Efecto de las metodologías analíticas en la cuantificación de bitartrato de epinefrina según la USP-43 y USP-44 / Effect of analytical methodologies on the quantification of epinephrine bitartrate according to USP-43 and USP-44

Introducción: El bitartrato de epinefrina, también conocido como epinefrina, es un ingrediente farmacéutico importante en el tratamiento de diversas enfermedades, pero su medición precisa es esencial para garantizar la seguridad del medicamento. La Farmacopea de los Estados Unidos (USP) establece los estándares para su análisis, pero la elección del método afecta la precisión de las mediciones. Este estudio investiga cómo los diferentes métodos afectan la medición del bitartrato de epinefrina según las versiones USP-43 y USP-44, que tienen implicaciones significativas para la calidad y la regulación de los medicamentos en el campo. Método: Se eligieron el método volumétrico y el método cromatográfico para comparación. Se utilizaron muestras de epinefrina bitartrato de alta pureza que cumplían con los estándares de la USP-43 y USP-44.Resultados: Los resultados obtenidos por ambos métodos se comparan entre sí y se evalúan según los límites de especificación definidos por USP-43 y USP-44. Los valores obtenidos para algunos parámetros, como la concentración y la pureza del bitartrato de epinefrina, varían considerablemente entre los distintos métodos analíticos. Conclusiones: Este estudio destaca la importancia de una cuidadosa selección del método analítico al evaluar el bitartrato de epinefrina según las directrices USP-43 y USP-44. La elección de la tecnología afecta a los resultados y, por tanto, a la calidad y seguridad de los productos farmacéuticos que contienen esta sustancia. Se recomienda validar el método en cada laboratorio y comparar los resultados con los estándares USP. (AU)

Introduction: Epinephrine bitartrate, also known as epinephrine, is an important pharmaceutical ingredient in the treatment of various diseases, but its accurate measurement is essential to ensure the safety of the drug. The United States Pharmacopeia (USP) sets the standards for its analysis, but the choice of method affects the precision of the measurements. This study investigates how different methods affect the measurements of epinephrine bitartrate based on USP-43 and USP-44, which have significant implications for drug quality and regulation in the field. Method: The volumetric method and chromatographic method were chosen for comparison. High-purity epineph-rine bitartrate samples that met USP-43 and USP-44 standards were used. Results: The results obtained by both methods are compared with and evaluated according to the specification lim-its defined by USP-43 and USP-44. The values obtained for some parameters, such as the concentration and purity of epinephrine tartrate, vary considerably between the different analytical methods. Conclusions: This study highlights the importance of carefully selecting analytical methods when evaluating epi-nephrine tartrate according to USP-43 and USP-44 guidelines. The choice of technology affects the results and, therefore, the quality and safety of the pharmaceutical products containing this substance. It is recommended to validate the method in each laboratory and compare the results with USP standards. (AU)

Análisis del intrusismo odontológico en Cataluña a través de sentencias judiciales, 1995-2020 / Analysis of intrusive dentistry in Catalonia through court rulings, 1995-2020

Introducción: El intrusismo en las profesiones sanitarias, y en la Odontología en concreto, sigue siendo un problema vigente a día de hoy, a pesar de los controles de la Administración y de los Colegios Profesionales. Este problema tipificado como delito en el Código Penal español afecta tanto a la Administración, que debe proteger a la sociedad de conductas nocivas, a los profesionales que ejercen dentro de la legalidad y también a la ciudadanía en general. Objetivo: Conocer la situación del delito de intrusismo en Odontología en las provincias de la Comunidad Autónoma de Cataluña entre los años 1995 y 2020. Material y método: Hemos utilizado las bases de datos de “Centro de Documentación del Consejo General del Poder Judicial” (CENDOJ) y “Westlaw de Aranzadi” para la búsqueda de sentencias judiciales utilizando los términos: intrusismo, odontólogo, estomatólogo, Barcelona, Lérida, Girona, Tarragona, Cataluña. Hemos realizado un estudio retrospectivo de las sentencias judiciales intentando conocer quince variables, entre otros, demandante, profesión del demandado, tipo de tratamientos odontológicos realizados y penas impuestas. Resultados: Se obtuvieron once sentencias y tres autos con diferentes resultados en las variables estudiadas. La profesión más habitual es el protésico dental seguido de odontólogos sin título homologado con la ayuda de un colaborador dentista. Los trabajos realizados son muy variados y las sanciones impuestas son muy bajas. Conclusiones: El papel de los Colegios de Dentistas es importante y necesario para que no se den este tipo de prácticas. Las sanciones no ejercen un efecto disuasorio sobre los intrusos. (AU)

