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A randomized, double blind, placebo-controlled pilot study to assess the efficacy of erenumab in individuals with temporomandibular disorder
No full textBackground: Erenumab has proven efficacious in treating migraine headache. Temporomandibular disorder (TMD) is a painful disorder which has high co-occurrence rates with migraine. We hypothesized that erenumab-aooe may also be beneficial in reducing pain in TMD-related myalgia.
Methods: This phase II randomized placebo-controlled clinical trial evaluated the safety and efficacy of the off-label use of erenumab in reducing TMD-related pain. The TMD diagnosis was established using the Diagnostic Criteria for Temporomandibular Disorders. The primary outcome was pain interference as assessed by the 0-to-10-point Brief Pain Inventory (BPI). Secondary outcomes were depression, anxiety and somatic symptoms; jaw function; and percent of days taking pain medication. Subjects were randomized at baseline to receive either erenumab 140 mg or placebo administered subcutaneously every 4 weeks for a total of five treatments. Outcome assessments were conducted at baseline, 4, 8, 12, 16, 20 and 24 weeks.
Results: Thirty subjects were enrolled with 15 randomized to each treatment group. Baseline pain was mild (BPI interference of 2.19; BPI severity of 2.95). There were no significant treatment effects at any time points with the between-group BPI interference at 24 weeks being -0.19 (95% confidence interval -1.94 to 1.56; p = 0.82). The outcomes were similar between erenumab and placebo for all outcomes except the Patient Health Questionnaire 4-item scale (PHQ-4) which showed that depression/anxiety symptoms were modestly worse (p = 0.03) in the erenumab group. Five participants withdrew during the trial (4 in erenumab arm, 1 in placebo arm).
Conclusions: Erenumab was not efficacious in reducing TMD myalgic pain in this phase II trial of 30 subjects with relatively mild pain
Enhancing Activity Engagement to Optimize Medicare Home Health Patient Outcomes: A Pilot RCT
No full textReducing task demands early in rehabilitation and gradually increasing them may enhance functional outcomes for patients receiving home health therapy. This pilot randomized controlled trial, completed in March 2025, examined the feasibility and preliminary effects of the Home-based Activity Reactivation Program, which integrates compensatory and restorative strategies to calibrate task demands as an adjuvant treatment to usual therapy. Forty-seven patients (mean age 82) were randomized to receive the Home-based Activity Reactivation Program plus usual therapy (n = 24) or usual therapy alone (n = 23). The Home-based Activity Reactivation Program was delivered in six weekly home visits, separate from usual therapy sessions. The primary outcome was Motor Skills from the Assessment of Motor and Process Skills; secondary outcomes included multiple measures of physical function. The Home-based Activity Reactivation Program demonstrated high acceptability, with 95% of completers reporting satisfaction and no severe or serious adverse events. Unexpectedly, the control group showed greater improvement in Motor Skills at postintervention (estimated difference -0.29 logits, p = 0.02), though this was not sustained at one-month follow-up. No significant between-group differences were found over time for secondary outcomes. These findings suggest that the Home-based Activity Reactivation Program did not yield superior outcomes compared to usual therapy alone. Potential contributing factors include limited intervention intensity, scheduling challenges, and practitioner bias. The study highlights the complexities of integrating and evaluating adjuvant interventions within routine home health care and underscores the need for further refinement and testing of the Home-based Activity Reactivation Program to optimize its effectiveness
Severe cibenzoline toxicity in hypertrophic obstructive cardiomyopathy successfully managed with extracorporeal membrane oxygenation and percutaneous transluminal septal myocardial ablation — A case report
No full textCibenzoline (CBZ), a class I antiarrhythmic drug, is used for patients with hypertrophic obstructive cardiomyopathy (HOCM). However, it requires careful monitoring in patients with renal dysfunction for potential toxicity. We present a case of severe CBZ toxicity in a 72-year-old woman with HOCM, previous ascending aortic dissection repair, and renal dysfunction. She was maintained on CBZ 300 mg daily despite fluctuating renal function. She presented with acute respiratory distress. On presentation, she was found to have bradycardia with QRS prolongation (340 ms) and markedly elevated CBZ levels (1973 ng/mL, therapeutic range: 200-800 ng/mL). She developed sudden cardiac arrest in the emergency room. Following cardiac arrest, venoarterial extracorporeal membrane oxygenation (VA-ECMO) was initiated. Direct hemoperfusion yielded minimal reduction in CBZ levels. With increased urine output, CBZ levels normalized, accompanied by electrocardiographic improvement. After VA-ECMO withdrawal, percutaneous transluminal septal myocardial ablation (PTSMA) was performed as definitive treatment to eliminate CBZ dependency. This case illustrates the complex interaction between HOCM, renal impairment, and CBZ toxicity, emphasizing the importance of careful drug monitoring in patients with renal impairment. Additionally, it demonstrates the potential role of PTSMA as a definitive treatment for selected patients with HOCM at high risk of medication-related complications.
Learning objectives: •Understand the pharmacokinetics of cibenzoline and its need for monitoring in elderly patients with hypertrophic obstructive cardiomyopathy (HOCM) and impaired renal function.•Recognize the mechanisms of cibenzoline toxicity and its acute management strategies, including mechanical circulatory support and direct hemoperfusion.•Identify the acute management strategies and long-term treatment options for complications arising from medical therapy in patients with HOCM
Resting state functional connectivity patterns associate with alcohol use disorder characteristics: Insights from the triple network model
No full textProlonged alcohol use results in neuroadaptations that mark more severe and treatment-resistant alcohol use. The goal of this study was to identify functional connectivity brain patterns underlying Alcohol Use Disorder (AUD)-related characteristics in fifty-five adults (31 female) who endorsed heavy alcohol use. We hypothesized that resting-state functional connectivity (rsFC) of the Salience (SN), Frontoparietal (FPN), and Default Mode (DMN) networks would reflect self-reported recent and lifetime alcohol use, laboratory-based alcohol seeking, urgency, and sociodemographic characteristics related to AUD. To test our hypothesis, we combined the triple network model (TNM) of psychopathology with a multivariate data-driven approach, regularized partial least squares (rPLS), to unfold concurrent functional connectivity (FC) patterns and their association with AUD-related characteristics. We observed three concurrent associations of interest: i) drinking and age-related cross communication between the SN and both the FPN and DMN; ii) family history density of AUD and urgency anticorrelations between the SN and FPN; and iii) alcohol seeking and sex-associated SN and DMN interactions. These findings provide an integrative interpretation for many individual findings reported in the literature relating functional connectivity signatures and AUD factors. Moreover, we identified a set of neural mechanisms and brain regions concomitant with AUD-related characteristics that can serve as potential treatment targets across clinical and preclinical models
Performance returns from aligning front-end digital technologies and Just-in-Time practices: empirical findings from the Brazilian manufacturing industry
No full textPurpose
The integration of front-end technologies such as automation, process simulation and augmented reality with Just-in-Time (JIT) practices can yield unforeseen outcomes in manufacturing due to complex dynamics. This study examines this integration’s impact on manufacturing firms' performance.
Design/methodology/approach
We design a survey questionnaire and distributed it among 353 Brazilian manufacturing firms to conduct our investigation. We utilize a combination of factorial and regression analyses with moderation within our final sample, composed of 262 manufacturing firms. Our goal is to examine the impact of aligning front-end technologies and JIT on the operational and economic performance of these manufacturing firms. We adopt complexity theory as our theoretical framework, recognizing and accommodating the intrinsic unpredictability and uncertainty inherent in complex scenarios such as technology adoption and its interplay with firm culture, adoption time and technology adoption resistance.
Findings
Our findings indicate that JIT influences the use of front-end technologies both positively and negatively. Regarding operational performance, JIT has a positive moderation effect on automation and a negative moderation effect on process simulation. Conversely, for economic performance, JIT positively moderates process simulation and negatively moderates automation.
Practical implications
We provide empirical evidence for managers to carefully assess the compatibility of technology adoption strategies with existing organizational culture and operational practices to maximize performance outcomes.
