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Michelantonio De Fano, Alberto Falorni, Massimo Malara, Francesca Porcellati, Carmine Giuseppe Fanelli Department of Medicine and Surgery, Endocrine and Metabolic Sciences Section, University of Perugia, Perugia, ItalyCorrespondence: Michelantonio De Fano; Carmine Giuseppe Fanelli, Email michelantonio.defano@gmail.com; carmine.fanelli@unipg.itAbstract: Patients suffering from acromegaly and Cushing’s Disease (CD) face the risk of several clinical complications. The onset of diabetes mellitus (DM) is among the most important: exposure to elevated growth hormone or cortisol levels is associated with insulin resistance (IR). DM contributes to increasing cardiovascular risk for these subjects, which is higher compared to healthy individuals. Hyperglycemia may also be caused by pasireotide, a second-generation somatostatin receptor ligand (SRLs), currently used for the treatment of these diseases. Accordingly, with 2014 medical expert recommendations, the management of hyperglycemia in patients with CD and treated with pasireotide is based on lifestyle changes, metformin, DPP-4 inhibitors (DPP-4i) and, subsequently, GLP-1 Receptor Agonists (GLP-1 RAs). There is no position for SGLT2-inhibitors (SGLT2-i). However, a very recent experts’ consensus regarding the management of pasireotide-induced hyperglycemia in patients with acromegaly suggests the use of GLP-1 RAs as first line treatment (in suitable patients) and the use of SGLT2-i as second line treatment in patients with high cardiovascular risk or renal disease. As a matter of fact, beyond the hypoglycemic effect of GLP1-RAs and SGLT2-i, there is increasing evidence regarding their role in the reduction of cardiovascular risk, commonly very high in acromegaly and CD and often tough to improve despite biochemical remission. So, an increasing use of GLP1-RAs and SGLT2-i to control hyperglycemia is desirable in these diseases. Obviously, all of that must be done with due attention in order to minimize the occurrence of adverse events. For this reason, large studies are needed to analyze the presence of potential limitations.Keywords: acromegaly, Cushing’s disease, pasireotide, hyperglycemia, diabetes mellitus, cardiovascular risk

La difusión de estrategias que apuntan a la desarticulación de los efectos del patriarcado en el lenguaje ha originado una gran discusión en torno a la legitimidad de los usos no sexistas de la lengua, lo que ha despertado el interés de distintos actores sociales, entre los cuales se encuentran academias de la lengua como la Real Academia Española y la Academia Chilena de la Lengua. Se analizan las ideologías lingüísticas que subyacen en las intervenciones que integran un ciclo de conferencias organizado por la Academia Chilena de la Lengua desde la perspectiva glotopolítica. El marco teórico proviene de los lineamientos teóricos y metodológicos de la Escuela Francesa del Análisis del Discurso. Los resultados muestran que las ideologías lingüísticas identificadas se anclan a un sistema ideológico de tipo hetero normado y patriarcal, en el cual la Academia Chilena de la Lengua busca relegitimarse: por un lado, a través de la construcción de una imagen de sí progresista, y, por el otro, desde el lugar de expertos.

Abstract The expansion of urbanization in natural environments increases interactions between wildlife, domestic animals, and humans. In Italy, the red fox (Vulpes vulpes) is one of the most common wild carnivores. This species can serve as a reservoir and sentinel host for several infectious diseases. We aimed to improve knowledge about the exposure of red foxes to selected zoonotic (Anaplasma spp, Ehrlichia spp., Borrelia spp., and hepatitis E virus) and carnivore-specific pathogens (canine parvovirus, canine distemper virus, pseudorabies virus, and Dirofilaria spp.) through a retrospective survey performed in the Tuscany region during the spring season of 2013. Using specific ELISAs and serum samples (n = 38) collected during a culling campaign, a prevalence of 2.6% for canine distemper virus, 18.4% for canine parvovirus, 5.2% for Anaplasma spp., 2.6% for Ehrlichia spp., 7.9% for Dirofilaria spp., 21.05% for hepatitis E virus, and 10.5% for pseudorabies virus was observed. Conversely, antibodies against Borrelia spp. were not identified in any of the animals. Our results revealed no significant sex-related differences in seroprevalence and confirmed hepatitis E virus as the most common pathogen in the analyzed samples. All of the animals that tested positive for tick-borne zoonotic agents presented ticks at the time of sampling. Our study confirms the exposure of red foxes in the Tuscany region to viral and bacterial infections raising medical and veterinary concern and indicating the need for large-scale surveillance to fully assess the epidemiological significance of these findings.