Introduction: Intrusiveness in the health professions, and in Dentistry in particular, continues to be a current problem today, despite the controls of the Administration and Professional Associations. This problem classified as a crime in the Spanish Criminal Code affects both the Administration, which must protect society from harmful conduct, professionals who practice within the law and also the general public. Aim: To know the situation of the crime of intrusion in Dentistry in the provinces of the Autonomous Community of Catalonia between the years 1995 and 2020. Material and method: We have used the databases of the “Documentation Center of the General Council of the Judiciary” (CENDOJ) and “Westlaw de Aranzadi” to search for court rulings using the terms: intrusismo, odontólogo, estomatólogo, Barcelona, Lleida, Girona, Tarragona, Catalonia. We have carried out a retrospective study of the judicial sentences trying to know fifteen variables, among others, plaintiff, defendant's profession, type of dental treatment performed and sentences imposed Results: Eleven sentences and three orders were obtained with different results in the variables studied. The most common profession is the dental technician followed by dentists without an approved degree with the help of a dentist collaborator. The work carried out is very varied and the sanctions imposed are very low. Conclusions: The role of the Colleges of Dentists is important and necessary so that this type of practice does not take place. Penalties do not exert a deterrent effect on intruders.

Guía internacional para una dosificación más segura de la clozapina en adultos mediante el uso de 6 titulaciones personalizadas de dosis basados en la etnicidad, la proteína C reactiva y los niveles de clozapina / An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels

Esta guía internacional propone mejorar los prospectos de la clozapina en todo el mundo mediante la inclusion de información sobre la titulación del fármaco en función de la ascendencia del paciente. Las bases de datos de reacciones adversas a medicamentos (RAM) sugieren que la clozapina es el tercer fármaco más tóxico en los Estados Unidos de América (EE. UU.) y que produce una mortalidad por neumonía en todo el mundo 4 veces mayor que la correspondiente a la agranulocitosis o la miocarditis. El rango terapéutico de referencia para las concentraciones séricas estables de clozapina es estrecho, de 350 a 600 ng/ml, con potencial de toxicidad y reacciones adversas más fecuentes a medida que aumentan las concentraciones. La clozapina se metaboliza principalmente por CYP1A2 (las mujeres no fumadoras requieren la dosis más baja y los hombres fumadores la dosis más alta). A través de la conversión fenotípica, la prescripción conjunta de inhibidores del metabolismo de la clozapina (incluidos los anticonceptivos orales y el valproato), la obesidad o la inflamación con elevaciones de la proteína C reactiva (PCR), pueden convertir al paciente en un metabolizador lento/pobre (MP). Las personas de ascendencia asiática (de Pakistán a Japón) o los habitantes originarios de las Américas tienen menor actividad de CYP1A2 y requieren dosis más bajas de clozapina para alcanzar concentraciones de 350 ng/ml. En los EE. UU. se recomiendan dosis diarias de 300-600 mg/día. La dosificación personalizada lenta puede prevenir RAM tempranas (incluidos el síncope, la miocarditis y la neumonía). La esencia de esta guía se fundamenta en 6 esquemas de titulaciones personalizadas para pacientes hospitalizados...(AU)

This is the Spanish translation of an international guideline which proposes improving clozapine package inserts worldwide by using ancestry-based: 1) dosing and 2) titration. Adverse drug reaction (ADR) databases suggest clozapine: 1) is the third most toxic drug in the United States (US), and 2) produces worldwide pneumonia mortality four times greater than that of agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers require the lowest dose and male smokers the highest dose). Poor metabolizer (PM) status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity or inflammation with C-reactive protein (CRP) elevations. People with ancestry from Asia (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/ml. Daily doses of 300-600 mg/day are recommended in the US. Slow personalized titration may prevent early ADRs (including syncope, myocarditis and pneumonia). The core of this guideline consists of six personalized titration schedules for inpatients...(AU)

Indirect partial volumetry in breast cancer-related lymphoedema: Distribution of oedema and clinical-diagnostic implications / Volumetría parcial indirecta en linfedema relacionado con cáncer de mama: distribución del edema e implicaciones clínico-diagnósticas

Introduction and objectives: Currently, the assessment of lymphoedema related to breast cancer (BCRL) is performed through the global perimeter volumetry. We implemented an additional system with partial measures (hand, forearm, and upper arm) that allows us to approximate the segmental distribution of oedema. We used this measurement tool to determine the oedema distribution and its evolution, as well as its possible impact on clinical assessment. Methods: We carried out a retrospective observational study of the patients referred to our service with suspected BCRL. Inclusion criteria: Unilateral breast cancer, availability of global and partial digital medical record, and follow-up for a minimum of 24 months. Of the 210 selected patients, 190 were considered affected (≥10% excess volume). We analysed at three time points (initial, final, and peak involvement) the oedema distribution and segmental predominance and its relationship with the evolutionary course and the severity of the process. We subsequently examined, at the initial timepoint, the concordance of the global assessment with the partial assessment for the clinical classification of the 210 patients in the initial sample. Results: The BCRL oedema was characteristically irregular, with the forearm being the most affected segment and the hand the least affected (RM ANOVA: p<0.001). The irregularity was related to its severity (χ2: p<0.001) and the evolutionary course (Student t-test: p<0.005 for the hand). Overall, disagreement of 46.67% was observed between the clinical classification of the global and partial assessment. Conclusions: This work supports the need to add partial volumetry to the commonly used global assessment.(AU)

