Comparative analysis of a portable smartphone­based electrocardiograph (D­Heart®) versus standard 6­leads electrocardiograph in the canine patient.

D-Heart® is a portable, smartphone-based device, which streams tracing via Bluetooth, enabling multiple leads electrocardiograms (ECGs) acquisition, currently used in human cardiology (Maurizi et al. 2017).The aim was to determine the accuracy of D­Heart® compared with the gold standard non­portable 6­lead electrocardiograph in the evaluation of cardiac rhythm in dogs.Standard 6­lead and D­Heart® ECGs were acquired in conscious dogs. Concordance between methods was assessed by weighted k Cohen index, with its relative significance, taking as end point variable standard 6­lead ECG group. Bland ­ Altman method (95% confidence level) was applied for P, PR, QRS, T and QT. Since differences didn’t follow a normal distribution, a non­parametric approach was used to determine limits of agreement. P was significant when < 0.05 (Maurizi et al. 2017). Amplitude of waves was not considered because currently the software doesn’t allow voltage variation.115 dogs of different weights and breeds admitted to the Cardiology Service of DIMEVET were enrolled. Mean age was 7,5±4 years. Most were intact males (45%, n=51). The most represented breed was mongrel (27%, n=32).Weighted Cohen's kappa test demonstrated excellent concordance in the evaluation of the heart rhythm (0.989, p<0.001), for ST segment morphology (0.991, p<0,001) and for T wave morphology (0.838, p=0.040). There was a 100% concordance in P morphology determination. P, PR, QRS, T and QT intervals comparison with Bland­Altman showed an extremely good concordance for D­Heart® measurements (95% limit of agreement ±0.9 ms for P, ±10 ms for PR, ±35 ms for QRS, ±5 ms for T wave). Less concordance resulted for QT (±80 ms).In Conclusion, D­Heart® proved effective accurate recording of ECG comparable to standard 6­lead electrocardiographs, opening new perspectives to improve diagnostic tools in veterinary cardiology. Future perspective will be the development of a telecardiology network and to improve arrhythmia’s diagnosis in small animal practice (Bruining et al., 2014; Haberman et al., 2015).

From micro- to nanostructured implantable device for local anesthetic delivery

Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release

Making the ‘Evolutionary Leap’: Using Open Knowledge Approaches to Improve Development Outcomes

The starting point of the Open Knowledge Hub project was our belief that the adoption of so-called ‘Open Knowledge’ approaches had the potential to improve the impact of research evidence on development outcomes and address inequalities in the visibility, accessibility and uptake of diverse knowledge about development. This paper describes what we learned about the drivers and motivations for knowledge organisations to engage with Open Knowledge approaches. It also addresses the issues and barriers to engagement that, we have argued, threaten to undermine these potential benefits. The paper looks at both direct learning from the project and external research evidence accumulated during our work

Preliminary evaluation of an ELISA kit for the detection of Aldosterone concentration in dog’s urine

Aldosterone is a corticosteroid hormone that plays a pivotal role in homeostatic regulation of water and salt reabsorption, blood volume and pressure. Aldosterone levels tent to rise in humans in hypertension, chronic and acute congestive heart failure (CHF); detrimental effects are opposed by drugs like ACE inhibitors and anti-mineralocorticoid. Aldosterone has a pulsatile secretion, so measurement in serum is less indicative than in urine, where concentration can be indexed to creatinine ratio for estimation of the 24-h aldosterone excretion.Few studies have evaluated aldosterone in canine urine patients, and none by ELISA. Aim of the study was to evaluate a commercial ELISA kit for measuring aldosterone in dog’s urine.Urine was collectedby free catchfrom four dogs. Two were healthy, one was affected by CHF and prescribed anti-mineralocorticoiddaily, one was affected by chronic kidney disease (CKD). Urine was centrifuged (1250g/5 min) and supernatant frozen (-20°C). Aldosterone was measured by a competitive ELISA previously validated for dogs. Twenty-four hours acid hydrolysis was performed on urinary samples before assay.The ELISA standard curve in a semi-log plot was linear between 2.5 and 3.9 ng/mL. Spike-and-recovery, linearity-of-dilution and parallelism experiments showed accuracy inmeasuring aldosterone in dog urine samples. The intra-assay coefficient of variation showed good reproducibility of the assay.Urinary samples are easy to collect, and the ELISA used in this preliminary study seems promising in determining aldosterone in dog urine. Its levels can be of great diagnostic and prognostic value for dogs affected by acute and chronic CHF, in order to assess the best therapeutic strategy. This preliminary analysis will be followed by further studies in patients affected by acute and chronic CHF

The BH4 domain of Bcl-XL rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals

Collective evidence indicates that motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is non-cell-autonomous and requires the interaction with the neighboring astrocytes. Recently, we reported that a subpopulation of spinal cord astrocytes degenerates in the microenvironment of motor neurons in the hSOD1G93A mouse model of ALS. Mechanistic studies in vitro identified a role for the excitatory amino acid glutamate in the gliodegenerative process via the activation of its inositol 1,4,5-triphosphate (IP3)-generating metabotropic receptor 5 (mGluR5). Since non-physiological formation of IP3 can prompt IP3 receptor (IP3R)-mediated Ca2+ release from the intracellular stores and trigger various forms of cell death, here we investigated the intracellular Ca2+ signaling that occurs downstream of mGluR5 in hSOD1G93A-expressing astrocytes. Contrary to wild-type cells, stimulation of mGluR5 causes aberrant and persistent elevations of intracellular Ca2+ concentrations ([Ca2+]i) in the absence of spontaneous oscillations. The interaction of IP3Rs with the anti-apoptotic protein Bcl-XL was previously described to prevent cell death by modulating intracellular Ca2+ signals. In mutant SOD1-expressing astrocytes, we found that the sole BH4 domain of Bcl-XL, fused to the protein transduction domain of the HIV-1 TAT protein (TAT-BH4), is sufficient to restore sustained Ca2+ oscillations and cell death resistance. Furthermore, chronic treatment of hSOD1G93A mice with the TAT-BH4 peptide reduces focal degeneration of astrocytes, slightly delays the onset of the disease and improves both motor performance and animal lifespan. Our results point at TAT-BH4 as a novel glioprotective agent with a therapeutic potential for AL

Association of Microvesicles With Graft Patency in Patients Undergoing CABG Surgery

Abstract Background Graft patency is one of the major determinants of long-term outcome following coronary artery bypass graft surgery (CABG). Biomarkers, if indicative of the underlying pathophysiological mechanisms, would suggest strategies to limit graft failure. The prognostic value of microvesicles (MVs) for midterm graft patency has never been tested. Objectives The aim of this study was to evaluate whether MV pre-operative signature (number, cellular origin, procoagulant phenotype) could predict midterm graft failure and to investigate potential functional role of MVs in graft occlusion. Methods This was a nested case-control substudy of the CAGE (CoronAry bypass grafting: factors related to late events and Graft patency) study that enrolled 330 patients undergoing elective CABG. Of these, 179 underwent coronary computed tomography angiography 18 months post-surgery showing 24% graft occlusion. Flow cytometry MV analysis was performed in 60 patients (30 per group with occluded [cases] and patent [control subjects] grafts) on plasma samples collected the day before surgery and at follow-up. Results Before surgery, cases had 2- and 4-fold more activated platelet-derived and tissue-factor positive MVs respectively than control subjects. The MV procoagulant capacity was also significantly greater. Altogether this MV signature properly classified graft occlusion (area under the curve 0.897 [95% confidence interval: 0.81 to 0.98]; p Conclusions The pre-operative signature of MVs is independently associated with midterm graft occlusion in CABG patients and a cumulative MV score stratifies patients' risk. Because the MV signature mirrors platelet activation, patients with a high MV score could benefit from a personalized antiplatelet therapy

Bioaccumulation of dioxin-like substances and selected brominated flame retardant congeners in the fat and livers of black pigs farmed within the Nebrodi Regional Park of Sicily.

An observational study was designed to assess the bioaccumulation of polychlorodibenzodioxins (PCDD) and polychlorodibenzofurans (PCDF), dioxin-like polychlorobiphenyls (DL-PCB), and 13 selected polybromodiphenylethers (PBDE) in autochthonous pigs reared in the Nebrodi Park of Sicily (Italy). Perirenal fat and liver samples were drawn from animals representative of three different outdoor farming systems and from wild pigs and then analyzed for the chemicals mentioned previously. The highest concentrations of PCDD + PCDF and DL-PCB were detected in the fat (0.45 and 0.35 pg World Health Organization toxicity equivalents [WHO-TE] per g of fat base [FB], respectively) and livers (12.7 and 3.28 pg WHO-TE per g FB) of the wild group, whereas the free-ranging group showed the lowest levels (0.05 and 0.03 pg WHO-TE per g FB in fat and 0.78 and 0.27 pg WHO-TE per g FB in livers). The sum of PBDE congeners was highest in wild pigs (0.52 ng/g FB in fat and 5.64 ng/g FB in livers) and lowest in the farmed group (0.14 ng/g FB in fat and 0.28 ng/g FB in livers). The contamination levels in fat and livers of outdoor pigs had mean concentration values lower than those levels reported for intensively indoor-farmed animals. In wild pigs, bioaccumulation was associated with their free grazing in areas characterized by bush fires. The results of this study aid to emphasize the quality of the environment as a factor to guarantee food safety in typical processed pig meat products, specifically from outdoor and extensive Nebrodi farming systems

A novel approach for the purification and proteomic analysis of pathogenic immunglobulin free light chains from serum

An excess of circulating monoclonal free immunoglobulin light chains (FLC) is common in plasma cell disorders. A subset of FLC, as amyloidogenic ones, possess intrinsic pathogenicity. Because of their complex purification, little is known on the biochemical features of serum FLC, possibly related to their pathogenic spectrum. We developed an immunopurification approach to isolate serum FLC from patients with monoclonal gammopathies, followed by proteomic characterization. Serum monoclonal FLC were detected and quantified by immunofixation and immunonephelometry. Immunoprecipitation was performed by serum incubation with agarose beads covalently linked to polyclonal anti-κ or λ FLC antibodies. Isolated FLC were analyzed by SDS-PAGE, 2D-PAGE, immunoblotting, mass spectrometry (MS). Serum FLC were immunoprecipitated from 15 patients with ALλ amyloidosis (serum λ FLC range: 98-2350mg/L), 5 with ALκ amyloidosis and 1 with κ light chain (LC) myeloma (κ FLC range: 266-2660mg/L), and 3 controls. Monoclonal FLC were the prevalent eluted species in patients. On 2D-PAGE, both λ and κ FLC originated discrete spots with multiple pI isoforms. The nature of eluted FLC and coincidence with the LC sequence from the bone marrow clone was confirmed by MS, which also detected post-translational modifications, including truncation, tryptophan oxidation, cysteinylation, peptide dimerization. Serum FLC were purified in soluble form and adequate amounts for proteomics, which allowed studying primary sequence and detecting post-translational modifications. This method is a novel instrument for studying the molecular bases of FLC pathogenicity, allowing for the first time the punctual biochemical description of the circulating forms

"Mi voglio bene": a pediatrician-based randomized controlled trial for the prevention of obesity in Italian preschool children

<p>Abstract</p> <p>Background</p> <p>The first years of life are crucial to start preventive interventions that can have an impact on lifestyle and later overweight and obesity. Under the Italian National Health System (INHS), children are cared for by family pediatricians who perform health balances at regular intervals. The Italian Society of Preventive and Social Pediatrics (SIPPS) has designed a randomized controlled trial (RCT) to evaluate the effectiveness of family pediatricians for the prevention of childhood obesity in preschool children. We report the rationale and protocol of such trial, named the "Mi voglio bene" ("I love myself") study.</p> <p>Methods</p> <p>"Mi voglio bene" is a parallel-arm RCT. Family pediatricians willing to participate to the trial will be randomly assigned to a control group and to an experimental group. The control group will provide the usual standard of care while the experimental group will implement 10 preventive actions (promotion of breastfeeding, avoidance of solid foods, control of protein intake, avoidance of sugar-sweetened beverages, avoidance of bottle, active means of transportation, identification of early adiposity rebound, limitation of television viewing, promotion of movement, and teaching portion size) at 10 time points during a 6-yr follow-up. The main outcome measures is the prevalence of overweight and obesity at 6 years of age. The experimental intervention is expected to reduce the prevalence of overweight and obesity from 25% to 20% and the study requires a total of 3610 children. Each pediatrician will enroll 30 consecutive newborns into the study so that a total of 120 pediatricians will participate to the study.</p> <p>Discussion</p> <p>"Mi voglio bene" is expected to provide important information for the INHS and possibly other institutional child care settings about the effectiveness of a pediatrician-based approach to the prevention of childhood obesity. We published this study protocol with the aim of opening a discussion with all people interested in fighting childhood obesity and to receive useful criticisms.</p

AIDS-Kaposi Sarcoma and Classic Kaposi Sarcoma: are different ultrasound patterns related to different variants?

<p>Abstract</p> <p>Background</p> <p>Kaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and in the natural history of AIDS-KS and Classic-KS have been described. The present randomised prospective-observational study aimed to investigate whether the ultrasound pattern and color Doppler flow imaging of vascularisation of skin lesions of patients with Classic KS (CKS) or AIDS-KS could provide useful information to the evaluation of clinical activity of the disease.</p> <p>Methods</p> <p>Cutaneous lesions of 24 patients with histologically confirmed KS were investigated using very high frequency ultrasound probes; 16 patients had CKS and 8 had AIDS-KS. HHV-8 infection was confirmed in all patients by investigating the specific humoral response to viral antigens. Immunological and virological parameters were also assessed to monitor HIV or HHV-8 viral infection. For each patient, a target skin lesion was selected on the basis of size (diameter from 0.4 to 2 cm). Each lesion was analyzed in terms of size, depth and color Doppler pattern.</p> <p>Results</p> <p>The B-mode ultrasound patterns of skin lesions did not differ when comparing CKS patients to AIDS-KS patients, whereas the color Doppler signal, which is associated with vascular activity, was detected in the KS lesions of 6/8 AIDS-KS patients (75.0%) and in 2/16 CKS (16,7%); the latter two patients showed a clinically progressive and extensive disease stage (IV B).</p> <p>Conclusions</p> <p>Our preliminary results suggest that small cutaneous KS lesions - in both CKS and AIDS-KS patients- display similar B-mode ultrasound patterns ( hypoechoic, well defined, superficial lesions). However, the color Doppler signal, which is associated with endothelial activity and angiogenesis, which play a substantial role in KS progression, could constitute a useful tool for evaluating disease activity.</p