Heroin self-administration induces sex-specific SUMOylation at early abstinence

Introduction: Opioid use disorder, particularly heroin use disorder (HUD), is a major medical challenge, marked by severe withdrawal symptoms and a high risk of relapse. Heroin abuse leads to severe withdrawal and high relapse rates, with neuroadaptations contributing to relapse. Sex-specific differences in heroin-induced neuroadaptations are poorly understood, limiting effective therapies. Posttranslational modifications (PTMs), such as SUMOylation, play a key role in regulating protein function and neuroplasticity. SUMOylation attaches SUMO proteins to lysine residues, altering protein activity and influencing addiction mechanisms. Understanding sex-specific PTMs like SUMOylation could reveal new therapeutic targets for heroin addiction.Methods: We employed a novel SUMO Capture Assay combined with liquid chromatography-mass spectrometry (LC-MS) to investigate SUMOylation in the nucleus accumbens (NAc) of rats subjected to heroin self-administration. Male and female rats underwent contingent heroin administration followed by a period of early abstinence. Global SUMOylation levels and specific SUMOylated proteins were analyzed to assess sex-specific differences in SUMOylation patterns.Results: Our analysis revealed significant sex-specific alterations in protein SUMOylation during early abstinence, notably, males exhibited selective SUMOylation of specific protein targets, including TCP-1η, a critical chaperone involved in protein folding. These findings suggest that SUMOylation may underlie sex-specific neurobiological responses to heroin abstinence and contribute to the persistent neuroadaptations associated with HUD.Conclusion: Preliminary studies show sex-specific changes in protein SUMOylation within the nucleus accumbens (NAc) during early abstinence from heroin self-administration. SUMO-Capture-LC/MS analysis revealed that SUMOylation occurs selectively in males on specific proteins, including TCP-1η, an important chaperone needed for protein folding. These findings suggest that SUMOylation may contribute to sex-specific neurobiological responses during heroin abstinence, highlighting potential targets for further investigation

Evaluating data-sharing policies and author compliance in leading pain journals: A cross-sectional analysis

Background: Reproducibility and transparency are essential pillars of high-quality biomedical research, particularly in chronic pain management, a field with significant societal and economic impacts. Despite increasing recognition of their importance, adherence to data-sharing practices remains inconsistent, with varying levels of engagement among top journals in pain and pain management (P&PM).Methods: Original research articles from five of the top P&PM journals were screened and analyzed for data-sharing statements (DSS). Furthermore, we identified influential variables on the inclusion of DSS in pain clinical-studies; and thematically analyzed their content to identify prevalent themes. Lastly, corresponding authors were contacted to assess their willingness to share their data.Results: A comprehensive literature review of clinical studies published between 2020 and 2023 identified 602 eligible articles. DSS inclusion varied significantly, with the Journal of Headache and Pain achieving 100% compliance, while others, such as the Journal of Pain and Symptom Management, lagged at 20%. Hierarchical logistic regression highlighted substantial journal-level variability, but no significant differences by study design. Thematic analysis revealed pervasive reliance on corresponding authors (68.97%) and conditional data availability (93.87%) as barriers to open data sharing. When contacted, only 34.38% of corresponding authors responded, with less than half providing data as promised.Conclusions: This cross-sectional study evaluated the use of data-sharing statements (DSS) in the five leading P&PM journals, analyzing trends and barriers to implementation. These findings underscore the need for stronger policies and resources to support transparency. Recommendations include adopting mandatory DSS policies, providing editorial support, and fostering collaborations to standardize open science practices across the field

Osseointegration’s effect on balance and perceived function in lower leg amputees: A critically appraised topic

Clinical Scenario: Lower extremity amputees commonly experience socket prosthesis (SP) complications that interfere with their perceived function and quality of life. Osseointegration (OI) is a new technique that requires implantation of the prosthesis directly into the intramedullary shaft of the residual limb. This alternative may be an answer for amputees who struggle with their SP and desire to regain comfortable and confident function with their prosthesis.Clinical Question: Does OI provide better functional and balance outcomes in lower extremity amputees than socket-prosthesis users?Summary of Findings: Participants with OI prostheses showed improvements in perceived balance and disability. There was little to no improvement in spatiotemporal measures during the 10-meter walk tests. However, all studies showed clinically important differences in ABC scores (d=-1.36 p=0.01)¹⁰ and 8.86 point improvement (MCID= 5.36)⁹.Clinical Bottom Line: Patients with lower extremity amputations may explore the option of OI as an alternative to SP. The outcomes measured show that OI produces the same functional ability as those with an SP, however it provides an increase in perceived balance and function which may positively affect their quality of life. OI does have its risks, but depending on the patient those risks may still be an improvement from the difficulties experienced with their SP.Strength of Recommendation: Consistent CEBM Level 3 findings support OI is an appropriate alternative to SP in providing increase perceived balance and function in lower extremity amputees

Examination of clinical trials for post-operative, non-opioid pain management within the National Library of Medicine’s Clinical Trials Database

Introduction/Objectives: Clinical trials are essential for the advancement of medical practice and patient care. In recent decades, opioids have been widely prescribed for managing post-operative pain, resulting in significant dependence and overuse. This study assesses recent clinical trials from the National Library of Medicine’s Clinical Trials database that utilize non-opioid treatment approaches for post-operative care.Design Methods: We searched for interventional trials registered at ClinicalTrials.gov from January 2009 through December 18, 2024. The trials were included in our analysis if they assessed only non-opioid post-operative pain management.Results: From the search of ClinicalTrials.gov, 52 trials were returned, from which 3 were excluded for being non-interventional and 2 were excluded for only including opioid treatments. Of the 47 trials included in the analysis, 22 (46.8%) were completed, 14 (29.8%) were active (or in enrolling or preenrolling stages), 7 (14.9%) were discontinued (suspended, terminated, or withdrawn) and 4 (8.5%) had unknown status. Among the completed trials, 21 (95.5%) used non-opioid drugs, while 1 (4.5%) used devices such as continuous local wound infusion (CLoWI). Of note, 11 (23.4%) of the 47 trials were specific to women, and 24 (51.0%) were conducted in the US.Discussion/Conclusion: Given the harms of opioid overuse, there is an urgent need for post-operative medical practices that reduce the risk of resultant dependence on these drugs. Our results showed that 47 non-opioid trials for post-operative pain have been registered since 2009. Among those trials, nearly half were conducted outside the United States, which is particularly noteworthy given the impact of the long-lasting opioid epidemic in the U.S. Additionally, nearly 1 in 4 trials were exclusive to females with the majority evaluating NSAIDS or local anesthetics as non-opioid alternatives for alleviating postoperative pain following cesarean section or gynecological surgery

Effectiveness of vestibular rehabilitation therapy in decreasing concussion symptoms in patients under the age of 60: A critically appraised topic

Clinical Scenario: Concussions, also known as mild traumatic brain injuries or traumatic brain injuries, are prevalent injuries sustained by both young and old. These injuries can leave people with lasting symptoms. Vestibular Rehabilitation Therapy (VRT) is a form of physical therapy which is comprised of exercises encouraging head and eye movements.Clinical Question: In patients ages twelve to sixty who have sustained a diagnosed concussion and have experienced symptoms for up to one year, does completing vestibular rehabilitation therapy efficiently return them to activities of daily living through symptom resolution sooner than conservative methods?Clinical Bottom Line: There is moderate evidence supporting the integration of VRT to concussion protocols in order to achieve efficient symptom resolution as soon as two weeks to return patients with diagnosed concussions to their activities of daily living.Strength of Recommendation: These findings suggest the Strength of Recommendation Taxonomy (SORT) Level B evidence¹² with a CEBM level 2 indicating the quality methods used by the included studies

Quantitative proteomic and phenotypic analysis of Chlamydomonas wild-type and lf4 mutant

