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The study of the interaction of synthetic protoporphyrin IX (PpIXs) and protoporphyrin IX extracted from Harderian glands of ssp Rattus novergicus albinus rats (PpIXe) with bovine serum albumin (BSA) was conducted in water at pH 7.3 and pH 4.5 by optical absorption and fluorescence spectroscopies. PpIXs is present as H- and J-aggregates in equilibrium with themselves and with monomers. The PpIXs charge is 2- at pH 7.3 and 1- at pH 4.5. This increases its aggregation at pH 4.5 and shifts the equilibrium in favor of J-aggregates. In spite of electrostatic attraction at pH 4.5, where BSA is positive, the binding constant (Kb) of PpIXs to BSA is 20% less than that at pH 7.3, where BSA is negative. This occurs because higher aggregation of PpIXs at pH 4.5 reduces the observed Kb value. At both pHs, water-soluble PpIXe exists in the monomeric form with the charge of 1- and its Kb exceeds that of PpIXs. At pH 4.5, its Kb is 12 times higher than that at pH 7.3 due to electrostatic attraction between the positively charged BSA and the negatively charged PpIXe. The higher probability of PpIXe binding to BSA makes PpIXe more promising as a fluorescence probe for fluorescence diagnostics and as a photosensitizer for photodynamic therapy. The existence of PpIXe in the monomeric form can explain its faster cell internalization. Aggregation reduces quantum yields and lifetimes of the PpIXs excited states, which explains higher phototoxicity of PpIXe toward malignant cells compared with PpIXs.

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BACKGROUND: Hyperprolactinaemia (HyperPRL) induced by psychotropic drugs is a high-prevalence consequence which has repercussions in psychical and mental health in the psychiatric population, so this research had the objective to expand which sociodemographic and clinical features are associated with prolactin (PRL) elevation in patients treated with antidepressant and/or antipsychotic drugs. METHODS: An observational, cross-sectional, comparative and retrolective study was conducted on 300 patients who received clinical attention in a third level of psychiatric care unit in Mexico during 2017. These patients have been reported to show PRL levels greater than 25 ng/mL among women and greater than 20 ng/mL among men. In the same way, sociodemographic and clinical variables were collected, as well as psychiatric diagnosis and type of psychopharmacological treatment used by the patients. RESULTS: HyperPRL was more frequent in women (80.7%) than men (19.3%). The mean levels of PRL were 68.94 ± 62.28 ng/mL with higher levels in women (71.9 ± 67.3, p=.02). Regarding the treatment, 78.3%, 71.3% and 49.7% consumed antipsychotics, antidepressants, and both drugs, respectively. The relationship between hyperPRL (>100 n/mL) and typical antipsychotics was dose-dependent (33.23 ± 13.24 mg, p=.01). In the multivariate regression models according to the type of treatment, as well as the demographic and clinical features, hyperPRL was associated independently with the use of antipsychotic treatment, pituitary adenoma and hypertension (R2=0.05). CONCLUSIONS: HyperPRL is a complex clinical syndrome frequent in the psychiatric population with detrimental long-term consequences, as well as its relationship with the use of psychotropic drugs as in the case of antipsychotics. Effective actions should be implemented in the prevention, approach and treatment of this condition paying special attention to the accompanying medical comorbidities.

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The study of the interaction of synthetic protoporphyrin IX (PpIXs) and protoporphyrin IX extracted from Harderian glands of ssp Rattus novergicus albinus rats (PpIXe) with bovine serum albumin (BSA) was conducted in water at pH 7.3 and pH 4.5 by optical absorption and fluorescence spectroscopies. PpIXs is present as H- and J-aggregates in equilibrium with themselves and with monomers. The PpIXs charge is 2− at pH 7.3 and 1− at pH 4.5. This increases its aggregation at pH 4.5 and shifts the equilibrium in favor of J-aggregates. In spite of electrostatic attraction at pH 4.5, where BSA is positive, the binding constant (Kb) of PpIXs to BSA is 20% less than that at pH 7.3, where BSA is negative. This occurs because higher aggregation of PpIXs at pH 4.5 reduces the observed Kb value. At both pHs, water-soluble PpIXe exists in the monomeric form with the charge of 1− and its Kb exceeds that of PpIXs. At pH 4.5, its Kb is 12 times higher than that at pH 7.3 due to electrostatic attraction between the positively charged BSA and the negatively charged PpIXe. The higher probability of PpIXe binding to BSA makes PpIXe more promising as a fluorescence probe for fluorescence diagnostics and as a photosensitizer for photodynamic therapy. The existence of PpIXe in the monomeric form can explain its faster cell internalization. Aggregation reduces quantum yields and lifetimes of the PpIXs excited states, which explains higher phototoxicity of PpIXe toward malignant cells compared with PpIXs.

