Long Island University

BackgroundMisalignment between actual and perceived balance ability provides relevant information to understand functional deficits and fall risk. However, few studies have provided a continuous quantification of misalignment in neurological populations such as people with Parkinson's disease (PD).ObjectiveDetermine whether a continuous quantification of misalignment between actual and perceived balance ability, discordance, relates to functional outcomes such as quality of life and cognition.MethodsActual (gait velocity), and perceived (Activities of Balance Confidence) balance, cognition (measured via a computer-based cognitive assessment), and mobility-related quality of life were captured in a clinical sample of 95 people with PD. Primary outcomes were quality of life and cognitive domains frequently altered in people with PD (global cognition & executive function). Secondary cognitive domains assessed were attention, memory, visuo-spatial, verbal function, and information processing. Linear and non-linear models assessed the relationship between discordance, quality of life, and cognition.ResultsDiscordance related to mobility-related quality of life, such that under-confidence was related to poorer quality of life. Non-linear (quadratic) models were shown to fit the discordance-Global cognition (p = 0.02) data better than linear models such that over- and under-confidence related to poorer cognition. Secondary cognitive domains were not robustly related to discordance.ConclusionsIn a clinical sample of people with PD, discordance was related to mobility-related quality of life and global cognition. Global cognition further exhibited a possible non-linear relationship to discordance indicating that over- or under-confidence may relate to poorer cognition. This work underscores the functional relevance of misalignment of actual and balance abilities.

Feline immunodeficiency virus (FIV) is a lentivirus that exhibits significant structural and pathological similarities to human immunodeficiency virus (HIV), establishing it as a valuable model for HIV vaccine development. In this study, artificial intelligence (AI) and immunoinformatics were employed to design a novel multi-epitope DNA vaccine targeting conserved regions of the FIV gag, pol, and env genes. Predicted B-cell and T-cell epitopes were evaluated for their capacity to induce strong immune responses while minimizing allergenic or toxic effects and were linked to the immune adjuvant PADRE. Structural analysis indicated that the vaccine construct is stable, soluble, and biocompatible, with a well-folded tertiary structure that binds Toll-like receptor 9 (TLR9) and elicits robust humoral and cellular immune responses. These findings identify a promising FIV vaccine candidate and provide insights for the development of next-generation HIV vaccines.

Background:Meniscus tears occur in tandem with other degenerative changes at the knee joint, making interpretation of imaging findings challenging. Meniscus tears, commonly treated by general physicians and musculoskeletal specialists, have significant treatment variability.Purpose/Hypothesis:The purpose of this study was to investigate whether big data analytical tools and natural language processing (NLP) of magnetic resonance imaging reports could identify factors that are predictive of treatment decisions in a large cohort of patients. It was hypothesized that surgical treatment would be associated with specific meniscus tear patterns.Study Design:Cross-sectional study; Level of evidence, 3.Methods:Deidentified electronic health records from approximately 5 million patients, available at Information Commons, were analyzed to identify patients with meniscus tears on knee MRI reports. NLP was used to extract descriptive features from MRI reports. Demographics and clinical and treatment data were recorded. Univariate and multivariate analyses were performed.Results:For 4013 patients with meniscus tears on MRI, physical therapy was the most common treatment (62.4% of patients). Opioid medications were prescribed to 25.6% of patients diagnosed with a meniscus tear. Surgery was performed for 19.6% of patients. A bucket-handle tear was the strongest predictor for receiving surgery. Meniscus tear patterns, the presence of degenerative changes, and demographic factors were independent predictors of treatment received.Conclusion:Meniscus tear types and other findings at the knee joint, along with demographic variables, are associated with treatment for meniscus tears. Bucket-handle and root tears were most likely to undergo surgical treatment, while patients on Medicare and those with arthrosis were more likely to be treated with nonoperative modalities. NLP of big data, including radiology findings, may have a role in providing clinical decision support for interpreting findings on knee MRIs. Prescription of opioid medications in meniscal tears was observed at a higher-than-expected rate.

