Recommendations from the Galician Oncological Society and the Galician Society of Nuclear Medicine for the use of 177Lu-PSMA-617 radioligand-therapy in prostate cancer.

Theragnostic is a type of precision medicine that uses molecules linked to radioactive isotopes for the diagnosis and treatment of diseases. In recent years, it has gained significant importance to treat neuroendocrine tumors and is currently being used in prostate cancer. Various radiopharmaceuticals have emerged for diagnosing and detecting lesions showing prostate-specific membrane antigen (PSMA) positivity on the Positron emission tomography/computed tomography scan, being the most widely used labeled with [68Ga] and [18F]. Its use as therapy in prostate cancer (PC) has been assessed in the VISION, TheraP, and PSMAfore clinical trials conducted with the radioligand [177Lu]Lu-PSMA-617, demonstrating significant antitumor activity. The aim of this article is to present practical recommendations, based on current available scientific evidence and on a multidisciplinary consensus, for the diagnosis and treatment with [177Lu]Lu-PSMA-617 in patients with PC.

First report of fatal fungemia due Fusarium oxysporum in a patient with COVID-19 in Ecuador.

Filamentous fungal infections are an important cause of systemic infections in immunocompromised patients. Fusarium genus members potentially cause disseminated infections, especially in patients with catheters, due to the ability to adhere to these devices. We describe a case of fatal fungemia due to Fusarium oxysporum in a patient with COVID-19 in Ecuador. The genus identification was carried out with conventional techniques and species identification by molecular and phylogenetic techniques through sequencing of the ITS region.

Taxes, Inequality, and Equal Opportunities.

Extreme inequality represents a grave challenge for impoverished individuals and poses a threat to economic growth and stability. Despite the fulfillment of affirmative action measures aimed at promoting equal opportunities, they often prove inadequate in effectively reducing inequality. Mathematical models and simulations have demonstrated that even when equal opportunities are present, wealth tends to concentrate in the hands of a privileged few, leaving the majority of the population in dire poverty. This phenomenon, known as condensation, has been shown to be an inevitable outcome in economic models that rely on fair exchange. In light of the escalating levels of inequality in the 21st century and the significant state intervention necessitated by the recent COVID-19 pandemic, an increasing number of scholars are abandoning neo-liberal ideologies. Instead, they propose a more robust role for the state in the economy, utilizing mechanisms such as taxation, regulation, and universal allocations. This paper begins with the assumption that state intervention is essential to effectively reduce inequality and to revitalize the economy. Subsequently, it conducts a comparative analysis of various taxation and redistribution mechanisms, with a particular emphasis on their impact on inequality indices, including the Gini coefficient. Specifically, it compares the effects of fortune and consumption-based taxation, as well as universal redistribution mechanisms or targeted redistribution mechanisms aimed at assisting the most economically disadvantaged individuals. The results suggest that fortune taxation are more effective than consumption-based taxation to reduce inequality.

Impact of Acute High Glucose on Mitochondrial Function in a Model of Endothelial Cells: Role of PDGF-C.

An increase in plasma high glucose promotes endothelial dysfunction mainly through increasing mitochondrial ROS production. High glucose ROS-induced has been implicated in the fragmentation of the mitochondrial network, mainly by an unbalance expression of mitochondrial fusion and fission proteins. Mitochondrial dynamics alterations affect cellular bioenergetics. Here, we assessed the effect of PDGF-C on mitochondrial dynamics and glycolytic and mitochondrial metabolism in a model of endothelial dysfunction induced by high glucose. High glucose induced a fragmented mitochondrial phenotype associated with the reduced expression of OPA1 protein, high DRP1pSer616 levels and reduced basal respiration, maximal respiration, spare respiratory capacity, non-mitochondrial oxygen consumption and ATP production, regarding normal glucose. In these conditions, PDGF-C significantly increased the expression of OPA1 fusion protein, diminished DRP1pSer616 levels and restored the mitochondrial network. On mitochondrial function, PDGF-C increased the non-mitochondrial oxygen consumption diminished by high glucose conditions. These results suggest that PDGF-C modulates the damage induced by HG on the mitochondrial network and morphology of human aortic endothelial cells; additionally, it compensates for the alteration in the energetic phenotype induced by HG.

Structural Analysis and Diversity of Calmodulin-Binding Domains in Membrane and Intracellular Ca2+-ATPases.

