Verbal test of practical judgment (VPJ): a new test of judgment that predicts functional skills for older adults.

OBJECTIVES: The clinical assessment of older adults' judgment is important for mitigating safety risks that often precipitate loss of independence. Our national survey of geriatric healthcare providers (N = 496; M years of experience = 17.11 ± 10.60) indicated that formal judgment tests are underutilized in clinical practice. We developed the Verbal Test of Practical Judgment (VPJ) as a new test of judgment for older adults intended to identify difficulty performing instrumental activities of daily living (IADL). METHOD: In two prospective studies, participants were long-term care facility residents (age ≥ 50) in Maryland, USA (Study 1, N = 51; Study 2, N = 110) referred to licensed psychologists for neuro-cognitive and mood evaluation by facility attending physicians. Psychometric analyses were performed to examine the construct validity of the VPJ. RESULTS: The VPJ evidenced adequate reliability and strong construct validity across both studies. Receiver operating characteristic analysis yielded an optimal VPJ cut score for identifying impaired judgment. The VPJ significantly predicted IADL performance beyond clinician and participant ratings. CONCLUSION: The VPJ appears to be a valid tool for assessing judgment among older adults with suspected cognitive impairment. VPJ score inferences can inform clinicians on the odds of requiring assistance for specific IADLs.

The Columbia Behavior Scale for Dementia (CBS-8): Validity and Reliability of a Rapidly Administered New Instrument for Dementia-Related Behaviors in Long-Term Care Settings.

We developed and evaluated the psychometric properties of the Columbia Behavior Scale for Dementia (CBS-8), a rapid instrument that assesses positive symptoms, to enhance behavioral and psychological symptoms of dementia (BPSD) assessment and treatment in long-term care. Psychometric analyses were performed on CBS-8 data from residents (N = 350, age ≥50 years) in 47 Maryland long-term care facilities referred for neurocognitive and mood evaluation. The CBS-8 demonstrated acceptable internal consistency (α = 0.78) and strong interrater reliability (intraclass correlation coefficient = 1.00). CBS-8 scores were correlated with greater cognitive impairment severity (r = -0.34). The diagnosis of dementia with behavioral disturbance had higher CBS-8 scores than other dementia types (e.g., vascular, unspecified) (p < 0.001, η2 = 0.40). Three CBS-8 factors-motor disinhibition, aggression, and psychosis-explained 65% of the variance in overall BPSD. The CBS-8 could enhance BPSD tracking and treatment, strengthen interdisciplinary collaboration, and aid nursing homes in meeting regulations on unnecessary medication use. [Research in Gerontological Nursing, 14(3), 160-168.].

Regulation of neuregulin 1beta1-induced MUC5AC and MUC5B expression in human airway epithelium.

Excessive mucus production has been linked to many of the pathologic features of respiratory diseases, including obstruction of the airways, decline in lung function, increased rates of mortality, and increased infections. The mucins, MUC5AC and MUC5B, contribute to the viscoelastic properties of mucus, and are found at elevated levels in the airways of individuals with chronic respiratory diseases. The T helper type 2 cell cytokine, IL-13, is known to regulate MUC5AC expression in goblet cells of the airways, although much less is known about the regulation of MUC5B expression. In a study to further understand the mediators of MUC5AC and MUC5B expression, neuregulin (NRG) 1beta1 was identified as novel regulator of goblet cell formation in primary cultures of human bronchial epithelial cells (HBECs). NRG1beta1 increased expression of MUCAC and MUC5B proteins in a time- and dose-dependent fashion in HBEC cultures. NRG1beta1-induced expression of MU5AC and MUC5B was shown to involve v-erb-b2 erythroblastic leukemia viral oncogene homolog (ErbB) and ErbB3 receptors, but not ErbB4 receptors. Treatment of HBECs with inhibitors of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase1/2, and phosphatidylinositol 3-kinase indicated that these kinases were involved in NRG1beta1-induced MUC5AC and MUC5B expression. Additionally, NRG1beta1 was shown to induce the phosphorylation of the ErbB2 receptor, AKT, and extracellular signal-regulated kinase 1/2. NRG1beta1 protein was found increased in the airways of antigen-challenged mice, together with increases in MUC5AC and MUC5B message. Together, these data indicate that NRG1beta1 is a novel mediator of MUC5AC and MUC5B expression in HBECs, and may represent a novel therapeutic target for mucus hypersecretion in respiratory diseases.

Activin-like kinase 5 (ALK5) mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by monocrotaline.

Mutations in the gene for the transforming growth factor (TGF)-beta superfamily receptor, bone morphogenetic protein receptor II, underlie heritable forms of pulmonary arterial hypertension (PAH). Aberrant signaling via TGF-beta receptor I/activin receptor-like kinase 5 may be important for both the development and progression of PAH. We investigated the therapeutic potential of a well-characterized and potent activin receptor-like kinase 5 inhibitor, SB525334 [6-(2-tert-butyl-5-{6-methyl-pyridin-2-yl}-1H-imidazol-4-yl)-quinoxaline] for the treatment of PAH. In this study, we demonstrate that pulmonary artery smooth muscle cells from patients with familial forms of idiopathic PAH exhibit heightened sensitivity to TGF-beta1 in vitro, which can be attenuated after the administration of SB525334. We further demonstrate that SB525334 significantly reverses pulmonary arterial pressure and inhibits right ventricular hypertrophy in a rat model of PAH. Immunohistochemical studies confirmed a significant reduction in pulmonary arteriole muscularization induced by monocrotaline (used experimentally to induce PAH) after treatment of rats with SB525334. Collectively, these data are consistent with a role for the activin receptor-like kinase 5 in the progression of idiopathic PAH and imply that strategies to inhibit activin receptor-like kinase 5 signaling may have therapeutic benefit.