TGFbeta1 enhances formation of cellular Abeta/apoE deposits in vascular myocytes

Brain injury increases the risk of Alzheimer's disease (AD) through unknown mechanisms. We studied deposition of amyloid-beta protein (Abeta) in cells exposed to transforming growth factor beta1 (TGFbeta1), a cytokine that regulates cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid transporter in the brain. The studies were conducted by using brain vascular smooth muscle cells that are engaged in beta-amyloidosis in vivo and produce Abeta in cell culture. We found that cell treatment with TGFbeta1 together with apoE4 strongly increased the amount of cellular Abeta. The intracellular Abeta co-localized with apoE but not with TGFbeta, similarly as in vascular beta-amyloid. Some cellular Abeta/apoE deposits increased in size and persisted in culture even after the TGFbeta1 and apoE4 were removed. The appearance of cellular deposits of Abeta was associated with increased production of the amyloid-beta precursor protein and cellular retention of its mature form. The results suggest that the concomitant presence of apoE and TGFbeta1 can trigger vascular beta-amyloidosis by inducing intracellular formation of stable Abeta/apoE deposits.     

Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV-associated dementia

Human immunodeficiency virus type 1 (HIV-1) infection often results in disorders of the central nervous system, including HIV-associated dementia (HAD). It is suspected that tumor necrosis factor-alpha (TNFalpha) released by activated and/or infected macrophages/microglia plays a role in the process of neuronal damage seen in AIDS patients. In light of earlier studies showing that the activation of the insulin-like growth factor I receptor (IGF-IR) exerts a strong neuroprotective effect, we investigated the ability of IGF-I to protect neuronal cells from HIV-infected macrophages. Our results demonstrate that the conditioned medium from HIV-1-infected macrophages, HIV/CM, causes loss of neuronal processes in differentiated PC12 and P19 neurons and that these neurodegenerative effects are associated with the presence of TNFalpha. Furthermore, we demonstrate that IGF-I rescues differentiated neurons from both HIV/CM and TNFalpha-induced damage and that IGF-I-mediated neuroprotection is strongly enhanced by overexpression of the wt IGF-IR cDNA and attenuated by the antisense IGF-IR cDNA. Finally, IGF-I-mediated antiapoptotic pathways are continuously functional in differentiated neurons exposed to HIV/CM and are likely supported by TNFalpha-mediated phosphorylation of I(kappa)B. All together these results suggest that the balance between TNFalpha and IGF-IR signaling pathways may control the extent of neuronal injury in this HIV-related experimental setting.     

Pre‐pandemic planning survey of healthcare workers at a tertiary care children’s hospital: ethical and workforce issues

Please cite this paper as: Cowden et al. (2010). Pre‐pandemic planning survey of healthcare workers at a tertiary care children’s hospital: ethical and workforce issues. Influenza and Other Respiratory Viruses 4(4), 213–222.Background  Prior to the development of written policies and procedures for pandemic influenza, worker perceptions of ethical and workforce issues must be identified.Objective  To determine the relationship between healthcare worker (HCW) reporting willingness to work during a pandemic and perception of job importance, belief that one will be asked to work, and sense of professionalism and to assess HCW’s opinions regarding specific policy issues as well as barriers and motivators to work during a pandemic.Methods  A survey was conducted in HCWs at The Children’s Hospital in Denver, Colorado, from February to June 2007. Characteristics of workers reporting willingness to work during a pandemic were compared with those who were unwilling or unsure. Importance of barriers and motivators was compared by gender and willingness to work.Results Sixty percent of respondents reported willingness to work (overall response rate of 31%). Belief one will be asked to work (OR 4·6, P < 0·0001) and having a high level of professionalism (OR 8·6, P < 0·0001) were associated with reporting willingness to work. Hospital infrastructure support staffs were less likely to report willingness to work during a pandemic than clinical healthcare professionals (OR 0·39, P < 0·001). Concern for personal safety, concern for safety of family, family’s concern for safety, and childcare issues were all important barriers to coming to work.Conclusions  Educational programs should focus on professional responsibility and the importance of staying home when ill. Targeted programs toward hospital infrastructure support and patient and family support staff stressing the essential nature of these jobs may improve willingness to work.     

Listening for recovery: the vocational success of people living with mental illness

BACKGROUND: Mental health occupational therapists work with some individuals who want employment but who are not successful at finding or keeping a job. PURPOSE: The purpose of this qualitative study was to suggest factors contributing to vocational success. METHOD: The investigators interviewed 8 participants who were recovering from psychosis. The interview texts were coded and analyzed for emerging themes. RESULTS: Three themes emerged that describe how the participants achieved vocational success: self-assessing their mental health regularly, actively working to maintain and improve their mental health, and striving to feel connected to others at work. The results are consistent with previous studies that found that a positive fit between a worker and the workplace is linked to the worker feeling connected to and valued by the workplace. PRACTICE IMPLICATIONS: This study suggests that supporting the ways individuals assess and promote their own mental health and recovery will contribute to their success at work. Occupational therapists are urged to help people find workplaces where they feel encouraged and comfortable as this appears to be an important factor in vocational success.     

