Serum proteins profile in Comisana lambs during the first month of life

Abstract. The aim of the present study was to measure the serum total proteins and the serum protein fractions (albumin, α1-, α2-, β-, and γ- globulins) of ten newborn lambs (Comisana breed) during the first 30 days of life in order to obtain useful information for neonatal care. From each animal, blood samples were collected via jugular venipuncture at the same hour (9.00) every 3 days for 30 days starting from birth (day 0). The concentrations of serum total proteins and albumin, α1-, α2-, β-, γ- globulins, and Albumin/Globulins (A/G) ratio were determined using an automated electrophoresis system. One-way repeated measures analysis of variance (ANOVA), followed by Bonferroni's test, was used to determine significant differences between mean values of the studied parameters from the 1st to the 30th day of the experimental period. Data analysis of variance showed a statistical effect of days of life on total proteins, albumin, α1-globulins, β-globulins, γ-globulins and ratio A/G during the first 30 days of life (P<0.0001), while no statistical significant effect of days of life was observed on α2-globulins during the experimental period (P=0.27). The obtained results indicated that passive transfer status, determined from serum immunoglobulin concentration 24 hours after birth, is a significant source of variation in preweaning growth performance in dairy lambs. These finding make a contribution to the knowledge of physiological adaptation in lambs during the first 30 days of life and give useful information for the diagnosis and treatment of neonatal diseases

Levels of serum osteocalcin and some electrolytes in foal during the first six months of life (Brief Report)

Abstract. Bone is a dynamic tissue characterized by continuous bone formation and bone resorption. The transformation of the primordial part of the long bones (the cartilaginous matrix during the embryonal period) into the definitive bone (lamellar bone tissue) is completed after puberty. Osteocalcin, also called the vitamin k-dependent protein of bone and synthesized predominantly by osteoblasts and in lower way by odontoblasts, is incorporated into the extracellular matrix of bone (LEPAGE et al. 2001) and it may function as a useful indicator of the equine bone growth rate which decreases considerably with age. In particular, osteocalcin or bone Gla-protein is a small abundant non-collagenous calcium binding protein, indigenous to the organic matrix of bone dentin and possibly other mineralized tissue, which circulates in the blood (LEPAGE et al. 1991). It is accepted as a marker of osteoblast activity (RISTELI and RISTELI 1993) and plays a not yet defined role in the regulation of bone turnover (BOSKEY et al. 1998)

New and developing therapies for AL amyloidosis

INTRODUCTION: Systemic light-chain (AL) amyloidosis is an infiltrative disorder associated with an underlying plasma cells dyscrasia, in which monoclonal immunoglobulin light chains accumulate in an abnormal misfolded form as amyloid fibrils in the extracellular space. Symptoms and prognosis are governed by which organs are affected, and cardiac involvement is the major determinant of survival. Diagnosis requires demonstration of amyloid deposition and confirmation of the fibril protein type. AREAS COVERED: This review will focus on the available treatments for systemic AL amyloidosis and on new drug targets and therapeutic approaches. EXPERT OPINION: At present, the choice of upfront treatment lies between autologous stem cell transplantation (ASCT) and combination chemotherapy. Chemotherapy agents include dexamethasone, melphalan, cyclophosphamide, thalidomide, bortezomib, lenalidomide, bendamustine in various combinations. Few randomized controlled trials have been performed in AL amyloidosis and treatment has been substantially influenced by clinical practice in myeloma. It has become clear that the best prospects of survival and preservation or improvement in amyloid related organ function require as near complete suppression as possible of the underlying hematological disorder. Future directions include therapies designed to target amyloid deposits directly, in particular anti-amyloid antibodies which are now well advanced in development and are showing great potential

Genome wide analyses reveal the population distinctiveness of the ‘Nera del Mela’ sheep

Italy has a long history of sheep breeding and counts several local populations that may represent a unique source of genetic diversity. Among these, Nera del Mela is a sheep genetic resource historically reared in Sicily but not officially recognised as a breed. In this study, we genotyped 36 individuals of Nera del Mela using the OvineSNP50K array, in order to estimate the genetic diversity and evaluate the population structure and relatedness with other Italian sheep breeds. Genetic diversity indices, and inbreeding estimated from runs of homozygosity (FROH) revealed a moderate level of variability. Runs of homozygosity islands mapped candidate genes involved in the adaptation to local environment and immune response. Population genetic analyses using different approaches highlighted the hypothesis that this sheep possesses a defined genetic structure, especially if compared with other recognised breeds, despite the influence of other populations such as the Sicilian breeds. Overall, our findings represent a starting point for the possible official acknowledgement of this population, for the creation of a conservation plan, and thus for preserving this genomic heritage.HIGHLIGHTS Nera de Mela sheep can be considered as a reservoir of genetic diversity. The results indicated a clear genetic differentiation from other populations and moderate level of genetic variability. Our findings represent a starting point for the creation of conservation plans

Autonomic abnormalities in patients with primary Sjogren&#8217;s syndrome &#8211; Preliminary results

Primary Sjogren's syndrome (pSS) is an autoimmune disease affecting exocrine glands and extra-glandular organs. There are conflicting reports on the presence of autonomic dysfunction in pSS and no data are available on the functional status of sympathetic outflow to the vessels and baroreceptor [baroreflex sensitivity (BRS)] control mechanisms. We investigated the cardiac (cBRS) and sympathetic (sBRS) baroreceptor modulation in both time and frequency domains and the cardiovascular autonomic profile in pSS patients compared to healthy controls. Autonomic symptoms were quantified by the Composite Autonomic Symptom Scale (COMPASS31) three-item questionnaire. The EULAR Sjogren's syndrome patient reported index (ESSPRI) questionnaire evaluated the magnitude of pSS clinical symptoms, i.e., fatigue, pain, and sicca symptoms. Electrocardiogram, beat-by-beat arterial pressure (AP) and respiratory activity were continuously recorded in 17 pSS patients and 16 healthy controls, while supine and during 75 degrees head-up tilt. In seven patients and seven controls, muscle sympathetic nerve activity (MSNA) was measured. Spectrum analysis of RR variability provided markers of cardiac vagal modulation (HFRR nu) and sympatho-vagal balance [low frequency (LF)/high frequency (HF)]. The power of LF (0.1 Hz) oscillations of systolic arterial pressure (SAP) variability (LFSAP) evaluated the vasomotor response to sympathetic stimulation. Compared to controls, pSS patients scored higher in total COMPASS31 (p &lt; 0.0001) and all ESSPRI subdomains (fatigue, p = 0.005; pain, p = 0.0057; dryness, p &lt; 0.0001). Abnormal scialometry (&lt;1.5 ml/15 min) and Schirmer tests (&lt;5 mm/5 min) were found in pSS patients and salivary flow rate was negatively associated with ESSPRI dryness (p = 0.0014). While supine, pSS patients had lower SEQ(cBRs) index of cardiac baroreceptor sensitivity, higher HFRRnu (p = 0.021), lower LF/HF (p = 0.007), and greater MSNA (p = 0.038) than controls. No differences were observed in LFSAP between groups. During orthostatic challenge, although LFSAP increased similarly in both groups, MSNA was greater in pSS patients (p = 0.003). At rest pSS patients showed lower cBR control and greater parasympathetic modulation. Furthermore, greater sympathetic nerve activity was observed in pSS patients while supine and in response to gravitational challenge. We hypothesized that such enhanced sympathetic vasoconstrictor activity might reflect an attempt to maintain blood pressure in a setting of likely reduced vascular responsiveness

Development and validation of the student attitudes and beliefs about authorship scale: a psychometrically robust measure of authorial identity

One approach to plagiarism prevention focuses on improving students’ authorial identity, but work in this area depends on robust measures. This paper presents the development of a psychometrically robust measure of authorial identity - the Student Attitudes and Beliefs about Authorship Scale. In the item generation phase, a pool of items was developed and assessed for content validity by subject matter experts. In the exploratory phase, data from 439 higher education students were used to identify a latent variable model with three factors: ‘authorial confidence’, ‘valuing writing’ and ‘identification with author’. In the confirmatory phase, data from 306 higher education students were used to test the three-factor model's reliability and validity. The three-factor structure was confirmed, and the results showed the SABAS has a stronger psychometric basis than previously available measures. This measure of authorial identity can be used with confidence in research and pedagogy to help students improve their authorial identity

Cardiac Structural and Functional Consequences of Amyloid Deposition by Cardiac Magnetic Resonance and Echocardiography and Their Prognostic Roles

OBJECTIVES: This cross-sectional study aimed to describe the functional and structural cardiac abnormalities that occur across a spectrum of cardiac amyloidosis burden and to identify the strongest cardiac functional and structural prognostic predictors in amyloidosis using cardiac magnetic resonance (CMR) and echocardiography. BACKGROUND: Cardiac involvement in light chain and transthyretin amyloidosis is the main driver of prognosis and influences treatment strategies. Numerous measures of cardiac structure and function are assessed by multiple imaging modalities in amyloidosis. METHODS: Three hundred twenty-two subjects (311 systemic amyloidosis and 11 transthyretin gene mutation carriers) underwent comprehensive CMR and transthoracic echocardiography. The probabilities of 11 commonly measured structural and functional cardiac parameters being abnormal with increasing cardiac amyloidosis burden were evaluated. Cardiac amyloidosis burden was quantified using CMR-derived extracellular volume. The prognostic capacities of these parameters to predict death in amyloidosis were assessed using Cox proportional hazards models. RESULTS: Left ventricular mass and mitral annular plane systolic excursion by CMR along with strain and E/e' by echocardiography have high probabilities of being abnormal at low cardiac amyloid burden. Reductions in biventricular ejection fractions and elevations in biatrial areas occur at high burdens of infiltration. The probabilities of indexed stroke volume, myocardial contraction fraction, and tricuspid annular plane systolic excursion (TAPSE) being abnormal occur more gradually with increasing extracellular volume. Ninety patients (28%) died during a median follow-up of 22 months (interquartile range: 10 to 38 months). Univariable analysis showed that all imaging markers studied significantly predicted outcome. Multivariable analysis showed that TAPSE (hazard ratio: 1.46; 95% confidence interval: 1.16 to 1.85; p < 0.01) and indexed stroke volume (hazard ratio: 1.24; 95% confidence interval: 1.04 to 1.48; p < 0.05) by CMR were the only independent predictors of mortality. CONCLUSIONS: Specific functional and structural abnormalities characterize different burdens of cardiac amyloid deposition. In a multimodality imaging assessment of a large cohort of amyloidosis patients, CMR-derived TAPSE and indexed stroke volume are the strongest prognostic cardiac functional markers

Observing response processes with eye tracking in international large-scale assessments: evidence from the OECD PIAAC assessment

This paper reports on a pilot study that used eye tracking techniques to make detailed observations of item response processes in the OECD Programme for the International Assessment of Adult Competencies (PIAAC). The lab-based study also recorded physiological responses using measures of pupil diameter and electrodermal activity. The study tested 14 adult respondents as they individually completed the PIAAC computer-based assessment. The eye tracking observations help to fill an ‘explanatory gap’ by providing data on variation in item response processes that are not captured by other sources of process data such as think aloud protocols or computer-generated log files. The data on fixations and saccades provided detailed information on test item response strategies, enabling profiling of respondent engagement and response processes associated with successful performance. Much of that activity does not include the use of the keyboard and mouse, and involves ‘off-screen’ use of pen and paper (and calculator) that are not captured by assessment log-files. In conclusion, this paper points toward an important application of eye tracking in large-scale assessments. This includes insights into response processes in new domains such as adaptive problem-solving that aim to identify individuals’ ability to select and combine resources from the digital and physical environment

Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis

Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration1,2. This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2)3 in mature human endothelial cells cultured in a serum-free three-dimensional matrix composed of a mixture of laminin, entactin and type-IV collagen (LEC matrix) ‘resets’ these endothelial cells to adaptable, vasculogenic cells, which form perfusable and plastic vascular plexi. Through chromatin remodelling, ETV2 induces tubulogenic pathways, including the activation of RAP1, which promotes the formation of durable lumens4,5. In three-dimensional matrices—which do not have the constraints of bioprinted scaffolds—the ‘reset’ vascular endothelial cells (R-VECs) self-assemble into stable, multilayered and branching vascular networks within scalable microfluidic chambers, which are capable of transporting human blood. In vivo, R-VECs implanted subcutaneously in mice self-organize into durable pericyte-coated vessels that functionally anastomose to the host circulation and exhibit long-lasting patterning, with no evidence of malformations or angiomas. R-VECs directly interact with cells within three-dimensional co-cultured organoids, removing the need for the restrictive synthetic semipermeable membranes that are required for organ-on-chip systems, therefore providing a physiological platform for vascularization, which we call ‘Organ-On-VascularNet’. R-VECs enable perfusion of glucose-responsive insulin-secreting human pancreatic islets, vascularize decellularized rat intestines and arborize healthy or cancerous human colon organoids. Using single-cell RNA sequencing and epigenetic profiling, we demonstrate that R-VECs establish an adaptive vascular niche that differentially adjusts and conforms to organoids and tumoroids in a tissue-specific manner. Our Organ-On-VascularNet model will permit metabolic, immunological and physiochemical studies and screens to decipher the crosstalk between organotypic endothelial cells and parenchymal cells for identification of determinants of endothelial cell heterogeneity, and could lead to advances in therapeutic organ repair and tumour targeting

Extracellular volume with bolus-only technique in amyloidosis patients: Diagnostic accuracy, correlation with other clinical cardiac measures, and ability to track changes in amyloid load over time

BACKGROUND: Extracellular volume (ECV) by T1 mapping requires the contrast agent distribution to be at equilibrium. This can be achieved either definitively with a primed contrast infusion (infusion ECV), or sufficiently with a delay postbolus (bolus-only ECV). For large ECV, the bolus-only approach measures higher than the infusion ECV, causing some uncertainty in diseases such as amyloidosis. PURPOSE: To characterize the relationship between the bolus-only and current gold-standard infusion ECV in patients with amyloidosis. STUDY TYPE: Bolus-only and infusion ECV were prospectively measured. POPULATION: In all, 186 subjects with systemic amyloidosis attending our clinic and 23 subjects with systemic amyloidosis who were participating in an open-label, two-part, dose-escalation, phase 1 trial. FIELD STRENGTH: Avanto 1.5T, Siemens Medical Solutions, Erlangen, Germany. ASSESSMENT: Bolus-only and infusion ECV were measured in all subjects using shortened modified Look-Locker inversion recovery (ShMOLLI) T1 mapping sequence. STATISTICAL TESTS: Pearson correlation coefficient (r); Bland-Altman; receiver operating characteristic (ROC) curve analysis. Linear regression model with a fractional polynomial transformation. RESULTS: The difference between the bolus-only and infusion myocardial ECV increased as the average of the two measures increased, with the bolus-ECV measuring higher. For an average ECV of 0.4, the difference was 0.013. The 95% limits of agreement for the two methods, after adjustment for the bias, were ±0.056. However, cardiac diagnostic accuracy was comparable (bolus-only vs. infusion ECV area under the curve [AUC] = 0.839 vs. 0.836), as were correlations with other clinical cardiac measures, and, in the trial patients, the ability to track changes in the liver/spleen with therapy. DATA CONCLUSION: In amyloidosis, with large ECVs, the bolus-only technique reads higher than the infusion technique, but clinical performance by any measure is the same. Given the work-flow advantages, these data suggest that the bolus-only approach might be acceptable for amyloidosis, and might support its use as a surrogate endpoint in future clinical trials. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017