Ultrafast 30-min infusion of a rituximab biosimilar (Truxima).

In this clinical trial, we demonstrate that ultrarapid fast infusion of rituximab (Truxima) in 30 min with oral premedication is feasible and secure for patients, and reduce the day-care hospital stays.

The Medical versus Zoological Concept of Outflow Tract Valves of the Vertebrate Heart.

The anatomical elements that in humans prevent blood backflow from the aorta and pulmonary artery to the left and right ventriclesare the aortic and pulmonary valves, respectively. Each valve regularly consists of three leaflets (cusps), each supported by its valvular sinus. From the medical viewpoint, each set of three leaflets and sinuses is regarded as a morpho-functional unit. This notion also applies to birds and non-human mammals. However, the structures that prevent the return of blood to the heart in other vertebrates are notably different. This has led to discrepancies between physicians and zoologists in defining what a cardiac outflow tract valve is. The aim here is to compare the gross anatomy of the outflow tract valvular system among several groups of vertebrates in order to understand the conceptual and nomenclature controversies in the field.

Características y evolución de los pacientes COVID-19 en un centro de salud urbano al inicio de la pandemia / Characteristics and evolution of COVID-19 in an urban Health Center at the pandemic beginning

OBJETIVO: Evaluar las características de los pacientes con SARS-CoV-2 y analizar diferencias entre los que requirieron asistencia hospitalaria y los seguidos ambulatoriamente. DISEÑO: Estudio observacional, descriptivo, retrospectivo. EMPLAZAMIENTO: 2 unidades básicas asistenciales de un centro de salud urbano en Salamanca (España). PARTICIPANTES: Pacientes ≥ 18 años diagnosticados de SARS-CoV-2 entre el 11 de marzo y el 20 de abril. MEDICIONES PRINCIPALES: Características clínico-epidemiológicas, diagnóstico, tratamiento y desenlace a fecha fin de estudio. RESULTADOS: Ciento veintidós pacientes (63,9% mujeres), 19,7% trabajadores sociosanitarios y 4,9% institucionalizados. Franja etaria predominante: 46-60 años, edad media: 52,1(DE 17,85). El 67,2% sin comorbilidad. Síntomas más prevalentes: febrícula (73,5%), tos (65,2%) y fiebre (43%). La edad media de los que requieren atención hospitalaria es mayor a los seguidos ambulatoriamente: 59,85 años (DE 16,22) vs. 50,78 (DE 17,88); p = 0,013. El 63,6% del total seguidos por Atención Primaria no presentó disnea, frente a 17 (14,1%) de los que acudieron a Urgencias; p = 0,001. No se realizaron pruebas confirmatorias al 2,5% de los que visitaron el hospital, frente al 61,5% de los seguidos ambulatoriamente; p = 0,0001; 26 acuden a Urgencias: 11 (9%) ingresaron y 2 (1,6%) fallecieron. El 52,5% no necesitó antibioterapia y el 70.5% no requirió inhaladores. El antipirético más empleado fue paracetamol (78.7%). CONCLUSIONES: Prevalencia en mujeres, personas sin comorbilidad y en la franja de edad de 46-60 años. Las pruebas complementarias y confirmatorias se realizaron mayoritariamente en asistencia hospitalaria. Predominancia de sintomatología leve y evolución favorable. Destacamos el papel de Atención Primaria en la detección, la intervención temprana y el seguimiento en casos graves

OBJETIVE: To evaluate SAR-COV-2 pacients' features. To analyse de diferences between those who required hospital care and those who didn't. DESIGN: Observational, descriptive and retrospective study. SETTING: Two medical practices of an urban health center in Salamanca (Spain). PARTICIPANTS: ≥ 18 years diagnosed with SAR-CoV-2 between March 11 th and April 20 th. MAIN MEASUREMENTS: clinical-epidemiological chatacteristics, diagnosis, treatment and outcome at the end of study RESULTS: 122 patients (63.9% female), 19.7% social and health care workers y 4.9% from nursing homes. Predominant age group: 46-60 years. 67.2% without comorbility. Predomint symptoms: low-grade fever (73.5%), cough (65.2%) y fever (43%). Average age of the patients requiring hospital care was higher: 59.85 (DE16.22) versus 50.78 (DE17.88) P = .013. 63.6% of all the patients monitored by Primary Health Care and 14.1% of patients that required assistance did not present dyspnea P = .001. Only 2.5% of the hospital-assisted patients, compared to 61.5% of Primary Health Care, were not tested P = .0001. 26 patients were attendedn at an emergency room: 11(9%) stayed and 2 (1.6%) passed away. No antibiotic or inhaler treatment for 52.5% and 70.5% respectively. The most used antipyretic treatment was paracetamol (78.7%). CONCLUSIONS: Prevalence in females, comorbility-free patients and in age range: 46-60 years. Complementary and confirmatory test were performed mainly in hospital care. Predominance of mild symptoms and favourable evolution. Highliting the role played by Primary Health Care in detection, early intervention and monitoring of severe cases

