Epigenetic reprogramming of muscle progenitors: inspiration for clinical therapies

In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD)

Different outcome of sarcoglycan missense mutation between human and mouse

Sarcoglycanopathies are rare autosomic limb girdle muscular dystrophies caused by mutations in one of the genes coding for sarcoglycan (α, β, δ, and γ-sarcoglycans). Sarcoglycans form a complex, which is an important part of the dystrophin-associated glycoprotein complex that protects sarcolemma against muscle contraction-induced damages. Absence of one of the sarcoglycan at the plasma membrane induces the disappearance of the whole complex and perturbs muscle fiber membrane integrity. We previously demonstrated that point mutations in the human sarcoglycan genes affects the folding of the corresponding protein, which is then retained in the endoplasmic reticulum by the protein quality control and prematurely degraded by the proteasome. Interestingly, modulation of the quality control using pharmacological compounds allowed the rescue of the membrane localization of the mutated sarcoglycan. Two previously generated mouse models, knock-in for the most common sarcoglycan mutant, R77C α-sarcoglycan, failed in reproducing the dystrophic phenotype observed in human patients. Based on these results and the need to test therapies for these fatal diseases, we decided to generate a new knock-in mouse model carrying the missense mutation T151R in the β-sarcoglycan gene since this is the second sarcoglycan protein with the most frequently reported missense mutations. Muscle analysis, performed at the age of 4 and 9-months, showed the presence of the mutated β-sarcoglycan protein and of the other components of the dystrophin-associated glycoprotein complex at the muscle membrane. In addition, these mice did not develop a dystrophic phenotype, even at a late stage or in condition of stress-inducing exercise. We can speculate that the absence of phenotype in mouse may be due to a higher tolerance of the endoplasmic reticulum quality control for amino-acid changes in mice compared to human

Out-of-hours primary care services: Demands and patient referral patterns in a Veneto region (Italy) Local Health Authority

open7PURPOSE: The aim of this study was to describe the characteristics of patients admitted to an out-of-hours (OOH) service and to analyze the related outputs. SETTING: A retrospective population-based cohort study was conducted by analyzing an electronic database recording 23,980 OOH service contacts in 2011 at a Local Health Authority in the Veneto Region (North-East Italy). METHOD: A multinomial logistic regression was used to compare the characteristics of contacts handled by the OOH physicians with cases referred to other services. RESULTS: OOH service contact rates were higher for the oldest and youngest age groups and for females rather than males. More than half of the contacts concerned patients who were seen by a OOH physician. More than one in three contacts related problems managed over the phone; only ≈10% of the patients were referred to other services. Many factors, including demographic variables, process-logistic variables and clinical characteristics of the contact, were associated with the decision to visit the patient's home (rather than provide telephone advice alone), or to refer patients to an ED or to a specialist. Our study demonstrated, even after adjusting, certain OOH physicians were more likely than their colleagues to refer a patient to an ED. CONCLUSION: Our study shows that OOH services meet composite and variously expressed demands. The determining factors associated with cases referred to other health care services should be considered when designing clinical pathways in order to ensure a continuity of care. The unwarranted variability in OOH physicians' performance needs to be addressed.Purpose: The aim of this study was to describe the characteristics of patients admitted to an out-of-hours (OOH) service and to analyze the related outputs. Setting: A retrospective population-based cohort study was conducted by analyzing an electronic database recording 23,980 OOH service contacts in 2011 at a Local Health Authority in the Veneto Region (North-East Italy). Method: A multinomial logistic regression was used to compare the characteristics of contacts handled by the OOH physicians with cases referred to other services. Results: OOH service contact rates were higher for the oldest and youngest age groups and for females rather than males. More than half of the contacts concerned patients who were seen by a OOH physician. More than one in three contacts related problems managed over the phone; only ≈10% of the patients were referred to other services. Many factors, including demographic variables, process-logistic variables and clinical characteristics of the contact, were associated with the decision to visit the patient's home (rather than provide telephone advice alone), or to refer patients to an ED or to a specialist. Our study demonstrated, even after adjusting, certain OOH physicians were more likely than their colleagues to refer a patient to an ED. Conclusion: Our study shows that OOH services meet composite and variously expressed demands. The determining factors associated with cases referred to other health care services should be considered when designing clinical pathways in order to ensure a continuity of care. The unwarranted variability in OOH physicians' performance needs to be addressed.openBuja, Alessandra; Toffanin, R; Rigon, S; Sandona', Paolo; Carraro, D; Damiani, G; Baldo, VincenzoBuja, Alessandra; Toffanin, R; Rigon, S; Sandona', Paolo; Carraro, D; Damiani, G; Baldo, Vincenz

