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Amyotrophic lateral sclerosis (ALS) is a fatal and intricate neurodegenerative disease that impacts upper and lower motor neurons within the central nervous system, leading to their progressive destruction. Despite extensive research, the pathogenesis of this multifaceted disease remains elusive. The United States Food and Drug Administration (FDA) has granted approval for seven medications designed to address ALS and mitigate its associated symptoms. These FDA-sanctioned treatments are Qalsody, Relyvrio, Radicava, Rilutek, Tiglutik, Exservan, and Nuedexta. In this review, the effects of these seven drugs on ALS based on their mechanism of action, dosing, and clinical presentations are comprehensively summarized. Each medication offers a distinct approach to manage ALS, aiming to alleviate the burdensome symptoms and slow the disease's progression, thereby improving the quality of life for individuals affected by this neurological condition. However, despite these advancements in pharmaceutical interventions, finding a definitive cure for ALS remains a significant challenge. Continuous investigation into ALS pathophysiology and therapeutic avenues remains imperative, necessitating further research collaborations and innovative approaches to unravel the complex mechanisms underlying this debilitating condition. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD), a rare autosomal dominant neurodegenerative disease, causes the gradual deterioration of neurons in the basal ganglia, specifically in the striatum. HD displays a wide range of symptoms, from motor disturbances such as chorea, dystonia, and bradykinesia to more debilitating symptoms such as cognitive decline, behavioral abnormalities, and psychiatric disturbances. Current research suggests the potential use of dietary interventions as viable strategies for slowing the progression of HD. Most notably, the Mediterranean, vegan, carnivore, paleo, and ketogenic diets have gained attention due to their hypothesized impact on neuroprotection and symptomatic modulation in various neurodegenerative disorders. Despite substantial nutritional differences among these diets, they share a fundamental premise—that dietary factors have an influential impact in modifying pertinent biological pathways linked to neurodegeneration. Understanding the intricate interactions between these dietary regimens and HD pathogenesis could open avenues for personalized interventions tailored to the individual's specific needs and genetic background. Ultimately, elucidating the multifaceted effects of these diets on HD offers a promising framework for developing comprehensive therapeutic approaches that integrate dietary strategies with conventional treatments. [ABSTRACT FROM AUTHOR]

In this article, we present a biphasic mixture theory based mathematical model for the hydrodynamics of interstitial fluid motion and mechanical behavior of the solid phase inside a solid tumor. The tumor tissue considered here is an isolated deformable biological medium. The solid phase of the tumor is constituted by vasculature, tumor cells, and extracellular matrix, which are wet by a physiological extracellular fluid. Since the tumor is deformable in nature, the mass and momentum equations for both the phases are presented. The momentum equations are coupled due to the interaction (or drag) force term. These governing equations reduce to a one-way coupled system under the assumption of infinitesimal deformation of the solid phase. The well-posedness of this model is shown in the weak sense by using the inf-sup (Babuska–Brezzi) condition and Lax–Milgram theorem in 2D and 3D. Further, we discuss a one-dimensional spherical symmetry model and present some results on the stress fields and energy of the system based on 𝐿2 and Sobolev norms. We discuss the so-called phenomena of “necrosis” inside a solid tumor using the energy of the system.

Risedronate sodium (RIS) exhibits limited bioavailability and undesirable gastrointestinal effects when administered orally, necessitating the development of an alternative formulation. In this study, mPEG-coated nanoparticles loaded with RIS-HA-TCS were created for osteoporosis treatment. Thiolated chitosan (TCS) was synthesized using chitosan and characterized using DSC and FTIR, with thiol immobilization assessed using Ellman's reagent. RIS-HA nanoparticles were fabricated and conjugated with synthesized TCS. Fifteen batches of RIS-HA-TCS nanoparticles were designed using the Box–Behnken design process. The nanoparticles were formulated through the ionic gelation procedure, employing tripolyphosphate (TPP) as a crosslinking agent. In silico activity comparison of RIS and RIS-HA-TCS for farnesyl pyrophosphate synthetase enzyme demonstrated a higher binding affinity for RIS. The RIS-HA-TCS nanoparticles exhibited 85.4 ± 2.21% drug entrapment efficiency, a particle size of 252.1 ± 2.44 nm, and a polydispersity index of 0.2 ± 0.01. Further conjugation with mPEG resulted in a particle size of 264.9 ± 1.91 nm, a PDI of 0.120 ± 0.01, and an encapsulation efficiency of 91.1 ± 1.17%. TEM confirmed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. In vitro release studies demonstrated significantly higher release for RIS-HS-TCS-mPEG (95.13 ± 4.64%) compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%), and a marketed formulation (74.69 ± 3.98%). Ex vivo gut permeation studies revealed an apparent permeability of 0.5858 × 10−1 cm/min for RIS-HA-TCS-mPEG, surpassing RIS-HA-TCS (0.4011 × 10−4 cm/min), RIS suspension (0.2005 × 10−4 cm/min), and a marketed preparation (0.3401 × 10−4 cm/min). [ABSTRACT FROM AUTHOR]

