Comparative exploration of mammalian deafness gene homologues in the Drosophila auditory organ shows genetic correlation between insect and vertebrate hearing.

Johnston's organ, the Drosophila auditory organ, is anatomically very different from the mammalian organ of Corti. However, recent evidence indicates significant cellular and molecular similarities exist between vertebrate and invertebrate hearing, suggesting that Drosophila may be a useful platform to determine the function of the many mammalian deafness genes whose underlying biological mechanisms are poorly characterized. Our goal was a comprehensive screen of all known orthologues of mammalian deafness genes in the fruit fly to better understand conservation of hearing mechanisms between the insect and the fly and ultimately gain insight into human hereditary deafness.

The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment.

The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8 T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8 T-cells on treatment which is rapidly reversed off-treatment.

Experiences of participating in a group-based sensory modulation intervention for mental health service users.

Background: People with mental health issues often experience difficulties with sensory modulation affecting occupational engagement. Research conducted in inpatient units has shown positive effects of individual sensory modulation interventions, however, research on experiences of group-based interventions in outpatient units is limited. Hence, a group-based sensory modulation intervention was adapted and tested within Swedish mental health outpatient units.

Assessment of AAV9 distribution and transduction in rats after administration through Intrastriatal, Intracisterna magna and Lumbar Intrathecal routes.

Challenges in obtaining efficient transduction of brain and spinal cord following systemic AAV delivery have led to alternative administration routes being used in clinical trials that directly infuse the virus into the CNS. However, data comparing different direct AAV injections into the brain remain limited making it difficult to choose optimal routes. Here we tested both AAV9-egfp and AAV9-fLuc delivery via intrastriatal (IST), intracisterna magna (ICM) and lumbar intrathecal (LIT) routes in adult rats and assessed vector distribution and transduction in brain, spinal cord and peripheral tissues.

Multi-modal molecular imaging maps the correlation between tumor microenvironments and nanomedicine distribution.

Gaining insight into the heterogeneity of nanoparticle drug distribution within tumors would improve both design and clinical translation of nanomedicines. There is little data showing the spatio-temporal behavior of nanomedicines in tissues as current methods are not able to provide a comprehensive view of the nanomedicine distribution, released drug or its effects in the context of a complex tissue microenvironment. A new experimental approach which integrates the molecular imaging and bioanalytical technologies MSI and IMC was developed to determine the biodistribution of total drug and drug metabolite delivered via PLA-PEG nanoparticles and to overlay this with imaging of the nanomedicine in the context of detailed tumor microenvironment markers.

Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly.

For more than 100 years, the fruit fly has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula , that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal.

A Suture Anchor-Based Repair Plus Reconstruction Using Acellular Human Dermal Allograft for Recurrent Sports-Related Patellar Tendon Rupture.

Recurrent traumatic patellar tendon rupture following early repair of a primary rupture is exceedingly rare; there is little technical literature on how to manage this potentially devastating injury. We describe here a suture anchor-based technique for revision repair augmented with an extensor reconstruction using acellular human dermal allograft.

The experience and meaning of recovery-oriented practice for nurses working in acute mental health services.

Since the 1990s, New Zealand mental health policy has shifted from a focus on the management of symptoms and risk to the recovery of psychological, social, cultural, and physical well-being. Despite a vision for recovery-oriented services being integrated within national and regional policies, there is growing concern that barriers to recovery-oriented service provision continue to exist. Such barriers include the attitudes, skills, and knowledge of front-line staff, as well as system issues.

Method to Investigate the Distribution of Water-Soluble Drug-Delivery Systems in Fresh Frozen Tissues Using Imaging Mass Cytometry.

Imaging mass cytometry (IMC) offers the opportunity to image metal- and heavy halogen-containing xenobiotics in a highly multiplexed experiment with other immunochemistry-based reagents to distinguish uptake into different tissue structures or cell types. However, in practice, many xenobiotics are not amenable to this analysis, as any compound which is not bound to the tissue matrix will delocalize during aqueous sample-processing steps required for IMC analysis. Here, we present a strategy to perform IMC experiments on a water-soluble polysarcosine-modified dendrimer drug-delivery system (S-Dends).

Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration.

An ever-increasing array of imaging technologies are being used in the study of complex biological samples, each of which provides complementary, occasionally overlapping information at different length scales and spatial resolutions. It is important to understand the information provided by one technique in the context of the other to achieve a more holistic overview of such complex samples. One way to achieve this is to use annotations from one modality to investigate additional modalities.

30-Day Outcomes of Operative Versus Nonoperative Management for Humeral Diaphyseal Fractures in Patients with Concomitant Hip Fractures.

Every year over 330,000 people are hospitalized for hip fractures in the US. Of those patients, approximately 4-5% of patients with hip fractures present with a concomitant upper extremity fracture. Upper extremity (UE) fractures account for an estimated 2 million fractures a year.

Experiences of sensory input in daily occupations for people with serious mental illness.

Background: There is growing evidence that people with serious mental illness have impaired capacity for processing sensory inputs which affects daily occupation. Although this is known, research regarding the target groups experiences of sensory inputs in daily occupations is lacking.

Aim: To investigate the experience of sensory input and strategies used in daily occupations among people with serious mental illness.

Empowerment, self and engagement in day center occupations: A longitudinal study among people with long-term mental illness.

Background: Day centers are a common form of mental health service internationally. They are aimed at enhancing occupational engagement and social relations, but there is a need to clarify the outcomes of day center programs, including the impact on important aspects of recovery such as empowerment.

Aims: The aim of this study was to explore whether perceived empowerment changed over time among Swedish day center users and whether self-esteem, quality of life, socio-demographic data and self-reported diagnosis, type of program and level of engagement in day center occupations could predict future empowerment.

Harnessing molecular motors for nanoscale pulldown in live cells.

Protein-protein interactions (PPIs) regulate assembly of macromolecular complexes, yet remain challenging to study within the native cytoplasm where they normally exert their biological effect. Here we miniaturize the concept of affinity pulldown, a gold-standard in vitro PPI interrogation technique, to perform nanoscale pulldowns (NanoSPDs) within living cells. NanoSPD hijacks the normal process of intracellular trafficking by myosin motors to forcibly pull fluorescently tagged protein complexes along filopodial actin filaments.

Balloon-Occluded Retrograde Transvenous Obliteration of a Gastric Vascular Malformation: An Innovative Approach to Treatment of a Rare Condition.

Arteriovenous malformations (AVMs) are a high-flow form of a vascular malformation, which can be found anywhere in the body. While historically treated surgically, a multidisciplinary approach utilizing multiple specialties and treatment modalities is now commonly employed. In order to effectively treat an AVM, the nidus must be targeted and eradicated, which can be done via multiple approaches.

Treatment with anti-gremlin 1 antibody ameliorates chronic hypoxia/SU5416-induced pulmonary arterial hypertension in mice.

The expression of the bone morphogenetic protein antagonist, Gremlin 1, was recently shown to be increased in the lungs of pulmonary arterial hypertension patients, and in response to hypoxia. Gremlin 1 released from the vascular endothelium may inhibit endogenous bone morphogenetic protein signaling and contribute to the development of pulmonary arterial hypertension. Here, we investigate the impact of Gremlin 1 inhibition in disease after exposure to chronic hypoxia/SU5416 in mice.

Optimizing arousal to manage aggression: a pilot study of sensory modulation.

The dominant model that informs clinical training for preventing violence and managing aggression posits arousal as mediated downwards from higher cortical structures. This view results in an often-misplaced reliance on verbal and cognitive techniques for de-escalation. The emergence of sensory modulation, via the Six Core Strategies, is an alternative or complementary approach that is associated with reduced rates of seclusion and restraint.

A phenomenological study of occupational engagement in recovery from mental illness.

Background: Recovery from mental illness has been described as a process involving personal growth and a search for meaning. Occupation is a primary medium for human development as well as the creation of life meaning, suggesting the exploration of recovery from an occupational perspective is warranted.

Purpose: To explore the experience and meaning of occupation for 713 people who self-identified as being in recovery from mental illness.

The use of palliative radiotherapy for bone metastasis.

Background: The value of palliative radiotherapy (PRT) for bone metastases is well established, but little is known about its use in the general population.

Purpose: To describe the use of PRT for bone metastases in Ontario.

Materials And Methods: This was a retrospective cohort study.