Equid herpesvirus 1 is neurotropic in mice, but latency from which infectious virus can be reactivated does not occur

Equid herpesvirus 1 (EHV-1) is the most common cause of virus-induced abortion in horses. After primary infection the virus becomes latent predominantly in the respiratory tract lymph nodes and the genome can also be detected in the peripheral nervous system. The role of mouse as a feasible model for the establishment of latency and reactivation of EHV-1 was investigated. Intracerebral and intranasal infections of 3- and 17-day-old mice were made and virus replication was confirmed by virus isolation and detected by indirect immunofluorescence (IIF) in brain. For reactivation studies, the mice were killed 8 weeks post infection and tissues were collected for cocultivation. In mice from both age groups, infectious virus was not detected by cocultivation. Following attempts to reactivate virus in vivo with corticosteroids, the viral antigen was detected at low levels by IIF and the expression of the gB gene by reverse transcription polymerase chain reaction (RT-PCR) in brain, trigeminal ganglia, olfactory lobe, lung and spleen. Virus was also detected by IIF following incubation of tissue explants in the growth medium containing pokeweed mitogen (PWM). These results show the limitations of the mouse model for investigating EHV-1 latency and highlights the issue of 'ineffective reactivation' of virus

Spectroscopic Studies of Anomalous Hydrodynamic Behaviour in Complex Fluids

Brillouin spectroscopy probes the thermally generated pressure fluctuations (sound waves) which propagate in a material. The resulting information on sound velocity and absorption provides a fast and efficient method of monitoring high frequency (GHz) dynamics in the system being studied. In certain cases, structural information may also be inferred from changes in the Brillouin spectrum as a function of temperature, pressure or composition (in the case of multi-component systems). The aim of the work presented in this thesis was to integrate Brillouin spectroscopy into current soft condensed matter research projects at Edinburgh, namely (i) hydration in methanol-water mixtures and (ii) the behaviour of hard-sphere colloidal dispersions. A Brillouin spectrometer based on a Fabry-Perot interferometer was developed and tested, resulting in a high-resolution instrument operating at variable scattering vector (exchanged momentum), temperature and pressure. The technical aspects of this work were carried out in collaboration with a colleague. Data analysis routines were designed and implemented, enabling calibrated Brillouin spectra to be produced automatically from raw experimental data. Excellent agreement with results on several materials studied in the literature confirmed the accuracy and sensitivity of the spectrometer. The molecular details of hydration in methanol-water mixtures are of great interest due to the prototypical amphiphilic nature of the methanol molecule. The effect of deep cooling on the Brillouin spectrum across a wide range of methanol concentrations was studied in detail, resulting in the first observation of an anomalous increase in sound velocity and maximum in sound absorption at intermediate compositions. A similar effect was then found at higher temperature in aqueous tertiary butanol, and was identified in a brief survey of several other aqueous solutions. High pressure Brillouin spectra indicate that this anomalous behaviour may also be present in pure water. It is suggested that these novel effects may be due to the presence of a relatively unperturbed water structure in the aqueous solutions studied, even at quite high solute concentration. Preliminary results from a neutron diffraction experiment performed on a 40% by mass methanol-water mixture were consistent with this hypothesis. Brillouin spectroscopy was also used to study the propagation of high frequency sound in monodisperse colloidal suspensions of sub-micron hard spheres. A second longitudinal sound mode was observed for scattering vectors of magnitude greater than pi/d where d is the diameter of the spheres. These results are the first reproduction and extension of the pioneering work in the field, which identified the additional mode with a surface acoustic excitation, propagating between adjacent spheres via an evanescent wave in the solvent. The new results show that the second mode is extinguished at a particular scattering vector - an effect not reported previously. It is suggested that this extinction is due to the minimum in the form factor for elastic scattering from a single sphere

