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BackgroundMusculoskeletal ultrasound (MSUS) and the multi-biomarker disease activity (MBDA) score are outcome measures that may aid in the management of rheumatoid arthritis (RA) patients. This study evaluated tofacitinib response by MSUS/MBDA scores and assessed whether baseline MSUS/MBDA scores or their early changes predict later clinical response.MethodsTwenty-five RA patients treated with tofacitinib were assessed at baseline, 2, 6 and 12-weeks. Power doppler (PDUS) and gray scale (GSUS) ultrasound scores, MBDA score, clinical disease activity index (CDAI), and disease activity score (DAS28) were obtained. Pearson correlations and multiple linear regression models were used to evaluate associations and identify predictors of response to therapy.ResultsMSUS, MBDA scores, CDAI, and DAS28 improved significantly over 12 weeks (p

Granulomatosis with polyangiitis (GPA) is one of three described anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Early diagnosis and treatment of GPA is paramount, as it may help prevent irreversible end-organ damage, especially renal and pulmonary failure. A 72-year-old male with a past medical history of lung adenocarcinoma in remission, chronic sinusitis status-post multiple sinus surgeries, and coronary artery disease presented with shortness of breath, dark urine, and asymmetric polyarthralgias. He had an acute kidney injury, leukocytosis, with urinalysis demonstrating pyuria and hematuria, without casts. Chest imaging showed cavitary nodular opacities in addition to interval increase of existing nodules compared to the most recent scan one month prior. His acute kidney injury progressed to renal failure requiring hemodialysis, and he developed an inflammatory polyarthritis. GPA was suspected clinically so he was started on high-dose intravenous corticosteroids, and subsequently plasmapheresis and rituximab. Serology returned with highly positive proteinase-3 antibodies, and cytoplasmic ANCA positivity on immunofluorescence. Renal biopsy demonstrated severely active pauci-immune glomerulonephritis. Several months after discharge, the patient passed away from gram positive bacteremia. This patient's recurrent sinusitis, pulmonary nodules, and subsequent renal failure were highly suggestive of GPA. A biopsy is recommended to confirm the diagnosis of GPA, but treatment should not be delayed if there is a high index of suspicion for the disease. Induction therapy with corticosteroids combined with rituximab or cyclophosphamide has significantly decreased the mortality of patients with GPA. Patients with GPA often have preceding history of nasopharyngeal and upper airway disease, and can present with fluctuating pulmonary infiltrates. Early recognition and treatment of patients with GPA can prevent life-threatening complications and reduce mortality.

Nanofluidic systems due to their unique transport properties play a crucial role in a lot of applications ranging from water desalination to sensors. Over the past few years, considering the simple structure of two-dimensional materials, significant efforts have been devoted to designing synthetic membranes for ion transport. However, expensive fabrication methods such as lithography techniques and some shortcomings such as scale-up difficulty, low pore density, poor mechanical stability, and biocompatibility limit their practical application. Herein, we demonstrate a scalable hierarchically porous membrane with three-dimensional (3D) interconnected nanochannels which is based on the silk fibroin (SF) fiber biomass and modifying the nanofluidic channels by in situ growth of zeolitic imidazolate framework-67 (ZIF-67) nanoparticles on the fiber surfaces. The ZIF-67/SF membrane with 400 μm thickness is a 3D interconnected network with a large positively charged surface area (54 m2 g–1) containing 1–5 nm pores estimated from density functional theory modeling. Surface-charge-governed ion transport through the nanofluidic channels of the ZIF-67/SF membrane is systematically explored, and characteristic higher-than-bulk ion conductivity was observed at low concentrations (≤10–3 M) of monovalent electrolytes (KCl, NaCl, NaOH, and HCl). Moreover, the ZIF-67/SF is stable and fully functional at elevated temperatures up to 60 °C and maintains its structural and operational properties under acidic and basic conditions. [ABSTRACT FROM AUTHOR]

The condensed extracellular matrix (ECM) surrounding cancer cells results in the formation of a biophysical barrier versus chemotherapeutic drug penetration into deeper regions of many solid malignancies. To cope with this drawback, the present study inquired the therapeutic potential of a hyaluronidase (Hyal)-modified hyperbranched poly-(amide amine) (PAMAM) loaded with an anticancer drug, methotrexate (MTX), to improve breast cancer chemoresistance. The focus is on reducing the hyaluronic acid accumulation as a major component of the tumor ECM. The decoration of the prepared pH-responsive nanoplatform with a relatively low density layer of polyethylene glycol (PEG) improved its stability and performance. These processes were characterized by different instruments and an enzymatic activity assessment. Despite the short half-life of pristine hyaluronidase, the Hyal-immobilized nanoplatform displayed enhanced enzyme stability, especially against protease degradation, and prolonged half-life after incubation in human plasma. The MTX loaded into carboxylate nanocarrier (PAMAM-MTX/SA/Hyal/PEG) exhibited an outstanding ability for controlled release of MTX. The results of the hemolysis assay confirmed the good blood compatibility of the as-prepared nanoplatform. The cytotoxicity assessment of various nanoformulations using an MTS-based assay on MCF-7 and MCF-10A cell lines revealed that PAMAM-MTX/SA/Hyal/PEG was more efficient against tumor cells than free MTX over 72 h. In addition, the effect of PAMAM-MTX/SA/Hyal/PEG against MCF-7 cells showed noteworthy induction of apoptosis and facilitated uptake by MCF-7 cells and penetration in MCF-7 3D tumor spheroids compared to free MTX. Thus, the synthesized nanoplatform indicated in vitro controlled release of MTX with the advantage of an adjuvant Hyal-based nanosystem. This outlook suggests a novel multifunctional nanoplatform to improve anticancer drug delivery systems by effective modulation of the tumor microenvironment. [ABSTRACT FROM AUTHOR]