Genetic and clinical peculiarities in a new family with hereditary hypophosphatemic rickets with hypercalciuria: a case report

Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder (OMIM #241530), characterized by decreased renal phosphate reabsorption that leads to hypophosphatemia, rickets, and bone pain; hypophosphatemia is believed to stimulate 1,25 dihydroxyvitamin D synthesis which, in turn, results in hypercalciuria. Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c sodium phosphate cotransporter encoded by the SLC34A3 gene. This report shows a family with a non-previously identified mutation in the SLC34A3 gene and exhibiting mild and different manifestations of HHRH. The probandus had hypophosphatemia, elevated serum 1,25 dihydroxyvitamin D concentrations, high serum alkaline phosphatase levels, hypercalciuria and nephrocalcinosis. The other members of the family presented some of these alterations: the mother, hypercalciuria and high 1,25 dihydroxyvitamin D concentrations; the son, hypercalciuria, high 1,25 dihydroxyvitamin D values and elevated alkaline phosphatases; the father, high alkaline phosphatases. The genetic analysis revealed the existence of a single mutation (G78R) in heterozygosis in the SLC34A3 gene in the probandus, her mother and her brother, but not in the father. These findings suggest that he mutation in heterozygosis likely gave rise to a mild phenotype with different penetrance in the three relatives and also indicates that the elevation of 1,25 dihydroxyvitamin D does not result from hypophosphatemia. Thus, this family raises some issues on the transmission and pathophysiology of hereditary hypophosphatemic rickets with hypercalciuria

Diagnostic performance of CerTest and Panbio antigen rapid diagnostic tests to diagnose SARS-CoV-2 infection

Objectives Antigen rapid diagnostic tests (Ag-RDT) have been developed as reliable tools to control the SARS-CoV-2 pandemic. The objective of our study was to evaluate the diagnostic performance of two Ag-RDTs. Methods We evaluated CerTest SARS-CoV-2 Ag One Step Card Test and Panbio COVID-19 Ag Rapid Test Device Ag-RDTs. We included 320 nasopharyngeal samples: 150 PCR negative samples to assess the specificity and 170 PCR positive samples to evaluate the sensitivity. We also evaluated their sensitivity according to cycle threshold (Ct) values and the time from the onset of symptoms. Tests were compared using the McNemar?s test and agreement was evaluated using the kappa score (k). Results Both Ag-RDTs showed a specificity of 100 %. Overall sensitivity was 53.5 % for CerTest and 60.0 % for Panbio. For samples with 25, sensitivity was 94.0 % for CerTest and 96.4 % for Panbio (p = 0.500). Regarding samples with Ct>25, sensitivity was 14.0 % for CerTest and 24.4 % for Panbio (p = 0.004). Sensitivity for samples within the first 5 days after the onset of symptoms were 84.8 % for CerTest and 91.3 % for Panbio (p = 0.250) and notably decreased for samples taken after the fifth day. Both Ag-RDTs showed an excellent agreement between them (agreement = 96.7 %, k = 0.920). Agreement with PCR was also excellent for high viral load samples (Ct<25) for CerTest (98.0 %, k = 0.954) and Panbio (98.8 %, k = 0.973). Conclusions CerTest SARS-CoV-2 and Panbio COVID-19 Ag showed excellent performance and agreement results for samples with high viral loads (Ct 25) or samples taken within the first 5 days after the onset of symptoms

Synthesis of SARS-CoV-2 Mpro inhibitors bearing a cinnamic ester warhead with in vitro activity against human coronaviruses

COVID-19 now ranks among the most devastating global pandemics in history. The causative virus, SARS-CoV-2, is a new human coronavirus (hCoV) that spreads among humans and animals. Great efforts have been made to develop therapeutic agents to treat COVID-19, and among the available viral molecular targets, the cysteine protease SARS-CoV-2 Mpro is considered the most appealing one due to its essential role in viral replication. However, the inhibition of Mpro activity is an interesting challenge and several small molecules and peptidomimetics have been synthesized for this purpose. In this work, the Michael acceptor cinnamic ester was employed as an electrophilic warhead for the covalent inhibition of Mpro by endowing some peptidomimetic derivatives with such a functionality. Among the synthesized compounds, the indole-based inhibitors 17 and 18 efficiently impaired the in vitro replication of beta hCoV-OC-43 in the low micromolar range (EC50 = 9.14 μM and 10.1 μM, respectively). Moreover, the carbamate derivative 12 showed an antiviral activity of note (EC50 = 5.27 μM) against another hCoV, namely hCoV-229E, thus suggesting the potential applicability of such cinnamic pseudopeptides also against human alpha CoVs. Taken together, these results support the feasibility of considering the cinnamic framework for the development of new Mpro inhibitors endowed with antiviral activity against human coronaviruses

Dificultades en el proceso de distribución, como elemento clave en la cadena de suministros