The current research investigated the development and evaluation of dual drug-loaded nanostructure lipidic carriers (NLCs) of green tea extract and Ribociclib. In silico study were performed to determine the effectiveness of combinational approach. The prepared NLCs were subjected to in vitro drug release, lipolysis, haemolysis and cell line studies to assess their in vivo prospect. In silico study was done to get docking score of EGCG (−8.98) close to Ribociclib (−10.78) in CDK-4 receptors. The prepared NLCs exhibited particle size (175.80 ± 3.51 nm); PDI (0.571 ± 0.012); and %EE [RBO (80.91 ± 1.66%) and GTE 75.98 ± 2.35%)] respectively. MCF-7 cell lines were used to evaluate the MTT assay, cellular uptake and antioxidant (ROS and SOD) of prepared NLCs. In vitro drug release showed the controlled release up to 72 h. In vitro lipolysis and in vitro haemolysis studies showed the availability of drugs at absorption sites and the greater in vivo prospects of NLCs respectively. Pharmacokinetic study revealed a 3.63-fold and 1.53-fold increment in RBO and GTE bioavailability in female Wistar rats respectively. The prominent potential of green tea extract and RBO-loaded NLCs in enhancing their therapeutic efficacy for better treatment of breast cancer. [ABSTRACT FROM AUTHOR]

In this article, we propose a mathematical model that describes hydrodynamics and deformation mechanics within a solid tumor which is embedded in or adjacent to a healthy (normal) tissue. The tumor and normal tissue regions are assumed to be deformable and the theory of mixtures is adapted to mass and momentum balance equations for fluid flow and tissue deformation mechanics in each region. The momentum balance equations are coupled via forces that interact between the phases (fluid and solid). Continuity of normal velocities, displacements, and normal stresses along with the Beaver–Joseph–Saffman condition are imposed at the interface between the tumor and tissue regions. The physiological transport parameters (such as hydraulic resistivity or permeability) are assumed to be heterogeneous and deformation dependent which makes the model nonlinear. We establish the existence of a weak solution using Galerkin and weak convergence methods. We show further that the solution is unique and depends continuously on the given data. [ABSTRACT FROM AUTHOR]

This project was designed to extract anti-hyperlipidaemic activity of simvastatin for the longer duration of time and the solubility enhancement of this BCS class II drug was also sought by preparing nanostructured lipid carrier (NLC). The method for NLC preparation involved melt-emulsification followed by ultrasonication. The developed formulation was optimized by 3-level, 3-factor Box-Behnken design. The independent variables were % lipid mixture, % surfactant and sonication time (minutes). The responses selected were particle size, PDI and entrapment efficiency. The optimized formulation had particle size 114.62 ± 5.65, PDI 0.210 ± 0.034 and entrapment efficiency 85.20 ± 7.98%. The optimized formulation was further characterized by TEM and SEM. Spherical shape and nano size distribution of the optimized formulation were confirmed by SEM and TEM, respectively. The DSC of optimized formulation hints for the loss of crystalline nature of drug whereas the FT-IR spectra reveal that there is no interaction between drug and excipients when incorporated in NLC. The drug release from the NLC was biphasic (burst release was followed by sustained release). The kinetic of drug release followed Fickian diffusion with Korsmeyer-Peppas model. When the antihyperlipidaemic activity of SMV-NLC was compared with SMV-suspension, it was found that SMV-NLC significantly decreased the total cholesterol and triglyceride level by 2.77 and threefolds, respectively. [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe, chronic psychiatric disorder characterized by delusions, hallucinations, cognitive impairments, and emotional dysregulation. This psychiatric illness is often resistant to treatment. This literature review aims to analyze the relationship between this complex psychological disorder and the gut microbiota found within the human body. The brain and gut are interconnected, and emerging research suggests a link between gut dysbiosis and schizophrenia. Gut dysbiosis refers to an imbalance or disruption in the composition and function of the gut microbiome. The studies comparing the gut microbiota of patients with schizophrenia to those without highlight significant differences at the phylum and genus levels, providing evidence of gut microbiome alteration. The lack of diversity of microbiota in schizophrenia patients can be altered and improved to a healthier microbiome by way of dietary intervention. Interventions that target the gut-brain axis, such as dietary probiotics or prebiotics, may help alleviate certain symptoms of schizophrenia and help improve patients' well-being. Understanding the complex interplay between gut microbiome health and schizophrenia may allow for the development of targeted interventions that alter the gut microbiome of patients with schizophrenia and, in turn, mitigate their symptoms and improve their quality of life., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ansari et al.)