Introducción y objetivos: Actualmente la volumetría perimetral global se utiliza para valorar el linfedema relacionado con cáncer de mama (LRCM). Nosotros implementamos un sistema adicional que permite aproximarse a la distribución segmentaria del edema mediante tres indicadores parciales: mano, antebrazo y brazo. Utilizamos esta herramienta para conocer la distribución del edema, su evolución y su posible repercusión en la valoración clínica. Metodología: Se realizó un estudio observacional retrospectivo de los pacientes remitidos a nuestro servicio con sospecha de LRCM. Criterios de inclusión: Cáncer de mama unilateral, con registros volumétricos en la historia clínica digital y 24 meses de seguimiento mínimo. De los 210 pacientes seleccionados, en 190 pacientes afectos (≥10% de exceso de volumen) se analizaron en tres momentos de medición (inicial, final y máxima afectación) la distribución del edema, su predominio segmentario y la relación con la evolución y la gravedad del proceso. Posteriormente se examinó la concordancia de los indicadores globales con los parciales en la valoración clínica de los 210 pacientes de la muestra inicial. Resultados: El LRCM fue característicamente irregular, siendo el antebrazo el segmento predominante y la mano el menos afecto (MR ANOVA: p<0,001). La irregularidad se relacionó con la gravedad del proceso (chi cuadrado: p<0,001) y su evolución (t de Student: p<0,005 para la mano). Además, se apreció, en conjunto, una discordancia en la valoración clínica del índice global con los índices parciales del 46,67% (W de Kendall=0,467). Conclusión: El estudio apoya la necesidad de añadir volumetría parcial a la valoración global habitualmente utilizada.(AU)

La edad y el uso de máscara oronasal se asocian con menor calidad en la titulación con CPAP autoajustable en domicilio en pacientes sin adaptación / Age and Oronasal Mask are Associated with Lower Quality in Automatic CPAP Titration at Home in Patients without Previous Adaptation

Introducción: se considera aceptable (TitAcept) una prueba con CPAP automático en domicilio (APAP) cuando su uso es ≥ a 4 horas/noche y el índice de apneas residuales (IAHr) ≤ 10 eventos/hora (AASM). Sin embargo, todas las variables relacionadas con la calidad de este procedimiento no se conocen completamente. Objetivo: evaluar la cali-dad de la titulación con APAP en el domicilio. Material y métodos: estudio retrospectivo en pacientes "naïve" de CPAP. El criterio de TitAcept seleccionó dos grupos y la regresión logística múltiple identificó predictores de prueba no aceptables. Resultados: incluimos 1325 TitAcept; 941 hombres (71%), edad: 57 ± 12,4 años, IMC: 32,3 ± 8,8 kg/m2, IAH: 34,2 ± 19 ev/h. La titulación alcanzó 3,4 ± 3,5 noches, adherencia: 379 minutos/noche; pre-sión efectiva: 8,7 ± 1,7 cm H2O, IAHr; 3,1 ± 2,4 ev/h y fugas 16,1 ± 8,7 litros/min. Fueron predictores; edad ≥ 50 años; OR: 1,62 (IC95%: 1,23-3,46), p: 0.0005 y máscara orona-sal; OR: 2,49 (IC95%: 1,79-3,46), p: 0.0001. Conclusiones: una significativa proporción de pacientes que realizaron una titulación no vigilada con APAP en domicilio no alcan-zaron criterios de calidad adecuada. La edad ≥ 50 años y el uso de máscara oronasal se asocian con menor calidad en la prueba, de acuerdo a criterios preestablecidos. (AU)

Introduction: automated CPAP (APAP) titration at home is considered acceptable (Tit-Accept) when its device is used ≥ 4 hours/night and the residual apnea index (AHIr) es ≤ 10 events/hour (AASM). However, all the variables related to quality of this procedure are not fully known. Objective: to assess the quality of the titration with APAP at home.Material and Methods: retrospective study in CPAP "naïve" patients. The TitAccept criteri-on selected two groups and multiple logistic regression identified predictors of non-ac-ceptable titration. Results: we included 1325 TitAccept; 941 men (71%), age: 57 ± 12.4 years, BMI: 32.3 ± 8.8 kg/m2, baseline AHI: 34.2 ± 19 ev/h. The titration reached 3.4 ± 3.5 nights, adherence: 379 minutes/night; effective pressure: 8.7 ± 1.7 cmH2O, AHIr; 3.1 ± 2.4 ev/h and leaks 16.1 ± 8.7 liters/min. The predictors were; age ≥ 50 years; OR: (AU)

A low-cost automated titration system for colorimetric endpoint detection.

