Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy.

Tissue-resident memory T (T) cells preferentially reside in peripheral tissues, serving as key players in tumor immunity and immunotherapy. The lack of effective approaches for expanding T cells and delivering these cells in vivo hinders the exploration of T cell-mediated cancer immunotherapy. Here, we report a nanoparticle artificial antigen-presenting cell (nano-aAPC) ex vivo expansion approach and an in vivo delivery system for T cells.

Alginate-based artificial antigen presenting cells expand functional CD8 T cells with memory characteristics for adoptive cell therapy.

The development of artificial Antigen Presenting Cells (aAPCs) has led to improvements in adoptive T cell therapy (ACT), an immunotherapy, for cancer treatment. aAPCs help to streamline the consistent production and expansion of T cells, thus reducing the time and costs associated with ACT. However, several issues still exist with ACT, such as insufficient T cell potency, which diminishes the translational potential for ACT.

Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming.

Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces.

Suprachoroidal gene transfer with nonviral nanoparticles in large animal eyes.

Suprachoroidal nonviral gene therapy with biodegradable poly(β-amino ester) nanoparticles (NPs) provides widespread expression in photoreceptors and retinal pigmented epithelial (RPE) cells and therapeutic benefits in rodents. Here, we show in a human-sized minipig eye that suprachoroidal injection of 50 μl of NPs containing 19.2 μg of GFP expression plasmid caused GFP expression in photoreceptors and RPE throughout the entire eye with no toxicity.

Predicting school uptake of The Daily Mile in Northern Ireland- a data linkage study with School Census Data and Multiple Deprivation Measures.

Background: Participating in physical activity benefits health, yet a majority of children remain inactive. The Daily Mile™ (TDM) originated in Scotland in 2012 with the aim of increasing primary school children's physical fitness. Despite being a practically feasible and popular initiative, it remains unclear the extent to which schools implement TDM, and whether TDM core principles are adhered to (i.

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial.

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51).

The long reach of juvenile and criminal legal debt: How monetary sanctions shape legal cynicism and adultification.

Previous research has established the deleterious long-term effects of juvenile legal system involvement such as increased risk of criminal legal system involvement as adults. This paper examines retrospective accounts of how that process occurs by exploring the following research question: how does one's involvement in the juvenile legal system, which includes monetary sanctions, shape peoples' views of law and legal institutions and with what consequences? Based on 19 interviews with adults who have legal debt from both juvenile and criminal legal systems, the paper focuses on four aspects of the long-reaching effects of juvenile legal involvement and juvenile monetary sanctions: legal socialization, adultification, legal cynicism, and future aspirations. In all these aspects, we show the organizational constraints that shape individuals' perspectives about the law and the impact of monetary sanctions on their lives.

Pediatric Upper Extremity Trauma Secondary to All-terrain Vehicle Use.

All-terrain vehicles (ATVs) have become popular with respect to recreational activities. Multiple orthopaedic and pediatric organizations currently recommend limiting use of ATVs to older age groups of children with supervision. These recommendations have not generally been adhered to, resulting in a disproportionate number of pediatric orthopaedic trauma, specifically of the upper extremities.

Physical activity in childhood and adolescence and future depressive symptoms: an 11-year prospective cohort study.

Background: Physical activity (PA) can reduce young peoples' risk of depressive symptoms. Associations between PA and depressive symptoms are often investigated over timeframes spanning minutes to weeks. Less is known about whether childhood/adolescent PA can predict depressive symptoms in early adulthood.

Constructed languages are processed by the same brain mechanisms as natural languages.

What constitutes a language? Natural languages share features with other domains: from math, to music, to gesture. However, the brain mechanisms that process linguistic input are highly specialized, showing little response to diverse non-linguistic tasks. Here, we examine constructed languages (conlangs) to ask whether they draw on the same neural mechanisms as natural languages, or whether they instead pattern with domains like math and programming languages.

MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants ( = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions.

Polymeric nanoparticle gel for intracellular mRNA delivery and immunological reprogramming of tumors.

Immuno-oncology therapies have been of great interest with the goal of inducing sustained tumor regression, but clinical results have demonstrated the need for improved and widely applicable methods. An antigen-free method of cancer immunotherapy can stimulate the immune system to recruit lymphocytes and produce immunostimulatory factors without prior knowledge of neoantigens, while local delivery reduces the risk of systemic toxicity. To improve the interactions between tumor cells and cytotoxic lymphocytes, a gene delivery nanoparticle platform was engineered to reprogram the tumor microenvironment (TME) in situ to be more immunostimulatory by inducing tumor-associated antigen-presenting cells (tAPCs) to activate cytotoxic lymphocytes against the tumor.

Episiotomy-assisted Incarcerated Femoral Nail Removal: Technical Note.

Introduction: Incarceration of intramedullary nails can pose a significant challenge. There are many reported techniques of nail removal, but when these fail, it can be difficult to determine how to proceed. Here, it is shown that a proximal femoral episiotomy can be used with great effect.

Ketamine-Assisted Group Psychotherapy for Frontline Healthcare Workers with COVID-19-Related Burnout and PTSD: A Case Series of Effectiveness/Safety for 10 Participants.

This study reports on 10 frontline healthcare workers, employed during the COVID-19 pandemic and experiencing symptoms of burnout and PTSD, treated with group ketamine-assisted psychotherapy (KAP) in a private outpatient clinic setting. Participants attended 6 sessions once weekly. These included 1 preparation session, 3 ketamine sessions (2 sublingual, 1 intramuscular), 2 integration sessions.

Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy.

Artificial antigen presenting cells are biomimetic particles that recapitulate the signals presented by natural antigen presenting cells in order to stimulate T cells in an antigen-specific manner using an acellular platform. We have engineered an enhanced nanoscale biodegradable artificial antigen presenting cell by modulating particle shape to achieve a nanoparticle geometry that allows for increased radius of curvature and surface area for T cell contact. The non-spherical nanoparticle artificial antigen presenting cells developed here have reduced nonspecific uptake and improved circulation time compared both to spherical nanoparticles and to traditional microparticle technologies.

A systematic review of the effect of The Daily Mile™ on children's physical activity, physical health, mental health, wellbeing, academic performance and cognitive function.

Background: A minority of children in the United Kingdom meet the recommended physical activity guidelines. One initiative which has been introduced to try and increase the physical activity levels of school children is The Daily Mile™ (TDM). The aim of this review was to determine the effect of TDM on children's physical activity levels, physical health, mental health, wellbeing, academic performance and cognitive function.

The contingent effect of incarceration on state health outcomes.

Introduction: This study examines how growth in the population of former prisoners affects rates of communicable diseases such as tuberculosis, syphilis, chlamydia, and HIV.

Methods: We estimate state-level fixed effects count models showing how the former prisoner population affected communicable disease in U.S.

Frequency, intensity and duration of muscle strengthening activity and associations with mental health.

Objectives: Despite growing emphasis on the benefits of physical activity for promoting mental health, inclusion of muscle-strengthening (MS) (e.g., body-weight exercises, resistance machines) activities is limited.

Outcomes of Tibiotalocalcaneal Hindfoot Fusion Nails Used for Acute Lower Extremity Trauma in a High-Risk Patient Population.

Objective: To determine the outcomes of high-risk patients treated with tibiotalocalcaneal hindfoot fusion nails.

Design: Retrospective case series.

Setting: Level I trauma center.

Decommission of a Heartmate 3 LVAD in a patient with left ventricular recovery.

Background: Left ventricular assist devices (LVADs) have been a significant development in the treatment of patients with advanced heart failure supporting circulation as a bridge to transplant, recovery, or long-term destination therapy. When ventricular recovery occurs, there are multiple described ways of proceeding. HM2 decommissions are well described with varying degrees of explant operations, less so in HM3 due to the novelty of the device.