Intravitreal enzyme replacement therapy slows retinopathy in late infantile ceroid lipofuscinosis type 2.

Ceroid lipofuscinosis type 2 (CLN2) is caused by biallelic pathogenic variants in the TPP1 gene, encoding lysosomal tripeptidyl peptidase 1 (TPP1). The classical late-infantile phenotype has an age of onset between 2 and 4 years and is characterized by psychomotor regression, myoclonus, ataxia, blindness, and shortened life expectancy. Vision loss occurs due to retinal degeneration, usually when severe neurological symptoms are already evident.

Peatland organic matter quality varies with latitude as suggested by combination of FTIR and Ramped Pyrolysis Oxidation.

We employed two compelling and distinct methods, Fourier Transform Infrared Spectroscopy (FTIR) and Ramped Pyrolysis Oxidation (Ramped PyrOx), to examine the quality of organic matter (OM) stored in four peatlands located along a latitudinal gradient (Tropical (4˚N), Subtropical (27˚N), Boreal (48˚N), and Polar (68˚N)). FTIR was used to quantify the relative abundance of carbohydrates, a relatively labile compound class, and aromatics, which are more recalcitrant, in a sample set of four peat cores. These samples were then prepared using Ramped PyrOx, a second, independent method of determining OM quality that mimics the natural diagenetic maturation of OM that would take place over long timescales.

Arachidonic Acid Directly Activates the Human DP2 Receptor.

Aberrant type 2 inflammatory responses are the underlying cause of the pathophysiology of allergic asthma, allergic rhinitis, and other atopic diseases, with an alarming prevalence in relevant parts of the Western world. A bulk of evidence points out the important role of the DP2 receptor in these inflammation processes. A screening of different polyunsaturated fatty acids at a fluorescence resonance energy transfer-based DP2 receptor conformation sensor expressed in human embryonic kidney (HEK) cells revealed an agonistic effect of the prostaglandin (PG)-D precursor arachidonic acid on DP2 receptor activity of about 80% of the effect induced by PGD In a combination of experiments at the conformation sensor and using a bioluminescence resonance energy transfer-based G protein activation sensor expressed together with DP2 receptor wild type in HEK cells, we found that arachidonic acid acts as a direct activator of the DP2 receptor, but not the DP1 receptor, in a concentration range considered physiologically relevant.

Barriers to stroke treatment: The price of long-distance from thrombectomy centers.

Background: Endovascular thrombectomy, the preferred treatment for acute large-vessel occlusion stroke, is highly time-dependent. Many patients live far from thrombectomy centers due to large geographical variations in stroke services. This study aimed to explore the consequences of long transport distance on the proportion of thrombectomy-eligible patients who underwent thrombectomy, the clinical outcomes with or without thrombectomy, the timelines for patients transported, and the diagnostic accuracy of large-vessel occlusion in primary stroke centers.

Alpha oscillations during visual selective attention are aberrant in youth and adults with cerebral palsy.

Our understanding of the neurobiology underlying cognitive dysfunction in persons with cerebral palsy is very limited, especially in the neurocognitive domain of visual selective attention. This investigation utilized magnetoencephalography and an Eriksen arrow-based flanker task to quantify the dynamics underlying selective attention in a cohort of youth and adults with cerebral palsy (n = 31; age range = 9 to 47 yr) and neurotypical controls (n = 38; age range = 11 to 49 yr). The magnetoencephalography data were transformed into the time-frequency domain to identify neural oscillatory responses and imaged using a beamforming approach.

Does clinical experience influence the effects of team simulation training in stroke thrombolysis? A prospective cohort study.

Objectives: After introducing a team simulation training programme at our hospital, we saw a reduction in door-to-needle times (DNT) for stroke thrombolysis but persisting variability prompting further investigation. Our objective is to examine this gap through assessing: (1) whether there is an association between DNT and the clinical experience of neurology registrars and (2) whether experience influences the benefits from attending simulation.

Design: Prospective cohort study.

Receipt of Opioid Agonist Treatment in provincial correctional facilities in British Columbia is associated with a reduced hazard of nonfatal overdose in the month following release.

Background: In many jurisdictions, policies restrict access to Opioid Agonist Treatment (OAT) in correctional facilities. Receipt of OAT during incarceration is associated with reduced risk of fatal overdose after release but little is known about the effect on nonfatal overdose. This study aimed to examine the association between OAT use during incarceration and nonfatal overdose in the 30 days following release.

Scoping Literature Review of Disease Modeling of the Opioid Crisis.

Opioid misuse continues to cause significant harm. To investigate current research, we conducted a scoping literature review of disease spread models of opioid misuse from January 2000 to December 2022. In total, 85 studies were identified and examined for the opioids modeled, model type, data sources used and model calibration and validation.

Adults with cerebral palsy exhibit uncharacteristic cortical oscillations during an adaptive sensorimotor control task.

Prior research has shown that the sensorimotor cortical oscillations are uncharacteristic in persons with cerebral palsy (CP); however, it is unknown if these altered cortical oscillations have an impact on adaptive sensorimotor control. This investigation evaluated the cortical dynamics when the motor action needs to be changed "on-the-fly". Adults with CP and neurotypical controls completed a sensorimotor task that required either proactive or reactive control while undergoing magnetoencephalography (MEG).

What is the ideal time to begin tapering opioid agonist treatment? A protocol for a retrospective population-based comparative effectiveness study in British Columbia, Canada.

Introduction: Opioid agonist treatment (OAT) tapering involves a gradual reduction in daily medication dose to ultimately reach a state of opioid abstinence. Due to the high risk of relapse and overdose after tapering, this practice is not recommended by clinical guidelines, however, clients may still request to taper off medication. The ideal time to initiate an OAT taper is not known.

Machine learning-based detection of acute psychosocial stress from body posture and movements.

Investigating acute stress responses is crucial to understanding the underlying mechanisms of stress. Current stress assessment methods include self-reports that can be biased and biomarkers that are often based on complex laboratory procedures. A promising additional modality for stress assessment might be the observation of body movements, which are affected by negative emotions and threatening situations.

DP2 receptor activity sensor suited for antagonist screening and measurement of receptor dynamics in real-time.

The DP2 receptor is a G-protein coupled receptor involved in allergic inflammation and is the target of recently developed antagonists already being tested in clinics. To get insights into DP2 receptor dynamics and to study its pharmacology on the level of the receptor, we constructed a fluorescence resonance energy transfer-based conformation sensor. The sensor reflects the selectivity profile of the DP2 receptor-wt and is suited for screening of agonists and antagonists due to its robust response.

Prescribing practices in opioid agonist treatment and changes in compliance to clinical dosing guidelines in British Columbia, Canada.

Background And Aim: In British Columbia, Canada, clinical guidelines for the treatment of opioid use disorders (OUD) were updated in 2017, during a period in which the potency and composition of the illicit drug supply changed rapidly. We aimed to describe changes in opioid agonist treatment (OAT) prescribing practices at the population level in a setting in which fentanyl and its analogs have become the primary illicit opioid of use.

Design, Setting And Participants: This was a population-based retrospective cohort study using three linked health administrative databases in British Columbia (BC), Canada.

Emplacement and associated sedimentary record of the Jurassic submarine salt allochthon of the Wurzeralm (Eastern Alps, Austria).

A fossil salt sheet emplaced in the Jurassic in submarine conditions is described in the Eastern Alps of Austria, providing unique insights into the emplacement of similar submarine structures and their potential control on depositional systems. The salt sheet is a plug-fed extrusion emplaced due to squeezing of a salt diapir under compression. The preserved mylonitic shear fabric in the evaporites indicates radial, south-directed emplacement of the salt sheet.

Implementation of pharmaceutical alternatives to a toxic drug supply in British Columbia: A mixed methods study.

Background: North America has been in an unrelenting overdose crisis for almost a decade. British Columbia (BC), Canada declared a public health emergency due to overdoses in 2016. Risk Mitigation Guidance (RMG) for prescribing pharmaceutical opioids, stimulants and benzodiazepine alternatives to the toxic drug supply ("safer supply") was implemented in March 2020 in an attempt to reduce harms of COVID-19 and overdose deaths in BC during dual declared public health emergencies.

Individuals With Multiple Sclerosis Exhibit More Regular Center of Mass Accelerations After Physical Therapy.

Objective: The purpose of this investigation was to explore if a physical therapy program involving strength, flexibility, balance, and walking can improve the uncharacteristic gait variability and overall mobility of persons living with multiple sclerosis (pwMS).

Design: Pre-post design to evaluate the mobility improvements after undergoing 6 weeks of a gait and balance physical therapy intervention.

Setting: The initial 2 weeks were conducted at a medical center under close supervision of a physical therapist.

The Public Health and Economic Impact of Drug Overdose Out-of-Hospital Cardiac Arrest in the United States.

Objective: To calculate disability-adjusted life years (DALY) and labor productivity loss due to drug overdose out-of-hospital cardiac arrest (DO-OHCA) and compare its contribution to the burden of disease and economic impact of all-cause nontraumatic out-of-hospital cardiac arrest (OHCA) in the US.

Methods: We performed a retrospective observational cohort analysis of all adult (age 18 years) nontraumatic emergency medical services-treated OHCA events, including those due to DO-OHCA, from the national Cardiac Arrest Registry to Enhance Survival (CARES) database from January 1, 2017 and December 31, 2020. The main outcome measures of interest were disability-adjusted life years, annual, and lifetime labor productivity loss over the 4-year study period.