myHealthHub for older adult inpatients to reduce loneliness, and improve patient engagement and mental health: protocol of a pilot randomized controlled trial.

Objectives: Older Canadian adults make up 85% of hospital stays which are associated with increased loneliness, stress, anxiety, and/or depression. There is a need for novel approaches to reduce loneliness and mental health outcomes in older adult hospital inpatients to prevent further strain on an already overwhelmed healthcare system.

Methods: This is a pilot randomized controlled trial (RCT) exploring the efficacy of a bedside multimodal interaction system, myHealthHub, on loneliness, quality of life (QOL), patient engagement, and other mental health outcomes compared to an active control group in older adult inpatients ( = 60) from baseline to 5-days.

SOX4-SMARCA4 complex promotes glycolysis-dependent TNBC cell growth through transcriptional regulation of Hexokinase 2.

Tumor cells rely on increased glycolytic capacity to promote cell growth and progression. While glycolysis is known to be upregulated in the majority of triple negative (TNBC) or basal-like subtype breast cancers, the mechanism remains unclear. Here, we used integrative genomic analyses to identify a subset of basal-like tumors characterized by increased expression of the oncogenic transcription factor SOX4 and its co-factor the SWI/SNF ATPase SMARCA4.

Clinical Profile of Adult Hemophilia Patients with Special Reference to FISH and WFHPE Score: An Observational Cross-sectional Study.

Background And Objectives: Hemophilia is an X-linked recessive inherited disease affecting the coagulation pathway due to congenital deficiencies in either factor VIII (hemophilia A) or factor IX (hemophilia B). The clinical assessment of a patient's functional ability and the state of joint conditions is carried out by the clinicians by administering questionnaires namely the Gilbert or the World Federation of Hemophilia Physical Examination (WFH-PE) score for joint condition and Functional Independence Score in Hemophilia (FISH) for joint function. Here, we have studied the clinical profile of adult hemophilia patients with the short- and long-term complications of the disease.

Atypical Presentation of Primary Hyperparathyroidism as Recurrent Pancreatitis: A Case Report With a Review of the Literature.

The majority of the patients with primary hyperparathyroidism (PHPT) are asymptomatic. The most common organ systems involved in PHPT are the kidneys and the skeletal system. In rare instances, acute or chronic pancreatitis may be presenting feature in PHPT patients.

Impact of Diabetes on Inpatient Length of Stay in Adult Mental Health Services in a Community Hospital Setting: A Retrospective Cohort Study.

Objective: Our aim in this study was to characterize the relationship between comorbid mental health diagnosis and diabetes type on inpatient length of stay (LOS).

Methods: This retrospective chart review study was conducted at a community hospital in Ontario, Canada. Individuals admitted to the inpatient mental health unit with a reported diagnosis of type 1 or type 2 diabetes were included in the analysis.

CPT1A and fatty acid β-oxidation are essential for tumor cell growth and survival in hormone receptor-positive breast cancer.

Chromosome 11q13-14 amplification is a defining feature of high-risk hormone receptor-positive (HR+) breast cancer; however, the mechanism(s) by which this amplicon contributes to breast tumorigenesis remains unclear. In the current study, proteogenomic analyses of >3000 breast tumors from the TCGA, METABRIC and CPTAC studies demonstrated that carnitine palmitoyltransferase 1A (), which is localized to this amplicon, is overexpressed at the mRNA and protein level in aggressive luminal tumors, strongly associated with indicators of tumor proliferation and a predictor of poor prognosis. genetic studies demonstrated that is required for and can promote luminal breast cancer proliferation, survival, as well as colony and mammosphere formation.

Biochemical aspects of hemoglobin-xenobiotic interactions and their implications in drug discovery.

Hemoglobin, a homodimeric globular protein, is found predominantly in red blood cells and in a small amount in blood plasma. Along with binding to certain native molecules, it also interacts with various xenobiotics. The present review aims at studying these interactions and the resultant tangible impact on the structure and function of the protein if any.

Cochlear Implantation in Pierre Robin Syndrome.

Hereditary hearing loss accounts for nearly 60% of deafness in developed countries and about 30% of them are syndromic. Pierre Robin Syndrome is one such condition. The patient with this syndrome usually presnts with triad of micrognathia, glossoptosis and cleft palate.

Physicochemical and functional characterization of trastuzumab-dkst, a trastuzumab biosimilar.

Preclinical comparative similarity studies of trastuzumab-dkst, a Herceptin biosimilar, are reported. Primary sequence and higher order structure and pharmacological mechanisms of action were compared using multiple techniques. Pharmacokinetics and repeat-dose toxicity were assessed in cynomolgus monkeys.

Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia.

Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, and BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, have presented as dose-limiting adverse events that may have prevented escalation to higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain of the four BET family proteins.

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036.

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes.

SOX4 and SMARCA4 cooperatively regulate PI3k signaling through transcriptional activation of TGFBR2.