Background: Normal health and development require cilia and flagella, which are essential organelles that are highly conserved across different species. The molecular mechanisms that regulate their assembly state, however, remain largely unknown. In Chlamydomonas, mutations in any of five long flagella (lf) genes result in cells that assemble flagella more than twice the length of wild-type cells. To learn more about the role of one of these genes, LF4 (which encodes a MAP kinase) we used a phenotypic analysis along with a global proteomic approach to identify differentially expressed proteins in the flagella and cell bodies of lf4 and wild-type cells.Methods: To determine the cell body volumes, cells were fixed with an equal volume of 1% glutaraldehyde and examined by phase contrast microscopy. Cell volume was determined with the following equation (4/3π[length/2][width/2]2). Quantitative LC-MS/MS was performed on equal amounts of protein from purified cell bodies and flagella. Resulting data was analyzed using MaxQuant (Version 1.5.2.8) and Perseus (version 1.5.5.3). In order to examine the effect of rapamycin on cell growth, cells were cultured on agar plates containing rapamycin and exposed to constant light.Results: As determined by microscopic analysis, there was a significant increase in the size of lf4 cell bodies compared to wild-type cells. As shown by analysis of the quantitative LC-MS/MS spectra, 66% of the total proteins were common between the two strains with 11% and 12% of flagella proteins and cell body proteins respectively being differentially expressed. Enrichment analysis revealed a decrease in proteins involved in protein synthesis but an increased expression of proteins involved in energy production in lf4 cell bodies compared to wild type. Differential expression of flagellar proteins was also seen in these two strains. For example, lf4 flagella had an increased expression of microtubule motor proteins while wild type had increased expression of proteins associated with organelles. Cells grown in the presence of rapamycin exhibited a dose-dependent decrease in viability and cell growth on both strains, although the effect was less pronounced in lf4.Conclusions: The observation that lf4 cell bodies are larger than wild-type cells suggest that regulation of both flagellar length and cell body size are impaired. The LF4 gene product could regulate both flagella and cell body size. The increase in flagella and cell body size are surprising given the decreased expression of proteins involved in transcription and translation. The increase in protein levels for proteins involved in energy production could reflect an increased energy requirement necessary for flagellar motility with the lf4 flagella

Clear as mud: Addressing visual plagiarism one Lunch & Learn at a time

This lightning talk covers the presenter’s Lunch & Learn program focusing on Visual Plagiarism. This program has garnered significant popularity among students at the Oklahoma State University School of Architecture. The presenter addresses the program's underlying motivations, the resources utilized for this activity, and ultimately, assesses the program's reception and overall success.falseLibrar

Capturing barriers to accessing free food resources for international students at Oklahoma State University: A photovoice study

Food insecurity among college students is a rising issue in the United States, particularly among international students. These students often face unique challenges in accessing and preparing food as they adapt to life in a new country. Many college campuses provide food assistance programs, including pantries and other free food resources. However, the effectiveness of these programs in reducing food insecurity depends on their full utilization. International students, in particular, often encounter barriers that limit their utilization of these resources. Despite their significance, these challenges remain under-researched and require further investigation. This study aimed to examine the barriers international students attending Oklahoma State University (OSU) face in accessing free food resources both on and off campus. The findings highlight the challenges international college students experience in accessing and utilizing free food resources on and off campus. College campuses may aim to address these logistical and nutritional concerns by providing resources that better suit international student cultural food needs and adjusting operational hours to better suit students’ schedules.Nutritional Science

Discrepancies in safety reporting for chronic back pain clinical trials: An observational study from ClinicalTrials.gov and publications