ALLE ORIGINI DEL LIBRO \ubfDELLA TUTELA DEI DIRITTI\ubf: \ubfSTORIA ESTERNA\ubf, NATURA ED ASCENDENZE LEGISLATIVE, DOTTRINALI E GIURISPRUDENZIALI DEL VI LIBRO DEL VIGENTE CODICE CIVILE

The contribution is devoted to the study of Book VI of the Italian Civil Code of 1942,investigating, in particular, the legislative policy choices, the peculiarity and the legal ideology that the legislator wanted to express with it, and checking whether they have found in the book "Della tutela dei diritti", as it was made, authentic expression. In light of the objectives it seemed useful to articulate the research along two main lines, autonomous and complementary at the same time, so that in case of convergence of their results, their synthesis might lead to stronger results. First we tried to reconstruct, in a more detailed manner possible, "external history" of the book "Della tutela dei diritti" on the assumption that the reconstruction of the events that formed the complex historical phenomenon that was the codification of italian private law may help to extrapolate these trends and those guideline that constitute the true soul of a code and, even more of the mere rules that make it up, allow to appreciate the spirit and character that are immanent to it. Secondly, we have retraced the specific events of the individual institutions that came together in Book VI, following the actual behavior in the historical (ie studying them in their legislative dimension, doctrinal, and, when possible, case law) in order to identify and verify the common characteristics, structural or functional, which may have led, in systematic adopted in 1942, the amalgamation. Survey which, among other things, could help determine whether the legislature's choice was "authoritarian," wich mean that is designed from scratch to impose a different legal architecture on which to develop future law, or necessitated, in the sense that the works conducted by dogmatic science and by case law upon the code of '65 in the light of new doctrinal influences would need to find a positive expression such as that in fact upheld

Implementasi strategi tutor sebaya (Peer Tutoring) dalam meningkatkan prestasi belajar Pendidikan Agama Islam kelas VIII-B di SMP Negeri 7 Probolinggo

ABSTRAK Dalam pembelajaran, agar tujuan pembelajaran dapat tercapai maka diperlukan penggunaan strategi yang tepat dan juga bantuan media pembelajaran yang sesuai. Sampai sekarang masih banyak pendidik yang menggunakan metode konvensional, seperti ceramah dan Tanya jawab, dengan metode ini peserta didik kurang antusias dalam menerima pembelajaran, dan dapat dikatakan semangat mengikuti pelajaran sangat lemah. Berangkat dari masalah di atas, maka rumusan masalah dalam penelitian ini adalah (1) bagaimana penerapan strategi tutor sebaya dalam meningkatkan prestasi belajar PAI siswa kelas VIII-B di SMP Negeri 7 Probolinggo? Dan (2) Apakah penerapan strategi tutor sebaya dapat meningkatkan prestasi belajar PAI siwa VIII-B di SMP Negeri 7 Probolinggo. Penelitian ini menggunakan desain penelitian tindakan kelas(class-room action research) dengan jenis penelitian mandiri. Teknik pengumpulan data dilakukan dengan menggunakan observasi, dokumentasi, dan test. Data yang bersifat kualitatif dianalisa deskriptif sedangkan data yang bersifat kuantitatif dianalisa dengan analisa deskriptif kuantitatif. Dari penelitian yang dilakukan di lapangan, strategi Tutor Sebaya (Peer Tutoring) dengan materi sujud, zakat, dan puasa dan terbukti dapat meningkatkan prestasi belajar siswa. Dari hasil observasi dan data empiris di lapangan menunjukkan bahwa penerapan strategi tutor sebaya terbukti dapat meningkatkan prestasi belajar Pendidikan Agama Islam siswa kelas VIII-B di SMP Negeri 7 Probolinggo. Hasil pre test menunjukkan nilai rata-rata sebesar 61, hasil siklus I (pertemuan pertama) menunjukkan nilai rata-rata 77 atau meningkat 26,23% sedangkan hasil nilai rata-rata pada siklus I (pertemuan kedua) adalah 90 atau meningkat 16,63 dari siklus I. Hal ini terbukti bahwa penerapan strategi tutor sebaya dapat meningkatkan prestasi belajar Pendidikan Agama Islam siswa VIII- B di SMP Negeri 7 Probolinggo. ABSTRACT In learning, so that learning objectives can be achieved it is necessary to use appropriate strategies and also support appropriate learning media. Until now there are many educators who use conventional methods, such as lectures and question and answer, with this method is less enthusiastic learners receive learning, and can be said to follow the spirit of the lesson is very weak. Departing from the above problems, the formulation of the problem in this study were (1) how the implementation of peer tutoring strategies in improving student achievement PAI-VIII class B in SMP Negeri 7 Probolinggo? And (2) Does the application of peer tutoring strategies can improve learning achievement PAI siwa VIII-B in SMP Negeri 7 Probolinggo. This study uses classroom action research design (class-room action research) with the kind of independent research. Data was collected using observation, documentation, and test. Qualitative data were analyzed descriptively while quantitative data was analyzed by quantitative descriptive analysis. From research conducted in the field, Peer tutoring strategies (Peer Tutoring) with prostration material, alms, and fasting and proven to increase spending the achievement rsiswa. From the observation and empirical data in the field shows that the implementation of peer tutoring strategies proven to improve student achievement Islamic Religious Education class VIII-B in SMP Negeri 7 Probolinggo. Pre-test results showed an average value of 61, the results of the first cycle (first meeting) shows the average value of 77, an increase of 26.23% while the average value in the first cycle (second meeting) is 90, an increase of 16.63 of cycle I. it is evident that the implementation of peer tutoring strategies to raise the achievement of students of Islamic Religious Education VIII-B in SMP Negeri 7 Probolinggo

Myoclonus dystonia and muscular dystrophy: ɛ-sarcoglycan is part of the dystrophin-associated protein complex in brain

BACKGROUND: Myoclonus-dystonia is a neurogenic movement disorder caused by mutations in the gene encoding ɛ-sarcoglycan. By contrast, mutations in the α-, β-, γ-, and δ-sarcoglycan genes cause limb girdle muscular dystrophies. The sarcoglycans are part of the dystrophin-associated protein complex in muscle that is disrupted in several types of muscular dystrophy. Intriguingly, patients with myoclonus-dystonia have no muscle pathology; conversely, limb-girdle muscular dystrophy patients have not been reported to have dystonia-associated features. To gain further insight into the molecular mechanisms underlying these differences, we searched for evidence of a sarcoglycan complex in the brain. METHODS: Immunoaffinity chromatography and mass spectrometry were used to purify ubiquitous and brain-specific ɛ-sarcoglycan directly from tissue. Cell models were used to determine the effect of mutations on the trafficking and assembly of the brain sarcoglycan complex. RESULTS: Ubiquitous and brain-specific ɛ-sarcoglycan isoforms copurify with β-, δ-, and ζ-sarcoglycan, β-dystroglycan, and dystrophin Dp71 from brain. Incorporation of a muscular dystrophy-associated β-sarcoglycan mutant into the brain sarcoglycan complex impairs the formation of the βδ-sarcoglycan core but fails to abrogate the association and membrane trafficking of ɛ- and ζ-sarcoglycan. CONCLUSIONS: ɛ-Sarcoglycan is part of the dystrophin-associated protein complex in brain. Partial preservation of ɛ- and ζ-sarcoglycan in brain may explain the absence of myoclonus dystonia-like features in muscular dystrophy patients. © 2016 International Parkinson and Movement Disorder Society

Origine et Processus de Minéralisation des Eaux Souterraines dans la Partie Sud du Marais Poitevin (Nouvelle-AquitaineFrance) et de Son Substratum Carbonaté de l’Oxfordien Supérieur

Le Marais Poitevin est un territoire exploité à des fins économiques. Les activités anthropiques dans cette zone humide mettent en péril l’équilibre qui préside à la recharge naturelle et à leur qualité. L’un des problèmes à résoudre avant d’envisager des solutions de préservation et de sauvegarde de ce territoire est de connaître l’origine et de comprendre le processus de minéralisation des eaux du marais. Pour atteindre ces objectifs, les diagrammes de Piper et de Schöller-Berkaloff couplés à une approche statistique (Analyse en composantes principales) ainsi qu’à la corrélation entre les éléments chimiques ont mis en évidence un phénomène complexe d’eaux bicarbonatées et de mer avec des teneurs atteignant 74%. Les eaux analysées sont proches de la neutralité dans le Marais Poitevin avec un pH moyen de 7,2. Cette étude montre que ces eaux souterraines se singularisent par une grande diversité de leurs faciès en fonction de la position géographique qu’elles occupent. Les eaux localisées à l’Ouest de la zone d’étude sont essentiellement chlorurées sodiques alors que celles localisées à l’Est présentent des faciès qui vont de chlorurés sodiques à bicarbonatés calciques en passant par les faciès bicarbonatés sodiques et sulfatés sodiques. Ainsi, deux origines quant à la minéralisation des eaux du Marais Poitevin ont été mises en évidence. Une minéralisation d’origine marine liée à une contamination des eaux du Marais Poitevin par de l’eau de mer, et une autre liée à la dissolution des minéraux carbonatés des formations encaissantes.   The Poitevin marsh, a territory exploited for economic purposes, is threatened by human activities. One of the problems to be solved before considering solutions for preservation and safeguarding of this territory is to know the origin and to understand the mineralization process of the Poitevin marsh groundwaters. To achieve these objectives, Piper and Schöller-Berkaloff diagrams coupled with a statistical approach (Principal Component Analysis) as well as the correlation between chemical elements highlighted a complex phenomenon of mixing bicarbonate and saline waters with contents reaching 74%. The results show that the waters are close to neutral with an average pH of 7.2. This study carried out on the Poitevin marsh groundwaters has made it possible to show that these waters are distinguished by a great diversity of facies depending on their geographical positions. Waters located to the west of the study area are essentially sodium-chloride type while those located to the East have facies ranging from sodium-chloride type to calcium-bicarbonate type, passing through sodium bicarbonate type and sodium sulfate type. So, two origins of the Poitevin marsh waters mineralization have been highlighted. Mineralization of marine origin linked to the contamination of Poitevin marsh groundwaters by sea water, and another linked to the dissolution of carbonate minerals from surrounding rocks

Origine et Processus de Minéralisation des Eaux Souterraines dans la Partie sud du Marais Poitevin (Poitou-CharentesFrance) et de Son Substratum Carbonaté de l’Oxfordien Supérieur

Le Marais Poitevin est un territoire exploité à des fins économiques. Les activités anthropiques dans cette zone humide mettent en péril l’équilibre qui préside à la recharge naturelle et à la qualité des eaux. L’un des problèmes à résoudre avant d’envisager des solutions de préservation et de sauvegarde de ce territoire est de connaitre l’origine et de comprendre le processus de minéralisation des eaux du marais. Pour atteindre ces objectifs, cette étude menée sur les eaux du Marais Poitevin a permis de montrer que les eaux souterraines du marais se singularisent par une grande diversité de faciès en fonction de la position géographique qu’elles occupent. Les eaux localisées à l’Ouest de la zone d’étude sont essentiellement chlorurées sodiques alors que celles localisées à l’Est présentent des faciès qui vont de chlorurés sodiques à bicarbonatés calciques en passant par les faciès bicarbonatés sodiques et sulfatés sodiques.L’approche statistique (Analyse en Composantes Principales) retenue pour cette étude, couplée à la corrélation entre les éléments chimiques, mettent en évidence un phénomène complexe de mélange d'eaux météoriques, bicarbonatées et salines. Ainsi, deux origines quant à la minéralisation des eaux du Marais Poitevin ont été mises en évidence. Une minéralisation d’origine marine liée à une contamination des eaux du Marais Poitevin par de l’eau de mer, et une autre liée à l'interaction entre les eaux souterraines et la roche encaissante.   The Poitevin marsh, a territory exploited for economic purposes, is threatened by human activities. One of the problems to be solved before considering solutions for preservation and safeguarding of this territory is to know the origin and to understand the mineralization process of the Poitevin marsh groundwaters. To achieve these objectives, this study carried out on the Poitevin marsh groundwaters has made it possible to show that these waters are distinguished by a great diversity of facies depending on their geographical positions. Waters located to the west of the study area are essentially sodium-chloride type while those located to the East have facies ranging from sodium-chloride type to calcium-bicarbonate type, passing through sodium bicarbonate type and sodium sulfate type. The statistical approach (principal component analysis) adopted for this study, coupled with the correlation between the chemical elements, highlights a complex phenomenon of mixing meteoric, bicarbonate and saline waters. So, two origins of the Poitevin marsh waters mineralization have been highlighted. Mineralization of marine origin linked to the contamination of Poitevin marsh groundwaters by sea water, and another to the interaction between Poitevin marsh groundwater and the surrounding rock

Origine et Processus de Minéralisation des Eaux Souterraines dans la Partie sud du Marais Poitevin (Poitou-CharentesFrance) et de Son Substratum Carbonaté de l’Oxfordien Supérieur

Le Marais Poitevin est un territoire exploité à des fins économiques. Les activités anthropiques dans cette zone humide mettent en péril l’équilibre qui préside à la recharge naturelle et à la qualité des eaux. L’un des problèmes à résoudre avant d’envisager des solutions de préservation et de sauvegarde de ce territoire est de connaitre l’origine et de comprendre le processus de minéralisation des eaux du marais. Pour atteindre ces objectifs, cette étude menée sur les eaux du Marais Poitevin a permis de montrer que les eaux souterraines du marais se singularisent par une grande diversité de faciès en fonction de la position géographique qu’elles occupent. Les eaux localisées à l’Ouest de la zone d’étude sont essentiellement chlorurées sodiques alors que celles localisées à l’Est présentent des faciès qui vont de chlorurés sodiques à bicarbonatés calciques en passant par les faciès bicarbonatés sodiques et sulfatés sodiques.L’approche statistique (Analyse en Composantes Principales) retenue pour cette étude, couplée à la corrélation entre les éléments chimiques, mettent en évidence un phénomène complexe de mélange d'eaux météoriques, bicarbonatées et salines. Ainsi, deux origines quant à la minéralisation des eaux du Marais Poitevin ont été mises en évidence. Une minéralisation d’origine marine liée à une contamination des eaux du Marais Poitevin par de l’eau de mer, et une autre liée à l'interaction entre les eaux souterraines et la roche encaissante.   The Poitevin marsh, a territory exploited for economic purposes, is threatened by human activities. One of the problems to be solved before considering solutions for preservation and safeguarding of this territory is to know the origin and to understand the mineralization process of the Poitevin marsh groundwaters. To achieve these objectives, this study carried out on the Poitevin marsh groundwaters has made it possible to show that these waters are distinguished by a great diversity of facies depending on their geographical positions. Waters located to the west of the study area are essentially sodium-chloride type while those located to the East have facies ranging from sodium-chloride type to calcium-bicarbonate type, passing through sodium bicarbonate type and sodium sulfate type. The statistical approach (principal component analysis) adopted for this study, coupled with the correlation between the chemical elements, highlights a complex phenomenon of mixing meteoric, bicarbonate and saline waters. So, two origins of the Poitevin marsh waters mineralization have been highlighted. Mineralization of marine origin linked to the contamination of Poitevin marsh groundwaters by sea water, and another to the interaction between Poitevin marsh groundwater and the surrounding rock

Determinants of out-of-hours service users' potentially inappropriate referral or non-referral to an emergency department: a retrospective cohort study in a local health authority, Veneto Region, Italy

BACKGROUND: A growing presence of inappropriate patients has been recognised as one of the main factors influencing emergency department (ED) overcrowding, which is a very widespread problem all over the world. On the other hand, out-of-hours (OOH) physicians must avoid delaying the diagnostic and therapeutic course of patients with urgent medical conditions. The aim of this study was to analyse the appropriateness of patient management by OOH services, in terms of their potentially inappropriate referral or non-referral of non-emergency cases to the ED. METHODS: This was an observational retrospective cohort study based on data collected in 2011 by the local health authority No. 4 in the Veneto Region (Italy). After distinguishing between patients contacting the OOH service who were or were not referred to the ED, and checking for patients actually presenting to the ED within 24\u2005hours thereafter, these patients' medical management was judged as potentially appropriate or inappropriate. RESULTS: The analysis considered 22\u2005662 OOH service contacts recorded in 2011. The cases of potentially inappropriate non-referral to the ED were 392 (1.7% of all contacts), as opposed to 1207 potentially inappropriate referrals (5.3% of all contacts). Age, nationality, type of disease and type of intervention by the OOH service were the main variables associated with the appropriateness of patient management. CONCLUSIONS: These findings may be useful for pinpointing the factors associated with a potentially inappropriate patient management by OOH services and thus contribute to improving the deployment of healthcare and the quality of care delivered by OOH services