Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities.

PURPOSE: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.

A quantitative global review of species population monitoring.

Species monitoring, defined here as the repeated, systematic collection of data to detect long-term changes in the populations of wild species, is a vital component of conservation practice and policy. We created a database of nearly 1200 schemes, ranging in start date from 1800 to 2018, to review spatial, temporal, taxonomic, and methodological patterns in global species monitoring. We identified monitoring schemes through standardized web searches, an online survey of stakeholders, in-depth national searches in a sample of countries, and a review of global biodiversity databases. We estimated the total global number of monitoring schemes operating at 3300-15,000. Since 2000, there has been a sharp increase in the number of new schemes being initiated in lower- and middle-income countries and in megadiverse countries, but a decrease in high-income countries. The total number of monitoring schemes in a country and its per capita gross domestic product were strongly, positively correlated. Schemes that were active in 2018 had been running for an average of 21 years in high-income countries, compared with 13 years in middle-income countries and 10 years in low-income countries. In high-income countries, over one-half of monitoring schemes received government funding, but this was less than one-quarter in low-income countries. Data collection was undertaken partly or wholly by volunteers in 37% of schemes, and such schemes covered significantly more sites and species than those undertaken by professionals alone. Birds were by far the most widely monitored taxonomic group, accounting for around half of all schemes, but this bias declined over time. Monitoring in most taxonomic groups remains sparse and uncoordinated, and most of the data generated are elusive and unlikely to feed into wider biodiversity conservation processes. These shortcomings could be addressed by, for example, creating an open global meta-database of biodiversity monitoring schemes and enhancing capacity for species monitoring in countries with high biodiversity. Article impact statement: Species population monitoring for conservation purposes remains strongly biased toward a few vertebrate taxa in wealthier countries.

Una Revisión Global Cuantitativa del Monitoreo Poblacional de Especies Resumen El monitoreo de especies, definido aquí como la recolección sistemática y repetida de datos para detectar cambios a largo plazo en las poblaciones de las especies silvestres, es un componente vital de la práctica y las políticas de la conservación. Generamos una base de datos de casi 1,200 esquemas, con un rango de fecha de inicio desde 1800 hasta 2018, para revisar los patrones espaciales, temporales, taxonómicos y metodológicos en el monitoreo global de especies. Identificamos los esquemas de monitoreo por medio de búsquedas estandarizadas en línea, una encuesta digital realizada a los actores, búsquedas a profundidad en una muestra de países y en una revisión global de las bases de datos sobre la biodiversidad. Estimamos el número total mundial de esquemas funcionales de monitoreo entre 3,300 y 15,000. Desde el 2000, ha habido un fuerte aumento en el número de esquemas nuevos que han iniciado en países de bajo o mediano ingreso y en países megadiversos, pero una disminución en los países de alto ingreso. El número total de esquemas de monitoreo en un país y su producto interno bruto per cápita tuvieron una correlación sólida y positiva. Los esquemas que estaban activos en 2018 lo habían estado en un promedio de 21 años en los países de alto ingreso, comparado con un promedio de 13 años en los países de mediano ingreso y de 10 años en los países de bajo ingreso. En los países de alto ingreso, más de la mitad de los esquemas de monitoreo recibieron financiamiento del gobierno, comparado con menos de un cuarto de los esquemas en los países de bajo ingreso. La recolección de datos se realizó parcial o totalmente por voluntarios en 37% de los esquemas, y dichos esquemas cubrieron significativamente más sitios y especies que aquellos realizados sólo por profesionales. Las aves fueron por mucho el grupo taxonómico más monitoreado, comprendiendo casi la mitad de todos los esquemas, pero este sesgo declinó con el tiempo. El monitoreo en la mayoría de los grupos taxonómicos todavía es disperso y descoordinado, y la mayoría de los datos generados son vagos y tienen poca probabilidad de alimentar procesos más amplios de conservación de biodiversidad. Estas deficiencias podrían abordarse, por ejemplo, creando una meta-base de datos globales abiertos de los esquemas de monitoreo de la biodiversidad y mejorando la capacidad para el monitoreo de especies en los países con alta biodiversidad.

Engineering the Structural and Electronic Phases of MoTe2 through W Substitution.

MoTe2 is an exfoliable transition metal dichalcogenide (TMD) that crystallizes in three symmetries: the semiconducting trigonal-prismatic 2H- or α-phase, the semimetallic and monoclinic 1T'- or ß-phase, and the semimetallic orthorhombic γ-structure. The 2H-phase displays a band gap of ∼1 eV making it appealing for flexible and transparent optoelectronics. The γ-phase is predicted to possess unique topological properties that might lead to topologically protected nondissipative transport channels. Recently, it was argued that it is possible to locally induce phase-transformations in TMDs, through chemical doping, local heating, or electric-field to achieve ohmic contacts or to induce useful functionalities such as electronic phase-change memory elements. The combination of semiconducting and topological elements based upon the same compound might produce a new generation of high performance, low dissipation optoelectronic elements. Here, we show that it is possible to engineer the phases of MoTe2 through W substitution by unveiling the phase-diagram of the Mo1-xWxTe2 solid solution, which displays a semiconducting to semimetallic transition as a function of x. We find that a small critical W concentration xc ∼ 8% stabilizes the γ-phase at room temperature. This suggests that crystals with x close to xc might be particularly susceptible to phase transformations induced by an external perturbation, for example, an electric field. Photoemission spectroscopy, indicates that the γ-phase possesses a Fermi surface akin to that of WTe2.

[Loss of appetite, night sweats, eczema, and axillary and inguinal lymph node swelling in a 28-year-old man]. / Inappetenz, Nachtschweiß, chronisches Ekzem und inguinale sowie axilläre Lymphknotenpakete bei einem 28-jährigen Patienten.

A 28-year-old man presented with loss of appetite, night sweats, eczema, and axillary and inguinal lymph node swelling. The tentative diagnosis of malignant lymphoma was made. To confirm the diagnosis, extirpation of a lymph node and a skin biopsy were performed. Systemic treatment with methylprednisolone resulted in an improvement of eczema and lymph node swelling. Because of the histological findings and clinical course, we diagnosed dermatopathic lymphadenopathy, also known as Pautrier-Woringer syndrome.

The androgen receptor CAG repeat polymorphism as a risk factor of low serum testosterone and its cardiometabolic effects in men.

Previous studies reported correlations of CAG repeat length with sex hormone serum concentrations and cardiometabolic risk factors, but were limited by small cross-sectional samples. We used data of 1859 men aged 20-79 years from the population-based Study of Health in Pomerania (SHIP) to investigate the direct and modulating effects of CAG repeat length on androgen action and cardiometabolic risk factors. We performed cross-sectional and longitudinal linear and Poisson regression models adjusted for age, smoking, physical activity, alcohol consumption and body mass index. The CAG repeat length was categorized into quartiles and low total testosterone (TT) defined according to the age-specific (by decades) 10th percentile, respectively. Age-adjusted cross-sectional linear regression models showed a positive association between CAG repeat length and serum testosterone concentrations [ß coefficient for TT, 0.099 (p = 0.028) and for free T, 0.002 (p = 0.001), respectively]. After a 5.0 year median follow-up period, men with CAG repeat length in the lowest quartile had an increased risk of incident low TT concentrations [relative risk (RR), 2.31; 95% confidence interval (CI), 1.18-4.55]. We found no direct association between CAG repeat length and cardiometabolic risk factors in cross-sectional and longitudinal multivariable linear regression analyses; whereas men with longer CAG repeat length and low TT concentrations showed the highest risk of incident MetS (RR, 1.51; 95% CI, 1.05-2.16). CAG repeat length is a risk factor of incident low TT concentrations and a contributing factor of testosterone-related cardiometabolic effects. The added clinical value of a combined assessment of CAG repeat length and serum TT concentrations merits further investigation.

Leaching of pharmaceuticals and personal care products in turfgrass soils during recycled water irrigation.

An important beneficial reuse of treated wastewater (recycled water) in arid and semiarid regions is landscape irrigation. However, the environmental fate, especially groundwater contamination potential, of trace contaminants such as pharmaceuticals and personal care products (PPCPs) is a significant concern that can hinder the acceptance and adoption of such reuses. In this study, we irrigated mature turfgrass plots with nonspiked tertiary treated wastewater for over 6 mo at 100 or 130% of the reference evapotranspiration rate (ETo) and collected leachate water at the 90-cm depth on a weekly basis. In the recycled water, all 14 target PPCPs were consistently found, and the mean levels of atenolol, gemfibrozil, meprobamate, carbamazepine, and sulfamethoxazole were above 100 ng L. However, only five compounds were detected in the leachate at trace levels. Trimethoprim and primidone were frequently found, whereas the detection of sulfamethoxazole, meprobamate and carbamazepine was less frequent (<50%). When detected, the overall mean concentration in the leachate was 10.2 ng L for trimethoprim, 7.1 ng L for primidone, and 2.9 to 12.4 ng L for carbamazepine, sulfamethoxazole, and meprobamate. The majority of the target PPCPs were completely removed. Given that the irrigation rates were higher than normal, this study clearly demonstrated the efficacy of turfgrass systems in attenuating PPCPs during recycled water irrigation. However, it is also apparent that some PPCPs are more susceptible to leaching than others, and these PPCPs thus merit further research attention.

[Geriatric multimorbidity in claims data - part 2 : diagnoses of hospitals and diagnoses from physicians in the ambulatory setting]. / Geriatrietypische Multimorbidität im Spiegel von Routinedaten - Teil 2 : Ambulante und stationäre Diagnosen bei geriatrisch versorgten und pflegebedürftigen Versicherten.

BACKGROUND: Due to demographics, characteristic multimorbidity in geriatric patients is resulting in increased social, medical, and healthcare challenges. Geriatric multimorbidity (GM) can be defined as the simultaneous occurrence of at least two diseases that require medical care with an interdisciplinary focus on independence in activities of daily living. Typical conditions of GM are, e.g., incontinence, cognitive impairment, frailty, and decubitus. MATERIAL AND METHODS: Part 2 of this study is based on claims data of 240,502 AOK insurants (AOK is one of the major health insurance companies of the German statutory health insurance system) aged ≥ 60 years with at least one admission to a hospital with a geriatric ward. Geriatric conditions (GCs) were ascertained in two ways: diagnoses from physicians in the ambulant care setting and diagnoses in a hospital setting in 2008. A total of 15 GC were assessed using diagnoses based on ICD-10 codes (as per suggestion from scientific geriatric societies). An insurant was defined as a person with GM, if he/she had at least two GCs. RESULTS: The proportion of GCs in ambulant or inpatient diagnoses of 240,502 insurants varied significantly in most cases. For specific GCs, considerably higher proportions of ambulant diagnoses (e.g., pain, impairment of vision, or hearing) or for inpatient diagnoses (e.g., electrolyte or fluid metabolism disorders, malnutrition, incontinence) were identified. Only on rare occasions were small differences observed comparing the proportions of specific GCs in the diagnoses of the two different care sectors. This finding reduces considerably the accordance between the two care sectors with reference to the presence or absence of a GC for ambulant or inpatient diagnoses. The main agreement was with the non-coding of specific GCs, not with ambulant or inpatient diagnoses. Insurants with a geriatric hospital admission or certain care level (level ≥ 1) generally had higher proportions for specific GCs for inpatient and ambulant diagnoses than non-geriatric treated insurants or insurants without a certain care level. Of the geriatric treated insurants and those with certain care levels, 90% were characterized by the presence of GM for both ambulant or inpatient diagnoses. This percentage is remarkably higher than for patients who featured no geriatric treatment or had no certain care level. CONCLUSION: The inclusion of ambulant diagnoses in addition to inpatient diagnosis offers comprehensive possibilities to identify insurants with GM in claims data. The contribution of the diagnoses of both care sectors for the identification of GC and GM varies with regard to attribute and insurant orientation. Furthermore, significant attribute-oriented overlap of insurants claiming geriatric treatments and insurants with certain care levels became visible, which can open new possibilities for simpler identification of a portion of patients with GM.

Development of an ultrasound-capable phantom with patient-specific 3D-printed vascular anatomy to simulate peripheral endovascular interventions.

PURPOSE: Today, ultrasound-guided peripheral endovascular interventions have the potential to be an alternative to conventional interventions that are still X-ray and contrast agent based. For the further development of this approach, a research environment is needed that represents the individual patient-specific endovascular properties as realistically as possible. Aim of the project was the construction of a phantom that combines ultrasound capabilities and the possibility to simulate peripheral endovascular interventions. MATERIAL AND METHODS: We designed a modular ultrasound-capable phantom with exchangeable patient specific vascular anatomy. For the manufacturing of the vascular pathologies, we used 3D printing technology. Subsequently, we evaluated the constructed simulator with regards to its application for endovascular development projects. RESULTS: We developed an ultrasound-capable phantom with an exchangeable 3D-printed segment of the femoral artery. This modality allows the study of several patient-specific 3D-printed pathologies. Compared to the flow properties of a human artery (male; age 28) the phantom shows realistic flow properties in the duplex ultrasound image. We proved the feasibility of the simulator by performing an ultrasound-guided endovascular procedure. Overall, the simulator showed realistic intervention conditions. CONCLUSIONS: With the help of the constructed simulator, new endovascular procedures and navigation systems, such as ultrasound-guided peripheral vascular interventions, can be further developed. Additionally, in our opinion, the use of such simulators can also reduce the need for animal experiments.

[Validation of the Temporal Experience of Pleasure Scale (TEPS) in a French-speaking environment]. / Validation française de l'échelle d'expérience temporelle du plaisir.

INTRODUCTION: Anhedonia is defined as a diminished capacity to experience pleasant emotion and is commonly included among the negative symptoms of schizophrenia. However, if patients report experiencing a lower level of pleasure than controls, they report experiencing as much pleasure as controls with online measurements of emotion. OBJECTIVE: The Temporal Experience of Pleasure Scale (TEPS) measures pleasure experienced in the moment and in anticipation of future activities. The TEPS is an 18-item self-report measurement of anticipatory (10 items) and consummatory (eight items) pleasure. The goal of this paper is to assess the psychometric characteristics of the French translation of this scale. METHODS: A control sample was composed of 60 women and 22 men, with a mean age of 38.1 years (S.D.: 10.8). Thirty-six were without qualification and 46 with qualified professional diploma. A sample of 21 patients meeting DSM IV-TR criteria for schizophrenia was recruited among the community psychiatry service of the department of psychiatry in Lausanne. They were five women and 16 men; mean age was of 34.1 years (S.D.: 7.5). Ten obtained a professional qualification and 11 were without qualification. None worked in competitive employment. Their mean dose of chlorpromazine equivalent was 431 mg (S.D.: 259). All patients were on atypical antipsychotics. The control sample fulfilled the TEPS and the Physical Anhedonia Scale (PAS). The patient sample fulfilled the TEPS and was independently rated on the Calgary Depression Scale and the Scale for Assessment of Negative Symptoms. For comparison with controls, patients were matched on age, sex and professional qualification. This required the supplementary recruitment of two control subjects. RESULTS: Results with the control sample indicate that the TEPS presents an acceptable internal validity with Crombach alphas of 0.84 for the total scale, 0.74 for the anticipatory pleasure scale and 0.79 for the consummatory pleasure scale. The confirmatory factor analysis indicated that the model is well adapted to our data (chi(2)/dl=1.333; df=134; p<0.0006; root mean square residual, RMSEA=0.064). External validity measured with the PAS showed R=-0.27 (p<0.05) for the consummatory scale and R=-0.26 for the total score. Comparisons between patients and matched controls indicated that patients were significantly lower than control on anticipatory pleasure (t=2.7, df(40), 2-tailed p=0.01; cohen's d=0.83) and on total score of the TEPS (t=2.8, df (40), 2-tailed p=0.01; cohen's d=0.87). The two samples did not differ on consummatory pleasure. The anticipatory pleasure factor and the total TEPS showed significant negative correlation with the SANS anhedonia, respectively R=-0.78 (p<0.01) for the anticipatory factor and R=-0.61 (p<0.01) for the total TEPS. There was also a negative correlation between the anticipatory factor and the SANS avolition of R=-0.50 (p<0.05). These correlations were maintained, with partial correlations controlling for depression and chlorpromazine equivalents. CONCLUSION: The results of this validation show that the French version of the TEPS has psychometric characteristics similar to the original version. These results highlight the discrepancy between results of direct or indirect report of experienced pleasure in patients with schizophrenia. Patients may have difficulties in anticipating the pleasure of future enjoyable activities, but not in experiencing pleasure once in an enjoyable activity. Medication and depression do not seems to modify our results, but this should be better controlled in a longitudinal study. The anticipatory versus consummatory pleasure distinction appears to be useful for the development of new psychosocial interventions, tailored to improve desire in patients suffering from schizophrenia. Major limitations of the study are the small size of patient sample and the under representation of men in the control sample.

