Features of Axial Spondyloarthritis in Two Multicenter Cohorts of Patients with Psoriasis, Uveitis, and Colitis Presenting with Undiagnosed Back Pain.

Objective: We aimed to assess the following: (1) the frequency of axial spondyloarthritis (axSpA) according to extra-articular presentation and HLA-B27 status, (2) clinical and imaging features that distinguish axSpA from non-axSpA, and (3) the impact of magnetic resonance imaging (MRI) on diagnosis and classification of axSpA.

Methods: The Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) study enrolled patients in two multicenter cohorts. Consecutive patients with undiagnosed chronic back pain attending dermatology, ophthalmology, and gastroenterology clinics with psoriasis (PsO), acute anterior uveitis (AAU), or inflammatory bowel disease (IBD) were referred to a local rheumatologist with special expertise in axSpA for a structured diagnostic evaluation.

In Silico Screening Accelerates Nanocarrier Design for Efficient mRNA Delivery.

Lipidic nanocarriers are a broad class of lipid-based vectors with proven potential for packaging and delivering emerging nucleic acid therapeutics. An important early step in the clinical development cycle is large-scale screening of diverse formulation libraries to assess particle quality and payload delivery efficiency. Due to the size of the screening space, this process can be both costly and time-consuming.

Pubococcygeal Line Versus H-line as MR Defecography Reference for Bladder Descent.

Introduction And Hypothesis: Magnetic resonance defecography imaging techniques have been used widely to study pelvic floor function and diagnose pelvic organ prolapse (POP). The aim of this study was to investigate the diagnostic accuracy of the H-line to detect bladder descent compared with the current landmark, the pubococcygeal line (PCL).

Methods: In this retrospective cohort study, patients who underwent MR defecography in our medical center and were diagnosed with moderate to severe cystocele by radiological measurements were recruited.

A systematic comparison between FEBio and PolyFEM for biomechanical systems.

Background And Objectives: Finite element simulations are widely employed as a non-invasive and cost-effective approach for predicting outcomes in biomechanical simulations. However, traditional finite element software, primarily designed for engineering materials, often encountered limitations in contact detection and enforcement, leading to simulation failure when dealing with complex biomechanical configurations. Currently, a lot of model tuning is required to get physically accurate finite element simulations without failures.

Sacrum and Coccyx Shape Changes During Pregnancy and After Delivery.

Remodeling of the sacrum and coccyx to accommodate pregnancy and delivery has been hypothesized but not directly quantified. This study aimed to quantify the remodeling of the sacrum and coccyx by comparing midsagittal lengths, angles, curvature, and shape between nulliparous, pregnant, and parous women using both 2 and 3 dimensional measures. Ninety pelvic magnetic resonance images of the pelvis were retrospectively collected and segmented.

C-1 Substituted isoquinolines potentiate the antimycobacterial activity of rifampicin and ethambutol.

Introduction: The emergence of extensively drug-resistant strains of threatens decades of progress in the treatment of a disease which remains one of the leading infectious causes of death worldwide. The development of novel antimycobacterial compounds is therefore essential to reinforce the existing antitubercular drug discovery pipeline. There is also interest in new compounds which can synergize with existing antitubercular drugs and can be deployed as part of a combination therapy.

Quantifying the effect of an endo-vaginal probe on position of the pelvic floor viscera and muscles.

Introduction And Hypothesis: Endovaginal ultrasound has long been hypothesized to have a significant effect on locations of what it visualizes. However, little work has directly quantified its effect. This study aimed to quantify it.

Effect of Squeeze, Cough, and Strain on Dynamic Urethral Function in Nulligravid Asymptomatic Women: A Cross-Sectional Cohort Study.

Importance: In the past, urethral shape, mobility, and urodynamics have been used to retrospectively demonstrate correlations with stress urinary incontinence. Our previous work has shown a relationship between urethral function and shape in symptomatic women.

Objective: This study aimed to characterize the effect of pelvic floor squeeze and strain maneuvers on urethral shapes and pressure in a cohort of patients without pelvic floor disorders.

Multimodal measurements of levator bowl volume in nulligravid asymptomatic women: endovaginal ultrasound versus MRI.