Originality/value
Our study advances complexity theory by elucidating the impacts of integrating front-end digital technologies with JIT practices within the unique scenario of the Brazilian manufacturing industry. More specifically, our theoretical framework offers a new perspective on the unpredictable nature of performance outcomes regarding technology adoption in operations
BCOR, BCORL1, and BCL6 Mutations in Pediatric Leukemias
No full textSomatic and epigenetic alterations contribute to myeloid leukemogenesis and play an important role in risk stratification and the optimization of treatment for myeloid malignancies. The significance of rare genetic alterations, such B-cell lymphoma-6 corepressor (BCOR) and B-cell lymphoma-6 corepressor-like protein 1 (BCORL1) mutations, in pediatric acute myeloid leukemias (AML) and myelodysplastic syndrome (MDS) is unknown. We present a case series of pediatric and adolescent patients, with de novo AML, harboring BCOR/BCORL1 mutations. Studies involving larger cohorts of patients are needed to further elucidate the role of BCOR/BCORL1 mutations in pediatric AML and MDS
A geological carbon cycle sink hosted by ocean crust talus breccias
No full textCalcium carbonate precipitation in ageing ocean crust sequesters carbon dioxide dissolved in seawater through seafloor weathering reactions, influencing atmospheric CO2 concentrations on million-year timescales. However, this crustal carbon sink, and the extent it balances CO2 degassing during crustal formation at mid-ocean ridges, remain poorly quantified due to limited sampling of the vast ridge flanks where CO2 uptake continues for millions of years. Here we quantify the carbon sink hosted within talus breccias that accumulated through mass wasting 61 million years ago during rift faulting at the slow spreading Mid-Atlantic Ridge, cored during International Ocean Discovery Program South Atlantic Transect Expedition 390. After 40 million years of carbonate cementation, these breccias contain ~7.5 wt% seawater-derived CO2, 2 to 40 times more than previously cored upper crust. Our estimates of talus breccia abundance based on fault geometries indicate that talus formed at slow-spreading ridges can accommodate a CO2 sink equivalent to a large proportion of the CO2 released during accretion of the underlying crust. The proportion of plate divergence accommodated by faulting, and hence talus abundance, increases nonlinearly with decreasing spreading rate. Consequently, past variations in spreading rate may have impacted the balance between ocean crust CO2 release and uptake in Earth’s carbon cycle
EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium
No full textMembrane proteins, such as the cystic fibrosis transmembrane-conductance regulator (CFTR), play a crucial role in gastrointestinal functions and health. Endoplasmic reticulum (ER) membrane protein complex (EMC), a multi-subunit insertase, mediates the incorporation of membrane segments into lipid bilayers during protein synthesis. Whether EMC regulates membrane proteins' processing and function in intestinal epithelial cells remains unclear. To investigate the role of EMC in the intestinal epithelium, we generated mice in which EMC subunit 3 (EMC3) was deleted in intestinal epithelial cells (EMC3ΔIEC). EMC3ΔIEC mice were viable but notably smaller compared with their wild-type littermates. Although the intestinal structure was generally maintained, EMC3ΔIEC crypts exhibited altered morphology, particularly at the base of the crypts with decreased goblet cells and paneth cells. Levels of multiple polytopic membrane proteins, including CFTR, were decreased in EMC3-deficient epithelial cells. Several calcium ATPase pumps were downregulated, and calcium mobilization was impaired in EMC3ΔIEC enteroids. CFTR-mediated organoid swelling in EMC3ΔIEC mice was impaired in response to both cAMP-dependent signaling and calcium-secretagogue stimulation. Our study demonstrated that EMC plays a critical role in maintaining intestinal epithelium homeostasis by regulating membrane protein biogenesis and intracellular calcium homeostasis. Maintaining intracellular calcium homeostasis may be a universal cellular function regulated by EMC.
NEW & NOTEWORTHY: We generated mice in which endoplasmic reticulum membrane protein complex (EMC) subunit 3 was deleted from intestinal epithelium cells and studied the molecular functions of EMC in vivo. Our findings demonstrate the importance of intestinal EMC in the biogenesis of membrane proteins in vivo, including CFTR, and highlight its critical role in maintaining intracellular calcium homeostasis and, consequently, in calcium-dependent functions in the intestine and beyond
Health Professional Students Prefer Study Advice from Institutionally Affiliated Sources Over Internet "Med-fluencers"
No full textStudents have access to countless sources of study advice, including medical professionals on social media known as "med-fluencers" However, not all sources are credible. This study explored who students viewed as credible sources and identified any factors that influenced their credibility. Prior to the first exam, allied health students in a doctoral-level gross anatomy course were presented with study advice videos featuring either a "med-fluencer," an anatomy professor from an external institution, an anatomy professor from the home institution, and a near-peer student. Students then completed the Measure of Ethos/Credibility (MEC), a construct that assesses the perceived competence, goodwill, and trustworthiness of an instructor. After the exam, students completed the MEC again. Students who completed both MECs were then invited to participate in a focus group. A total of 35 students completed the pre-exam MEC, and 16 students completed the post-exam MEC, resulting in 10 matched pairs. Before and after the first exam, the home professor received the highest MEC score, followed closely by the external professor and near-peer student, then the med-fluencer. Thematic analysis also indicated that although the near-peer had the least expertise, students preferred their advice due to their recent experience in their specific course. Overall, allied health students viewed professors as the most credible sources of study advice but preferred to use the advice of near-peers due to their recent experience in their specific gross anatomy course. Conversely, the med-fluencer was viewed as the least credible due to their distance from the students and their course