Impaired 11β-hydroxysteroid dehydrogenase type 2 activity in kidney disease disrupts 11-oxygenated androgen biosynthesis.

Context: 11-oxygenated androgens are a group of adrenal-derived steroids that require peripheral activation. In vitro data highlight a putative role for 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) in 11-oxygenated androgen biosynthesis, converting 11β-hydroxyandrostenedione (11OHA4) to 11-ketoandrostenedione (11KA4), the direct precursor of the potent androgen 11-ketotestosterone (11KT). As the kidney is the major site of HSD11B2 expression, we hypothesized that patients with chronic kidney disease (CKD) would have reduced 11-oxygenated androgen biosynthesis due to impaired HSD11B2 activity.

Inflammation dynamically regulates steroid hormone metabolism and action within macrophages in rheumatoid arthritis.

Rationale: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages.

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.

Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.

Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data.

Biomechanical Comparison of 5 Different Fixation Constructs in a Trapeziometacarpal Joint Arthrodesis Model.

Purpose: Trapeziometacarpal joint (TMC) arthrodesis has a high rate of nonunion. This biomechanical analysis sought to determine the stiffness of 5 fixation methods in a TMC joint arthrodesis model.

Methods: Five fixation constructs were tested in a validated porcine model: crossed 1.

Cortisol excess in chronic kidney disease - A review of changes and impact on mortality.

Chronic kidney disease (CKD) describes the long-term condition of impaired kidney function from any cause. CKD is common and associated with a wide array of complications including higher mortality, cardiovascular disease, hypertension, insulin resistance, dyslipidemia, sarcopenia, osteoporosis, aberrant immune function, cognitive impairment, mood disturbances and poor sleep quality. Glucocorticoids are endogenous pleiotropic steroid hormones and their excess produces a pattern of morbidity that possesses considerable overlap with CKD.

Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system.

Variation in CFHR3 determines susceptibility to meningococcal disease by controlling factor H concentrations.

Neisseria meningitidis protects itself from complement-mediated killing by binding complement factor H (FH). Previous studies associated susceptibility to meningococcal disease (MD) with variation in CFH, but the causal variants and underlying mechanism remained unknown. Here we attempted to define the association more accurately by sequencing the CFH-CFHR locus and imputing missing genotypes in previously obtained GWAS datasets of MD-affected individuals of European ancestry and matched controls.

Osteoarticular Infections in Pediatric Hospitals in Europe: A Prospective Cohort Study From the EUCLIDS Consortium.

Background: Pediatric osteoarticular infections (POAIs) are serious diseases requiring early diagnosis and treatment.

Methods: In this prospective multicenter cohort study, children with POAIs were selected from the European Union Childhood Life-threatening Infectious Diseases Study (EUCLIDS) database to analyze their demographic, clinical, and microbiological data.

Results: A cohort of 380 patients with POAIs, 203 with osteomyelitis (OM), 158 with septic arthritis (SA), and 19 with both OM and SA, was analyzed.

The intra-muscular course and distribution of the anterior interosseous nerve within pronator quadratus: An anatomical study.

Background: The anterior interosseous nerve (AIN) is a terminal motor branch of the median nerve innervating the following three muscles from proximal to distal: Flexor pollicis longus (FPL), the radial half of flexor digitorum profundus (FDP), and the pronator quadratus (PQ). The aim of this study was to define the course of the AIN within the PQ to aid surgeons performing distal radial procedures.

Methods: Ten embalmed cadaveric forearms were dissected to identify the path of the AIN within PQ.

Waveguide Mach-Zehnder biosensor with laser diode pumped integrated single-mode silicon nitride organic hybrid solid-state laser.

Single-mode organic solid-state lasers with direct emission into an optical waveguide are attractive candidates for cost-efficient coherent light sources employed in photonic lab-on-a-chip biosensors. Here, we present a combination of a dye-doped organic solid-state distributed feedback laser with a highly sensitive optical waveguide Mach-Zehnder interferometer on a silicon nitride photonic platform. This organic-hybrid laser allows for optical pumping with a laser diode in an alignment tolerant manner, which facilitates applications in point-of-care diagnostics.

In vivo human retinal swept source optical coherence tomography and angiography at 830 nm with a CMOS compatible photonic integrated circuit.

Photonic integrated circuits (PIC) provide promising functionalities to significantly reduce the size and costs of optical coherence tomography (OCT) systems. This paper presents an imaging platform operating at a center wavelength of 830 nm for ophthalmic application using PIC-based swept source OCT. An on-chip Mach-Zehnder interferometer (MZI) configuration, which comprises an input power splitter, polarization beam splitters in the sample and the reference arm, and a 50/50 coupler for signal interference represents the core element of the system with a footprint of only [Formula: see text].

Global Deletion of 11β-HSD1 Prevents Muscle Wasting Associated with Glucocorticoid Therapy in Polyarthritis.

Glucocorticoids provide indispensable anti-inflammatory therapies. However, metabolic adverse effects including muscle wasting restrict their use. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) modulates peripheral glucocorticoid responses through pre-receptor metabolism.

Toward optical coherence tomography on a chip: in vivo three-dimensional human retinal imaging using photonic integrated circuit-based arrayed waveguide gratings.

In this work, we present a significant step toward in vivo ophthalmic optical coherence tomography and angiography on a photonic integrated chip. The diffraction gratings used in spectral-domain optical coherence tomography can be replaced by photonic integrated circuits comprising an arrayed waveguide grating. Two arrayed waveguide grating designs with 256 channels were tested, which enabled the first chip-based optical coherence tomography and angiography in vivo three-dimensional human retinal measurements.

Multi-channel swept source optical coherence tomography concept based on photonic integrated circuits.

In this paper, we present a novel concept for a multi-channel swept source optical coherence tomography (OCT) system based on photonic integrated circuits (PICs). At the core of this concept is a low-loss polarization dependent path routing approach allowing for lower excess loss compared to previously shown PIC-based OCT systems, facilitating a parallelization of measurement units. As a proof of concept for the low-loss path routing, a silicon nitride PIC-based single-channel swept source OCT system operating at 840 nm was implemented and used to acquire in-vivo tomograms of a human retina.

11βHSD1 Inhibition with AZD4017 Improves Lipid Profiles and Lean Muscle Mass in Idiopathic Intracranial Hypertension.

Background: The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH).

Slot-Waveguide Silicon Nitride Organic Hybrid Distributed Feedback Laser.

One of the major barriers for a widespread commercial uptake of silicon nitride photonic integrated circuits for cost-sensitive applications is the lack of low-cost monolithically integrated laser light sources directly emitting into single-mode waveguides. In this work, we demonstrate an optically pumped organic solid-state slot-waveguide distributed feedback laser designed for a silicon nitride organic hybrid photonic platform. Pulsed optical excitation of the gain medium is achieved by a 450 nm laser diode.

Integrated silicon nitride organic hybrid DFB laser with inkjet printed gain medium.

The provision of a coherent light source is a prerequisite for a variety of photonic integrated circuits. The integration of semiconductor laser diodes in disposable photonic devices in fields such as biosensing is, however, impeded by the competitive pricing in this application area. In this work, we demonstrate lasing of an alternative laser light source, namely an integrated hybrid organic solid-state distributed feedback laser for a silicon nitride photonic platform.

Analysis of silicon nitride partial Euler waveguide bends.

In this work, we present a detailed analysis of individual loss mechanisms in silicon nitride partial Euler bends at a wavelength of 850 nm. This structure optimizes the transmission through small radii optical waveguide bends. The partial Euler bend geometry balances losses arising from the transition from the straight to the bend waveguide mode and radiative losses of the bend waveguide mode.

Kidney transplantation in ANCA-associated vasculitis.

The kidney is commonly affected in patients with ANCA-associated vasculitis (AAV), causing end-stage renal disease (ESRD) in 20-40% of cases. Kidney transplantation is the treatment of choice for eligible patients with ESRD due to AAV. This review provides a summary of patient and graft outcome after kidney transplantation in AAV patients, the risk of relapse and the optimal time of transplantation.

Transfer Printing Technology as a Straightforward Method to Fabricate Chemical Sensors Based on Tin Dioxide Nanowires.

Metal oxide multi-nanowire-based chemical gas sensors were manufactured by a fast and simple transfer printing technology. A two-step method employing spray pyrolysis deposition and a thermal annealing process was used for SnO 2 nanowires fabrication. A polydimethylsiloxane stamp was used to transfer the SnO 2 nanowires on two different gas sensing devices-Si-based substrates and microhotplate-based platform chips.