The plasma membrane and autoinhibited Ca2+-ATPases contribute to the Ca2+ homeostasis in a wide variety of organisms. The enzymatic activity of these pumps is stimulated by calmodulin, which interacts with the target protein through the calmodulin-binding domain (CaMBD). Most information about this region is related to all calmodulin modulated proteins, which indicates general chemical properties and there is no established relation between Ca2+ pump sequences and taxonomic classification. Thus, the aim of this study was to perform an in silico analysis of the CaMBD from several Ca2+-ATPases, in order to determine their diversity and to detect specific patterns and amino acid selection in different species. Patterns related to potential and confirmed CaMBD were detected using sequences retrieved from the literature. The occurrence of these patterns was determined across 120 sequences from 17 taxonomical classes, which were analyzed by a phylogenetic tree to establish phylogenetic groups. Predicted physicochemical characteristics including hydropathy and net charge were calculated for each group of sequences. 22 Ca2+-ATPases sequences from animals, unicellular eukaryotes, and plants were retrieved from bioinformatic databases. These sequences allow us to establish the Patterns 1(GQILWVRGLTRLQTQ), 3(KNPSLEALQRW), and 4(SRWRRLQAEHVKK), which are present at the beginning of putative CaMBD of metazoan, parasites, and land plants. A pattern 2 (IRVVNAFR) was consistently found at the end of most analyzed sequences. The amino acid preference in the CaMBDs changed depending on the phylogenetic groups, with predominance of several aliphatic and charged residues, to confer amphiphilic properties. The results here displayed show a conserved mechanism to contribute to the Ca2+ homeostasis across evolution and may help to detect putative CaMBDs.

Discontinuation of mechanical bowel preparation in advanced ovarian cancer surgery: an enhanced recovery after surgery (ERAS) initiative.

OBJECTIVE: To investigate the impact of discontinuation of mechanical bowel preparation in advanced ovarian cancer surgery within the context of the ERAS program. METHODS: We retrospectively reviewed the medical records of patients with advanced ovarian cancer who underwent cytoreductive surgery with simultaneous colon and/or rectal resection from January 2012 to November 2020. Patients were divided into two groups based on whether preoperative mechanical bowel preparation (MBP) was given (pre-ERAS) or not (post-ERAS). Patient characteristics, including duration of antibiotic treatment, surgical complexity, and incidence of surgical and nonsurgical complications, were compared. RESULTS: During the study period, 114 patients who underwent colon and/or rectal resection were examined, of whom 39 received MBP and 75 did not receive MBP (NMBP). On comparison between the two groups, no significant differences were noted in the assessed patient characteristics, including mean age, FIGO stage, ASA class, BMI, or residual tumor. One patient (2.6%) in the MBP group, and 4 patients (5.3%) in the NMBP group experienced an anastomotic leakage (p = 0.11). No significant differences were found with respect to surgical site infection. (p = 0.5). CONCLUSION: MBP was not associated with any specific benefit for advanced ovarian cancer surgery. Gynecologic oncologists who use MBP should consider discontinuing this practice.

Routine Immunization Programs for Children during the COVID-19 Pandemic in Ecuador, 2020-Hidden Effects, Predictable Consequences.

The COVID-19 pandemic has led to a global disruption of several services, including routine immunizations. This effect has been described in several countries, but there are few detailed studies in Latin America and no reports in Ecuador. Therefore, this work aims to quantify the reduction in routine immunizations for infants during the 2020 COVID-19 pandemic in Ecuador. 2018, 2019, and 2020 data were obtained from the Ministry of Health, Ecuador. The number of doses and the extent of immunization coverage was descriptively compared for four vaccines: rotavirus (ROTA), poliovirus (PV), pneumococcal (PCV), and pentavalent (PENTA) vaccines. There was no significant difference in doses applied during the 2018 and 2019 years. However, a significant (p < 0.05) drop of 137,000 delivered doses was observed in 2020 compared to the pre-pandemic years. Reductions in the percentage of coverage were more pronounced for the PENTA vaccine (17.7%), followed by PV (16.4%), ROTA (12%), and PCV vaccines (10.7%). Spatial analysis shows a severe impact on vaccination coverage on provinces from the Coast and Highland regions of the country. The pandemic has significantly impacted the immunization programs for infants across Ecuador. This retrospective analysis shows an urgent need to protect vulnerable zones and populations during public health emergencies.

