Methotrexate promotes the release of granulocyte-macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 signaling.

Background: Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators.

Welding techniques and manganese concentrations in blood and brain: Results from the WELDFUMES study.

This study used whole-brain mapping to investigate the effect of different welding processes on manganese (Mn) accumulation in the brain. Exposure measurements were performed at the welders' workplaces about 3 weeks before a magnetic resonance imaging (MRI) examination. The welders were categorized into three main groups based on welding method, and the T1-relaxation rate (R1) was measured using quantitative MRI (qMRI).

Ten years of detecting Neoehrlichia mikurensis infections in Sweden: demographic, clinical and inflammatory parameters.

Purpose: To increase knowledge about the varied clinical manifestations of human infection with the emerging tick-borne pathogen Neoehrlichia mikurensis.

Methods: All patients diagnosed in Sweden with N. mikurensis infection during a 10-year period (2013-2023) were investigated regarding their demographic factors, risk factors, comorbidities, clinical signs and symptoms, and laboratory results.

Deconvoluting Nonlinear Catalyst-Substrate Effects in the Intramolecular Dirhodium-Catalyzed C-H Insertion of Donor/Donor Carbenes Using Data Science Tools.

Interactions between catalysts and substrates can be highly complex and dynamic, often complicating the development of models to either predict or understand such processes. A dirhodium(II)-catalyzed C-H insertion of donor/donor carbenes into 2-alkoxybenzophenone substrates to form benzodihydrofurans was selected as a model system to explore nonlinear methods to achieve a mechanistic understanding. We found that the application of traditional methods of multivariate linear regression (MLR) correlating DFT-derived descriptors of catalysts and substrates leads to poorly performing models.

Potential sources of contamination on textiles and hard surfaces identified as high-touch sites near the patient environment.

The hospital environment represents an important mediator for the transmission of healthcare-associated infections through direct and indirect hand contact with hard surfaces and textiles. In this study, bacteria on high-touch sites, including textiles and hard surfaces in two care wards in Sweden, were identified using microbiological culture methods and 16S rDNA sequencing. During a cross-sectional study, 176 high-touch hard surfaces and textiles were identified and further analysed using microbiological culture for quantification of total aerobic bacteria, Staphylococcus aureus, Clostridium difficile and Enterobacteriacae.

One-Pot Assembly and Synthetic Applications of Geminal Acyl/Alkoxy Tetrasubstituted Allenes.

Polysubstituted allenes are useful synthetic intermediates in many applications, offering structural complexity, modularity, and their axial chirality in further transformations. While acyl and alkoxy-substituted allenes are known, there are currently few examples of allenes containing both functionalities and no reports of geminally substituted acyl/alkoxy allenes being isolated and characterized. Herein, we report the synthesis of tetrasubstituted allenes featuring a novel geminal acyl/alkoxy substitution.

Divergent Asymmetric Synthesis of Panowamycins, TM-135, and Veramycin F Using C-H Insertion with Donor/Donor Carbenes.

Panowamycins are a group of isochroman-based natural products first isolated from Streptomyces sp. K07-0010 in 2012 by Satoshi Ōmura and co-workers that exhibit modest anti-trypanosomal activity. Herein we demonstrate the first syntheses of these natural products and their epimers.

Monitoring Older Adult Blood Pressure Trends at Home as a Proxy for Brain Health.

Even when older adults monitor hypertension at home, it is difficult to understand trends and share them with their providers. MyHealthNetwork is a dashboard designed for patients and providers to monitor blood pressure readings to detect hypertension and ultimately warning signs of changes in brain health. A multidisciplinary group in a Digital Health course at Tufts University School of Medicine used Design Thinking to formulate a digital solution to promote brain health among older adults in the United States (US).

Stress urinary incontinence is caused predominantly by urethral support failure.

Whales are mammals that can dive to depths of > 1000 m without the high water pressure pushing open their mouth or anus. The same is true for the female urethra. The meatus externus and internus are seals that cannot be pushed open by high water pressures.

Correction: Enantioselective synthesis of isochromans and tetrahydroisoquinolines by C-H insertion of donor/donor carbenes.

[This corrects the article DOI: 10.1039/C9SC05111B.].

A physical phantom for amine chemical exchange saturation transfer (CEST) MRI.

Objective: To develop a robust amine chemical exchange saturation transfer (CEST) physical phantom, validate the temporal stability, and create a supporting software for automatic image processing and quality assurance.

