Impact of balance on the energetic cost of walking and gait speed.

Background: Examine the relationship between balance test performance and the energetic cost of walking (ECW) and gait speed.

Methods: Cross-sectional and longitudinal analyses of data from the Baltimore Longitudinal Study of Aging. Men (48%) and women aged 60-96 years enrolled in the BLSA between 2007 and 2020 (n = 1132).

Perceived sleep quality predicts aggressive offending in adolescence and young adulthood.

Background: There are profound consequences when developing youth do not get adequate sleep. Adolescents who experience poor sleep may be more likely to engage in offending behavior. While there is a documented association between the number of hours youth sleep and their likelihood of offending, it is unclear how youths' perceptions of their sleep quality contribute to offending.

Use of a Novel Trigger Tool to Identify Palliative Care Needs in Surgical Patients at a National Referral Hospital in Kenya: A Pilot Study.

Addressing unmet palliative care needs in high-risk surgical patients in low- and middle-income countries must include innovative approaches to limitations in personnel and culturally acceptable assessment modalities. We assessed the utility of a novel seven-item "Step-1" trigger tool in identifying surgical patients who may benefit from palliative care. All adult patients (≥18 years) on general surgery, neurosurgery, and orthopedic surgery wards were enrolled over a four-month period.

Tracing nutrient pollution from industrialized animal production in a large coastal watershed.

One of the highest concentrations of swine and poultry concentrated animal feeding operations (CAFOs) in North America is located on the Coastal Plain of North Carolina, in which the Cape Fear River basin is located. The CAFOs produce vast amounts of manure causing loading of nutrients and other pollutants to receiving waters. With the Cape Fear River basin vulnerable to nutrient pollution, as are many other watersheds with CAFOs, δC and δN stable isotopic signatures were identified from water samples collected within the Northeast Cape Fear, Black, and lower Cape Fear River watersheds to trace nutrient sources and their distribution downstream.

DO POSITIVE PERCEPTIONS OF CORRECTIONAL STAFF MITIGATE INSTITUTIONAL VIOLENCE AMONG YOUTHFUL OFFENDERS?

Juvenile justice facilities can be dangerous places for adolescents and may promote violent behavior among incarcerated youth. With high rates of violence among detained juveniles, youth who do not feel safe may resort to violent behavior to protect themselves. However, this "cycle of violence" may be interrupted if youth can turn to correctional staff for support.

Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Clinical success of autologous CD19-directed chimeric antigen receptor T cells (CAR Ts) in acute lymphoblastic leukemia and non-Hodgkin lymphoma suggests that CAR Ts may be a promising therapy for hematological malignancies, including multiple myeloma. However, autologous CAR T therapies have limitations that may impact clinical use, including lengthy vein-to-vein time and manufacturing constraints. Allogeneic CAR T (AlloCAR T) therapies may overcome these innate limitations of autologous CAR T therapies.

Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.

4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab.

My Hypertension Education and Reaching Target (MyHEART): Development and Dissemination of a Patient-Centered Website for Young Adults with Hypertension.

Background: Young adults (18 to 39 years old) with hypertension have the lowest rates of blood pressure control (defined as blood pressure less than 140/90 mmHg) compared to other adult age groups. Approximately 1 in 15 young adults have high blood pressure, increasing their risk of future heart attack, stroke, congestive heart failure, and/or chronic kidney disease. Many young adults reported having few resources to address their needs for health education on managing cardiovascular risk.

A novel CXCR4 antagonist IgG1 antibody (PF-06747143) for the treatment of hematologic malignancies.

The chemokine receptor CXCR4 is highly expressed and associated with poor prognosis in multiple malignancies. Upon engagement by its ligand, CXCL12, CXCR4 triggers intracellular signaling pathways that control trafficking of cells to tissues where the ligand is expressed, such as the bone marrow (BM). In hematologic cancers, CXCR4-driven homing of malignant cells to the BM protective niche is a key mechanism driving disease and therapy resistance.

Modulation of P2X3 and P2X2/3 Receptors by Monoclonal Antibodies.

Purinergic homomeric P2X3 and heteromeric P2X2/3 receptors are ligand-gated cation channels activated by ATP. Both receptors are predominantly expressed in nociceptive sensory neurons, and an increase in extracellular ATP concentration under pathological conditions, such as tissue damage or visceral distension, induces channel opening, membrane depolarization, and initiation of pain signaling. Hence, these receptors are considered important therapeutic targets for pain management, and development of selective antagonists is currently progressing.

Integration of Palliative Care Into Comprehensive Cancer Treatment at Moi Teaching and Referral Hospital in Western Kenya.

Purpose: The prognosis for the majority of patients with cancer in Kenya is poor, with most patients presenting with advanced disease. In addition, many patients are unable to afford the optimal therapies required. Therefore, palliative care is an essential part of comprehensive cancer care.

Anti-IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function.

Genetic variation in the IL-7 receptor-α (IL-7R) gene is associated with susceptibility to human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism of IL-7Rα antibody in a mouse model of T1D. IL-7Rα antibody induces durable, complete remission in newly onset diabetic mice after only two to three injections.

Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pH-sensitive binding to PCSK9.

Target-mediated clearance and high antigen load can hamper the efficacy and dosage of many antibodies. We show for the first time that the mouse, cynomolgus, and human cross-reactive, antagonistic anti-proprotein convertase substilisin kexin type 9 (PCSK9) antibodies J10 and the affinity-matured and humanized J16 exhibit target-mediated clearance, resulting in dose-dependent pharmacokinetic profiles. These antibodies prevent the degradation of low density lipoprotein receptor, thus lowering serum levels of LDL-cholesterol and potently reducing serum cholesterol in mice, and selectively reduce LDL-cholesterol in cynomolgus monkeys.

A new era in clinical genetic testing for hypertrophic cardiomyopathy.

Building on seminal studies of the last 20 years, genetic testing for hypertrophic cardiomyopathy (HCM) has become a clinical reality in the form of targeted exonic sequencing of known disease-causing genes. This has been driven primarily by the decreasing cost of sequencing, but the high profile of genome-wide association studies, the launch of direct-to-consumer genetic testing, and new legislative protection have also played important roles. In the clinical management of hypertrophic cardiomyopathy, genetic testing is primarily used for family screening.

Implications of hypertrophic cardiomyopathy transmitted by sperm donation.

Context: Sperm donation is an increasingly common practice for achieving pregnancy in the absence of a male partner or when fertility is problematic. The unintended consequence in which genetic diseases are unwittingly transmitted to offspring is an underrecognized public health issue not previously prioritized by US Food and Drug Administration guidelines.

Objective: To report the clinical circumstances and implication of hypertrophic cardiomyopathy (HCM) transmitted by sperm donation to recipients.

The ACTCellerate initiative: large-scale combinatorial cloning of novel human embryonic stem cell derivatives.

Human embryonic stem cells offer a scalable and renewable source of all somatic cell types. Human embryonic progenitor (hEP) cells are partially differentiated endodermal, mesodermal and ectodermal cell types that have not undergone terminal differentiation and express an embryonic pattern of gene expression. Here, we describe a large-scale and reproducible method of isolating a diverse library of clonally purified hEP cell lines, many of which are capable of extended propagation in vitro.

Modulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia.

A phenotypic cell-based assay for inhibitors of the G (2) DNA damage checkpoint was used to screen plant extracts from the US National Cancer Institute Natural Products Repository. It revealed activity in a methanol extract from the common ragweed Ambrosia artemisiifolia. Assay-guided fractionation led to the identification of the sesquiterpene lactones psilostachyins A and C as novel checkpoint inhibitors.

New okadaic acid analogues from the marine sponge Merriamum oxeato and their effect on mitosis.

Inhibitors of the G2 DNA damage checkpoint can selectively sensitize cancer cells with impaired p53 tumor suppressor activity to killing by DNA-damaging drugs or ionizing radiation and have been proposed as a promising therapeutic strategy. An extract from the Northeastern Pacific marine sponge Merriamum oxeato showed G2 checkpoint inhibitory activity, and fractionation identified the known dinoflagellate toxin dinophysistoxin 1 (1) and the two novel analogues 27-O-acetylokadaic acid (2) and 27-O-acetyldinophysistoxin 1 (3) as the active compounds. The mixture of 1, 2, and 3 was extremely potent at inhibiting the G2 checkpoint (IC(50) = 1 ng/mL) and cellular protein Ser/Thr phosphatases (IC(50) = 1 ng/mL), and it radiosensitized MCF-7 breast cancer cells expressing mutated p53 at all concentrations tested.