[Characteristics and evolution of COVID-19 in an urban Health Center at the pandemic beginning']. / Características y evolución de los pacientes COVID-19 en un centro de salud urbano al inicio de la pandemia.

OBJETIVE: To evaluate SAR-COV-2 pacients' features. To analyse de diferences between those who required hospital care and those who didn't. DESIGN: Observational, descriptive and retrospective study. SETTING: Twomedical practices of an urban health center in Salamanca (Spain). PARTICIPANTS: ≥18 years diagnosed with SAR-CoV-2 between March 11th and April 20th. MAIN MEASUREMENTS: clinical-epidemiological chatacteristics, diagnosis, treatment and outcome at the end of study RESULTS: 122 patients (63.9% female), 19.7% social and health care workers y 4.9% from nursing homes. Predominant age group: 46-60 years. 67.2% without comorbility. Predomint symptoms: low-grade fever (73.5%), cough (65.2%) y fever (43%). Average age of the patients requiring hospital care was higher: 59.85 (DE16.22) versus 50.78 (DE17.88) P=.013. 63.6% of all the patients monitored by Primary Health Care and 14.1% of patients that required assistance did not present dyspnea P=.001. Only 2.5% of the hospital-assisted patients, compared to 61.5% of Primary Health Care, were not tested P=.0001. 26 patients were attendedn at an emergency room: 11(9%) stayed and 2 (1.6%) passed away. No antibiotic or inhaler treatment for 52.5% and 70.5% respectively. The most used antipyretic treatment was paracetamol (78.7%). CONCLUSIONS: Prevalence in females, comorbility-free patients and in age range: 46-60 years. Complementary and confirmatory test were performed mainly in hospital care. Predominance of mild symptoms and favourable evolution. Highliting the role played by Primary Health Care in detection, early intervention and monitoring of severe cases.

Vitamin D Receptor Polymorphisms and Non-Melanoma Skin Cancer Risk: A Case-Control Study.

Exposure to sunlight is the major source of vitamin D and the main environmental cause of non-melanocytic skin cancers. Vitamin D, partly mediated through the vitamin D receptor (VDR), has potential therapeutic applications in skin cancer. The aim of this study was to investigate the association of BsmI and ApaI VDR polymorphisms among patients with non-melanoma cancers and controls. An observational case-control study was conducted in a sample of 154 subjects. We observed no significant effects between these polymorphisms and skin cancer risk. When stratified for gender, GG and AG BsmI polymorphisms significantly increased the risk of basal cell carcinomas in males. In relation to ApaI, all three polymorphisms significantly increased the risk of basal cell carcinoma in males. When stratified for age, we found that being 70 years of age or younger was a protective factor against both skin cancers. Being a female and 70 years old or younger was a protective factor for basal cell carcinoma. A comparison of the frequencies of the VDR genotypes in patients older than 70 years vs. 70 years or younger also revealed age-dependent variations in patients with non-melanoma skin cancer. Our study suggests a role for VDR polymorphisms in non-melanoma skin cancer development.

Pigmentation of the aortic and pulmonary valves in C57BL/6J x Balb/cByJ hybrid mice of different coat colours.

Neural crest-derived melanocytes have been recorded in several parts of the mammalian heart but not in the pulmonary valve. We report here the presence of melanin-containing cells in the leaflets (cusps) of both the aortic and pulmonary valves. A total of 158 C57BL/6J x Balb/cByJ hybrid mice exhibiting four coat colours, namely black, white, agouti and non-agouti brown, were examined. We sought for any relationship between the presence of melanocytes in the valves and the coat colour of the animals. The pigmentation levels of the leaflets were accomplished using a scale of five pigment intensities. White mice lacked pigment in the heart. In 10.5% of the remaining animals, there were melanocytes in the pulmonary valve leaflets. Thus, this is the first study to report the presence of such cells in the pulmonary valve of mammals. Melanocytes occurred in the leaflets of the aortic valves of 87.2% of mice. The incidence of melanocytes and the pigmentation level of the leaflets did not statistically differ according to the coat colours of the animals. This disagrees with previous observations, indicating that the amount of melanocytes in the heart reflects that of the skin. The incidence and distribution of melanocytes in aortic and pulmonary valves are consistent with the notion that the formation of the arterial valves is mediated by specific subpopulations of neural crest cells. We hypothesize that melanocytes, even not producing melanin, may be more frequent in the heart than previously thought, exerting presumably an immunological function.

MAP17 (PDZK1IP1) and pH2AX are potential predictive biomarkers for rectal cancer treatment efficacy.

Rectal cancer represents approximately 10% of cancers worldwide. Preoperative chemoradiotherapy increases complete pathologic response and local control, although it offers a poor advantage in survivorship and sphincter saving compared with that of radiotherapy alone. After preoperative chemoradiotherapy, approximately 20% of patients with rectal cancer achieve a pathologic complete response to the removed surgical specimen; this response may be related to a better prognosis and an improvement in disease-free survival. However, better biomarkers to predict response and new targets are needed to stratify patients and obtain better response rates. MAP17 (PDZK1IP1) is a small, 17 kDa non-glycosylated membrane protein located in the plasma membrane and Golgi apparatus and is overexpressed in a wide variety of human carcinomas. MAP17 has been proposed as a predictive biomarker for reactive oxygen species, ROS, inducing treatments in cervical tumors or laryngeal carcinoma. Due to the increase in ROS, MAP17 is also associated with the marker of DNA damage, phosphoH2AX (pH2AX). In the present manuscript, we examined the values of MAP17 and pH2AX as surrogate biomarkers of the response in rectal tumors. MAP17 expression after preoperative chemoradiotherapy is able to predict the response to chemoradiotherapy, similar to the increase in pH2AX. Furthermore, we explored whether we can identify molecular targeted therapies that could help improve the response of these tumors to radiotherapy. In this sense, we found that the inhibition of DNA damage with olaparib increased the response to radio- and chemotherapy, specifically in tumors with high levels of pH2AX and MAP17.

La intención es lo que cuenta. Una revisión sobre la detección del engaño en intenciones / It's the intention that counts. A review on deception detection focused on intentions

Durante años la investigación sobre detección del engaño ha estado guiada por las teorías clásicas que sustentaban la idea de que el mentiroso emitía indicadores conductuales que lo delataban. Dentro de las nuevas líneas de investigación, ha surgido la detección del engaño focalizado en intenciones. Haremos un repaso de los estudios sobre la detección del engaño focalizados en intenciones futuras. Explicaremos brevemente el pensamiento episódico futuro (EFT), a continuación las primeras aproximaciones en este campo a través de la comparativa entre el engaño sobre hechos pasados vs futuros. Veremos además aquellos estudios que utilizan las preguntas inesperadas en un dominio no anticipado (fase de planificación de un viaje, calidad de esa planificación y sobre el pensamiento episódico futuro), y finalizaremos por los que manejan la evidencia de manera estratégica

For years the research on deception detection has been guided by classical theories that support the idea that the liar gives out behavioral indicators which betray him/her. Within the new lines of research, deception detection focused on intentions has emerged. In this paper we review the studies on deception detection focused on intentions. We briefly explain episodic future thought (EFT) and the first approaches in this field through the comparison of deception detection in past and future events. Additionally, we take a look at the studies that use unexpected questions in a non-anticipated domain (trip planning phase, quality of the planning, and EFT), and we finish by discussing the ones that use evidence strategically

Discovery of a Highly Selective NAMPT Inhibitor That Demonstrates Robust Efficacy and Improved Retinal Toxicity with Nicotinic Acid Coadministration.

NAMPT, an enzyme essential for NAD+ biosynthesis, has been extensively studied as an anticancer target for developing potential novel therapeutics. Several NAMPT inhibitors have been discovered, some of which have been subjected to clinical investigations. Yet, the on-target hematological and retinal toxicities have hampered their clinical development. In this study, we report the discovery of a unique NAMPT inhibitor, LSN3154567. This molecule is highly selective and has a potent and broad spectrum of anticancer activity. Its inhibitory activity can be rescued with nicotinic acid (NA) against the cell lines proficient, but not those deficient in NAPRT1, essential for converting NA to NAD+ LSN3154567 also exhibits robust efficacy in multiple tumor models deficient in NAPRT1. Importantly, this molecule when coadministered with NA does not cause observable retinal and hematological toxicities in the rodents, yet still retains robust efficacy. Thus, LSN3154567 has the potential to be further developed clinically into a novel cancer therapeutic. Mol Cancer Ther; 16(12); 2677-88. ©2017 AACR.

Cardiac, mandibular and thymic phenotypical association indicates that cranial neural crest underlies bicuspid aortic valve formation in hamsters.

Bicuspid aortic valve (BAV) is the most prevalent human congenital cardiac malformation. It may appear isolated, associated with other cardiovascular malformations, or forming part of syndromes. Cranial neural crest (NC) defects are supposed to be the cause of the spectrum of disorders associated with syndromic BAV. Experimental studies with an inbred hamster model of isolated BAV showed that alterations in the migration or differentiation of the cardiac NC cells in the embryonic cardiac outflow tract are most probably responsible for the development of this congenital valvular defect. We hypothesize that isolated BAV is not the result of local, but of early alterations in the behavior of the NC cells, thus also affecting other cranial NC-derived structures. Therefore, we tested whether morphological variation of the aortic valve is linked to phenotypic variation of the mandible and the thymus in the hamster model of isolated BAV, compared to a control strain. Our results show significant differences in the size and shape of the mandible as well as in the cellular composition of the thymus between the two strains, and in mandible shape regarding the morphology of the aortic valve. Given that both the mandible and the thymus are cranial NC derivatives, and that the cardiac NC belongs to the cephalic domain, we propose that the causal defect leading to isolated BAV during embryonic development is not restricted to local alterations of the cardiac NC cells in the cardiac outflow tract, but it is of pleiotropic or polytopic nature. Our results suggest that isolated BAV may be the forme fruste of a polytopic syndrome involving the cranial NC in the hamster model and in a proportion of affected patients.

Litiasis biliar complicada tratada satisfactoriamente mediante colangiografía percutánea y drenaje biliar en lactante de 2 meses / Complicated bile duct stones successfully treated by percutaneous cholangiography and biliary drainage catheter in a 2-month-old infant

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Characterization of the new AmpC ß-lactamase FOX-8 reveals a single mutation, Phe313Leu, located in the R2 loop that affects ceftazidime hydrolysis.

A novel class C ß-lactamase (FOX-8) was isolated from a clinical strain of Escherichia coli. The FOX-8 enzyme possessed a unique substitution (Phe313Leu) compared to FOX-3. Isogenic E. coli strains carrying FOX-8 showed an 8-fold reduction in resistance to ceftazidime relative to FOX-3. In a kinetic analysis, FOX-8 displayed a 33-fold reduction in kcat/Km for ceftazidime compared to FOX-3. In the FOX family of ß-lactamases, the Phe313 residue located in the R2 loop affects ceftazidime hydrolysis and alters the phenotype of E. coli strains carrying this variant.

Design, synthesis and structure-activity-relationship of 1,5-tetrahydronaphthyridines as CETP inhibitors.

This Letter describes the discovery and SAR optimization of 1,5-tetrahydronaphthyridines, a new class of potent CETP inhibitors. The effort led to the identification of 21b and 21d with in vitro human plasma CETP inhibitory activity in the nanomolar range (IC(50)=23 and 22nM, respectively). Both 21b and 21d exhibited robust HDL-c increase in hCETP/hApoA1 dual heterozygous mice model.

Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health.

BACKGROUND AND PURPOSE: A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. PATIENTS AND METHODS: Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. RESULTS: A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. CONCLUSIONS: The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines.

Distant and new mutations in CTX-M-1 beta-lactamase affect cefotaxime hydrolysis.