Adrenocortical autoantibodies (ACA), present in 60-80% of patients with idiopathic Addison's disease, are conventionally detected by indirect immunofluorescence (IIF) on frozen sections of adrenal glands. The large-scale use of IIF is limited in part by the need for a fluorescence microscope and the fact that histological sections cannot be stored for long periods of time. To circumvent these restrictions we developed a novel peroxidase-labelled protein A (PLPA) technique for the detection of ACA in patients with Addison's disease and compared the results with those obtained with the classical IIF assay. We studied serum samples from 90 healthy control subjects and 22 patients with Addison's disease, who had been clinically classified into two groups: idiopathic (N = 13) and granulomatous (N = 9). ACA-PLPA were detected in 10/22 (45%) patients: 9/13 (69%) with the idiopathic form and 1/9 (11%) with the granulomatous form, whereas ACA-IIF were detected in 11/22 patients (50%): 10/13 (77%) with the idiopathic form and 1/9 (11%) with the granulomatous form. Twelve of the 13 idiopathic addisonians (92%) were positive for either ACA-PLPA or ACA-IIF, but only 7 were positive by both methods. In contrast, none of 90 healthy subjects was found to be positive for ACA. Thus, our study shows that the PLPA-based technique is useful, has technical advantages over the IIF method (by not requiring the use of a fluorescence microscope and by permitting section storage for long periods of time). However, since it is only 60% concordant with the ACA-IIF method, it should be considered complementary instead of an alternative method to IIF for the detection of ACA in human sera.

En este artículo se presentan los resultados de una Revisión Sistemática de la Literatura de los estudios de actitudes lingüísticas en el ámbito hispanohablante chileno, realizados entre 2010 y 2020, con el afán de determinar los temas tratados, las metodologías, los resultados de los estudios, y si existe algún vacío en la literatura. La revisión se ha hecho en las bases de datos WoS, Scopus y SciELO a través del descriptor Linguistic attitudes y ha generado un total de 12 artículos. Se concluye que la mayoría de los estudios se ha llevado a cabo en Santiago y con técnica directa; además, se plantean algunos temas que no han sido abordados y que podría ser interesante averiguar, como las actitudes hacia el lenguaje no sexista.

Autoimmune Addison’s disease is a rare complex disease, which has not yet been characterized by non-biased genetic studies. Here, the authors perform the first GWAS for the disease, identifying nine loci including two coding variants in the gene Autoimmune Regulator (AIRE).

Landslides and slope failures represent critical hazards for both the safety of local communities and the potential damage to economically relevant infrastructure such as roads, hydroelectric plants, pipelines, etc. Numerous surveillance methods, including ground-based radar, InSAR, Lidar, seismometers, and more recently computer vision, are available to monitor landslides and slope instability. However, the high cost, complexity, and intrinsic technical limitations of these methods frequently require the design of alternative and complementary techniques. Here, we provide an improved methodology for the application of image-based computer vision in landslide and rockfall monitoring. The newly developed open access Python-based software, Akh-Defo, uses optical flow velocity, image differencing and similarity index map techniques to calculate land deformation including landslides and rockfall. Akh-Defo is applied to two different datasets, notably ground- and satellite-based optical imagery for the Plinth Peak slope in British Columbia, Canada, and satellite optical imagery for the Mud Creek landslide in California, USA. Ground-based optical images were processed to evaluate the capability of Akh-Defo to identify rockfalls and measure land displacement in steep-slope terrains to complement LOS limitations of radar satellite images. Similarly, satellite optical images were processed to evaluate the capability of Akh-Defo to identify ground displacement in active landslide regions a few weeks to months prior to initiation of landslides. The Akh-Defo results were validated from two independent datasets including radar-imagery, processed using state of the art SqueeSAR algorithm for the Plinth Peak case study and very high-resolution temporal Lidar and photogrammetry digital surface elevation datasets for the Mud Creek case study. Our study shows that the Akh-Defo software complements InSAR by mitigating LOS limitations via processing ground-based optical imagery. Additionally, if applied to satellite optical imagery, it can be used as a first stage preliminary warning system (particularly when run on the cloud allowing near real-time processing) prior to processing more expensive but more accurate InSAR products such as SqueeSAR.

