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Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ferri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The spectroscopic and imaging performance of energy-resolved photon counting detectors, based on new sub-millimetre boron oxide encapsulated vertical Bridgman cadmium zinc telluride linear arrays, are presented in this work. The activities are in the framework of the AVATAR X project, planning the development of X-ray scanners for contaminant detection in food industry. The detectors, characterized by high spatial (250 µm) and energy (<3 keV) resolution, allow spectral X-ray imaging with interesting image quality improvements. The effects of charge sharing and energy-resolved techniques on contrast-to-noise ratio (CNR) enhancements are investigated. The benefits of a new energy-resolved X-ray imaging approach, termed window-based energy selecting, in the detection of low- and high-density contaminants are also shown.

The fragmentation of the natural habitat is a process that is exponentially increasing worldwide and represents one of the biggest threats to biological diversity. Habitat destruction and fragmentation have a major impact on landscapes and may also affect ecosystems, populations, and species. The ongoing anthropogenic process can result in habitat loss for some species, habitat creation for others, reduced patch size, and increased distance between patches, which may lead to local extinction. We analyzed the effects of patch size and isolation on lichens in Quercus pubescens woods surrounding the city of Potenza (south Italy). We randomly sampled 11 forest patches with homogeneous environmental variables using circular plots with a 10 m radius; the patches ranged from 0.3 to 30 ha. For each plot, we collected data about presence and abundance of epiphytic lichens. We performed the analyses at the patch level using linear regression and multivariate analysis, searching for effects on species richness, life forms, and community compositions. Multivariate analyses were used to study the effect of fragmentation on the structure of lichen vegetation. We investigated the main predictor of lichen species richness in habitat fragmentations and concluded that patch area per se is an important (positive) driver of lichen species richness in Mediterranean peri-urban forests.

High-flux X-ray measurements with high-energy resolution and high throughput require the mitigation of pile-up and dead time effects. The reduction of the time width of the shaped pulses is a key approach, taking into account the distortions from the ballistic deficit, non-linearity, and time instabilities. In this work, we will present the performance of cadmium−zinc−telluride (CdZnTe or CZT) pixel detectors equipped with digital shapers faster than the preamplifier peaking times (ballistic deficit pulse processing). The effects on energy resolution, throughput, energy-linearity, time stability, charge sharing, and pile-up are shown. The results highlight the absence of time instabilities and high-energy resolution (<4% FWHM at 122 keV) when ballistic deficit pulse processing (dead time of 90 ns) was used in CZT pixel detectors. These activities are in the framework of an international collaboration on the development of spectroscopic imagers for medical applications (mammography, computed tomography) and non-destructive testing in the food industry.

The wine pomace is the main winery by-products that suppose an economic and environmental problem and their use as a functional ingredient are being increasingly recognized as a good and inexpensive source of bioactive compounds. In this sense, it is known the potential health properties of wine pomace products in the prevention of disorders associated with oxidative stress and inflammation such as endothelial dysfunction, hypertension, hyperglycemia, diabetes, obesity. Those effects are due to the bioactive compounds of wine pomace and the mechanisms concern especially modulation of antioxidant/prooxidant activity, improvement of nitric oxide bioavailability, reduction of pro-inflammatory cytokines and modulation of antioxidant/inflammatory signal pathways. This review mainly summarizes the mechanisms of wine pomace products as modulators of oxidative status involved in cell pathologies as well as their potential therapeutic use for cardiovascular diseases. For this purpose, the review provides an overview of the findings related to the wine pomace bioactive compounds profile, their bioavailability and the action mechanisms for maintaining the redox cell balance involved in health benefits. The review suggests an important role for wine pomace product in cardiovascular diseases prevention and their regular food intake may attenuate the development and progression of comorbidities associated with cardiovascular diseases.

Red wine pomace products (WPP) have antimicrobial activities against human pathogens, and it was suggested that they have a probable anti- Listeria effect. This manuscript evaluates the intestinal cell monolayer invasive capacity of Listeria monocytogenes strains obtained from human, salmon, cheese, and L. innocua treated with two WPP (WPP-N and WPP-C) of different polyphenol contents using Caco-2 and SW480 cells. The invasion was dependent of the cell line, being higher in the SW480 than in the Caco-2 cell line. Human and salmon L. monocytogenes strains caused cell invasion in both cell lines, while cheese and L. innocua did not cause an invasion. The phenolic contents of WPP-N are characterized by high levels of anthocyanin and stilbenes and WPP-C by a high content of phenolic acids. The inhibitory effect of the WPPs was dependent of the strain and of the degree of differentiation of the intestinal cells line. The inhibition of Listeria invasion by WPPs in the SW480 cell line, especially with WPP-C, were higher than the Caco-2 cell line inhibited mainly by WPP-N. This effect is associated with the WPPs' ability to protect the integrity of the intestinal barrier by modification of the cell-cell junction protein expression. The gene expression of E-cadherin and occludin are involved in the L. monocytogenes invasion of both the Caco-2 and SW480 cell lines, while the gene expression of claudin is only involved in the invasion of SW480. These findings suggest that WPPs have an inhibitory L. monocytogenes invasion effect in gastrointestinal cells lines.

In this paper, we develop a forecasting model for the spread of COVID-19 infection at a provincial (i.e., EU NUTS-3) level in Italy by using official data from the Italian Ministry of Health integrated with data extracted from daily official press conferences of regional authorities and local newspaper websites. This data integration is needed as COVID-19 death data are not available at the NUTS-3 level from official open data channels. An adjusted time-dependent SIRD model is used to predict the behavior of the epidemic; specifically, the number of susceptible, infected, deceased, recovered people and epidemiological parameters. Predictive model performance is evaluated using comparison with real data.

The functional renal epithelium is composed of differentiated and polarized tubular cells with a strong actin cortex and specialized cell-cell junctions. If, under pathological conditions, these cells have to resist higher kidney osmolarity, they need to activate diverse mechanisms to survive external nephrotoxic agents such as inflammation and oxidative stress. Wine pomace polyphenols exert protective effects on renal cells. In this study, two wine-pomace products and their protective effects upon promotion and preservation of normal cell differentiation and attenuation of oxalate-induced type II epithelial mesenchymal transition (EMT) are evaluated. Treatment with gastrointestinal and colonic bioavailable fractions from red (rWPP) and white (wWPP) wine pomaces, both in the presence and the absence of oxalate, showed similar cell numbers and nuclear size than the non-treated differentiated MDCK cells. Immunofluorescence analysis showed the reduction of morphological changes and the preservation of cellular junctions for the rWPP and wWPP pre-treatment of cells exposed to oxalate injury. Hence, both rWPP and wWPP attenuated oxalate type II EMT in MDCK cells that conserved their epithelial morphology and cellular junctions through the antioxidant activities of grape pomace polyphenols., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors.)

Endothelial dysfunction is associated with cardiovascular diseases and involves a chronic inflammatory process that together with oxidative stress increases the permeability of the vascular endothelium. The aim of this study was to evaluate the role of red and white wine pomace products (rWPPs and wWPPs) in the maintenance of endothelial integrity in hyperglycemia of EA.hy926 endothelial cells. EA.hy926 endothelial cells exposed to hyperglycemia were treated with the in vitro digested fractions of rWPPs and wWPPs. A Real Time Cellular Analysis (RTCA) system was used to evaluate the endothelial monolayer integrity after INF-γ stimulation of pre-treated endothelial cells with the digested fractions. The changes in cell viability, NO, ROS and NOX4 were recorded and actin cytoskeleton and E-cadherin junctions were evaluated by immunofluorescence. All digested fractions prevent the hyperglycemic actions in the cell viability and NO/ROS balance. The inflammatory mediator INF-γ and hyperglycemia caused a decrease in RTCA adhesion of the EA.hy926 endothelial cell monolayer. Pre-treatment with all digested fractions enhanced the EA.hy926 endothelial monolayer integrity and maintained actin cytoskeleton and E-cadherin junctions. These in vitro studies elucidate that the anti-hyperglycemic and anti-inflammatory actions of wine pomace products involve a decrease in ROS production and the stabilization of junction proteins via modulation of VE-cadherin and actin cytoskeleton suggesting a potential prevention of endothelial damage by these natural products.

Feline parvovirus (FPV) causes severe gastroenteritis and leukopenia in cats; the outcome is poor. Information regarding specific treatments is lacking. Class A CpG oligodeoxynucleotides (CpG-A) are short single-stranded DNAs, stimulating type I interferon production. In cats, CpG-A induced an antiviral response in vivo and inhibited FPV replication in vitro. The aim was to prospectively investigate the effects of CpG-A on survival, clinical score, hematological findings, antiviral response (cytokines), viremia, and fecal shedding (real-time qPCR) in cats naturally infected with FPV. Forty-two FPV-infected cats were randomized to receive 100 µg/kg of CpG-A ( n = 22) or placebo ( n = 20) subcutaneously, on admission and after 48 h. Blood and fecal samples were collected on admission, after 1, 3, and 7 days. All 22 cats showed short duration pain during CpG-A injections. The survival rate, clinical score, leukocyte and erythrocyte counts, viremia, and fecal shedding at any time-point did not differ between cats treated with CpG-A (50%) and placebo (40%). Antiviral myxovirus resistance ( Mx ) gene transcription increased in both groups from day 1 to 3 ( p = 0.005). Antibodies against FPV on admission were associated with survival in cats ( p = 0.002). In conclusion, CpG-A treatment did not improve the outcome in cats with FPV infection. FPV infection produced an antiviral response.

Background: Erythrocytes of diabetic cats have decreased superoxide dismutase activity, possibly indicative of oxidative stress., Hypothesis: Erythrocytes of diabetic cats undergo oxidative stress, which is caused by hyperglycemia and hyperlipidemia, and improves with treatment., Animals: Twenty-seven client-owned cats with diabetes mellitus, 11 matched healthy cats, and 21 purpose-bred healthy cats., Methods: Prospective study. Advanced oxidized protein products, carbonyls (protein oxidation by-products), and thiols (antioxidants) were quantified in erythrocyte membrane, thiobarbituric acid reactive substances (TBAR, lipid peroxidation by-products), and thiols in erythrocyte cytoplasm of all cats. Comparison were performed between diabetic and matched healthy cats, between diabetic cats achieving remission or not, and among purpose-bred cats after 10 days of hyperglycemia (n = 5) or hyperlipidemia (n = 6) versus controls treated with saline (n = 5) or untreated (n = 5)., Results: Compared with controls, erythrocytes of diabetic cats initially had higher median membrane carbonyls (4.6 nmol/mg total protein [range: 0.1-37.7] versus 0.7 [0.1-4.7], P < .001) and lower cytoplasmic TBAR (1.9 nmol/mg [0.5-2.4] versus 2.4 [1.4-3.5] P < .001), and thiols (419 nmol/mg [165-621] versus 633 [353-824], P < 0.001). After 12-16 weeks of treatment in diabetic cats, carbonyls decreased by 13% (P < .001), but remained higher (P < .001) and TBAR and thiols lower (P = .02, P < .001) than those in controls. No differences were observed between diabetic cats achieving remission or not, and among purpose-bred cats., Conclusions and Clinical Importance: Diabetes mellitus is associated with increased protein oxidation and reduced antioxidant defenses, which persist during treatment and remission, although mild improvement in protein oxidation occurs. Short-term hyperglycemia or hyperlipidemia does not cause oxidative stress. The reason for decreased TBAR remains unknown., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Wine pomace by-products are an important source of phenolic acids with significant health benefits. However, phenolic acid bioavailability in vivo has been little studied and there are few comparative studies on bioavailability between red and white wine pomace and the effect of intake of different doses. The qualitative and quantitative profile of phenolic acid metabolites in plasma and urine samples from Wistar rats was obtained by gas chromatography/mass detection, after oral administration of four doses (50, 100, 150, and 300 mg) of both the red and the white wine pomace products (rWPP and wWPP, respectively). The antioxidant capacity of the plasma samples assessed by both the ABTS and the FRAP levels was also evaluated. The results showed that neither the bioavailability nor the antioxidant capacity in vivo of the rWPP increased at high doses. However, both parameters were dependent on the intake of the wWPP.

Pheochromocytoma is frequent in dogs and carries a guarded prognosis. Current histological criteria may not predict malignant behavior in dogs, similar to humans. In humans, characterization of tumors has been refined using the pheochromocytoma of the adrenal gland scaled score (PASS) and by immunohistochemistry. The study aim was to investigate PASS and immunohistochemical markers used in humans in 24 dogs with pheochromocytoma that underwent adrenalectomy. Dogs with pheochromocytomas were reviewed and tumors collected. Histological sections were evaluated to apply the PASS and were single-labeled for chromogranin A, Ki-67, COX-2, p53, BCL-2, c-erbB-2, vascular endothelial growth factor, and S100. Survival, age, and vascular and capsular invasion were compared for PASS and immunohistochemical markers; results of PASS were also compared for each marker. Associations between markers were tested. PASS and immunohistochemical markers did not differ for survival, age, and vascular and capsular invasion. Tumors showing BCL-2 expression in >50% cells had lower PASS than those with lower expression (PASS: 7 ± 2 vs 9 ± 2; P = .011). Tumors positive for S100 had higher PASS than those that were negative (PASS: 10 ± 2 vs 7 ± 2; P = .001). Results of the different markers were not associated. In conclusion, in the context of canine pheochromocytoma, PASS and the selected immunohistochemical markers are not associated with survival, age, or vascular or capsular invasion. The higher PASS in S100-positive tumors may indicate that pheochromocytomas developing morphologic changes acquire S100 expression. The significance of lower PASS in tumors with elevated BCL-2 expression is uncertain. Overall, the use of PASS and the present immunohistochemical markers may not be useful in dogs with pheochromocytoma.

[ 99m Tc][TcN-DBODC(5) is the lead candidate of a class of cationic complexes proposed as myocardial imaging agents (MPIAs). Phase I clinical studies showed that its clinical properties were comparable to those of the commercially available agents. Thus, modification of [ 99m Tc]TcN-DBODC(5), directed to obtain an ideal myocardial imaging without interference from the adjacent organ activities, is desirable. This work describes the pharmacological and pharmacokinetic development of four new complexes of general formula [ 99m Tc][Tc(N)(DASD)(PNP n)] + , [ 99m Tc]TcN-DASD( n) (DASD = 1,4-dioxa-8-azaspiro[4,5]decandithiocarbamate; PNP n = bisphosphinoamine), proposed as improved MPIAs. Among the tested compounds, [ 99m Tc]TcN-DASD(5) and [ 99m Tc]TcN-DASD(7) showed enhanced heart uptake compared with the gold standards, with a rapid liver washout and superior heart-to-liver ratio. These features might shorten the duration of imaging procedures below 30 min, consenting the early acquisition of high-quality images. In addition, mechanistic studies were performed in cellulo by using human drug-sensitive and drug-resistant cancer cell lines, obtaining results which might be conveniently applied to tumor imaging.

OBJECTIVE To determine survival estimates and outcome predictors for shelter cats with feline panleukopenia virus (FPV) infection. DESIGN Retrospective cohort study. ANIMALS 177 shelter cats with FPV infection. PROCEDURES Medical records of cats treated for FPV infection from 2011 through 2013 were reviewed to collect information pertaining to signalment; history; results of physical examination, CBC, serum biochemical analysis, and blood gas analysis; and treatments (antimicrobials, antiparasitics, antivirals, antiemetics, analgesics, crystalloid or colloid solutions, and blood products). Survival time and outcome predictors were determined by means of Kaplan-Meier estimation, logistic regression, and mixed-model ANOVA. RESULTS Median survival time after hospital admission was 3 days; 20.3% (36/177) of cats survived to discharge from the hospital. Risk of nonsurvival was greater in cats with (vs without) signs of lethargy, rectal temperature < 37.9°C (I00.2°F), or low body weight at hospital admission. Lower (vs higher) leukocyte count on days 3,4, and 7 of hospitalization, but not at admission, was associated with nonsurvival. Amoxicillin-clavulanic acid, antiparasitics, and maropitant but not interferon-ω were associated with survival, whereas glucose infusion was associated with nonsurvival. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that FPV infection carried a poor prognosis for shelter cats. Several variables measured at admission or during hospitalization were associated with outcome. Remarkably and contrary to the existing literature, leukopenia at admission had no association with outcome, possibly owing to early prevention of complications.

Charge losses at the inter-pixel gap are typical drawbacks in cadmium-zinc-telluride (CZT) pixel detectors. In this work, an original technique able to correct charge losses occurring after the application of charge-sharing addition (CSA) is presented. The method, exploiting the strong relation between the energy after CSA and the beam position at the inter-pixel gap, allows the recovery of charge losses and improvements in energy resolution. Sub-millimetre CZT pixel detectors were investigated with both uncollimated radiation sources and collimated synchrotron X-rays, at energies below and above the K-shell absorption energy of the CZT material. The detectors are DC coupled to fast and low-noise charge-sensitive preamplifiers (PIXIE ASIC) and followed by a 16-channel digital readout electronics, performing multi-parameter analysis (event arrival time, pulse shape, pulse height). Induced-charge pulses with negative polarity were also observed in the waveforms from the charge-sensitive preamplifiers (CSPs) at energies >60 keV. The shape and the height of these pulses were analysed, and their role in the mitigation of charge losses in CZT pixel detectors. These activities are in the framework of an international collaboration on the development of energy-resolved photon-counting systems for spectroscopic X-ray imaging (5-140 keV).

Background: Stent implantation is the treatment of choice for adolescents and adults with aortic coarctation (CoAo). Despite excellent short-term results, 20%-40% of the patients develop arterial hypertension later in life, which was attributed to inappropriate response of the aortic baroreceptors to increased stiffness of the ascending aorta (ASAO), either congenital or induced by CoAo repair. In particular, it has been hypothesized that stent itself may cause or sustain hypertension. Therefore, we aimed to study the hemodynamic and structural impact following stent implantation in the normal aorta of a growing animal., Methods: Eight female sheep completed the study and a stent was implanted in four. Every 3 mo we measured blood pressure of the anterior and posterior limbs and left ventricular function by echocardiography. Twelve months later invasive pressure was measured under baseline and simulated stress conditions. Expression of genes indicating oxidative stress (OS), endothelial dysfunction (ED) and stiffness, as well as pathological examination were performed in ascending (ASAO) and descending aorta (DSAO)., Results: SOD1 and MMP9 gene expression were higher in ASAO of the stented animals, compared to DSAO and controls, while NOS3 was decreased. No differences were found in blood pressure and echocardiographic parameters. No histological differences were found in the aorta of the two groups of animals., Conclusions: Stent does not affect central and peripheral hemodynamics, cardiac structure and function even in the long term. However, the finding of markers of OS and increased stiffness of ASAO, proximal to the stent, points to molecular mechanisms for increased cardiovascular risk of patients with stented CoAo., (© 2016 The Authors Congenital Heart Disease published by Wiley Periodicals, Inc.)

Dead-time losses are well recognized and studied drawbacks in counting and spectroscopic systems. In this work the abilities on dead-time correction of a real-time digital pulse processing (DPP) system for high-rate high-resolution radiation measurements are presented. The DPP system, through a fast and slow analysis of the output waveform from radiation detectors, is able to perform multi-parameter analysis (arrival time, pulse width, pulse height, pulse shape, etc.) at high input counting rates (ICRs), allowing accurate counting loss corrections even for variable or transient radiations. The fast analysis is used to obtain both the ICR and energy spectra with high throughput, while the slow analysis is used to obtain high-resolution energy spectra. A complete characterization of the counting capabilities, through both theoretical and experimental approaches, was performed. The dead-time modeling, the throughput curves, the experimental time-interval distributions (TIDs) and the counting uncertainty of the recorded events of both the fast and the slow channels, measured with a planar CdTe (cadmium telluride) detector, will be presented. The throughput formula of a series of two types of dead-times is also derived. The results of dead-time corrections, performed through different methods, will be reported and discussed, pointing out the error on ICR estimation and the simplicity of the procedure. Accurate ICR estimations (nonlinearity < 0.5%) were performed by using the time widths and the TIDs (using 10 ns time bin width) of the detected pulses up to 2.2 Mcps. The digital system allows, after a simple parameter setting, different and sophisticated procedures for dead-time correction, traditionally implemented in complex/dedicated systems and time-consuming set-ups.

Helicobacter pylori (H. pylori) is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world's population. It is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and shows a deep association with primary gastric B-cell lymphoma and gastric adenocarcinoma. Recently, the medical research focused on the modification of the gastric environment induced by H. pylori infection, possibly affecting the absorption of nutrients and drugs as well as the production of hormones strongly implicated in the regulation of appetite and growth. Interestingly, the absorption of iron and vitamin B12 is impaired by H. pylori infection, while infected subjects have lower basal and fasting serum levels of ghrelin and higher concentration of leptin compared to controls. Since leptin is an anorexigenic hormone, and ghrelin stimulates powerfully the release of growth hormone in humans, H. pylori infection may finally induce growth retardation if acquired very early in the childhood and in malnourished children. This review is focused on the nutritional effects of H. pylori infection, such as the reduced bioavailability or the malabsorbption of essential nutrients, and of gastrointestinal hormones, as well as on the relationship between H. pylori and the metabolic syndrome.

Despite the fact that sheep are a widely used animal model in cardiovascular research, reference values for transthoracic echocardiography in normal growing animals are not available. Eight healthy female lambs underwent two-dimensional, M-mode and pulsed wave Doppler echocardiographic examination at 100 days of age and every three months thereafter over a 12-month period. The study was conducted under sedation with midazolam, butorphanol and constant rate infusion of intravenous propofol. Their growth phase was completed at about one year of age. All the echocardiographic parameters considered were significantly correlated with body weight and age class except for the left ventricular systolic and diastolic diameters. Functional indices were not correlated to body weight or age except for the E-point to septal separation distance (EPSS). Doppler-derived parameters were not influenced by independent variables. Transthoracic echocardiography can be considered an applicable method for cardiovascular research using a growing lamb animal model after appropriate adjustments for age and body size.

The aim of this study was to investigate the effects of long-distance road transport (19 h, from Poland to Italy) during 2 seasons (summer vs. winter) on clinical and hematological variables in calves. The environmental temperature range that could compromise the thermoregulation system (thermal stress) of the calves was tested. For the 7 Holstein calves in each transport, the BW and rectal temperature (RT) were measured, and blood samples were collected at the farm of origin, before loading at the transit center (T2), after unloading at the farm of destination (T3), and 1, 2, 3, and 4 d after arrival. The body temperature (BT) and heart rate (HR) were continuously monitored from T2 to T3. The data were statistically analyzed according to a mixed model that considered the fixed effects of transport (repeated measurements), season of journey, and their interaction. Within the observed temperature-humidity index (THI) range (30 to 80), effective thermoregulation allowed the calves to maintain their BT with small physiologic changes to prevent thermal stress, particularly in the summer. With no seasonal differences, the HR was greater at loading than unloading (120 vs. 115 beats per min; P = 0.012). As for the transport effect, the BW was less (P < 0.001) after unloading, and the RT was greater (P = 0.004). This effect was more marked in summer. The hematological variables indicated a moderate effect of transport on the hydration condition, reactive and muscular systems, and metabolism, although hematocrit (P = 0.004), erythrocytes, cortisol, NEFA, β-hydroxybutyrate, lactate, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase activity (P < 0.001), and total protein (P = 0.007) were greater after unloading. This was confirmed by a moderate decrease in total leukocytes (P = 0.031) and glucose concentration (P = 0.002). The changes in the clinical variables were similar for both seasons even though in the summer, hematocrit (P < 0.001), urea (P = 0.008), and total protein (P = 0.010) increased and glucose concentration (P = 0.038) decreased. In conclusion, the data did not show a pronounced effect attributable to the season of the journey. Long-distance road transport leads to notable changes in clinical and hematological variables at the end of the journey. However, these variables remained within their physiological ranges and returned to basal values within a few days after the journey.

This report deals with the first benign intraosseous tumor of the maxillofacial skeleton ever documented in a species of the Homo genus, to our knowledge. The lower jaw, which belonged to a representative of Homo neanderthalensis, indicated that expansive processes with bone remodeling were already present in ancient times, showing no difference with similar disease patterns found daily in modern Homo sapiens., (Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.

Purpose: Direct measurement of mammographic x-ray spectra under clinical conditions is a difficult task due to the high fluence rate of the x-ray beams as well as the limits in the development of high resolution detection systems in a high counting rate environment. In this work we present a detection system, based on a CdTe detector and an innovative digital pulse processing (DPP) system, for high-rate x-ray spectroscopy in mammography., Methods: The DPP system performs a digital pile-up inspection and a digital pulse height analysis of the detector signals, digitized through a 14-bit, 100 MHz digitizer, for x-ray spectroscopy even at high photon counting rates. We investigated on the response of the digital detection system both at low (150 cps) and at high photon counting rates (up to 500 kcps) by using monoenergetic x-ray sources and a nonclinical molybdenum anode x-ray tube. Clinical molybdenum x-ray spectrum measurements were also performed by using a pinhole collimator and a custom alignment device., Results: The detection system shows excellent performance up to 512 kcps with an energy resolution of 4.08% FWHM at 22.1 keV. Despite the high photon counting rate (up to 453 kcps), the molybdenum x-ray spectra, measured under clinical conditions, are characterized by a low number of pile-up events. The agreement between the attenuation curves and the half value layer values, obtained from the measured spectra, simulated spectra, and from the exposure values directly measured with an ionization chamber, also shows the accuracy of the measurements., Conclusions: These results make the proposed detection system a very attractive tool for both laboratory research and advanced quality controls in mammography.

According to a 2 x 2 crossover design, 14 Holstein dairy cows were fed two isoenergetic diets based on either grass hay (GH) or maize silage (MS). Milk samples were collected during the third week of each period, and fatty acid (FA) profiles were analyzed using gas chromatography. The data obtained were subjected to ANOVA. Dietary treatment had no effect on either dry matter intake or milk yield. Milk from animals fed the GH-diet contained lower concentrations of saturated FAs (61.9 vs. 63.4% of total FAs; P < 0.05) and higher levels of polyunsaturated FAs (PUFAs) (6.1 vs. 5.8; P < 0.01). Feeding additional hay also increased conjugated linoleic acid and n-3 FA levels and decreased C16:0 levels. Increases in both PUFAs and n-3 FAs resulted in lower (P < 0.01) atherogenic and thrombogenic indices in milk from animals fed the GH diet compared with those fed the MS diet. A complete substitution of GH for MS appeared to improve milk FA profiles, even using different types of concentrates to provide a balanced diet.

Mastitis is the most frequent and costly disease in dairy herds, as it negatively affects yield and milk quality. The presence of clinical mastitis is quite easy to asses, whereas the diagnosis of the subclinical form can be more difficult and requires laboratory assays. Somatic cell count (SCC) is widely used as a rapid and low-cost indicator of mastitis, even if is not useful in discriminating between the clinical and subclinical form. As amyloid A has been investigated as a marker of mastitis, the aim of this study was to assess the potential value of measuring amyloid A in serum and milk and the correlation with SCC in the diagnosis of subclinical mastitis. The reliability of two different ELISA kits for the measurement of amyloid A in milk was also tested. During a 1-month trial period, 21 cows were assigned to three experimental groups according to their health status: 6 cows with clinical mastitis (CM), 10 cows with subclinical mastitis (SM) and 5 healthy cows (HE). Amyloid A was measured both in serum (SAA) and in quarter milk samples (mAA) with a serum ELISA kit, and in quarter milk samples (MAA) with a milk ELISA kit. SCC, total microbial count (TMC) and bacterial examination of the milk were also carried out. After a log transformation, the data were submitted to ANOVA and linear regression. TMC was significantly higher in cows with clinical mastitis, while no differences were observed between the other two experimental groups. SCC and MAA levels were significantly different among the three groups. mAA concentrations were similar between cows with subclinical and clinical mastitis, and SAA was not affected by mastitis. A significant correlation between SCC and MAA or mAA was detected, while no correlation was recorded between SAA and mAA. A close relationship between MAA and mAA was noticeable even at low concentrations, suggesting MAA as a potential physiological marker of subclinical mastitis.

A series of experiments on rats have been performed, to study the effects of long time (50 days) exposure to electromagnetic fields of extremely low frequency (ELF, i.e. less than 100 Hz) and amplitude (non thermal), testing whether the metabolic processes would be affected. The background lies on recent observations on the behaviour of isolated enzymes in vitro exposed to EFL fields. In these experiments, the cyclotron (or Larmor) frequency of the metallic ion has been used to "stimulate" the metalloproteins redox-active site, thus obtaining a clear variation of the enzyme functionality. In this paper we have extended for the first time the check to more complex animal metabolism. The novelty of this approach implies that a large amount of data had to be analyzed since it was not possible, in principle, to select only a few parameters among all the potential effects. Several biochemical parameters have been evaluated by comparing their values during the periods of exposure (field ON) and non exposure (field OFF). The evidence that long term exposure to electromagnetic fields with a well defined frequency may have relevant effects on parameters such as body weight, blood glucose and fatty acid metabolism has been obtained.

Hemojuvelin (HJV) positively modulates the iron regulator hepcidin, and its mutations are the major cause of juvenile hemochromatosis (JH), a recessive disease leading to iron overload. Defective HJV reduces hepcidin up-regulation both in humans and in Hjv-deficient mice. To investigate the JH pathogenesis and the functional properties of human HJV we studied the biosynthesis and maturation of 6 HJV pathogenic mutants in HeLa and HepG2 cells. We show that proteolytic processing is defective in mutants F170S, W191C, and G320V, but not in G99V and C119F. Moreover, we show that mutants G99V and C119F are targeted to the cell surface, while F170S, W191C, G320V, and R326X (lacking the glycosilphosphatidylinositol [GPI] anchor) are mainly retained in the endoplasmic reticulum, although all mutants are released as soluble forms (s-HJV) in a proportion that is modulated by iron supplementation. Membrane HJV (m-HJV) is mainly composed of the cleaved protein, and its level is increased by iron in wild-type (WT) mice but not in the mutants. Altogether, the data demonstrate that the loss of HJV membrane export is central to the pathogenesis of JH, and that HJV cleavage is essential for the export. The results support a dual function for s- and m-HJV in iron deficiency and overload, respectively.

Ferritin is an iron storage protein made of 24 subunits. Previous mutational analyses showed that ferritin C-terminal region has a major role in protein stability and assembly but is only marginally involved in the mechanism of iron incorporation. However, it has recently been shown that patients who carry alterations of ferritin C-terminal sequence caused by nucleotide insertions show neurological disorders possibly related to altered protein functionality and cellular iron deregulation. To re-evaluate the role of this region, five mutants of mouse H-ferritin were produced by 2-nucleotide insertions that modified the last 6-29 residues and extended the sequence of 14 amino acids. The mutants were expressed in Escherichia coli and analysed for solubility, stability and capacity to incorporate iron. The alteration of the last 6-residue non-helical extension had no evident effect on the properties of ferritin, while solubility and capacity to assemble in ferritin shells decreased progressively with the extension of the modified region. The results also showed that the modification of even a part of the terminal E-helix abolished the capacity of ferritin to incorporate iron during expression in the cells, probably caused by conformational modification of the hydrophobic channels. The data support the hypothesis that the pathogenic mutations alter cellular iron homeostasis.

Hepcidin is a small peptide that acts as a regulator of systemic iron homeostasis. To study some of its functional properties, a synthetic cDNA for the minimal, 20-amino-acid, form of human hepcidin was cloned into different constructs for expression in Escherichia coli. The fusion ferritin-hepcidin produced molecules retaining most of ferritin structural and functional properties, including ferroxidase and iron incorporation activities. However, it showed spectroscopic properties compatible with the presence of iron-sulfur complexes on the hepcidin moiety, which was buried into protein cavity. Similar complexes were reconstituted by in vitro incubation of the iron-free protein with iron and sulfide salts. Two other unrelated fusion products were constructed, which, when expressed in E. coli, formed insoluble aggregates retaining a large proportion of total bacterial iron. Analysis of the solubilized preparations showed them to contain iron-sulfur complexes. We concluded that the cysteine-rich hepcidin acts as an iron-sequestering molecule during expression in E. coli. This may have implications for the biological functions of this key protein of iron metabolism.

Background: Hereditary hemochromatosis is a recessive disorder characterized by iron accumulation in parenchymal cells, followed by organ damage and failure. The disorder is mainly attributable to the C282Y and H63D mutations in the HFE gene, but additional mutations in the HFE, transferrin receptor 2 (TfR2), and hepcidin genes have been reported. The copresence of mutations in different genes may explain the phenotypic heterogeneity of the disorder and its variable penetrance., Methods: We used denaturing HPLC (DHPLC) for rapid DNA scanning of the HFE (exons 2, 3, and 4), hepcidin, and TfR2 (exons 2, 4 and 6) genes in a cohort of 657 individuals with altered indicators of iron status., Results: DHPLC identification of C282Y and H63D HFE alleles was in perfect agreement with the restriction endonuclease assay. Fourteen DNA samples were heterozygous for the HFE S65C mutation. In addition, we found novel mutations: two in HFE (R66C in exon 2 and R224G in exon 4), one in the hepcidin gene (G71D), and one in TfR2 (V22I), plus several intronic or silent substitutions. Six of the seven individuals with hepcidin or TfR2 coding mutations carried also HFE C282Y or S65C mutations., Conclusion: DHPLC is an efficient method for mutational screening for the genes involved in hereditary hemochromatosis and for the study of their copresence.

We found that tumor necrosis factor alpha (TNFalpha)-induced apoptosis in HeLa cells was accompanied by a approximately 2-fold increase in H- and L-ferritin and a decrease in transferrin receptor, two indices of increased iron availability. Iron supplementation and overexpression of H-ferritin or its mutant with an inactivated ferroxidase center reduced by about approximately 50% the number of apoptotic cells after TNFalpha-treatment, while overexpression of L-ferritin was ineffective. The data indicate that H-ferritin has an anti-apoptotic activity unrelated to its ferroxidase activity and to its capacity to modify cellular iron metabolism.

Background: Oxidant stress has a pathogenic role in uremic anemia, possibly interfering with erythropoietin (EPO) function and red blood cell (RBC) survival. Therefore, it is expected that antioxidant therapy might exert a beneficial effect on these parameters., Methods: To test this hypothesis, we investigated some oxidant stress indices, anemia levels, and RBC survival in 47 hemodialysis (HD) patients randomly assigned to three groups. Patients in groups A (n = l8) and B (n = 20) were on dialysis therapy using conventional cellulosic and synthetic membranes and were administered high and low doses of recombinant human EPO (rHuEPO), respectively. Patients in group C (n = 9) were dialyzed with vitamin E-modified membranes (CL-Es) and investigated in a two-step prospective study. In step Cl, patients were administered rHuEPO doses similar to those of group A. In step C2, rHuEPO doses were reduced to those of group B. As oxidant stress markers, we determined in plasma the susceptibility of lipids to undergo iron-catalyzed oxidation (reactive oxygen molecules [ROMs] test) and malondialdehyde-4-hydroxynonenal (MDA-4HNE), alpha-tocopherol (alpha-T), total thiol (-SH), and total antioxidant activity. RBC survival was measured using the chromium 51 T/2 technique in 22 patients., Results: Results show that: (1) high rHuEPO doses (groups A and C1) were associated with decreased ROM production, low alpha-T levels, and slightly increased -SH levels compared with corresponding groups on low rHuEPO doses (groups B and C2); (2) treatment with CL-Es (group C) increased plasma alpha-T and decreased -SH levels; these data were associated with decreased indices of lipid peroxidation, particularly MDA-4HNE 1evels, only in patients administered low rHuEPO doses; (3) alpha-T concentration influenced RBC survival, which was remarkably decreased in HD patients; patients treated with CL-Es showed a better degree of anemia correction; and (4) alpha-T level correlated negatively with -SH level and seemed to be independent of the extent of peroxidation and oxidizability of plasma lipids., Conclusion: Both EPO and CL-E can influence plasma antioxidants and, to an extent, lipid peroxidation processes. However, this study shows that even in patients treated with low rHuEPO doses, RBC survival close to normal and sufficient correction of anemia are achieved only when appropriate alpha-T levels are reached., (Copyright 2002 by the National Kidney Foundation, Inc.)

Background: The oxidative damage of RBC membranes in hemodialysis (HD) patients increases red blood cell (RBC) susceptibility to hemolysis and impairs cell survival. Reduction of the oxidative stress might lead to better control of anemia and reduction of the erythropoietin (rhEPO) dose., Methods: We studied 38 stable HD patients, given a mean dose of rhEPO of 104+/-65 U/kg BW/week, at baseline and during antioxidant treatment with either a full or a 50% dose of EPO. Antioxidant treatment involved the combined use of glutathione, GSH (1200 mg i.v. at the end of each dialysis session) and a vitamin E-bonded HD membrane, CL-E. RBC and reticulocyte counts were done monthly. RBC survival (51Cr T/2) was assayed in 18 patients before and after the end of the study. Oxidative status was determined in 10 patients by measuring plasma concentrations of malondyhaldeide-4-hydroxynonenal (MDA-4HNE), reactive oxygen molecular species (ROMs), and oxydized-LDL (oxLDL) as indices of oxidative stress, alpha-tocopherol and total thiols as single antioxidants, and TAS as a marker of total antioxidant plasma activity., Results: Antioxidant treatment significantly reduced the high basal plasma concentrations of MDA4HNE and oxLDL, and significantly increased those of alpha-tocopherol, whereas TAS and thiols were unmodified. These changes lasted after the reduction of EPO. Anemia significantly improved with treatment, due to a significant increase in RBC survival. A close direct linear relationship was detected between plasma levels of vitamin E and hemoglobin., Conclusions: Adequate control of oxidative stress achieves better control of anemia in HD patients. Since several antioxidant systems are impaired in uremia, the combined use of the CL-E membrane and GSH seems to be the best antioxidant therapy so far, with significant saving of the rhEPO dose.

Patients undergoing long-term hemodialysis (HD) exhibit increased levels of oxidative stress, likely contributing to the increased rate of cardiovascular disease. The present study represents a critical evaluation of some of the most widely used oxidative indicators, as applied to the monitoring of hemodialysis-associated oxidative stress. Total plasma antioxidant capacity was determined by two independent procedures, the total antioxidant status (TAS) and the ferric reducing ability of plasma (FRAP) methods. Plasma lipid peroxidation was assessed by determining the peroxidation products malonaldehyde and 4-hydroxynonenal (MDA-4HNE) as well as lipid hydroperoxides ("Fox-2" and "d-ROMs" methods). Total plasma thiols and plasma alpha-tocopherol were also determined. MDA-4HNE levels were higher in HD patients and decreased following HD, possibly due to passive diffusion across dialysis filters. d-ROMs were also higher in HD patients but exhibited a further increase following the dialysis procedure. Serum alpha-tocopherol did not show any significant differences. Plasma thiols were lower in HD patients and were restored following HD. Plasma total antioxidant capacity determined with either method was unexpectedly higher in HD patients compared to controls, and decreased following HD. These data indicate that, of the biomarkers studied, d-ROMs level is the one more accurately reflecting the oxidative alterations taking place in HD patients, while determination of MDA-4HNE fails to detect oxidation occurring during the HD sessions. In addition, our findings point out that the determination of total antioxidant capacity in HD patients is severely affected by the concomitant fluctuations in plasma urate levels and therefore needs careful interpretation.

The authors report their experience with a patient suffering from an intralobar bronchopulmonary sequestration (IBS). The lesion was misdiagnosed as metapneumonic lung abscess. IBS is a rare, diagnostically binding lung congenital malformation. So far, TC and MR angiography achieve pathognomonic findings with low invasivity. The best treatment of IBS could be surgical resection.

Splenic artery pseudoaneurysms are the most common of visceral artery pseudoaneurysms. Splenic pseudoaneurysms appear to have developed as a consequence of inflammatory processes adjacent to the splenic artery, particularly acute pancreatitis and chronic pancreatitis with associated pseudocysts. They are often asymptomatic and picked up on abdominal examination for ultrasound or CT scanning for other conditions. Complications include rupture with retroperitoneal hemorrhage or intraperitoneal hemorrhage. Two cases of splenic pseudoaneurysms, following acute pancreatitis, are reported between the years 1987 and 1996.

To assess the efficacy and safety of different doses of the alpha-1 blocker terazosin on long-term therapy, 12 essential hypertensives (7 males, 5 females, aged 27-61) were investigated. The study was conducted according to the Latin square design and each patient underwent 4 periods of treatment with 2, 5, 10 mg/day terazosin and placebo, in a double-blind, randomized order. Each treatment lasted 4 weeks. In comparison to placebo, a fall in diastolic pressure was observed already with the 2 mg/daily dose, with a decrease > 10 mmHg in 7 patients (responders). Body weight increased in a dose dependent manner, while atrial natriuretic peptide, serum glucose and insulin during oral glucose tolerance test, total cholesterol, HDL and LDL cholesterol, triglycerides were unaffected. It is concluded that terazosin is effective and safe in essential hypertensives already at 2 mg daily dose. Further reduction in blood pressure at higher doses is likely to be counteracted by salt and water retention.

The authors report on the last 100 cases of intervention in which thyroid pathology has been used and also prove how, in their experience, thyroglobulin is an MO, highly specific for CDT. In some cases its dosage changes even in the course of benign thyroid pathology but the value has never exceeded, in these cases, twice the norm. This also confirms, therefore the importance of this MO for the follow up of patients operated on using CDT.

Spirometric test failure has been defined as failure by a subject to meet the acceptability and/or reproducibility criteria laid down by the American Thoracic Society for measurements derived from forced expiratory maneuvers. The prevalence and determinants of spirometric test failure were examined in 416 men and women aged 20 to 45 yr working in an office environment. In this study population, 11.5% (28 men and 20 women) exhibited test failure for forced expiratory volume in one second (FEV1). The main determinant of test failure in men was bronchial hyperresponsiveness to methacholine challenge (odds ratio 6.7; confidence interval 1.7, 27.1) and in women being a current smoker (odds ratio 4.02; confidence interval 1.13, 14.33). There was also a relationship to eczema in both men and women, but not at a statistically significant level. When FEV1 variability was defined as the difference (in milliliters) between the two best FEV1 values and the results of men and women combined for analysis, significant predictors were a history of eczema, recurrent chest illness in the past 3 yr, and level of bronchial responsiveness to inhaled methacholine. These findings contribute to the gathering evidence that test failure may be of itself an indicator of impaired respiratory health, and its association with bronchial hyperresponsiveness to methacholine in men suggests that in them test failure is related to airway lability, but in women the relationship to smoking suggests an irritative mechanism.

A case of primary mucinous carcinoid of the ovary observed in a 52-year-old woman is reported after some remarks on the various histogenetic theories. The observation of this extremely rare cancer was fortuitous during surgery carried out for benign pathology in the contralateral organ. Careful postoperative controls absolutely excluded the possibility of a metastatic tumour. The patient was treated by combining surgery with chemotherapy and eight months after operation is apparently free of cancer.

In the medically underserved Bronx, NY, a hospital's gerontology center provides screening, health education, and outpatient services to elderly residents in the community.