The Burden and Management of Dyslipidemia: Practical Issues

Abstract The objective of this study is to describe briefly the burden of dyslipidemia, and to discuss and present strategies for health professionals to improve dyslipidemia management, based on a review of selected literature focusing on interventions for dyslipidemia treatment adherence. Despite the availability of effective lifestyle and pharmaceutical therapies for dyslipidemias, they continue to present a significant economic burden in the United States. Adherence to evidence-based guidelines for the treatment of dyslipidemias is unsatisfactory. The reasons for medication nonadherence are complex and specific to each patient. The lack of progress in achieving optimal lipid targets is caused by many factors: patient (medication adherence, cost of medication, literacy), medication (adverse effects, complexity of regimen), provider (lack of adherence to evidence-based practice guidelines, poor communication), and the US healthcare system (being focused on acute care rather than prevention, lack of continuity of care, general lack of use of an electronic health record). Combined interventions that target each part of the system have been effective in improving treatment adherence and achieving lipid goals. Patients, providers, pharmacists, and employers all play a role in management of dyslipidemia. No single approach will solve the complex issue of improving dyslipidemia management. The required lifestyle changes are known and effective medications are available. The challenge is for all interested parties?including nurses, nurse practitioners, doctors, pharmacists, other health care professionals, employers, and health plans?to help patients achieve behavioral changes. (Population Health Management 2012;15:302?308)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98471/1/pop%2E2011%2E0081.pd

EHV-1 gene63 is not essential for in vivo replication in horses and mice, nor does it affect reactivation in the horse: Short Communication

The aim of this study was to investigate the role of immediate early gene (gene63) in the pathogenesis of equine herpesvirus 1 (EHV-1) acute and latent infections in equine and murine models. EHV-1 gene63 mutant virus (g63mut) along with EHV-1 (Ab4) was used for intracerebral and intranasal infection of 3 and 17-day-old mice. Both viruses were recovered at the same frequency from tissues after infection. Two Welsh ponies were infected via the intranasal route with each of the viruses. Acute infection was monitored by virus isolation from nasal swabs and peripheral blood leukocytes. Six weeks post infection, peripheral blood leukocytes were taken from ponies and in vitro reactivation was positive for both viruses. At autopsy, both viruses were isolated by co-cultivation from bronchial and submandibular lymph nodes. These findings indicate that the mutation of EHV-1 gene63 does not play a role in the establishment and reactivation from latency

Asthma Disease Management: A Worksite-Based Asthma Education Program

Asthma accounts for an estimated 3 million workdays lost each year in the United States in addition to reduced worker productivity. Although asthma disease management programs are relatively common in managed care organizations, they have generally not been offered at the workplace. Seventy-six employees participated in a five-session worksite-based asthma education program. A total of 47 of 76 (61.8%) employees completed baseline and 12-month follow-up Asthma Therapy Assessment Questionnaires (ATAQ). The ATAQ includes measurement of poor asthma control, behavior/attitude barriers, knowledge barriers, patient/provider communication barriers, and efficiency. Significant improvement was noted in measures of asthma control (p < 0.05), communication (p < 0.005), knowledge (p < 0.001), and the total ATAQ Index declined from 5.53 to 4.04 (p < 0.001). Employee satisfaction results for the program were exceptionally high. A worksite-based asthma education program should reduce medical care costs, worker absenteeism, and improve worker productivity. The worksite can be a very effective location for disease education programs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63128/1/109350701300038208.pd

Worker Productivity Loss Associated with Arthritis

This study at a major financial services corporation sought to investigate the association of arthritis with on-the-job productivity, also termed "presenteeism." Using a modified version of the Work Limitations Questionnaire (WLQ) incorporated into a Health Risk Appraisal (HRA), 17,685 employees responded to the survey in 2002. Of the 16,651 respondents meeting inclusion criteria, 2,469 (14.8%) reported having arthritis, and 986 (39.9% of those with arthritis) also reported that they were under medical care and/or taking medication for arthritis. Employees with arthritis were older, predominantly female, and reported a higher number of comorbidities. Although all four domains of the WLQ (physical, time, mental, and output) were impacted by arthritis, the greatest productivity effect, as expected, was on physical work tasks. Health risks also play a role in the relationship between arthritis and presenteeism, with high-risk individuals reporting 7%–10% additional loss of productivity compared to lowrisk individuals. In addition, those who reported receiving medication and/or treatment for arthritis had a 2.5% excess productivity loss independently attributed to their arthritis, which equals approximately $1,250 per employee per year, or$5.4 million to the corporation. This arthritis effect was discernible in those with low and moderate levels of health risk, but was not as evident in those with high health risks; in that group, health-associated decrements in productivity were much larger. Arthritis is associated with work productivity loss. Disease management programs should focus on pain management and arthritis-associated health risks and comorbidities in order to significantly decrease arthritis-related losses in on-the-job productivity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63221/1/dis.2006.9.131.pd