Study of taxes, regulations and inequality using machine learning algorithms.

Genetic machine learning (ML) algorithms to train agents in the Yard-Sale model proved very useful for finding optimal strategies that maximize their wealth. However, the main result indicates that the more significant the fraction of rational agents, the greater the inequality at the collective level. From social and economic viewpoints, this is an undesirable result since high inequality diminishes liquidity and trade. Besides, with very few exceptions, most agents end up with zero wealth, despite the inclusion of rational behaviour. To deal with this situation, here we include a taxation-redistribution mechanism in the ML algorithm. Previous results show that simple regulations can considerably reduce inequality if agents do not change their behaviour. However, when considering rational agents, different types of redistribution favour risk-averse agents, to some extent. Even so, we find that rational agents looking for optimal wealth can always arrive to an optimal risk, compatible with a particular choice of parameters, but increasing inequality. This article is part of the theme issue 'Kinetic exchange models of societies and economies'.

Trastornos metabólicos urinarios en pacientes urolitiásicos con enfermedad renal poliquística y sin ella / Urinary metabolic disorders in urolithiasis patients with and without polycystic kidney disease

Introducción: La urolitiasis se ha incrementado en las últimas décadas. La enfermedad renal poliquística autosómica dominante (ERPAD), enfermedad renal hereditaria más frecuente, ocupa un lugar preponderante. Objetivos: Identificar la frecuencia de presentación de los trastornos metabólicos urinarios en pacientes litiásicos cubanos con ERPAD y sin ella Métodos: Estudio descriptivo, transversal. Fueron estudiados 579 pacientes adultos sin ERPAD, seleccionados por muestreo simple aleatorio y los 21 pacientes con ERPAD, del total de pacientes con litiasis urinaria que se realizó estudio metabólico renal en el Laboratorio de Fisiopatología Renal del Instituto de Nefrología, en el periodo 2010-2015. Los datos fueron tomados de la historia clínica y del informe de estudio metabólico renal. La información se procesó de forma automatizada (SPSS 22.0). Se utilizó el promedio, desviación estándar, análisis de distribución de frecuencias y el test de homogeneidad. Resultados: En los pacientes con ERPAD predominó el sexo femenino (57,1 por ciento), mientras que en los pacientes sin ERPAD, el masculino (63,4 por ciento). Los trastornos más frecuentes en la población no poliquística fueron hipercalciuria (45,3 por ciento) e hipofosfatemia (17,1 por ciento). En los poliquísticos, aclaramiento aumentado de ácido úrico (38,1 por ciento) e hipercalciuria (23,8 por ciento). Se encontraron diferencias estadísticamente significativas para aumento del aclaramiento de ácido úrico (p = 0,01) e hiperfosfatemia (p = 0,04). Conclusiones: Los principales trastornos metabólicos de los pacientes litiásicos, tanto poliquísticos como no poliquísticos, son el aclaramiento de ácido úrico aumentado, hipercalciuria, hiperuricosuria e hipofosfatemia, aunque el orden de presentación es diferente. El aclaramiento de ácido úrico aumentado y la hiperfosfatemia se presentan con mayor frecuencia en los pacientes litiásicos poliquísticos(AU)

Introduction: Urolithiasis has increased in recent decades. Autosomal dominant polycystic kidney disease (ADPKD), the most common of all hereditary kidney diseases, occupies a predominant position in terms of incidence. Objectives: Identify the frequency of occurrence of urinary metabolic disorders in Cuban urolithiasis patients with and without ADPKD. Methods: A descriptive cross-sectional study was conducted of 579 adult patients without ADPKD selected by simple random sampling, and 21 patients with ADPKD, from the total urolithiasis patients undergoing renal metabolic evaluation at the Renal Physiopathology Laboratory of the Institute of Nephrology in the period 2010-2015. Data were obtained from medical records and reports of renal metabolic studies. Information was processed with the statistical software SPSS version 22.0. Average and standard deviation were estimated and use was made of frequency distribution analysis and homogeneity testing. Results: A predominance was found of female sex among patients with ADPKD (57.1 percent) and male sex among patients without ADPKD (63.4 percent). The most common disorders were hypercalciuria (45.3 percent) and hypophosphatemia (17.1 percent) in the non-polycystic population, and increased uric acid clearance (38.1 percent) and hypercalciuria (23.8 percent) in polycystic patients. Statistically significant differences were found in uric acid clearance increase (p = 0.01) and hyperphosphatemia (p = 0.04). Conclusions: The main metabolic disorders of lithiasis patients, polycystic as well as non-polycystic, are increased uric acid clearance, hypercalciuria, hyperuricosuria and hypophosphatemia, with a varying order of presentation. Increased uric acid clearance and hyperphosphatemia are more common in polycystic lithiasis patients(AU)

A store-operated Ca2+-entry in Trypanosoma equiperdum: Physiological evidences of its presence.

The Trypanosomatidae family encompasses many unicellular organisms responsible of several tropical diseases that affect humans and animals. Livestock tripanosomosis caused by Trypanosoma brucei brucei (T. brucei), Trypanosoma equiperdum (T. equiperdum) and Trypanosoma evansi (T. evansi), have a significant socio-economic impact and limit animal protein productivity throughout the intertropical zones of the world. Similarly, to all organisms, the maintenance of Ca2+ homeostasis is vital for these parasites, and the mechanism involved in the intracellular Ca2+ regulation have been widely described. However, the evidences related to the mechanisms responsible for the Ca2+ entry are scarce. Even more, to date the presence of a store-operated Ca2+ channel (SOC) has not been reported. Despite the apparent absence of Orai and STIM-like proteins in these parasites, in the present work we demonstrate the presence of a store-operated Ca2+-entry (SOCE) in T. equiperdum, using physiological techniques. This Ca2+-entry is induced by thapsigargin (TG) and 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ), and inhibited by 2-aminoethoxydiphenyl borate (2APB). Additionally, the use of bioinformatics techniques allowed us to identify putative transient receptor potential (TRP) channels, present in members of the Trypanozoon family, which would be possible candidates responsible for the SOCE described in the present work in T. equiperdum.

Mortalidad de los enfermos renales crónicos en edad laboral en Cuba / Mortality of chronic kidney patients of working ages in Cuba

Introducción: La enfermedad renal crónica constituye un gran problema de salud en el mundo y en Cuba. Para el año 2040 puede convertirse en la quinta causa más común de años de vida potencialmente perdidos a nivel mundial y es una importante causa de gastos para la salud, la economía y el seguro social de los países. Objetivo: Caracterizar la mortalidad en pacientes renales crónicos en edad laboral en Cuba, en los años 2011-2017, según variables sociodemográficas seleccionadas. Métodos: Investigación transversal descriptiva. El universo estuvo constituido por los 5 716 fallecidos con enfermedad renal crónica. La información fue tomada de las bases de datos de mortalidad de la Dirección Nacional de Estadísticas, del Ministerio de Salud Pública. Se estudiaron las variables: edad, sexo, ocupación y principales causas de muerte. Se calcularon tasas brutas, así como tasas de mortalidad específicas. Resultados: En la edad laboral la mortalidad por enfermedad renal crónica presentó oscilaciones del año 2011 al 2017. La edad media al morir fue 53.7 años, los mayores de 61 años, hombres, presentaron el mayor riesgo (16 por 10 000 habitantes). La tasa en la población económicamente activa desocupada fue de 33 por 10 000 habitantes. El riesgo fue mayor en las ocupaciones elementales (9 por 10 000 habitantes). La enfermedad renal hipertensiva fue la principal causa de muerte (17 por 100 000 habitantes). Conclusiones: Existe ligero incremento de la mortalidad, en hombres el riesgo es mayor, la tasa más alta es en población económicamente activa desocupada y en las ocupaciones elementales. La principal causa de muerte es la enfermedad renal hipertensiva(AU)

Introduction: Chronic kidney disease constitutes a major health problem in Cuba and worldwide. By 2040 it may become the fifth most common cause of years of life potentially lost, worldwide, and a major cause of health expenses, economy and social security. Objective: To describe mortality in chronic kidney patients of working ages in Cuba, from 2011to 2017, according to selected sociodemographic variables. Methods: This is descriptive cross-sectional research. The universe consisted of 5,716 deceased subjects with chronic kidney disease. The information was taken from the mortality databases of the National Directorate of Statistics, from the Ministry of Public Health. The variables were studied age, sex, occupation and main causes of death. Gross and specific mortality rates were calculated. Results: In working age, mortality from chronic kidney disease fluctuated from 2011 to 2017. The mean age at death was 53.7 years, those over 61 years of age, men, had the highest risk (16 per 10,000 inhabitants). The rate in the economically active unemployed population was 33 per 10,000 inhabitants. The risk was higher in basic occupations (9 per 10,000 inhabitants). Hypertensive kidney disease was the leading cause of death (17 per 100,000 population). Conclusions: There is a slight increase in mortality, the risk is higher in men, the highest rate is in the economically active unemployed population and in basic occupations. The leading cause of death is hypertensive kidney disease(AU)

Nutrient dynamics of corn fed to livestock in conservation-based agroecosystems in neotropical savannas / Dinâmica de nutrientes em milho para alimentação de gado em agroecossistemas baseados na conservação de savanas neotropicais

Mineral deficiencies in soil-plant-animal relations are linked to chemical properties and reproductiveproblems in grazing animals. The objective of this study was to determine the dynamics of K, Ca, and Mgin the green leaf biomass of two types of introduced forages, Brachiaria dyctioneura (Bd) and Centrosema macrocarpum (Cm), compared to the natural vegetation of the neotropical savannah (NS) in an agricultural ecosystem. The three types of vegetation, associated with the corn crop, served as livestock feed during the dry season. The soils nutrient content (0-15 cm depth), the production and nutritional dynamics of green leaf biomass, and leaf/stem relationships in the fields during the grazing period were determined. In the corn crop-livestock agroecosystem, K decreased (%) in concentration as the grazing period progressed, presenting the following trend: Bd>Cm>NS. The dynamics of Ca and Mg in green leaf biomass increased slightly (p<0.05) by the end of the grazing period for Bd and Cm, in contrast to a significant decrease in the natural vegetation of the savannah. The concentration of K in the soil did not reveal significant differences between ground cover and NS plants, and the soils under Cm evidenced thehighest percentage of Ca. A higher percentage of Mg was observed in the soil planted with Cm. For the three types of vegetation, an improvement was observed in the nutritional quality of the forage and soil and in the yield (kg/ha). These findings are valuable contributions within the context of production in savannas and to forage quality for livestock.(AU)

Deficiências minerais no eixo solo-planta-animal estão relacionadas as propriedades químicas e estão ligadas a problemas reprodutivos em animais em pastejo. O objetivo deste estudo foi determinar a dinâmica de K, Ca e Mg na biomassa foliar verde de dois tipos de forrageiras introduzidas (Brachiaria dyctioneura (Bd) e Centrosema macrocarpum (Cm)) em relação à vegetação natural do cerrado (NS) em um ecossistema agrícola. Os três tipos de vegetação, associados ao cultivo do milho, serviam de ração para o gado durante a estação seca. Foram determinados o conteúdo de nutrientes no solo (0-15 cm de profundidade), a produção de biomassa de folhas verdes e sua dinâmica nutricional e as relações folha-colmo nas lavouras durante o pastejo. No agroecossistema milho-pecuária, o K apresentou redução (%) em sua concentração com o avanço do período de pastejo, apresentando a seguinte tendência: Bd> Cm> NS. A dinâmica do Ca e Mg na biomassa foliar verde aumentou ligeiramente (p <0,05) ao final do período de pastejo em Bd e Cm, contrastando com uma diminuição significativa na vegetação natural do cerrado. A concentração de K no solo não apresentou diferenças significativas entre as plantas de cobertura e o NS, sendo que os solos sob Cm apresentaram a maior porcentagem de Ca. Uma maior porcentagem de Mg foi observada no solo plantado com Cm. Nos três tipos de vegetação examinados, observou-se melhora na qualidade nutricional da forragem e solo e na produtividade (kg/ha). Essas descobertas são contribuições valiosas nos contextos de produção das savanas e na qualidade da forragem para o gado.(AU)

Nutrient dynamics of corn fed to livestock in conservation-based agroecosystems in neotropical savannas / Dinâmica de nutrientes em milho para alimentação de gado em agroecossistemas baseados na conservação de savanas neotropicais

