Doctors as Device Manufacturers? Regulation of Clinician-Generated Innovation in the ICU.

Critical care physicians are rich sources of innovation, developing new diagnostic, prognostic, and treatment tools they deploy in clinical practice, including novel software-based tools. Many of these tools are validated and promise to actively help patients, but physicians may be unlikely to distribute, implement, or share them with other centers noncommercially because of unsettled ethical, regulatory, or medicolegal concerns. This Viewpoint explores the potential barriers and risks critical care physicians face in disseminating device-related innovations for noncommercial purposes and proposes a framework for risk-based evaluation to foster clear pathways to safeguard equitable patient access and responsible implementation of clinician-generated technological innovations in critical care.

Unconventional Imaging Methods in Psoriatic Arthritis.

Purpose Of Review: Psoriatic arthritis (PsA) is a complex heterogeneous inflammatory disease that affects about one-third of patients with psoriasis. PsA leads to significant physical impairment and reduced quality of life. Therefore, early diagnosis and intervention are critical for improving long-term outcomes.

Paucity of viral infection symptoms in patients with immune-mediated inflammatory diseases.

Objectives: Although patients with immune-mediated inflammatory diseases (IMID) are thought to be more susceptible to viral infections, it is unclear whether their presentation differs between patients with IMID and healthy controls. This study aimed to investigate the symptom pattern of common viral infections in patients with IMID and compare it with controls without IMIDs.

Design: A cross-sectional study conducted between 1 February and 30 April 2020, using a questionnaire.

Intergenerational risk of preterm birth in First Nations Australians: a population-based cohort study from the Northern Territory, Australia.

Background: PTB increases the risk of health problems such as chronic renal disease and diabetes in later life and adverse impacts are inversely correlated with gestational age at birth. Rates of PTB in the Northern Territory (NT) of Australia are amongst the highest nationally and globally, with First Nations babies most affected. This study assessed the magnitude and potential drivers of intergenerational PTB recurrence in the NT.

Experimental demonstration of a Grover-Michelson interferometer.

We present a low-resource and robust optical implementation of the four-dimensional Grover coin, a four-port linear-optical scatterer that augments the low dimensionality of a regular beam-splitter. While prior realizations of the Grover coin required a potentially unstable ring cavity to be formed, this version of the scatterer does not exhibit any internal interference. When this Grover coin is placed in another system, it can be used for interferometry with a higher-dimensional set of optical field modes.

Analysis of the cryptic biosynthetic gene cluster encoding the RiPP curacozole reveals a phenylalanine-specific peptide hydroxylase.

Curacozole is representative of a cyanobactin-like sub-family of ribosomally synthesized and post-translationally modified peptides (RiPPs). The molecule is distinguished by its small macrocyclic structure, a poly-azole sequence that includes a phenyloxazole moiety, and a d--Ile residue. The enzymatic steps required for its formation are not well understood.

Doctors as Device Manufacturers? Regulation of Clinician-Generated Innovation in the ICU.

Critical care physicians are rich sources of innovation, developing new diagnostic, prognostic, and treatment tools they deploy in clinical practice, including novel software-based tools. Many of these tools are validated and promise to actively help patients, but physicians may be unlikely to distribute, implement, or share them with other centers noncommercially because of unsettled ethical, regulatory, or medicolegal concerns. This Viewpoint explores the potential barriers and risks critical care physicians face in disseminating device-related innovations for noncommercial purposes and proposes a framework for risk-based evaluation to foster clear pathways to safeguard equitable patient access and responsible implementation of clinician-generated technological innovations in critical care.

PGC-1α regulation by FBXW7 through a novel mechanism linking chaperone-mediated autophagy and the ubiquitin-proteasome system.

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a key regulator of mitochondrial biogenesis and antioxidative defenses, and it may play a critical role in Parkinson's disease (PD). F-box/WD repeat domain-containing protein (FBXW7), an E3 protein ligase, promotes the degradation of substrate proteins through the ubiquitin-proteasome system (UPS) and leads to the clearance of PGC-1α. Here, we elucidate a novel post-translational mechanism for regulating PGC-1α levels in neurons.

NEARER SCAN (LENO BESIK) evaluation of a task-sharing echocardiographic active case finding programme for rheumatic heart disease in Australia and Timor-Leste: protocol for a hybrid type II effectiveness-implementation study.

Introduction: Rheumatic heart disease (RHD) is underdiagnosed globally resulting in missed treatment opportunities and adverse clinical outcomes. We describe the protocol for a study which aims to co-design, implement and conduct an evaluation of a task-sharing approach to echocardiographic active case finding for early detection and management of RHD in high-risk settings in Australia and Timor-Leste.

Methods And Analysis: Echocardiograms will be obtained by trained local staff using hand-held echocardiographic devices employing the 'Single Parasternal Long Axis view with a Sweep of the Heart' (SPLASH) technique and interpreted by experts remote from the site of acquisition.

Inter-laboratory study for extraction testing of medical devices.

Biocompatibility evaluation of medical devices often relies on chemical testing according to ISO 10993-18 as a critical component for consideration. However, the precision associated with these non-targeted chemical characterization assessments has not been well established. Therefore, we have conducted a study to characterize intra-laboratory (repeatability) and inter-laboratory (reproducibility) variability associated with chemical testing of extractables from polymeric materials.

A Siah3 of relief: A role for mitophagy as a fail-safe during developmental axon pruning.

Developmental axon pruning is controlled by a careful balance of pro- and anti-apoptotic signals, which are activated in response to external cues to sculpt mature neuronal circuitry. In this issue of , Abraham define a safeguard against apoptotic axon pruning and illustrate that Siah3 represses Parkin-mediated mitophagy to control the availability of axonal mitochondria that activate the pruning process.

Storing liquid chromatographic separations on surface energy traps: decoupling the LC and the mass spectrometer.

We report a micro-fractionation device for high performance liquid chromatography-mass spectrometry to archive chromatographic separations on an array of optimized surface energy traps (SETs). The method has the potential to significantly alter nanoflow LC-MS workflow, decoupling separation and analysis. The wetting characteristics of the SETs cause the HPLC eluent stream to spontaneously split into droplet microfractions.

Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.

Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2.

Objectives: Our goal was to investigate the effects of genetic variants on risk and time to LID.

Young-GRAPPA 2023: The Future Is Bright.

Two years after its inception, Young Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (Y-GRAPPA) has established itself as a productive network for junior investigators and clinicians. The group's achievements in the last year include updating the educational GRAPPA slide library, the "Bring a Derm" campaign to expand the GRAPPA community to include more dermatologists, and the publication of multiple "Do Not Miss" newsletters covering the highlights on PsDs from the major international conferences (American Academy of Dermatology [AAD] Annual Meeting, European Alliance of Associations for Rheumatology [EULAR] Congress, European Academy of Dermatology and Venereology [EADV] Congress, and American College of Rheumatology [ACR] Convergence).

Higher orthorexia tendency among female fashion models: an empirical international study.

Purpose: Female fashion models are more at risk for developing eating disorders than non-models due to the intense occupational pressure they face. The present study focuses on assessing whether female models are more prone to report orthorexia nervosa signs and symptoms than non-models.

Methods: Female fashion models (n = 179, mean age: 25.

New government drug repurposing programs: Opportunities and uncertainties.

Drug repurposing can be cheaper and faster than developing new compounds. Yet, it remains underused, partially because of regulatory and intellectual property challenges. Policy-makers in the United States and Europe have created seven drug development programs that aim to overcome these challenges using a variety of different strategies.

Anatomical pattern of entheseal and synovial fibroblast activation in patients with psoriasis and its risk of developing psoriatic arthritis.

Objectives: To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by gallium-labelled fibroblast activation protein inhibitor-04 (Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA).

Methods: We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with Ga-FAPI-04. Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings.

Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids.

Glucocorticoids represent the mainstay of therapy for a broad spectrum of immune-mediated inflammatory diseases. However, the molecular mechanisms underlying their anti-inflammatory mode of action have remained incompletely understood. Here we show that the anti-inflammatory properties of glucocorticoids involve reprogramming of the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and consequent inhibition of the inflammatory response.

Risk of developing psoriatic arthritis in psoriasis cohorts with arthralgia: exploring the subclinical psoriatic arthritis stage.

Objective: Subjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis.

Methods: Patients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts.

Twelve Years of Drug Prioritization to Help Accelerate Disease Modification Trials in Parkinson's Disease: The International Linked Clinical Trials Initiative.

In 2011, the UK medical research charity Cure Parkinson's set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson's disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data.