Recent studies have shown that low preoperative resilience may lead to inferior outcomes following arthroscopic rotator cuff repair. Therefore, the purpose of this systematic review is to evaluate whether preoperative patient resilience is associated with outcome measures, including patient-reported outcome measurements (PROMs) and sleep quality, following arthroscopic rotator cuff repair. To perform the review, a literature search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the PubMed and Embase databases to gather studies related to the influence of preoperative resilience on postoperative outcomes of rotator cuff repair. Methodological quality and risk of bias were assessed using the Methodological Index for Non-randomized Studies (MINORS). Seven studies with 584 patients were included. Of 36 total reported postoperative outcomes, including PROMs and sleep quality, 14 had a significant positive correlation with higher preoperative resilience. One study reported that higher resilience was significantly correlated with worse sleep quality at a two-week follow-up but not at further follow-ups of up to 24 weeks. Significant differences in outcomes between patients with varying levels of resilience were assessed in five studies, all of which found that patients with higher resilience had significantly better outcomes or no significant differences in outcomes between patients with varying levels of preoperative resilience. In no study was it reported that patients with low resilience had better outcomes. Overall, approximately half of all reported postoperative outcome data was found to be significantly associated with preoperative resilience. Therefore, clinicians should preemptively identify those with low resilience and administer psychological interventions to limit inferior outcomes following arthroscopic rotator cuff repair., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Akhtar et al.)

Abstract: Physical medicine and rehabilitation has rapidly been garnering interest as health care increases the emphasis on rehabilitation and management for acute and chronic diseases. This study analyzes recent geographical trends of physical medicine and rehabilitation residents via physical medicine and rehabilitation residents from 2019 to 2023, which were identified from publicly available data. The relative distribution from medical school to residency, medical school to preliminary program, and preliminary program to residency were analyzed. These locations were categorized as within 100 miles, same state, same region, or different region. Odds ratio were calculated for the aforementioned relative locations with respect to the presence of a home residency program. A total of 1836 residents were included. The majority of residents (51%) stayed within the same region as their medical school. Residents from medical schools with a home program were more likely to stay within 100 miles (odds ratio: 3.64), the same state (odds ratio: 3.19), and same region (odds ratio: 2.56). Overall, physical medicine and rehabilitation residents are likely to stay within the same region as their medical school and preliminary year. In addition, the presence of a home program significantly increases the odds of matching within 100 miles, same state, and same region., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Sirtuins (SIRT) are a class of histone deacetylases that regulate important metabolic pathways and play a role in several disease processes. Of the seven mammalian homologs currently identified, sirtuin 1 (SIRT1) is the best understood and most studied. It has been associated with several neurodegenerative diseases and cancers. As such, it has been further investigated as a therapeutic target in the treatment of disorders such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD). SIRT1 deacetylates histones such as H1 lysine 26, H3 lysine 9, H3 lysine 56, and H4 lysine 16 to regulate chromatin remodeling and gene transcription. The homolog has also been observed to express contradictory responses to tumor suppression and tumor promotion. Studies have shown that SIRT1 may have anti-inflammatory properties by inhibiting the effects of NF-κB, as well as stimulating upregulation of autophagy. The SIRT1 activators resveratrol and cilostazol have been shown to improve Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores in AD patients. In this review, we aim to explore the various roles of SIRT1 with regard to neuroprotection and neurodegeneration., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Razick et al.)