Materials And Methods: The phantom was designed as an assembled laser-cut acrylic rack and 18 vials of phantom solutions, prepared with different pHs, glycine concentrations, and gadolinium concentrations. We evaluated glycine concentrations using ultraviolet absorbance for 70 days and measured the pH, relaxation rates, and CEST contrast for 94 days after preparation.

T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3Th2 phenotype.

Background: The majority of CD4 T helper (Th) cells found in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) express CXCR3, a receptor associated with Th1 cells. In blood, subsets of Th2 and Th17 cells also express CXCR3, but it is unknown if these cells are present in RA SF or how cytokines from these subsets affect cytokine/chemokine secretion by fibroblast-like synoviocytes (FLS) from patients with RA.

Methods: We examined the proportions of Th1, Th2, CXCR3Th2, Th17, CXCR3Th17, Th1Th17, peripheral T helper (TPh) and T follicular helper (TFh) cells in paired SF and blood, as well as the phenotype of TPh and TFh cells in RA SF (n = 8), by the use of flow cytometry.

Urethral closure occurs by recoiling, pressure transmission, and a guarding reflex.

Enhörning's abdominal pressure transmission theory (ET) is built on Pascal's law of fluid pressures. A theory that rejects ET also rejects this basic physical law and cannot be considered scientifically sound. The integral theory (IT) of female stress urinary incontinence rejects ET.

Enantioselective synthesis of isochromans and tetrahydroisoquinolines by C-H insertion of donor/donor carbenes.

Reports of C-H insertions forming six-membered rings containing heteroatoms are rare due to Stevens rearrangements occurring after nucleophilic attack on the carbene by a heteroatom. Using donor/donor carbenes and Rh(-PTAD) as a catalyst, we have synthesized a collection of isochroman substrates in good yield, with excellent diastereo- and enantioselectivity, and no rearrangement products were observed. Furthermore, we report the first synthesis of six-membered rings containing nitrogen by C-H insertion to form tetrahydroisoquinolines.

Transition Metal Catalyzed Insertion Reactions with Donor/Donor Carbenes.

Donor/donor carbenes are relatively new in the field of carbene chemistry; although applications in C-H and X-H insertion reactions are few in number, they demonstrate exquisite chemo- and stereo-selectivity. Recent reports have shown that C-H, N-H, B-H, O-H, S-H, Si-H, Ge-H, Sn-H and P-H insertion reactions are feasible with a variety of transition metal catalysts, both inter- and intramolecularly. Furthermore, high degrees of diastereo- and enantioselectivity have been observed in several cases.

Biomonitoring of Metal Exposure During Additive Manufacturing (3D Printing).

Background: Additive manufacturing (AM) is a rapidly expanding new technology involving challenges to occupational health. Here, metal exposure in an AM facility with large-scale metallic component production was investigated during two consecutive years with preventive actions in between.

Methods: Gravimetric analyzes measured airborne particle concentrations, and filters were analyzed for metal content.

The urethral hanging theory and how it relates to Enhörning's theory and the integral theory.

Introduction And Hypothesis: The article discusses three theories of stress urinary incontinence, the urethral hanging theory, Enhörning's theory, and the integral theory.

Methods: The abdominal pressure transmission theory proposed by Enhörning is often misunderstood. It is regularly interpreted to mean that, in cases of stress urinary incontinence, the bladder neck descends outside the abdominal cavity, and treatment must involve elevating or repositioning the bladder neck.

Group differences in normal neuropsychological test performance for older non-Hispanic White and Black/African American adults.

Objective: Although researchers have documented the influence of cultural factors on neuropsychological test performance, few studies have examined the distribution of test scores among neurologically healthy older adults from different ethnic groups. The objective of this study was to determine whether there are group differences in neuropsychological test score distributions with ethnicity-specific norms for non-Hispanic White and Black/African American older adults.

Method: Participants from the National Alzheimer's Coordinating Center were selected if they were not diagnosed with dementia within 5 years (Mage = 75.

The Rheumatoid Arthritis Risk Gene AIRE Is Induced by Cytokines in Fibroblast-Like Synoviocytes and Augments the Pro-inflammatory Response.

The autoimmune regulator AIRE controls the negative selection of self-reactive T-cells as well as the induction of regulatory T-cells in the thymus by mastering the transcription and presentation of tissue restricted antigens (TRAs) in thymic cells. However, extrathymic AIRE expression of hitherto unknown clinical significance has also been reported. Genetic polymorphisms of have been associated with rheumatoid arthritis (RA), but no specific disease-mediating mechanism has been identified.