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The measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQCML) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs.

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RESUMEN Objetivo. Identificar nematodos de la familia Anisakidae en el pez de consumo Mugil curema. Materiales y métodos. Para este estudio, se recolectaron 16 peces Lisa (M. curema) del puerto de Tumaco, una ciudad en la costa colombiana del Pacífico. La identificación morfológica de las larvas se realizó mediante taxonomía clásica y se calculó el porcentaje de infestación de larvas. Para la identificación molecular, se realizó una PCR múltiple con cebadores para las especies Anisakis physeteris, Pseudoterranova decipiens, Anisakis simplex sensu stricto, Contracaecum osculatum, Hysterothylacium aduncum y Anisakis pegreffii. Resultados. La revisión taxonómica permitió la identificación de larvas de tipo II del género Anisakis y larvas del género Pseudoterranova. Las larvas se aislaron principalmente del intestino, donde se encontró que el 94% de los peces estaban parasitados por nematodos anisakidos. La PCR multiplex permitió la identificación de la especie A. physeteris (Larva tipo II) y P. decipiens. Conclusiones. Este estudio es el primer reporte de nematodo Anisakidae en Tumaco, Colombia. Estos resultados proporcionan una justificación convincente para un estudio adicional sobre la familia Anisakidae en Colombia, como un problema de salud pública.

ABSTRACT Objective: Identification nematodes Anisakidae family in Mugil curema fish. Materials and methods: For this study, 16 Lisa fish (Mugil curema) were obtained from the port of Tumaco, a city on the Colombian Pacific coast. Morphological identification of larvae was made by classical taxonomy and the percentage of larval infestation was calculated. For molecular identification, a multiplex PCR was carried out with primers for six species, Anisakis physeteris, Pseudoterranova decipiens, Anisakis simplex sensu stricto, Contracaecum osculatum, Hysterothylacium aduncum and Anisakis pegreffii. Results: The taxonomic revision enabled the identification of type II larvae of the genus Anisakis and larvae of the genus Pseudoterranova. The larvae were isolated mainly from the intestine, where it was found that 94% of the fish were parasitized by anisakid nematodes. The multiplex PCR enabled the identification of the species A. physeteris (Larva type II), and P. decipiens. Conclusions: This study is the first report of nematode Anisakidae on Tumaco, Colombia. These results provide a compelling justification for further study into the Anisakidae family in Colombia, as a public health problem.

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PURPOSE: The Spanish Society of Medical Oncology (SEOM) has carried out a study to analyse the conditions of access to oncology drugs in clinical practice in Spain. For the first time, the access of predictive biomarkers has also been analyzed. METHODS: A questionnaire was sent to 146 hospitals in Spain to collect information on the process of approval of 11 oncology drugs of an unquestionable clinical benefit and five predictive biomarkers of mandatory determination for specific treatments. RESULTS: Results highlight the still existing differences in the access of oncology drugs, as well as the newly identified differences in the access to predictive biomarkers between Autonomous Communities (AACC) in Spain, as well as between different hospitals within the same Autonomous Community. Conclusions The SEOM considers it necessary to reduce the differences identified, increase homogeneity, and improve conditions of access to oncology drugs and biomarkers, and makes proposals to address these issues.

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Cervical cancer is associated with the human papilloma virus (HPV) and nowadays is the fourth most frequent cancer among women. One of the treatments for this disease is based on the application of imiquimod. In this study, we postulated that the use of imiquimod in nanoemulsion results in a better antitumoral effect than the drug administered in its nonencapsulated form for the treatment of cervical cancer. Permeability studies using vaginal mucosa, as membrane, and in vitro studies involving cervical cancer cells (viability, clonogenic assay, and cell death analysis) were performed. We showed that low amount of encapsulated imiquimod permeated the vaginal mucosa. However, a higher percentage of cells died after the treatment with low amount (3.0 µmol L-1) of the formulation compared to the free drug. In addition, the innovative formulation presented a combinatory mechanism of cell death involving autophagy and apoptosis. Our results demonstrate that the imiquimod-loaded nanoemulsioncan be an alternative product for the treatment of cervical cancer validating the hypothesis.

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Calodium hepaticum (Trichinellida: Capillaridae) is a parasitic nematode of mammals distributed worldwide. Although this parasite can infect the liver of a wide diversity of mammals (including humans), it is mostly associated with Muroidea hosts. Sigmodontinae rodents were recently recognized as important hosts of this parasite in Argentina, but the impact of this parasitism on these hosts has not been established. Here we report results of histopathological analyses of 40 livers of Akodon azarae infected with C. hepaticum. Lesions were classified into 4 categories: level 0, absence of lesions; level 1, with focal granulomatous hepatitis; level 2, presence of multifocal granulomatous hepatitis, fibrosis and focal necrosis with neutrophils, and level 3, absence of intact adult parasites, diffuse distribution, necrosis, and fibrosis. Most samples presented lesions of level 2 (55%), but all categories of lesions were found. This is the first study to describe the lesions caused by C. hepaticum in the liver of Sigmodontinae rodents, and the results suggest that infection by this parasite is costly to A. azarae populations.

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AIM: To define recommendations that permit safe management of antineoplastic medication, minimise medication errors and improve the safety of cancer patients undergoing treatment. METHODS: By reviewing the literature and consulting the websites of various health organisations and agencies, an expert committee from the Spanish Society of Hospital Pharmacy and the Spanish Society of Medical Oncology defined a set of safe practices covering all stages of providing cancer therapy to patients. The Spanish Society of Oncology Nursing revised and endorsed the final list. RESULTS: In total, 68 recommendations arranged in five sections were defined. They include issues concerning the training of health professionals, the technological resources needed, treatment planning, informing the patient and his/her family, the processes of prescribing, preparing, dispensing and administering cancer therapy (orally, parenterally or intrathecally), assessing patient adherence and treatment toxicity. CONCLUSIONS: It is essential for healthcare establishments to implement specific measures designed to prevent medication errors, in order to ensure the safety of cancer patients treated with antineoplastic medication.

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Breast cancer is the most common cancer in women in our country and it is usually diagnosed in the early and potentially curable stages. Nevertheless, around 20-30% of patients will relapse despite appropriate locoregional and systemic therapies. A better knowledge of this disease is improving our ability to select the most appropriate therapy for each patient with a recent diagnosis of an early stage breast cancer, minimizing unnecessary toxicities and improving long-term efficacy.

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Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided.

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Intestinal parasitic infections cause a not insignificant number of chronic diarrhea in children, however, with the sociodemographic change that our country has experienced, the number of cases and new parasites (immigration from tropical endemic areas) could increase. We report the case of an immunocompetent patient who presents with chronic diarrhea associated with Strongyloides stercoralis infection. The patient migrated two years ago from an endemic area for this helminth. The diagnosis is challenging, and the chances of a successful outcome depend on the administration of the antiparasitic.

Las infecciones parasitarias intestinales provocan un número no despreciable de causas de diarrea crónica en niños, sin embargo, con el cambio sociodemográfico que ha vivido nuestro país se podría incrementar el número de casos y de nuevos parásitos (inmigración de áreas endémicas tropicales). Reportamos el caso de un paciente inmunocompetente, que presenta cuadro de diarrea crónica asociada a infección por Strongyloides stercoralis. El paciente habría migrado hace dos años desde zona endémica para este helminto. El diagnóstico es desafiante y las posibilidades de un resultado exitoso dependen de la administración del antiparasitario.

