Mucosal Penetrative Polymeric Micelle Formulations for Insulin Delivery to the Respiratory Tract.

Purpose: Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers.

Evaluation of Anticancer Efficacy of D-α-Tocopheryl Polyethylene-Glycol Succinate and Soluplus Mixed Micelles Loaded with Olaparib and Rapamycin Against Ovarian Cancer.

Purpose: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer.

Wrinkle-Improving Effect of Novel Peptide That Binds to Nicotinic Acetylcholine Receptor.

Wrinkles, one of the most common signs of aging, are primarily caused by the continuous contraction of muscles. Muscle contraction is induced by the binding of acetylcholine (ACh), released at the neuromuscular junction, to nicotinic acetylcholine receptor (nAChR) present on the muscle cell surface. In this study, we aimed to develop a wrinkle-improving peptide that inhibits the binding of ACh to nAChR using peptide phage display technology.

Preparation and Evaluation of Inhalable Microparticles with Improved Aerodynamic Performance and Dispersibility Using L-Leucine and Hot-Melt Extrusion.

Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles.

Data-based modeling of cerebral hemodynamics quantifies impairment of cerebral blood flow regulation in type-2 diabetes.

We studied the regulation dynamics of cerebral blood velocity (CBv) at middle cerebral arteries (MCA) in response to spontaneous changes of arterial blood pressure (ABP), termed dynamic cerebral autoregulation (dCA), and end-tidal CO as proxy for blood CO tension, termed dynamic vasomotor reactivity (DVR), by analyzing time-series data collected at supine rest from 36 patients with Type-2 Diabetes Mellitus (T2DM) and 22 age/sex-matched non-diabetic controls without arterial hypertension. Our analysis employed a robust dynamic modeling methodology that utilizes Principal Dynamic Modes (PDM) to estimate subject-specific dynamic transformations of spontaneous changes in ABP and end-tidal CO (viewed as two "inputs") into changes of CBv at MCA measured via Transcranial Doppler ultrasound (viewed as the "output"). The quantitative results of PDM analysis indicate significant alterations in T2DM of both DVR and dCA in terms of two specific PDM contributions that rise to significance (p < 0.

Clinical Relevance of Plasma Prolylcarboxypeptidase Level in Patients with Idiopathic Acute Optic Neuritis.

This study evaluated the plasma concentration of prolylcarboxypeptidase (PRCP) and its clinical relevance in patients with idiopathic acute optic neuritis (ON). We investigated the expression of PRCP in the optic nerves of experimental autoimmune optic neuritis (EAON)-induced mice. Peripheral blood samples were collected from ON patients (n = 20) and healthy controls (n = 20).

Generation of human TMEM16F-specific affibodies using purified TMEM16F.

TMEM16 family proteins are involved in a variety of functions, including ion transport, phospholipid scrambling, and the regulation of membrane proteins. Among them, TMEM16F has dual functions as a phospholipid scramblase and a nonselective ion channel. TMEM16F is widely expressed and functions in platelet activation during blood clotting, bone formation, and T cell activation.

Impaired dynamic cerebral autoregulation measured in the middle cerebral artery in patients with vertebrobasilar ischemia is associated with autonomic failure.

Objectives: To assess whether vertebrobasilar artery ischemia (VBI) affects cortical cerebral blood flow (CBF) regulation.

Material And Methods: 107 consecutive patients (mean age 65 ± 15 years; women 21) with VBI underwent structured stroke care with assessment of dynamic cerebral autoregulation (dCA) in both middle cerebral arteries (MCAs) by transfer function analysis using spontaneous oscillations of blood pressure (BP) and CBF velocity that yields by extraction of phase and gain information in the very low (0.02-0.

Risk Factors Associated with Fixation Failure in Intertrochanteric Fracture Treated with Cephalomedullary Nail.

Purpose: Cephalomedullary (CM) nailing is widely performed in treatment of elderly patients with femoral intertrochanteric fractures. However, in cases of fixation failure, re-operation is usually necessary, thus determining factors that may contribute to fixation failure is important. In this study, we examined factors affecting the occurrence of fixation failure, such as age or fracture stability, after CM nailing in elderly patients.

Gemcitabine and rapamycin-loaded mixed polymeric thermogel for metastatic pancreatic cancer therapy.

Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death and has a poor 5-year overall survival. The superior therapeutic benefits of combination or co-administration of drugs as intraperitoneal chemotherapy have increased interest in developing strategies to deliver chemotherapeutic agents to patients safely. In this study, we prepared a gel comprising the thermosensitive poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) polymer and gemcitabine (GEM), which is currently used as the primary chemotherapy for PDAC and rapamycin (RAPA), a mammalian TOR (mTOR) inhibitor, to deliver the drug through intraperitoneal injection.

Characterization of Channeling Effects Applied to Extended-Release Matrix Tablets Containing Pirfenidone.

Pirfenidone (PRF) is an anti-fibrotic agent that has been approved by the Food and Drug Administration (FDA) for the treatment of mild to moderate idiopathic pulmonary fibrosis. However, the current oral administration dosing regimen of PRF is complex and requires high doses. Patients are instructed to take PRF three times daily, with each dose consisting of up to three capsules or tablets (600 mg/d or 1.

Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)--Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer.

Purpose: We aimed to inhibit ovarian cancer (OC) development by interfering with microtubule polymerization and inhibiting mTOR signaling. To achieve this, previously developed micelles containing fenbendazole and rapamycin were applied.

