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Lycaon pictus (Temminck, 1820), the African wild dog, is a moderately sized carnivore with dog-like appearance and irregularly mottled black, yellow-brown, and white pelage. It has a head–body length of 76–112 cm, tail length of 30–41 cm, shoulder height of 61–78 cm, and body weight of 17–36 kg. Lycaon pictus has four toes on each foot, differentiating it from other canids; is the only extant species within the genus with no subspecies; and is unlikely to be confused with any other canid. Lycaon pictus was once widespread throughout sub-Saharan Africa inhabiting nearly all environments and now inhabits grasslands, montane savanna, and open woodlands. Lycaon pictus is recognized as “Endangered” (EN) by the U.S. Fish and Wildlife Service and the International Union for Conservation of Nature.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

To profile and correlate KRAS mutations with outcome in stage III colon cancer (CC) patients who underwent adjuvant chemotherapy following curative resection surgery.In this retrospective study, eligible patients were those with resected stage III CC who underwent 6-months adjuvant chemotherapy, either with fluoropyrimidine monotherapy (FP) or with oxaliplatin-based regimens (O-FP). Disease-free survival (DFS) and overall survival (OS) were analyzed and computed using the Kaplan-Meier method and the log-rank test.The study population included 148 patients (n=65 FP and n=83 O-FP). We identified KRAS mutations in 41/148 (27%) patients, of which 18 (44%) received FP and 23 (56%) O-FP. Five-year DFS and OS were significantly higher in patients with KRAS wild-type vs. mutant [DFS: 78 vs. 56%, HR: 0.47 (95% CI: 0.25; 0.87), p=0.01; OS: 73 vs. 68%, HR: 0.44 (95% CI: 0.21; 0.88), p=0.01]. In patients treated with FP, the 5-year DFS and OS was significantly improved in the KRAS wild-type vs. mutant group, respectively [DFS: 80 vs. 43%, HR: 2.88 (95% CI: 0.67; 3.76), p=0.014; OS: 85 vs. 68%, HR: 0.27 (95% CI: 0.10; 0.73), p=0.005]. Conversely, 5-year DFS and OS were not statistically different for patients with KRAS wild-type vs. mutations treated with O-FP, respectively [DFS: 78 vs. 65%, HR: 1.59 (95% CI: 0.67; 3.76), p=0.281; OS: 80 vs. 75%, HR: 0.73 (95% CI: 0.55; 2.12), p=0.57)].Our results suggest that curatively resected stage III CC patients exhibiting wild-type KRAS status might benefit from FP alone. Conversely, an oxaliplatin-containing regimen should be recommended in KRAS mutated patients.

Stable isotope analysis of diet has become a common tool in conservation research. However, the multiple sources of uncertainty inherent in this analysis framework involve consequences that have not been thoroughly addressed. Uncertainty arises from the choice of trophic discrimination factors, and for Bayesian stable isotope mixing models (SIMMs), the specification of prior information; the combined effect of these aspects has not been explicitly tested. We used a captive feeding study of gray wolves (Canis lupus) to determine the first experimentally-derived trophic discrimination factors of C and N for this large carnivore of broad conservation interest. Using the estimated diet in our controlled system and data from a published study on wild wolves and their prey in Montana, USA, we then investigated the simultaneous effect of discrimination factors and prior information on diet reconstruction with Bayesian SIMMs. Discrimination factors for gray wolves and their prey were 1.97‰ for δ13C and 3.04‰ for δ15N. Specifying wolf discrimination factors, as opposed to the commonly used red fox (Vulpes vulpes) factors, made little practical difference to estimates of wolf diet, but prior information had a strong effect on bias, precision, and accuracy of posterior estimates. Without specifying prior information in our Bayesian SIMM, it was not possible to produce SIMM posteriors statistically similar to the estimated diet in our controlled study or the diet of wild wolves. Our study demonstrates the critical effect of prior information on estimates of animal diets using Bayesian SIMMs, and suggests species-specific trophic discrimination factors are of secondary importance. When using stable isotope analysis to inform conservation decisions researchers should understand the limits of their data. It may be difficult to obtain useful information from SIMMs if informative priors are omitted and species-specific discrimination factors are unavailable.