Assessment of treatment patterns associated with injectable disease-modifying therapy among relapsing-remitting multiple sclerosis patients.

BACKGROUND: Availability of oral disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS) may affect injectable DMT (iDMT) treatment patterns. OBJECTIVE: The objective of this paper is to evaluate iDMT persistency, reasons for persistency lapses, and outcomes among newly diagnosed RRMS patients. METHODS: Medical records of 300 RRMS patients initiated on iDMT between 2008 and 2013 were abstracted from 18 US-based neurology clinics. Eligible patients had ≥3 visits: pre-iDMT initiation, iDMT initiation (index), and ≥1 visit within 24 months post-index. MS-related symptoms, relapses, iDMT treatment patterns (i.e. persistency, discontinuation, switching, and restart), and reasons for non-persistency were tracked for 24 months. RESULTS: At 24 months, iDMT persistency was 61.0%; 28.0% of patients switched to another DMT, 8.0% discontinued, and 3.0% stopped and restarted the same iDMT. The most commonly identified reasons for non-persistency were perceived lack of efficacy (22.2%), adverse events (18.8%), and fear of needles/self-injecting (9.4%). At 24 months, 38.0% of patients had experienced a relapse and 11.0% had changes in MRI lesion counts. Patients without MS-related symptoms at index reported increases in the incidence of these symptoms at 24 months. CONCLUSIONS: Non-persistency with iDMT remains an issue in the oral DMT age. Many patients still experienced relapses and disease progression, and should consider switching to more effective therapies.

Leaching of N-nitrosodimethylamine (NDMA) in turfgrass soils during wastewater irrigation.

N-nitrosodimethylamine (NDMA) is a carcinogenic by-product of chlorination that is frequently found in municipal wastewater effluent. NDMA is miscible in water and negligibly adsorbed to soil, and therefore may pose a threat to ground water when treated wastewater is used for landscape irrigation. A field study was performed in the summer months under arid Southern California weather conditions to evaluate the leaching potential of NDMA in turfgrass soils during wastewater irrigation. Wastewater was used to irrigate multiple turfgrass plots at 110 to 160% evapotranspiration rate for about 4 mo, and leachate was continuously collected and analyzed for NDMA. The treated wastewater contained relatively high levels of NDMA (114-1820 ng L(-1); mean 930 ng L(-1)). NDMA was detected infrequently in the leachate regardless of the soil type or irrigation schedule. At a method detection limit of 2 ng L(-1), NDMA was only detected in 9 out of 400 leachate samples and when it was detected, the NDMA concentration was less than 5 ng L(-1). NDMA was relatively persistent in the turfgrass soils during laboratory incubation, indicating that mechanisms other than biotransformation, likely volatilization and/or plant uptake, contributed to the rapid dissipation. Under conditions typical of turfgrass irrigation with wastewater effluent it is unlikely that NDMA will contaminate ground water.

