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Exploring the Impact of Perceived Racial Discrimination on Cognitive Decline in Adults Over 45
No full textThis study explored the association between perceived racial discrimination and subjective cognitive decline among adults 45 years and older in the United States. Secondary data analysis was conducted using the 2023 Behavioral Risk Factor Surveillance System (BRFSS) survey. The sample consisted of respondents from states that included responses from the Cognitive Decline and Reactions to Race optional modules in the BRFSS. Data analysis included univariate, bivariate, and logistic regression analysis, while accounting for the complex sampling design. The results of this study indicated that adults who reported worse racial treatment, both in general and in healthcare, were more likely to report cognitive decline, with the highest prevalence reported among Black adults. Perceived racial discrimination is significantly associated with subjective cognitive decline, necessitating the need for culturally-tailored healthcare practices and policies to reduce these racial disparities in cognitive health outcomes
Mind Over Matter: Do Nootropics Hold the Key to Fighting Alzheimer’s?
No full textAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. Nootropics, a class of cognitive-enhancing compounds, have recently emerged as potential therapeutic agents for mitigating the cognitive impairments associated with AD. This paper reviews the current evidence regarding the efficacy (or lack thereof) of different treatments used in the past for treating Alzheimer’s, including cholinesterase inhibitors and anti-Aβ antibodies. The findings are compared to those using various nootropics, including natural supplements and synthetic compounds, in modulating neurobiological pathways relevant to AD pathology. Mechanisms of action such as neuroprotection, antioxidant activity, acetylcholine modulation, and anti-inflammatory effects are explored. Preclinical studies demonstrate promising results, showing improved synaptic plasticity and neuronal survival, while clinical trials report mixed but encouraging outcomes in cognitive performance, particularly in early-stage AD patients. Despite this potential, limitations such as small sample sizes, inconsistent dosing regimens, and limited long-term data impede definitive conclusions. Further rigorous randomized controlled trials are necessary to establish the safety, efficacy, and mechanisms of nootropics in Alzheimer’s disease treatment. This review highlights the need for a multidisciplinary approach to fully understand the therapeutic value of nootropics in addressing the cognitive deficits of Alzheimer’s disease
Aripiprazole Lauroxil Every 2 Months or Paliperidone Palmitate Monthly for Acute Schizophrenia: A Post Hoc Analysis of PANSS Five-Factor Scores in the ALPINE Trial
No full textPurpose: The randomized, controlled Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study (NCT03345979) evaluated the efficacy and safety of aripiprazole lauroxil (AL) administered every-2-months in patients with schizophrenia. Primary results indicating significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores with AL or active control (paliperidone palmitate [PP] monthly) were reported previously. In this post hoc analysis, treatment effects based on a PANSS five-factor model were assessed. Patients and Methods: Adult patients with an acute exacerbation of schizophrenia were enrolled as inpatients, randomized to AL (1064 mg every 2 months) or PP (156 mg monthly), discharged after 2 weeks, and then followed as outpatients through week 25. PANSS five-factor scores at baseline and weeks 4, 9, and 25 were analyzed in this post hoc analysis. Within-group changes from baseline were summarized by treatment group using the last-observation-carried-forward method for imputation; no formal testing of statistical significance was performed. Results: Of 200 patients randomized to AL (n=99) or PP (n=101), 99 patients (AL, n=56; PP, n=43) completed study treatment. Improvement in PANSS factor scores was observed with AL from baseline to week 25. Mean (standard error [SE]) changes at week 25 were −3.5 (0.42) (negative); −5.4 (0.56) (positive); −3.4 (0.39) (disorganized thought); −1.9 (0.32) (uncontrolled hostility/excitement); and −3.1 (0.37) (anxiety/depression). For PP, week 25 PANSS factor improvements (mean [SE]) for the negative, positive, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression factors were −3.4 (0.48), −6.0 (0.49), −4.0 (0.35), −2.2 (0.30), and −3.5 (0.41), respectively. Conclusion: In this post hoc analysis of patients with acutely exacerbated schizophrenia treated with AL 1064 mg every-2-months or PP 156 mg monthly, numerical improvements in PANSS five-factor scores were observed over time. These results support the primary efficacy findings based on PANSS total score and suggest that efficacy extends to these clinically important symptom domains
Inhibition of NAMPT as a Therapeutic Strategy to Suppress Tumor Growth in Lymphangioleiomyomatosis
No full textLymphangioleiomyomatosis (LAM) is a rare, progressive lung disease driven by mutations in the TSC1 or TSC2 genes, leading to constitutive mTORC1 activation and uncontrolled cell proliferation. Current therapies, like rapamycin effectively stabilize disease progression but mainly exert cytostatic effects and promote autophagy, a survival mechanism in LAM cells. These limitations highlight the need for the development of innovative therapies to achieve more effective and lasting results. To explore alternative therapeutic targets, we investigated the role of nicotinamide phosphoribosyltransferase (NAMPT), a key regulator of NAD+ biosynthesis, in LAM and TSC2-deficient cells using a potent inhibitor, FK866. Our study demonstrates that FK866 depletes NAD+ levels in these cells, exerting a dual effect by activating AMPK and subsequently inhibiting mTORC1 signaling while suppressing autophagy. Unlike rapamycin, FK866 does not induce compensatory Akt activation, significantly inhibits LAM cell proliferation and induces apoptosis. Additionally, using an in vivo chicken egg chorioallantoic membrane (CAM) model, we showed that FK866 treatment significantly reduces LAM tumor growth compared to controls suggesting that NAMPT inhibition disrupts metabolic and survival pathways critical for TSC2-deficient cell viability and tumor progression. Our results establish NAMPT as a promising therapeutic target for LAM, offering a two-prong strategy to suppress tumor growth and enhance apoptosis, providing an alternative to current mTOR-based therapies
Construction and Characterization of Chimeric Fcγr T Cells for Universal T Cell Therapy
No full textBackground: Several approaches are being explored for engineering off-the-shelf chimeric antigen receptor (CAR) T cells. In this study, we engineered chimeric Fcγ receptor (FcγR) T cells and tested their potential as a versatile platform for universal T cell therapy. Methods: Chimeric FcγR (CFR) constructs were generated using three distinct forms of FcγR, namely CD16A, CD32A, and CD64. The functionality of CFR T cells was evaluated through degranulation assays, specific target lysis experiments, in vitro cytokine production analysis, and assessment of tumor xenograft destruction specificity in mouse models using different monoclonal antibodies (MoAbs). Results: Three types of CFR T cells were engineered, 16s3, 32-8a, 64-8a CFR T cells. In the presence of rituximab (RTX), cytotoxicity of all three types of CFR T cells against CD20+ Raji-wt, K562-CD20+, and primary tumor cells was significantly higher than that of the mock T cells (P \u3c 0.001). When herceptin was used, all three types of CFR T cells exhibited significant cytotoxicity against HER2+ cell lines of SK-BR-3, SK-OV-3, and HCC1954 (P \u3c 0.001). The cytotoxicity of 64-8a CFR T cells was significantly inhibited by free human IgG at a physiological dose (P \u3c 0.001), which was not observed in 16s3, 32-8a CFR T cells. Compared to 32-8a CFR T cells, 16s3 CFR T cells exhibited more prolonged cytotoxicity than 32-8a CFR T cells (P \u3c 0.01). In in vivo assays using xenograft models, 16s3 CFR T cells significantly prolonged the survival of mice xenografted with Raji-wt cells in the presence of RTX (P \u3c 0.001), and effectively reduced tumor burden in mice xenografted with SK-OV-3 cells in the presence of herceptin (P \u3c 0.05). No significant non-specific cytotoxicity of CFR T cells was found in vivo. Conclusion: The anti-tumor effects of the CFR T cells in vitro and in xenograft mouse models are mediated by specific MoAbs such as RTX and herceptin. The CFR T cells therefore have the features of universal T cells with specificity directed by MoAbs. 16s3 CFR T cells are chosen for clinical trials
Traumatic Brain Injury and Artificial Intelligence: Shaping the Future of Neurorehabilitation—A Review
No full textTraumatic brain injury (TBI) is a leading cause of disability and death globally, presenting significant challenges for diagnosis, prognosis, and treatment. As healthcare technology advances, artificial intelligence (AI) has emerged as a promising tool in enhancing TBI rehabilitation outcomes. This literature review explores the current and potential applications of AI in TBI management, focusing on AI’s role in diagnostic tools, neuroimaging, prognostic modeling, and rehabilitation programs. AI-driven algorithms have demonstrated high accuracy in predicting mortality, functional outcomes, and personalized rehabilitation strategies based on patient data. AI models have been developed to predict in-hospital mortality of TBI patients up to an accuracy of 95.6%. Furthermore, AI enhances neuroimaging by detecting subtle abnormalities that may be missed by human radiologists, expediting diagnosis and treatment decisions. Despite these advances, ethical considerations, including biases in AI algorithms and data generalizability, pose challenges that must be addressed to optimize AI’s implementation in clinical settings. This review highlights key clinical trials and future research directions, emphasizing AI’s transformative potential in improving patient care, rehabilitation, and long-term outcomes for TBI patients