Daniele Cappellani,1 Enrico Macchia,1 Alberto Falorni,2 Piero Marchetti3 1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy; 2Department of Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perugia, Italy; 3Department of Clinical and Experimental Medicine, Division of Metabolism and Cell Transplantation, University of Pisa, Pisa, ItalyCorrespondence: Daniele CappellaniDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Ospedale Cisanello, via Paradisa 2, Pisa 56124, ItalyTel +39 50 995001Fax +39 50 578772Email d.cappellani@hotmail.itAbstract: Insulin autoimmune syndrome (IAS), also named Hirata’s disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). IAS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (ie, a medication or a viral infection) acts on an underlying predisposing genetic background. IAS pathogenesis involves the formation of insulin-IAA complexes that induce glycemic alterations with a double-phase mechanism: IAA prevent insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. The gold standard for the definitive diagnosis is the finding of IAA in a blood sample. Because IAS is frequently a self-remitting disease, its management mostly consists of supportive measures, such as dietary modifications, aimed at preventing the development of hypoglycemia. Pharmacological therapies may occasionally be necessary for patients presenting with severe manifestations of IAS. Available therapies may include drugs that reduce pancreatic insulin secretion (somatostatin analogues and diazoxide, for instance) and immunosuppressive agents (glucocorticoids, azathioprine and rituximab). The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.Keywords: insulin autoimmune syndrome, IAS, Hirata, hypoglycemia, autoimmunity

Microelectromechanical systems (MEMS) are nowadays widespread in the sensor market, with several different applications. New production techniques and ever smaller device geometries require a continuous investigation of potential failure mechanisms in such devices. This work presents an experimental on-chip setup to assess the geometry- and material-dependent strength of stoppers adopted to limit the deformation of movable parts, using an electrostatically actuated device. A series of comb-finger and parallel plate capacitors are used to provide a rather large stroke to a shuttle, connected to the anchors through flexible springs. Upon application of a varying voltage, failure of stoppers of variable size is observed and confirmed by post-mortem ΔC–V curves. The results of the experimental campaign are collected to infer the stochastic property of the strength of polycrystalline, columnar silicon films.

The circulation of strategies that aim to dismantle the effects of patriarchy in language has given rise to discussions around the legitimacy of non-sexist uses of language, awakening the interest of different social actors including language institutions such as the Royal Spanish Academy and the Chilean Academy of Language. From the glottopolitical perspective, the objective of this study is to analyze the linguistic ideologies that underlie the interventions that form part of a cycle of conferences organized by the Chilean Academy of Language. The corpus was analyzed under the theoretical and methodological guidelines of the French school of Discourse Analysis. The results show that the linguistic ideologies underlying the interventions are anchored on a heteronormative and patriarchal ideological system, in which the Chilean Academy of Language seeks to legitimize itself: on the one hand, through the construction of a progressive self-image, and, on the other, from their role as experts. [ABSTRACT FROM AUTHOR]

The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator (AIRE) gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Once synthesized, the self-antigens are presented to, and cause deletion of, the self-reactive thymocyte clones. The clinical diagnosis of APS1 is based on the classic triad idiopathic hypoparathyroidism (HPT)—chronic mucocutaneous candidiasis—autoimmune Addison's disease (AAD), though new criteria based on early non-endocrine manifestations have been proposed. HPT is in most cases the first endocrine component of the syndrome; however, APS1-associated AAD has received the most accurate biochemical, clinical, and immunological characterization. Here is a comprehensive review of the studies on APS1-associated AAD from initial case reports to the most recent scientific findings.

Insulin autoimmune syndrome (IAS), or Hirata disease, is a rare hypoglycaemic disorder caused by the presence of high titer of insulin autoantibodies (IAA) in patients without previous exposure to exogenous insulin. Even though its pathogenesis is not fully understood, striking evidences link IAS to previous exposure to sulphydryl-containing medications, like alpha-lipoic acid, a widely used nutritional supplement. Although challenging, a careful differential diagnosis from other causes of hyperinsulinaemic hypoglycaemia (such as insulinoma) is mandatory, since these conditions require different therapeutic approaches. In the present study, we report a 35-year-old woman originally from Sri Lanka who was referred to our University Hospital on suspicion of occult insulinoma. Her medical history was positive for endometriosis, treated with estroprogestins and alpha-lipoic acid. The latter supplement was begun 2 weeks before the first hypoglycaemic episode. Our tests confirmed the presence of hypoglycaemia associated with high insulin and C-peptide concentrations. When insulin concentrations were compared using different assays, the results were significantly different. Moreover, insulin values significantly decreased after precipitation with polyethylene glycol. An assay for IAA proved positive (530 U/mL). A genetic analysis revealed the presence of HLA-DRB1*04,15, an immunogenetic determinant associated with IAS. On the basis of clinical data we avoided a first-line approach with immunosuppressive treatments, and the patient was advised to modify her diet, with the introduction of frequent low-caloric meals. During follow-up evaluations, glucose levels (registered trough a flash glucose monitoring system) resulted progressively more stable. IAA titer progressively decreased, being undetectable by the fifteenth month, thus indicating the remission of the IAS.