Introduction And Hypothesis: Measurements of levator bowl volume using advanced imaging, may be predictive of pelvic floor muscle function. The aim of this study was to compare the volume of the levator bowl using both magnetic resonance imaging (MRI) and endovaginal ultrasound (EVU) of healthy asymptomatic women.

Methods: All participants underwent a comprehensive interview including completion of the Pelvic Floor Distress Inventory Questionnaire-20 questionnaire, pelvic examination with a pelvic organ prolapse quantification evaluation, MRI, and EVU.

Synovial fluid mesenchymal progenitor cells from patients with juvenile idiopathic arthritis demonstrate limited self-renewal and chondrogenesis.

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases affecting joints with a prevalence of one in a thousand children. There is a growing body of literature examining the use of mesenchymal stem/progenitor cells (MPCs) for the treatment of adult and childhood arthritis, however, we still lack a clear understanding of how these MPC populations are impacted by arthritic disease states and how this could influence treatment efficacy. In the current study we examined the immunophenotyping, self-renewal ability and chondrogenic capacity (in vitro and in vivo) of synovial derived MPCs from normal, JIA and RA joints.

pH-sensitive packaging of cationic particles by an anionic block copolymer shell.

Cationic non-viral vectors show great potential to introduce genetic material into cells, due to their ability to transport large amounts of genetic material and their high synthetic versatility. However, designing materials that are effective without showing toxic effects or undergoing non-specific interactions when applied systemically remains a challenge. The introduction of shielding polymers such as polyethylene glycol (PEG) can enhance biocompatibility and circulation time, however, often impairs transfection efficiency.

Quantifying the physiologic motions of the pelvic viscera during evacuation in nulligravid asymptomatic women.

Introduction And Hypothesis: Pelvic organ prolapse (POP) is often diagnosed during an in-office examination, which looks for motion of the vaginal wall while performing a strain maneuver. It is believed that the pelvic organs in adequately supported women are relatively stationary. This study was aimed at investigating the physiological displacements of pelvic organs using MR defecography.

Core-crosslinked, temperature- and pH-responsive micelles: design, physicochemical characterization, and gene delivery application.

Stimuli-responsive block copolymer micelles can provide tailored properties for the efficient delivery of genetic material. In particular, temperature- and pH-responsive materials are of interest, since their physicochemical properties can be easily tailored to meet the requirements for successful gene delivery. Within this study, a stimuli-responsive micelle system for gene delivery was designed based on a diblock copolymer consisting of poly(,-diethylacrylamide) (PDEAm) as a temperature-responsive segment combined with poly(aminoethyl acrylamide) (PAEAm) as a pH-responsive, cationic segment.

The impact of anionic polymers on gene delivery: how composition and assembly help evading the toxicity-efficiency dilemma.

Cationic polymers have been widely studied for non-viral gene delivery due to their ability to bind genetic material and to interact with cellular membranes. However, their charged nature carries the risk of increased cytotoxicity and interaction with serum proteins, limiting their potential in vivo application. Therefore, hydrophilic or anionic shielding polymers are applied to counteract these effects.

Characterization of the MurT/GatD complex in towards validating a novel anti-tubercular drug target.

Objectives: Identification and validation of novel therapeutic targets is imperative to tackle the rise of drug resistance in tuberculosis. An essential Mur ligase-like gene (Rv3712), expected to be involved in cell-wall peptidoglycan (PG) biogenesis and conserved across mycobacteria, including the genetically depleted , was the primary focus of this study.

Methods: Biochemical analysis of Rv3712 was performed using inorganic phosphate release assays.

Urethral support in female urinary continence part 2: a computational, biomechanical analysis of Valsalva.

Introduction And Hypothesis: In Part 1, we observed urethral mechanics during Valsalva that oppose current continence theories. In this study, we utilize a finite element model to elucidate the role of supportive tissues on the urethra during Valsalva. By determining the sensitivity of urethral motion and deformations to variations in tissue stiffnesses, we formulate new hypotheses regarding mechanisms of urethral passive closure.

Improved gene delivery to K-562 leukemia cells by lipoic acid modified block copolymer micelles.

Although there has been substantial progress in the research field of gene delivery, there are some challenges remaining, e.g. there are still cell types such as primary cells and suspension cells (immune cells) known to be difficult to transfect.

Solely aqueous formulation of hydrophobic cationic polymers for efficient gene delivery.

Cationic polymers are promising gene delivery vectors due to their ability to bind and protect genetic material. The introduction of hydrophobic moieties into cationic polymers can further improve the vector efficiency, but common formulations of hydrophobic polymers involve harsh conditions such as organic solvents, impairing intactness and loading efficiency of the genetic material. In this study, a mild, aqueous formulation method for the encapsulation of high amounts of genetic material is presented.

Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis.

Background: The rise of antimicrobial drug resistance in Mycobacterium tuberculosis coupled with the shortage of new antibiotics has elevated TB to a major global health priority. Repurposing drugs developed or used for other conditions has gained special attention in the current scenario of accelerated drug development for several global infectious diseases. In a similar effort, previous studies revealed that carprofen, a non-steroidal anti-inflammatory drug, selectively inhibited the growth of replicating, non-replicating and MDR clinical isolates of M.

Antimicrobial and Efflux Pump Inhibitory Activity of Carvotacetones from Against Mycobacteria.

Carvotacetones () isolated from were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains mc 155, ATCC 23366, and BCG ATCC 35734. The minimum inhibitory concentrations (MICs) of the carvotacetones were detected through high-throughput spot culture growth inhibition (HT-SPOTi) and microbroth dilution assays. In order to assess the potential of the compounds and to accumulate ethidium bromide (EtBr) in and , a microtiter plate-based fluorometric assay was used to determine efflux activity.

Outcomes with Biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) in Older Patients Treated for Rheumatoid Arthritis.

Background: Biological disease-modifying antirheumatic drugs (bDMARDs) are recommended for rheumatoid arthritis (RA), but older patients reportedly experience more adverse events (AEs) and show variable treatment response. The objective of this study was to evaluate AEs and effectiveness of bDMARDs in a cohort of older patients.

Methods: AE and treatment effectiveness (based on DAS28 scores) data from a prospective provincial pharmacovigilance program for the years 2006-2009 in patients 55-64, 65-74, and 75+ years of age were compared.

Tuning of endosomal escape and gene expression by functional groups, molecular weight and transfection medium: a structure-activity relationship study.

The use of genetic material by non-viral transfer systems is still in its initial stages, but there are high expectations for the development of targeted therapies. However, nucleic acids cannot enter cells without help, they must be well protected to prevent degradation and overcome a variety of biological barriers, the endosomal barrier being one of the greatest cellular challenges. Herein, the structure-property-relationship was investigated in detail, using well-defined polymers.

Flavonoids as Novel Efflux Pump Inhibitors and Antimicrobials Against Both Environmental and Pathogenic Intracellular Mycobacterial Species.

Therapeutic treatment options for opportunistic non-tuberculous mycobacterial (NTM) infection and/or serious mycobacterial infections such as tuberculosis (TB) and leprosy are limited due to the spread of antimicrobial resistance mechanism. Plant-derived natural compounds as prospective efflux pump inhibitors may present a promising adjunct to conventional chemotherapy by enhancing mycobacterial susceptibility to antibiotics. This study served to evaluate the antimicrobial and resistance-modifying profile of a range of plant-derived flavonoids against the mycobacterial model strains: , , and BCG.

Catalytic direct amidations in tert-butyl acetate using B(OCHCF).

Catalytic direct amidation reactions have been the focus of considerable recent research effort, due to the widespread use of amide formation processes in pharmaceutical synthesis. However, the vast majority of catalytic amidations are performed in non-polar solvents (aromatic hydrocarbons, ethers) which are typically undesirable from a sustainability perspective, and are often poor at solubilising polar carboxylic acid and amine substrates. As a consequence, most catalytic amidation protocols are unsuccessful when applied to polar and/or functionalised substrates of the kind commonly used in medicinal chemistry.

Cell wall peptidoglycan in Mycobacterium tuberculosis: An Achilles' heel for the TB-causing pathogen.

Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis, remains one of the leading causes of mortality across the world. There is an urgent requirement to build a robust arsenal of effective antimicrobials, targeting novel molecular mechanisms to overcome the challenges posed by the increase of antibiotic resistance in TB. Mycobacterium tuberculosis has a unique cell envelope structure and composition, containing a peptidoglycan layer that is essential for maintaining cellular integrity and for virulence.