The CTX-M ß-lactamases are an increasingly prevalent group of extended-spectrum ß-lactamases (ESBL). Point mutations in CTX-M ß-lactamases are considered critical for enhanced hydrolysis of cefotaxime. In order to clarify the structural determinants of the activity against cefotaxime in CTX-M ß-lactamases, screening for random mutations was carried out to search for decreased activity against cefotaxime, with the CTX-M-1 gene as a model. Thirteen single mutants with a considerable reduction in cefotaxime MICs were selected for biochemical and stability studies. The 13 mutated genes of the CTX-M-1 ß-lactamase were expressed, and the proteins were purified for kinetic studies against cephalothin and cefotaxime (as the main antibiotics). Some of the positions, such as Val103Asp, Asn104Asp, Asn106Lys, and Pro107Ser, are located in the (103)VNYN(106) loop, which had been described as important in cefotaxime hydrolysis, although this has not been experimentally confirmed. There are four mutations located close to catalytic residues-Thr71Ile, Met135Ile, Arg164His, and Asn244Asp-that may affect the positioning of these residues. We show here that some distant mutations, such as Ala219Val, are critical for cefotaxime hydrolysis and highlight the role of this loop at the top of the active site. Other distant substitutions, such as Val80Ala, Arg191, Ala247Ser, and Val260Leu, are in hydrophobic cores and may affect the dynamics and flexibility of the enzyme. We describe here, in conclusion, new residues involved in cefotaxime hydrolysis in CTX-M ß-lactamases, five of which are in positions distant from the catalytic center.

Persistence of immunological alterations after thymectomy in Good's syndrome: a clue to its pathogenesis.

Analyzing the phenotypic characterization of the immune system cells involved in the pathogenesis of immunodeficiency with thymoma (Good's syndrome) is difficult due to the low number of studies on that subject. We describe the immunological alterations observed in a case of Good's syndrome, and we summarize the pathogenic explanations found in the literature.

Pancreatitis aguda e ictericia obstructiva secundaria a metástasis de cáncer de pulmón / Acute pancreatitis and obstructive jaundice secondary to metastases from lung cancer

El cáncer de pulmón es una de las neoplasias más frecuentes. La clínica se debe al propio tumor, a su extensión o a los síndromes paraneoplásicos asociados. A pesar de que las metástasis de localización biliopancreática son frecuentes, la afectación en esta región como inicio de una neoplasia pulmonar, tanto en la forma de pancreatitis como en la de ictericia obstructiva, es rara. Exponemos nuestra experiencia clínica mediante la presentación de 2 casos de pancreatitis aguda y uno de ictericia obstructiva como forma de inicio de una neoplasia pulmonar avanzada junto con una breve revisión bibliográfica, que confirma la ausencia de protocolos de actuación en esta situación (AU)

Lung cancer is one of the most frequent neoplasms. The symptoms are due to the cancer itself, its extension, and associated paraneoplastic syndromes. Although biliopancreatic metastases are common, biliopancreatic involvement as the initial symptom of lung cancer—whether as pancreatitis or obstructive jaundice—is rare. We describe our clinical experience, reporting two patients with acute pancreatitis and one patient with obstructive jaundice as the clinical presentation of advanced lung cancer. We also provide a brief review that highlights the absence of guidelines in this situation (AU)

[Acute pancreatitis and obstructive jaundice secondary to metastases from lung cancer]. / Pancreatitis aguda e ictericia obstructiva secundaria a metástasis de cáncer de pulmón.

Lung cancer is one of the most frequent neoplasms. The symptoms are due to the cancer itself, its extension, and associated paraneoplastic syndromes. Although biliopancreatic metastases are common, biliopancreatic involvement as the initial symptom of lung cancer--whether as pancreatitis or obstructive jaundice--is rare. We describe our clinical experience, reporting two patients with acute pancreatitis and one patient with obstructive jaundice as the clinical presentation of advanced lung cancer. We also provide a brief review that highlights the absence of guidelines in this situation.

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers.

BACKGROUND: The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE).A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups.The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. RESULTS: Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE epsilon4 allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p < 0.001 and OR = 6.71, 95%CI 3.36-13.41, p < 0.001 respectively). In AD patients this effect was greater in women.In MCI patients such as synergistic effect was only found between AG and APOE epsilon4 allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95%CI 1.69-20.42, p < 0.01). CONCLUSION: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon4 allele that proves greater in women with AD.