L'orario di lavoro

L'orario di lavoro rappresenta una tematica centrale nell'ambito del rapporto di lavoro. Si è avvertita fin dai tempi più remoti la necessità di disciplinare la materia, al fine di tutelare la salute dei lavoratori, salvo poi riscontrare come la modulazione degli orari di lavoro potesse rappresentare anche un'efficace strumento di intervento a salvaguardia dei livelli occupazionali. Dopo una disamina dell'evoluzione normativa in tema di orario di lavoro viene affrontata la tematica alla luce della riforma operata dal D.Lgs. n. 66/2003, con cui si è data piena attuazione ai contenuti della direttiva 104/93/CE. Segue un approfondimento dei vari istituti così come regolati dalla nuova disciplina con particolare attenzione ai limiti di orario di lavoro e alla pause. Parte della dissertazione è stata dedicata, infine, alle esigenze di conciliazione tra tempi di vita e di lavoro emerse a seguito dei profondi cambiamenti socio-culturali avvenuti nel nostro paese

Fibrinolysis protease receptors promote activation of astrocytes to express pro-inflammatory cytokines.

BACKGROUND:Astrocytes contribute to the crosstalk that generates chronic neuro-inflammation in neurological diseases; however, compared with microglia, astrocytes respond to a more limited continuum of innate immune system stimulants. Recent studies suggest that the fibrinolysis system may regulate inflammation. The goal of this study was to test whether fibrinolysis system components activate astrocytes and if so, elucidate the responsible biochemical pathway. METHODS:Primary cultures of astrocytes and microglia were prepared from neonatal mouse brains. The ability of purified fibrinolysis system proteins to elicit a pro-inflammatory response was determined by measuring expression of the mRNAs encoding tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and chemokine (C-C motif) ligand 2 (CCL2). IκBα phosphorylation also was measured. Plasminogen activation in association with cells was detected by chromogenic substrate hydrolysis. The activity of specific receptors was tested using neutralizing antibodies and reagents. RESULTS:Astrocytes expressed pro-inflammatory cytokines when treated with plasminogen but not when treated with agonists for Toll-like Receptor-4 (TLR4), TLR2, or TLR9. Microglia also expressed pro-inflammatory cytokines in response to plasminogen; however, in these cells, the response was observed only when tissue-type plasminogen activator (tPA) was added to activate plasminogen. In astrocytes, endogenously produced urokinase-type plasminogen activator (uPA) converted plasminogen into plasmin in the absence of tPA. Plasminogen activation was dependent on the plasminogen receptor, α-enolase, and the uPA receptor, uPAR. Although uPAR is capable of directly activating cell-signaling, the receptor responsible for cytokine expression and IκBα phosphorylation response to plasmin was Protease-activated Receptor-1 (PAR-1). The pathway, by which plasminogen induced astrocyte activation, was blocked by inhibiting any one of the three receptors implicated in this pathway with reagents such as εACA, α-enolase-specific antibody, uPAR-specific antibody, the uPA amino terminal fragment, or a pharmacologic PAR-1 inhibitor. CONCLUSIONS:Plasminogen may activate astrocytes for pro-inflammatory cytokine expression through the concerted action of at least three distinct fibrinolysis protease receptors. The pathway is dependent on uPA to activate plasminogen, which is expressed endogenously by astrocytes in culture but also may be provided by other cells in the astrocytic cell microenvironment in the CNS

Evaluación de la Calidad Físico Química y Microbiológica de la Leche cruda que se expende en el Cantón Bolívar Provincia del Carchi

