Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Northern Latitude but Not Season Is Associated with Increased Rates of Hospitalizations Related to Inflammatory Bowel Disease: Results of a Multi-Year Analysis of a National Cohort

Background and Aims: There is growing evidence that the incidence and severity of inflammatory bowel disease (IBD) may be geographically and seasonally related. Why these associations are observed remains unclear. We assessed the impact of geographic location, season, and exposure to ultraviolet light on disease severity by measuring national hospital IBD-related discharge rates. Methods: Utilizing the Nationwide Inpatient Sample (NIS), we identified all patients with IBD-related discharges from 2001–2007. Patients were included if they were discharged from states above the 40th parallel (north) or at or below the 35th parallel (south); and their discharge fell within the winter (January, February, and March) or summer (July, August, and September). Groups of patients were assessed comparing north to south within each season, and summer to winter within each region. UV index was recorded from the National Weather Service data and compared to monthly discharge rates. Results: There was a consistent pattern of increased IBD-related hospitalization rates in northern states compared to southern states for both ulcerative colitis and Crohn’s disease. Differences in IBD-related hospitalization rates by season, however, were not uniform across the years studied. UV index was significantly inversely associated although not proportional to discharge rates for both Crohn’s disease and ulcerative colitis. Conclusions: In the US, there is a significant increased rate of IBD-related hospitalizations in the northern compared to southern states, which not fully explained by differences in UV exposure.</p

Northern Latitude but Not Season Is Associated with Increased Rates of Hospitalizations Related to Inflammatory Bowel Disease: Results of a Multi-Year Analysis of a National Cohort

<div><p>Background and Aims</p><p>There is growing evidence that the incidence and severity of inflammatory bowel disease (IBD) may be geographically and seasonally related. Why these associations are observed remains unclear. We assessed the impact of geographic location, season, and exposure to ultraviolet light on disease severity by measuring national hospital IBD-related discharge rates.</p><p>Methods</p><p>Utilizing the Nationwide Inpatient Sample (NIS), we identified all patients with IBD-related discharges from 2001–2007. Patients were included if they were discharged from states above the 40^th parallel (north) or at or below the 35^th parallel (south); and their discharge fell within the winter (January, February, and March) or summer (July, August, and September). Groups of patients were assessed comparing north to south within each season, and summer to winter within each region. UV index was recorded from the National Weather Service data and compared to monthly discharge rates.</p><p>Results</p><p>There was a consistent pattern of increased IBD-related hospitalization rates in northern states compared to southern states for both ulcerative colitis and Crohn’s disease. Differences in IBD-related hospitalization rates by season, however, were not uniform across the years studied. UV index was significantly inversely associated although not proportional to discharge rates for both Crohn’s disease and ulcerative colitis.</p><p>Conclusions</p><p>In the US, there is a significant increased rate of IBD-related hospitalizations in the northern compared to southern states, which not fully explained by differences in UV exposure.</p></div

Discharge OR comparing seasons within each region as well as geography within each season.

<p>For each year, the OR were calculated for all IBD, UC only, and CD only.</p

Multivariate analysis comparing south versus north.

<p>Variables included in the multivariate analysis included race, age, and payer status.</p

X-ray Activated Nanoplatforms for Deep Tissue Photodynamic Therapy

Photodynamic therapy (PDT), the use of light to excite photosensitive molecules whose electronic relaxation drives the production of highly cytotoxic reactive oxygen species (ROS), has proven an effective means of oncotherapy. However, its application has been severely constrained to superficial tissues and those readily accessed either endoscopically or laparoscopically, due to the intrinsic scattering and absorption of photons by intervening tissues. Recent advances in the design of nanoparticle-based X-ray scintillators and photosensitizers have enabled hybridization of these moieties into single nanocomposite particles. These nanoplatforms, when irradiated with diagnostic doses and energies of X-rays, produce large quantities of ROS and permit, for the first time, non-invasive deep tissue PDT of tumors with few of the therapeutic limitations or side effects of conventional PDT. In this review we examine the underlying principles and evolution of PDT: from its initial and still dominant use of light-activated, small molecule photosensitizers that passively accumulate in tumors, to its latest development of X-ray-activated, scintillator–photosensitizer hybrid nanoplatforms that actively target cancer biomarkers. Challenges and potential remedies for the clinical translation of these hybrid nanoplatforms and X-ray PDT are also presented

X-ray Activated Nanoplatforms for Deep Tissue Photodynamic Therapy

Photodynamic therapy (PDT), the use of light to excite photosensitive molecules whose electronic relaxation drives the production of highly cytotoxic reactive oxygen species (ROS), has proven an effective means of oncotherapy. However, its application has been severely constrained to superficial tissues and those readily accessed either endoscopically or laparoscopically, due to the intrinsic scattering and absorption of photons by intervening tissues. Recent advances in the design of nanoparticle-based X-ray scintillators and photosensitizers have enabled hybridization of these moieties into single nanocomposite particles. These nanoplatforms, when irradiated with diagnostic doses and energies of X-rays, produce large quantities of ROS and permit, for the first time, non-invasive deep tissue PDT of tumors with few of the therapeutic limitations or side effects of conventional PDT. In this review we examine the underlying principles and evolution of PDT: from its initial and still dominant use of light-activated, small molecule photosensitizers that passively accumulate in tumors, to its latest development of X-ray-activated, scintillator&ndash;photosensitizer hybrid nanoplatforms that actively target cancer biomarkers. Challenges and potential remedies for the clinical translation of these hybrid nanoplatforms and X-ray PDT are also presented