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Multicentre preclinical randomized controlled trials (pRCTs) are a valuable tool to improve experimental stroke research, but are challenging and therefore underused. A common challenge regards the standardization of procedures across centres. We here present the harmonization phase for the quantification of sensorimotor deficits by composite neuroscore, which was the primary outcome of two multicentre pRCTs assessing remote ischemic conditioning in rodent models of ischemic stroke. Ischemic stroke was induced by middle cerebral artery occlusion for 30, 45 or 60 min in mice and 50, 75 or 100 min in rats, allowing sufficient variability. Eleven animals per species were video recorded during neurobehavioural tasks and evaluated with neuroscore by eight independent raters, remotely and blindly. We aimed at reaching an intraclass correlation coefficient (ICC) ≥0.60 as satisfactory interrater agreement. After a first remote training we obtained ICC = 0.50 for mice and ICC = 0.49 for rats. Errors were identified in animal handling and test execution. After a second remote training, we reached the target interrater agreement for mice (ICC = 0.64) and rats (ICC = 0.69). In conclusion, a multi-step, online harmonization phase proved to be feasible, easy to implement and highly effective to align each centre’s behavioral evaluations before project’s interventional phase.

The normal menstrual cycle requires a delicate interplay between the hypothalamus, pituitary and ovary. Therefore, its length is an important indicator of female reproductive health. Menstrual cycle length has been shown to be partially controlled by genetic factors, especially in the follicle-stimulating hormone beta-subunit (FSHB) locus. A genome-wide association study meta-analysis of menstrual cycle length in 44 871 women of European ancestry confirmed the previously observed association with the FSHB locus and identified four additional novel signals in, or near, the GNRH1, PGR, NR5A2 and INS-IGF2 genes. These findings not only confirm the role of the hypothalamic–pituitary–gonadal axis in the genetic regulation of menstrual cycle length but also highlight potential novel local regulatory mechanisms, such as those mediated by IGF2.

Many clinical conditions affecting children can be associated with a loss of bone mass and quality, leading to an increased risk of fracture over the life. Actually, different techniques are available to assess bone density and/or bone quality, but their employment in children and adolescents requires the acknowledgement of their characteristics and reference values, as well as of age, sex and pubertal stage of the patient. In this paper, the main densitometric techniques are described, and the principal conditions potentially affecting bone health in young people are indicated, with the intention of providing a small guide to prevent fractures in people at risk.

The remodelling process of bone acted by osteoblastic and osteoclastic cells allows the tissue to maintain its integrity and mechanical properties. Systemic factors, such as hormonal status, nutrition, physical inactivity, exposure to smoking, alcohol, or particular drugs, as well as a local variation in the load, can influence bone turnover, and consequently, bone mass. In this paper, physical and biochemical factors are described, which are crucially important during the period of growth, i.e. childhood and adolescence, for the construction of a healthy bone.

The prevalence of pediatric obesity is increasing and many patients are followed by specialized centers or private doctors. The aim of this study was to verify short- and medium term results of a therapeutic approach based on nutritional intervention in a large pediatric population: 1383 subjects (695 females, 688 males) aged 10.1 +/- 2.7 yr, followed in 11 pediatric departments in Italy. No difference was found between centers in age, height, weight, BMI and IBW. The drop-out rate after the first visit was 30.2% (58.1% IBW140%) in females and 34.2% (70.7% IBW140%) in males. After two years of follow-up only 9.7% of females and 6.4% of males remained on treatment. Of these patients only 7.3% of females and 6.4% of males had IBW120%. These data show that an approach based on nutritional intervention alone is not sufficient for long-term treatment of pediatric obesity. Only an approach started early and involving the family can produce permanent results.

Cultural heritage constitutive materials can provide excellent substrates for microbial colonisation, highly influenced by thermo-hygrometric parameters. In cultural heritage-related environments, a detrimental microbial load may be present both on artworks surface and in the aerosol. Confined environments (museums, archives, deposits, caves, hypogea) are characterised by peculiar structures and different thermo-hygrometric conditions, influencing the development of a wide range of microbial species, able to induce artefact biodeterioration and to release biological particles in the aerosol (spores, cellular debrides, toxins, allergens) potentially dangerous for the human health (visitors/users). In order to identify the real composition of the biological consortia, highlighting also the symbiotic relationships between microorganisms (cyanobacteria, bacteria, fungi) and macro-organisms (plants, bryophyte, insects), an interdisciplinary approach is needed. The results from in vitro culture, microscopy and molecular biology analysis are essential for a complete understanding of both microbial colonisation of the cultural objects and the potential relationship with illness to human. Concerning the bioaerosol, of crucial importance are the time and techniques for sampling.

0. Introduzione. — 1. Il diritto primitivo come ordinamento giuridico completamente decentralizzato basato sulla vendetta di sangue. — 1.1. I sistemi vendicatori come prima forma di diritto. — 1.2. Il diritto come tecnica sociale di motivazione indiretta basata su sanzioni coercitive. — 2. La vendetta di sangue come fenomeno sociale nella prospettiva sociologica e antropologica. — 2.1. L’aspetto soggettivo del carattere sociale della vendetta. — 2.2. L’aspetto oggettivo del carattere sociale della vendetta. — 3. La vendetta di sangue come fenomeno normativo nella teoria pura del diritto. — 3.1. La vendetta di sangue e il principio di imputazione. — 3.2. Il vendicatore come organo della comunità e il monopolio dell’uso della forza. — 4. La vendetta di sangue nell’evoluzione del diritto come specifica tecnica sociale. — 4.1. La vendetta di sangue come ordinamento giuridico decentralizzato. — 4.2. Dagli ordinamenti vendicatori al diritto degli stati moderni. — 4.3. La graduale differenziazione e centralizzazione delle tre fasi dell’applicazione del diritto. — 4.4. La rilevanza della dimensione procedurale nella teoria della vendetta di sangue di Kelsen.

The biodeterioration of organic and inorganic materials, as well as polymers, is a complex of alteration processes induced by the growing and metabolic activity of organisms. It can be recognized on monuments, wall paintings, stone, wood, paper, vegetal/animal fibers, and parchment artworks. As defined by Hueck, 1968, biodeterioration is “any undesirable change in the properties of a material caused by the vital activities of organisms”; this definition is accepted as the meaning of the phenomenon. Both macroorganisms (such as animals, plants, and mosses) and microorganisms (such as autotrophic or heterotrophic bacteria, microfungi, cyanobacteria, algae, and lichens) represent the triggers of biodeterioration for cultural heritage. Understanding the morphological and physiological features of the biodeteriogens is required to establish the kind of interaction that occurs with the material and to assess the cause-effect of the biodeterioration action of a specific identified biological agent. For a complete evaluation of biodeterioration, a proper sampling and identification of the majority of biodeteriogens are required. Therefore, in order to apply a prompt and effective conservation to limit further damage, evaluating and quantifying the presence of biological systems that induce damage in heritage materials is indispensable.

Realazioni tra luipi, pastorizia e cani da pastore in Sicilia

The hypothalamic–pituitary–gonadal axis is of relevance in many processes related to the development, maturation and ageing of the male. Through this axis, a cascade of coordinated activities is carried out leading to sustained testicular endocrine function, with gonadal testosterone production, as well as exocrine function, with spermatogenesis. Conditions impairing the hypothalamic–pituitary–gonadal axis during paediatric or pubertal life may result in delayed puberty. Late-onset hypogonadism is a clinical condition in the ageing male combining low concentrations of circulating testosterone and specific symptoms associated with impaired hormone production. Testosterone therapy for congenital forms of hypogonadism must be lifelong, whereas testosterone treatment of late-onset hypogonadism remains a matter of debate because of unclear indications for replacement, uncertain efficacy and potential risks. This Primer focuses on a reappraisal of the physiological role of testosterone, with emphasis on the critical interpretation of the hypogonadal conditions throughout the lifespan of the male individual, with the exception of hypogonadal states resulting from congenital disorders of sex development. Fil: Salonia, Andrea. Università Vita-Salute San Raffael; Italia Fil: Rastrelli, Giulia. University of Florence; Italia Fil: Hackett, Geoffrey. University of Bedfordshire; Reino Unido Fil: Seminara, Stephanie B.. Massachusetts General Hospital ; Department Of Medicine ; Harvard Medical School; Estados Unidos Fil: Huhtaniemi, Ilpo T.. University College London; Estados Unidos Fil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Hellstrom, Wayne J. G.. University of Tulane; Estados Unidos Fil: Palmert, Mark R.. University of Toronto; Canadá Fil: Corona, Giovanni. University of Florence; Italia Fil: Dohle, Gert R.. Erasmus University Medical Centre; Países Bajos Fil: Khera, Mohit. Baylor College of Medicine; Fil: Chan, Yee-Ming. Harvard Medical School; Estados Unidos Fil: Maggi, Mario. University of Florence; Italia

Adorno’s critique of Hegel goes beyond the terms of a facile opposition between a positive and reconciled formula of dialectics and a negative version that insists on unresolved conflict. It should not be simplistically placed under the sign of reiteration of the negative. On the contrary, one could say that what is damaged by Adorno’s philosophical proposal is precisely the negative in a radical sense affecting the fate of dialectics tout court. This is because the deeper meaning of Adorno’s reference to the non-identical appears, precisely, as an instance of suppression of dialectical thinking as such. That is to say, the non-identical can reveal its face only to a gaze that, paradoxically, does not consider it mainly from the point of view of negation.

L'ontologia dei fenomeni giuridici si inscrive nell'ambito della più ampia ontologia dei fenomeni istituzionali, e condivide con essa alcune proprietà peculiari. Nell'ambito del diritto e dei fenomeni istituzionali vi sono infatti fenomeni che sono normativamente impossibili non perché vietati, ma perché non vi sono regole costitutive che ne costituiscano il tipo. L'articolo indaga la natura della relazione fra type, token ed effetti di un atto nell'ambito dei fenomeni istituzionali, comparandola con le differenti relazioni che contraddistinguono l'ambito dei fenomeni naturali. Attraverso la distinzione dei concetti di atipicità privativa e atipicità negativa e di tipo analogico e tipo katalogico, viene proposta l'ipotesi che, nell'ambito dei fenomeni giuridici e istituzionali e a differenza dei fenomeni naturali, il type costituisca il prius logico delle sue occorrenze, e che pertanto l'ontologia istituzionale sia primariamente un'ontologia di types.