The Potential of Spinal Cord Stimulation in Treating Spinal Cord Injury.

Purpose Of The Review: In the United States, spinal cord injuries affect approximately 18,000 individuals annually, most commonly resulting from mechanical trauma. The consequent paraplegia severely impairs motor functions, creating an urgent need for innovative therapeutic strategies that extend beyond traditional rehabilitation and pharmacotherapy. This review assesses the effectiveness of Spinal Cord Stimulation (SCS) in improving motor function in patients with spinal cord injuries, with a particular focus on paraplegia.

Fabrication of a micropatterned shape-memory polymer patch with L-DOPA for tendon regeneration.

A scaffold design for tendon regeneration has been proposed, which mimics the microstructural features of tendons and provides appropriate mechanical properties. We synthesized a temperature-triggered shape-memory polymer (SMP) using the ring-opening polymerization of polycaprolactone (PCL) with polyethylene glycol (PEG) as a macroinitiator. We fabricated a micropatterned patch using SMP capillary force lithography, which mimicked a native tendon, for providing physical cues and guiding effects.

Harnessing the AI/ML in Drug and Biological Products Discovery and Development: The Regulatory Perspective.

Artificial Intelligence (AI) has the disruptive potential to transform patients' lives via innovations in pharmaceutical sciences, drug development, clinical trials, and manufacturing. However, it presents significant challenges, ethical concerns, and risks across sectors and societies. AI's rapid advancement has revealed regulatory gaps as existing public policies struggle to keep pace with the challenges posed by these emerging technologies.

GnRH Peptide Antagonist: Comparative Analysis of Chemistry and Formulation with Implications for Clinical Safety and Efficacy.

Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems.

Associations of Voice Metrics with Postural Function in Parkinson's Disease.

Background: This study aimed to explore the potential associations between voice metrics of patients with PD and their motor symptoms.

Methods: Motor and vocal data including the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Harmonic-Noise Ratio (HNR), jitter, shimmer, and smoothed cepstral peak prominence (CPPS) were analyzed through exploratory correlations followed by univariate linear regression analyses. We employed these four voice metrics as independent variables and the total and sub-scores of the UPDRS-III as dependent variables.

Dysregulation of FURIN and Other Proprotein Convertase Genes in the Progression from HPV Infection to Cancer.

Productive infections of oncogenic human papillomaviruses (HPVs) are closely linked to the differentiation of host epithelial cells, a process that the virus manipulates to create conditions favorable to produce virion progeny. This viral interference involves altering the expression of numerous host genes. Among these, proprotein convertases (PCs) have emerged as potential oncogenes due to their central role in cellular functions.

Feasibility and Acceptability of Integrating Acupuncture for Management of Multiple Symptoms in Medically Underserved Breast Cancer Survivors.

Background/objectives: Breast cancer survivors undergoing long-term endocrine therapy often experience multiple symptoms, including pain, fatigue, sleep disturbance, hot flashes, anxiety, and depression. This study explored the feasibility and acceptability of integrating acupuncture for symptom management in medically underserved breast cancer survivors.

Methods: This randomized controlled trial was conducted at two clinics serving medically underserved populations.

Affordable mRNA Novel Proteins, Recombinant Protein Conversions, and Biosimilars-Advice to Developers and Regulatory Agencies.

mRNA technology can replace the expensive recombinant technology for every type of protein, making biological drugs more affordable. It can also expedite the entry of new biological drugs, and copies of approved mRNA products can be treated as generic or biosimilar products due to their chemical nature. The introduction of hundreds of new protein drugs have been blocked due to the high cost of recombinant development.

Gonadal Hormone Changes with Aging and Their Impact on Chronic Pain.

Chronic pain, pain that lasts beyond three months, is a common finding in the elderly. It is often due to musculoskeletal conditions but can be precipitated by other factors as well. While physiological systems decline with aging, chronic pain is influenced by changes in hormone profiles as men and women enter into andropause and menopause, respectively.

Biomarker Investigation Using Multiple Brain Measures from MRI Through Explainable Artificial Intelligence in Alzheimer's Disease Classification.

As the leading cause of dementia worldwide, Alzheimer's Disease (AD) has prompted significant interest in developing Deep Learning (DL) approaches for its classification. However, it currently remains unclear whether these models rely on established biological indicators. This work compares a novel DL model using structural connectivity (namely, BC-GCN-SE adapted from functional connectivity tasks) with an established model using structural magnetic resonance imaging (MRI) scans (namely, ResNet18).

Anterior Cruciate Ligament Mechanical Response to Load in the Setting of Changes to the Medial Meniscus.

The anterior cruciate ligament (ACL) is a major ligament in the knee joint, and its function is crucial for both the movement and stability of the knee. Our research takes a novel approach by investigating the effect of meniscus tears on the ACL, how such tears will impact the stress on the ACL, and its overall compensation in response to the changes in the meniscus. : This study aims to investigate how the ACL compensates for the change in knee joint stability and contact pressures due to partial horizontal cleavage tears (HCTs) in the meniscus, such as partial meniscectomy and partial transplantation on knee joint stability and contact pressures.

Regeneration of the skin wound by two different crosslinkers: and studies.

Objectives: For designing a suitable hydrogel, two crosslinked Alginate/ Carboxymethyl cellulose (Alg/CMC) hydrogel, using calcium chloride (Ca) and glutaraldehyde (GA) as crosslinking agents were synthesized and compared.

Materials And Methods: All samples were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Blood compatibility (BC), Blood clotting index (BCI), weight loss (WL), water absorption (WA), pH, and Electrochemical Impedance Spectroscopy (EIS). Cell viability and cell migration were investigated using the MTT assay and the wound scratch test, respectively.

Sociodemographic inequities in overall survival among younger and older women with cervical cancer.

Purpose:  Older Black women and women living in areas of low socioeconomic status (SES) diagnosed with cervical cancer (CC) have worse overall survival (OS). The objective was to investigate associations between OS and race/ethnicity and sociodemographic factors in younger (21-64 years) and older women (≥ 65 years) diagnosed with CC using Surveillance, Epidemiology, and End Results Program data.

Methods:  This retrospective, population-based cohort study included 39,000 women ≥ 21 years diagnosed with CC diagnosed between 2006 and 2020.

Timing of exercise differentially impacts adipose tissue gain in male adolescent rats.

Circadian rhythms of metabolic, hormonal, and behavioral fluctuations and their alterations can impact health. An important gap in knowledge in the field is whether the time of the day of exercise and the age of onset of exercise exert distinct effects at the level of whole-body adipose tissue and body composition. The goal of the present study was to determine how exercise at different times of the day during adolescence impacts the adipose tissue transcriptome and content in a rodent model.

Fiber- and acetate-mediated modulation of MHC-II expression on intestinal epithelium protects from Clostridioides difficile infection.

Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4 intraepithelial lymphocytes (IELs). The influence of dietary fibers on MHC-II expression is mediated by its metabolic product, acetate, and its receptor, free fatty acid receptor 2 (FFAR2).

Cemdomespib Therapy Slows the Progression of Neuromuscular Weakness and Demyelination in the R75W-Connexin 32 Animal Model of Charcot-Marie-Tooth 1X Disease.

Mutations in connexin 32 (Cx32) are a common cause of Charcot-Marie-Tooth 1X (CMT1X) disease, an inherited peripheral neuropathy characterized by progressive neuromuscular weakness and demyelination. There are no approved pharmacologic therapies for CMT1X, and identifying new treatments that slow the onset and severity of neuromuscular decline may aid disease management. Cemdomespib is an orally bioavailable small molecule that improved demyelination and neuromuscular junction (NMJ) morphology in mice lacking Cx32 expression.

High dynamic range widefield fundus photography with transcranial illumination: a contrast agent-free method for non-mydriatic choroidal imaging.

The choroid, a critical vascular layer beneath the retina, is essential for maintaining retinal function and monitoring chorioretinal disorders. Existing imaging methods, such as indocyanine green angiography (ICGA) and optical coherence tomography (OCT), face significant limitations, including contrast agent requirements, restricted field of view (FOV), and high costs, limiting accessibility. To address these challenges, we developed a nonmydriatic, contrast agent-free fundus camera utilizing transcranial near-infrared (NIR) illumination.