Ultrasonic backscatter and attenuation (11-27 MHz) variation with collagen fiber distribution in ex vivo human dermis

This ex vivo study explores the relationship of ultrasonic attenuation and backscatter to dermal microarchitecture by comparing ultrasonic measurements of these parameters (11-27 MHz) to a microscopic analysis of three parameters describing the collagen distribution (mean thickness and spacing of collagen bundles along the insonification direction and the percent area occupied by collagen). Skin samples (N= 31) were obtained from patients undergoing breast or abdominal reduction surgery. Radio-frequency (rf) signals were acquired in a B-scan format using an ultrasound system developed for skin imaging (Ultrasons Technologies, Tours, France). Ultrasonic data were analyzed to calculate average integrated backscatter (IBS in dB) and frequency dependence of backscatter (n, dimensionless) of each specimen at depths centered approximately 370,620 and 880 microm beneath the skin surface. Average integrated attenuation coefficient (IA in dB.cm(-1)) and frequency dependence of attenuation coefficient (beta in dB.cm(-1).MHz(-1)) were estimated across the depth between 240 and 1,000 microm. The three collagen distribution parameters were estimated using digitized microcopic fields from matched regions of histological sections stained with hematoxylin-eosin-saffron. No significant correlation was identified between collagen distribution parameters and IA or beta. For the most superficial depth studied in abdominal skin, n was inversely correlated to collagen bundle thickness (r = -0.67,p = 0.002) and percent area (r = -0.65,p = 0.003). At the same depth, IBS was inversely correlated to percent area of collagen (r = -0.51,p = 0.03). The rather high collagen packing (48 to 82% area) measured in histological sections and the inverse relationship observed between IBS and percent area of collagen suggest that a packing factor should be included in models relating skin collagen distribution to ultrasound spectral parameters. A better understanding of the relationship between ultrasound parameters and the microarchitecture of the dermis should help to interpret changes in ultrasonic parameters observed during in vivo ultrasonic skin examinations.     

B vitamin status and inflammatory markers

Limited evidence has suggested that low levels of circulating pyridoxal-5'-phosphate (PLP) may be associated with elevation of the inflammatory marker, C-reactive protein (CRP). We sought to determine whether the reported association of CRP with PLP was specific versus generalizable to other inflammation or hemostasis markers. Among 519 healthy middle aged adults in the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed the cross-sectional relation of homocysteine, plasma and dietary B vitamin levels with multiple markers implicated in inflammation, endothelial dysfunction, or thrombogenesis: CRP, fibrinogen, white blood cell count, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, factor VIII, and von Willebrand factor. There was no significant association (P>0.05) of von Willebrand factor, I-CAM, or V-CAM with any of the plasma or dietary measures examined, and no marker was associated significantly with serum homocysteine. Contrary to our hypothesis, plasma PLP was not associated with CRP concentration. A higher white blood cell count was associated with lower B vitamin status (lower plasma PLP and folate, lower dietary B6 and B12), though not with use of vitamin supplements. In ostensibly healthy adults, B-vitamin status is not a strong correlate of circulating levels of inflammatory markers, cellular adhesion molecules, or thrombogenic factors.     

Skin assessment and pressure ulcer care in hospital-based skilled nursing facilities

The Minimum Data Set, a comprehensive assessment tool for nursing home residents, is used for clinical decision-making, research, quality improvement, and Medicare and Medicaid reimbursement. Within the Minimum Data Set, pressure ulcers and skin condition are evaluated. Because information about pressure ulcer prevalence and care in hospital-based skilled nursing facilities is sparse, a study was conducted to: a) determine pressure ulcer prevalence upon admission to hospital-based skilled nursing facilities in the state of Missouri, and b) ascertain methods of assessment, treatment, and documentation of skin and pressure ulcer care in these facilities. Prevalence data were obtained from analysis of the Minimum Data Set data, and a survey was conducted to obtain skin care practices. The vast majority of residents (96%) were admitted from acute care facilities, and pressure ulcer prevalence on admission was 18.4% +/- 8.0%. Seventy-seven percent (77%) of the 88 surveys mailed were returned. The Braden or Norton Scale for risk assessment is reportedly used by 55% of facilities; whereas, 35% use a facility-developed tool. Commonly reported pressure ulcer prevention/treatment interventions used include: dietitian referral, use of barrier ointments, and a written repositioning schedule. Incontinence management and minimizing the head of bed elevation were infrequently used. Nearly one-half (47%) of facilities reported daily reassessment and documentation of wound status, suggesting less-than-optimal, time-consuming wound care practices. Despite the limitations inherent in survey designs and the use of databases such as the Minimum Data Set, the results of this study suggest that pressure ulcers are a common problem in acute care and hospital-based skilled nursing facilities and research-based risk assessment, prevention, and wound assessment strategies have not been widely implemented. The results of this study provide a basis for developing educational programs and a guide for future research.     

Age-Related Differences in the Structure of Genetic and Environmental Contributions to Types of Peer Victimization

The goal of the present investigation was to clarify and compare the structure of genetic and environmental influences on different types (e.g., physical, verbal) of peer victimization experienced by youth in pre-/early adolescence and mid-/late adolescence. Physical, verbal, social, and property-related peer victimization experiences were assessed in two twin samples (306 pairs, ages 9–14 and 294 pairs, ages 15–20). Cholesky decompositions of individual differences in victimization were conducted, and independent pathway (IP) and common pathway (CP) twin models were tested in each sample. In the younger sample, a Cholesky decomposition best described the structure of genetic and environmental contributors to peer victimization, with no evidence that common additive genetic or environmental factors influence different types of peer victimization. In the older sample, common environmental factors influenced peer victimization types via a general latent liability for peer victimization (i.e., a CP model). Whereas the pre-/early adolescent sample demonstrated no evidence of a shared genetic and environmental structure for different types of peer victimization, the mid-/late adolescent sample demonstrates the emergence of an environmentally-driven latent liability for peer victimization across peer victimization types.