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Purpose: Our aim was to assess retinal venous diameter and segmented retinal layer thickness variation in acute systemic hypoxia with and without acetazolamide and to relate these changes to high altitude headache (HAH), as a proxy for intracerebral pathophysiology., Methods: A total of 20 subjects participated in a 4-day ascent to the Margherita Hut (4,559 m) on Monte Rosa in the Italian Alps. Each participant was randomized to either oral acetazolamide 250 mg twice daily or placebo. A combination of digital imaging and optical coherence tomography was used to measure retinal vessel diameter and retinal layer thickness. Clinically-assessed HAH was recorded., Results: A total of 18 participants had usable digital and OCT images, with 12 developing HAH. Significant thickening was seen only in the two inner layers of the retina, the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) at P = 0.012 and P = 0.010, respectively, independent of acetazolamide. There was a significant positive correlation between HAH and both retinal venous diameter (T = 4.953, P = 0.001) and retinal artery diameter (T = 2.865, P = 0.015), with both unaffected by acetazolamide (F = 0.439, P = 0.518)., Conclusions: Retinal venous diameter correlates positively with HAH, adding further evidence for the proposed venous outflow limitation mechanism. The inner layers of the retina swelled disproportionately when compared to the outer layers under conditions of systemic hypoxia. Acetazolamide does not appear to influence altitudinal changes of retinal layers and vasculature.

Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Dysfunction of other organs is an important cause of poor outcomes from AKI. Ample clinical and epidemiologic data show that AKI is associated with distant organ dysfunction in lung, heart, brain, and liver. Recent advancements in basic and clinical research have demonstrated physiologic and molecular mechanisms of distant organ interactions in AKI, including leukocyte activation and infiltration, generation of soluble factors such as inflammatory cytokines/chemokines, and endothelial injury. Oxidative stress and production of reactive oxygen species, as well as dysregulation of cell death in distant organs, are also important mechanism of AKI-induced distant organ dysfunction. This review updates recent clinical and experimental findings on organ crosstalk in AKI and highlights potential molecular mechanisms and therapeutic targets to improve clinical outcomes during AKI., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The introduction of wide field optical coherence tomography (WF-OCT) has provided newer insights in the imaging of peripheral choroid. We evaluated choroidal thickness (CT) and large choroidal vessel thickness (LCVT) of 20 eyes in horizontal and vertical meridians using WF-OCT. A high-definition line scan through the fovea in both horizontal and vertical meridian was captured in primary and extremes of gaze to obtain scans up to mid-equator. CT and LCVT measurements were done across predefined points in macular area and all quadrants. LCVT was calculated after identifying a large choroidal vessel near choroidoscleral interface. The main outcome measures were differences in CT and LCVT in macular and four quadrants. Mean CT (331.23 ± 76.34 µ) and LCVT (201.46 ± 54.31 µ) in vertical macular segment were significantly more than CT (245.79 ± 55.38 µ; p = 0.0002) and LCVT (150.48 ± 52.58 µ; p = 0.004) in horizontal macular segment. CT at peripheral points in all quadrants was significantly reduced as compared to subfoveal CT (all p values < 0.05) with maximum reduction in inferior quadrant (64.5%). Using linear regression, only quadrant had a significant effect on CT and LCVT (both p < 0.001). CT and LCVT are highest at the macular area with reduction towards the periphery. The contribution of LCVT to CT is less at the fovea compared to other peripheral points.

Flow cytometry (FC) is widely applied to characterize and stage nodal lymphomas in dogs because it has a short turnaround time, requires minimally invasive sampling, and allows contemporary evaluation of neoplastic cells in the primary lesion and of blood and marrow involvement. We investigated advantages and limitations of FC in suspected extranodal lymphomas in dogs. The likelihood of obtaining a suitable FC sample was significantly lower for aspirates of extranodal lesions than for lymph node aspirates. However, we noted no differences among different extranodal lesion sites. We also describe FC results for 39 samples compatible with extranodal lymphoma. A dominant population of large cells was easily identified on morphologic FC scattergrams in many cases. Phenotypic aberrancies were frequently present, mainly in T-cell lymphomas. Lymphoma cells were distinguishable from normal residual lymphocytes in >85% of cases, facilitating the quantification of putative blood and marrow involvement by FC. Despite the high percentage of non-diagnostic samples (32 of 73, >40%), we support the inclusion of FC in the diagnostic workup of suspected extranodal lymphomas in dogs, in conjunction with histopathology. Histopathology is the gold standard for diagnosing lymphoma, provides relevant information, including tissue invasion and epitheliotropism, but has a longer turnaround time.

Purpose: To report variation of choroidal vascularity index (CVI) in macular and mid-equator areas in healthy subjects using wide-field optical coherence tomography (WF-OCT)., Design: Prospective, cross-sectional study., Methods: Setting: Two-center study., Study Population: Twenty eyes of 20 healthy subjects., Observation Procedure: Single high-definition scans passing through the fovea in both vertical and horizontal meridians were studied. Images were taken in primary gaze and extremes of gaze and a manual montage was created. A previously reported semi-automated algorithm was used to calculate the CVI in macular, superior, inferior, temporal, and nasal quadrants., Main Outcome Measures: Difference in CVI in macular area and 4 quadrants., Results: Twenty eyes from 20 subjects were enrolled in the study. The mean age was 28.85 ± 6.29 years with men comprising 9 of the 20 subjects (45.0%). The refractive error (spherical equivalent) ranged from -3.00 to +0.75 diopters. The average CVI in the macular area (40.01 ± 7.67) was significantly smaller than in any of the other fundus areas (all P < .01). The maximum CVI was seen in the nasal quadrant (50.84 ± 5.64), followed by inferior (47.93 ± 9.31), temporal (46.14 ± 7.06), and superior (45.72 ± 7.69). The nasal quadrant was found to have the least coefficient of variation (CV) of CVI (0.11) while the inferior and macular area had the highest CV (0.19)., Conclusions: We report CVI in WF-OCT in healthy young individuals. CVI seems to have a wide topographic variation. The macular area had the least CVI. CVI values are more consistent with lesser CV in the nasal quadrant compared to the other quadrants and macular area., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Canine breeds may be considered good animal models for the study of genetic predisposition to cancer, as they represent genetic clusters. From epidemiologic and case collection studies it emerges that some breeds are more likely to develop lymphoma or specific subtypes of lymphoma but available data are variable and geographically inconsistent. This study was born in the context of the European Canine Lymphoma Network with the aim of investigating the breed prevalence of canine lymphoma in different European countries and of investigating possible breed risk of lymphoma overall and/or different lymphoma subtypes., Results: A total of 1529 canine nodal lymphoma cases and 55,529 control cases from 8 European countries/institutions were retrospectively collected. Odds ratios for lymphoma varied among different countries but Doberman, Rottweiler, boxer and Bernese mountain dogs showed a significant predisposition to lymphoma. In particular, boxers tended to develop T-cell lymphomas (either high- or low-grade) while Rottweilers had a high prevalence of B-cell lymphomas. Labradors were not predisposed to lymphoma overall but tended to develop mainly high-grade T-cell lymphomas. In contrast with previous studies outside of Europe, the European golden retriever population did not show any possible predisposition to lymphoma overall or to specific subtypes such as T-zone lymphoma., Conclusion: Further prospective studies with more precise and consistent subtype identification are needed to confirm our retrospective results and to create the basis for the investigation of possible genes involved in different predispositions.

Purpose: (1) To collect a dataset of normative Early Treatment Diabetic Retinopathy Study (ETDRS) thickness map values for single retinal layers automatically segmented by Spectralis (Heidelberg Engineering, Heidelberg, Germany) spectral-domain OCT (SD-OCT) in a healthy white population. (2) To test the effect of age, sex, and axial length (AXL) on such values., Design: Cross-sectional study., Subjects: Healthy adult emmetropic white subjects with no history of ongoing or past conditions known to affect retinal anatomy., Methods: SD-OCT scans (30 × 25-degree volume) centered on the fovea were collected. Retinal-layer automatic segmentation was performed. Mean thickness values of 9 ETDRS sectors were calculated for each layer in 1 eye from each subject. The effect of age, sex, and AXL on the thickness of the central subfield, inner ring (IR), and outer ring (OR) of the ETDRS grid was tested. Scans were performed twice on a subset of patients to assess the repeatability of measurements., Main Outcome Measures: Retinal-layer thickness., Results: Two hundred eyes from 200 subjects (110 females, mean age 39.9±13.9 years [range 20-74 years]) were used for this study. The mean AXL was 24.30±1.07 mm (range 22.23-27.14 mm). Full retinal thickness was higher in males regardless of the subfield (all P < 0.05). Ganglion cell layer thickness correlated positively with AXL in the C (P = 0.02) but negatively in the OR (P = 0.0001). The inner plexiform layer was thicker in males in the IR (P = 0.01) and thinner in longer eyes in the OR (P = 0.002). The inner nuclear layer was thicker in males in the C and the IR (P = 0.002 and P = 0.0009, respectively). The outer plexiform layer thickness did not change with age and gender but correlated positively with AXL in the C (P = 0.009). Males had thicker outer nuclear layers in all subfields (all P < 0.05). The thickness of the nerve fiber layer and retinal pigment epithelium was not affected by the studied variables in any subfield. The intraclass correlation coefficient ranged from 0.872 for the outer plexiform layer to 0.990 for the retinal nerve fiber layer and the ganglion cell layer., Conclusions: The thickness values of each retinal layer in a large white population are provided. The thickness of retinal layers is influenced by gender, sex, and AXL, with a variable extent depending on the analyzed ETDRS map ring., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To correlate changes in choroidal thickness and vascularity index with disease activity in patients with neovascular age-related macular degeneration (nAMD)., Methods: Eyes diagnosed with AMD that had two sequential visits within 12 months and that had no choroidal neovascularization (CNV) or had inactive CNV at the first visit were included. Those that had active CNV at follow-up were enrolled as cases. Eyes that did not developed a CNV or that were still inactive at the second visit were enrolled as controls. Disease activity was based on optical coherence tomography (OCT) and fluorescein angiography findings. Subfoveal choroidal thickness (SCT), mean choroidal thickness (MCT), and choroidal vascularity index (CVI) were assessed on enhanced depth imaging OCT and compared between the baseline and follow-up visit. Subgroup analysis accounting for lesion type and previous treatment, if any, were performed., Results: Sixty-five eyes from 60 patients (35 females) and 50 age- and sex-matched controls were included. At the active visit, cases had an increase from 164 ± 67 μm to 175 ± 70 μm in mean ± SD SCT and from 144 ± 45 μm to 152 ± 45 μm in MCT (both P < 0.0001). The mean CVI also increased at from 54.5% ± 3.3% to 55.4% ± 3.8% (P = 0.04). Controls did not show significant changes in choroidal measurements between the two visits. Mean SCT, MCT, and CVI values were similar for previously treated and treatment-naive eyes., Conclusions: Choroidal thickness and CVI significantly increased with active disease in nAMD eyes. Changes in choroidal thickness may predict CNV development or recurrence before they are otherwise evident clinically.

Purpose: To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases., Design: Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis., Participants: Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4)., Methods: Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging., Main Outcome Measures: Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging., Results: Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 μm and 65.4±27.9 μm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns., Conclusions: Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: To evaluate baseline features and morphologic changes of vitreoretinal adhesion and outer retinal layers outside the macula after intravitreal ocriplasmin injection. To study the relation between vitreous detachment and attenuation of retinal outer segments signal., Methods: Retrospective cases series of 15 eyes. Each eye was scanned with the 55° wide-field optical coherence tomography lens in 6 different locations, three horizontal B-scan (central, temporal, and nasal) and three vertical B-scan (central, superior, and inferior) at baseline, 1 week, 1 month, 3 months, and 6 months after injection., Results: After ocriplasmin injection, vitreomacular traction (VMT) resolved in 12 patients (80%), 3 of them presenting a complete posterior vitreous detachment. Eight patients (53%) showed a panretinal attenuation of photoreceptors outer segment signal, 7 with VMT resolution and 1 with non-posterior vitreous detachment and no VMT resolution. In three patients after VMT resolution the attenuation involved also areas with no posterior vitreous detachment. The attenuation resolved during follow-up in 7/8 eyes (87.5%)., Conclusion: Intravitreal ocriplasmin injection induced resolution of VMT in most cases and more rarely a release of vitreopapillary adhesion and a complete posterior vitreous detachment. An acute panretinopathy was visible in more than half of the patients and was not related to vitreous detachment.

Background/aims: To systematically compare the intermodality and inter-reader agreement for two blue-light confocal fundus autofluorescence (FAF) systems., Methods: Thirty eyes (21 patients) with a diagnosis of geographic atrophy (GA) were enrolled. Eyes were imaged using two confocal blue-light FAF devices: (1) Spectralis device with a 488 nm excitation wavelength (488-FAF); (2) EIDON device with 450 nm excitation wavelength and the capability for 'colour' FAF imaging including both the individual red and green components of the emission spectrum. Furthermore, a third imaging modality (450-RF image) isolating and highlighting the red emission fluorescence component (REFC) was obtained and graded. Each image was graded by two readers to assess inter-reader variability and a single image for each modality was used to assess the intermodality variability., Results: The 95% coefficient of repeatability (1.35 mm 2 for the 488-FAF-based grading, 8.13 mm 2 for the 450-FAF-based grading and 1.08 mm 2 for the 450-RF-based grading), the coefficient of variation (1.11 for 488-FAF, 2.05 for 450-FAF, 0.92 for 450-RF) and the intraclass correlation coefficient (0.994 for 488-FAF, 0.711 for 450-FAF, 0.997 for 450-RF) indicated that 450-FAF-based and 450-RF-based grading have the lowest and highest inter-reader agreements, respectively. The GA area was larger for 488-FAF images (median (IQR) 2.1 mm 2  (0.8-6.4 mm 2 )) than for 450-FAF images (median (IQR) 1.0 mm 2  (0.3-4.3 mm 2 ); p<0.0001). There was no significant difference in lesion area measurement between 488-FAF-based and 450-RF-based grading (median (IQR) 2.6 mm 2  (0.8-6.8 mm 2 ); p=1.0)., Conclusion: The isolation of the REFC from the 450-FAF images allowed for a reproducible quantification of GA. This assessment had good comparability with that obtained with 488-FAF images., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Canine nodal marginal zone lymphoma (nMZL) is classified as an indolent lymphoma. Such lymphomas are typified by low mitotic rate and slow clinical progression. While the clinical behaviour of canine splenic MZL has been described, characterized by an indolent course and a good prognosis following splenectomy, there are no studies specifically describing nMZL. The aim of this study was to describe the clinical features of and outcome for canine nMZL. Dogs with histologically confirmed nMZL undergoing a complete staging work-up (including blood analysis, flow cytometry [FC] on lymph node [LN], peripheral blood and bone marrow, imaging, histology and immunohistochemistry on a surgically removed peripheral LN) were retrospectively enrolled. Treatment consisted of chemotherapy or chemo-immunotherapy. Endpoints were response rate (RR), time to progression (TTP) and lymphoma-specific survival (LSS). A total of 35 cases were enrolled. At diagnosis, all dogs showed generalized lymphadenopathy. One-third was systemically unwell. All dogs had stage V disease; one-third also had extranodal involvement. The LN population was mainly composed of medium-sized CD21+ cells with scant resident normal lymphocytes. Histology revealed diffuse LN involvement, referring to "late-stage" MZL. Median TTP and LSS were 149 and 259 days, respectively. Increased LDH activity and substage b were significantly associated with a shorter LSS. Dogs with nMZL may show generalized lymphadenopathy and an advanced disease stage. Overall, the outcome is poor, despite the "indolent" designation. The best treatment option still needs to be defined., (© 2017 John Wiley & Sons Ltd.)

