Towards a traceable divider for composite voltage waveforms below 1 kV

open3Voltage divider · Composite and combined voltages · Traceability · Scale factor calibration · Step response · Measurement uncertaintyIn the framework of the European Project 19NRM07 HV-com2 supporting the standardization in high-voltage testing with composite and combined wave shapes, a divider to employ in a test set-up for validation of electrical devices submitted to composite voltages below 1 kV has been developed at the Istituto Nazionale di Ricerca Metrologica (INRIM) and currently is under extensive testing. After a simulation stage, an available divider has been modified to comply with the IEC 60,060 requirements in terms of step response and scale factor. To be suitably fast in replying to step voltages, an adjustment of the components of the low-voltage arm has been made. The divider has been calibrated with traceability to the relevant INRIM National Standards and characterized exploiting its scale factor at different voltages and frequencies. The divider has been then inserted in a set-up with a sinusoidal generator, an impulse generator and coupling–blocking elements to carry out tests at low voltages (below 1 kV) with single voltages. In these tests, the divider showed a satisfactory attitude as converting device and its scale factor is traceable with suitable uncertaintyopenGalliana, F.; Caria, S. E.; Roccato, P. E.Galliana, F.; Caria, S. E.; Roccato, P. E

Optimizing detection of RET and PPARg rearrangements in thyroid neoplastic cells using a home-brew tetracolor probe

BACKGROUND Fluorescence in situ hybridization (FISH) to identify specific DNA target sequences in the nuclei of nondividing cells of numerous solid neoplasms has contributed to the introduction of molecular cytogenetics as a useful adjunct to cytology, leading recently to the "marriage" of the 2 disciplines. Numerous cancer molecular markers can now be investigated using different technical approaches, at both the gene and expression levels, in biopsies of various suspected cancers, including differentiated thyroid carcinoma. The limited amount of bioptic material is often insufficient to carry out multiple tests, and optimizing handling of the biopsy is desirable. METHODS We have developed a home-brew tetracolor break-apart probe able to simultaneously identify the 2 most common genetic alterations in differentiated thyroid carcinoma: RET/PTC variants in papillary thyroid carcinoma and PAX8/PPARg fusion and variants in follicular thyroid carcinoma. RESULTS The probe had 100% specificity, 99.5% sensitivity, and >= 3% cutoff. The probe was tested on RET/PTC and PAX8/PPARg RT-PCR positive controls, and feasibility was assessed in 368 thyroid nodule fine-needle aspirations (FNA). In the latter analysis, 24 FNAs had split RET signal, and 9 had split PPARg signal. FISH analysis of available surgically removed nodules confirmed the sensitivity of FISH in detecting abnormal clones and oligoclones. CONCLUSIONS The home-brew tetracolor probe showed high feasibility, optimizing the use of the biological material in relation to the available molecular tests and maximizing the FISH experimental and slide-scoring times. This probe may be considered an alternative to RT-PCR when recovery and quality of RNA amplification from FNA are insufficient

Rubella in Sub-Saharan Africa and sensorineural hearing loss: a case control study

Rubella infection can affect several organs and cause birth defects that are responsible for congenital rubella syndrome (CRS). Congenital hearing loss is the most common symptom of this syndrome, occurring in approximately 60% of CRS cases. Worldwide, over 100 000 babies are born with CRS every year. There is no specific treatment for rubella, but the disease is preventable by vaccination. Since 1969, the rubella vaccine has been implemented in many countries, but in Africa, only a few countries routinely immunize against rubella. The aim of this study was to estimate the rate of infection from the wild-type rubella virus in São Tomé and Príncipe by determining rubella seroprevalence with a DBS method. The goal of this study was to reinforce the need for implementation of the rubella vaccine in this country. As secondary objectives, the validation of a DBS method was first attempted and an association between seroprevalence and hearing loss was assessed.info:eu-repo/semantics/publishedVersio

The Immune Landscape of Papillary Thyroid Cancer in the Context of Autoimmune Thyroiditis

Simple Summary The association between papillary thyroid cancer and Hashimoto's thyroiditis went through a long-standing human debate recently elucidated by the establishment of a novel mouse model. Papillary thyroid carcinoma is an excellent model for studying the tumor immune microenvironment because it is naturally accompanied by immune cells, making it a good candidate for the treatment with immune checkpoint inhibitors. Papillary thyroid cancer (PTC) often co-occurs with Hashimoto's thyroiditis, an association that has long been reported in clinical studies, remaining controversial. Experimental evidence has recently shown that pre-existing thyroiditis has a beneficial effect on PTC growth and progression by a distinctive expansion of effector memory CD8 T cells. Although the link between inflammation and PTC might involve different components of the immune system, a deep characterization of them which includes T cells, B cells and tertiary lymphoid structures, Mye-loid cells, Neutrophils, NK cells and dendritic cells will be desirable. The present review article considers the role of the adaptive and innate immune response surrounding PTC in the context of Hashimoto's thyroiditis. This review will focus on the current knowledge by in vivo and in vitro studies specifically performed on animals' models; thyroid cancer cells and human samples including (i) the dual role of tumor-infiltrating lymphocytes; (ii) the emerging role of B cells and tertiary lymphoid structures; (iii) the role of myeloid cells, dendritic cells, and natural killer cells; (iv) the current knowledge of the molecular biomarkers implicated in the complex link between thyroiditis and PTC and the potential implication of cancer immunotherapy in PTC patients in the context of thyroiditis

A Novel p.Leu213X Mutation in GJB2 Gene in a Portuguese Family

info:eu-repo/semantics/publishedVersio

Human neuronal cell lines as an in vitro toxicological tool for the evaluation of novel psychoactive substances

Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxy-methamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death

Foramen caróticoclinoideo en cráneos humanos: incidencia, morfometría y sus implicaciones clínicas

The caroticoclinoid foramen is an inconstant structure, formed by the union of the anterior and middle clinoid processes. The aim of this study was to perform an incidence and morphometry of the caroticoclinoid foramen in Brazilian human skulls and discuss its clinical implications. Eighty dry human skulls with sex distinction were used, and 3 groups of incidence were determined: General, sex, and sides. The morphometry was performed using a manual caliper and the major diameter of the foramina was measured; the values were also divided in general, according to sex and sides. The incidence of skulls with at least one foramen was 8.5%. According to the sides, 8.5% of the skulls showed foramen on the right side and 2.5% on the left. We found 2.5% of the skulls with bilateral foramen and 6.25% with unilateral foramen. In relation to sex, the foramens were found in 5% of male skulls and 12.5% of female skulls. The major diameter of this structure presented on mean, values of 5.23 mm on general, 5.18 mm on the right side and 5.35 mm on the left, 5.30 mm in male skulls and 5.18 mm in female skulls. The anatomical characteristics of this foramen should be considered in view of its clinical implications associated with neurosurgery as clinoid process removal, and symptoms as headache due to internal carotid artery alterations in this region. In conclusion knowledge of this structure supports the diagnosis and treatment of clinical complications related to this variation.The caroticoclinoid foramen is an inconstant structure, formed by the union of the anterior and middle clinoid processes. The aim of this study was to perform an incidence and morphometry of the caroticoclinoid foramen in Brazilian human skulls and discuss its clinical implications. Eighty dry human skulls with sex distinction were used, and 3 groups of incidence were determined: General, sex, and sides. The morphometry was performed using a manual caliper and the major diameter of the foramina was measured; the values were also divided in general, according to sex and sides. The incidence of skulls with at least one foramen was 8.5%. According to the sides, 8.5% of the skulls showed foramen on the right side and 2.5% on the left. We found 2.5% of the skulls with bilateral foramen and 6.25% with unilateral foramen. In relation to sex, the foramens were found in 5% of male skulls and 12.5% of female skulls. The major diameter of this structure presented on mean, values of 5.23 mm on general, 5.18 mm on the right side and 5.35 mm on the left, 5.30 mm in male skulls and 5.18 mm in female skulls. The anatomical characteristics of this foramen should be considered in view of its clinical implications associated with neurosurgery as clinoid process removal, and symptoms as headache due to internal carotid artery alterations in this region. In conclusion knowledge of this structure supports the diagnosis and treatment of clinical complications related to this variation292427431Das, S., Suri, R., Kapur, V., Ossification of caroticoclinoid ligament and its clinical importance in skull-based surgery (2007) São Paulo Med. J, 125, pp. 351-353Dodo, Y., Ishida, H., Incidence of nonmetric cranial variant in several population samples from East Asia and North America (1987) J. Anthrop. Soc. Nippon, 95, pp. 161-167Dolenc, V.V., A combined epi and subdural direct approach to carotidophthalmic artery aneurysms (1985) J. Neurosurg, 5, pp. 667-672Donald, P.J., (1998) Surgery of the Skull Base, , Philadelphia, Lippincott- RavenErturk, M., Kayalioglu, G., Govsa, F., Anatomy of the clinoidal region with special emphasis on the caroticoclinoid foramen and interclinoid osseous brid- ge in a recent Turkish population (2004) Neurosurg. Rev, pp. 22-26Gupta, N., Ray, B., Ghosh, S., A study on anterior clinoid process and optic strut with emphasis on variations of caroticoclinoid foramen (2005) Nep. Med. Coll. J, 7, pp. 140-144Hochstetter, F., Über die Taenia interclinoidea,die Commissura alicochlearis und die Cartilago supracochlearis des menschlichen Primordialkraniums.Gegenbaurs Morph (1940) Jahrb, 84, pp. 220-243Inoue, T., Rhoton Jr., A.L., Theele, D., Barry, M.E., Surgical approaches to the cavernous sinus:A microsurgical study (1990) Neurosurg, 6, pp. 903-932Kier, E.L., Embryology of the normal optic canal and its anomalies.An anatomic and roentgenographic stud (1966) Invest. Radiol, 1, pp. 346-362Kobayashi, S., Kyoshima, K., Gibo, H., Hedge, S.A., Takemae, T., Sugita, K., Carotid cave aneurysms of the internal carotid artery (1989) J. Neurosurg, 70, p. 216Lee, H.Y., Chung, I.H., Choi B., Y., Anterior, C., (1997) Yonsei Med. J, 38, pp. 151-154Narolewski, R., Significance of anatomic variants of bony surroundings of the internal carotid artery and their significance for lateral surgical approaches to the cavernous sinus (2003) Ann. Acad. Med. Stetin, 49, pp. 205-229Saka, E., Ozdoǧmus, O., Tulay, C., Gürdal, E., Uzün, I., The anatomy of the carotico-clinoid foramen and its relation with the internal carotid artery (2003) Surg. Radiol. Anat, 25, pp. 241-246Reisch, R., Vutskits, L., Filippi, R., Patonay, L., Fries, G., Perneczky, A., Topographic microsurgical anatomy of the paraclinoid carotid artery (2002) Neurosurg Rev, 25, pp. 177-183Sekhar, L.N., Akin, O., Anatomical study of the cavernous sinus emphasizing operative approaches and related vascular and neural reconstruction (1987) Neurosurg, 21, pp. 806-816Seoane, E., Rhoton, A.L., Oliveira, E., Microsurgical anatomy of the dural collar (carotid collar) and rings around the clinoid segment of the internal carotid artery (1998) Neurosurg, 42, pp. 869-886Sicher, H., du Brul, E.L., (1977) Oral Anatomy, , 6ed. Rio de Janeiro, Guanabara KooganStandring, S., Overview of the Development of the Head and Neck Head: Skull and Mandible Gray's anatomy: The anatomical basis of clinical practice, p. 2005. , New York, ElsevierEl foramen caróticoclinoideo es una estructura inconstante formada por la unión de la procesos clinoides anterior y medio. El objetivo de este estudio fue revisar la incidencia y la morfometría del foramen caróticoclinoideo en cráneos humanos brasileños y discutir sus implicaciones clínicas. Se utilizaron 80 cráneos humanos secos, de ambos sexos, determinando tres variables: sexo y lados derecho e izquierdo. La morfometría se realizó con un cáliper manual midiéndose el diámetro máximo del foramen. La incidencia de cráneos con al menos un foramen fue de 8,5%. El 8,5% de los cráneos presentó un foramen en el lado derecho y el 2,5% en el izquierdo. El 2,5% de los cráneos presentó un foramen bilateral y el 6,25% un foramen unilateral. En relación al sexo, los forámenes se encontraron en el 5% de los cráneos de hombres y el 12,5% de los cráneos de mujeres. El diámetro máximo de esta estructura presentó en promedio, valores de 5,23 mm; 5,18 mm en el lado derecho y 5,35 mm en el izquierdo; 5,30 mm en cráneos de hombres y 5.18 mm en cráneos de mujeres. Las características anatómicas de este foramen deben ser consideradas debido a las implicaciones clínicas asociadas a la neurocirugía, como la eliminación del proceso clinoides y a síntomas como cefaleas producto de alteraciones en la arteria carótida interna en esta región. En conclusión, el conocimiento de esta estructura mejora el diagnóstico y tratamiento de las complicaciones clínicas relacionadas con esta variació

Gender effect, quality of life and genetic biomarkers in a Portuguese sample with ARHL with or without tinnitus

Trabalho apresentado em Symposium & 56th Inner Ear Biology Workshop, 7-10 setembro de 2019, Pádua, ItáliaN/

Synthesis, Antitumor and Antiviral In Vitro Activities of New Benzotriazole-Dicarboxamide Derivatives

Cancer and viral infections continue to threaten humankind causing death worldwide. Hence, the discovery of new anticancer and antiviral agents still represents a major scientific goal. Heterocycles designed to mimic the chemical structure of natural pyrimidines and purines have been designed over the years, exerting their activity acting as false substrates on several different targets. We reported a series of bis-benzotriazole-dicarboxamide derivatives which inhibit viral helicase of poliovirus, and hence we planned structure modifications to obtain different series of new dicarboxamides. Here, the synthesis and characterization of 56 new compounds: 31 bis-benzotriazole dicarboxamides and 25 mono-substituted acidic derivatives are reported. The synthesized compounds were tested for their antiviral and antitumor activity. Mostly, compounds 4a, 4c and 4d showed antiviral activity against tested Picornaviruses, Coxsackievirus B5 and Poliovirus-1. Likewise, four derivatives (3b, 3d, 4d, 9b) showed notable antiproliferative activity inhibiting cell growth in two distinct antitumor screenings. Compound 3b was selected as the antitumor lead compound for the wide range of activity and the potency proved. The lead compound was proved to induce apoptosis in SK-MES1 tumor cells, in a dose-dependent manner

Inhibition of enterovirus a71 by a novel 2-phenyl-benzimidazole derivative

Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern at the global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, widespread A71 enterovirus also occurred in European countries. EV-A71 infection causes hand-foot-mouth disease (HFMD), herpangina, and fever. However, it can sometimes induce a variety of neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and acute flaccid paralysis. We identified new benzimidazole derivatives and described theirin vitrocytotoxicity and broad-spectrum anti-enterovirus activity. Among them, derivative 2b resulted in interesting activity against EV-A71, and therefore it was selected for further investigations. Compound 2b proved to be able to protect cell monolayers from EV-A71-induced cytopathogenicity, with an EC50 of 3 µM. Moreover, Vero-76 cells resulted in being significantly protected from necrosis and apoptosis when treated with 2b at 20 and 80 µM. Compound 2b reduced viral adsorption to Vero-76 cells, and when evaluated in a time-of-addition assay, the derivative had the highest effect when added during the infection period. Moreover, derivative 2b reduced viral penetration into host cells. Besides, 2b did not affect intestinal monolayers permeability, showing no toxic effects. A detailed insight into the efficacy of compound 2b against EV-A71 showed a dose-dependent reduction in the viral titer, also at low concentrations. Mechanism of action investigations suggested that our derivative can inhibit viral endocytosis by reducing viral attachment to and penetration into host cells. Pharmacokinetic and toxicity predictions validated compound 2b as a good candidate for furtherin vivoassays