Asthma as an Inflammatory Reason of Tracheobronchial PSMA Uptake.

ABSTRACT: A 53-year-old man with persisting increased serum prostate-specific antigen level (9.53 ng/mL) and repeated negative prostate biopsies was referred for a PET/CT with 68 Ga-PSMA-11. The PET/CT revealed focal uptake in the prostate suggestive of localized prostate cancer. Incidentally, it also showed a diffuse uptake in the tracheobronchial tree suspicious for a benign etiology. Because of the clinical history of asthma exacerbation in the previous week, further supplementary studies were performed showing a pathological fractional exhaled nitric oxide level (92 ppb; reference values, <25 ppb) and mild airway obstruction in the spirometry. These findings confirmed asthma as an inflammatory etiology of the tracheobronchial PSMA uptake.

New records, and molecular detection of vector-borne pathogens in Felicola subrostratus from eastern Mexico.

The study of lice associated with domestic cats is a neglected area of veterinary parasitology. In particular, the presence of the cat louse Felicola subrostratus, a small Ischnoceran species found in the fur of the domestic cat, is rarely recognized. In America, this species has been reported across six countries. Although it was also recently reported in Mexico, no studies on the molecular identification of the specimens or the monitoring of potential bacterial, and protozoan pathogens have been carried out. Thus, this work aimed to collect, and identify lice associated with domestic and free ranging cats from the states of Veracruz and Tabasco, using amplification and sequencing of the mitochondrial cytochrome c oxidase subunit I (COI), and the ribosomal 18S rDNA genes, and to monitor selected vector-borne bacterial (Bartonella, Mycoplasma, and Rickettsia) and protozoan (Babesia, and Hepatozoon) agents. Only entire lice were used for molecular host and pathogen identification. Eighty-one lice, identified as F. subrostratus, were recovered from five infested cats, and 30 were selected for molecular identification and pathogen surveillance. Analysis of the COI and 18S rDNA partial sequences showed a similarity of 96.79%-100% with sequences of F. subrostratus from the US. Mycoplasma haemofelis and Hepatozoon canis DNA was detected in three and four samples, respectively. This work provides new collection locations for F. subrostratus, and the first sequences of the COI and 18S rDNA genes from Mexico. It also reports two pathogenic microorganisms found in the lice.

SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy.

The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex is one of the most remarkably altered epigenetic regulators in cancer. Pathogenic mutations in genes encoding SWI/SNF-related proteins have been recently described in many solid tumors, including rare and aggressive malignancies with rhabdoid features with no standard therapies in advanced or metastatic settings. In recent years, clinical trials with targeted drugs aimed at restoring its function have shown discouraging results. However, preclinical data have found an association between these epigenetic alterations and response to immune therapy. Thus, the rationale for immunotherapy strategies in SWI/SNF complex alteration-related tumors is strong. Here, we review the SWI/SNF complex and how its dysfunction drives the oncogenesis of rhabdoid tumors and the proposed strategies to revert this alteration and promising novel therapeutic approaches, including immune checkpoint inhibition and adoptive cell therapy.

When Less May Be Enough: Dose Selection Strategies for Immune Checkpoint Inhibitors Focusing on AntiPD-(L)1 Agents.

Early clinical trials investigating antiPD(L)-1 agents rarely reached a maximum tolerated dose (MTD), and efficacy signals were observed even at the lowest dose levels. Most extended treatment intervals investigated indicated that these drugs do not follow a direct dose-toxicity or dose-efficacy relationship. Within this context and considering the high cost of antiPD(L)-1 agents, there is a significant debate on whether lower doses or the administration of such agents at an extended interval should be prospectively evaluated in already-approved agents, or at least be considered in novel combination trials involving antiPD(L)-1 drugs. Herein, we review the dosing, overall response rates, and incidence of treatment-related adverse events of antiPD(L)-1 agents in early dose-escalation trials and discuss the appropriateness of recommended Phase 2 dose selection as well as the final regulatory approved doses of such agents. Efficacy and safety data from randomized dose-range Phase 2 trials and real-world data (RWD) on the usage of lower doses and/or non-standard extended treatment intervals are also examined. As the accumulating evidence suggests lower doses or extended dosing intervals of antiPD(L)-1 may achieve a similar clinical benefit in comparison to the currently approved doses, we address the clinical and financial toxicity implications of using potentially higher doses than necessary. Last, we discuss ways to resolve the current dosing conundrum of antiPD-(L)1 agents such as performing near-equivalence studies and propose a framework for future development of immunotherapeutics to find the lowest efficacious dose instead of MTD.

Toward a machine learning model for a primary diagnosis of Guillain-Barré syndrome subtypes.

Guillain-Barré Syndrome (GBS) is a neurological disorder affecting people of any age and sex, mainly damaging the peripheral nervous system. GBS is divided into several subtypes, in which only four are the most common, demanding different treatments. Identifying the subtype is an expensive and time-consuming task. Early GBS detection is crucial to save the patient's life and not aggravate the disease. This work aims to provide a primary screening tool for GBS subtypes fast and efficiently without complementary invasive methods, based only on clinical variables prospected in consultation, taken from clinical history, and based on risk factors. We conducted experiments with four classifiers with different approaches, five different filters for feature selection, six wrappers, and One versus All (OvA) classification. For the experiments, we used a data set that includes 129 records of Mexican patients and 26 clinical representative variables. Random Forest filter obtained the best results in each classifier for the diagnosis of the four subtypes, in the same way, this filter with the SVM classifier achieved the best result (0.6840). OvA with SVM classifier reached a balanced accuracy of 0.8884 for the Miller-Fisher (MF) subtype.

A Multidimensional Mass Spectrometry-Based Workflow for De Novo Structural Elucidation of Oligosaccharides from Polysaccharides.

Carbohydrates play essential roles in a variety of biological processes that are dictated by their structures. However, characterization of carbohydrate structures remains extremely difficult and generally unsolved. In this work, a de novo mass spectrometry-based workflow was developed to isolate and structurally elucidate oligosaccharides to provide sequence, monosaccharide compositions, and glycosidic linkage positions. The approach employs liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based methods in a 3-dimensional concept: one high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS) analysis for oligosaccharide sequencing and two ultra high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ MS) analyses on fractionated oligosaccharides to determine their monosaccharides and linkages compositions. The workflow was validated by applying the procedure to maltooligosaccharide standards. The approach was then used to determine the structures of oligosaccharides derived from polysaccharide standards and whole food products. The integrated LC-MS workflow will reveal the in-depth structures of oligosaccharides.

Pulmonary Artery Sarcoma With Low 18F-FDG Uptake.

ABSTRACT: A 75-year-old man presented with dyspnea for more than 2 months, with blood test showing low platelet count and cardiac ultrasound showing severe pulmonary hypertension (>54 mm Hg). A CT pulmonary angiogram showed a filling defect in the pulmonary trunk, right and left pulmonary arteries, raising the possibilities of pulmonary embolism or artery sarcoma. FDG PET/CT was performed for further evaluation and showed low uptake in the pulmonary wall, which supported the diagnosis of pulmonary embolism. Patient was treated with anticoagulants with no changes on repeated CT pulmonary angiogram. Patient underwent surgery, and histopatological examination revealed a pulmonary artery sarcoma.

Tyrosine Kinase Receptors in Oncology.

Tyrosine kinase receptors (TKR) comprise more than 60 molecules that play an essential role in the molecular pathways, leading to cell survival and differentiation. Consequently, genetic alterations of TKRs may lead to tumorigenesis and, therefore, cancer development. The discovery and improvement of tyrosine kinase inhibitors (TKI) against TKRs have entailed an important step in the knowledge-expansion of tumor physiopathology as well as an improvement in the cancer treatment based on molecular alterations over many tumor types. The purpose of this review is to provide a comprehensive review of the different families of TKRs and their role in the expansion of tumor cells and how TKIs can stop these pathways to tumorigenesis, in combination or not with other therapies. The increasing growth of this landscape is driving us to strengthen the development of precision oncology with clinical trials based on molecular-based therapy over a histology-based one, with promising preliminary results.

A nonenzymatic method for cleaving polysaccharides to yield oligosaccharides for structural analysis.

Polysaccharides are the most abundant biomolecules in nature, but are the least understood in terms of their chemical structures and biological functions. Polysaccharides cannot be simply sequenced because they are often highly branched and lack a uniform structure. Furthermore, large polymeric structures cannot be directly analyzed by mass spectrometry techniques, a problem that has been solved for polynucleotides and proteins. While restriction enzymes have advanced genomic analysis, and trypsin has advanced proteomic analysis, there has been no equivalent enzyme for universal polysaccharide digestion. We describe the development and application of a chemical method for producing oligosaccharides from polysaccharides. The released oligosaccharides are characterized by advanced liquid chromatography-mass spectrometry (LC-MS) methods with high sensitivity, accuracy and throughput. The technique is first used to identify polysaccharides by oligosaccharide fingerprinting. Next, the polysaccharide compositions of food and feces are determined, further illustrating the utility of technique in food and clinical studies.

Large vessel vasculitis secondary to granulocyte-colony stimulating factor.

Aortitis is a rare entity that may cause fever of unknown origin. This entity has a wide various etiologies, which main cause is rheumatologic, but not only. Iatrogenia has also been described, including chemotherapy and supporting treatment (like granulocyte-colony stimulating factor in oncological patients. The evidence in favour of this pharmacological link is growing. The differential diagnosis of fever, in febrile neutropenia setting, can be difficult to itemize.

Science production of pesticide residues in honey research: A descriptive bibliometric study.

This work aims to provide a comprehensive study of the available research information on pesticide residues in honey through literature analysis. The research advancements within this research field from 1948 to 2019 are addressed using the Web of Science database. The results from the 685 articles analyzed indicate that this research field is in the focus of interest nowadays (Price index: 47.5%). The yearly production increased steadily from 2001 on, and authors, journals, and institutions followed Lotka's law. On the other hand, Pico, Y (Spain) (2.5%), Journal of Chromatography A (5.8%), the USA (15.0%) and Agricultural Research Service (USA) (4.0%) were the most productive author, journal, country and institution, respectively. The research hotspots of this field, according to keyword analysis, are related to the chromatographic techniques for the determination of pesticides such as imidacloprid, neonicotinoids, or coumaphos in honey and derivate products such as propolis and wax.

Úlcera negra en pierna / Black ulcer in leg

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Author Correction: Sporadic nesting reveals long distance colonisation in the philopatric loggerhead sea turtle (Caretta caretta).

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Sporadic nesting reveals long distance colonisation in the philopatric loggerhead sea turtle (Caretta caretta).

The colonisation of new suitable habitats is crucial for species survival at evolutionary scale under changing environmental conditions. However, colonisation potential may be limited by philopatry that facilitates exploiting successful habitats across generations. We examine the mechanisms of long distance dispersal of the philopatric loggerhead sea turtle (Caretta caretta) by analysing 40 sporadic nesting events in the western Mediterranean. The analysis of a fragment of the mitochondrial DNA and 7 microsatellites of 121 samples from 18 of these nesting events revealed that these nests were colonising events associated with juveniles from distant populations feeding in nearby foraging grounds. Considering the temperature-dependent sex determination of the species, we simulated the effect of the incubation temperature and propagule pressure on a potential colonisation scenario. Our results indicated that colonisation will succeed if warm temperature conditions, already existing in some of the beaches in the area, extend to the whole western Mediterranean. We hypothesize that the sporadic nesting events in developmental foraging grounds may be a mechanism to overcome philopatry limitations thus increasing the dispersal capabilities of the species and the adaptability to changing environments. Sporadic nesting in the western Mediterranean can be viewed as potential new populations in a scenario of rising temperatures.

Síndrome neuroléptico maligno: dificultades en el diagnóstico diferencial / Neuroleptic malignant syndrome: difficulties in the differential diagnosis

El síndrome neuroléptico maligno es una patología poco frecuente y, en ocasiones, difícil de diagnosticar debido a la variabilidad en cuanto a la forma de presentación y evolución. La importancia de su detección precoz está en la instauración de un tratamiento adecuado lo antes posible, ya que sus complicaciones son potencialmente letales en caso de no realizarse a tiempo. El caso clínico que presentamos sirve como ejemplo representativo de la heterogeneidad clínica de dicha entidad, ya que la sintomatología larvada del paciente, su forma de presentación oscilante unido a la lenta evolución del mismo plantearon dudas en cuanto al diagnóstico, lo que hizo necesario el estudio diferencial con diferentes patologías. Por otra parte, y aunque hay distintas medicaciones que pueden provocarlo, son los neurolépticos los principales en poder desencadenarlo. La combinación de estos y las fórmulas de liberación retardada favorecen la lentitud en la resolución del cuadro clínico (AU)

Neuroleptic malignant syndrome is a rare disease. It is sometimes difficult to diagnose because of its variability in presentation and evolution. The importance of early detection is the establishment of an appropriate treatment as soon as possible, as its complications are potentially lethal if not treated on time. The clinical case presented serves as a representative example of the clinical heterogeneity of the entity, as the overt symptoms of the patient, its form of oscillating presentation coupled with its slow evolution, raised doubts about the diagnosis. This required a differential study with different pathologies. On the other hand, and although there are various medications that can cause it, neuroleptics are the leading ones that can trigger it. The combination of these and time-release formulas favour the slow resolution of the clinical picture (AU)