Methods: Herein, we prepared micelles for drug delivery using fenbendazole and rapamycin at a 1:2 molar ratio and methoxy poly(ethylene glycol)--poly(caprolactone)(mPEG--PCL) via freeze-drying.

Dynamic effects of cholinergic blockade upon cerebral blood flow autoregulation in healthy adults.

Cerebral flow autoregulation (CFA) is a homeostatic mechanism critical for survival. The autonomic nervous system (ANS) plays a key role in maintaining proper CFA function. More quantitative studies of how the ANS influences CFA are desirable.

Validation of Age-adjusted Ideal Sagittal Alignment in Terms of Proximal Junctional Failure and Clinical Outcomes in Adult Spinal Deformity.

Study Design: Retrospective study.

Objective: To validate the age-adjusted ideal sagittal alignment in terms of proximal junctional failure (PJF) and clinical outcomes.

Summary Of Background: It is reported that optimal sagittal correction with regard to the age-adjusted ideal sagittal alignment reduces the risk of PJF development.

Enhanced Recognition of Amputated Wrist and Hand Movements by Deep Learning Method Using Multimodal Fusion of Electromyography and Electroencephalography.

Motion classification can be performed using biometric signals recorded by electroencephalography (EEG) or electromyography (EMG) with noninvasive surface electrodes for the control of prosthetic arms. However, current single-modal EEG and EMG based motion classification techniques are limited owing to the complexity and noise of EEG signals, and the electrode placement bias, and low-resolution of EMG signals. We herein propose a novel system of two-dimensional (2D) input image feature multimodal fusion based on an EEG/EMG-signal transfer learning (TL) paradigm for detection of hand movements in transforearm amputees.

The Dynamic Relationship Between Cortical Oxygenation and End-Tidal Transient Changes Is Impaired in Mild Cognitive Impairment Patients.

Recent studies have utilized data-based dynamic modeling to establish strong association between dysregulation of cerebral perfusion and Mild Cognitive Impairment (MCI), expressed in terms of impaired CO dynamic vasomotor reactivity in the cerebral vasculature. This raises the question of whether this is due to dysregulation of central mechanisms (baroreflex and chemoreflex) or mechanisms of cortical tissue oxygenation (CTO) in MCI patients. We seek to answer this question using data-based input-output predictive dynamic models.

Dianthiamides A-E, Proline-Containing Orbitides from .

Orbitides are plant-derived small cyclic peptides with a wide range of biological activities. Phytochemical investigation of the whole plants of was performed with the aim to discover new bioactive orbitides. Five undescribed proline-containing orbitides, dianthiamides A-E (-), were isolated from a methanolic extract of .

Local Infiltration Analgesia Versus Femoral Nerve Block for Pain Control in Anterior Cruciate Ligament Reconstruction: A Systematic Review With Meta-analysis.

Background: Anterior cruciate ligament reconstruction (ACLR) is often performed on an outpatient basis; thus, effective pain management is essential to improving patient satisfaction and function. Local infiltration analgesia (LIA) and femoral nerve block (FNB) have been commonly used for pain management in ACLR. However, the comparative efficacy and safety between the 2 techniques remains a topic of controversy.

Prediction of Diabetic Sensorimotor Polyneuropathy Using Machine Learning Techniques.

Diabetic sensorimotor polyneuropathy (DSPN) is a major complication in patients with diabetes mellitus (DM), and early detection or prediction of DSPN is important for preventing or managing neuropathic pain and foot ulcer. Our aim is to delineate whether machine learning techniques are more useful than traditional statistical methods for predicting DSPN in DM patients. Four hundred seventy DM patients were classified into four groups (normal, possible, probable, and confirmed) based on clinical and electrophysiological findings of suspected DSPN.

Co-Spray Dried Nafamostat Mesylate with Lecithin and Mannitol as Respirable Microparticles for Targeted Pulmonary Delivery: Pharmacokinetics and Lung Distribution in Rats.

Coronavirus disease 2019 (COVID-19), caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide. Nafamostat mesylate (NFM) suppresses transmembrane serine protease 2 and SARS-CoV-2 S protein-mediated fusion. In this study, pharmacokinetics and lung distribution of NFM, administered via intravenous and intratracheal routes, were determined using high performance liquid chromatography analysis of blood plasma, lung lumen using bronchoalveolar lavage fluid, and lung tissue.

Optimization and Pharmacokinetic Evaluation of Synergistic Fenbendazole and Rapamycin Co-Encapsulated in Methoxy Poly(Ethylene Glycol)--Poly(Caprolactone) Polymeric Micelles.

Purpose: We aimed to develop a nanocarrier formulation incorporating fenbendazole (FEN) and rapamycin (RAPA) with strong efficacy against A549 cancer cells. As FEN and RAPA are poorly soluble in water, it is difficult to apply them clinically in vivo. Therefore, we attempted to resolve this problem by encapsulating these drugs in polymeric micelles.

Hyoid Bone Tracking in a Videofluoroscopic Swallowing Study Using a Deep-Learning-Based Segmentation Network.

Kinematic analysis of the hyoid bone in a videofluorosopic swallowing study (VFSS) is important for assessing dysphagia. However, calibrating the hyoid bone movement is time-consuming, and its reliability shows wide variation. Computer-assisted analysis has been studied to improve the efficiency and accuracy of hyoid bone identification and tracking, but its performance is limited.