Dysregulation of PI3K/Akt signaling is a dominant feature in basal-like or triple-negative breast cancers (TNBC). However, the mechanisms regulating this pathway are largely unknown in this subset of aggressive tumors. Here we demonstrate that the transcription factor SOX4 is a key regulator of PI3K signaling in TNBC.

Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer.

The underlying molecular heterogeneity of cancer is responsible for the dynamic clinical landscape of this disease. The combination of genomic and proteomic alterations, including both inherited and acquired mutations, promotes tumor diversity and accounts for variable disease progression, therapeutic response, and clinical outcome. Recent advances in high-throughput proteogenomic profiling of tumor samples have resulted in the identification of novel oncogenic drivers, tumor suppressors, and signaling networks; biomarkers for the prediction of drug sensitivity and disease progression; and have contributed to the development of novel and more effective treatment strategies.

C2 IgM Natural Antibody Enhances Inflammation and Its Use in the Recombinant Single Chain Antibody-Fused Complement Inhibitor C2-Crry to Target Therapeutics to Joints Attenuates Arthritis in Mice.

Natural IgM antibodies (NAbs) have been shown to recognize injury-associated neoepitopes and to initiate pathogenic complement activation. The NAb termed C2 binds to a subset of phospholipids displayed on injured cells, and its role(s) in arthritis, as well as the potential therapeutic benefit of a C2 NAb-derived ScFv-containing protein fused to a complement inhibitor, complement receptor-related y (Crry), on joint inflammation are unknown. Our first objective was to functionally test mAb C2 binding to apoptotic cells from the joint and also evaluate its inflammation enhancing capacity in collagen antibody-induced arthritis (CAIA).

Evaluation of Diagnostic Accuracy of Magnetic Resonance Imaging in Posterior Ligamentum Complex Injury of Thoracolumbar Spine.

Study Design: Prospective diagnostic imaging study.

Purpose: The stability of the thoracic and lumbar spine depends significantly on the posterior ligamentum complex (PLC). Therefore, it is essential to diagnose PLC injuries accurately before deciding on a treatment plan for thoracolumbar injury patients.

The Outcome of Structured Education in Adults With Type 2 Diabetes Mellitus and Substance Use Disorder: A Literature Review.

Objective: Structured diabetes education for patients is a cornerstone of therapy; it empowers the patients by giving them appropriate tools for the self-management of the illness. The objective of this work was to determine how substance use disorder influences the outcome of structured diabetes education in patients with type 2 diabetes mellitus, and whether patients with substance use disorder are less likely to benefit because of their addiction issues.

Methods: Only clinical trials involving substance use, which were randomized, in the context of type 2 diabetes mellitus were included.

Efficacy of Depression Management in an Integrated Psychiatric-Diabetes Education Clinic for Comorbid Depression and Diabetes Mellitus Types 1 and 2.

Objectives: Patients with type 1 and type 2 diabetes mellitus (DM) are 2 times as predisposed to developing mood disorders, such as major depressive disorder (MDD), compared with patients without diabetes. Management of comorbid MDD and DM remains a challenge because patients often suffer from poor medication compliance, lifestyle factors and refractory depression. Integration of psychiatric care into diabetes education clinics (DECs) has been suggested as an effective method of managing the comorbid conditions.

Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer.

Proteins of the bromodomain and extra-terminal (BET) domain family are epigenetic readers that bind acetylated histones through their bromodomains to regulate gene transcription. Dual-bromodomain BET inhibitors (DbBi) that bind with similar affinities to the first (BD1) and second (BD2) bromodomains of BRD2, BRD3, BRD4 and BRDt have displayed modest clinical activity in monotherapy cancer trials. A reduced number of thrombocytes in the blood (thrombocytopenia) as well as symptoms of gastrointestinal toxicity are dose-limiting adverse events for some types of DbBi.

Clinico-Radiological Efficacy of Posterior Instrumentation, Decompression, and Transpedicular Bone Grafting in Osteoporotic Burst Fracture Associated with Neurological Deficit.

Objective: The aim of this study is to evaluate clinico-radiological outcomes of posterior surgery (decompression + instrumentation + transpedicular bone graft) in osteoporotic burst fracture associated with neurological deficit [OFND].

Materials And Methods: Forty patients with neurological deficit due to delayed osteoporotic vertebral collapse managed by posterior surgery (decompression + instrumentation + transpedicular bone graft) with minimum 2 years follow-up were included in the study. Approval from the Institutional Review Board was taken.

Integrative proteogenomic analyses of human tumours identifies ADNP as a novel oncogenic mediator of cell cycle progression in high-grade serous ovarian cancer with poor prognosis.

Background: Despite toxic side effects and limited durable response, the current standard-of-care treatment for high grade serous ovarian cancer (HGSOC) remains platinum/taxane-based chemotherapy. Given that the overall prognosis has not improved drastically over the past several decades, there is a critical need to understand the underlying mechanisms that lead to tumour development and progression.

Methods: We utilized an integrative proteogenomic analysis of HGSOC tumours applying a poor prognosis gene expression signature (PPS) as a conceptual framework to analyse orthogonal genomic and proteomic data from the TCGA (n = 488) and CPTAC (n = 169) studies.