La cadena de suministro es el conjunto de procesos para posicionar e intercambiar materiales, servicios, productos semi-terminados, productos terminados, operaciones de post acabado logístico, de posventa y logística inversa, así como de información, en la logística integrada que va des de la procuración y adquisición de materia prima hasta la entrega y puesta en servicio de productos terminados al consumidor final. Todas las empresas están de un modo u otro en una cadena de suministro, dado que no son autosuficientes en un mercado cada vez más especializado. La selección de proveedores, combinada con los clientes, crean el núcleo de la cadena de suministro de una empresa. La tecnología juega un papel importante al facilitar la integración con los clientes, así como con proveedores de materiales y servicios.The supply chain is the set of processes to position and exchange materials, Services, semi-finished products, finished products, post-finishing operations. logistics, after-sales and reverse logistics, as well as information, in integrated logistics that in the process of Finished products to the final consumer. All companies are in one way or another in a supply chain, since they are not Self-sufficient in an increasingly specialized market. The selection of suppliers, combined with customers, they create the core of a company's supply chain. The Technology plays an important role in facilitating integration with customers, as well as with Suppliers of materials and services

X-linked hypophosphatemia and growth

X-Linked hypophosphatemia (XLH) is the most common form of hereditary rickets caused by loss-of function mutations in the PHEX gene. XLH is characterized by hypophosphatemia secondary to renal phosphate wasting, inappropriately low concentrations of 1,25 dihydroxyvitamin D and high circulating levels of fibroblast growth factor 23 (FGF23). Short stature and rachitic osseous lesions are characteristic phenotypic findings of XLH although the severity of these manifestations is highly variable among patients. The degree of growth impairment is not dependent on the magnitude of hypophosphatemia or the extent of legs´ bowing and height is not normalized by chronic administration of phosphate supplements and 1α hydroxyvitamin D derivatives. Treatment with growth hormone accelerates longitudinal growth rate but there is still controversy regarding the potential risk of increasing bone deformities and body disproportion. Treatments aimed at blocking FGF23 action are promising, but information is lacking on the consequences of counteracting FGF23 during the growing period. This review summarizes current knowledge on phosphorus metabolism in XLH, presents updated information on XLH and growth, including the effects of FGF23 on epiphyseal growth plate of the Hyp mouse, an animal model of the disease, and discusses growth hormone and novel FGF23 related therapies

Selective in vitro and in silico butyrylcholinesterase inhibitory activity of diterpenes and rosmarinic acid isolated from Perovskia atriplicifolia Benth. and Salvia glutinosa L.

Cholinesterase inhibition is one of the most treatment strategies against Alzheimer's disease (AD) where metal accumulation is also strongly associated with pathology of the disease. In the current study, we assessed inhibitory effect against acetyl- (AChE) and butyrylcholinesterase (BChE) and metal-chelating capacity of twelve diterpenes: arucadiol, miltirone, tanshinone IIa, 1-oxomiltirone, cryptotanshinone, 1,2-didehydromiltirone, 1,2-didehydrotanshinone IIa, 1b-hydroxycryptotanshinone, 15,16- dihydrotanshinone, tanshinone I, isotanshinone II, 1(S)-hydroxytanshinone IIa, and rosmarinic acid, isolated from Perovskia atriplicifolia and Salvia glutinosa. The compounds were tested at 10 µg/mL using ELISA microtiter assays against AChE and BChE. QSAR and molecular docking studies have been also performed on the active compounds. All of the compounds showed higher [e.g., IC50 = 1.12 ± 0.07 µg/mL for 1,2-didehydromiltirone, IC50 = 1.15 ± 0.07 µg/mL for cryptotanshinone, IC50 = 1.20 ± 0.03 µg/mL for arucadiol, etc.)] or closer [1,2-didehydrotanshinone IIa (IC50 = 5.98 ± 0.49 µg/mL) and 1(S)-hydroxytanshinone IIa (IC50 = 5.71 ± 0.27 µg/mL)] inhibition against BChE as compared to that of galanthamine (IC50 = 12.56 ± 0.37 µg/mL), whereas only 15,16-dihydrotanshinone moderately inhibited AChE (65.17 ± 1.39%). 1,2-Didehydrotanshinone IIa (48.94 ± 0.26%) and 1(S)-hydroxytanshinone IIa (47.18 ± 5.10%) possessed the highest metal-chelation capacity. The present study affords an evidence for the fact that selective BChE inhibitors should be further investigated as promising candidate molecules for AD therapy.Ciencias AmbientalesCiencias de la AlimentaciónFarmaciaIngeniería, Industria y ConstrucciónMedicin

Maytansinol functionalization:towards useful probes for studying microtubule dynamics

11 p.-7 fig.-4 tab. 7 schem.Maytansinoids are a successful class of natural and semisynthetic tubulin binders, known for their potent cytotoxic activity. Their wider application as cytotoxins and chemical probes to study tubulin dynamics has been held back by the complexity of natural product chemistry. Here we report the synthesis of long-chain derivatives and maytansinoid conjugates. We confirmed that bulky substituents do not impact their high activity or the scaffold's binding mode. These encouraging results open new avenues for the design of new maytansine-based probes.This work was supported by the H2020-MSCA-ITN-2019 (860070 TUBINTRAIN), Ministerio de Ciencia e Innovación PID2019-104545RB−I00 (JFD), Proyecto de Investigación en Neurociencia Fundación Tatiana Pérez de Guzmán el Bueno 2020, and by the European Union NextGenerationEU (J.F.D.). Open Access Funding provided by $INSTITUTION within the CRUI-CARE Agreement.Peer reviewe

La reparación económica a la víctima en el sistema de justicia

En este libro se recogen las investigaciones llevadas a cabo en el marco de los Trabajos Fin de Grado de la Universidad Carlos III de Madrid en los dobles grados de Derecho y Administración de Empresas, Derecho y Economía durante los cursos 2015/16 y 2016/17. El objetivo principal es evaluar la eficacia de la reparación económica a la víctima. Para ello, se realizó un estudio de campo de las ejecutorias en los Juzgados de lo Penal y la Audiencia Provincial de Madrid en dos etapas, octubre de 2015 y octubre de 2016, , excluyendo delitos menores y delitos relacionados con delitos de tránsito y violencia de género, así como aquellos donde no hubiera víctima.Este trabajo ha sido subvencionado en parte por los proyectos DER2015-66435-P y MTM2014-56535-R, Ministerio de Economía y Competitividad, y se enmarca en el Proyecto innovación docente de la Universidad Carlos III de Madrid titulado Eficacia y Eficiencia de la Justicia, curso 2016/2017.Prólogo / Daniel Peña (pp. 19-20). -- La ineficacia del sistema español en la compensación a través del proceso / Helena Soleto y Aurea Grané (pp. 23-97). -- Asistencia jurídica y turno de oficio para la víctima / Alicia Calvo Barceló (pp. 101-138). -- Competencia judicial en ejecución penal / Alberto Rodríguez Abad (pp. 141-175). -- El fiscal en la ejecución / María García Navarro (pp. 177-214). -- La participación de la víctima en la ejecución / Sara González Pérez (pp. 215-247). -- Investigación patrimonial del condenado / Radad Sennouni El Harti (pp. 249-277). -- La suspensión de la pena privativa y libertad condicional / Sara Jiménez Olbea (pp. 281-306). -- La insolvencia del condenado / Catalina Guzmán Guzmán (pp. 307-324). -- Eficacia del pago y percepción de impunidad: consecuencias de la reparación en el condenado / Rosa González Espejo (pp. 325-342). -- Delitos contra la libertad sexual / María Belén Combarros Gómez (pp. 345-386). -- La víctima del delito de trata de seres humanos e inmigración ilegal / Eduardo Sagra González (pp. 387-407). -- La reparación en violencia de género / Marina García-Navas Gómez (pp. 409-439). -- Reparación en delitos contra la Administración Pública / Irea Riobó Mayo (pp. 441-459). -- La reparación económica en el caso Madrid Arena / Lucía Gimeno Malumbres (pp. 461-487). -- La reparación en el proceso de menores / Miriam López-Terradas Paniagua (pp. 489-513). -- La atenuante por reparación del daño / Adriana Noel Afonso Carracedo (pp. 517-540). -- Reparación y modelos de justicia reparativa / Victoria Martínez Martínez (pp. 541-567). -- Elementos básicos de justicia restaurativa / Mireia Galindo Perpiñán (pp. 569-614). -- El acuerdo de reparación en la justicia reparativa / Ainhoa Berrocal Cañadas (pp. 615-634). -- La indemnización a las víctimas en el Derecho comparado / Alba Peña Díaz (pp. 637-650). -- Las indemnizaciones de la Ley 35/1995 / Inmaculada Ramírez Rodríguez (pp. 651-702). -- El pago de indemnizaciones por el Estado en terrorismo / Ana Pérez Campón (pp. 703-734)

A qué sabe el norte?

Libro que compila saberes de las recetas ancestrales y sabores tradicionales de la gastronomía Nortesantandereana, recopila 3 rutas de turismo gastronómico que conjuga 30 municipios de norte de santander y más de 300 tipos de sopas, platos fuertes y postres.Book that compiles knowledge of ancestral recipes and traditional flavors of gastronomy Nortesantandereana, compiles 3 routes of gastronomic tourism that brings together 30 municipalities of northern Santander and more than 300 types of soups, main dishes and desserts.Ruta del durazno y el agua -- Ruta del oro negro -- Ruta del río y la gran convención -- Las mujeres de la independencia -- Honrando a nuestros portadores del saber -- A qué sabe el norte-recetarioPrimera ediciónna230 página

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica