West Nile Virus Infection in Sheep.

West Nile virus (WNV) infection has been detected in many species of birds and mammals, but scant information is available about the disease in small ruminants. West Nile virus was diagnosed in 6 sheep with neurological signs and encephalitis, in California between 2002 and 2014. All sheep had severe lymphoplasmacytic meningoencephalitis. Lymphoplasmacytic myelitis was also detected in 2 sheep where the spinal cord was examined. Brain tissue was positive for WNV detected by polymerase chain reaction in 6 of 6 sheep and by immunohistochemistry (IHC) in 5 of 6 sheep. Viral antigen was not detected by IHC in extraneural tissues in the 3 sheep examined. West Nile virus RNA was sequenced from 2 of 6 sheep, and each one clusters closely with WNV isolated from mosquito pools from nearby locations at similar times. West Nile virus was the most common cause of viral encephalitis in sheep diagnosed at this laboratory between 2002 and 2014, accounting for 6 of 9 sheep.

A retrospective evaluation of furosemide and mannitol for prevention of cisplatin-induced nephrotoxicity.

WHAT IS KNOWN AND OBJECTIVE: Nephrotoxicity is a recognized side effect of cisplatin chemotherapy. However, the optimal strategy for preventing cisplatin-induced nephrotoxicity, if any, remains unclear. The primary objective for this study was to determine whether mannitol or furosemide provides better nephroprotection when administered with hydration prior to weekly, low-dose cisplatin concurrently with whole pelvic radiotherapy. METHODS: Clinical data were abstracted from all women who underwent chemoradiation for FIGO IB2-IVA cervical cancer at a regional safety net health system between January 2009 and December 2014. Creatinine clearance was estimated using the IDMS-traceable MDRD Study Equation. Descriptive statistics were used to summarize patient demographics. Cox proportional hazard models were used to identify factors associated with hypomagnesemia and survival. RESULTS AND DISCUSSION: A total of 133 women received 656 weekly doses of single-agent cisplatin (40 mg/m2 ) concomitant with whole pelvic radiation. Furosemide (20 mg) was administered intravenously prior to 341 cisplatin doses, whereas mannitol (24 g) was administered prior to 315 doses. Significant magnesium wasting was observed after the second weekly cisplatin infusion regardless of whether furosemide or mannitol was utilized. Repetitive low-dose cisplatin infusion had no impact on measured levels of serum creatinine or estimated glomerular filtration rate. Prior history of hypertension, diabetes mellitus, hepatitis C infection and acute gastrointestinal toxicity were each associated with early onset of hypomagnesemia. WHAT IS NEW AND CONCLUSIONS: Repetitive administration of low-dose cisplatin concurrent with whole pelvic radiation is associated with magnesium wasting. However, choice of diuretic with pretreatment hydration had no significant impact on the severity of this adverse effect.

Is Hypertension Diagnostic Testing and Diagnosis Associated With Psychological Distress?

BACKGROUND: Psychological impacts of hypertension diagnostic testing and new hypertension diagnoses are unclear. METHODS: BP-CHECK was a randomized diagnostic study conducted in 2017-2019 in an integrated healthcare system. Participants with no hypertension diagnosis or medications and elevated blood pressure (BP) were randomized to one of three diagnostic regimens: (i) Clinic, (ii) Home, or (iii) Kiosk. Participants completed questionnaires at baseline, after completion of the diagnostic regimens, and at 6 months. Outcomes included changes from baseline in health-related quality of life (HRQOL), BP-related worry, and thoughts about having a stroke or heart attack. RESULTS: Participants (n = 482) were mostly over age 50 (77.0%), and White race (80.3%). HRQOL did not significantly change from baseline to 3 weeks or 6 months. Among all participants, BP-related worry and concerns about having a heart attack or stroke increased significantly from baseline to 3 weeks, with heart attack and stroke concerns significantly higher in the Kiosk compared Clinic and Home groups. At 6 months, thoughts about having a heart attack or stroke returned to baseline overall and in the Kiosk group, however BP-related worry was significantly higher among those with, compared to those without, a new hypertension diagnosis. CONCLUSIONS: The hypertension diagnostic process did not lead to short-term or intermediate-term changes in self-reported HRQOL. However, BP-related worry increased short-term and persisted at 6 months among individuals with a new hypertension diagnosis. Results warrant validation in more representative populations and additional exploration of the impacts of this worry on psychological well-being and hypertension control. CLINICALTRIALS.GOV IDENTIFIER: NCT03130257.

Patient experiences with blood pressure measurement methods for hypertension diagnosis: Qualitative findings from the BP-CHECK study.

BACKGROUND: Out-of-office blood pressure (BP) measurement is recommended when making a new hypertension diagnosis. In practice, however, hypertension is primarily diagnosed using clinic BP. The study objective was to understand patient attitudes about accuracy and patient-centeredness regarding hypertension diagnostic methods. METHODS: Qualitative study within a randomized controlled diagnostic study conducted between May 2017 and March 2019 comparing the accuracy and acceptability of BP measurement methods among patients in an integrated healthcare delivery system. All participants completed 24-hour ambulatory blood pressure monitoring (ABPM), plus either clinic BP, home BP monitoring (HBPM), or kiosk BP diagnostic testing. Qualitative interviewees (aged 31-76 years, n=35) were recruited from the main study. RESULTS: Participants who completed HBPM found it to be comfortable and low burden, and believed it produced accurate results. Participants in the clinic arm described clinic measurements as inconvenient. Participants in the kiosk arm overall did not favor kiosks due to concerns about accuracy and privacy. Participants described ABPM as the most accurate method due to repeated measurements over the 24-hour period in real-world contexts, but many found it uncomfortable and disruptive. Participants also noted methods that involved repeated measures such as HBPM and ABPM particularly influenced their understanding of whether or not they had hypertension. CONCLUSIONS: Hypertension diagnostic methods that include more BP measurements help patients gain a deeper understanding of BP variability and the lower reliability of infrequent measurements in clinic. These findings warrant implementing strategies to enhance out-office BP diagnostic testing in primary care.

Bovine respiratory syncytial virus and Histophilus somni interaction at the alveolar barrier.

Our previous studies showed that Histophilus somni and bovine respiratory syncytial virus (BRSV) act synergistically in vivo to cause more severe bovine respiratory disease than either agent alone causes. Since H. somni surface and secreted immunoglobulin binding protein A (IbpA) causes retraction of bovine alveolar type 2 (BAT2) cells and invasion between BAT2 cells in vitro, we investigated mechanisms of BRSV-plus-H. somni infection at the alveolar barrier. BRSV treatment of BAT2 cells prior to treatment with IbpA-rich H. somni concentrated culture supernatant (CCS) resulted in increased BAT2 cell rounding and retraction compared to those with either treatment alone. This mimicked the increased alveolar cell thickening in calves experimentally infected with BRSV followed by H. somni compared to that in calves infected with BRSV or H. somni alone. BRSV-plus-H. somni CCS treatment of BAT2 cells also enhanced paracellular migration. The effect of matrix metalloproteinases (MMPs) was investigated as well because microarray analysis revealed that treatment with BRSV plus H. somni synergistically upregulated BAT2 cell expression of mmp1 and mmp3 compared to that in cells treated with either agent alone. Enzyme-linked immunosorbent assay (ELISA) confirmed that MMP1 and MMP3 protein levels were similarly upregulated. In collagen I and collagen IV (targets for MMP1 and MMP3, respectively) substrate zymography, digestion was increased with supernatants from dually treated BAT2 cells compared with those from singly treated cells. Enhanced breakdown of collagen IV in the basal lamina and of fibrillar collagen I in the adjacent interstitium in the dual infection may facilitate dissemination of H. somni infection.

Factors associated with non-compliance with hormone therapy cessation before screening mammography.

OBJECTIVES: To evaluate factors associated with non-compliance with discontinuation of hormone therapy (HT) within a study on the effect of HT cessation on mammography performance. METHODS: This randomized, controlled trial was conducted at Group Health, a health plan in Washington State, USA. Eligibility included: age 45-80 years; due for screening ('study') mammogram; and prior screening mammogram while using HT. We randomized 1704 women to no cessation (n = 567), 1-month (n = 570), or 2-month cessation (n = 567), and called participants before cessation to review instructions. We collected self-reported data at randomization (baseline) and before the study mammogram, including symptoms and compliance. This analysis includes women randomized to 1-month or 2-month cessation with complete baseline and follow-up questionnaires (n = 883). RESULTS: Most participants were using unopposed estrogen (63.3%) and intended to continue HT (90%); 9.6% were non-compliant with HT cessation. Comparing 2-month vs. 1-month cessation, the age and body mass index (BMI)-adjusted relative risk (RR) for non-compliance was 1.72 (95% confidence interval (CI) 1.12-2.60). Baseline variables associated with non-compliance included: age ≤55 vs. >55 years (RR 2.34; 95% CI 1.34-4.41); BMI < 25 vs. BMI ≥30 kg/m 2 (RR 1.63; 95% CI 1.01-2.63); unopposed estrogen vs. estrogen plus progestin (RR 1.59; 95% CI 1.01-2.51); using HT to manage sleep (RR 1.80; 95% CI 1.20-2.71); severe vs. no night sweats (RR 1.68; 95% CI 1.03-2.74); and night sweats that interfered with sleep (RR 1.78; 95% CI 1.02-3.11). CONCLUSIONS: Non-compliance with HT cessation before screening mammogram was associated with younger age, lower BMI, symptom severity and use of unopposed estrogen. Alternatives for menopause symptom management are needed to assist women with HT cessation.

Imaging of memory-specific changes in the distribution of protein kinase C in the hippocampus.

Activation of protein kinase C (PKC) can mimic the biophysical effects of associative learning on neurons. Furthermore, classical conditioning of the rabbit nictitating membrane (a form of associative learning) produces translocation of PKC activity from the cytosolic to the membrane compartments of the CA1 region of the hippocampus. Evidence is provided here for a significant change in the amount and distribution of PKC within the CA1 cell field of the rabbit hippocampus that is specific to learning. This change is seen at 1 day after learning as focal increments of [3H]phorbol-12,13-dibutyrate binding to PKC in computer-generated images produced from coronal autoradiographs of rabbit brain. In addition, 3 days after learning, the autoradiographs suggest a redistribution of PKC within CA1 from the cell soma to the dendrites.

Impacts of climate change on snow accumulation and melting processes over mountainous regions in Northern California during the 21st century.

A point-location-based analysis of future climate change impacts on snow accumulation and melting processes was conducted over three study watersheds in Northern California during a 90-year future period by means of snow regime projections. The snow regime projections were obtained by means of a physically-based snow model with dynamically downscaled future climate projections. Then, atmospheric and snow-related variables, and their interrelations during the 21st century were investigated to reveal future climate change impacts on snow accumulation and melting processes. The analysis shows large reductions in snow water equivalent (SWE), snowfall to precipitation (S/P) ratio, and snowmelt through the 21st century. Timing of the peak of the SWE and snowmelt will also change in the future. Meanwhile, the analysis in this study shows that air temperature rise will affect, but will not dominate the future change in snowmelt over the study watersheds. This result implies the importance of considering atmospheric variables other than air temperature, such as precipitation, shortwave radiation, relative humidity, and wind speed even if these variables will not clearly change during the 21st century.

Thoracotomy for the management of recurrent vaginal leiomyosarcoma.

Vaginal leiomyosarcoma is a rare malignancy for which little data exists to guide treatment decisions. We describe a patient diagnosed with primary vaginal leiomyosarcoma who underwent hysterectomy and upper vaginectomy followed by whole pelvic radiation. Approximately 3 months after her initial treatment, she presented with an isolated pulmonary recurrence, which resolved after 12 cycles of chemotherapy. Nineteen months later, a second recurrence was found at the same site. This metastasis was resected and she has remained without evidence of further disease for more than 24 months. Similar to patients diagnosed with uterine sarcomas, resection of pulmonary metastases may offer women with recurrent vaginal leiomyosarcoma improved survival with good quality of life. Thoracotomy should be considered for women diagnosed with pulmonary recurrences of this disease.

Integrating global land-cover and soil datasets to update saturated hydraulic conductivity parameterization in hydrologic modeling.

Soil properties play an important role in watershed hydrology and environmental modeling. In order to model realistic hydrologic processes, it is necessary to obtain compatible soil data. This study introduces a new method that integrates global soil databases with land use/land cover (LULC) databases to better represent saturated hydraulic conductivity (Ks) which is one of the most important soil properties in hydrologic modeling. The Ks is modified by means of uniting physical infiltration mechanisms with hydrologic soil-LULC complexes from lookup tables from USDA-SCS (1985). This approach enables assimilation of available coarse resolution soil parameters by the finer resolution global LULC datasets. In order to test the performance of the proposed approach, it has been incorporated into the Watershed Environmental Hydrology (WEHY) model to simulate hydrologic conditions over the Cache Creek Watershed (CCW) and Shasta Dam Watershed (SDW) in Northern California by means of different soil datasets. Soil dataset S1 was obtained from the local soil database including SSURGO (Web soil survey, USDA). The second soil dataset (S2) is the global ISRIC soil data SoilGrids-1km obtained from World Soil Information. Soil dataset S4 is global FAO soil data. The third (S3) and fifth (S5) soil datasets were calculated by integrating the LULC into global soil datasets (S2, S4), respectively. The results of this study suggest that the proposed approach can provide a fine resolution soil dataset through integration of LULC and soil data, which can improve the estimation of soil hydraulic parameters and the performance of hydrologic modeling over the target watersheds. Within this framework, the new approach of this study can be applied widely in many parts of the world by means of the global soil and LULC databases.

Analysis of future climate change impacts on snow distribution over mountainous watersheds in Northern California by means of a physically-based snow distribution model.

The impacts of climate change on snow distribution through the 21st century were investigated over three mountainous watersheds in Northern California by means of a physically-based snow distribution model. The future climate conditions during a 90-year future period from water year 2010 to 2100 were obtained from 13 future climate projection realizations from two GCMs (ECHAM5 and CCSM3) based on four SRES scenarios (A1B, A1FI, A2, and B1). The 13 future climate projection realizations were dynamically downscaled at 9 km resolution by a regional climate model. Using the downscaled variables based on the 13 future climate projection realizations, snow distribution over the Feather, Yuba, and American River watersheds (FRW, YRW, and ARW) was projected by means of the physically-based snow model. FRW and YRW watersheds cover the main source areas of the California State Water Project (SWP), and ARW is one of the key watersheds in the California Central Valley Project (CVP). SWP and CVP are of great importance as they provide and regulate much of the California's water for drinking, irrigation, flood control, environmental, and hydro-power generation purposes. Ensemble average snow distribution over the study watersheds was calculated over the 13 realizations and for each scenario, revealing differences among the scenarios. While the snow reduction through the 21st century was similar between A1B and A2, the snow reduction was milder for B1, and more severe for A1FI. A significant downward trend was detected in the snowpack over nearly the entire watershed areas for all the ensemble average results.

Alternaria aerosol during a bovine respiratory syncytial virus infection alters the severity of subsequent re-infection and enhances IgE production.

BACKGROUND: Previous studies with cattle and rodent models have shown that bovine and human RSV infections influence the immune response to inhaled allergen. In the present study, we extended these observations to examine the effect of fungal allergen Alternaria alternata aerosol exposure (prior to and during BRSV infection) on the immune response and clinical outcome of a secondary BRSV infection. METHODS: Calves were either Alternaria (Alt)/mock Alt (mAlt) and BRSV/mBRSV exposed. Exposures began on day -6 and continued every other day until day 6 post infection. A second set of aerosols/infection began on day 103 and continued as before. Clinical outcome during infections was measured in each group. IgG1, IgA, and IgE responses to Alternaria were measured in serum or bronchiolar alveolar lavage fluid (BALF). Cytokine responses, including IL-4, were also measured. RESULTS: Alternaria did not influence primary infection; however, the Alt/BRSV group had less disease than mAlt/BRSV group (median clinical score 8 vs 476.5; p

Histochemical and immunohistochemical evidence of a bacterium associated with lesions of epizootic bovine abortion.

