ± SEM) in the MMF+PLA group and 2.09 ± 1.28 in the MMF+PFD group (LSM treatment difference -0.14; P = 0.93). Median time to achieve a ≥3% improvement in FVC-% was numerically faster in the MMF+PFD versus MMF+PLA group (12.3 vs 17.8 months, respectively), but the difference was not significant (P = 0.33). For secondary outcomes, only the change over 18 months in the Patient-Reported Outcomes Measurement Information System 29-item physical function score, favoring MMF+PFD, reached statistical significance (P = 0.04). Although other related patient-reported outcomes (PROs) numerically favored the MMF+PFD group, as did quantitative high-resolution computed tomography measures of ILD, the differences between groups did not reach statistical significance. Early withdrawals from study medication and adverse events of special interest were numerically greater with MMF+PFD (n = 8 vs 2 and n = 20 vs 7, respectively).
Conclusion: In this underpowered study, there was no statistically significant treatment difference in overall change in FVC-% between groups. MMF+PFD was not as well tolerated as MMF+PLA
Exploring Art Therapy in Alcoholism Detoxification: A Survey on Materials and Therapeutic Directives
No full textIUIThis study aimed to identify the most commonly used materials, directives, and therapeutic approaches
employed in art therapy for individuals undergoing detox for alcohol use disorder (AUD). To explore these
practices, 32 art therapy clinicians with experience in the substance use population completed an online survey.
The survey included questions related to demographics, types of materials and directives, levels of complexity
and structure, and engagement across levels of the Expressive Therapies Continuum (ETC). While it was
anticipated that kinesthetic and sensory art making modalities, along with structured directives would be most
prevalent, the results revealed a wide range of contradictory responses, specifically concerning levels of the
ETC and directive structure. These findings highlight the diversity of clinical approaches in this setting and may
serve as a foundational reference for future research aimed at deepening our understanding of effective art
therapy interventions in AUD detox contexts