An auto titrator system was developed to accurately and precisely detect colorimetric endpoints for spectrochemical titrations. This system was constructed using inexpensive components such as a Raspberry Pi® single-board computer, 3D-printed components, and a commercially available spectral sensor. The auto titrator was evaluated by performing a standard method for determination of water hardness. Regardless of analyst experience, the auto titrator performed better than the traditional titration approach that involves manual dosing of titrant and visual detection of the endpoint. Inter-day, intra-day, inter-instrumental, and intra-instrumental validation studies were performed to establish the accuracy and precision of endpoint detection. The auto titrator eliminates the subjective bias in color perception and produces accurate and precise endpoint results.

Determinação do período de estabilidade de soluções volumétricas rotineiramente utilizadas em laboratórios de análises químicas / Determination of the stability period of volumetric solutions routinely used in chemical analysis laboratories / Determinación del período de estabilidad de las soluciones volumétricas utilizadas habitualmente en los laboratorios de análisis químicos

As soluções volumétricas são rotineiramente utilizadas nos laboratórios, principalmente nos processos de síntese de produtos e nas análises quantitativas de matéria-prima e/ou produto acabado, entretanto poucos são os estudos que abordam a estabilidade destas soluções. Considerando que a qualidade das soluções volumétricas pode afetar os procedimentos de análises químicas e consequentemente induzir a erros, e ainda que, a Farmacopeia Brasileira (2010) não cita tempo máximo de utilização dessas soluções padronizadas, a avaliação da estabilidade das mesmas é importante. Sendo assim, o objetivo do trabalho foi avaliar a estabilidadede 10 soluções volumétricas, empregadas rotineiramente em laboratórios de análises químicas, com o intuito de estabelecer o período que essas soluções permanecem estáveis, isto é, sem sofrer alteração na concentração. As metodologias de preparo e padronização das soluções volumétricas seguiram os métodos descritos na Farmacopeia Brasileira (2010), sendo as mesmas padronizadas no momento do preparo e a cada 20 dias, por um período de 180 dias. As soluções contendo ácidos e bases, bem como as soluções de iodato de potássio e nitrato de prata, permaneceram constantes durante o período de análises. As soluções de EDTA, iodo, nitrito de sódio, permanganato de potássio e tiossulfato de sódio apresentaram estabilidade inferior a 180 dias, tornando necessária a realização de padronização periódica. As soluções volumétricas utilizadas nos laboratórios apresentam diferentes estabilidades, o que ressalta a importância da determinação do período que as mesmas se mantêmcom as concentrações estáveis, evitando possíveis alterações de resultados nas análises químicas.

Volumetric solutions are routinely used in laboratories, mainly in product synthesis processes and in quantitative analyzes of raw materials and/or finished products, however there are few studies that address the stability of these solutions. Considering that the quality of volumetric solutions can affect chemical analysis procedures and consequently induce errors, and even though the Brazilian Pharmacopoeia (2010) does not mention the maximum time for using these standardized solutions, the evaluation of their stability is important. Therefore, the aim of this work was to evaluate the stability of 10 volumetric solutions, routinely used in chemical analysis laboratories, in order to establish the period that these solutions remain stable without changing their concentrations. The methodologies for preparing and standardizing the volumetric solutions followed the methods described in the Brazilian Pharmacopoeia (2010), being standardized at the time of preparation and every 20 days, for a period of 180 days. Solutions containing acids and bases, as well as potassium iodate and silver nitrate solutions, were stable during the analysis period. The solutions of EDTA, iodine, sodium nitrite, potassium permanganate and sodium thiosulfate showed stability less than 180 days, making it necessary to carry out periodic standardization of these solutions. The volumetric solutions used in the laboratories have different stabilities, which highlights the importance of determining the period in which they remain stable, avoiding possible changes in results in chemical analyzes.

Las soluciones volumétricas se utilizan de forma rutinaria en los laboratorios, principalmente en los procesos de síntesis de productos y en el análisis cuantitativo de materias primas y/o productos acabados. Sin embargo, existen pocos estudios que aborden la estabilidad de estas soluciones. Considerando que la calidad de las soluciones volumétricas puede afectar los procedimientos de análisis químico y consecuentemente inducir a errores, y también que, la Farmacopea Brasileña (2010) no menciona el tiempo máximo de uso de estas soluciones estandarizadas, la evaluación de su estabilidad es importante. Así, el objetivo del trabajo fue evaluar la estabilidad de 10 soluciones volumétricas, utilizadas rutinariamente en los laboratorios de análisis químico, con el fin de establecer el período en que estas soluciones permanecen estables, es decir, sin sufrir alteraciones en la concentración. Las metodologías de preparación y estandarización de las soluciones volumétricas siguieron los métodos descritos en la Farmacopea Brasileña (2010), siendo las mismas estandarizadas en el momento de la preparación y cada 20 días, por un período de 180 días. Las soluciones que contienen ácidos y bases, así como las soluciones de yodato de potasio y nitrato de plata, permanecieron constantes durante el periodo de análisis. Las soluciones de EDTA, yodo, nitrito de sodio, permanganato de potasio y tiosulfato de sodio fueron estables durante menos de 180 días, por lo que fue necesario realizar estandarizaciones periódicas. Las soluciones volumétricas utilizadas en los laboratorios presentan diferentes estabilidades, lo que pone de manifiesto la importancia de determinar el periodo que permanecen con concentraciones estables, evitando posibles cambios en los resultados en los análisis químicos.