Synchronous primary aneurysmal bone cysts: A rare case report and literature review.

Aneurysmal bone cysts (ABCs) are rare benign osteolytic tumors which occur most frequently within the first two decades of life and can lead to pathological fractures. They have characteristic imaging and histologic features and have historically been classified into two types: primary ABCs, which are true neoplasms linked to specific oncogenes, and secondary ABCs, which are preceded by other bone lesions. The occurrence of multiple concurrent primary ABCs is exceedingly rare; with only a few cases reported in the published literature.

Cytotoxic and Noncytotoxic Steroidal Constituents of .

(-)-Cryptanoside A () was identified previously as a major cytotoxic component of the stems of collected in Laos, which mediates its activity by targeting Na/K-ATPase (NKA), with hydrogen bonds formed between its 11- and 4'-hydroxy groups and NKA being observed in its docking profile. In a continuing investigation, and its 17-epimer, (-)-17--cryptanoside A (), and the new (+)-2-hydroxyandrosta-4,6-diene-3-one-17-carboxylic acid () and the known (+)-2,21-dihydroxypregna-4,6-diene-3,20-dione or 2-hydroxy-6,7-didehydrocortexone () pregnane-type steroids were isolated from . In addition, (-)-11,4'-di--acetylcryptanoside A () has been synthesized from the acetylation of .

Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.

Half the world's population is at risk of developing a malaria infection, which is caused by parasites of the genus . Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need to develop novel compounds and better understand common mechanisms of resistance. We previously identified a novel tetrahydro-β-carboline compound, PRC1590, which potently kills the malaria parasite.

Social Determinants, Mental Well-Being, and Disrupted Life Transitions Among Young Adults with Disabling Mental Health Conditions.

This study sought to understand how young adults (age 18-25) with histories of mental health disorders are coping with disrupted transitions to adulthood during the COVID-19 pandemic. A cross-sectional web survey was conducted in March-June 2021 of 967 US young adults with pre-pandemic psychiatric disability to assess their current psychiatric status, interrupted transitions, and associations with social determinants including income, community participation, and social context. Mental health was assessed with the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and PTSD Checklist-Civilian Version.

Secondary bile acid derivatives are contributors to the fecal bile acid pool and associated with bile acid modulating nutrients.

Objective: Accumulation of hydrophobic bile acids is linked with cancer development. However, derivatives of deoxycholic acid (DCA) and lithocholic acid (LCA) produced via bacterial metabolism may mitigate the proinflammatory and cytotoxic effects of hydrophobic bile acids. The impact of diet on secondary bile acid (BA) derivative production has not been determined.

Preparation, Modification, Quantitation, and Dentin Biomodification Activity of Selectively Enriched Proanthocyanidins.

To date, quantitative analysis of proanthocyanidin (PAC) containing materials including plant extracts and fractions depends on colorimetric assays or phloroglucinolysis/thiolysis combined with UV-HPLC analysis. Such assays are of limited accuracy, particularly lack specificity, require extensive sample preparation and degradation, and need appropriate physical reference standards. To address this analytical challenge and toward our broader goal of developing new plant-sourced biomaterials that chemically and mechanically modulate the properties of dental tissue for clinical interventions, we have characterized 12 different PAC DESIGNER (Depletion and Enrichment of Select Ingredients Generating Normalized Extract Resources) materials.

Coats disease presenting with vitreous hemorrhage and neovascular glaucoma.

Purpose: To describe a patient with Coats disease with an atypical presentation of neovascular glaucoma and vitreous hemorrhage.

Observations: A 15-year-old male presented with five days of pain, redness, and swelling and was found to have neovascular glaucoma in his right eye. Further evaluation revealed Coats disease stage 3AI with a subtotal exudative retinal detachment inferiorly, telangiectatic vessels, and vitreous hemorrhage.

Predictors of outcome in patients with presumed reversible cerebral vasoconstriction syndrome (RCVS).

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is thought to be benign by nature, but a proportion of patients still suffer from neurological deficits on follow-up.

Objective: To understand what factors may influence a patient's recovery from RCVS.

Methods: The Clinical Research Data Warehouse at this institution was employed to search the medical records for patients with diagnosis and treatment of RCVS (2010-2021).