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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.
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ABSTRACT: Physical Medicine and Rehabilitation (PM&R) has rapidly been garnering interest as healthcare increases the emphasis on rehabilitation and management for acute and chronic diseases. This study analyzes recent geographical trends of PM&R residents via PM&R 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 (OR) 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 (OR: 3.64), the same state (OR: 3.19), and same region (OR: 2.56). Overall, PM&R residents are likely to stay within the same region as their medical school and preliminary year. Additionally, the presence of a home program significantly increases the odds of matching within 100 miles, same state, and same region.
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Integrating innovation and environmental responsibility has become important in pursuing sustainable industrial practices in the contemporary world. These twin imperatives have stimulated research into developing methods that optimize industrial processes, enhancing efficiency and effectiveness while mitigating undesirable ecological impacts. This objective is exemplified by the emergence of biochar derived from the thermo-chemical transformation of biomass. This review examines biochar production methods and their potential applications across various aspects of the iron and steel industries (ISI). The technical, economic, and sustainable implications of integrating biochar into the ISI were explored. Slow pyrolysis and hydrothermal carbonization are the most efficient methods for higher biochar yield (25-90%). Biochar has several advantages- higher heating value (30-32 MJ/kg), more porosity (58.22%), and significantly larger surface area (113 m2/g) compared to coal and coke. However, the presence of biochar often reduces fluidity in a coal-biochar mixture. The findings highlighted that biochar production and implementation in ISI often come with higher costs, primarily due to the higher expense of substitute fuels compared to traditional fossil fuels. The economic viability and societal desirability of biochar are highly uncertain and vary significantly based on factors such as location, feedstock type, production scale, and biochar pricing, among others. Furthermore, biomass and biochar supply chain is another important factor which determines its large scale implementation. Despite these challenges, there are opportunities to reduce emissions from BF-BOF operations by utilizing biochar technologies. Overall, the present study explored integrating diverse biochar production methods into the ISI aiming to contribute to the ongoing research on sustainable manufacturing practices, underscoring their significance in shaping a more environmentally conscious future.
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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.
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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.
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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.
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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).
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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.
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The aim of this investigation was to develop and analyze a tacrolimus and thymoquinone co-loaded nanostructured lipid carriers (TAC-THQ-NLCs)-based nanogel as a new combinatorial approach for the treatment of psoriasis. The NLCs were formulated by an emulsification-solvent-evaporation technique using glyceryl monostearate, Capryol 90 (oil), and a mixture of Tween 80 and Span 20 as a solid lipid, liquid lipid, and surfactant, respectively. Their combination was optimized using a three-factor and three-level Box-Behnken design (33-BBD). The optimized TAC-THQ-NLCs were observed to be smooth and spherical with a particle size of 144.95 ± 2.80 nm, a polydispersity index of 0.160 ± 0.021, a zeta potential of -29.47 ± 1.9 mV, and an entrapment efficiency of >70% for both drugs. DSC and PXRD studies demonstrated the amorphous state of TAC and THQ in the lipid matrix of the NLCs. An FTIR analysis demonstrated the excellent compatibility of the drugs with the excipients without interactions. The TAC-THQ-NLC-based nanogel (abbreviated as TAC-THQ-NG) exhibited a good texture profile and good spreadability. The in vitro release study demonstrated a sustained drug release for 24 h from the TAC-THQ-NG that followed the Korsmeyer-Peppas kinetic model with a Fickian diffusion mechanism. Moreover, the TAC-THQ-NG revealed significantly higher dose-dependent toxicity against an HaCaT cell line compared to a TAC-THQ suspension gel (abbreviated as TAC-THQ-SG). Furthermore, the developed formulations demonstrated antioxidant activity comparable to free THQ. Confocal microscopy revealed improved permeation depth of the dye-loaded nanogel in the skin compared to the suspension gel. Based on these findings, it was concluded that TAC-THQ-NG is a promising combinatorial treatment approach for psoriasis.
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Exemestane (EXE), an irreversible aromatase inhibitor, is primarily used as a first-line therapy for estrogen receptor-positive breast cancer patients. However, complex physicochemical characteristics of EXE limit its oral bioavailability (<10%) and anti-breast cancer efficacy. The present study aimed to develop a novel nanocarrier system to improve the oral bioavailability and anti-breast cancer efficacy of EXE. In this perspective, EXE-loaded TPGS-based polymer lipid hybrid nanoparticles (EXE-TPGS-PLHNPs) were prepared by the nanoprecipitation method and evaluated for their potential in improving oral bioavailability, safety, and therapeutic efficacy in the animal model. EXE-TPGS-PLHNPs showed significantly higher intestinal permeation in comparison to EXE-PLHNPs (without TPGS) and free EXE. After oral administration, EXE-TPGS-PLHNPs and EXE-PLHNPs revealed 3.58 and 4.69 times higher oral bioavailability in Wistar rats compared to the conventional EXE suspension. The results of the acute toxicity experiment suggested that the developed nanocarrier was safe for oral administration. Furthermore, EXE-TPGS-PLHNPs and EXE-PLHNPs represented much better anti-breast cancer activity in Balb/c mice bearing MCF-7 tumor xenograft with tumor inhibition rate of 72.72% and 61.94% respectively in comparison with the conventional EXE suspension (30.79%) after 21 days of oral chemotherapy. In addition, insignificant changes in the histopathological examination of vital organs and hematological analysis further confirm the safety of the developed PLHNPs. Therefore, the findings of the present investigation advocated that the encapsulation of EXE in PLHNPs can be a promising approach for oral chemotherapy of breast cancer.
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Neoplasias da Mama , Nanopartículas , Humanos , Ratos , Animais , Camundongos , Feminino , Polímeros/uso terapêutico , Disponibilidade Biológica , Ratos Wistar , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Androstadienos/farmacologia , Androstadienos/uso terapêutico , LipídeosRESUMO
PURPOSE: The current research investigated the development and evaluation of dual drug-loaded nanostructure lipidic carriers (NLCs) of green tea extract and Ribociclib. METHOD: 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. RESULTS: 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. CONCLUSION: The prominent potential of green tea extract and RBO-loaded NLCs in enhancing their therapeutic efficacy for better treatment of breast cancer.
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Nanoestruturas , Neoplasias , Ratos , Animais , Feminino , Antioxidantes , Lipídeos/química , Hemólise , Ratos Wistar , Nanoestruturas/química , Portadores de Fármacos/química , Tamanho da Partícula , Excipientes , CháRESUMO
At present, cancer is the most deadly disease and one of the most common causes of death worldwide providing different obstacles to chemotherapy including non-specific biodistribution of chemotherapeutic drugs, dose-related adverse effects, development of metastasis and chemoresistance. Nanoparticle-based targeted delivery of chemotherapeutics gained enormous attention in the treatment of solid tumors as they provide many significant advantages including prolonged drug release, enhanced systemic half-life, decreased toxicity and targeted drug delivery. Polymer-lipid hybrid nanoparticles (PLHNPs) are the most effective nanoplatform that develop from building blocks of polymers and lipids. PLHNPs combine the unique advantages of both lipid-based nanoparticles as well as polymeric nanoparticles. PLHNPs integrate biocompatible polymers and biomimetic lipids in their architecture, which imparts PLHNPs with wide versatility for delivering chemotherapeutic drugs of different physicochemical characteristics to their target site of action. The hybrid architecture of PLHNPs provides many exceptional advantages such as small particle size, encapsulation of more than one anticancer drugs, high drug loading capacity and modified drug release profile. Furthermore, the surface decoration of PLHNPs improves the therapeutic potential of the chemotherapeutic drug by selective targeting of tumor tissue and reduces the side effects by decreasing non-specific biodistribution. This review highlights the challenges in the treatment of solid tumors by using nanoparticles system, rationale and targeting strategies of PLHNPs in the targeted treatment of solid tumors, and current progress of PLHNPs in the management of different types of solid tumors.