Influence of age and vaccination interval on canine parvovirus, distemper virus, and adenovirus serum antibody titers.

Canine core vaccine titer screenings are becoming increasingly popular in veterinary practice as a tool to guide vaccination decisions, despite a lack of supportive, peer-reviewed evidence-based literature. Additionally, it has been suggested that the canine core vaccine duration of host protective immunity can persist past the currently recommended vaccination interval. Thus, this study evaluated serum antibody titers against three core antigens in dogs with known vaccination histories and lifestyles, analyzing the effect of life stage, exposure risk, and time since last vaccination (TSLV). Clinically healthy dogs (n = 188) presenting to the primary care services of three colleges of veterinary medicine were selected to represent a variety of ages, breeds, and vaccination history. Serum antibody titers for canine parvovirus (CPV), canine distemper virus (CDV), and canine adenovirus-2 (CAV2) were measured via virus neutralization and hemagglutination inhibition. CAV2 and CPV titers decreased, while CDV titers had a decreasing trend with increasing time since last vaccination or vaccination interval. When assessing circulating antibody levels historially associated with protective immunity across various vaccination intervals, 62% (95%CI 36-82%; 8/13) of dogs had positive titers for CDV 5 years post last vaccination, while 92% (95%CI 67-99%; 12/13) of dogs were positive for CAV2 and CPV. Both advanced age and life stage were associated with lower titers and thus, identify a canine population cohort likely at higher disease risk. The results of this study revealed that patient duration of core vaccine-mediated immunity changes with a number of variables, with animal aging and time since vaccination influencing host humoral immunity. This provides further support for the performance of canine core antibody titers to assess whether a vaccine booster and/or specific type of booster is warranted.

Cross-sectional characterization of renal function in cats with caudal stomatitis.

OBJECTIVES: The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats. METHODS: A cross-sectional, case-control study was conducted on 44 client-owned cats with CS that were prospectively enrolled and evaluated for a Comprehensive Oral Health Assessment and Treatment at one of four institutions. Renal function was assessed with measurement of serum creatinine, urea nitrogen, serum symmetric dimethylarginine, urinalysis, urine protein:creatinine ratio and urine protein electrophoresis. Affected gingiva was biopsied to confirm the diagnosis of stomatitis. Renal biochemical analyses from the experimental group were compared with those of 44 age-matched controls without CS enrolled prospectively or retrospectively after presenting to the primary institution for routine healthcare. Control cats were included if they were clinically stable, their chronic illnesses were well managed and minimal dental disease was present on examination. Renal biomarkers were compared between groups using a t-test or the Mann-Whitney U-test. Frequency of azotemia, proteinuria and the clinical diagnosis of renal disease were compared using Fisher's exact test. RESULTS: Relative to the control group, cats in the CS group had significantly lower serum creatinine (P <0.001) and albumin concentrations (P <0.001), urine specific gravity (P = 0.024) and hematocrit (P = 0.003), and higher serum phosphorus (P <0.001), potassium (P <0.001) and globulin concentrations (P <0.001), white blood cell count (P <0.001) and urine protein:creatinine ratio (P = 0.009). There were no significant differences in serum symmetric dimethylarginine or urea nitrogen concentrations. No clinically significant findings were noted on urine protein electrophoresis. There were no significant differences in the frequency of azotemia, proteinuria or renal disease categories between the two groups. CONCLUSIONS AND RELEVANCE: The present study does not demonstrate a significant difference in the frequency of kidney disease between cats with and without CS. Longitudinal evaluation is warranted to investigate the relationship between renal disease and CS.

Evaluation of renal values during treatment for heartworm disease in 27 client-owned dogs.