El presente trabajo se basa en la “EVALUACIÓN DE LA CALIDAD FÍSICO-QUÍMICA Y MICROBIOLÓGICA DE LA LECHE CRUDA QUE SE EXPENDE EN EL CANTÓN BOLÍVAR PROVINCIA DEL CARCHI”. En el cantón Bolívar, provincia del Carchi, se expende a la población leche cruda en tarros de aluminio y barriles de plástico, generalmente en camionetas abiertas. Al no existir control de la calidad de la leche que se expende, el Departamento de Gestión Ambiental del Municipio solicita a la Facultad de Ingeniería en Ciencias Agropecuarias y Ambientales de la Universidad Técnica del Norte que se realice un control para determinar que muestras de leche cumplen con lo establecido en la NTE INEN 09, además el cuidado en el momento del ordeño, recolección, transporte, conservación, higiene y adulteraciones por diversos procedimientos, condiciones que ayudan a mantener una leche de calidad. Por tratarse de un experimento donde el factor en estudio es la leche cruda, para el análisis estadístico se aplicó un Diseño Completamente al Azar (D.C.A), con doce tratamientos con tres repeticiones cada uno, un análisis funcional de prueba de Tukey al 5 % para tratamientos, además de calcularse el coeficiente variación (C.V) y la unidad experimental estuvo conformada por un litro de leche cruda por tratamiento. Los tratamientos fueron seleccionados al azar de tres parroquias. Los Andes, García Moreno y Bolívar. Las variables analizadas fueron: determinación de la densidad a 15 ºC, determinación de la acidez titulable, prueba de alcohol, detección de almidón, cuantificación de peróxido de hidrógeno, contenido de grasa, determinación de sólidos no grasos, determinación de sólidos totales, determinación del punto de congelación, agua añadida, contenido de proteínas, contenido de cenizas, presencia de antibióticos, contaje de microorganismos aerobios mesófilos, contaje de Enterobacterias y contaje de Células Somáticas. La fase experimental de la presente investigación se realizó en el “Laboratorio de Uso Múltiple de la Universidad Técnica del Norte”, ubicado en la ciudad de Ibarra. Los análisis determinación de presencia de antibióticos y contaje de células somáticas se los efectuó en el Laboratorio de Calidad de Leche de la Universidad Politécnica Salesiana ubicado en Cayambe

Elaboración de materiales didácticos, para la enseñanza de la lectoescritura en niños de octavo año con necesidades educativas específicas de la unidad educativa La Libertad

This study has been carried out with the purpose of determining the problems of literacy. This research helps to solve the learning problems that have been generated with the eighth-year students of Basic Education in the La Libertad Educational Unit in the area of ​​Literature for the teaching of Literacy based on special educational needs, through a qualitative approach, using the fieldwork method, developed in four previous periods: The first phase is based on sampling, the second phase is the preparation of the teacher's didactic materials, the third phase is the implementation of the teaching materials practice and the fourth is the evaluation with the support of educational resources in student learning, in which five didactic materials will be designed to develop linguistic skills for literacy in primary students, without losing sight of the criteria for the valuation. It should be noted that the use of didactic materials is not enough. For this reason, it is necessary to carry out curricular adaptations, in the progress of the study the background of the subject is briefly explained, the theoretical foundation, the pedagogical and philosophical references, the curricular mesh of the Ministry of Education, the didactic strategies applied in the classroom and the importance of teaching materials in educationEste estudio se ha llevado a cabo con el proposito de determinar los problemas de la lectoescritura. Esta investigación ayuda a resolver los inconvenientes de aprendizaje que se ha generado en los estudiantes de octavo año de Educacion Básica en la Unidad Educativa La Libertad de en área de Literatura para la enseñanza de la Lectoescritura en función de las necesidades educativas especificas, por médio de un enfoque cualitativo, mediante el método trabajo de campo, desarrollado en cuatro períodos previos: La primera fase se sustenta en un muestreo, la segunda fase es la elaboración materiales didácticos del professor, la tercera fase es la ejecución de la práctica de los materiales pedagógicos y la cuarta es la evaluación con apoyo de los recursos educativos en el aprendizaje de los estudiantes, en la que se diseñaran cinco materiales didácticos que desarrollen la destreza de la lingüística para la lectoescritura en los estudiantes, sin perder de vista los critérios para la valoración. Cabe destacar que el uso de los materiales didácticos no son suficiente. Por eso es necesario realizar adaptaciones curriculares, en el avance del estudio se explica brevemente los antecedentes de la temática, la fundamentación teórica, los referentes pedagógicos y filosóficos, la malla curricular del Ministerio de Educación, las estrategias didáctica aplicadas en el aula y la importancia de los materiales didácticos en la educación

Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations

Benign hereditary chorea (BHC) is a rare genetically heterogeneous movement disorder, in which conventional neuroimaging has been reported as normal in most cases. Cystic pituitary abnormalities and features of empty sella have been described in only 7 patients with BHC to date. We present 4 patients from 2 families with a BHC phenotype, 3 of whom underwent targeted pituitary MR imaging and genetic testing. All four patients in the two families displayed a classic BHC phenotype. The targeted pituitary MR imaging demonstrated abnormal pituitary sella morphology. Genetic testing was performed in three patients, and showed mutations causing BHC in three of the patients, as well as identifying a novel nonsense mutation of the TITF1/NKX2-1 gene in one of the patients. The presence of the abnormal pituitary sella in two affected members of the same family supports the hypothesis that this sign is a distinct feature of the BHC phenotype spectrum due to mutations in the TITF1 gene. Interestingly, these abnormalities seem to develop in adult life and are progressive. They occur in at least 26% of patients affected with Brain-lung-thyroid syndrome. As a part of the management of these patients we recommend to perform follow-up MRI brain with dedicated pituitary imaging also in adult life as the abnormality can occur years after the onset of chorea

Data on protein abundance alteration induced by chronic exercise in mdx mice model of Duchenne muscular dystrophy and potential modulation by apocynin and taurine

Here we present original data related to the research paper entitled “Proteome analysis in dystrophic mdx mouse muscle reveals a drastic alteration of Key Metabolic and Contractile Proteins after chronic exercise and the potential modulation by anti-oxidant compounds” (Gamberi et al., 2018) [1]. The dystrophin-deficient mdx mouse is the most common animal model for Duchenne muscular dystrophy. The mdx mice phenotype of the disorder is milder than in human sufferers and it can be worsened by chronic treadmill exercise. Apocynin and taurine are two antioxidant compounds proved to be beneficial on some pathology related parameters (Schröder and Schoser, 2009) [2]. This article reports the detailed proteomic data on protein abundance alterations, in tibialis anterior muscle of mdx mice, induced by chronic exercise protocol. A selected group of mdx mice was also treated with apocynin and taurine during this protocol. Detailed MS data, comparison between mdx vs wild type, exercised mdx vs wild type, and complete analysis of spot variation are provided. Furthermore, in wild type mice subjected to the same exercise protocol, the abundance of key proteins, resulted modified in exercised mdx, were analyzed by western blot

A long-term treatment with taurine prevents cardiac dysfunction in mdx mice

Taurine is an amino acid abundantly present in heart and skeletal muscle. Duchenne muscular dystrophy (DMD) is a genetic disorder in which the absence of dystrophin leads to skeletal muscle wasting and heart failure. An altered taurine metabolism has been described in dystrophic animals and short-term taurine administration exerts promising amelioration of early muscular alterations in the mdx mouse model of DMD. To reinforce the therapeutic and nutraceutical taurine potential in DMD, we evaluated the effects of a long-term treatment on cardiac and skeletal muscle function of mdx mice in a later disease stage. Taurine was administered in drinking water (1 g/kg/day) to wt and mdx mice for 6 months, starting at 6 months of age. Ultrasonography evaluation of heart and hind limb was performed, in parallel with in vivo and ex vivo functional tests and biochemical, histological and gene expression analyses. 12-month-old mdx mice showed a significant worsening of left ventricular function parameters (shortening fraction, ejection fraction, stroke volume), which were significantly counteracted by the taurine treatment. In parallel, histologic signs of damage were reduced by taurine along with the expression of proinflammatory myocardial IL-6. Interestingly, no effects were observed on hind limb volume and percentage of vascularization or on in vivo and ex vivo muscle functional parameters, suggesting a tissue-specific action of taurine in relation to the disease phase. A trend toward increase in taurine was found in heart and quadriceps from treated animals, paralleled by a slight decrease in mdx mice plasma. Our study provides evidences that taurine can prevent late heart dysfunction in mdx mice, further corroborating the interest on this amino acid toward clinical trials

Contractile efficiency of dystrophic mdx mouse muscle: In vivo and ex vivo assessment of adaptation to exercise of functional end points

Progressive weakness is a typical feature of Duchenne muscular dystrophy (DMD) patients and is exacerbated in the benign mdx mouse model by in vivo treadmill exercise. We hypothesized a different threshold for functional adaptation of mdx muscles in response to the duration of the exercise protocol. In vivo weakness was confirmed by grip strength after 4, 8 and 12 weeks of exercise in mdx mice. Torque measurements revealed that exercise-related weakness in mdx mice correlated with the duration of the protocol, while wild-type (wt) mice were stronger. Twitch and tetanic forces of isolated diaphragm and extensor digitorum longus (EDL) muscles, were lower in mdx compared to wt mice. In mdx, both muscle types exhibited greater weakness after a single exercise bout, but only in EDL after a long exercise protocol. As opposite to wt muscles, mdx EDL ones did not show any exercise-induced adaptations against eccentric contraction force drop. qRT-PCR analysis confirmed the maladaptation of genes involved in metabolic and structural remodeling, while damage-related genes remained significantly upregulated and angiogenesis impaired. Phosphorylated AMP kinase level increased only in exercised wt muscle. The severe histopathology and the high levels of muscular TGF-β1 and of plasma matrix metalloproteinase-9 confirmed the persistence of muscle damage in mdx mice. Then, dystrophic muscles showed a partial degree of functional adaptation to chronic exercise, although not sufficient to overcome weakness nor signs of damage. The improved understanding of the complex mechanisms underlying maladaptation of dystrophic muscle paves the way to a better managment of DMD patients

Growth hormone secretagogues modulate inflammation and fibrosis in mdx mouse model of Duchenne muscular dystrophy

IntroductionGrowth hormone secretagogues (GHSs) exert multiple actions, being able to activate GHS-receptor 1a, control inflammation and metabolism, to enhance GH/insulin-like growth factor-1 (IGF-1)-mediated myogenesis, and to inhibit angiotensin-converting enzyme. These mechanisms are of interest for potentially targeting multiple steps of pathogenic cascade in Duchenne muscular dystrophy (DMD).MethodsHere, we aimed to provide preclinical evidence for potential benefits of GHSs in DMD, via a multidisciplinary in vivo and ex vivo comparison in mdx mice, of two ad hoc synthesized compounds (EP80317 and JMV2894), with a wide but different profile. 4-week-old mdx mice were treated for 8 weeks with EP80317 or JMV2894 (320 µg/kg/d, s.c.).ResultsIn vivo, both GHSs increased mice forelimb force (recovery score, RS towards WT: 20% for EP80317 and 32% for JMV2894 at week 8). In parallel, GHSs also reduced diaphragm (DIA) and gastrocnemius (GC) ultrasound echodensity, a fibrosis-related parameter (RS: ranging between 26% and 75%). Ex vivo, both drugs ameliorated DIA isometric force and calcium-related indices (e.g., RS: 40% for tetanic force). Histological analysis highlighted a relevant reduction of fibrosis in GC and DIA muscles of treated mice, paralleled by a decrease in gene expression of TGF-β1 and Col1a1. Also, decreased levels of pro-inflammatory genes (IL-6, CD68), accompanied by an increment in Sirt-1, PGC-1α and MEF2c expression, were observed in response to treatments, suggesting an overall improvement of myofiber metabolism. No detectable transcript levels of GHS receptor-1a, nor an increase of circulating IGF-1 were found, suggesting the presence of a novel receptor-independent mechanism in skeletal muscle. Preliminary docking studies revealed a potential binding capability of JMV2894 on metalloproteases involved in extracellular matrix remodeling and cytokine production, such as ADAMTS-5 and MMP-9, overactivated in DMD.DiscussionOur results support the interest of GHSs as modulators of pathology progression in mdx mice, disclosing a direct anti-fibrotic action that may prove beneficial to contrast pathological remodeling