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Abstract Introduction Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting approximately 5% of the world population, with symptoms that may persist into adulthood. Despite the findings on the clinical course of this disorder, information regarding comorbidity patterns, psychosocial and executive functioning in adult life in those with and without ADHD in Latin American samples is scarce. Objective The aim of this study is to compare the comorbidity pattern, psychosocial, and executive functioning of adults with and without ADHD from a clinical sample. Method One hundred and fifty-one patients between 20 and 45 years, with screened positively on ASRS-V1.1, were invited to continue an evaluation process as part of clinical research program (PROMETEO): 1) K-SADS-PL Mx interview, 2) MINI-Plus interview, ASRS-V1-1 18 item version, BRIEF self-reported questionnaire, SCQA-ADHD, and 3) Individual case review by clinical expert in ADHD. Results Individuals in the ADHD group had a higher average of comorbid disorders (2.5 SD 1.1 vs. 1.3 SD 1.0 respectively, F = .439; t = -6.621; df = 149; p < .001), more likelihood of procrastinating (OR = 6.5; 95% CI[2.6, 16.2]; z = 4.0) and were more likely to present difficulties in both the behavior regulation index (OR = 104.9; 95% CI[31.8, 345.7]; z = 7.65) and the metacognitive index (OR = 94.79; 95% CI[29.10, 308.76]; z = 7.56) compared to the non-ADHD group, regardless of gender. Discussion and conclusions Our results indicate that the ADHD adult group presented with more comorbidity, and worse psychosocial and executive functioning than non-ADHD adults.

Resumen Introducción El trastorno por déficit de atención con hiperactividad (TDAH) es un trastorno del neurodesarrollo que afecta aproximadamente al 5% de la población mundial, persistiendo hasta la adultez. A pesar de los hallazgos acerca del curso clínico de este trastorno, la información es escasa con respecto a los patrones de comorbilidad, funcionamiento psicosocial y ejecutivo en la vida adulta entre aquellos con y sin TDAH en muestras latinoamericanas. Objetivo Comparar el patrón de comorbilidad, el funcionamiento psicosocial y ejecutivo de adultos con y sin TDAH de una muestra clínica. Método Ciento cincuenta y un pacientes entre 20 y 45 años, quienes inicialmente presentaron un tamizaje positivo del ASRS-V1.1, fueron evaluados dentro de un programa de investigación clínica (PROMETEO) con los siguientes instrumentos: 1) la entrevista K-SADS-PL-Mx, 2) la entrevista MINI-Plus, la version de 18 items del ASRS-V1-1, y los cuestionarios autoaplicados BRIEF y SCQA-ADHD y 3) Revisión de cada caso por un clínico experto en el diagnóstico de TDAH. Resultados El grupo de TDAH comparado con aquel sin TDAH presentó un mayor promedio de trastornos comórbidos (2.5 DE 1.1 vs 1.3 DE 1.0 respectivamente, F = .439; t = -6.621; gl = 149; p < .001), mayor probabilidad de procrastinar (OR = 6.5; 95% IC[2.6, 16.2]; z = 4.0), y mayor probabilidad de presentar dificultades tanto en el índice de regulación de la conducta (OR = 104.9; 95% IC[31.8, 345.7]; z = 7.65) como en el índice metacognitivo (OR = 94.79; 95% IC[29.10, 308.76]; z = 7.56) independientemente del sexo. Discusión y conclusión Nuestros resultados señalan que los adultos con TDAH presentan mayor comorbilidad y peor funcionamiento psicosocial y ejecutivo que los adultos sin TDAH.

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AIM: To assess the prevalence and prognostic significance of additional intrathoracic findings (AIFs) in patients with cancer and pulmonary embolism (PE). AIFs were considered alterations other than the characteristic ones intrinsic to PE or changes in cardiovascular morphology. METHODS: Subjects have been taken from a Spanish national multidisciplinary and multicenter study of PE and cancer who were treated between 2004 and 2015. The endpoint was the appearance of serious complications or death within 15 days. RESULTS: The registry contains 1024 eligible patients; 41% diagnosed by computed tomography pulmonary angiography versus 59% by non-angiographic CT. Serious complications occurred within 15 days in 18.9%, [95% confidence interval (CI), 16.6-21.4%] and 9.5% (95% CI 7.9-11.5%) died. At least one AIF was seen in 72.6%. The most common AIFs were as follows: pulmonary nodules (30.9%), pleural effusion (30.2%), tumor progression (28.3%), atelectasis (19.0%), pulmonary infarct (15.2%), emphysema (13.4%), pulmonary lymphangitic carcinomatosis (4.5%), and pneumonia (6.1%). Patients with AIF exhibited a higher complication rate at 15 days: 21.9% versus 13.0%, odds ratio (OR) 1.8 (95% CI 1.2-2.8), P = 0.03, and 15-day mortality: 15.0% versus 7.3%, OR 1.9 (95% CI 1.1-3.2), P = 0.020. Patients with pneumonia, pneumothorax, pulmonary edema, pulmonary nodules, tumor progression, pulmonary fibrosis, and pleural effusion showed an excess of adverse events. CONCLUSIONS: Additional intrathoracic findings are highly prevalent and significantly impact prognosis in patients with PE and cancer, making them germane to the classification of this population.

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Despite the fact that thromboembolism is relatively common in oncology patients and that the interrelationship between thrombotic risk and specific mechanisms of tumorigenesis has long been known, many cardinal elements of prevention and treatment remain unresolved. Among the existing knowledge gaps, the need to validate the Ay scale and compare it to the Khorana index, develop, and standardize the use of predictive biomarkers for thrombotic risk, conduct clinical trials in thromboprophylaxis adapted to thrombotic risk, evaluate the efficacy and safety of direct anticoagulants, select patients who can benefit from anticoagulants for antitumor treatment, validate the EPIPHANY study decision tree to choose patients with low-risk pulmonary embolism, and accumulate more practical experience in special situations (rethrombosis, prolonged therapy beyond 6 months, etc.) are especially remarkable. These gray areas surrounding cancer-related thromboembolism explain why it continues to be a relatively common cause of serious events, at times interfering significantly with the development of new tumor-fighting strategies.

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Observational studies using registry data make it possible to compile quality information and can surpass clinical trials in some contexts. However, data heterogeneity, analytical complexity, and the diversity of aspects to be taken into account when interpreting results makes it easy for mistakes to be made and calls for mastery of statistical methodology. Some questionable research practices that include poor analytical data management are responsible for the low reproducibility of some results; yet, there is a paucity of information in the literature regarding specific statistical pitfalls of cancer studies. In addition to proposing how to avoid or solve them, this article seeks to expose ten common problematic situations in the analysis of cancer registries: convenience, dichotomization, stratification, regression to the mean, impact of sample size, competing risks, immortal time and survivor bias, management of missing values, and data dredging.

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Since its publication more than 15 years ago, the MASCC score has been internationally validated any number of times and recommended by most clinical practice guidelines for the management of febrile neutropenia (FN) around the world. We have used an empirical data-supported simulated scenario to demonstrate that, despite everything, the MASCC score is impractical as a basis for decision-making. A detailed analysis of reasons supporting the clinical irrelevance of this model is performed. First, seven of its eight variables are "innocent bystanders" that contribute little to selecting low-risk candidates for ambulatory management. Secondly, the training series was hardly representative of outpatients with solid tumors and low-risk FN. Finally, the simultaneous inclusion of key variables both in the model and in the outcome explains its successful validation in various series of patients. Alternative methods of prognostic classification, such as the Clinical Index of Stable Febrile Neutropenia, have been specifically validated for patients with solid tumors and should replace the MASCC model in situations of clinical uncertainty.

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Nowadays in human and animal andrology flow cytometry is recognized as a robust tool for the evaluation of sperm quality and function. However, in this particular field, this technique has not reached the sophistication of other areas of biology and medicine. In recent years more sophisticated flow cytometers are being introduced in andrology laboratories, and the number of tests that can be potentially used in the evaluation of the sperm physiology has increased accordingly. In this review recent advances in the evaluation of sperm will be discussed; representing new techniques in flow cytometry, many of them able to measure simultaneously, in a single test, different degrees of damage in different sperm regions and/or changes in functionality.

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Recent aspects of sperm biology that readily impact on reproductive medicine and biotechnology are briefly overviewed in this paper. The new concept of reactive oxygen species (ROS) homeostasis, and its implications on sperm functions, the heterogeneous nature of the ejaculate and the epigenetic information contained will be overviewed. Additionally, the concept of sperm senescence will be discussed as some aspects of sperm oocyte interaction.

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Recent aspects of sperm biology that readily impact on reproductive medicine and biotechnology are briefly overviewed in this paper. The new concept of reactive oxygen species (ROS) homeostasis, and its implications on sperm functions, the heterogeneous nature of the ejaculate and the epigenetic information contained will be overviewed. Additionally, the concept of sperm senescence will be discussed as some aspects of sperm oocyte interaction.(AU)

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