Mineral deficiencies in soil-plant-animal relations are linked to chemical properties and reproductiveproblems in grazing animals. The objective of this study was to determine the dynamics of K, Ca, and Mgin the green leaf biomass of two types of introduced forages, Brachiaria dyctioneura (Bd) and Centrosema macrocarpum (Cm), compared to the natural vegetation of the neotropical savannah (NS) in an agricultural ecosystem. The three types of vegetation, associated with the corn crop, served as livestock feed during the dry season. The soil’s nutrient content (0-15 cm depth), the production and nutritional dynamics of green leaf biomass, and leaf/stem relationships in the fields during the grazing period were determined. In the corn crop-livestock agroecosystem, K decreased (%) in concentration as the grazing period progressed, presenting the following trend: Bd>Cm>NS. The dynamics of Ca and Mg in green leaf biomass increased slightly (p<0.05) by the end of the grazing period for Bd and Cm, in contrast to a significant decrease in the natural vegetation of the savannah. The concentration of K in the soil did not reveal significant differences between ground cover and NS plants, and the soils under Cm evidenced thehighest percentage of Ca. A higher percentage of Mg was observed in the soil planted with Cm. For the three types of vegetation, an improvement was observed in the nutritional quality of the forage and soil and in the yield (kg/ha). These findings are valuable contributions within the context of production in savannas and to forage quality for livestock.

Deficiências minerais no eixo solo-planta-animal estão relacionadas as propriedades químicas e estão ligadas a problemas reprodutivos em animais em pastejo. O objetivo deste estudo foi determinar a dinâmica de K, Ca e Mg na biomassa foliar verde de dois tipos de forrageiras introduzidas (Brachiaria dyctioneura (Bd) e Centrosema macrocarpum (Cm)) em relação à vegetação natural do cerrado (NS) em um ecossistema agrícola. Os três tipos de vegetação, associados ao cultivo do milho, serviam de ração para o gado durante a estação seca. Foram determinados o conteúdo de nutrientes no solo (0-15 cm de profundidade), a produção de biomassa de folhas verdes e sua dinâmica nutricional e as relações folha-colmo nas lavouras durante o pastejo. No agroecossistema milho-pecuária, o K apresentou redução (%) em sua concentração com o avanço do período de pastejo, apresentando a seguinte tendência: Bd> Cm> NS. A dinâmica do Ca e Mg na biomassa foliar verde aumentou ligeiramente (p <0,05) ao final do período de pastejo em Bd e Cm, contrastando com uma diminuição significativa na vegetação natural do cerrado. A concentração de K no solo não apresentou diferenças significativas entre as plantas de cobertura e o NS, sendo que os solos sob Cm apresentaram a maior porcentagem de Ca. Uma maior porcentagem de Mg foi observada no solo plantado com Cm. Nos três tipos de vegetação examinados, observou-se melhora na qualidade nutricional da forragem e solo e na produtividade (kg/ha). Essas descobertas são contribuições valiosas nos contextos de produção das savanas e na qualidade da forragem para o gado.

Macroscopic and microscopic perspectives for adoption of technologies in the USA.

Adoption of a new technology depends on many factors. Marketing, advertising, social interactions, and personal convictions are relevant features when deciding to adopt, or not, a new technology. Thus, it is very important to determine the relative weight of these factors when introducing a new technology. Here we discuss an agent based model to investigate the behavior of agents exposed to advertising and social contacts. Agents may follow the social pressure, or maybe contrarians, acting against the majority, to decide if they adopt or not a new technology. First, we solve analytically the model that relies on the above quoted factors. Then, we compare the theoretical results with empirical data concerning the adoption of innovations by American households during the 20th century. The analysis of the diffusion dynamics process is done either for the whole period, or by periods based on the so-called technical-economic paradigms, according to Freeman and Perez. Three different periods are considered: before 1920, from 1920 to 1970, and after 1970. We study the evolution of the model parameters for each technical-economic period. Finally, by adjusting the key parameters we are able to collapse all the data into a universal curve that describes all the adoption processes.

Embryo placement in IVF and reproductive outcomes: a cohort analysis and review.

OBJECTIVE: The objective of the present study was to determine the influence of the embryo placement depth on the endometrial cavity in relation to the reproductive outcomes, after frozen-thawed embryo transfer performed under transabdominal ultrasound guidance. METHODS: Retrospective cohort study that evaluated the influence of the embryo placement depth in the endometrial cavity in relation to the reproductive outcomes of patients submitted to cryotransfer cycles at a private assisted reproduction clinic, from 2012 to 2017. The patients were classified according to three variables: <10mm, 10 to 15mm and >15mm. The primary outcome was clinical pregnancy, and the secondary outcomes were miscarriage, ongoing pregnancy and live birth. The data was summarized as relative risk, with a 95%CI. RESULTS: Clinical and ongoing pregnancy rates were higher in the 10-15mm and >15mm Groups, when compared to the <10mm Group; there was no statistical difference between the groups in terms of miscarriage and live birth rates. We performed a subsequent analysis, using the same sample of patients, comparing only the <10mm and ≥10mm variables. The ≥10mm Group had better reproductive outcomes, with higher clinical and ongoing pregnancy rates. CONCLUSION: Pregnancy rates are influenced by embryo transfer site, and better results can be achieved when the tip of the catheter is placed in the central area of the endometrial cavity, especially when the distance from the endometrial fundus is >10mm.

Pharmacokinetic Evaluation of Nimotuzumab in Patients With Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by an overexpression and mislocalization of epidermal growth factor receptor (EGFR) to the apical membranes of cystic epithelial cells. Nimotuzumab is a humanized antibody that recognizes an extracellular domain III of human EGFR. The aim of this study was to assess the pharmacokinetic behavior of nimotuzumab in patients with ADPKD given as a single dose. A phase I, single-center, and noncontrolled open clinical study was conducted. Five patients were enrolled at each of the following fixed-dose levels: 50, 100, 200, and 400 mg. Intravenous continuous infusions of nimotuzumab were administered every 14 days during a year, except the first administration, when blood samples were drawn during 28 days for pharmacokinetic assessments. Subjects were closely monitored during the trial and at completion of the administration of nimotuzumab, including the anti-idiotypic response. For the first time, nimotuzumab was used for treating a nononcological disease. The administration of nimotuzumab showed dose-dependent kinetics. Nimotuzumab does not develop anti-idiotypic response against the murine portion present in the hypervariable region of the antibody present in the serum of the patients treated. No significant differences were found in the systemic clearance between the 100- and 400-mg dose, which indicates that the optimal biological dose is in this range of dose.

Identification and characterization of a calmodulin binding domain in the plasma membrane Ca2+-ATPase from Trypanosoma equiperdum.

The plasma membrane Ca2+-ATPase (PMCA) from trypanosomatids lacks a classical calmodulin (CaM) binding domain, although CaM stimulated activities have been detected by biochemical assays. Recently we proposed that the Trypanosoma equiperdum CaM-sensitive PMCA (TePMCA) contains a potential 1-18 CaM-binding motif at the C-terminal region of the pump. In the present study, we evaluated the potential CaM-binding motifs using CaM from Trypanosoma cruzi and either the recombinant full length TePMCA C-terminal sequence (P14) or synthetic peptides comprising different regions of the C-terminal domain. We demonstrated that P14 and a synthetic peptide corresponding to residues 1037-1062 (which contains the predicted 1-18 binding motif) competed efficiently for binding to TcCaM, exhibiting similar IC50s of 200 nM. A stable complex of this peptide and TcCaM was formed in the presence of Ca2+, as determined by native-polyacrylamide gel electrophoresis. A predicted structure obtained by molecular docking showed an interaction of the 1-18 binding motif with the Ca2+/CaM complex. Moreover, when the peptide was incubated with CaM and Ca2+, a blue shift in the tryptophan fluorescence spectrum (from 350 to 329 nm) was observed. Substitutions at W1039 and F1056, strongly decreased both CaM-peptide interaction and the complex assembly. Our results demonstrated the presence of a functional 1-18 motif at the TePMCA C-terminal domain. Furthermore, on the basis of spectrofluorometric assays and the resulting structure modeled by docking we propose that the L1042 and W1060 residues might also participate as anchors to form a 1-4-18-22 motif.

Oral dydrogesterone vs. vaginal progesterone capsules for luteal-phase support in women undergoing embryo transfer: a systematic review and meta-analysis.

OBJECTIVE: To identify, appraise, and summarize the evidence from randomized controlled trials (RCTs) comparing oral dydrogesterone to vaginal progesterone capsules for luteal-phase support (LPS) in women offered fresh or frozen embryo transfers following in vitro fertilization. METHODS: Two independent authors screened the literature for papers based on titles and abstracts, then selected the studies, extracted data, and assessed the risk of bias. Dydrogesterone and progesterone were compared based on risk ratios (RR) and the precision of the estimates was assessed through the 95% confidence interval (CI). RESULTS: An electronic search performed on June 7, 2017 retrieved 376 records, nine of which were papers deemed eligible and included in this systematic review and quantitative analysis. Good quality evidence indicates that oral dydrogesterone provided at least similar results than vaginal progesterone capsules on live birth/ongoing pregnancy (RR=1.08, 95%CI=0.92-1.26, I2=29%, 8 RCTs, 3,386 women) and clinical pregnancy rates (RR 1.10, 95% CI 0.95 to 1.27; I2=43%; 9 RCTs; 4,061 women). Additionally, moderate quality evidence suggests there is no relevant difference on miscarriage rates (RR=0.92, 95%CI=0.68-1.26, I2=6%, 8 RCTs, 988 clinical pregnancies; the quality of the evidence was downgraded because of imprecision). CONCLUSIONS: Good quality evidence from RCTs suggest that oral dydrogesterone provides at least similar reproductive outcomes than vaginal progesterone capsules when used for LPS in women undergoing embryo transfers. Dydrogesterone is a reasonable option and the choice of either of the medications should be based on cost and side effects.

Epidemic spreading in multiplex networks influenced by opinion exchanges on vaccination.

Through years, the use of vaccines has always been a controversial issue. People in a society may have different opinions about how beneficial the vaccines are and as a consequence some of those individuals decide to vaccinate or not themselves and their relatives. This attitude in face of vaccines has clear consequences in the spread of diseases and their transformation in epidemics. Motivated by this scenario, we study, in a simultaneous way, the changes of opinions about vaccination together with the evolution of a disease. In our model we consider a multiplex network consisting of two layers. One of the layers corresponds to a social network where people share their opinions and influence others opinions. The social model that rules the dynamic is the M-model, which takes into account two different processes that occurs in a society: persuasion and compromise. This two processes are related through a parameter r, r < 1 describes a moderate and committed society, for r > 1 the society tends to have extremist opinions, while r = 1 represents a neutral society. This social network may be of real or virtual contacts. On the other hand, the second layer corresponds to a network of physical contacts where the disease spreading is described by the SIR-Model. In this model the individuals may be in one of the following four states: Susceptible (S), Infected(I), Recovered (R) or Vaccinated (V). A Susceptible individual can: i) get vaccinated, if his opinion in the other layer is totally in favor of the vaccine, ii) get infected, with probability ß if he is in contact with an infected neighbor. Those I individuals recover after a certain period tr = 6. Vaccinated individuals have an extremist positive opinion that does not change. We consider that the vaccine has a certain effectiveness ω and as a consequence vaccinated nodes can be infected with probability ß(1 - ω) if they are in contact with an infected neighbor. In this case, if the infection process is successful, the new infected individual changes his opinion from extremist positive to totally against the vaccine. We find that depending on the trend in the opinion of the society, which depends on r, different behaviors in the spread of the epidemic occurs. An epidemic threshold was found, in which below ß* and above ω* the diseases never becomes an epidemic, and it varies with the opinion parameter r.

Pleuropulmonary Blastoma: A Single-center Case Series of 6 Patients.

Pleuropulmonary blastoma (PPB) is a rare malignancy of childhood which when left untreated often shows pathologic progression resulting in a more aggressive neoplasm with an increasingly poor prognosis. Because of this it is important to diagnose and initiate treatment early. However, early stage PPB can appear as a cystic lung lesion on imaging and can be easily misdiagnosed given the rarity of the malignancy. Moreover, current therapeutic guidelines for these lesions are not well established, making treatment decisions and management difficult for clinicians. DICER1 mutations are known to be present in a majority of PPBs with or without a germline mutation and may be part of a familial tumor predisposition syndrome. The clinical, pathologic, and genetic data of 6 patients are summarized here. Two patients with type I PPB and 4 patients with type II PPB underwent surgical and chemotherapeutic treatment and all are alive and without recurrence 1 to 13 years after treatment. With increasing awareness of PPB, it is important for clinicians to consider this malignant entity in the evaluation and treatment of patients presenting with a cystic lung abnormality, especially in cases with a history strongly suggestive of a DICER1 mutation.