Suplemento alimentar de vitamina C: fiscalização durante o período de adequação à nova legislação / Vitamin C dietary supplement: inspection during adequacy period of new legislation

Os suplementos à base de vitamina C são amplamente consumidos pela população, evidenciando a importância da fiscalização desses produtos. Em julho de 2018, a ANVISA (Agência Nacional de Vigilância Sanitária) publicou as novas regulamentações sobre suplementos alimentares, estabelecendo-se o prazo de 60 meses para as empresas se adequarem a essas normas. O presente trabalho teve como objetivo determinar os teores de vitamina C, comparar os valores analisados com os declarados na informação nutricional e avaliar os dizeres de rotulagem em produtos à base dessa vitamina. Os teores de vitamina C foram determinados por titulação potencio métrica e as análises de rotulagem foram realizadas com base nas legislações da ANVISA em doze amostras de suplementos colhidos pelas Vigilâncias Sanitárias do Estado de São Paulo. Os teores de vitamina C avaliados estavam de acordo com os declarados na informação nutricional do rótulo, com exceção de uma amostra que apresentou teor abaixo do valor declarado. Em relação aos dizeres de rotulagem, sete amostras (58%) apresentaram um ou mais itens em desacordo com a legislação, mostrando a necessidade de monitoramento constante desse tipo de produto. O trabalho representa um estudo preliminar de avaliação dos suplementos no período de adequação às novas regulamentações (AU).

Vitamin C-based supplements are widely consumed by the population, highlighting the importance of monitoring these products. In July 2018, the ANVISA (National Health Surveillance Agency) published new regulations for dietary supplements,setting a 60 months deadline for companies to comply with these standards.The objective of the present work was to evaluate the contents of vitamin C, and compare the analyzed/real values with those reported on the nutrition facts label, and to evaluate the labeling of vitamin supplements. Vitamin C contents were determined by potentiometric titration, and labeling analysis were performed based on ANVISA legislation in twelve samples of supplements collected by the Sanitary Surveillance of the State of São Paulo.The contents of vitamin C were in accordance with those declared in the nutritional information on the label, with the exception of one sample that presented content below the declared value. Regarding the labeling analysis, seven samples (58%) presented one or more items in disagreement with the legislation, showing the need for constant monitoring of this type of product.The work represents a preliminary study to evaluate the supplements in the adequacy period of new regulations (AU).

A hybrid strategy combining solution NMR spectroscopy and isothermal titration calorimetry to characterize protein-nanodisc interaction.

NMR is a powerful tool for characterizing intermolecular interactions at atomic resolution. However, the nature of the complex interactions of membrane-binding proteins makes it difficult to elucidate the interaction mechanisms. Here, we demonstrated that structural and thermodynamic analyses using solution NMR spectroscopy and isothermal titration calorimetry (ITC) can clearly detect a specific interaction between the pleckstrin homology (PH) domain of ceramide transport protein (CERT) and phosphatidylinositol 4-monophosphate (PI4P) embedded in the lipid nanodisc, and distinguish the specific interaction from nonspecific interactions with the bulk surface of the lipid nanodisc. This NMR-ITC hybrid strategy provides detailed characterization of protein-lipid membrane interactions.

Electrochemical Performance of Na3V2(PO4)2F3 Electrode Material in a Symmetric Cell.

A NASICON-based Na3V2(PO4)2F3 (NVPF) cathode material is reported herein as a potential symmetric cell electrode material. The symmetric cell was active from 0 to 3.5 V and showed a capacity of 85 mAh/g at 0.1 C. With cycling, the NVPF symmetric cell showed a very long and stable cycle life, having a capacity retention of 61% after 1000 cycles at 1 C. The diffusion coefficient calculated from cyclic voltammetry (CV) and the galvanostatic intermittent titration technique (GITT) was found to be ~10-9-10-11, suggesting a smooth diffusion of Na+ in the NVPF symmetric cell. The electrochemical impedance spectroscopy (EIS) carried out during cycling showed increases in bulk resistance, solid electrolyte interphase (SEI) resistance, and charge transfer resistance with the number of cycles, explaining the origin of capacity fade in the NVPF symmetric cell. Finally, the postmortem analysis of the symmetric cell after 1000 cycles at a 1 C rate indicated that the intercalation/de-intercalation of sodium into/from the host structure occurred without any major structural destabilization in both the cathode and anode. However, there was slight distortion in the cathode structure observed, which resulted in capacity loss of the symmetric cell. The promising electrochemical performance of NVPF in the symmetric cell makes it attractive for developing long-life and cost-effective batteries.

Protonation of the oxo-bridged heme/copper assemblies: Modeling the oxidized state of the cytochrome c oxidase active site.