Loss pathways of N-nitrosodimethylamine (NDMA) in turfgrass soils.

N-nitrosodimethylamine (NDMA) is a potent carcinogen that is often present in municipal wastewater effluents. In a previous field study, it was observed that NDMA did not leach through turfgrass soils following 4 mo of intensive irrigation with NDMA-containing wastewater effluent. To better understand the loss pathways for NDMA in landscape irrigation systems, a mass balance approach was employed using in situ lysimeters treated with 14C-NDMA. When the lysimeters were subjected to irrigation and field conditions after NDMA application, very rapid dissipation of NDMA was observed for both types of soil used in the field plots. After only 4 h, total 14C activity in the lysimeters decreased to 19.1 to 26.1% of the applied amount, and less than 1% of the activity was detected below the 20-cm depth. Analysis of plant materials showed that less than 3% of the applied 14C was incorporated into the plants, suggesting only a minor role for plant uptake in removing NDMA from the vegetated soils. The rapid dissipation and limited downward movement of NDMA in the in situ lysimeters was consistent with the negligible leaching observed in the field study, and suggests volatilization as the only significant loss pathway. This conclusion was further corroborated by rapid NDMA volatilization found from water or a thin layer of soil under laboratory conditions. In a laboratory incubation experiment, prolonged wastewater irrigation did not result in enhanced NDMA degradation in the soil. Therefore, although NDMA may be present at relatively high levels in treated wastewater, gaseous diffusion and volatilization in unsaturated soils may effectively impede significant leaching of NDMA, minimizing the potential for ground water contamination from irrigation with treated wastewater.

Prediction of individual prosthesis size for valve-sparing aortic root reconstruction based on geometric features.

Valve-sparing aortic root reconstruction is an up- and-coming approach for patients suffering from aortic valve insufficiencies which promises to significantly reduce complications. However, the success of the treatment strongly depends on the challenging task of choosing the correct size of the prosthesis, for which, up to now, surgeons solely have to rely on their experience. Here, we present a novel machine learning based approach, which might make it possible to predict the size of the prosthesis from pre-operatively acquired ultrasound images. We utilize support vector regression to train a prediction model on three geometric features extracted from the ultrasound data. In order to evaluate the accuracy and robustness of our approach we created a large data base of porcine aortic root geometries in a healthy state and an artificially dilated state. Our results indicate that prediction of correct prosthesis sizes is feasible. Furthermore, they suggest that it is crucial that the training data set faithfully represents the diversity of aortic root geometries.

Application of the ASVCP guidelines for the establishment of haematologic and biochemical reference intervals in Icelandic horses in Austria.

BACKGROUND: Despite the increasing popularity of Icelandic horses, published reference intervals (RIs) in this breed are rare. Due to their isolation and their small gene pool, alterations in some variables are likely and some possible breed-specific peculiarities have been described. The purpose of the present study was the establishment of comprehensive RIs in Icelandic horses according to recently published guidelines. In a prospective observational study, blood samples were collected from the jugular vein of 142 Icelandic horses into EDTA and serum tubes. Reference intervals were established for haematologic and biochemical analytes on the Advia 2120i™ and the Dimension ExL™ by established methods. RIs were defined as central 95 % intervals bounded by the 2.5th and 97.5th percentiles with their 90 % confidence intervals, calculated according to recently published ASVCP guidelines. An inhouse-developed quality control system using observed total allowable error was used for the surveillance of the internal quality control preceding the measurements. RESULTS: The RIs were as follows: haematocrit: 0.29-0.39, RBC: 5.79-8.63 T/l, haemoglobin: 102.0-142.3 g/l, MCV: 42-51 fl, platelets: 146-263 G/l, WBC: 4.13-8.57 G/l, segs: 1.98-4.73 G/l, lymphocytes: 1.25-3.49 G/l, monocytes: 0.06-0.31 G/l, eosinophils: 0.04-0.50 G/l, glucose: 4.0-5.7 mmol/l, urea: 3.2-6.4 mmol/l, creatinine: 79.6-141.4 µmol/l, total protein: 54.4-72.9 g/l, albumin: 27.7-36.8 g/l, total bilirubin: 8.1-21.1 µmol/l, triglycerides: 0.03-0.44 mmol/l, cholesterol: 1.75-2.90 mmol/l, ALP: 1.35-3.55 µkat/l, AST: 4.52-8.80 µkat/l, GLDH: 0.0-0.18 µkat/l, GGT: 0.11-0.39 µkat/l, CK: 2.53-6.52 µkat/l, LDH: 3.32-7.95 µkat/l, iron: 16.4-39.9 µmol/l, calcium: 2.69-3.19 mmol/l, phosphate: 0.5-1.3 mmol/l, magnesium: 0.6-0.9 mmol/l, sodium: 134-141 mmol/l, potassium: 3.6-4.7 mmol/l, chloride: 100-105 mmol/l. CONCLUSIONS: Reference intervals of several haematologic and biochemical analytes differed from the transferred historical reference intervals applied to equine samples in the authors' laboratory. These might be of clinical importance in some analytes such as creatine kinase.

Determination of the nucleotide sequence flanking the deletion (0.762 to 0.789 map units) in the genome of an intraperitoneally avirulent HSV-1 strain HFEM.

Herpes simplex virus type 1 (HSV-1) strain HFEM which harbours a deletion of 4.1 kbp in its genome (0.762 to 0.789 map units, HpaI DNA fragment P of HSV-1), is apathogenic for mice and tree shrews by the intraperitoneal application route. The exact position of this deletion was determined by DNA sequence analysis. This analysis was performed using the recombinant plasmid pU18HSHF-XmI-B which harbours the flanking genome regions (0.752 to 0.762 and 0.789 to 0.7895 map units) of the deletion in the genome of HSV-1 HFEM, and the recombinant plasmids pU18HSF-XmI-B, pU18HSF-AS, and pHSF-BB-BsH-D, harbouring particular regions of the genome of the virulent HSV-1 strain F at the coordinates 0.752 to 0.761, 0.786 to 0.790, and 0.762 to 0.771, respectively. The comparison of the DNA sequence of this region with the DNA sequences of the corresponding genome regions of the pathogenic HSV-1 strain F and HSV-1 strain 17 showed that the 5' end of the deletion in the genome of HSV-1 HFEM starts at the nucleotide position 3774 of the BamHI DNA fragment B from HSV-1/17. This position is 71 bp upstream of the UL/RL junction of the HSV-1 genome. The 3' terminus of the deletion ends at the nucleotide position 7226 of the BamHI DNA fragment B from HSV-1/17. The position is within the incomplete ninth repetitive box (ACTCC-CACGCACCCCC) and is located 36 bp upstream of the 3' end of the IE 110 mRNA.

Replacement of the deletion in the genome (0.762-0.789 mu) of avirulent HSV-1 HFEM using cloned MluI DNA fragment (0.7615-0.796 mu) of virulent HSV-1 F leads to generation of virulent intratypic recombinant.

The HFEM strain of HSV-1 is apathogenic for the tree shrew by the intraperitoneal (i.p.) route because of a deletion in the genome coordinates 0.762-0.789. Insertion of the MluI DNA fragment (coordinates 0.7615-0.789) cloned from HSV-1 strain F, which is pathogenic for the tree shrew, restored the i.p. pathogenicity to strain HFEM. The recombinant designated R-M1-C1 was highly pathogenic for the tree shrew, but slightly virulent for inbred mouse strain A. It thus appears that the viral DNA sequence involved in the i.p. pathogenicity of HSV-1 is located within the genome coordinates 0.761-0.796. This sequence is recognized differently by the cellular elements involved in HSV-1 infection in the tree shrew and the mouse.

Calcium attenuates cardiovascular reactivity to sodium and stress in blacks.

The roles of dietary and behavioral factors in the etiology of hypertension are not well understood. Vulnerability to hypertension is thought to be affected by a complex interaction of nutritional, genetic, neurophysiological, and psychosocial influences. We studied cardiovascular reactivity to sodium and stress in a group of 29 normotensive young men who were vulnerable to hypertension by virtue of familial and/or racial factors. Subjects with positive and negative parental histories of hypertension were provided all meals for five days during which blood pressure was monitored before each meal. Two groups were given 300 mEq/day dietary sodium with either 1100 mg/day or 410 mg/day dietary calcium. A third group consumed a 10mEq sodium diet with low dietary calcium. On the fifth day of the diet all subjects were tested for cardiovascular reactivity using a modified Stroop test as a mentally challenging task. Adaptation of systolic blood pressure (SBP) from the first to the fifth breakfast was most pronounced in subjects consuming high calcium with high sodium. Perseveration of SBP reactivity to repeated mental challenge was found in subjects who consumed high sodium with low calcium and in subjects with positive parental histories of hypertension. The perseverative phenomenon was particularly well-defined in subjects who had the highest urinary excretion of calcium. Our findings suggest a prophylactic influence of dietary calcium and its retention on cardiovascular reactivity to sodium and stress. We also elucidate a theoretical proposition concerning the role of neurophysiological inhibitory capacity in the transition from normotension to the chronic dysregulatory state of essential hypertension.

Differential expression of CD95, Bcl-2, and Bax in rat gastric chief and parietal cells.

Apoptotic cell death is common in the inflamed gastric mucosa, but its role in the regulation of cell homeostasis in normal gastric mucosa is unknown. We investigated the expression of CD95, Bcl-2, and Bax and their roles in the regulation of apoptosis in normal rat gastric mucosa and in cultures of highly enriched rat chief and parietal cells by immunostaining, Western blotting, and FACS. In intact tissue CD95, Bcl-2, and Bax were localized predominantly in the glandular base region in chief cells. In freshly isolated cells, expression of CD95, Bcl-2, and Bax was much more pronounced in chief cells than in parietal cells. A lower intracellular Bcl-2/Bax ratio suggesting a higher susceptibility to apoptosis was noticed in chief rather than in parietal cells. In extended cultures of parietal and chief cells, Bax expression was upregulated and Bcl-2 expression was downregulated. These regulatory changes, presumably caused by in vitro effects, were not associated with an increase in spontaneous apoptosis. Treatment of chief and parietal cells with Fas-ligand induced apoptosis of all CD95 expressing cells. Expression of CD95, Bcl-2, and Bax predominantly in chief cells suggests that in this cell type regulation of apoptosis may differ from that in parietal cells. Binding of FasL with functionally active CD95 receptors on chief and parietal cells may be relevant for induction of apoptosis in inflamed gastric mucosa.

Pleiotropic effects of hepatocyte growth factor in proximal tubule involve different signaling pathways.

Hepatocyte growth factor (HGF) accelerates renal tubule cell regeneration and induces tubulogenic differentiation via the intracellular tyrosine kinase (TK) domain of its receptor, the proto-oncogene c-Met. We tested whether different signaling pathways may be involved by examining HGF binding and effects on cell proliferation, migration, scattering, and tubulogenic differentiation in the bipolar differentiating rabbit proximal tubule cell line PT-1 under serum-free conditions in the presence or absence of the protein TK inhibitors (PTKIs) herbimycin-A, genistein, methyl-2,5-dihydroxycinnamate, and geldanamycin. These PTKIs inhibit pp60(c-src), a nonreceptor TK involved in cell-growth control. HGF bound to a single high-affinity receptor class, increased microvilli numbers 1.5-fold, enhanced cell proliferation and migration 1.8-fold, and stimulated formation of tubule structures 2.2-fold. PTKI inhibited the mitogenic and motogenic effects of HGF with different potencies and comparable maximal effects but had no specific influence on HGF-induced tubulogenic cell differentiation. These data underline the importance of pp60(c-src) in mediating mitogenic and motogenic effects of HGF, whereas stimulation of tubulogenic cell differentiation may be transduced by a pp60(c-src)-independent pathway.