BACKGROUND: Canine heartworm disease (CHD) caused by Dirofilaria immitis remains a common preventable disease with increasing incidence in some parts of the USA. The treatment guidelines of the American Heartworm Society (AHS) currently recommend monthly macrocyclic lactone administration, 28 days of doxycycline given orally every 12 h and three injections of melarsomine dihydrochloride (1 injection on day 2 of treatment followed 30 days later by 2 injections 24 h apart). Minocycline has also been utilized when doxycycline is unavailable. The systemic effects of CHD, which particularly impact cardiac and renal function, have been described, with infected dogs often experiencing renal damage characterized by an increase in serum concentrations of renal biomarkers. Although the AHS treatment protocol for CHD has been shown to be safe and effective in most cases, the potential for complications remains. No study as of yet has evaluated changes in symmetric dimethylarginine (SDMA), a sensitive marker of renal function, during treatment for CHD. The purpose of the present study was to evaluate renal function in dogs by measuring serum creatinine and SDMA concentrations during the adulticide treatment period. METHODS: Serum creatinine and SDMA concentrations were measured in 27 client-owned dogs affected by CHD at the following time points: prior to starting doxycycline or minocycline therapy (baseline), during doxycycline or minocycline therapy (interim), at the time of the first dose of melarsomine (first dose), at the time of the second dose of melarsomine (second dose) and at the dog's follow-up visit after treatment, occurring between 1 and 6 months after completion of therapy (post-treatment). Concentrations of creatinine and SDMA were compared between time points using a mixed effects linear model. RESULTS: Mean SDMA concentrations following the second dose of melarsomine were significantly lower (-1.80 ug/dL, t-test, df = 99.067, t = -2.694, P-Value = 0.00829) than baseline concentrations. There were no other statistically significant differences in the concentration of either biomarker between the baseline and the other time points in CHD dogs undergoing treatment. CONCLUSIONS: The results suggest that the current AHS protocol may not have a substantial impact on renal function.

Maternal rotating night shift work before pregnancy and offspring stress markers.

BACKGROUND: Recent studies suggest an intergenerational influence of stress such that maternal exposure even before pregnancy could impact offspring health outcomes later in life. In humans, investigations on the impact of maternal stressors on offspring health outcomes, including stress-sensitive biomarkers, have largely been limited to extreme stressors. Prior studies have not addressed more moderate maternal stressors, such as rotating night shift work, on offspring stress markers in young adulthood. METHODS: We investigated the association between maternal rotating night shift work before conception and offspring salivary cortisol and alpha amylase (sAA) patterns in young adulthood among mothers enrolled in the Nurses' Health Study II (NHSII) and their offspring participating in the Growing Up Today Study 2 (GUTS2). Our sample included over 300 mother-child pairs where, between 2011 and 2014, the children provided 5 saliva samples over the course of one day. We used piecewise linear mixed models to compare awakening responses, overall slopes as well as several other diurnal patterns of cortisol and sAA between offspring born to shift working versus non-shift working mothers. RESULTS: Offspring born to shift working mothers had a flattened late decline in cortisol (percent differences in slope (%D): 2.1%; 95%CI: 0.3, 3.8) and their sAA awakening response was steeper (%D -37.4%; 95%CI: -59.0, -4.4), whereas sAA increase before bedtime appeared less pronounced (%D -35.9%; 95%CI: -55.3, -8.3), compared to offspring born to mothers without shift work. For cortisol, we observed a significant difference in the Area Under the Curve (AUC) (%D 1.5%; 95%CI: 0.3, 2.7) with higher AUC for offspring of mothers who worked rotating night shifts. In offspring-sex-stratified analyses we found differences primarily among males. CONCLUSION: Our results provide some - albeit modest - evidence that maternal rotating night shift work-a moderate stressor-influences offspring stress markers. Future studies with larger samples sizes, more detailed exposure assessment (particularly during maternal pregnancy), and multiple offspring biomarker assessments at different developmental stages are needed to further investigate these associations.

Inscription of silicon waveguides using picosecond pulses.

Direct writing of single-mode waveguides into crystalline silicon using ps laser pulses is presented. The embedded structures were fabricated by moving the focal position along the beam axis with the help of a long distance microscope objective. In situ monitoring during inscription was performed to analyze the processing dynamics. The waveguide generation is based on pronounced multi-pulse interaction at moderate pulse energies around 100 nJ. All samples were characterized in terms of mode field distribution and damping losses. Calculations indicate an induced refractive index change in the range of 10-3 to 10-2. Moreover, a Y-splitter was realized to demonstrate the potential of this process.

Friday night ventilation: a safety starting tool kit for mechanically ventilated patients.

We wish to report here a practical approach to an acute respiratory distress syndrome (ARDS) patient as devised by a group of intensivists with different expertise. The referral scenario is an intensive care unit of a Community Hospital with limited technology, where a young doctor, alone, must deal with this complicate syndrome during the night. The knowledge of pulse oximetry at room air and at 100% oxygen allows to estimate the PaO2 and the cause of hypoxemia, shunt vs. VA/Q maldistribution. The ARDS severity (mild [200

Diabetogenic glucose and insulin concentrations modulate transcriptome and protein levels involved in tumour cell migration, adhesion and proliferation.

BACKGROUND: During the last decade, epidemiological studies uncovered the tremendous impact of metabolic syndrome/diabetes mellitus type 2 (DM T2) as risk factors of the progression of cancer. Therefore, we studied the impact of diabetogenic glucose and insulin concentrations on the activities of tumour cells, because little is known about how high glucose and insulin levels are influencing gene activities causing changes in the signal cascade activities with respect to kinases involved in the proliferation and migration of cancer cells. METHODS: To address this question we analysed the activity of more than 400 gene signatures related to (i) cell cycle, (ii) cell movement as well as (iii) signal transduction. We examined transcriptomes of kinases (PKCα, PI3K), cadherins (E-, N- VE-), integrins and cyclins by comparing physiological (5.5 mM) vs diabetogenic (11 mM) glucose concentrations (without and with insulin). RESULTS: Proliferation assays revealed that high levels of glucose (11 mM) and insulin (100 ng ml(-1)) did promote the proliferation of the tumour cell lines HT29, SW480, MCF-7, MDA MB468, PC3 and T24. Using a 3D-migration assay, we have shown that high glucose concentrations caused increased motility rates of the tumour cells. The increase in migratory activity at high glucose and insulin concentrations was mediated by an activation of PI3K, PKCα and MLCK, as figured out by the pharmacological inhibitors wortmannin, Go6976 and ML-7. CONCLUSION: We present molecular and functional data, which could help to understand how hyperglycaemia and hyperinsulinemia might trigger tumour cell proliferation and motility in patients, too.

A survey of medical image registration on graphics hardware.

The rapidly increasing performance of graphics processors, improving programming support and excellent performance-price ratio make graphics processing units (GPUs) a good option for a variety of computationally intensive tasks. Within this survey, we give an overview of GPU accelerated image registration. We address both, GPU experienced readers with an interest in accelerated image registration, as well as registration experts who are interested in using GPUs. We survey programming models and interfaces and analyze different approaches to programming on the GPU. We furthermore discuss the inherent advantages and challenges of current hardware architectures, which leads to a description of the details of the important building blocks for successful implementations.

Connexin 43 expression in human hypertrophied heart due to pressure and volume overload.

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.

Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney.

The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms alpha and beta were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific.

[MRI-based diagnosis of giant cell arteritis]. / Differentialdiagnose eines un- spezifischen Beschwerdebildes: Riesenzellarteriitis (Morbus Horton).

The giant cell arteritis and its symptoms are usually non-specific and accompanied with symptoms of polymyalgia rheumatica. As complications of the giant cell arteritis ischemia, infarction or rupture of the damaged vessel can occur. We report on a 56-year-old female patient, who suffered for one year about weight loss, tiredness and intolerance as well as symptoms of polymyalgia rheumatica. Gastroscopy and colonoscopy showed normal findings. In the context of the malignancy search we made a computer tomography and magnet resonance tomography. The data showed an enlargement and an enhancement of the aorta, which led us to the suspicion of a giant cell arteritis. We started immediately with a medical treatment. The biopsy of the arteries temporales supported histological the diagnosis.

CD28-mediated costimulation impacts on the differentiation of DC vaccination-induced T cell responses.