The influence of transition metal solutes on dislocation core structure and values of Peierls stress and barrier in tungsten

Several transition metals were examined to evaluate their potential for improving the ductility of tungsten. The dislocation core structure and Peierls stress and barrier of $1/2$ screw dislocations in binary tungsten-transition metal alloys (W$_{1-x}$TM$_{x}$) were investigated using first principles electronic structure calculations. The periodic quadrupole approach was applied to model the structure of $1/2$ dislocation. Alloying with transition metals was modeled using the virtual crystal approximation and the applicability of this approach was assessed by calculating the equilibrium lattice parameter and elastic constants of the tungsten alloys. Reasonable agreement was obtained with experimental data and with results obtained from the conventional supercell approach. Increasing the concentration of a transition metal from the VIIIA group, i.e. the elements in columns headed by Fe, Co and Ni, leads to reduction of the $C^\prime$ elastic constant and increase of elastic anisotropy A=$C_{44}/C^\prime$. Alloying W with a group VIIIA transition metal changes the structure of the dislocation core from symmetric to asymmetric, similar to results obtained for W$_{1-x}$Re$_{x}$ alloys in the earlier work of Romaner {\it et al} (Phys. Rev. Lett. 104, 195503 (2010))\comments{\cite{WRECORE}}. In addition to a change in the core symmetry, the values of the Peierls stress and barrier are reduced. The latter effect could lead to increased ductility in a tungsten-based alloy\comments{\cite{WRECORE}}. Our results demonstrate that alloying with any of the transition metals from the VIIIA group should have similar effect as alloying with Re.Comment: 12 pages, 8 figures, 3 table

Body composition in older acute stroke patients after treatment with individualized, nutritional supplementation while in hospital

<p>Abstract</p> <p>Background</p> <p>Individualized, nutritional support reduced undernutrition among older stroke patients and improved quality of life in our recent randomized, controlled trial. Weight control thus seems to be important after stroke, and methods for monitoring nutritional status need to be simple and non-invasive. Here we aimed to assess if the nutritional intervention altered body composition in men and women in this study cohort, and also to examine the correlation between the methods for assessing body-, fat- and fat-free mass.</p> <p>Methods</p> <p>Acute stroke patients > 65 years at nutritional risk were randomized to either individualized, nutritional treatment with energy- and protein rich supplementation (intervention, n = 58) or routine, nutritional care (control, n = 66) while in hospital. Body composition was assessed with anthropometry and bioelectrical impedance. The follow-up period was three months.</p> <p>Results</p> <p>During the first week while in hospital, weight loss was smaller in the intervention group compared with the controls (P = 0.013). After three months weight- and fat loss were significant in both men and women. Whereas no significant differences were found in changes in body composition between the male study groups, in the women both weight loss (P = 0.022) and fat loss (P = 0.005) was smaller in the intervention group compared with the controls. A high correlation (r = 0.87) between mid upper arm circumference (MUAC) and body mass index (BMI) was found.</p> <p>Conclusions</p> <p>Individualized nutritional support to older stroke patients in hospital was beneficial for maintaining an adequate body mass and body composition the first week and seemed to have a preventive effect on fat loss among women, but not among men after three months. Measurement of MUAC may be used in the assessment of nutritional status when BMI cannot be obtained.</p> <p>Trial registration</p> <p>This trial is registered with ClinicalTrials.gov, number NCT00163007.</p

MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness

Malignant Catarrhal Fever Induced by Alcelaphine herpesvirus 1 Is Associated with Proliferation of CD8+ T Cells Supporting a Latent Infection

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2′-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection