Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. Previously, The ENCODE consortium mapped biochemical signals across many cell types and tissues and integrated these data to develop a Registry of 0.9 million human and 300 thousand mouse candidate cis-Regulatory Elements (cCREs) annotated with potential functions.
View Article and Find Full Text PDFEnhancing the aqueous solubility via amorphization of crystalline poor glass-forming drugs represents a challenge, particularly when drug dosing is high. In such scenarios, there is often a need for high polymer loadings, leading to an increase in the dosage form mass and less patient acceptability. This work investigated the role that polymer type and after-melt cooling rate had upon the amorphicity of solid dispersions (SDs) containing high levels of naproxen and three commonly used polymeric excipients: Eudragit® EPO, Kollidon® VA64, and Soluplus®.
View Article and Find Full Text PDFBackground As part of preoperative patient evaluations, it is customary to estimate the likelihood of difficulties during laryngoscopy and intubation. A diverse array of predictors is frequently employed by anesthesiologists to anticipate difficult laryngoscopy (DL); however, no single predictor has been established as the gold standard. In the present study, we compared routine preoperative ultrasound-guided airway examination and clinical airway examination in predicting DL in patients coming for elective surgery.
View Article and Find Full Text PDFThis study describes the physicochemical characterisation of interpenetrating hydrogel networks (IHNs) composed of either poly(hydroxyethylmethacrylate, p(HEMA)) or poly(methacrylic acid, p(MAA)), and Pluronic block copolymers (grades F127, P123 and L121). IHNs were prepared by mixing the acrylate monomer with Pluronic block copolymers followed by free radical polymerisation. p(HEMA)-Pluronic blends were immiscible, evident from a lack of interaction between the two components (Raman spectroscopy) and the presence of the glass transitions (differential scanning calorimetry, DSC) of the two components.
View Article and Find Full Text PDFOver the last 15 years, a small number of paediatric artemisinin-based combination therapy products have been marketed. These included Riamet® and Coartem® dispersible tablets, a combination of artemether and lumefantrine, co-developed by the Medicines for Malaria Venture and Novartis. Disappointingly, patient compliance, requirement for high-fat meal, and sporadic drug dissolution behaviours following administration still result in considerable challenges for these products.
View Article and Find Full Text PDFThere has been a significant volume of work investigating the design and synthesis of new crystalline multicomponent systems via examining complementary functional groups that can reliably interact through the formation of noncovalent bonds, such as hydrogen bonds (H-bonds). Crystalline multicomponent molecular adducts formed using this approach, such as cocrystals, salts, and eutectics, have emerged as drug product intermediates that can lead to effective drug property modifications. Recent advancement in the production for these multicomponent molecular adducts has moved from batch techniques that rely upon intensive solvent use to those that are solvent-free, continuous, and industry-ready, such as reactive extrusion.
View Article and Find Full Text PDFBackground: Zebrafish are vertebrates with a high potential of regeneration after injury in the central nervous system. Therefore, they have emerged as a useful model system for studying traumatic spinal cord injuries.
New Method: Using larval zebrafish, we have developed a robust paradigm to model the effects of anterior spinal cord injury, which correspond to the debilitating injuries of the cervical and thoracic regions in humans.
Recent commentaries have proposed 'all-world ageing' as a new perspective for social scientific ageing research. It is based on the theoretical observation that the ageing process involves all forms of entities co-ageing relationally with each other, and with their surrounds. Its disciplinary implications hence being that what we categorize as ageing in social scientific ageing research should not be limited to human bodies, and that ageing non-humans should be brought under its purview.
View Article and Find Full Text PDFBackground: A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication.
Aims: To develop and evaluate a model that could predict the risk of TRS in routine clinical practice.
Method: We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis.
Lipid-based drug delivery systems hold immense promise in addressing critical medical needs, from cancer and neurodegenerative diseases to infectious diseases. By encapsulating active pharmaceutical ingredients - ranging from small molecule drugs to proteins and nucleic acids - these nanocarriers enhance treatment efficacy and safety. However, their commercial success faces hurdles, such as the lack of a systematic design approach and the issues related to scalability and reproducibility.
View Article and Find Full Text PDFMost genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from the PsychENCODE Consortium and other published sources to construct a comprehensive atlas of candidate brain cis-regulatory elements. Using deep learning, we model these elements' sequence syntax and predict how binding sites for lineage-specific transcription factors contribute to cell type-specific gene regulation in various types of glia and neurons.
View Article and Find Full Text PDFUnderstanding the interplay between kinetics and thermodynamics of polymer-mediated liquid-liquid phase separation is crucial for designing and implementing an amorphous solid dispersion formulation strategy for poorly water-soluble drugs. This work investigates the phase behaviors of a poorly water-soluble model drug, celecoxib (CXB), in a supersaturated aqueous solution with and without polymeric additives (PVP, PVPVA, HPMCAS, and HPMCP). Drug-polymer-water ternary phase diagrams were also constructed to estimate the thermodynamic behaviors of the mixtures at room temperature.
View Article and Find Full Text PDFTherapeutic deep eutectic solvents (THEDES) have been attracting increasing attention in the pharmaceutical literature as a promising enabling technology capable of improving physicochemical and biopharmaceutical properties for difficult-to-deliver drug compounds. The current literature has explored amide local anaesthetics and carboxylic acid nonsteroidal anti-inflammatories (NSAIDs) as commonly used THEDES formers for their active hydrogen-bonding functionality. However, little is known about what happens within the "deep eutectic" region where a range of binary compositions present simply as a liquid with no melting events detectable across experimentally achievable conditions.
View Article and Find Full Text PDFThe study objective was to design and characterise herein unreported polyologels composed of a range of diol and triol solvents and polyvinyl methyl ether-co-maleic acid (PVM/MA) and, determine their potential suitability for the treatment of periodontal and related diseases in the oral cavity using suitable in vitro methodologies. Polyologel flow and viscoelastic properties were controlled by the choice of solvent and the concentration of polymer. At equivalent polymer concentrations, polyologels prepared with glycerol (a triol) exhibited the greatest elasticity and resistance to deformation.
View Article and Find Full Text PDFTo end the HIV epidemic as a public health threat, there is urgent need to increase the frequency, depth and intentionality of bidirectional and mutually beneficial collaboration and coordination between the USA and global HIV/AIDS response. The US Health Resources and Services Administration (HRSA) is uniquely positioned to showcase bidirectional learning between high-income and low-income and middle-income countries (LMICs) in the fight against HIV. For 30 years, HRSA has successfully administered the Ryan White HIV/AIDS Program (RWHAP), the largest federal programme designed specifically for people with HIV in the USA.
View Article and Find Full Text PDFThe cellular environment is crowded with macromolecules of different shapes and sizes. The effect of this macromolecular crowding has been studied in a variety of synthetic crowding environments: two popular examples are the compact colloid-like Ficoll macromolecule and the globular protein bovine serum albumin (BSA). Recent studies have indicated that a significant component of bound or surface-associated water in these crowders reduces the available free volume.
View Article and Find Full Text PDFPurulent pericarditis is a rare but serious medical condition caused by an infection that spreads to the pericardial space surrounding the heart. Gram-positive organisms are the most common pathogens associated with purulent pericarditis. However, there has been a shift in recent years toward gram-negative bacteria.
View Article and Find Full Text PDFOccup Med (Lond)
December 2023
Background: Loneliness is a risk factor for a range of mental and physical health problems and has gained increasing interest from policy-makers and researchers in recent years. However, little attention has been paid to loneliness at work and its implications for workers and employers.
Aims: Identify workplace, health and personal factors associated with workplace loneliness.
Moisture was frequently used as dielectric heating source in classical microwave-able systems to facilitate microwave-induced in situ amorphization, however such systems may face the potential of drug hydrolysis. In this study, solid thermolytic salts were proposed to function as moisture substitutes and their feasibility and impacts on microwave-induced in situ amorphization were investigated. It was found that NHHCO was a promising solid alkaline salt to facilitate both microwave-induced in situ amorphization and in situ salt formation of acidic indomethacin (IND).
View Article and Find Full Text PDFBackground COVID-19-related critical illness affects multiple organs and causes a variety of metabolic derangements in the body's physiology that are not proven with the current level of evidence. Insulin resistance and deranged blood sugar control due to COVID-19 have been major problems when managing diabetic patients with hyperglycaemia when they are admitted with COVID-19 pneumonia. There is a lack of abundant literature to prove the excess insulin requirements of COVID-19 and to quantify their insulin needs scientifically.
View Article and Find Full Text PDFChronic non-bacterial osteomyelitis (CNO), also known as non-bacterial osteitis, is a chronic autoinflammatory disease of unknown aetiology that primarily occurs in the paediatric population, although rare cases of adult-onset disease also exist. CNO has non-specific clinical and radiological presentations, and the affected population often present with bone pain of insidious onset secondary to sterile bony inflammation that can be associated with swelling, focal tenderness, and warmth at the affected sites. The pattern of bony involvement appears to be dependent on the age of onset, with adults frequently having axial skeletal lesions and children and adolescents often being affected in the appendicular skeletal sites.
View Article and Find Full Text PDFPurpose: To compare loop gain (LG) before and during pharmacological increases in cerebral blood flow (CBF) at high altitude (HA). Loop gain (LG) describes stability of a negative-feedback control system; defining the magnitude of response to a disturbance, such as hyperpnea to an apnea in periodic breathing (PB). "Controller-gain" sensitivity from afferent peripheral (PCR) and central-chemoreceptors (CCR) plays a key role in perpetuating PB.
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