Objectives Flow cytometry (FC) is becoming increasingly popular among veterinary oncologists for the diagnosis of lymphoma or leukaemia. It is accurate, fast and minimally invasive. Several studies of FC have been carried out in canine oncology and applied with great results, whereas there is limited knowledge and use of this technique in feline patients. This is mainly owing to the high prevalence of intra-abdominal lymphomas in this species and the difficulty associated with the diagnostic procedures needed to collect the sample. The purpose of the present study is to investigate whether any pre-analytical factor might affect the quality of suspected feline lymphoma samples for FC analysis. Methods Ninety-seven consecutive samples of suspected feline lymphoma were retrospectively selected from the authors' institution's FC database. The referring veterinarians were contacted and interviewed about several different variables, including signalment, appearance of the lesion, features of the sampling procedure and the experience of veterinarians performing the sampling. Statistical analyses were performed to assess the possible influence of these variables on the cellularity of the samples and the likelihood of it being finally processed for FC. Results Sample cellularity is a major factor in the likelihood of the sample being processed. Moreover, sample cellularity was significantly influenced by the needle size, with 21 G needles providing the highest cellularity. Notably, the sample cellularity and the likelihood of being processed did not vary between peripheral and intra-abdominal lesions. Approximately half of the cats required pharmacological restraint. Side effects were reported in one case only (transient swelling after peripheral lymph node sampling). Conclusions and relevance FC can be safely applied to cases of suspected feline lymphomas, including intra-abdominal lesions. A 21 G needle should be preferred for sampling. This study provides the basis for the increased use of this minimally invasive, fast and cost-effective technique in feline medicine.

Background/aims: To investigate the presence of short-wave fluorophores within regions of age-related macular degeneration (AMD)-associated macular atrophy (MA) area., Methods: This is a prospective, observational, cross-sectional case series. 25 eyes (18 patients) with late AMD and clinically identified MA were enrolled. Eyes were imaged using a confocal light-emitting diode blue-light fundus autofluorescence (FAF) device (EIDON, CenterVue, Padua, Italy) with 450 nm excitation wavelength and the capability for 'colour' FAF imaging, including both the individual red and green components of the emission spectrum. To produce images with a high contrast for isolating the green component, the red component was subtracted from the total FAF image. The main outcome measure was the presence of green emission fluorescence component (GEFC) within the MA area. Volume spectral domain optical coherence tomography (SD-OCT) scans were obtained through the macula and the OCT was correlated with the MA lesions identified on the FAF images, including regions of increased GEFC., Results: Of the investigated eyes, 11 out of 25 (44.0 %) showed the absence of GEFC in the MA area, whereas 14 eyes (56.0%) were characterised by GEFC within the MA area. The presence and distribution of GEFC in the MA area correlated with the presence of hyper-reflective material over Bruch's membrane on the corresponding SD-OCT scans., Conclusion: Short-wave fluorophores, which contribute to the GEFC, are present in the MA area and appear to correspond to residual debris or drusenoid material. Short-wavelength fluorophores revealed by colour FAF imaging may warrant further study., Competing Interests: Competing interests: PL: financial support—Bayer, Centervue, Genentech, Novartis, Roche; GS: financial support—Novartis, Alcon, Bayer, Allergan, Boehringer Ingelheim, Genentech, Roche, Zeiss Meditec, Heidelberg Engineering, Optos, Centervue; SRS: financial support—Allergan, Carl Zeiss Meditec, Genentech, Iconic, Novartis, Optos, Optovue, Regeneron, Thrombogenics., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To describe vitreal, retinal, and choroidal features of eyes affected by Endogenous candida endophthalmitis (ECE) analyzed by spectral domain optical coherence tomography (SD-OCT) and to evaluate their clinical impact., Methods: Medical records and SD-OCT images from eyes diagnosed with ECE at four retina and uveitis tertiary referral centers were retrospectively evaluated. Spectral domain optical coherence tomography images were analyzed to evaluate the structural changes occurring in the vitreous, the retina, and the choroid in areas involved by ECE. Baseline and final best-corrected visual acuity were correlated with SD-OCT findings., Results: Fifteen eyes from nine patients were enrolled. Vitreous involvement (vitreous cells, posterior hyaloid thickening) was detected in 13/15 eyes. Peculiar hyper-reflective preretinal aggregates obscuring the underlying retina because of a shadowing effect ("rain-cloud" sign) were noticed in all eyes with vitreous involvement. Two patterns of retinal and choroidal findings were identified: the first (six eyes) confined within the inner retinal layers (Intraretinal Pattern), the second (nine eyes) involving both retina (full thickness) and choriocapillaris (Chorioretinal Pattern). None of the eyes showed both patterns. None of the eyes, regardless the pattern, showed choroidal thickening. Baseline best-corrected visual acuity was not associated with OCT pattern (P = 0.09). On the contrary, final best-corrected visual acuity was significantly higher in patients showing Intraretinal Pattern (∼20/25, 0.06 ± 0.08 LogMAR) than in subjects with Chorioretinal Pattern (∼20/50, 0.44 ± 0.30 LogMAR) (P = 0.01)., Conclusion: Endogenous candida endophthalmitis showed peculiar features on SD-OCT. Two distinct patterns of chorioretinal involvement influencing the final best-corrected visual acuity were identified. Spectral domain optical coherence tomography could be useful in the diagnosis, management, and outcome prediction in ECE.

Flow cytometry (FC) is increasingly being used for immunophenotyping and staging of canine lymphoma. The aim of this retrospective study was to assess pre-analytical variables that might influence the diagnostic utility of FC of lymph node (LN) fine needle aspirate (FNA) specimens from dogs with lymphoproliferative diseases. The study included 987 cases with LN FNA specimens sent for immunophenotyping that were submitted to a diagnostic laboratory in Italy from 2009 to 2015. Cases were grouped into 'diagnostic' and 'non-diagnostic'. Pre-analytical factors analysed by univariate and multivariate analyses were animal-related factors (breed, age, sex, size), operator-related factors (year, season, shipping method, submitting veterinarian) and sample-related factors (type of sample material, cellular concentration, cytological smears, artefacts). The submitting veterinarian, sample material, sample cellularity and artefacts affected the likelihood of having a diagnostic sample. The availability of specimens from different sites and of cytological smears increased the odds of obtaining a diagnostic result. Major artefacts affecting diagnostic utility included poor cellularity and the presence of dead cells. Flow cytometry on LN FNA samples yielded conclusive results in more than 90% of cases with adequate sample quality and sampling conditions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the reproducibility of parafoveal microvascular anatomy of 7 different optical coherence tomography angiography (OCT-A) devices by comparing vessel density (VD), fractal dimension (FD), and foveal avascular zone (FAZ) of superficial and deep capillary plexus in healthy volunteers., Design: Reliability analysis., Methods: Consecutive healthy volunteers presenting at the Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan in the same clinic visit were imaged by 7 different OCT-A devices: Optovue RTVue XR Avanti (Optovue, Inc, Fremont, California, USA), prototype Spectralis OCT-A (Spectralis; Heidelberg Engineering, Heidelberg, Germany), AngioPlex (Cirrus 5000 HD-OCT; Carl Zeiss Meditec, Inc, Dublin, California, USA), prototype PlexElite (Carl Zeiss Meditec), RS-3000 Advance (Nidek, Gamagori, Japan), OCT-HS100 (Canon, Tokyo, Japan), and Revo NX (Optopol Technology SA, Zawiercie, Poland). OCT-A examinations were performed using a 3 × 3 mm volume scan pattern centered on the fovea. Mean VD, FD, and FAZ values between the instruments were compared., Results: The 7 different devices presented measurements with different mean values, with only a limited number of comparisons not significantly different between the instruments. Moreover, Bland-Altman analysis revealed that the limits of agreement for all the comparisons were not acceptable. Regression analysis was used in the development of tables to compare various devices, despite which large standard errors were found for both intercepts and slope conversion values., Conclusions: Our results suggest that the comparison between instruments is nearly impossible and the set of measurements from the various instruments are not interchangeable regarding VD, FD, and FAZ for both the superficial and deep capillary plexus., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We investigated the growth of ultra-thin Fe films on Ir(1 1 1) by means of in situ low energy electron diffraction and spin-resolved photoemission techniques. We observe a (1  ×  1) diffraction pattern, characteristic of the fcc substrate, below four monolayers (ML). Then, a complex superstructure starts to develop, compatible with the formation of bcc-like Fe domains aligned with the substrate according to the Kourdjumov-Sachs orientation relationships. The analysis of the diffraction patterns reveals a progressive evolution towards a fully relaxed bcc lattice, characteristic of bulk Fe. Both photoemission (filled states) and inverse photoemission (empty states) results show characteristic features related to the contribution of the Fe layer, evolving towards those observed on the Fe (1 1 0) bcc surface. Spin resolution allows to detect a spectral polarization above 4 ML, corresponding to the formation of bcc Fe, which gradually increases indicating the formation of an in-plane magnetized ferromagnetic layer in thick films. No in-plane net magnetization is detected in thinner films, independent of the sample temperature down to 30 K. Following recent investigations on the Fe/Ir(1 1 1) system with microscopy techniques, we link this observation to the stabilization of a non collinear spin structure yielding an overall nil magnetization.

Background: Copy number variations are genome polymorphism that influence phenotypic variation and are an important source of genetic variation in populations. The aim of this study was to investigate genetic variability in the Mexican Creole chicken population using CNVs., Results: The Hidden Markov Model of the PennCNV software detected a total of 1924 CNVs in the genome of the 256 samples processed with Axiom® Genome-Wide Chicken Genotyping Array (Affymetrix). The mapped CNVs comprised 1538 gains and 386 losses, resulting at population level in 1216 CNV regions (CNVRs), of which 959 gains, 226 losses and 31 complex (i.e. containing both losses and gains). The CNVRs covered a total of 47 Mb of the whole genome sequence length, corresponding to 5.12% of the chicken galGal4 autosome assembly., Conclusions: This study allowed a deep insight into the structural variation in the genome of unselected Mexican chicken population, which up to now has not been genetically characterized. The genomic study disclosed that the population, even if presenting extreme morphological variation, cannot be organized in differentiated genetic subpopulations. Finally this study provides a chicken CNV map based on the 600 K SNP chip array jointly with a genome-wide gene copy number estimates in a native unselected for more than 500 years chicken population.

Genomic and genetic variation among six Italian chicken native breeds (Livornese, Mericanel della Brianza, Milanino, Bionda Piemontese, Bianca di Saluzzo and Siciliana) were studied using single nucleotide polymorphism (SNP) and copy number variants (CNV) as markers. A total of 94 DNA samples genotyped with Axiom® Genome-Wide Chicken Genotyping Array (Affymetrix) were used in the analyses. The results showed the genetic and genomic variability occurring among the six Italian chicken breeds. The genetic relationship among animals was established with a principal component analysis. The genetic diversity within breeds was calculated using heterozygosity values (expected and observed) and with Wright's F-statistics. The individual-based CNV calling, based on log R ratio and B-allele frequency values, was done by the Hidden-Markov Model (HMM) of PennCNV software on autosomes. A hierarchical agglomerative clustering was applied in each population according to the absence or presence of definite CNV regions (CNV were grouped by overlapping of at least 1 bp). The CNV map was built on a total of 1003 CNV found in individual samples, after grouping by overlaps, resulting in 564 unique CNV regions (344 gains, 213 losses and 7 complex), for a total of 9.43 Mb of sequence and 1.03% of the chicken assembly autosome. All the approaches using SNP data showed that the Siciliana breed clearly differentiate from other populations, the Livornese breed separates into two distinct groups according to the feather colour (i.e. white and black) and the Bionda Piemontese and Bianca di Saluzzo breeds are closely related. The genetic variability found using SNP is comparable with that found by other authors in the same breeds using microsatellite markers. The CNV markers analysis clearly confirmed the SNP results.

Canine T-zone lymphoma (TZL) is a peculiar lymphoma subtype characterized by an indolent clinical course and aberrant CD45-negative phenotype, commonly recognized by flow cytometry (FC). Recent studies have described clinical presentation and behavior, but to date the mechanisms behind the loss of CD45 protein expression have never been investigated. The aims of this study were: 1) to confirm the absence of CD45 in canine TZL via the concomitant use of FC and immunohistochemistry with two different sources of antibody; and 2) to investigate the amount of CD45 transcript and the presence of CD45 gene in the neoplastic cells of dogs affected by TZL. 57 lymph node aspirates were included in the present study: 40 (70.2%) TZLs, 7 (12.3%) high grade T-cell lymphomas and 10 (17.5%) reactive lymph nodes. Neoplastic cells and normal T-cells were isolated from TZL and reactive lymph nodes, respectively, via cell sorting. Immunohistochemistry was performed on 2 TZL, 2 reactive lymph nodes and 2 Peripheral T-cell Lymphomas. Total RNA and genomic DNA were extracted from lymph-nodes aspirates. Two different quantitative real-time PCR experiments were designed, to determine the amount of the CD45 transcript and of the corresponding gene fragment. All TZL cases were negative for CD45 at immunohistochemistry. CD45 transcript amount was significantly lower in TZL compared to controls (p<0.001). This difference was not significant (p=0.584) for CD45 DNA load, that was similar between TZL and controls. Moreover, CD45 transcript amount was inversely correlated with the percentage of neoplastic cells in each TZL sample (p=0.010). These results confirm that CD45 protein is lacking on cell surface irrespective of the technique and antibody source adopted. This phenotypic aberrancy is apparently due to the absence of gene transcription, as CD45 DNA was present, whereas CD45 transcript was virtually absent in the neoplastic cells. The data here reported support further studies investigating possible factors impairing CD45 gene transcription., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Evidences have been provided of a crucial role of multimodal audio-visuomotor processing in subserving the musical ability. In this paper we investigated whether musical audiovisual stimulation might trigger the activation of motor information in the brain of professional pianists, due to the presence of permanent gestures/sound associations. At this aim EEG was recorded in 24 pianists and naive participants engaged in the detection of rare targets while watching hundreds of video clips showing a pair of hands in the act of playing, along with a compatible or incompatible piano soundtrack. Hands size and apparent distance allowed self-ownership and agency illusions, and therefore motor simulation. Event-related potentials (ERPs) and relative source reconstruction showed the presence of an Error-related negativity (ERN) to incongruent trials at anterior frontal scalp sites, only in pianists, with no difference in naïve participants. ERN was mostly explained by an anterior cingulate cortex (ACC) source. Other sources included "hands" IT regions, the superior temporal gyrus (STG) involved in conjoined auditory and visuomotor processing, SMA and cerebellum (representing and controlling motor subroutines), and regions involved in body parts representation (somatosensory cortex, uncus, cuneus and precuneus). The findings demonstrate that instrument-specific audiovisual stimulation is able to trigger error shooting and correction neural responses via motor resonance and mirroring, being a possible aid in learning and rehabilitation., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Purpose: To detect choriocapillaris changes by enhanced depth imaging optical coherence tomography (EDI-OCT) in areas of choriocapillaris hypoperfusion visualized on indocyanine green angiography., Methods: Combined indocyanine green angiography and EDI-OCT from patients diagnosed with inflammatory choriocapillaris hypoperfusion were retrospectively analyzed. The EDI-OCTs were compared with indocyanine green angiography to detect choriocapillaris changes suggestive of choriocapillaris hypoperfusion in both active stage (AS) and inactive stage of the disease. The EDI-OCT was graded by two independent observers for choriocapillaris pattern (normal/altered) and reflectivity (hyper/hypo/isoreflective) changes. Manual measurements of choriocapillaris thickness were obtained. Interobserver agreement was assessed using Cohen's kappa, and differences in groups were assessed using McNemar's test., Results: Forty-two lesions from 11 eyes (8 patients, 3 males) were analyzed. Three patients (4 eyes, 17 lesions) were diagnosed with serpiginous choroiditis, and 5 patients (7 eyes, 25 lesions) were diagnosed with acute posterior multifocal placoid pigmented epitheliopathy. All the lesions demonstrated choriocapillaris hyporeflectivity on EDI-OCT during AS and isoreflectivity during inactive stage. The characteristic choriocapillaris dotted pattern was absent during AS. Choriocapillaris thickness at the sites of hypoperfusion was significantly higher during AS (63.07 ± 16.47 μm) than in inactive stage (22.92 ± 7.65 μm) (P < 0.001). Disruption of retinal pigment epithelium during AS was strongly associated with choriocapillaris atrophy during follow-up (P < 0.001)., Conclusion: The EDI-OCT shows characteristic choriocapillaris changes suggestive of choriocapillaris hypoperfusion that correlate with ischemia on indocyanine green angiography during both AS and inactive stage of the disease.

Purpose: To assess the status of choriocapillaris in eyes with macular atrophy secondary to age-related macular degeneration (AMD) (geographic atrophy [GA]) and Stargardt disease (STGD) using optical coherence tomography angiography (OCTA)., Design: Prospective, observational case series., Participants: A total of 14 patients (20 eyes) affected by GA and 10 patients (20 eyes) affected by STGD., Methods: Each patient underwent a complete ophthalmological examination including fundus autofluorescence (FAF), dynamic simultaneous fluorescein angiography (FA) and indocyanine green angiography (ICGA), enhanced-depth imaging optical coherence tomography (EDI-OCT) (HRA+OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany), and OCTA using AngioVue technologies (Optovue Inc, Freemont, CA)., Main Outcome Measures: An evaluation of the status of choriocapillaris in the 2 groups was performed., Results: Patients' mean age was 75 years for subjects with GA (median, 76 years; range, 63-88 years) and 61 years for STGD (median, 62 years; range, 40-74 years). Atrophy was bilateral in 42% (n = 6) of subjects with GA and 100% (n = 10) of subjects with STGD. In the early frames, FA displayed hyperfluorescence in the atrophic area in 100% (n = 20) of eyes affected by GA and 20% (n = 4) of eyes affected by STGD; dark choroid was present in 0% of GA eyes and 65% of STGD eyes (n = 13). Atrophy in ICGA late frames was hypofluorescent in 20% (n = 4) of GA eyes and 100% (n = 20) of STGD eyes. A ring at atrophy margins was detected in both FA (90%, n = 18) and ICGA (100%, n = 20) in STGD eyes. Mean subfoveal choroidal thickness was 156 μm (147, 42-362 μm) for GA eyes and 168 μm (167, 55-320 μm) for STGD eyes (P = 0.59). At OCTA evaluation, GA eyes showed persisting, rarefied choriocapillaris in correspondence of retinal pigment epithelium (RPE) atrophy in 80% (n = 16) of cases, whereas eyes affected by STGD had disappearance of this tissue in 100% (n = 20; P < 0.0001)., Conclusions: Analysis of macular atrophy by OCTA in patients with STGD revealed an extensive loss of choriocapillaris in the central area with persisting tissue at its margins, whereas in those with GA the area of RPE loss showed persistent but rarefied choriocapillaris., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the feasibility of a telemedical approach for diabetic retinopathy (DR) screening in the Italian population and to evaluate advantages/disadvantages in comparison to standard slit-lamp funduscopic examination (SFE)., Methods: This 1-year, Italian, single-center, observational study evaluated semiautomatic fundus photography (FP) DR screening, performed during routine type 2 diabetes (T2D) systemic visits and examined remotely. Adults with T2D underwent SFE and 3-field FP. The study was divided into 2 stages (stage 1 validated the screening procedure, stage 2 evaluated the screening impact on the clinical practice). Annual costs of SFE ± FP screening were compared. Patients completed a DR screening questionnaire., Results: Of 1,281 T2D patients enrolled, 61% were male (mean age 65.69 ± 12.64 years). In stage 1, 71% and 15% of patients were considered nongradable when FP was performed before (BPD) versus after pupil dilation (APD). The FP specificity was higher with APD vs BPD (79% vs 25%); therefore, FP APD only was used for stage 2. Of 1,281 patients screened using FP APD, 240 (18.7%) had unreadable images; 64.3% did not have DR, and 17.0% were diagnosed with DR. There was a cost saving of €801.25 when screening was performed using FP. Overall, 98% of patients had a positive opinion of FP screening., Conclusions: The telemedicine approach provides a convenient, simple test that is well-received by patients and minimizes unnecessary referrals. Telemedicine may also reduce screening costs in our setting.

Learning to play a musical instrument is a demanding process requiring years of intense practice. Dramatic changes in brain connectivity, volume, and functionality have been shown in skilled musicians. It is thought that music learning involves the formation of novel audio visuomotor associations, but not much is known about the gradual acquisition of this ability. In the present study, we investigated whether formal music training enhances audiovisual multisensory processing. To this end, pupils at different stages of education were examined based on the hypothesis that the strength of audio/visuomotor associations would be augmented as a function of the number of years of conservatory study (expertise). The study participants were violin and clarinet students of pre-academic and academic levels and of different chronological ages, ages of acquisition, and academic levels. A violinist and a clarinetist each played the same score, and each participant viewed the video corresponding to his or her instrument. Pitch, intensity, rhythm, and sound duration were matched across instruments. In half of the trials, the soundtrack did not match (in pitch) the corresponding musical gestures. Data analysis indicated a correlation between the number of years of formal training (expertise) and the ability to detect an audiomotor incongruence in music performance (relative to the musical instrument practiced), thus suggesting a direct correlation between knowing how to play and perceptual sensitivity.

Burkitt lymphoma (BL) is a highly aggressive B cell neoplasm. Although intensive polychemotherapy regimens have proven very effective, they are associated with significant toxicities. Therefore, more rational therapies that selectively target the molecular abnormalities of BL are needed. Recent data suggest that the tyrosine kinase SRC could represent a therapeutic target for BL. We found that new pyrazolo[3,4-d]pyrimidine SRC inhibitors exerted a significant cytotoxic effect and induced apoptosis on two BL cell lines, as determined by MTS assays, cytofluorimetric analyses and caspase 3 assay. Notably, our SRC inhibitors proved to be more effective than the well-known SRC inhibitor PP2 [4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine] in BL cells. Moreover, our small molecules induced a G 2/M arrest in BL cells through a possible new mechanism, whereby SRC inhibition hinders an AKT-WEE1-cyclin-dependent kinase 1 (CDK1) axis, leading to inhibition of CDK1, the main trigger of entry into mitosis. By using a small-molecule inhibitor of WEE1, a crucial CDK1 negative regulator, we were able to shift the balance toward apoptosis rather than growth arrest and enhance the efficacy of the SRC inhibitors, suggesting a possible use of these selective drugs in combination for a safe and efficient treatment of BL.

Medulloblastoma is the most common malignant brain tumor in children, and despite improvements in the overall survival rate, it still lacks an effective treatment. Src plays an important role in cancer, and recently high Src activity was documented in medulloblastoma. In this report, we examined the effects of novel pyrazolo-[3,4-d]-pyrimidine derivative Src inhibitors in medulloblastoma. By MTS assay, we showed that the pyrimidine derivatives indicated as S7, S29, and SI163 greatly reduce the growth rate of medulloblastoma cells by inhibiting Src phosphorylation, compared with HT22 non-neoplastic nerve cells. These compounds also halt cells in the G(2)/M phase, and this effect likely occurs through the regulation of cdc2 and CDC25C phosphorylation, as shown by Western blot. Moreover, the exposure to pyrimidine derivatives induces apoptosis, assayed by the supravital propidium iodide assay, through modulation of the apoptotic proteins Bax and Bcl2, and inhibits tumor growth in vivo in a mouse model. Notably, S7, S29, and SI163 show major inhibitory effects on medulloblastoma cell growth compared with the chemotherapeutic agents cisplatin and etoposide. In conclusion, our results suggest that S7, S29, and SI163 could be novel attractive candidates for the treatment of medulloblastoma or tumors characterized by high Src activity.

Objective: In marathon runners changes in red blood cell count, haematocrit and haemoglobin in relation to haemodilution have been reported. Moreover, it has been hypothesized that strenuous exercise induces oxidant stress through several different mechanisms. This study investigated the haematological variables, iron status and oxidative indices before, immediately and 48 h after a race in 8 healthy trained males aged 33-44 years running a 21-km marathon in 79 +/- 3 min., Methods: The haematological parameters were determined by standard procedures. Erythropoietin and soluble-transferrin receptor were evaluated immunoenzymatically. Nontransferrin-bound iron (NTBI) was assayed by high-performance liquid chromatography after nitrilotriacetic acid chelation. Malonyldialdehyde (MDA) concentration was assayed colorimetrically., Results: The total number of reticulocytes rose significantly after the run with a significant increase in the high-RNA-content fraction (14 +/- 5, p < 0.0006). Erythropoietin rose by 26% (15.0 +/- 2.8 mU/ml, p < 0.004) and by 25% (14.9 +/- 2.13 mU/ml, p < 0.02) immediately and 48 h after the race, respectively. Serum iron and serum ferritin remained unchanged but NTBI and serum MDA increased significantly immediately after running (1.16 +/- 0.40 mmol/l, p < 0.0008; 0.76 +/- 0.16 mmol/l, p < 0.0001). Significant positive correlations at any time between MDA and polymorphonuclear neutrophils (p = 0.0005), MDA and NTBI (p = 0.0018), polymorphonuclear neutrophils and NTBI (p = 0.0008) and between lactate dehydrogenase and NTBI (p = 0.0212) were observed., Conclusions: The erythropoietic changes observed in marathon runners are the results of several interacting mechanisms that involve either the haemopoietic system per se or erythrocyte haemolysis and oxidative stress.

This study describes the prevalence rate of overweight and thinness in a population of teens living in two different areas of Italy and explores the body self-image perception and unhealthy eating behaviours and strategies to lose weight. A questionnaire was administered to a sample of 2,121 teenage students (1,084 males, 1,037 females). Results showed that teen females and males build and perceive their body images in very different ways. Most of the overall sample perceived their weight as normal, while a relevant 31.6% defined themselves as overweight and another 4.4% as heavily overweight. Analysis based on BMI (calculated through self-referred weight and height) showed that only 9.2% of our sample could be considered overweight and 1.7% obese. Most of female teen students (485 out of 1,037) were trying to lose weight, demonstrating that strategies to lose weight were undertaken also by girls perceiving themselves as normal in relation to body weight. 46.8% girls were using strategies to lose weight compared with 21.9% boys. These strategies included very problematic behaviours like self-induced vomiting (3.3% F vs 1.7% M) and dieting pills (2.8% F vs 1.5% M) undertaken along with more usual thinning strategies like dieting and exercising. Girls were more prone than boys to exercise as a way to lose weight (41% vs 31.7%). This study showed that there is a deep gap between actual weight and perceived body-image and weight. This study is one of the first of this kind in Italy and calls for primary prevention and health education programs aimed at improving teen body-image as a strategy to reduce the eating disorder epidemics spreading among young people.

In this study 1656 Gorgonzola cheeses, collected from October 2003 to April 2004 in the same industrial plant located in Lombardia (Italy), were analysed in order to evaluate their level of contamination with Listeria monocytogenes after packaging, as well as at the end of the shelf life. A subset of Gorgonzola isolates was submitted to automated EcoRI ribotyping to evaluate their DUP-IDs (DuPont identification library code) and their level of genetic diversity. The isolate ribotyping profiles were included in an on-line database named PathogenTracker database. The strain DUP-IDs and the similarities between Gorgonzola isolates and PathogenTracker human sporadic strains allowed to evaluate the potential virulence of Gorgonzola-associated strains. The L. monocytogenes detection rates observed in the cheese samples monitored after packaging and at the end of the shelf life were 2.1% and 4.8%, respectively. Seventy percent of the strains genotyped were classified in the same ribotype, labelled as 204 S5, indicating that L. monocytogenes population associated to Gorgonzola cheese shows a low level of genetic diversity. Ninety percent of the strains were classified in DUP-IDs belonging to the II pathogenicity lineage identified for L. monocytogenes. That lineage includes serotype 1/2a, 1/2c and 3c strains, associated to the 35% of the human sporadic isolates described in the literature as causing listeriosis. Moreover, 16.7% of Gorgonzola isolates showed a similarity >or=99% with PathogenTracker human sporadic strains. The results of this study showed that the incidence of L. monocytogenes in Gorgonzola cheeses commercialised by the plant tested was lower than that observed in other Italian blue-veined cheeses by other authors. However, it increased during cheese storage and it become double at the end of the cheese shelf life, ranging from 30 to 60 days after packaging.

A method for quantitative analysis of platelet deposition under flow is discussed here. The model system is based upon perfusion of blood platelets over an adhesive substrate immobilized on a glass coverslip acting as the lower surface of a rectangular flow chamber. The perfusion apparatus is mounted onto an inverted microscope equipped with epifluorescent illumination and intensified CCD video camera. Characterization is based on information obtained from a specific image analysis method applied to continuous sequences of microscopical images. Platelet recognition across the sequence of images is based on a time-dependent, bidimensional, gaussian-like pdf. Once a platelet is located,the variation of its position and shape as a function of time (i.e., the platelet history) can be determined. Analyzing the history we can establish if the platelet is moving on the surface, the frequency of this movement and the distance traveled before its resumes the velocity of a non-interacting cell. Therefore, we can determine how long the adhesion would last which is correlated to the resistance of the platelet-substrate bond. This algorithm enables the dynamic quantification of trajectories, as well as residence times, arrest and release frequencies for a high numbers of platelets at the same time. Statistically significant conclusions on platelet-surface interactions can then be obtained. An image analysis tool of this kind can dramatically help the investigation and characterization of the thrombogenic properties of artificial surfaces such as those used in artificial organs and biomedical devices.

Aim: The study evaluates the efficacy of a set of objective parameters for monitoring facial swelling in a group of patients treated with clarithromycin., Methods: Fifty consecutive patients suffering from dental abscesses (22 in the maxillary arch and 28 in the mandibular arch) were enrolled. All these patients underwent antibiotic treatment with clarithromycin in a new formulation as a single daily dose (500 mg/day for 6 days). Pain and changes in facial swelling were evaluated at baseline and each day for 6 days through subjective parameters (visual analogic scale, VAS) and objective parameters (6 different tape measurements on the skin surface above the abscess)., Results: Pain and swelling recorded by patient and dentist (using VAS scores) showed statistically significant decreases (p<0.01) on days 2, 3 and 4, while no further significant variation was observed during days 4, 5 or 6. As regards the objective parameters to quantify facial swelling, the maximum dimensional change (from baseline to final values) in the mandibular arch was obtained with measurement 6 (mean value 2.27+/-0.53 cm); the maximum dimensional change in the maxillary arch was obtained with the sum of the other 5 measurements (mean value 6.34+/-4.09 cm)., Conclusion: The use of a single or a combination of linear measurements might provide a sensitive and reproducible method to evaluate facial swelling objectively and could be very useful in monitoring the efficacy of new antibiotics and to compare the results from different studies.

We describe herein a novel in vitro approach that can be used effectively to obtain valuable insights into the role of platelets, various coagulation proteins as well as proteins of the subendothelial extracellular matrix involved in the hemostatic and thrombotic processes occurring under microgravity. At difference with other experimental approaches proposed in the past our device operates in a closed system and under different shear forces, which better mimics flow conditions occurring in vessels. Furthermore our device by allowing real time monitoring of the thrombotic process and its underlying mechanisms can be regarded as a reliable system for the precise assessment of platelet function.

A group of 1.085 students (582 M, 503 F) attending high school (742) and nursing school (343) filled in an anonymous questionnaire on their sexual habits and their knowledge of contraception and sexually transmitted diseases. Overall, 57% of the study population had already a complete sexual intercourse at a mean age of 16,4 (SD +/- 1,8). 74% had 1-3 sexual partners, whereas 28% had more than 3. All students affirmed that it was possible to prevent sexually transmitted diseases and 92,6% indicated correct methods. However 10% of students did not know that AIDS is transmitted sexually as 47% hepatitis B. The responses made by nursing students were more correct that those of high school students.

Familial hypertension, glomerular hemodynamic alterations, and dysregulation of tubulo-glomerular feedback (TGFB) have all been associated with the development of chronic renal failure. In the present study we evaluated renal and glomerular hemodynamics and TGFB responses in healthy kidney donors either with or without familial hypertension, before and after nephrectomy. Para-amino-hippurate plasma clearance (CPAH) and inulin plasma clearance (CInu) were measured in 15 kidney donors before and 1 year after nephrectomy. All subjects were normotensive and were kept in a sodium-replete state. Both clearances were measured after 40 min of constant infusion of PAH and Inu, as well as 20, 30, 50, and 60 min after the intravenous administration of acetazolamide (5 mg/kg). Glomerular hemodynamics were calculated by means of the Gomez formulae. Nephrectomy caused the expected decreases in CPAH and CInu and increase in the filtration fraction (all P < .0001). The decrease in renal resistances of the remaining kidney was greater at the afferent (-24%, P = .0075) than at the efferent arteriolar level (-17%, P < .0001). The TGFB activation was not altered by nephrectomy or by familial hypertension. Effective renal plasma flow (ERPF) decrease after TGFB activation appeared earlier than glomerular filtration rate (GFR) decrease before (P = .01), but not after, nephrectomy (P = .48). The presence of familial hypertension was associated with increased glomerular pressure (P = .0004). This study suggests that uninephrectomy in healthy human subjects causes a greater decrease in afferent arteriolar resistances, but that TGFB responses are not quantitatively altered. Familial hypertension is associated with a tendency toward higher glomerular pressures.

Primary effusion lymphoma (PEL) is a peculiar B-cell lymphoma characterized by infection by human herpesvirus type-8/Kaposi sarcoma-associated herpesvirus (HHV-8/KSHV) and by preferential growth in the serous body cavities. Histogenetic studies have suggested that PEL originates from B cells at a late stage of differentiation. In this study, we have investigated PEL for the expression status of MUM1/IRF4 (multiple myeloma 1/interferon regulatory factor 4) protein, which is involved in physiological B-cell maturation and represents a histogenetic marker of late B-cell differentiation. Using multiple detection assays, all cases of PEL (n = 22) were found to express MUM1/IRF4 molecules. MUM1/IRF4 expression was a selective feature of PEL among lymphomas involving the serous body cavities as secondary lymphomatous effusions generally failed to express the protein. In reactive lymphoid tissues, MUM1/ IRF4 expression clustered with advanced stages of B-cell differentiation. Comparison of MUM1/IRF4 expression with that of other histogenetic markers defined two phenotypic variants of PEL, i.e. MUM1/IRF4+, CD138/syndecan-1+, B-cell antigen- (20 out of 22 cases) and MUM1/IRF4+, CD138/syndecan-1-, B-cell antigen+ (2 out of 22 cases), suggesting a certain degree of heterogeneity in the disease histogenesis. The implications of these data are threefold. First, MUM1/IRF4 expression corroborates the notion that PEL originates from post-germinal centre, preterminally differentiated B-cells. Second, MUM1/IRF4 may help in the differential diagnosis of PEL among other lymphomas involving the serous body cavities. Finally, MUM1/IRF4 may interact with HHV-8/KSHV-encoded interferon regulatory factors (IRFs) and thus contribute to PEL escape from interferon-mediated control of viral infection.

It is believed that angiotensin converting-enzyme (ACE) inhibitors lower proteinuria by acting on glomerular hemodynamics. This hypothesis predicts that the urinary excretion of a tubular protein should be unaffected by ACE inhibition. In the present study we have compared the excretion of albumin and Tamm-Horsfall Glycoprotein (THGP), a protein secreted only by renal tubules, before and after ACE inhibition. Urinary protein excretion was measured with the Phast System, a method based on SDS polyacrylamide gel electrophoresis followed by silver staining, in 15 essential hypertensives, after at least 4 weeks of wash-out from any drug and after 2 months of ACE inhibition with oral Quinapril. After 2 months of ACE inhibition, blood pressure (BP), body weight, urinary output, heart rate, plasma glucose, plasma and urinary creatinine, urate and electrolytes, and creatinine clearance, were not different from baseline values. Plasma ACE activity decreased from 76 +/- 7 to 10 +/- 4 U/mL (mean +/- SEM, 2 tails paired t test, p = 0.0001). Both albumin and THP urinary excretions decreased from 51 +/- 6 to 43 +/- 4 mg/ 24 h (p = 0.05) and from 19 +/- 3 to 12 +/- 1 mg/24 h (p = 0.02), respectively. This unexpected result suggests that ACE inhibitors may act also at the level of renal tubular cells.

Primary lymphomatous effusions are represented by cases of non-Hodgkin's lymphoma (NHL) which grow in liquid phase in the serous body cavities in the absence of solid tumour masses. Based on morphologic, immunophenotypic, virologic and genotypic features, primary lymphomatous effusions are distinguished into body cavity-based lymphoma (BCBL), Burkitt's lymphoma (BL) and immunoblastic large-cell lymphoma. The histogenesis and pathogenesis of primary lymphomatous effusions are virtually unclarified. In this study, we have established 2 cell lines (CRO-AP/1 and CRO-AP/2) representative of 2 distinct categories of primary lymphomatous effusion, BCBL (CRO-AP/2) and BL (CRO-AP/1). Both CRO-AP/1 and CRO-AP/2 carry monoclonal re-arrangements of the immunoglobulin genes which are identical to those of the respective parental tumours. Consistent with its BCBL origin, CRO-AP/2 is characterised by a non-B, non-T phenotype and harbours infection by HHV-8 (approx. 100 viral copies/cell) and Epstein-Barr virus. Conversely, CRO-AP/1 expresses several B cell-associated antigens, lacks HHV-8 infection and carries the genetic hallmark of BL, i.e., a chromosomal breakpoint of band 8q24. CRO-AP/1 and CRO-AP/2 may be valuable for the biologic characterization of primary lymphomatous effusions, particularly since the number of available cell lines derived from such lymphomatous effusions is extremely limited.

CD40 is a membrane glycoprotein expressed on normal and neoplastic B lymphocytes. Stimulation through CD40 regulates important cellular functions, but the effects depend on its membrane density. While extensive studies have characterized CD40 in non-Hodgkin lymphomas of immunocompetent individuals, little is known on the characteristics of this molecule in lymphomas arising in immunocompromised hosts. The aim of this study was to characterize the pattern of CD40 expression in an in vitro model constituted by AIDS small non-cleaved lymphoma (SNCCL) cell lines. The analysis of CD45 isoforms, a group of molecules alternatively spliced during B cell differentiation, has been chosen to correlate this process to the number of CD40 molecules per cell in these cell lines. Since Apo 1/Fas expression is upregulated on B lymphocytes after CD40 ligation and this expression is functionally relevant, we wanted to know whether a different CD40 pattern in AIDS-SNCCL cell lines could influence CD95 expression. We have shown that 3 of these cell lines (PA 682, Es III, and HBL-2) have high membrane CD40 expression (> 100,000 molecules/cell); they release large amounts of soluble CD40 (sCD40) in culture supernatants (>500 pg/ml), are CD45RA/RO double labelled, and express the Apo 1/Fas (CD95) antigen. On the contrary, low CD40 membrane antigen cell lines (BRGIgA, HBL-2, NC 71, AS 283A, and LAM C3+, < 50,000 molecules/cell) release low amounts of sCD40 (<300 pg/ml), are CD45RA+ but CD45RO-, and do not express CD95. EBV has no role in CD40 and CD45 isoform behaviour, because EBV superinfection of the EBV negative, low membrane CD40 HBL-2 cell line does not modify CD40 membrane expression, sCD40 production, or CD45 isoform and CD95 expression. Our data suggest that membrane CD40 in AIDS-SNCCL cell lines might be a key element in the regulation of their pathophysiology by influencing the expression of CD45 isoforms and of CD95, and by the release of its soluble form.

Acquired abnormalities of red cell membrane protein composition in 37 patients with a positive direct antiglobulin test have been studied: 17 patients had true autoimmune haemolytic anaemia and 20 were HIV-infected subjects with a positive direct antiglobulin test but without signs of haemolysis. The study was carried out by performing sodium dodecyl sulphate polyacrylamide gel electrophoresis of ghost proteins followed by densitometric evaluation of the areas under the peaks, normalized by the total (alpha + beta) spectrin content. Results show a significant decrease of bands 3, 4.1 and 4.2 over spectrin in patients with autoimmune haemolysis as compared to controls; at least in a small subset of patients, different specificities recognized by autoantibodies do not seem to account for these abnormalities which are reproducible independently from the molecular size of bands immunoprecipitated by autoantibodies. A similar decrease of protein 4.2 but not of band 3 staining intensity is also noticeable in HIV patients with a positive direct antiglobulin test. These results are consistent with the hypothesis that, following interactions between autoantibodies and autoantigens, modifications occur on membrane proteins resembling a variety of quantitative defects described in inherited haemolytic anaemias, and mainly the "vertical interaction defects' of hereditary spherocytosis. Moreover, the decrease of band 3 staining intensity seems to represent a feature of patients with immune mediated haemolysis and not only with autoantibody binding.

The mechanism of (&mgr;-H)(&mgr;-alkenyl)Re(2)(CO)(8) formation upon UV irradiations of Re(2)(CO)(10) in presence of olefin (styrene, trans-stilbene, 4-methyl-1-cyclohexane, and ethylene) was investigated by laser flash photolyses. Such photoproducts result from reactions of the olefin with eq-Re(2)(CO)(9). No reactions of Re(CO)(5) leading to hydride alkenyl products were observed. Dependences of the reaction rate on olefin concentration and solvent revealed an additional intermediate formed after the addition of the olefin to eq-Re(2)(CO)(9) and before the appearance of the &mgr;-hydrido-&mgr;-alkenyl products.

Bone remodeling requires cooperation between osteoclasts and other specialized or accessory bone cell populations by mechanisms that have not been completely elucidated. Here we describe the expression and functional role of the proto-oncogene c-kit and of its specific ligand stem cell factor (SCF) on human osteoclasts, osteoblasts, and stromal cells derived from different sources. Our results indicate that primary osteoclasts in imprints of metaphyseal bone and giant cell tumors (GCTs) of bone, as well as a bone marrow-derived preosteoclast cell line of human origin (FLG 29.1), expressed immunodetectable c-kit protein. In contrast, tissue osteoclasts did not react with anti-SCF antibodies, and barely detectable levels of SCF mRNA and protein were found in FLG 29.1 cells. Conversely, a strong expression of membrane bound-SCF was found in primary cultured bone marrow stromal cells, in a stromal cell line (C433) derived from the mononuclear component of GCT of bone, and in a human cell line with osteoblast features (Saos-2). FLG 29.1 preosteoclast cells displayed about 29,000 binding sites/cell of a single class of high affinity c-kit receptors (Kd 6.12 x 10(-10) mol/L) with a molecular weight of about 140 kDa, along with a structurally normal c-kit mRNA. Proliferation of FLG 29.1 preosteoclast cells was stimulated by exogenous SCF, indicating that c-kit was capable of transducing growth signals. Finally, in vitro adhesion of FLG 29.1 cells to primary bone marrow stromal cells, GCT-derived stromal cells (C433), and Saos-2 osteoblast cells was significantly inhibited by an excess of soluble SCF or by monoclonal antibodies recognizing SCF binding sites on the c-kit receptor. These results indicate that c-kit is constitutively expressed on human osteoclasts and that it may be directly implicated in cell contact-dependent interaction of osteoclasts with other specialized or accessory cell populations of the bone microenvironment. Our observations suggest a role for SCF in human diseases characterized by abnormal bone resorption and remodeling.