The paper reviews the possibilities offered by the advent of nanotechnology for regulating the interaction between electromagnetic fields and bio-systems with unprecedented flexibility and specificity. In particular, it discuss how the exploitation of magnetic nanoparticles and magnetic fields can lead to significant advances in clinical and diagnostic applications, and to the opening of a completely new scenario: the true remote control of nanomachines and biological systems.

A manufacturing process for the production of Anti-thrombin IIII concentrate is described, which is based primarily on Heparin Sepharose affinity chromatography. The process includes two sequential viral inactivation/removal procedures, applied to the fraction eluted from the column, the first by heating in aqueous solution at 60 degrees C for 10 h and the second by nanofiltration. Using viral validation on a scaled-down process both treatments proved to be effective steps; able to inactivate or remove more than 4 logs of virus, and their combined effect (>8 logs) assured the safety of the final product. Viral validation studies of the Heparin Sepharose chromatographic step demonstrated a consistency of the affinity of the resin for viruses over repeated use (16 runs), thus providing evidence of absence of cross-contamination from one batch to the next. It was concluded that the process of ATIII manufacturing provides a high level of confidence that the product will not transmit viruses.

Stable isotope analysis of diet has become a common tool in conservation research. However, the multiple sources of uncertainty inherent in this analysis framework involve consequences that have not been thoroughly addressed. Uncertainty arises from the choice of trophic discrimination factors, and for Bayesian stable isotope mixing models (SIMMs), the specification of prior information; the combined effect of these aspects has not been explicitly tested. We used a captive feeding study of gray wolves (Canis lupus) to determine the first experimentally-derived trophic discrimination factors of C and N for this large carnivore of broad conservation interest. Using the estimated diet in our controlled system and data from a published study on wild wolves and their prey in Montana, USA, we then investigated the simultaneous effect of discrimination factors and prior information on diet reconstruction with Bayesian SIMMs. Discrimination factors for gray wolves and their prey were 1.97‰ for δ13C and 3.04‰ for δ15N. Specifying wolf discrimination factors, as opposed to the commonly used red fox (Vulpes vulpes) factors, made little practical difference to estimates of wolf diet, but prior information had a strong effect on bias, precision, and accuracy of posterior estimates. Without specifying prior information in our Bayesian SIMM, it was not possible to produce SIMM posteriors statistically similar to the estimated diet in our controlled study or the diet of wild wolves. Our study demonstrates the critical effect of prior information on estimates of animal diets using Bayesian SIMMs, and suggests species-specific trophic discrimination factors are of secondary importance. When using stable isotope analysis to inform conservation decisions researchers should understand the limits of their data. It may be difficult to obtain useful information from SIMMs if informative priors are omitted and species-specific discrimination factors are unavailable.

Background and Objectives The presence of B19 virus in blood poses a risk of transmission of the virus via blood or blood products. Screening processes for manufacturing should be aimed at achieving production plasma pools with B19 virus contamination levels below 104 genome equivalents/ml (geq/ml) in order to prevent transmission of infection through plasma derivatives. Materials and Methods The suitability of a competitor plasmid as an internal analytical standard for the detection of B19 virus in plasma pools was assessed by using a competitive polymerase chain reaction (PCR) assay. Seventy-five plasma pools, each consisting of 960 single donations, were analysed for B19 virus contamination following a lysis treatment. Results The amount of competitor plasmid in the competitive PCR assay established, with good accuracy, a threshold value for discrimination of the viral load in plasma pools. Analysis of samples from plasma pools showed that 12% of pools were contaminated with B19 virus at levels above the set threshold value. Conclusions The competitive PCR assay developed proved to be effective for discrimination of the B19 virus contamination level in screening of plasma pools for manufacturing.

The Italian National Law 281 of 1991 forbids the euthanatization of free-ranging dogs, unless they have an incurable illness or are proved to be dangerous. Without neglecting the undeniable benefits of the "no-kill" policy, nevertheless it has brought about a chronic overpopulation in shelters and, as a result, higher costs of management and welfare problems since some dogs remain in the shelter for life. In 2004-2008, the Istituto Zooprofilattico Sperimentale of the Lazio and Tuscany regions carried out a survey in the Lazio Region to verify the effects of the Italian National Law 281/91 on free-ranging dog management following 15 years from its implementation. One of the aims of the study was an assessment of the welfare of dogs in a shelter sample (8 shelters out of 47 censused in the Lazio Region). 97 mixed-breed dogs were selected, their behaviour was studied and a blood sample was taken for each dog in order to determine the individual blood concentration of cortisol and the amount of oxidative damage (level of dRoms), as well as the amount of antioxidants to cope with it. Moreover, the total leukocyte count (leukogram) was accomplished. We ran general backward stepwise regression models using "level of antioxidant", "level of dRoms" and "level of serum cortisol" as dependent variables respectively. The results showed that the most important variable that improved the level of welfare of dogs consisted in having the opportunity to regularly go out of the cage for a walk, whereas other variables like gender, size of the cage (small, medium, large), being alone in the cage, and being neutered/entire, had no significant effect on the physiological indicators of welfare. Dogs that enjoyed the regular walk had a higher total antioxidant capacity, and performed a lower frequency of displacing activities and stereotyped behaviour. Moreover, oxidative stress parameters seem to be indicators well matched with behavioural indicators of stress. Thus, for the first time, markers of oxidative status are utilised for the welfare evaluation in the domestic dog. Furthermore, the results of this paper give some suggestion about how small steps can help to improve shelters and, furthermore, this paper intends to solicit the debate on the no-kill policy.

Interleukin-2 (IL-2) is a cytokine with proven activity against metastatic renal cell carcinoma (RCC) and malignant melanoma (MM). The intravenous administration of high-dose IL-2 is limited by important cardiovascular side effects such as hypotension, fluid retention, arrhythmias, and myocardial ischemia, which often cause dose reduction and/or treatment withdrawal. The occurrence of these toxic events is not predicted by routine pretreatment examinations. The aim of the present study was to test the reliability of serial echocardiography in predicting subsequent cardiac adverse effects in patients undergoing IL-2 administration. In 19 patients (15 men, 4 women; median age: 51 years, range 27-71 years; 10 affected by metastatic RCC and 9 affected by MM) we performed two-dimensional and Doppler echocardiography before and immediately after 28 continuous intravenous infusions (CIVI) of IL-2 at the dose of 18 MIU/m2/day for 4 days. Left ventricular systolic function and the diastolic transmitral flow pattern were assessed before and after IL-2 administration. Significant changes of two indexes of left ventricular filling were noted: a decrease of the ratio of maximal flow velocity in early diastole to that in late diastole (E/A) (basal: 1.12 +/- 0.46, mean +/- SD; posttreatment: 0.83 +/- 0.27; p < 0.01) and an increase of the percentage of the atrial contribution to left ventricular filling (basal: 37.75 +/- 11.58%; posttreatment: 49.43 +/- 16.48%; p < 0.01). Eight major cardiovascular events causing IL-2 infusion withdrawal were observed (two ischemic electrocardiographic modifications, three grade III-IV hypotension, one atrial fibrillation, one pericardial effusion, one acute heart failure). These major cardiovascular events were observed more often when an abnormal basal E/A ratio < 1.0 (p < 0.05) was found. We conclude that Doppler transmitral flow pattern analysis before and subsequent to IL-2 infusion is a useful and easily available procedure for the monitoring of cardiac modifications during CIVI IL-2 administration. It might also predict a major cardiovascular event during IL-2 administration. Patients with basal E/A ratio < 1.0 should be more carefully monitored during treatment and/or should be treated with lower IL-2 doses to avoid cardiovascular toxicity.

This paper reviews the possibilities offered by the advent of nanotechnology for regulating the interaction between electromagnetic fields and bio-systems with unprecedented flexibility and specificity. In particular, we discuss how the exploitation of magnetic nanoparticles and magnetic fields can lead to significant advances in clinical and diagnostic applications, and to the opening of a completely new scenario: the true remote control of nanomachines and biological systems.

A short-version (15-week long) of school-based nutrition education program called "Bring Fruit to School" to enhance primary schoolchildren's fruit and vegetable (FV) intake was evaluated. We recruited 199 primary schoolchildren from 8 classes (grade 2-5). The primary end-point was an increase in the children's FV intake. The intervention period lasted 15 weeks, and was divided into three phases: weeks 1-5, weeks 6-10 and weeks 11-15. The FV intake of the schoolchildren was also monitored in a subsequent follow-up period (16th-32nd week). By week 15, 92 (46.2%, P.001) schoolchildren increase fruit intake and 91 (45.7%, P.001) increase vegetable intake. The FV intake increased during the intervention period and was constant in follow-up. The BFtS program is an effective means to promote primary schoolchildren's FV intake, and was implemented in Italy by the Food and Nutrition Service of Foggia's Local Health Authority. It could be extended to many other countries by local nutrition agencies, such as associations for nutrition.

Light scattering experiments on solutions of bovine CO-hemoglobin have revealed that a substantial component of the interactions responsible for the protein stability versus tetramer-to-dimer dissociation is due to electrostatic effects. Their magnitude has been estimated to reach \ensuremath{\simeq}4 kcal/mole (\ensuremath{\simeq}0.15 eV) at pH=5 compared with the nonelectrostatic term which is of the order of 7 kcal/mole (\ensuremath{\simeq}0.3 eV).

This paper describes an uncommon radiation treatment of the external ear, with ultrasound (US) transmission gel used as bolus device to compensate for the irregularity of the target surface.Postoperative radiotherapy for cutaneous carcinoma was performed with a single high-energy electron beam directed over the ear auricle. Due to the irregular surface of the target, a "missing tissue" compensator was employed. Daily, after patient positioning, the concha was filled and flattened with US gel, and a dose of 54 Gy in 27 fractions was delivered.Water equivalence of the gel was verified by comparing the gel's computed tomography (CT) number [Hounsfield units (HU)] and density with the corresponding values for water and another commercial bolus device. Whereas ultrasound gel and water had comparable values (HU: 0; density 1 g/cm(3) for both), the corresponding values for the commercial device were slightly higher (HU: 80; density 1.02 g/cm(3)).Ultrasound gel proved to be an easy, fast and cheap compensating tool. Its water equivalence allows it to be used as an alternative to water, though easier to position and with lower risk of displacement. Thus, it is recommendable as a practical tool for most irregular sites. Further investigations are warranted to validate this solution in more complex irradiation techniques.

The presence of B19 virus in blood poses a risk of transmission of the virus via blood or blood products. Screening processes for manufacturing should be aimed at achieving production plasma pools with B19 virus contamination levels below 104 genome equivalents/ml (geq/ml) in order to prevent transmission of infection through plasma derivatives.The suitability of a competitor plasmid as an internal analytical standard for the detection of B19 virus in plasma pools was assessed by using a competitive polymerase chain reaction (PCR) assay. Seventy-five plasma pools, each consisting of 960 single donations, were analysed for B19 virus contamination following a lysis treatment.The amount of competitor plasmid in the competitive PCR assay established, with good accuracy, a threshold value for discrimination of the viral load in plasma pools. Analysis of samples from plasma pools showed that 12% of pools were contaminated with B19 virus at levels above the set threshold value.The competitive PCR assay developed proved to be effective for discrimination of the B19 virus contamination level in screening of plasma pools for manufacturing.

Cell-to-cell adhesion is mediated by cadherins (integral membrane proteins), which form a complex with catenins (cytoplasmatic proteins). While E-cadherin expression has been extensively studied in many human skin diseases, less is known about the expression levels of catenins in oral blistering diseases. The purpose of this study was to evaluate the role of these proteins in the pathogenesis of acantholysis in oral pemphigus vulgaris. We evaluated by immunohistochemistry beta- and gamma-catenin expression in 7 cases of oral pemphigus vulgaris (PV) at various stages of the disease and, as controls, in 18 healthy patients. Healthy cases showed, as reported in the literature, a strong reactivity with both beta- and gamma-catenins, with the intensity of staining progressively decreasing from the spinous to the keratinised layers of epithelium, which had a prevalent cellular membrane expression. In PV patients, we detected a loss of membrane expression of these molecules with a progressive displacement of the signal toward the cytosol and, for gamma-catenin, nuclear dislocation, particularly in areas with intense acantholysis.

The synthesis and the solution behavior of the linear peptides containing a beta-homo (beta-H) leucine residue-Boc-Leu-beta-HLeu-Leu-OMe, Boc-beta-HLeu-Leu-beta-HLeu-Leu-OMe, and Boc-Leu-beta-HLeu-Leu-beta-HLeu-Leu-OMe-as well as the solid structure of the tripeptide, are reported. The conformational behavior of the peptides was investigated in solution by two-dimensional nmr. Our data support the existence in solution with different families of conformers in rapid interchange. The crystals of the tripeptide are orthorhombic, space group P2(1)2(1)2, with a = 15.829(1) A, b = 29.659(1) A, c = 6.563(1) A, and Z = 4. The structure has been solved by direct methods and refined to final R1 and wR2 indexes of 0.0530 and 0.1436 for 2420 reflections with I2sigma(I). In the solid state, the tripeptide does not present intramolecular H bonds, and the peptide backbone of the two leucine residues adopts a quasi-extended conformation. For the beta-HLeu residue, the backbone conformation is specified by the torsion angles straight phi(2) = -120.9(4) degrees, mu(2) = 56.7(4) degrees, psi(3) = -133.2(4) degrees. The side chains of the three residues assume the same conformation (g(-), g(-), trans), and all peptide bonds, except the urethane group at the N-terminus, are in the trans conformation. Preliminary conformational energy calculations carried out on the Ac-NH-beta-HAla-NHMe underline that the conformations with mu angle equal to 180 degrees and 60 degrees assume lower energy with respect to the others. In addition, we found a larger conformational freedom for the psi angle with respect to the straight phi angle.

The clearance of apoptotic cells is crucial to avoid chronic inflammation and autoimmunity. Little is known about the factors that regulate it in vivo. We show that granulocyte-macrophage colony-stimulating factor (GM-CSF) administration to carcinoma patients confers to their leukocytes a significantly higher ability to phagocytose apoptotic cells than before (P < 0.005). GM-CSF increased the concentration of monocytes and polymorphonuclear leukocytes in the peripheral blood and activated circulating polymorphonuclear leukocytes. Both effects abated early after treatment, whereas phagocytosis of apoptotic cells was still significantly higher after 18 days compared with basal values (P < 0.005 and P < 0.025 for monocytes and polymorphonuclear leukocytes, respectively). On in vitro phagocytosis of apoptotic cells monocytes, but not polymorphonuclear leukocytes, up-regulated MHC class II membrane expression. These findings are consistent with the possibility that GM-CSF endows both scavenger and antigen-presenting leukocytes with the ability to internalize apoptotic tumor cells. J. Leukoc. Biol. 67: 174–182; 2000.

Despite the frequent occurrence of traumatic lesions of the oral mucosa, patients suffering from these conditions seldom refer to the clinician. This is due to the easy recognition of aetiologic agents, thus enabling patients to eliminate them.

The crystal structure of human T state hemoglobin crosslinked with bis(3,5-dibromo-salicyl) sebacate has been determined at 1.9 A resolution. The final crystallographic R factor is 0.168 with root-mean-square deviations (RMSD) from ideal bond distance of 0.018 A. The 10-carbon sebacyl residue found in the beta cleft covalently links the two betaLys82 residues. The sebacyl residue assumes a zigzag conformation with cis amide bonds formed by the NZ atoms of betaLys82's and the sebacyl carbonyl oxygens. The atoms of the crosslink have an occupancy factor of 1.0 with an average temperature factor for all atoms of 34 A2. An RMSD of 0.27 for all CA's of the tetramer is observed when the crosslinked deoxyhemoglobin is compared with deoxyhemoglobin refined by using a similar protocol, 2HHD [Fronticelli et al. J. Biol. Chem. 269: 23965-23969, 1994]. Thus, no significant perturbations in the tertiary or quaternary structure are introduced by the presence of the sebacyl residue. However, the sebacyl residue does displace seven water molecules in the beta cleft and the conformations of the beta1Lys82 and beta2Lys82 are altered because of the crosslinking. The carbonyl oxygen that is part of the amide bond formed with the NZ of beta2Lys82 forms a hydrogen bond with side chain of beta2Asn139 that is in turn hydrogen-bonded to the side chain of beta2Arg104. A comparison of the observed conformation with that modeled [Bucci et al. Biochemistry 35:3418-3425, 1996] shows significant differences. The differences in the structures can be rationalized in terms of compensating changes in the estimated free-energy balance, based on differences in exposed surface areas and the observed shift in the side-chain hydrogen-bonding pattern involving beta2Arg104, beta2Asn139, and the associated sebacyl carbonyl group.

The extension of the blisters of pemphigus to the esophagus is relatively uncommon, especially in patients treated with corticosteroids who appear to be in clinical remission. The aim of this study was to evaluate the esophagus in eight patients affected by oral pemphigus in various stages of the disease. Upper gastrointestinal endoscopy revealed esophageal involvement in five patients (two men and three women); three had blisters or erosions in the upper esophagus, whereas two showed red longitudinal lines along the entire organ. Direct immunofluorescence was positive in all eight patients. It is suggested that endoscopic examination of esophageal mucosa is an objective criterion by which to judge the success of therapy of pemphigus vulgaris.

Experiments were done in anesthetized rats to determine systemic hemodynamic and renal functional effects of isovolemic exchange transfusion with either 5% albumin or hemoglobin cross-linked with bis (3,5-dibromosalicyl) fumarate (XLHb) in volumes ranging from 1 to 6.3 ml.100 gm-1. Hematocrit decreased in proportion to increasing exchange volumes with either fluid. Exchange with increasing volumes of albumin led to progressive decreases in blood pressure. Exchange of 1 ml.100 gm-1 of XLHb was associated with an increase in blood pressure, whereas with larger exchanges, blood pressure returned to and was maintained at control values even for exchanges as large as 6.3 ml.100 gm-1. An increase of similar magnitude in glomerular filtration rate occurred with both fluids. Net and fractional sodium excretion (FENa) increased significantly with both transfusion fluids; the increase was significantly larger for XLHb than for albumin. Maximal FENa excretion with albumin was about 8% but exceeded 6% with XLHb. Pretreatment with indomethacin (5 mg.kg-1.day-1 for 3 days) did not blunt the diuresis that occurred with an exchange of 2 ml.100 gm-1 XLHb. It is concluded that 5% XLHb, as compared with 5% albumin, better supports systemic blood pressure, especially as exchange volume increases, possibly as a result of hemoglobin-induced increased vascular tone. Although a decrease in hematocrit may play a role in the diuresis observed with either fluid, the greater diuresis with XLHb must be due to some additional factor; the mechanism does not appear to involve prostaglandins.