Evaluation of a Home-Based, Nurse Practitioner-led Advanced Illness Care Program.

Objectives: In the United States, people with serious illness often experience gaps and discontinuity in care. Gaps are frequently exacerbated by limited mobility, need for social support, and challenges managing multiple comorbidities. The Advanced Illness Care (AIC) Program provides nurse practitioner-led, home-based care for people with serious or complex chronic illnesses that specifically targets palliative care needs and coordinates with patients' primary care and specialty health care providers.

Keeping COVID out: a collaborative approach to COVID-19 is associated with a significant reduction in self-harm in young people in custody.

Objective: To describe the collaboration between Youth Justice New South Wales (YJNSW) and Justice Health and Forensic Mental Health Network (JHFMHN) during the early COVID-19 Response (CR) across the six Youth Justice centres in NSW, and the reduced incidence of self-harm noted over this period.

Methods: Narrative article with analysis of self-harm incident data during the initial CR period of March to May 2020, compared to the same period in 2019.

Results: During the initial CR period (March to May 2020), there was a highly significant, four-fold reduction in self-harming incidents recorded by both YJNSW and JHFMHN compared with the equivalent time period in 2019 ( < .

University of Pittsburgh Medical Center Home Transitions Multidisciplinary Care Coordination Reduces Readmissions for Older Adults.

Objectives: To compare rates of 30- and 90-day hospital readmissions and observation or emergency department (ED) returns of older adults using the University of Pittsburgh Medical Center (UPMC) Health Plan Home Transitions (HT) with those of Medicare fee-for-service (FFS) controls without HT.

Design: Retrospective cohort study.

Setting: Analysis of home health and hospital records from 8 UPMC hospitals in Allegheny County, Pennsylvania, from July 1, 2015, to April 30, 2017.

Structure-based design of 2-aminopyridine oxazolidinones as potent and selective tankyrase inhibitors.

Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors.

Development of novel dual binders as potent, selective, and orally bioavailable tankyrase inhibitors.

Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have been shown to directly bind to axin proteins, which negatively regulate the Wnt pathway by promoting β-catenin degradation. Inhibition of tankyrases may offer a novel approach to the treatment of APC-mutant colorectal cancer.

Discovery of novel, induced-pocket binding oxazolidinones as potent, selective, and orally bioavailable tankyrase inhibitors.

Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates β-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of β-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties.

Discovery of a class of novel tankyrase inhibitors that bind to both the nicotinamide pocket and the induced pocket.

Potent and selective inhibitors of tankyrases have recently been characterized to bind to an induced pocket. Here we report the identification of a novel potent and selective tankyrase inhibitor that binds to both the nicotinamide pocket and the induced pocket. The crystal structure of human TNKS1 in complex with this "dual-binder" provides a molecular basis for their strong and specific interactions and suggests clues for the further development of tankyrase inhibitors.

Structure-Based Design of Potent and Selective CK1γ Inhibitors.

Aberrant activation of the Wnt pathway is believed to drive the development and growth of some cancers. The central role of CK1γ in Wnt signal transduction makes it an attractive target for the treatment of Wnt-pathway dependent cancers. We describe a structure-based approach that led to the discovery of a series of pyridyl pyrrolopyridinones as potent and selective CK1γ inhibitors.

Health perceptions and levels of attachment: owners and pets exercising together.

Background: Obesity is a parallel problem in canine and human populations. We describe health perceptions and levels of companion animal attachment in a cohort of dog owners.

Methods: As part of a larger trial examining the impact of veterinary counseling on activity levels of dog owners and their pets, owners presenting to a veterinary referral center were asked to self-report perceived levels of health and attachment to their dog (Lexington Attachment to Pets Scale).

2-Phenylamino-6-cyano-1H-benzimidazole-based isoform selective casein kinase 1 gamma (CK1γ) inhibitors.

Screening of the Amgen compound library led to the identification of 2-phenylamino-6-cyano-1H-benzimidazole 1a as a potent CK1 gamma inhibitor with excellent kinase selectivity and unprecedented CK1 isoform selectivity. Further structure-based optimization of this series resulted in the discovery of 1h which possessed good enzymatic and cellular potency, excellent CK1 isoform and kinase selectivity, and acceptable pharmacokinetic properties.

Who will be the faculty of the future? Results of a 5-year study growing educators using an immersive third postgraduate year (PGY-3) faculty development mini-fellowship.

Background: Residency education requires large numbers of skilled teaching faculty. Potential faculty can often be identified during residency training.

Aims: Employ a 4-week immersive faculty development mini-fellowship to enhance the teaching skills of selected PGY-3 residents and study outcomes over 5 years.

Blisters on the battlefield: the prevalence of and factors associated with foot friction blisters during Operation Iraqi Freedom I.

Background: Foot friction blisters in military personnel lessen a soldier's mobility, concentration, and critical decision-making skills.

Objective: To determine the prevalence of and factors associated with friction blisters during deployment in all military personnel who nonurgently presented to the 28th Combat Support Hospital.

Methods: A cross-sectional survey was performed at the 28th Combat Support Hospital.

Practice tools to meet the complex needs of older vulnerable military beneficiaries.

The elderly military beneficiary is a valued, high-risk, high-cost, and complex individual with unique medical needs. Attention to common geriatric syndromes (such as incontinence) and quality end-of-life care is critical in this population. Care of older adults is part of every adult medical and surgical specialty and represents a significant portion of the care rendered by the Military Health System (MHS)--a system that is currently oriented to warrior care and the care of young adults and families.

Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/"triple-negative" breast cancer cell lines growing in vitro.

Dasatinib is an orally active small molecule kinase inhibitor of both the src and abl proteins. To evaluate the potential role of dasatinib in breast cancer we used 39 human breast cancer cell lines that have been molecular profiled using Agilent Microarrays. They represent both luminal and basal breast cancer subtypes based on the relative gene expression of cytokeratin (CK) 8/CK18 and CK5/CK17, respectively, and those that have undergone an epithelial-to-mesenchymal transition (post-EMT) based on their expression of vimentin and the loss of CKs.

HER-2 overexpression differentially alters transforming growth factor-beta responses in luminal versus mesenchymal human breast cancer cells.

Introduction: Amplification of the HER-2 receptor tyrosine kinase has been implicated in the pathogenesis and aggressive behavior of approximately 25% of invasive human breast cancers. Clinical and experimental evidence suggest that aberrant HER-2 signaling contributes to tumor initiation and disease progression. Transforming growth factor beta (TGF-beta) is the dominant factor opposing growth stimulatory factors and early oncogene activation in many tissues, including the mammary gland.

Dying, death, and medical education: student voices.

Background: Medical schools require time for end-of-life topic. However, there is very little medical literature that directly addresses how medical students and residents are to behave, manage emotion, and confront their own grieving process when patients die.

Objective: The purpose of this study was to understand how preclinical medical students describe feelings toward the death of a hypothetical patient in order to affect curricular change at our institution.

Recent translational research: microarray expression profiling of breast cancer--beyond classification and prognostic markers?

Genomic expression profiling has greatly improved our ability to subclassify human breast cancers according to shared molecular characteristics and clinical behavior. The logical next question is whether this technology will be similarly useful for identifying the dominant signaling pathways that drive tumor initiation and progression within each breast cancer subtype. A major challenge will be to integrate data generated from the experimental manipulation of model systems with expression profiles obtained from primary tumors.

Novel consensus DNA-binding sequence for BRCA1 protein complexes.

Increasing evidence continues to emerge supporting the early hypothesis that BRCA1 might be involved in transcriptional processes. BRCA1 physically associates with more than 15 different proteins involved in transcription and is paradoxically involved in both transcriptional activation and repression. However, the underlying mechanism by which BRCA1 affects the gene expression of various genes remains speculative.

Are children of military parents more physically fit than children of civilian parents?

Background And Objectives: It is not known whether parental activity levels influence children's physical fitness. Members of the military are required to maintain standards of physical fitness, whereas the civilian population is not. We conducted this study to compare fitness levels of children in military and civilian families.

Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer.

Background: HER-2/neu, which encodes a receptor tyrosine kinase, is amplified and overexpressed in 20%-25% of human breast cancers. Such tumors are often resistant to hormone therapy. Despite a general inverse association between HER-2/neu amplification/overexpression and estrogen receptor (ER) and/or progesterone receptor (PR) expression, a fraction of patients are both HER-2/neu- and hormone receptor (HR)-positive.