Epizootic bovine abortion (EBA), a tick-transmitted disease of pregnant cattle grazing foothill pastures, is a major cause of reproductive failure in California and adjacent states. Affected fetuses develop a chronic disease, resulting in late-term abortion or premature calving. Despite investigations spanning 50 years, to the authors' knowledge, the etiologic agent of EBA has not yet been isolated from affected fetuses or the tick vector. The diagnosis of EBA is based on gross and microscopic lesions. Recently, documentation that the etiologic agent is susceptible to antibiotics and identification of a unique 16S deltaproteobacterial rDNA gene sequence in 90% of thymus tissues from aborted fetuses have supported the role of a bacterial infection as the cause of EBA. To determine whether bacteria could be detected in the tissues, histochemical staining and immunohistochemical procedures were used on formalin-fixed, paraffin-embedded tissues. Use of a modified Steiner silver stain revealed small numbers of intracytoplasmic bacterial rods in 37 of 42 thymic samples from EBA-affected fetuses. Improved detection was achieved by use of immunohistochemical staining with serum from EBA-affected fetuses that resulted in detection of numerous bacterial rods in the cytoplasm of histiocytic cells in the thymus from all 42 EBA-affected fetuses. Immunohistochemical examination of additional tissues from 21 field and experimental EBA cases revealed positively stained intracytoplasmic bacterial rods in many organs with inflammatory lesions. Use of the modified Steiner stain and immunohistochemical staining of tissues from negative-control fetuses failed to reveal organisms. To the authors' knowledge, this is the first report to document morphologic evidence of a bacterium associated with the lesions of EBA.

Isolation of deficiencies in the Arabidopsis genome by gamma-irradiation of pollen.

Chromosomal deficiencies are a useful genetic tool in fine-scale genetic mapping and the integration of physical and visible marker genetic maps. Viable overlapping deficiencies may permit gene cloning by subtractive procedures and provide a means of analyzing the functional importance of different chromosomal regions. A method is described for isolation of deficiencies in the Arabidopsis genome which encompass specific loci and other extended chromosomal regions. The technique employs pollen mutagenized by gamma-irradiation to pollinate marker lines homozygous for recessive mutations. Deficiencies at specific loci were detected by screening for marker phenotypes in the F1. Screening for lethal mutations in the F1/F2 confirmed specific deficiencies and revealed other deficiencies that did not overlap the marker loci. Further evidence for such mutations was provided by distorted F2 segregation of the chromosomal markers linked to putative deficiencies. Maintainable (transmissible) and non-transmissible deficiencies were demonstrated by their pattern of inheritance in subsequent generations.

Survey of farmer knowledge and attitudes to endemic disease management in South Australia, with a focus on bovine viral diarrhoea (bovine pestivirus).

OBJECTIVE: We aimed to establish the attitudes of South Australian cattle farmers towards endemic animal disease prevention and control, with a particular focus on the awareness of and attitudes towards bovine viral diarrhoea (BVD). METHODS: This cross-sectional postal survey involved mailing a questionnaire to all South Australian cattle owners with 35 or more head of cattle. RESULTS: Worms and lice were the most common animal disease concerns. Less than half of responding farmers were adequately vaccinating their herds against clostridial diseases, but 53.0% stated that they utilised quarantine procedures. Less than 20% of respondents had actively taken part in BVD educational opportunities, or had vaccinated or tested their herd for BVD; less than 20% of respondents were actively involved in any systematic control of Johne's disease. Overall, farmers' actual knowledge of BVD was lower than their perceived understanding, although their interest in BVD and its control was high. CONCLUSIONS: Disease prevention measures such as vaccination, quarantine and participation in systematic control schemes were used by a minority of respondents. The results suggest that respondents acknowledge BVD as an important and relevant disease, despite many believing it was not a problem in their herd. Interest in BVD appears to be high and it is likely that an education program would be well received.

The Accuracy of an Electronic Pulmonary Embolism Severity Index Auto-Populated from the Electronic Health Record: Setting the stage for computerized clinical decision support.

BACKGROUND: The Pulmonary Embolism (PE) Severity Index identifies emergency department (ED) patients with acute PE that can be safely managed without hospitalization. However, the Index comprises 11 weighted variables, complexity that can impede its integration into contextual workflow. OBJECTIVE: We designed a computerized version of the PE Severity Index (e-Index) to automatically extract the required variables from discrete fields in the electronic health record (EHR). We tested the e-Index on the study population to determine its accuracy compared with a gold standard generated by physician abstraction of the EHR on manual chart review. METHODS: This retrospective cohort study included adults with objectively-confirmed acute PE in four community EDs from 2010-2012. Outcomes included performance characteristics of the e-Index for individual values, the number of cases requiring physician editing, and the accuracy of the e-Index risk category (low vs. higher). RESULTS: For the 593 eligible patients, there were 6,523 values automatically extracted. Fifty one of these needed physician editing, yielding an accuracy at the value-level of 99.2% (95% confidence interval [CI], 99.0%-99.4%). Sensitivity was 96.9% (95% CI, 96.0%-97.9%) and specificity was 99.8% (95% CI, 99.7%-99.9%). The 51 corrected values were distributed among 47 cases: 43 cases required the correction of one variable and four cases required the correction of two. At the risk-category level, the e-Index had an accuracy of 96.8% (95% CI, 95.0%-98.0%), under-classifying 16 higher-risk cases (2.7%) and over-classifying 3 low-risk cases (0.5%). CONCLUSION: Our automated extraction of variables from the EHR for the e-Index demonstrates substantial accuracy, requiring a minimum of physician editing. This should increase user acceptability and implementation success of a computerized clinical decision support system built around the e-Index, and may serve as a model to automate other complex risk stratification instruments.

Computer-regulated constant pressure ischemia in the rat: the animal model.

A system permitting computer control of partial ischemia in the normotensive rat brain was developed. Right carotid cannulation and bilateral subclavian artery occlusion made the input of blood to the brain dependent solely on left carotid artery flow. Perfusion pressure was controlled by partial compression of this artery with a balloon. The system can produce a range of partial ischemic states maintaining perfusion pressures from 4 to 20 mm Hg. The adequacy of the servo-control system was evaluated in greater detail at requested perfusion pressures of 7 and 12 mm Hg in 14 male Sprague-Dawley rats (300-450 g). Experimentally obtained cerebral perfusion pressures of 6.84 (SD = 0.25, n = 7) and 11.72 (SD = 0.89, n = 7) mm Hg, respectively, demonstrate the efficacy of the system. CBFs were concurrently measured at four separate bilaterally symmetric anatomic sites (cortex, hippocampus, thalamus, and substantia nigra). Significant intra- and interhemispheric differences were found to exist, with regional flows monitored ipsilaterally to the carotid balloon exceeding those of the opposite hemisphere. In summary, this acute model of cerebral ischemia permits control of perfusion pressure over the entire critical partial ischemic range.

A tissue-specific transcription enhancer element in the human immunoglobulin lambda light chain locus.

An 8.0-kb EcoRI fragment of the human immunoglobulin (Ig) lambda light chain locus carrying the Ke-Oz- and Ke-Oz+ constant region genes and flanking sequences was studied for the presence of a transcriptional enhancer. Two types of assays were used. In the first, we measured the ability of recombinant plasmids carrying the 8.0-kb Ig fragment covalently linked to the aminoglycoside phosphotransferase (aph) gene to transform mouse myeloma or mouse fibroblast cells to geneticin resistance. In the second, we used RNA spot and Northern blot hybridization analyses to determine the relative levels of aph specific RNA transiently expressed after DNA transfection. In fibroblast cells, the transformation frequencies were independent of the presence of the Ig fragment in the vector and there was no difference in the level of transient expression of the aph gene. In myeloma cells, the Ig fragment enhanced at least 10-fold both the number of transformants and the level of aph gene expression over that obtained with vector alone. These results indicate the presence of a tissue-specific transcriptional enhancer in the 8.0-kb EcoRI fragment of the human Ig C lambda locus.

Periodic alternating gaze deviation in infancy.

Periodic alternating gaze is a rarely reported phenomenon. We have observed two cases that are unique in their early onset at birth and infancy. Multiple congenital defects of the posterior cranial fossa were present on MRI in both cases. A prominent abnormality shared by both was absence of normal structures in the region of the inferior cerebellar vermis. Periodic alternating gaze appears to be associated with pathologic changes in the hindbrain in these and other reported cases.

Circadian rhythms and variability of the clinical electro-oculogram.

Clinical electro-oculograms (EOGs) were recorded from six normal subjects over 24 hr time periods for a total number of 70 EOG'S. Results indicate an inverse relationship exists between the light/dark (L/D) ratio and the dark-trough potential. No relationship was found between the light-peak potential and the L/D ratio. Both the dark-trough potential and the L/D ratio showed a circadian periodicity over working daylight hours and rather aberrant behavior in late evening and early morning hours. Circadian contributions to the L/D ratio are estimated to be between 20% and 50% of the total variability in the normal individuals studied. We suggest the optimal time for single measurements of EOG pathology should be around midday.