Introduction: Chronic back pain (CBP) is a leading cause of disability worldwide and is commonly managed with pharmacological, non-pharmacological, and surgical interventions. However, adverse event (AE) reporting for these therapies often lacks transparency, raising concerns about the accuracy of safety data. This study aimed to quantify inconsistencies in AE reporting between ClinicalTrials.gov and corresponding randomized controlled trial (RCT) publications, emphasizing the importance of comprehensive safety reporting to improve clinical decision-making and patient care.Methods: We conducted a retrospective analysis of Phase 2–4 CBP RCTs registered on ClinicalTrials.gov between 2009, when the submission of AE information became legally required, and 2023. Data extraction focused on AE reporting, trial sponsorship, and discrepancies in serious adverse events (SAEs), other adverse events (OAEs), mortality, and treatment-related withdrawals between registry entries and corresponding publications. Statistical analyses were performed to evaluate reporting inconsistencies, adhering to STROBE guidelines for observational studies.Results: A total of 114 registered trials were identified, with 40 (35.1%) corresponding publications. Among these, 67.5% were industry-sponsored. Only 4 (10%) publications fully reported adverse events (AEs) without discrepancies, while 36 (90%) contained at least one inconsistency compared to ClinicalTrials.gov. Discontinuation due to AEs was explicitly reported in 24 (60%) of ClinicalTrials.gov entries and in 30 (75%) of publications, with discrepancies in 16 trials (40%). Serious adverse events (SAEs) were reported differently in 15 (37.5%) publications; 80% reported fewer SAEs than ClinicalTrials.gov. Other adverse events (OAEs) showed discrepancies in 37 (92.5%) publications, with 43.2% reporting fewer and 54.1% reporting more OAEs.Discussion: This study highlights pervasive discrepancies in AE reporting for CBP trials, undermining the reliability of published safety data. Inconsistent reporting poses risks to clinical decision-making and patient safety. Adopting standardized reporting guidelines, such as CONSORT Harms, and ensuring transparent updates in publications could enhance the accuracy and trustworthiness of safety data. Journals and regulatory bodies should enforce compliance and future efforts should develop mechanisms to monitor and correct reporting inconsistencies, enhancing the trustworthiness of safety data in clinical research

Investigation into the intraoperative management of the difficult pediatric airway: A scoping review

Introduction/Objectives: Pediatric airways can pose a significant challenge to anesthesia providers. Almost 20% of pediatric patients undergoing general anesthesia are considered to have a difficult airway due to congenital anomalies, craniofacial deformities, trauma, or infection. The majority of children with difficult airways can be identified preoperatively, but the variety of clinical scenarios in which difficult airways can quickly arise requires an individualized approach that considers the underlying condition and the patient’s physiological status. The objective of this scoping review is to identify clinical challenges and complications, summarize outcomes of airway methods, and identify existing knowledge gaps to guide future airway management research.Methods: We performed a literature search using the Ovid (Embase), MEDLINE (PubMed), SCOPUS, Web of Science, and Cochrane databases for articles on pediatric airways that were published in the 10-year period spanning from 2014 to 2024 and written in English. Included studies were systematic reviews, meta-analyses, retrospective database reviews, clinical trials, case-control studies, cross-sectional analyses, and cohort studies. The data was imported into Rayaan, and two independent investigators screened records for inclusion criteria in a masked, duplicate fashion. Investigators then completed a data extraction form that identified the frequencies, types, and complications of airway methods used to provide anesthetic care.Results: The initial database search yielded 1,097 articles, and 82 ultimately met the inclusion criteria to be evaluated in our study. The sample in our study consisted of research from 50 different journals. The most frequent journal featured in our sample was Cureus: Journal of Medical Sciences, with 11 studies (11/82; 13.4%). The continent with the most studies was Asia, with 43 studies (43/82; 52.4%). Case reports/Case series comprised most of the study design types (62/82; 75.6%), followed by Cohort studies (15/82; 18.3%). There was only one of each, a Randomized Controlled Trial and systematic review with meta-analysis. The studies focused on anatomical/congenital difficult airways most commonly (42/82; 51.2%). The approach/technique included in these studies was most commonly direct laryngoscopy (36/82; 43.9%), fiberoptic bronchoscopy (37/82; 45.1%), and video laryngoscopy (39/82; 47.6%).Conclusion: In conclusion, the importance of a proper preoperative examination to identify anatomical, pathological, or physiological characteristics of pediatric patients cannot be emphasized enough. This scoping review provides an overview of the current techniques and methods of intraoperative pediatric difficult airway management and identifies the knowledge gaps and areas for future research. More systematic research, like randomized controlled trials and systematic reviews, could benefit the anesthetic community with different approaches to handling these critical situations