Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria

BACKGROUND: Mucosal delivery of therapeutic protein drugs or vaccines is actively investigated, in order to improve bioavailability and avoid side effects associated with systemic administration. Orally administered bacteria, engineered to produce anti-inflammatory cytokines (IL-10, IL-1Ra), have shown localised ameliorating effects in inflammatory gastro-intestinal conditions. However, the possible systemic effects of mucosally delivered recombinant bacteria have not been investigated. RESULTS: B. subtilis was engineered to produce the mature human IL-1 receptor antagonist (IL-1Ra). When recombinant B. subtilis was instilled in the distal colon of rats or rabbits, human IL-1Ra was found both in the intestinal lavage and in the serum of treated animals. The IL-1Ra protein in serum was intact and biologically active. IL-1-induced fever, neutrophilia, hypoglycemia and hypoferremia were inhibited in a dose-dependent fashion by intra-colon administration of IL-1Ra-producing B. subtilis. In the mouse, intra-peritoneal treatment with recombinant B. subtilis could inhibit endotoxin-induced shock and death. Instillation in the rabbit colon of another recombinant B. subtilis strain, which releases bioactive human recombinant IL-1β upon autolysis, could induce fever and eventually death, similarly to parenteral administration of high doses of IL-1β. CONCLUSIONS: A novel system of controlled release of pharmacologically active proteins is described, which exploits bacterial autolysis in a non-permissive environment. Mucosal administration of recombinant B. subtilis causes the release of cytoplasmic recombinant proteins, which can then be found in serum and exert their biological activity in vivo systemically

The measurement of left—right asymmetries in the Simon effect: A fine-grained analysis

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Occurrence of pathogenic and faecal Escherichia coli in layer hens

A total of 117 Escherichia coli from colibacillosis affected (APEC) and clinically healthy birds (AFEC) were serotyped and tested for the presence of virulence genes: iss, tsh, cva. A total of 54.5% E. Coli were typeable and 15 different serogroups were identified. The most common serogroups among APEC strains were O78, O2 and O128, whereas O139 was predominant in faecal strains from healthy birds. Iss, tsh e cva were more frequently detected among the septicaemic E. coli strains. The association of virulence genes was observed. Particularly, the pathotype iss-tsh-cva was present in 46.5% of APEC strains. Referring to serogroups, E. coli O78 and O2 originating from colibacillosis affected birds were always isstsh- cva positive but did not share virulence genes when they came from healthy birds

Estructura de costos del servicio de barrido de calles y su impacto ambiental en la ciudad de Huancayo - Periodo 2016

Para la investigación, sobre la Variable 1 Estructura de Costos del Servicio de Limpieza Pública, tiene como referencia la Guía elaborado por el Ministerio del Ambiente, siempre en cuando este servicio es administrado directamente por la entidad, en este caso por la Municipalidad Provincial de Huancayo; sin embargo, en cuanto al costo directo para el presente caso, está considerado el importe del Contrato con la empresa Diestra Concesión SAC. Para la Variable 2 Impacto Ambiental, existen diversos conceptos, a fin de uniformizar en el presente trabajo, se describe según el Glosario de Términos de la Gestión Ambiental Peruana señalado por el MINAM (2012), como una Alteración, positiva o negativa, de uno o más de los componentes del ambiente, provocada por la acción de un proyecto; en nuestro caso al aire, suelo y agua. Como hipótesis científica, se ha formulado así: Existe relación directa y significativa entre La estructura de costos del servicio de barrido de calles y los Impactos ambientales Como método de investigación se considera el científico, por su carácter el tipo de investigación es descriptiva; el nivel es Correlacional, la muestra se ha tomado por conveniencia a 20 integrantes, 5 Directivos de la empresa Diestra Concesión Huancayo S.A.Cy 15 funcionarios Administrativos de la Municipalidad Provincial de Huancayo. Para la recolección de datos se ha elaborado el cuestionario de encuesta con 11 ítems por cada variable, proponiendo 5 alternativas de respuestas. De acuerdo al análisis descriptivo de las variables y dimensiones, se presentan los resultados de la investigación. Para determinar la correlación de las variables se utilizó la prueba de Rho de Spearman, habiendo permitido encontrar respuestas a los problemas planteados, además de lograr la verificación de los objetivos establecidos, para rechazar o aceptar las hipótesis científicas planteadas. Para finalizar, se presenta la conclusión general de que, existe una relación positiva fuerte de 0.509 puntos entre las variables Estructura de costos de barrido de calles y los impactos ambientales en la ciudad de Huancayo, período 2016.Tesi

Role of serial ultrasound screening of venous thrombosis in oncologic children with central lines

Objective: Pediatric oncology patients are more likely to develop venous thromboembolic events related to central venous catheter (CVC). Study aim was to determine the incidence of catheter related thrombosis (CRT) in a cohort of pediatric oncology patients using vascular ultrasound (US). Methods: Consecutive children of a single cancer referral center, requiring medium to long term CVC implantation, were screened for CRT, using serial ultrasound exams. Measurements and main results: US examinations were taken 15, 30 and 90 days after CVC implantation. A total of 113 catheters were studied in 103 patients (median age 10.5 years old). Ultrasound screening was completed in 80.5% patients. Apart from three subjects, US investigations were well tolerated. Patients were followed for a median of 87 days. No symptomatic CRT was recorded throughout. Three cases of asymptomatic thrombosis were identified with early US screening; incidence of CRT events for 1000 catheter-days was 0.11. The presence of previous catheter-related infection and an history of one or more previous CVC placement were identified as risk factors. Conclusions: In our pediatric patients the incidence of CRT is low. Ultrasound monitoring is well tolerated and allows detecting asymptomatic CRT. Patients with previous CVC infection or insertion seem to have a higher risk of CRT (p =0.003 and p = 0.043 respectively). Keywords: Central venous catheters, Venous thrombosis, Vascular ultrasound, Vascular catheter infections, Childre

Correlates of spinal deforming index (SDI) in HIV-positive patients naive and on treatment

Methods HIV-infected subjects naive or on stable HAART were included. Vertebral deformities were identified using SDI (according to semiquantitative method by Genant), calculated by summing the deformity grades of all vertebrae (T4 to L4); pathological deformities are defined as follow: grade 1 between 20–25%, grade 2 between 26–40%, and grade 3 > >40%. According to WHO criteria, osteopenia and osteoporosis were diagnosed in patients having spine BMD calculated as -1 << T-score << -2.5 and T-score ≤≤2.5, respectively. The correlation between SDI and spine BMD was evaluated by univariate and multivariate linear regression. [Other variables considered: gender, age, current CD4 count, CD4 nadir, BMI, lipid parameters, alcohol intake, smoking habit, physical activity, family history for bone fracture, months of ARV exposure, and co-infection with hepatitis viruses; only the variables with p <<0.2 in univariate analyses were included in the final model.

Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication

INTRODUCTION: Lactic acidosis can develop during biguanide (metformin and phenformin) intoxication, possibly as a consequence of mitochondrial dysfunction. To verify this hypothesis, we investigated whether body oxygen consumption (VO2), that primarily depends on mitochondrial respiration, is depressed in patients with biguanide intoxication. METHODS: Multicentre retrospective analysis of data collected from 24 patients with lactic acidosis (pH 6.93 +/- 0.20; lactate 18 +/- 6 mM at hospital admission) due to metformin (n = 23) or phenformin (n = 1) intoxication. In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI). In 13 additional cases, C(a-v)O2, but not CI, was available. RESULTS: On day 1, VO2 was markedly depressed (67 +/- 28 ml/min/m2) despite a normal CI (3.4 +/- 1.2 L/min/m2). C(a-v)O2 was abnormally low in both patients either with (2.0 +/- 1.0 ml O2/100 ml) or without (2.5 +/- 1.1 ml O2/100 ml) CI (and VO2) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO2 (P < 0.001) and C(a-v)O2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32). CONCLUSIONS: VO2 is abnormally low in patients with lactic acidosis due to biguanide intoxication. This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia

Collection by trained pediatricians or parents of mid-turbinate nasal flocked swabs for the detection of influenza viruses in childhood

This study evaluated the efficiency of pediatric mid-turbinate nasal flocked swabs used by parents in 203 children aged 6 months to 5 years with signs and symptoms of respiratory disease. Two nasal samples were collected from each child in a randomised sequence: one by a trained pediatrician and one by a parent. The real-time polymerase chain reaction influenza virus detection rates were similar in the samples collected using the two methods (Cohen's kappa = 0.86), as were the cycle threshold values. In comparison with the pediatrician-collected samples, the sensitivity and specificity of the parental collections were respectively 89.3% (95% confidence interval [CI]: 77.8-100%) and 97.7% (95% CI: 95.5-100%), and the positive and negative predictive values were respectively 86.2% (95% CI: 73.7-95.1%) and 98.2% (95% CI: 96.4-100%). The children were significantly more satisfied with the parental collections (median values ± standard deviation, 1.59 ± 0.55 vs 3.51 ± 0.36; p < 0.0001). These findings show that mid-turbinate nasal flocked swabs specifically designed for infants and children can be used by parents without reducing the influenza virus detection rate. Moreover, the direct involvement of parents significantly increases patient acceptance, thus simplifying collection and suggesting that this novel swab design should be considered for epidemiological surveys and vaccine efficacy studies

Non-invasive estimation of intracranial pressure by diffuse optics: a proof-of-concept study

Intracranial pressure (ICP) is an important parameter to monitor in several neuropathologies. However, because current clinically accepted methods are invasive, its monitoring is limited to patients in critical conditions. On the other hand, there are other less critical conditions for which ICP monitoring could still be useful; therefore, there is a need to develop non-invasive methods. We propose a new method to estimate ICP based on the analysis of the non-invasive measurement of pulsatile, microvascular cerebral blood flow with diffuse correlation spectroscopy. This is achieved by training a recurrent neural network using only the cerebral blood flow as the input. The method is validated using a 50% split sample method using the data from a proof-of-concept study. The study involved a population of infants (n = 6) with external hydrocephalus (initially diagnosed as benign enlargement of subarachnoid spaces) as well as a population of adults (n = 6) with traumatic brain injury. The algorithm was applied to each cohort individually to obtain a model and an ICP estimate. In both diverse cohorts, the non-invasive estimation of ICP was achieved with an accuracy of 0.9) and good concordance (Lin's concordance correlation coefficient >0.9) in comparison with standard clinical, invasive ICP monitoring. This preliminary work paves the way for further investigations of this tool for the non-invasive, bedside assessment of ICP.This work leading to the results was funded by the European Union’s Horizon 2020 project “BitMap: Brain injury and trauma monitoring using advanced photonics” (No. 675332); Fundació CELLEX Barcelona; Ministerio de Economía y Competitividad /FEDER (PHOTODEMENTIA, DPI2015-64358-C2-1-R); Instituto de Salud Carlos III / FEDER (MEDPHOTAGE, DTS16/00087 and PI18/00468); the “Severo Ochoa” Programme for Centers of Excellence in R&D (SEV-2015-0522); the Obra social “laCaixa” Foundation (LlumMedBcn); Institució CERCA, AGAUR-Generalitat (2017 SGR 1380); LASERLAB-EUROPE IV; KidsBrainIT (ERA-NET NEURON) and la Fundació La Marató de TV3 (201709.31 and 201724.31).Peer ReviewedPostprint (author's final draft