Coprophagia in a patient with borderline personality disorder

Background and Objectives: Human coprophagia is a rare phenomenon with severe medical and social consequences. So far, coprophagia has mainly been associated with severe mental retardation, schizophrenia, dementia, and depression. We report a case of coprophagia in a 30-year-old woman with Borderline Personality Disorder (DSM-IV). This case report illustrates the severity of symptoms and maladaptive social consequences of severe personality disorders, comparable to those of patients with schizophrenia. Pharmacological interventions and, particularly intensive psychotherapy might be effective for patients diagnosed with borderline personality disorder displaying severe behavior disorders. The treatment of choice for coprophagia is aversive behavioral interventionThis study was funded in part by the National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD), Fondo de Investigación Sanitaria (FIS) [grant number PI060092]; Fondo de Investigación Sanitaria FIS [grant number RD06/0011/0016]; ETES [grant number PI07/90207]; the Conchita Rabago Foundation, the Harriet and Esteban Vicente Foundation, the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBERSAM (Intramural Project, P91B; Rio Hortega CM08/00170 –Dr. Hilario Blasco-Fontecilla), the Alicia Koplowitz foundation, and the National Institutes of Health, USA [grant number K24MH072712

CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure

Immunotherapy with T cells genetically modified with chimeric antigen receptors (CARs) has shown significant clinical efficacy in patients with relapsed/refractory B-cell lymphoma. Nevertheless, more than 50% of treated patients do not benefit from such therapy due to either absence of response or further relapse. Elucidation of clinical and biological features that would predict clinical response to CART19 therapy is of paramount importance and eventually may allow for selection of those patients with greater chances of response. In the last 5 years, significant clinical experience has been obtained in the treatment of diffuse large B-cell lymphoma (DLBCL) patients with CAR19 T cells, and major advances have been made on the understanding of CART19 efficacy mechanisms. In this review, we discuss clinical and tumor features associated with response to CART19 in DLBCL patients as well as the impact of biological features of the infusion CART19 product on the clinical response. Prognosis of DLBCL patients that fail CART19 is poor and therapeutic approaches with new drugs are also discussed

Autophagy-Mediated Exosomes as Immunomodulators of Natural Killer Cells in Pancreatic Cancer Microenvironment

Pancreas ductal adenocarcinoma is a highly aggressive cancer with an incredible poor lifespan. Different chemotherapeutic agents’ schemes have been tested along the years without significant success. Furthermore, immunotherapy also fails to cope with the disease, even in combination with other standard approaches. Autophagy stands out as a chemoresistance mechanism and is also becoming relevant as responsible for the inefficacy of immunotherapy. In this complex scenario, exosomes have emerged as a new key player in tumor environment. Exosomes act as messengers among tumor cells, including tumor microenvironment immune cells. For instance, tumor-derived exosomes are capable of generating a tolerogenic microenvironment, which in turns conditions the immune system behavior. But also, immune cells-derived exosomes, under non-tolerogenic conditions, induce tumor suppression, although they are able to promote chemoresistance. In that way, NK cells are well known key regulators of carcinogenesis and the inhibition of their function is detrimental for tumor suppression. Additionally, increasing evidence suggests a crosstalk between exosome biogenesis and the autophagy pathway. This mini review has the intention to summarize the available data in the complex relationships between the autophagy pathway and the broad spectrum of exosomes subpopulations in pancreatic cancer, with focus on the NK cells response.Fil: Papademetrio, Daniela Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Garcia, Maria Noe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Grasso, Daniel Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas; ArgentinaFil: Alvarez, Elida Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentin

Geometry Diagnostics of a Stellar Flare from Fluorescent X-rays

We present evidence of Fe fluorescent emission in the Chandra HETGS spectrum of the single G-type giant HR 9024 during a large flare. In analogy to solar X-ray observations, we interpret the observed Fe K$\alpha$ line as being produced by illumination of the photosphere by ionizing coronal X-rays, in which case, for a given Fe photospheric abundance, its intensity depends on the height of the X-ray source. The HETGS observations, together with 3D Monte Carlo calculations to model the fluorescence emission, are used to obtain a direct geometric constraint on the scale height of the flaring coronal plasma. We compute the Fe fluorescent emission induced by the emission of a single flaring coronal loop which well reproduces the observed X-ray temporal and spectral properties according to a detailed hydrodynamic modeling. The predicted Fe fluorescent emission is in good agreement with the observed value within observational uncertainties, pointing to a scale height $\lesssim 0.3$\rstar. Comparison of the HR 9024 flare with that recently observed on II Peg by Swift indicates the latter is consistent with excitation by X-ray photoionization.Comment: accepted for publication on the Astrophysical Journal Letter

Preference of acromegaly patients for treatment attributes in Spain

Acromegaly; Growth hormone; Quality of lifeAcromegàlia; Hormona del creixement; Qualitat de vidaAcromegalia; Hormona del crecimiento; Calidad de vidaObjective Acromegaly is a rare disease caused by increased growth hormone secretion and a subsequent increase in insulin-like growth factor I (IGF-I) levels. Patients display multiple comorbidities that affect their quality of life (QoL). Treatment aims to maintain good biochemical control, tumour control and reduce the risk of comorbidities; however, their impact on QoL has been overlooked until recently. We interviewed patients to explore their preferences with regard to treatment attributes. Design A cross-sectional study based on interviews and a discrete choice experiment (DCE) in a Spanish cohort. Methods Adult patients diagnosed with acromegaly ≥1 year before the start of the study and under treatment were included. Treatment attributes were collected from patient testimony during face-to-face interviews. Then, a DCE was performed to elicit patient preferences for certain treatment attributes. Results Sixty-seven patients completed the study. QoL improvement was the most important treatment attribute (37%), followed by IGF-I control (20%), blood sugar control (17%) and tumour control (13%). Secondary attributes were pain associated with the route of administration (7%), diarrhoea (2%), administration method (2%) and storage conditions (2%). We then calculated the theoretical share of preference for existing treatments, based on the individual preference utility for each attribute and level. Pegvisomant obtained the highest share of preference overall, and the highest preference as a second-line treatment (53 and 95%, respectively). Conclusions QoL greatly influences patient treatment preference. Since acromegaly patients are informed and aware of their disease, treatment choices should always be shared with patients.This study was funded by Pfizer (Spain)

Propuesta estratégica de inbound marketing para fidelización de los clientes actuales del estudio contable Ramírez a través de redes sociales

Como consecuencia de que el entorno digital ha ido avanzando a pasos agigantados, las empresas, en la actualidad, han tenido que optar por estrategias de marketing diferentes a las convencionales, siendo obligadas a migrar a plataformas virtuales en donde no solo consiguen nuevos adeptos sino que interactúan con sus clientes y generan un valor diferencial en ellos. Por tal motivo, el presente trabajo de investigación tiene como finalidad identificar el nivel de impacto que tienen las estrategias convencionales del Estudio Contable Ramírez entre sus clientes actuales. Para tal fin, se aplicaron 229 encuestas a todos los clientes, con el propósito de poder segmentarlos según el entorno digital, reconocer su nivel de satisfacción, el grado de lealtad y los atributos de valor diferenciales de la empresa. Esta información recolectada junto con las entrevistas realizadas a distintos expertos en marketing y comunicación digital sirvieron para la estructuración de una estrategia de comunicación digital basada en el modelo de Inbound Marketing lo suficientemente efectiva para lograr la fidelización de los clientes del Estudio Contable Ramírez.As a result of the digital environment progressing by leaps and bounds, companies have now had to opt for different marketing strategies than conventional ones, being forced to migrate to virtual platforms where not only get new adepts, but also Interact with their customers and generate differential value in them. For this reason, this research work has the purpose of identifying the level of impact of the conventional strategies of the Accounting Study Ramírez among its current clients. For this purpose, 229 surveys were applied to all clients, in order to be able to segment them according to the digital environment, to recognize their level of satisfaction, the degree of loyalty and the differential value attributes of the company. This information collected together with the interviews carried out to different experts in marketing and digital communication served to structuring a digital communication strategy based on the Inbound Marketing model that was effective enough to achieve the loyalty of the clients of Estudio Contable Ramírez

Minimal irreversible quantum mechanics. The decay of unstable states

Brownian motion is modelled by a harmonic oscillator (Brownian particle) interacting with a continuous set of uncoupled harmonic oscillators. The interaction is linear in the coordinates and the momenta. The model has an analytical solution that is used to study the time evolution of the reduced density operator. It is derived in a closed form, in the one-particle sector of the model. The irreversible behavior of the Brownian particle is described by a reduced density matrix.Comment: 39 pages, 2 figure

Blood Biomarkers to Predict Long-Term Mortality after Ischemic Stroke

Biomarcador; Endostatina; Accident cerebrovascular isquèmicBiomarcador; Endostatina; Accidente cerebrovascular isquémicoBiomarker; Endostatin; Ischemic strokeStroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z-scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007–0.048), p quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke.This work has been funded by Instituto de Salud Carlos III (PI18/00804) and by La Fundació La Marató (Reg. 84/240 proj. 201702). Neurovascular Research Laboratory takes part in the Spanish stroke research network INVICTUS+ (RD16/0019/0021). L.R. is supported by a pre-doctoral fellowship from the Instituto de Salud Carlos III (IFI17/00012)

Relationship Between the Quorum Network (Sensing/Quenching) and Clinical Features of Pneumonia and Bacteraemia Caused by A. baumannii

Acinetobacter baumannii (Ab) is one of the most important pathogens associated with nosocomial infections, especially pneumonia. Interest in the Quorum network, i.e., Quorum Sensing (QS)/Quorum Quenching (QQ), in this pathogen has grown in recent years. The Quorum network plays an important role in regulating diverse virulence factors such as surface motility and bacterial competition through the type VI secretion system (T6SS), which is associated with bacterial invasiveness. In the present study, we investigated 30 clinical strains of A. baumannii isolated in the “II Spanish Study of A. baumannii GEIH-REIPI 2000-2010” (Genbank Umbrella Bioproject PRJNA422585), a multicentre study describing the relationship between the Quorum network in A. baumannii and the development of pneumonia and associated bacteraemia. Expression of the aidA gene (encoding the AidA protein, QQ enzyme) was lower (P < 0.001) in strains of A. baumannii isolated from patients with bacteraemic pneumonia than in strains isolated from patients with non-bacteraemic pneumonia. Moreover, aidA expression in the first type of strain was not regulated in the presence of environmental stress factors such as the 3-oxo-C12-HSL molecule (substrate of AidA protein, QQ activation) or H2O2 (inhibitor of AidA protein, QS activation). However, in the A. baumannii strains isolated from patients with non-bacteraemic pneumonia, aidA gene expression was regulated by stressors such as 3-oxo-C12-HSL and H2O2. In an in vivo Galleria mellonella model of A. baumannii infection, the A. baumannii ATCC 17978 strain was associated with higher mortality (100% at 24 h) than the mutant, abaI-deficient, strain (carrying a synthetase enzyme of Acyl homoserine lactone molecules) (70% at 24 h). These data suggest that the QS (abaR and abaI genes)/QQ (aidA gene) network affects the development of secondary bacteraemia in pneumonia patients and also the virulence of A. baumannii.National Plan for Scientific ResearchTechnological Development and Innovation PI16/01163ISCIII-Deputy General Directorate for Evaluation and Promotion of Research-European Regional Development Fund A way of Making EuropeInstituto de Salud Carlos IIIMiguel Servet Research Programme SERGAS and ISCIIIXunta de Galicia (GAIN, Axencia de Innovación

Comparison Study of an Optimized Ultrasound-Based Method versus an Optimized Conventional Method for Agar Extraction, and Protein Co-Extraction, from Gelidium sesquipedale

Agar is a hydrocolloid found in red seaweeds, which has been of industrial interest over the last century due to its multiple applications in the food, cosmetic, and medical fields. This polysaccharide, extracted by boiling for several hours, is released from the cell wall of red seaweeds. However, the environmental impact coming from the long processing time and the energy required to reach the targeted processing temperature needs to be reduced. In this study, a response surface methodology was employed to optimize both conventional extraction and ultrasound-assisted extractions. Two different models were successfully obtained (R2 = 0.8773 and R2 = 0.7436, respectively). Additionally, a further re-extraction confirmed that more agar could be extracted. Protein was also successfully co-extracted in the seaweed residues. Optimized conditions were obtained for both the extractions and the re-extraction of the two methods (CE: 6 h, 100 °C; and UAE: 1 h, 100% power). Finally, FT-IR characterization demonstrated that the extracts had a similar spectrum to the commercial agar. Compared to commercial samples, the low gel strength of the agar extracts shows that these extracts might have novel and different potential applications