In this study on model compounds for the resting oxidized state of the iron­copper binuclear center in cytochrome c oxidase (CcO), we describe the synthesis of a new µ-oxo-heme/Cu complex, [(TPP)FeIII-O-CuII(tmpa)][B(C6F5)4] (2) {TPP: tetraphenyl porphyrinate(2-); TMPA: tris(2-pyridylmethylamine)}, as well as two protonation events for three µ-oxo-heme/Cu complexes with varying peripheral substituents on the heme site. The addition of increasing amounts of strong acid to these µ-oxo-heme/Cu systems successively led to the generation of the corresponding µ-hydroxo, µ-aquo, and the dissociated complexes. The heme/Cu assemblies bridged through a water ligand are reported here for the first time and the 1H NMR and 19F NMR spectral properties are consistent with antiferromagnetically coupled high-spin iron(III) and copper(II) centers. By titration using a series of protonated amines, the pKa values for the corresponding µ-hydroxo-heme/Cu species (i.e., the first protonation event) have been reported and compared with the pKa ranges previously estimated for related systems. These synthetic systems may represent structural models for the oxidized FeIII-X-CuII resting state, or turnover intermediates and can be employed to clarify the nature of proton/electron transfer events in CcO. SYNOPSIS: The resting oxidized state of the cytochrome c oxidase active site contains an Fea3-OHx-CuB moiety. Here, we investigated two successive protonation events, for a series of µ-oxo-heme/Cu assemblies and reported the pKa values for the first protonation event. The µ-aquo-heme/Cu complexes described here are the first examples of such systems.

Valores de densidad en la escala de grises en Tomografía Computarizada de Haz Cónico: alcances y limitaciones / Grayscale Values in Cone Beam Computed Tomography: Scope and Limitations

ABSTRACT: Cone-beam computed tomography (CBCT) is a 3D imaging technique widely used in maxillofacial diagnosis. The grayscale value (GSV) is a number that represents the amount of attenuation of the X-ray beam by the material contained in each voxel or structural unit of the tomographic volume. Similarly, in computed tomography (CT) used in medical radiology, the attenuation values are standardized in the Hounsfield Unit (HU) scale. Although GSV may have interesting potential applications in maxillofacial diagnosis, it is essential to know that HU differ from GSV. The latter are susceptible to multiple technical factors during the tomographic acquisition, so their value can vary among different CBCT scanners or when technical parameters are modified. Hence, GSV should not be extrapolated between different CBCT machines, and their use should be cautious while more investigation is available considering various equipment and acquisition protocols.

RESUMEN: La tomografía computarizada de haz cónico (CBCT, por sus siglas en inglés) es una técnica de imagen 3D ampliamente usada en diagnóstico maxilofacial. El valor de densidad en la escala de grises (DEG) es una cifra que corresponde al grado de atenuación de los rayos x del material representado en cada vóxel o unidad estructural de la tomografía. De forma similar, en los sistema de tomografía computarizada de uso médico (CT) el valor de atenuación está estandarizado en las Unidades Hounsfield (UH). Aunque los valores de DEG pueden tener interesantes usos potenciales en el apoyo de diagnóstico en el área dentoalveolar, es importante conocer que los valores UH no son los mismos a los valores DEG, y que los valores de DEG son susceptibles a múltiples factores técnicos durante la adquisición de la tomografía, por lo que se pueden obtener resultados distintos entre equipos y al variar parámetros técnicos en las tomas. Por lo tanto sus valores no deben extrapolarse entre equipos y su uso debe ser cauteloso mientras se realiza mayor investigación específica para cada equipo y para cada protocolo de adquisición.

Comparison of prenatal anti-D titration testing by gel and tube methods: A review of the literature.

BACKGROUND: Antenatal titration testing is traditionally performed using a manual tube test. Tube testing has limitations; it is a manual, time-consuming method with wide interobserver variability. Gel-based testing is an attractive alternative because it is more precise and can be automated. This study's objective was to summarize the published literature that assessed the relationship between titrations performed by tube and gel for anti-D alloimmunized pregnancies. STUDY DESIGN AND METHODS: A comprehensive literature search was performed. Articles were selected if research was original and compared at least five pairs of anti-D titration tests performed by gel and tube. Differences in the number of dilutions between gel and tube methods were compared overall by study and cell type using linear models. RESULTS: A total of 512 articles were identified; eight were included, and titer data from 384 tube and gel pairs were abstracted. The median anti-D titer in tube was 8 (range 0-2048) and by gel was 64 (range 0-4096). Anti-D gel titration results were 2.1 (95% CI; 1-3.3) additional dilutions greater than in tube. Most studies utilized double-dose reagent cells for testing. At a tube titer of 16, the sensitivity and specificity of gel titrations is maximal (91% and 94% respectively) at a gel titer of 64. CONCLUSION: Overall, titrations performed by gel were two dilutions higher than the corresponding tube titer. For titrations, double-dose reagent cells should be considered to standardize practice. A rigorous prospective study is needed to compare tube titrations with gel titrations using a standardized process.

Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy.

BACKGROUND: Regional citrate anti-coagulation (RCA) is the recommended anti-coagulation for continuous renal replacement therapy (CRRT). Citrated replacement fluids provide convenience but may compromise effluent delivery when adjusted to maintain circuit ionised calcium levels (circuit-iCa). This study aims to evaluate the effect of RCA titration on the delivered CRRT effluent dose. METHODS: This prospective observational study evaluated patients on RCA-CRRT in continuous veno-venous hemodiafiltration mode. Citrated replacement fluid was titrated to target circuit-iCa 0.26-0.40 mmol/L. Patients were then stratified into 'reduced-dose' who required citrate down-titration and 'stable-dose' who did not. RESULTS: Data from 200 RCA-CRRT sessions were collected. The reduced-dose RCA group (n = 114) had higher median initial citrate dose (3.00 vs 2.50; P < 0.001) but lower time-averaged dose (2.49 vs 2.60; P < 0.001). In addition, median prescribed effluent dose was 33.3 mL/kg/h (28.6-39.2) but median delivered effluent dose was significantly lower at 29.9 mL/kg/h (25.4-36.9; P < 0.001). Mortality was higher in the reduced-dose RCA group (39.5% vs 25.6%; P = 0.022) and in patients with delivered-to-prescribed effluent dose ratio of < 0.9 vs ≥ 0.9 (51.3% vs 29.2%; P = 0.014). CONCLUSION: RCA titration can significantly impact delivered CRRT effluent dose. Measures should be taken to address the CRRT dose deficit and prevent poor outcomes due to inadequate dialysis.

Análisis volumétrico e influencia del trombo intraluminal tras la reparaciónendoluminal del aneurisma de aorta abdominal / Volumetric analysis and influence of intraluminal thrombus after endoluminal repair of abdominal aortic aneurysm

Objetivo: la precisión de la predicción del riesgo de rotura mediante control ultrasonográfico y angiotomografía computarizada está todavía lejos del método de diagnóstico óptimo para el aneurisma de aorta abdominal (AAA). El objetivo de este estudio es realizar un análisis volumétrico del saco aneurismático, comparar sus modificaciones con las del diámetro máximo, estudiar la evolución del volumen del trombo intraluminal (ILT) después de la reparación endovascular del AAA. Métodos: se analizaron un total de 144 AAA reparados por la EVAR electiva. Se realizó una angiotomografía en el periodo preoperatorio, 6-12 meses después de la intervención quirúrgica. Se calculó el diámetro máximo, el volumen del saco aneurismático y el volumen de la ILT en los tres momentos. Se determinó la modificación del diámetro, el volumen total y el volumen del trombo intraluminal (%). Se comparó la modificación del diámetro máximo con el volumen total de los aneurismas y entre el volumen total del aneurisma y el volumen del trombo intraluminal. Resultados: la media de los cambios en el diámetro máximo del AAA y el volumen después de la EVAR fue de -2,16 ± 8,20 mm y 84,4 ± 23,32 cc, respectivamente. Hubo un aumento en el volumen de AAA de 92,22 % y 57,34 % a los 6 y 12 meses en pacientes con endofugas (22.03 ± 19.03 cc a los 12 meses del periodo posoperatorio). La modificación media del ITL y del saco aneurismático fue de 0,59 ± 0,17 y 0,52 ± 1,8 para los pacientes con AAA presurizados y no presurizados, respectivamente (p = 0,308). Conclusión: el análisis volumétrico de los AAA reparados mediante tratamiento endovascular es una medida más preciso que la medición del diámetro máximo para determinar la expansión del saco aneurismático.(AU)

Purpose: the accuracy of risk prediction by ultrasonic control and computerized angiotomography is still far from the optimal diagnostic method for abdominal aortic aneurysm (AAA). The objective of this study is to perform a volumetric analysis of the AAA sac to detect alterations and to follow-up the evolution of the volume of the intraluminal thrombus (ILT) and its influence on the overall evolution after the EVAR. Methods: a total of 144 AAAs repaired by elective EVAR were analyzed. An angiotomography was carried out in the preoperative period, 6-12 months after the operation. The maximum-diameter, aneurysmal sac volume, and ILT volume were calculated each time. We determined the modification of the diameter, total-volume and intraluminal-thrombus volume (%). We made a comparison between the modification of the maximum-diameter and the total-volume of the aneurysms and between the total-volume of the aneurysm and the volume of ILT. Results: the average changes in the maximum diameter of AAA and the volume after EVAR was -2.16 ± 8.20 mm and 84.4 ± 23.32 cc, respectively. There was an increase in AAA-volume of 92.22 % and 57.34 % at 6 and 12 months in patients with endoleaks (22.03 ± 19.03 cc at 12 months of postoperative-period). The means of the ILT and AAA sac ratios were respectively 0.59 ± 0.17 and 0.52 ± 1.8 in AAA in sac growth and in stable or contracted AAA sac groups (p = 0.308). Conclusion: volumetric analysis of AAA repaired by EVAR is a more sensitive measure to determine the expansion of the aneurysm sac than the measurement of the maximum diameter of the aneurysm.(AU)

Similar glycaemic control and risk of hypoglycaemia with patient- versus physician-managed titration of insulin glargine 300 U/mL across subgroups of patients with T2DM: a post hoc analysis of ITAS.

AIMS: The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. METHODS: This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. RESULTS: HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00-pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p < 0.05). CONCLUSIONS: Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. CLINICAL TRIAL REGISTRATION: EudraCT 2015-001167-39.

THE MAKING OF A FOOTPRINT IN PROTEIN FOOTPRINTING: A REVIEW IN HONOR OF MICHAEL L. GROSS.

Within the past decade protein footprinting in conjunction with mass spectrometry has become a powerful and versatile means to unravel the higher order structure of proteins. Footprinting-based approaches has demonstrated the capacity to inform on interaction sites and dynamic regions that participate in conformational changes. These findings when set in a biological perspective inform on protein folding/unfolding, protein-protein interactions, and protein-ligand interactions. In this review, we will look at the contribution of Dr. Michael L. Gross to protein footprinting approaches such as hydrogen deuterium exchange mass spectrometry and hydroxyl radical protein footprinting. This review details the development of novel footprinting methods as well as their applications to study higher order protein structure. © 2020 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd. Mass Spec Rev.

Volume measurement of mandibular teeth pulp chamber as a prediction tool of gender and ethnicity in a Brazilian population / Medição do volume da câmara pulpar de dentes inferiores como ferramenta de predição de gênero e etnia em uma população brasileira

Objective: Forensic dentistry has used some methods for the human identification process. However, there is a need to study characteristics that are able to perform identification more specifically, increasing accuracy. Considering the role of dental arch assessment in prediction of gender and ethnicity, the purpose of this study was to assess the volume of pulp chamber as a mean to obtain new forensic evidence. Material and methods: For this task, 1.190 cone beam computed tomography (CBCT) images were retrospectively selected and subdivided according to the population number, gender, age and ethnicity. All DICOM files were imported to the open-source software ITK-SNAP®(http://www.itksnap.org/pmwiki/pmwiki.php). The segmentation process was performed in all pulp chamber aiming to obtain pulp tissue ́s volume. Results: As a result, the pulp chamber volume of mandibular canine teeth showed to be larger in white population than in non-white (P-value = 0.003) and in male individuals in comparison with female (P-value = 0.038). Conclusion: These results, however, must be confirmed by future studies with a larger sample size and by the assessment of other variables, including texture analysis and density of dental tissues. (AU)

Objetivo: A odontologia forense tem usado alguns métodos para o processo de identificação humana. Porém, há a necessidade de estudar características que consigam de forma mais específica realizar a identificação aumentando a precisão. Considerando o papel da avaliação da arcada dentária na predição de gênero e etnia, o objetivo deste estudo foi avaliar o volume da câmara pulpar mandibular como meio de obtenção de novas evidências periciais. Material e métodos: Foram selecionadas 1.190 imagens de tomografia computadorizada de feixe cônico (TCFC) e subdivididas de acordo com o número da população, sexo, idade e etnia. Todos os arquivos em formato DICOM foram importados para o software de código aberto ITK-SNAP® (http://www.itksnap.org/pmwiki/pmwiki.php) onde o processo de segmentação foi realizado em todas as câmaras pulpares visando a obtenção da volumetria. Resultados: Como resultado, o volume da câmara pulpar dos caninos inferiores mostrou-se maior na população branca do que na não branca (P-valor = 0,003), no sexo masculino em comparação ao feminino (P-valor = 0,038). Conclusão: Esses resultados, entretanto, devem ser confirmados por estudos futuros com maior tamanho amostral e pela avaliação de outras variáveis, incluindo análise de textura e densidade dos tecidos dentários. (AU)

Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants.

Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier protein. Hence obtaining a free amino or carboxylic group during the structural transformation is an important part of the synthesis. Namely, these groups can be used to form the requisite peptide bond between the hapten and the carrier protein. Focusing on this basic principle, six nor-morphine compounds were treated with ethyl acrylate and ethyl bromoacetate, while the prepared esters were hydrolyzed to obtain the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives which are considered as potential haptens. The next step was the coupling phase with glycine ethyl ester, but the reactions did not work or the work-up process was not accomplishable. As an alternative route, the normorphine-compounds were N-alkylated with N-(chloroacetyl)glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine side chain. The acid-base properties of these molecules are characterized in detail. In the N-carboxyalkyl derivatives, the basicity of the amino and phenolate site is within an order of magnitude. In the glycine derivatives the basicity of the amino group is significantly decreased compared to the parent compounds (i.e., morphine, oxymorphone) because of the electron withdrawing amide group. The protonation state of the carboxylate group significantly influences the basicity of the amino group. All of the glycine ester and the glycine carboxylic acid derivatives are currently under biological tests.