Costimulatory signals such as the ones elicited by CD28/B7 receptor ligation are essential for efficient T cell activation but their role in anti-tumour immune responses remains controversial. In the present study we compared the efficacy of DC vaccination-induced melanoma specific T cell responses to control the development of subcutaneous tumours and pulmonary metastases in CD28-deficient mice. Lack of CD28-mediated costimulatory signals accelerated tumour development in both model systems and also the load of pulmonary metastases was strongly increased by the end of the observation period. To scrutinize whether lack of CD28 signalling influences priming, homing or effector function of Trp-2(180-188)/K(b)-reactive T cells we investigated the characteristics of circulating and tumour infiltrating T cells. No difference in the frequency of Trp-2(180-188)/K(b)-reactive CD8+ T cells could be demonstrated among the cellular infiltrate of subcutaneous tumours after DC vaccination between both genotypes. However, the number of IFN-gamma-producing Trp-2-reactive cells was substantially lower in CD28-deficient mice and also their cytotoxicity was reduced. This suggests that CD28-mediated costimulatory signals are essential for differentiation of functional tumour-specific CD8+ T-effector cells despite having no impact on the homing of primed CD8+ T cells.

Loss of nonclassical MHC molecules MIC-A/B expression during progression of uveal melanoma.

Uveal melanoma differs from cutaneous melanoma with respect to aetiology, metastatic behaviour and immune biology. The notion that loss of classical MHC class I molecules in uveal melanoma lesions is associated with an improved prognosis suggests that NK cells act as the predominant cells responsible for immune surveillance of this tumour. Consequently, immune escape mechanisms of uveal melanoma should impair the innate immunity. To this end, expression of the ligand for the NK receptor NKG2D, that is, MIC-A/B was expressed by 50% of primary tumours, but none of the metastatic lesions. MIC+ tumours were characterised by a NKG2D+ infiltrate, which was absent in MIC- lesions subsequent to chemoimmune therapy. Strikingly, MIC-A/B expression in metastatic lesions was observed subsequent to chemotherapy with fotemustine in one case. In summary, MIC/NKG2D interactions seem to be involved in the immune surveillance of primary uveal melanomas, whereas for metastatic tumours this ligand/receptor system seems not to be relevant, thus, suggesting an immune selection of MIC negative tumour cells.

Comparative analysis of ras proto-oncogene mutations in selected mammalian tumors.

Point mutations within ras proto-oncogenes are frequently detected in human malignancies and in different types of experimentally induced tumors in animals. In contrast to findings in experimental animal models of carcinogenesis, little is known about the incidence of ras mutations in naturally occurring animal tumors. In the present study, we investigated whether point mutations, particularly within the mutational hot-spot codons 12, 13, and 61, occur at comparable frequencies in human malignancies and spontaneously occurring tumors in other mammalian species. Two hundred seventy-nine of the most frequent canine and feline neoplasms were analyzed for changes in mutational hot-spot regions of the N-, Ki-, and Ha-ras genes. DNA fragments from exons 1 and 2 of all three ras genes were amplified by polymerase chain reaction, and the presence of point mutations was assessed by single-strand conformation polymorphism analysis and direct sequencing of amplified products. Only one sample, a case of canine melanoma, exhibited an Ha-ras mutation. Thus, our data strongly suggested that ras mutations at the hot-spot loci are apparently very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine and feline tumors investigated. These observations were in marked contrast to those in experimental rodent models of carcinogen-induced mammary and skin tumors that described a consistent association with Ha- or Ki-ras activation. The role of ras oncogene activation in related human malignancies therefore cannot be readily inferred from studies of experimental carcinogenesis in animal models.

Intensity modulated proton therapy: a clinical example.

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.

The sound of activism.

ABSTRACT A longtime advocate for female empowerment and equality, Boden Sandstrom has worked for political change in many arenas. In the 1960s, she began a career as a librarian, but soon made activism her full-time job, working for feminist, leftist and socialist causes. In the 1970s, she found a way to turn her lifelong passion for music into a career as a sound engineer. Once established in that profession, she began donating her services to political events, marches, demonstrations, and rallies. After thirteen years of running her own company, called Woman Sound,Inc. (later City Sound Productions,Inc.), she turned to the study of ethnomusicology. She is now Program Manager and Lecturer for the Ethnomusicology Program at the University of Maryland, where she is also working on her doctorate in that subject. She continues to freelance as a sound engineer and serve as a technical producer for major events.