A phenomenological inquiry into the costs and consequences of insomnia for veterans with serious mental illness.

Many individuals with serious mental illness (i.e. schizophrenia spectrum, bipolar or major depressive disorders, with serious functional impairments) have insomnia symptoms.

Vaccines targeting activating mutations elicit anti-tumor immune responses and suppress estrogen signaling in therapy resistant ER+ breast cancer.

ER+ breast cancers (BC) are characterized by the elevated expression and signaling of estrogen receptor alpha (, which renders them sensitive to anti-endocrine therapy. While these therapies are clinically effective, prolonged treatment inevitably results in therapeutic resistance, which can occur through the emergence of gain-of-function mutations in . The central importance of and development of mutated forms of suggest that vaccines targeting these proteins could potentially be effective in preventing or treating endocrine resistance.

Beyond Neoantigens: Antigens Derived from Tumor Drivers as Cancer Vaccine Targets.

A vaccine targeting HER2, a nonmutated but overexpressed tumor antigen, readily primed T cells for ex vivo expansion and adoptive transfer with minimal toxicity. This regimen led to intramolecular epitope spreading in a majority of patients and offers a treatment modality that may improve outcomes for patients with metastatic breast cancer expressing HER2. See related article by Disis et al.

Key takeaways for knowledge expansion of early-career scientists conducting Transdisciplinary Research in Energetics and Cancer (TREC): a report from the TREC Training Workshop 2022.

The overall goal of the annual Transdisciplinary Research in Energetics and Cancer (TREC) Training Workshop is to provide transdisciplinary training for scientists in energetics and cancer and clinical care. The 2022 Workshop included 27 early-to-mid career investigators (trainees) pursuing diverse TREC research areas in basic, clinical, and population sciences. The 2022 trainees participated in a gallery walk, an interactive qualitative program evaluation method, to summarize key takeaways related to program objectives.

Identifying positive and negative use of non-technical skills by anesthesiologists in the clinical operating room: An exploratory descriptive study.

Background: Teamwork is a critical competency in high-risk settings like the operating room (OR). While conventional approaches focus on describing and learning from negative performance, there may be value in learning from high-performing behaviour, particularly in specialties where serious safety events are relatively rare. This study aimed to explore both the positive and negative use of non-technical skills by anesthesia practitioners in the OR and situate them within the clinical OR context.

Clinical trials of self-replicating RNA-based cancer vaccines.

Therapeutic cancer vaccines, designed to activate immune effectors against tumor antigens, utilize a number of different platforms for antigen delivery. Among these are messenger RNAs (mRNA), successfully deployed in some prophylactic SARS-CoV2 vaccines. To enhance the immunogenicity of mRNA-delivered epitopes, self-replicating RNAs (srRNA) that markedly increase epitope expression have been developed.

Highly stressful events and posttraumatic stress disorder symptoms among veterinary professionals: Prevalence and associations with mental health and job-related outcomes.

Objective: Explore the relationship between highly stressful events in veterinary medicine and mental health outcomes such as posttraumatic stress disorder (PTSD).

Method: Using narratives of highly stressful work events from 359 veterinary professionals, we calculated the prevalence of PTSD using both the standard Criterion A from DSM-5-TR and an expanded definition of a traumatic event that included animals as victims. Bivariate correlations were performed to probe for relationships between exposure to highly stressful events and other negative mental health outcomes.

Motivational Interviewing Effects on Positive Airway Pressure Therapy (PAP) Adherence: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: This systematic review and meta-analysis examined Motivational Interviewing (MI) effects on positive airway pressure (PAP) adherence and related outcomes.

Method: Medline, CIHANL, Psych Info, Web of Science, PubMed, and Cochrane Database of Systematic Reviews were searched for randomized controlled trials published from peer-reviewed journals in English from 1990 to 2021 that compared objective PAP adherence among adults with obstructive sleep apnea (OSA) in a MI and non-MI intervention. A random effects meta-analysis model was completed at the 1-to-2-week, and 1-, 2-, 3-, and 12-month follow-up, and risk of bias was analyzed with the Cochrane Risk of Bias Tool.

How do US military veterans with serious mental illness manage insomnia? A phenomenological analysis.

Insomnia is a prevalent experience for individuals with serious mental illness, and is one of the most common reasons for mental health referrals in the Veterans Health Administration. Insomnia also critically impacts psychiatric, cognitive and somatic outcomes. However, there is limited information about how people with serious mental illness (i.

Trastuzumab/pertuzumab combination therapy stimulates antitumor responses through complement-dependent cytotoxicity and phagocytosis.

Two HER2-specific mAbs, trastuzumab and pertuzumab (T+P), combined with chemotherapy comprise standard-of-care treatment for advanced HER2+ breast cancers (BC). While this antibody combination is highly effective, its synergistic mechanism-of-action (MOA) remains incompletely understood. Past studies have suggested that the synergy underlying this combination occurs through the different mechanisms elicited by these antibodies, with pertuzumab suppressing HER2 heterodimerization and trastuzumab inducing antitumor immunity.

Combination of ultrasound-based mechanical disruption of tumor with immune checkpoint blockade modifies tumor microenvironment and augments systemic antitumor immunity.

Background: Despite multimodal adjuvant management with radiotherapy, chemotherapy and hormonal therapies, most surgically resected primary breast cancers relapse or metastasize. A potential solution to late and distant recurrence is to augment systemic antitumor immunity, in part by appropriately presenting tumor antigens, but also by modulating the immunosuppressive tumor microenvironment (TME). We previously validated this concept in models of murine carcinoma treated with a novel predominately microcavitating version of high-intensity focused ultrasound (HIFU), mechanical high-intensity focused ultrasound (M-HIFU).

Art Activities in Long-Term Care: A Scoping Review.

Outcomes of using art in therapy overlap with goals of occupational therapy with older adults in long-term care, which include improving and maintaining health and well-being through engagement in occupations. There is a lack of evidence about how art activities could complement or inform occupational therapy. The purpose of this scoping review is to map existing literature about how art activities are used in long-term care.

HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of numerous oncogenic drivers, including the androgen receptor and its variants, to detect aggressive prostate cancer. We linked a near-infrared fluorescing molecule to an HSP90 binding drug and demonstrated that this probe (designated HS196) was highly sensitive and specific for detecting implanted prostate cancer cell lines with greater uptake by more aggressive subtypes.

Defecatory Dysfunction.

Normal defecation is a complex and coordinated physiologic process that involves the rectum, anus, anal sphincter complex, and pelvic floor muscles. Any alteration of this process can be considered defecatory dysfunction, a term that covers a broad range of disorders, including slow-transit constipation, functional constipation, and functional or anatomic outlet obstruction. Evaluation should include history, physical, and consideration of additional testing such as colonoscopy, colonic transit studies, defecography, and/or anorectal manometry.

Canadian Airway Focus Group updated consensus-based recommendations for management of the difficult airway: part 1. Difficult airway management encountered in an unconscious patient.

Purpose: Since the last Canadian Airway Focus Group (CAFG) guidelines were published in 2013, the literature on airway management has expanded substantially. The CAFG therefore re-convened to examine this literature and update practice recommendations. This first of two articles addresses difficulty encountered with airway management in an unconscious patient.

HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase.

HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the initial oncogenic event. Here a Cancer rainbow mouse simultaneously expressing fluorescently barcoded wildtype (HER2), exon-16 null (HER2), and N-terminally truncated (HER2) HER2 isoforms is used to trace tumorigenesis from initiation to invasion.

Canadian Airway Focus Group updated consensus-based recommendations for management of the difficult airway: part 2. Planning and implementing safe management of the patient with an anticipated difficult airway.

Purpose: Since the last Canadian Airway Focus Group (CAFG) guidelines were published in 2013, the published airway management literature has expanded substantially. The CAFG therefore re-convened to examine this literature and update practice recommendations. This second of two articles addresses airway evaluation, decision-making, and safe implementation of an airway management strategy when difficulty is anticipated.

Intratumoral Plasmid IL12 Expands CD8 T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti-PD-1 Therapy.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed.