14 research outputs found
A Salt in the Buffer Zone: Potassium Dysregulation Drives Glioma Growth?
Glioma Epileptiform Activity and Progression Are Driven by IGSF3-Mediated Potassium Dysregulation
Curry RN, Aiba I, Meyer J, Lozzi B, Ko Y, McDonald MF, Rosenbaum A, Cervantes A, Huang-Hobbs E, Cocito C, Greenfield JP, Jalali A, Gavvala J, Mohila C, Harmanci AS, Noebels J, Rao G, Deneen B. Neuron. 2023;111(5): 682-695. doi:https://doi.org/10.1016/j.neuron.2023.01.013
Seizures are a frequent pathophysiological feature of malignant glioma. Recent studies implicate peritumoral synaptic dysregulation as a driver of brain hyperactivity and tumor progression; however, the molecular mechanisms that govern these phenomena remain elusive. Using scRNA-seq and intraoperative patient ECoG recordings, we show that tumors from seizure patients are enriched for gene signatures regulating synapse formation. Employing a human-to-mouse in vivo functionalization pipeline to screen these genes, we identify IGSF3 as a mediator of glioma progression and dysregulated neural circuitry that manifests as spreading depolarization (SD). Mechanistically, we discover that IGSF3 interacts with Kir4.1 to suppress potassium buffering and found that seizure patients exhibit reduced expression of potassium handlers in proliferating tumor cells. In vivo imaging reveals that dysregulated synaptic activity emanates from the tumor-neuron interface, which we confirm in patients. Our studies reveal that tumor progression and seizures are enabled by ion dyshomeostasis and identify SD as a driver of disease
Are Genetic Therapies for Epilepsy Ready for the Clinic?
In recent years, there has been a significant increase in preclinical studies to test genetic therapies for epilepsy. Some of these therapies have advanced to clinical trials and are being tested in patients with monogenetic or focal refractory epilepsy. This article provides an overview of the current state of preclinical studies that show potential for clinical translation. Specifically, we focus on genetic therapies that have demonstrated a clear effect on seizures in animal models and have the potential to be translated to clinical settings. Both therapies targeting the cause of the disease and those that treat symptoms are discussed. We believe that the next few years will be crucial in determining the potential of genetic therapies for treating patients with epilepsy
Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting
Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic
The efficacy of higher versus lower dose exercise in rotator cuff tendinopathy: A systematic review of randomised controlled trials
Aim: to compare the effectiveness and harms of higher exercise dose, including higher exercise load and/or higher volume, with lower exercise dose (lower load and/or lower volume) in people with rotator cuff tendinopathy Design: Systematic review (PROSPERO: CRD42017077478) Data sources: CENTRAL, MEDLINE, EMBASE, CINAHL from inception to March 2019. Eligibility criteria: Randomised controlled trials comparing higher versus lower dose exercise. Data extraction and risk of bias: Two authors independently determined eligibility, extracted data and assessed risk of bias using the Cochrane tool. Outcomes were function and pain (overall, activity, night), and proportion of participants with adverse events. The primary endpoint was >six weeks to three months (other endpoints included up to six weeks & beyond three months) and GRADE was used to assess evidence certainty. Results: Three trials (N=283), none at low risk of bias for all domains, were included. Low certainty evidence (1 trial, N=102) indicated improved function (20 points [95% CI 12 to 28 points] on 0-100 point scale) with higher load and volume exercise at three months, but little or no clinically important between-group difference in activity or night pain (overall pain not reported). Very low certainty evidence (1 trial, N=120) indicated higher load exercise conferred no function benefits over lower load exercise at six weeks. Very low certainty evidence (1 trial, N=61) indicated benefit of uncertain clinical importance in function with higher versus lower volume exercise at three months and clinically important benefit at >3 months (pain outcomes not reported). Risk of adverse events was uncertain. Conclusions: There are few studies that investigate higher dose exercise for rotator cuff tendinopathy. Low to very low certainty and conflicting evidence found about the value of higher versus lower dose exercise for people with rotator cuff tendinopathy
From Data to Software to Science with the Rubin Observatory LSST
The Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) dataset
will dramatically alter our understanding of the Universe, from the origins of
the Solar System to the nature of dark matter and dark energy. Much of this
research will depend on the existence of robust, tested, and scalable
algorithms, software, and services. Identifying and developing such tools ahead
of time has the potential to significantly accelerate the delivery of early
science from LSST. Developing these collaboratively, and making them broadly
available, can enable more inclusive and equitable collaboration on LSST
science.
To facilitate such opportunities, a community workshop entitled "From Data to
Software to Science with the Rubin Observatory LSST" was organized by the LSST
Interdisciplinary Network for Collaboration and Computing (LINCC) and partners,
and held at the Flatiron Institute in New York, March 28-30th 2022. The
workshop included over 50 in-person attendees invited from over 300
applications. It identified seven key software areas of need: (i) scalable
cross-matching and distributed joining of catalogs, (ii) robust photometric
redshift determination, (iii) software for determination of selection
functions, (iv) frameworks for scalable time-series analyses, (v) services for
image access and reprocessing at scale, (vi) object image access (cutouts) and
analysis at scale, and (vii) scalable job execution systems.
This white paper summarizes the discussions of this workshop. It considers
the motivating science use cases, identified cross-cutting algorithms,
software, and services, their high-level technical specifications, and the
principles of inclusive collaborations needed to develop them. We provide it as
a useful roadmap of needs, as well as to spur action and collaboration between
groups and individuals looking to develop reusable software for early LSST
science.Comment: White paper from "From Data to Software to Science with the Rubin
Observatory LSST" worksho
From Data to Software to Science with the Rubin Observatory LSST
editorial reviewedThe Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) dataset will dramatically alter our understanding of the Universe, from the origins of the Solar System to the nature of dark matter and dark energy. Much of this research will depend on the existence of robust, tested, and scalable algorithms, software, and services. Identifying and developing such tools ahead of time has the potential to significantly accelerate the delivery of early science from LSST. Developing these collaboratively, and making them broadly available, can enable more inclusive and equitable collaboration on LSST science. To facilitate such opportunities, a community workshop entitled "From Data to Software to Science with the Rubin Observatory LSST" was organized by the LSST Interdisciplinary Network for Collaboration and Computing (LINCC) and partners, and held at the Flatiron Institute in New York, March 28-30th 2022. The workshop included over 50 in-person attendees invited from over 300 applications. It identified seven key software areas of need: (i) scalable cross-matching and distributed joining of catalogs, (ii) robust photometric redshift determination, (iii) software for determination of selection functions, (iv) frameworks for scalable time-series analyses, (v) services for image access and reprocessing at scale, (vi) object image access (cutouts) and analysis at scale, and (vii) scalable job execution systems. This white paper summarizes the discussions of this workshop. It considers the motivating science use cases, identified cross-cutting algorithms, software, and services, their high-level technical specifications, and the principles of inclusive collaborations needed to develop them. We provide it as a useful roadmap of needs, as well as to spur action and collaboration between groups and individuals looking to develop reusable software for early LSST science
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries