Pulmonary vascular endothelial growth factor-C in development and lung injury in preterm infants

RATIONALE: In mice, vascular endothelial growth factor-C (VEGF-C) plays an important role in development of the lymphatic system and in pathogenesis of pulmonary inflammation. Its role in development of the lymphatic system in human lung and in lung injury in newborns remains unclear. OBJECTIVES: We studied the role of VEGF-C in developing human lung, and in acute and chronic lung injury in preterm infants. METHODS: Included in the immunohistochemistry study were 10 fetuses, 15 control neonates without primary lung disease, 15 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia. Tracheal aspirate fluid samples of intubated very-low-birth-weight infants during Postnatal Weeks 1-5 were analyzed with ELISA. RESULTS: Bronchiolar staining for VEGF-C was observed in all 48 samples. Alveolar epithelial staining was seen in most fetuses (8/10). In addition, staining was observed in alveolar macrophages in bronchopulmonary dysplasia (4/8), and late respiratory distress syndrome (2/7). VEGF receptor-3 (VEGFR-3) staining was observed in lymphatic endothelium adjacent to vascular endothelium. VEGF-C was expressed consistently in tracheal aspirate fluid, being highest during the first 2 postnatal days. Antenatal administration of glucocorticoids was associated with higher VEGF-C in tracheal aspirate fluid. CONCLUSIONS: The pattern of pulmonary VEGF-C and VEGFR-3 protein expression and consistent VEGF-C protein appearance in tracheal aspirate fluid in human preterm infants indicate a role for VEGF-C in the physiologic development of the lymphatic system of the lung.     

<Emphasis Type="Italic">In Vitro</Emphasis> Comparison of the Effect of Stent Configuration on Wall Shear Stress Using Time-resolved Particle Image Velocimetry

Time resolved particle image velocimetry was used to measure wall shear stress (WSS) and oscillatory shear index (OSI) within a 3.0 mm diameter compliant vessel model implanted with an Abbott Vascular XIENCE V^® stent in five configurations: baseline, over-expanded, increased vessel diameter, two overlapped stents, and increased stent length. Flow through unstented vessels was also tested for comparison. Flow conditions featured a realistic coronary pressure-flow offset and reversal at average flow rates corresponding to resting (Re = 160, f = 70 bpm) and exercise conditions (Re = 300, f = 120 bpm). Comparisons revealed that the WSS was similar for all cases behind the first strut and downstream of the device, indicating that changes in configuration have little effect downstream. However, there were notable differences within each stent revealing reduced WSS values for all cases due to the stent-imposed expansion of the vessel wall (0.20–9.29 dynes/cm² for Re = 160 and d = 3.0 mm). Over-expanding the stent with a second balloon affected the alignment of the stent geometry, and led to higher WSS at the inlet and lower values at mid-stent. The overlapped stents showed disturbed flow and a WSS deficit region downstream of the overlapped region. Analysis of the longer stent showed that the WSS within the vessel recovers with distance. An overall correlation was noted between decreased WSS values and elevated OSI. Results of this study are important because decreased WSS has been implicated in endothelial cell changes and increased restenosis, and clinical research has shown that a link exists between deployment configurations and negative patient outcomes.     

Novel HIV integrase inhibitors with anti-HIV activity: insights into integrase inhibition from docking studies

The mechanism of integrase is generally accepted to be dependant on the presence of two divalent metal ions in the active site. However, the only available crystal structures of HIV-1 integrase contain either one or no metal ions, hampering structure-based design studies of integrase inhibitors. For this reason, a two-metal ion model of integrase was constructed. This model was used for computational docking studies with novel diketoacid integrase inhibitors containing pyrimidine nucleobase scaffolds. The docking protocol allowed for some steric contact between the ligand and protein during docking simulations, which implicitly accounted for potential conformational changes in the protein as a result of binding viral DNA or the ligand. The results suggest that the aromatic rings in these diketo acids bind to regions close to the viral DNA and may interfere with mobility of a vital catalytic loop. The docking data also suggest that the ligand can be prevented from adopting a favourable conformation by changes in the relative orientation of its diketo side-chain and aromatic rings. The docked pose of each of the active compounds coordinated both of the metal ions present in the active site of integrase through the diketo acid functionality of these compounds. This result is more consistent with theoretical data on inhibitor mechanism, and thus recommends this docking approach over rigid use of one-metal ion models derived from current crystal structures of integrase.     

Knowledge of memory aging in adulthood

The Knowledge of Memory Aging Questionnaire (KMAQ) measures laypersons' knowledge of memory changes in adulthood for research or educational purposes. Half of the questions pertain to normal memory aging and the other half cover pathological memory deficits due to non-normative factors, such as adult dementia. In this study, we compared memory knowledge in middle age adults (40-59 years), young-old adults (60-79 years) and very old adults (80 years and over). These data were collected as a part of the Louisiana Healthy Aging Study, a multidisciplinary population-based study that examines the determinants of healthy aging in adulthood. Results indicated that very old adults performed more poorly overall. Follow-up analyses revealed that they endorsed stereotyped views of normal memory aging more often than did the other age groups. Analyses of response accuracy by gender yielded comparable performance for men and women. Implications for research and the design of educational programs are considered.     

Cardiac sequelae in Brooklyn after the September 11 terrorist attacks

BACKGROUND: Terrorism, such as the attacks on the World Trade Center (WTC) on September 11, 2001, result in higher stress-related disorders, especially in those persons in close proximity. HYPOTHESIS: Cardiac events resulting from the September 11, 2001 tragedy have not been detailed near the WTC. METHODS: Patients admitted to the Telemetry and Coronary Care Units at New York Methodist Hospital 4 miles from the WTC 60 days prior to and after the September 11 attacks were analyzed. In all, 1,653 admissions were reviewed: 427 records pre 9/11/2001 and 422, 393, and 411 records in the post-9/11/2001, pre-9/11/2000, and post-9/11/2000 data sets, respectively. Patients were categorized based on diagnosis: acute myocardial infarction (MI), unstable angina (UA), tachyarrhythmia (TA), and others (including syncope and congestive heart failure). RESULTS: There was a significant difference in the proportion of the various cardiac diagnoses post 9/11/01 (p = 0.008 by chi-square analysis). Compared with pre 9/11/2001, there were significantly more patients with acute MI (15.5 vs. 11.2%) and TA (19.9 vs. 13.6%) but fewer with UA (39.6 vs. 47.3%) after the terrorist attacks. The distribution of cardiac events during a similar period of time in 2000 revealed no such pattern. CONCLUSIONS: There was a significant increase in acute MI and TA and a smaller increase in UA after the September 11 attacks. The difference did not appear to be due to temporal variation. It appears that stress likely contributed to an increase in TA by itself or with ischemia, resulting in progression of UA to acute MI.     

Memory Interventions and Quality of Life for Older Adults with Dementia

ABSTRACT

In this article we focus on memory remediation activities for older adults with cognitive impairment. Memory interventions that promote retention of simple information, such as a caregiver name, may have important emotional consequences for affected individuals and their families. The inclusion of memory activities in long-term care facilities offers a new and creative direction for programming with potential benefits for clients, staff, and families. We describe recent studies that demonstrate the efficacy of the spaced retrieval technique for improving memory for simple associations in older adults with probable Alzheimer's disease (AD). We present data that address quality-of-life issues for persons who participate in a spaced retrieval memory training program. These data strongly suggest that memory remediation activities should be included as a component of current best practices for memory-impaired older adults in long-term care settings.