Breast cancer is the most prevalent and leading cause of cancer-related mortality among women worldwide. The triple-negative subtype, the most aggressive form of the disease, is associated with the poorest prognosis. In order to improve the treatment of these patients, we have synthesized a phyto-chemo drug conjugate composed of cisplatin and eugenol, two molecules with synergistic anti-cancer effects. Eugenoplatin was synthesized and characterized by HPLC, LC/MS, and 1H-NMR, while its physicochemical properties were predicted by in silico analysis using the Biovia Discovery Studio. The cytotoxic effects of eugenoplatin were first tested in vitro using the WST1 and the flow cytometry techniques. Cell proliferation, migration, and invasion abilities were assessed using the xCELLigence Real-Time Cell Analysis. The changes in gene expression were determined by proteomics analysis (LC/MS), immunoblotting, immunofluorescence, and quantitative RT-PCR. The effect of the drug on breast cancer stem cells was determined by the tumorsphere formation assay, and cell sorting was utilized to isolate a specific breast cancer sub-population of cells. Furthermore, orthotopic tumor xenografts were used to test the potential therapeutic value of eugenoplatin in vivo. The novel DNA-damaging molecule (eugenoplatin) has shown higher cytotoxicity through induction of apoptosis, and strong inhibition of cell growth via cell cycle delay at G2/M phase in different cell lines. In addition, eugenoplatin targeted cancer stem cells through inhibition of the β-catenin signaling pathway. These effects were confirmed in humanized orthotopic tumor xenografts, wherein the eugenoplatin-dependent tumor growth inhibition was more than 10-fold stronger than the cisplatin repressive effect, with a potent inhibitory effect on cancer stem cell biomarkers. This was associated with the suppression of various cancer-related signaling pathways, including STAT3/NF-κB, AKT/mTOR, and ERK. Furthermore, eugenoplatin down-regulated the pro-angiogenic factors VEGF-A, IL-6, and IL-8, and repressed angiogenesis both in vitro and in tumor xenografts. In silico analysis has suggested good permeability, good absorption, and higher bioavailability for eugenoplatin, which is also unlikely to be mutagenic, carcinogenic, or hepatotoxic. These results indicate that eugenoplatin, a novel DNA-damaging agent that can also target cancer stem cells, could be of great therapeutic value for TNBC patients.

Stigma remains a significant barrier to educational attainment for individuals with criminal records or mental illness, yet little is known about how college students perceive peers with these stigmatized backgrounds. Undergraduates (N = 307) were randomly assigned to one of three conditions to assess attitudes toward peers with: (a) no disclosed background (control), (b) a mental health diagnosis, or (c) a criminal record. They completed a version of the Situational Attitudes Scale (SAS), wherein they read a series of short vignettes and rated their emotional reactions (e.g., anger, fear) to each scenario. Participants also responded to open-ended questions about societal and personal attitudes toward individuals in their assigned condition. SAS scores were statistically similar between the control and mental illness conditions, whereas the criminal background condition scored significantly lower than both. Sentiment analysis of open-ended responses revealed a nuanced pattern: responses to the criminal background condition were rated significantly less positive than the other two, whereas the mental illness condition was also rated lower than the control. Respondents in the Control and Mental Illness conditions rated their own treatment of their target groups more positively than society (possibly a false uniqueness effect), whereas sentiment was similar across prompts for the Criminal condition. Stigma toward students with criminal backgrounds may differ in both form and intensity than toward other groups. These results underscore the value of combining direct and indirect measures of stigma to capture subtle but meaningful variations in how bias is expressed. Given the critical role of educational attainment as both a social determinant of health and a protective factor against recidivism, addressing campus climate is essential—not only to support students with stigmatized backgrounds, but also to advance equity and well-being within academic institutions and the communities they serve.

Introduction: Methocarbamol is a skeletal muscle relaxant commonly used in multimodal analgesia and has been shown to reduce postoperative opioid use. Due to the presence of polyethylene glycol, its intravenous (IV) formulation is contraindicated in patients with renal impairment per prescribing information. However, clinical evidence supporting this caution is limited. This study aimed to evaluate safety of the short-term use of IV methocarbamol in hospitalized patients with impaired renal function. Methods: We conducted a multicenter, retrospective cohort study comparing patients with baseline renal impairment (study group) to those with normal renal function (control group). Adults hospitalized for 48 hours or longer who received at least 3 doses of IV methocarbamol were included. Exclusion criteria included dialysis at admission, uncontrolled sepsis, diabetic ketoacidosis, or drug overdose. Primary outcomes were a composite of mortality, new renal replacement therapy, and persistent renal dysfunction, as well as the incidence of acute kidney injury (AKI). Secondary outcomes included in-hospital mortality, length of stay, and metabolic acidosis. Safety outcomes included central nervous system (CNS) effects, hypotension, bradycardia, and drug discontinuation. Results: Of 250 patients, 96 were in the study group and 154 in the control group. The study group was older (75.2 vs. 53.9 years, p < 0.001), had lower creatinine clearance (47.6 vs. 89.2 mL/min, p < 0.001), and more chronic kidney disease (33.3 percent vs. 1.3 percent, p < 0.001). The control group received higher cumulative methocarbamol doses (5000 vs. 3875 mg, p < 0.001) and opioids (167.5 vs. 126.3 morphine equivalents, p = 0.011). The incidence of AKI was similar (6.3 percent vs. 3.9 percent, p = 0.397); no patients required new dialysis or had persistent renal dysfunction. Acid-base parameters and metabolic acidosis rates did not differ significantly. CNS effects, hypotension, bradycardia, and adverse events leading to discontinuation were rare and comparable. Conclusions: IV methocarbamol was well tolerated in patients with renal impairment and was not associated with increased renal or systemic toxicity. These findings support its short-term safety in this population when used appropriately.

Pleural mesothelioma (PM) is an uncommon yet deadly cancer linked to asbestos exposure. The lack of effective early diagnosis and treatment leads to reduced life expectancy among patients with PM. This study aims to identify a novel molecular target inhibitor to develop more effective therapeutics for PM. Our drug screening assay showed that the fatty acid synthase (FASN) inhibitor cerulenin demonstrates strong and selective antiproliferative properties against NF2/CDKN2A(p16)-deficient PM cells, surpassing the effects of C75, cisplatin or pemetrexed. FASN protein is frequently detected in NF2/p16-deficient PM tumor-derived tissues (15/15, 100%), but rarely in NF2/p16-intact PM tumors (8/25, 32%). Notably, cerulenin administration successfully reduced the growth of NF2/p16-deficient PM tumors in xenografted mice. Cerulenin inhibits mitochondrial fission by targeting dynamin-related protein 1 (DRP1) in NF2/p16-deficient cells. Moreover, the disruption of the FASN gene leads to increased ubiquitination of DRP1. These findings suggest that FASN might play a role in the tumorigenesis of PM cells through the regulation of mitochondrial dynamics. This research offers a novel perspective on the potential development of precision medicine for PM.

Objective: We report a unique case of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) possibly related to administering daptomycin and ceftaroline for persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We describe treatment strategies and challenges of determining drug causality when multiple antimicrobials are administered. Case: A 78-year-old male developed SJS/TEN during week 6 of daptomycin and ceftaroline therapy. Other antimicrobials administered within the previous 8 weeks included vancomycin, meropenem, piperacillin/tazobactam, levofloxacin, and fluconazole. Causality was assessed using the Algorithm of Drug Causality for Epidermal Necrolysis, which indicated probable association with ceftaroline and possible association with daptomycin. Management included discontinuing both agents, transferring to a burn intensive care unit, wound care, and treatment with intravenous immunoglobulin. Discussion/Conclusion: Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of daptomycin and ceftaroline is rare. Appropriate and timely diagnosis and management by a multidisciplinary team led to favorable clinical outcomes.