Gestión en Consulta de Enfermería, en Atención Primaria, del paciente hipertenso y en riesgo cardiovascular. Propuesta de manejo de la MAPA y AMPA / Management in the nursing surgery of primary care for patients with high blood pressure or with a cardiovascular risk. Suggestion for the use the APM and SMAP

Objetivo principal. Analizar la necesidad de crear y gestionar una consulta enfermera en Atención Primaria dirigida exclusivamente a la detección, seguimiento y derivación del paciente en riesgo cardiovascular e hipertenso. Metodología. Haciendo uso de la evidencia científica disponible, considerar las ventajas de la puesta en práctica de un sistema de atención enfermera al paciente en riesgo cardiovascular que contenga los siguientes puntos principales: 1) Valoración del riesgo; 2) Estrategias de intervenciones enfermeras y actividades; 3) Registro correcto en la historia única de salud del usuario; 4) Seguimiento. Resultados principales. Homogeneizar las actividades enfermeras dentro de la práctica clínica del paciente con riesgo cardiovascular en Atención Primaria, evitar la inercia clínica y conseguir un buen seguimiento del paciente con hipertensión arterial. Conclusión principal. La puesta en práctica de un sistema protocolizado y estandarizado enfermero mejora el control y la adherencia al tratamiento del paciente en riesgo cardiovascular e hipertenso (AU)

Objective. Analyze the necessity of creating and managing a nursing surgery in Primary Care focused exclusively on the discovery, following up and derivation in the cardiovascular risk patient. Methods. Making use of the available Scientific evidence, consider the advantages of putting into practice a system for a nurse to attend the necessities of a patient with a cardiovascular risk taking into consideration the following: 1) Estimating the risk; 2) Stratagies for nursing supervision and activities; 3) The correct registration of medical diagnosis of the patient; 4) Monitoring. Results. To enable nurses to treat cardiovascular patients in Primary Care, to reduce the time the patient would have to wait to be attended and to supervise the patient’s progress. Conclusions. Making it possible for nurses to use the same registered standard system for controlling the treatment of cardiovascular patients (AU)

Towards a predictive model for Guillain-Barré syndrome.

The severity of Guillain-Barré Syndrome (GBS) varies among subtypes, which can be mainly Acute Inflammatory Demyelinating Polyneuropathy (AIDP), Acute Motor Axonal Neuropathy (AMAN), Acute Motor Sensory Axonal Neuropathy (AMSAN) and Miller-Fisher Syndrome (MF). In this study, we use a real dataset that contains clinical, serological, and nerve conduction tests data obtained from 129 GBS patients. We apply C4.5 decision tree, SVM (Support Vector Machines) using a Gaussian kernel, and kNN (k Nearest Neighbour) to predict four GBS subtypes. Accuracies were calculated and averaged across 30 10-fold cross-validation (10-FCV) runs. C4.5 obtained 0.9211 (±0.0109), kNN 0.9179 (±0.0041), and SVM 0.9154 (±0.0069). This is an ongoing research project and further experiments are being conducted.

[MANAGEMENT IN THE NURSING SURGERY OF PRIMARY CARE FOR PATIENTS WITH HIGH BLOOD PRESSURE OR WITH A CARDIOVASCULAR RISK. SUGGESTION FOR THE USE OF THE APM AND SMAP]. / Gestión en Consulta de Enfermería, en Atención Primaria, del paciente hipertenso y en riesgo cardiovascular. PROPUESTA DE MANEJO DE LA MAPA Y AMPA.

OBJECTIVE: Analyze the necessity of creating and managing a nursing surgery in Primary Care focused exclusively on the discovery, following up and derivation in the cardiovascular risk patient. METHODS: Making use of the available Scientific evidence, consider the advantages of putting into practice a system for a nurse to attend the necessities of a patient with a cardiovascular risk taking into consideration the following: 1) Estimating the risk; 2) Stratagies for nursing supervision and activities; 3) The correct registration of medical diagnosis of the patient; 4) Monitoring. RESULTS: To enable nurses to treat cardiovascular patients in Primary Care, to reduce the time the patient would have to wait to be attended and to supervise the patient's progress. CONCLUSIONS: Making it possible for nurses to use the same registered standard system for controlling the treatment of cardiovascular patients.