Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1

Antiviral restriction factors are host cellular proteins that constitute a first line of defense blocking viral replication and propagation. In addition to interfering at critical steps of the viral replication cycle, some restriction factors also act as innate sensors triggering innate responses against infections. Accumulating evidence suggests an additional role for restriction factors in promoting antiviral cellular immunity to combat viruses. Here, we review the recent progress in our understanding on how restriction factors, particularly APOBEC3G, SAMHD1, Tetherin, and TRIM5α have the cell-autonomous potential to induce cellular resistance against HIV-1 while promoting antiviral innate and adaptive immune responses. Also, we provide an overview of how these restriction factors may connect with protein degradation pathways to modulate anti-HIV-1 cellular immune responses, and we summarize the potential of restriction factors-based therapeutics. This review brings a global perspective on the influence of restrictions factors in intrinsic, innate, and also adaptive antiviral immunity opening up novel research avenues for therapeutic strategies in the fields of drug discovery, gene therapy, and vaccines to control viral infections

El passaport a la professió al Grau de Psicologia: indicador de qualitat del procés d'ensenyament-aprenentatge

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524Des del curs 2012-13, al llarg del Grau de Psicologia s’ofereix un programa d’orientació professional, de caràcter voluntari i personalitzat, que respon a les directrius de l’Estratègia Europa 2020, del Pla marc Horitzó 2020, i de l’Espai Europeu d’Educació Superior. Després de tres anys, ja es poden analitzar uns primers resultats a través del nombre d’inscripcions, qüestionaris de satisfacció i els exercicis realitzats d’autoconeixement i d’exploració del món professional

Primers resultats del Passaport a la Professió a Farmàcia

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524En el curs 2012/13, el deganat de la Facultat de Farmàcia va iniciar una activitat d’orientació professionalanomenada Seminari “Passaport a la Professió” dissenyada conjuntament amb el Servei d’Atenció al’Estudiant de la Universitat de Barcelona i dirigida especialment a l’alumnat interessat en realitzar l’assignatura“Pràctiques en empreses”. Aquesta activitat es va aprovar com a Projecte de Millora i Innovació Docent al’any 2013.En el curs 2012/13, el deganat de la Facultat de Farmàcia va iniciar una activitat d’orientació professional dirigida especialment a l’alumnat interessat en realitzar pràctiques en empreses i anomenada Seminari “Passaport a la Professió-Farmàcia. És un projecte dissenyat amb la implicació de tres agents: la Facultat de Farmàcia, les companyies farmacèutiques i el Servei d’Atenció a l’Estudiant (SAE). Aquesta activitat va gaudir d’un Projecte de Millora i Innovació Docent a l’any 2013. La present comunicació pretén analitzar el grau de participació i satisfacció dels alumnes al llarg d’aquests tres cursos acadèmics. El nombre d'estudiants inscrits al llarg d'aquests anys ha estat de 207 alumnes i en algunes sessions s'ha aconseguit omplir l’Aula Magna el 100% amb alumnes sense inscripció prèvia i interessats en la temàtica. Al llarg d’aquests anys, l’activitat s’ha consolidat a la Facultat de Farmàcia considerant que l’alumne la percep com una oportunitat anual per conèixer la realitat professional de la farmàcia així com els requisits d’accés al món laboral. A més, el nombre d’alumnes que ha sol·licitat participar en el programa de pràctiques en empreses dins de l’assignatura optativa ha incrementat al llarg dels cursos, així com el nombre d’empreses participants, consolidant-se algunes de les tradicionalment ja hi participaven. Per altra banda, aquesta activitat ha afavorit un millor coneixement entre l’alumnat de Farmàcia sobre les altres accions d’orientació universitàries del SAE (Club de Feina, Monogràfics del Club de Feina, cursos de Formació en Competències, Entrevistes d’Orientació, Simulacions personalitzades d’entrevistes de feina). L’avaluació del programa es basa per una banda, amb els qüestionaris al finalitzar el període de pràctiques en indústries farmacèutiques i per l’altra, dels qüestionaris de satisfacció a cada una de les sessions del seminari Passaport a la Professió

El dietista-nutricionista en Atención Primaria: una aproximación viable

II Congreso de Alimentación, Nutrición y Dietética. Avances en Nutrición y Dietética Clínica: Prevención, Tratamiento y Gestión - Rol del Dietista-Nutricionist

Viral and Cellular factors leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors

Human immunodeficiency virus type 1 (HIV-1) viremic nonprogressors (VNPs) represent a very rare HIV-1 extreme phenotype. VNPs are characterized by persistent high plasma viremia and maintenance of CD41 T-cell counts in the absence of treatment. However, the causes of nonpathogenic HIV-1 infection in VNPs remain elusive. Here, we identified for the first time two VNPs who experienced the loss of CD41 homeostasis (LoH) after more than 13 years. We characterized in deep detail viral and host factors associated with the LoH and compared with standard VNPs and healthy controls. The viral factors determined included HIV-1 coreceptor usage and replicative capacity. Changes in CD41 and CD81 T-cell activation, maturational phenotype, and expression of CCR5 and CXCR6 in CD41 T-cells were also evaluated as host-related factors. Consistently, we determined a switch in HIV-1 coreceptor use to CXCR4 concomitant with an increase in replicative capacity at the LoH for the two VNPs. Moreover, we delineated an increase in the frequency of HLA-DR1CD381 CD41 and CD81 T cells and traced the augment of naive T-cells upon polyclonal activation with LoH. Remarkably, very low and stable levels of CCR5 and CXCR6 expression in CD41 T-cells were measured over time. Overall, our results demonstrated HIV-1 evolution toward highly pathogenic CXCR4 strains in the context of very limited and stable expression of CCR5 and CXCR6 in CD41 T cells as potential drivers of LoH in VNPs. These data bring novel insights into the correlates of nonpathogenic HIV1 infection. Importance: The mechanism behind nonpathogenic human immunodeficiency virus type 1 (HIV-1) infection remains poorly understood, mainly because of the very low frequency of viremic nonprogressors (VNPs). Here, we report two cases of VNPs who experienced the loss of CD41 T-cell homeostasis (LoH) after more than 13 years of HIV-1 infection. The deep characterization of viral and host factors supports the contribution of viral and host factors to the LoH in VNPs. Thus, HIV-1 evolution toward highly replicative CXCR4 strains together with changes in T-cell activation and maturational phenotypes were found. Moreover, we measured very low and stable levels of CCR5 and CXCR6 in CD41 T-cells over time. These findings support viral evolution toward X4 strains limited by coreceptor expression to control HIV-1 pathogenesis and demonstrate the potential of host-dependent factors, yet to be fully elucidated in VNPs, to control HIV-1 pathogenesis.This research was supported by a Gilead Fellowship (grant GLD15/0298) and La Caixa Foundation (grant LCF/PR/PR16/11110026). M.C.-L. is a Beatriu de Pinós postdoctoral fellow (grant BP 00075) supported by the Government of Catalonia’s Secretariat for Universities and Research of the Ministry of Economy and Knowledge. J.G.P. was supported by the ISCIII (grant CP15/00014). E.J.-M. was funded by Redes Temáticas de Investigación en SIDA (ISCIII RETIC RD16/0025/0041); Acción Estratégica en Salud; Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008–2011; and Instituto de Salud Carlos III. E.J.-M. was cofunded by European Regional Development Fund/European Social Fund (FEDER) “Investing in your future.” J.M.-P. is supported by the Spanish Ministry of Science and Innovation (grant PID2019-109870RB-I00). J.G.P. and M.C.-L. designed the study, supervised experiments and data. J.G.P., M.C.-L., and A.K. contributed to data interpretation. M.C.-L., R.P., E.J.-M., M.P., and C.C. performed experiments, analyzed, and interpreted the data. J.D. carried out the clinical follow-up and patient identification. M.C.-L., D.O., M.P., and C.C. performed data analysis. M.C.-L., A.K., M.P., C.L.-G., B.C., J.M.-P., and J.G.P. performed manuscript writing, critical revision, and discussion. We declare no conflict of interest.S

Recomendación para la determinación de HER2 en cáncer de mama : Consenso nacional de la sociedad española de anatomía patológica (SEAP) y de la sociedad española de oncología médica (SEOM)

La identificación de los carcinomas de mama con amplificación/sobreexpresión de HER2 es crítica en la práctica clínica diaria ya que estas neoplasias requieren un tratamiento específico que incluye el uso de terapias dirigidas. Tanto las técnicas de hibridación in situ como las técnicas inmunohistoquímicas son métodos apropiados para la identificación de cánceres de mama HER2 positivos. Sin embargo, numerosos estudios, incluidos los desarrollados por la Asociación para la Garantía de Calidad en Patología de la SEAP (AGCP) y la experiencia de centros de referencia nacionales en la determinación de HER2 han puesto de manifiesto importantes problemas de reproducibilidad entre laboratorios. Por estos motivos, patólogos expertos en la determinación de HER2 de estos centros de referencia, así como oncólogos médicos con una contrastada actividad en cáncer de mama, en representación de las sociedades respectivas (SEAP y SEOM), han trabajado para debatir y consensuar las recomendaciones nacionales de determinación de HER2. Estas recomendaciones se basan no sólo en la experiencia de los participantes en el consenso, sino también en la experiencia internacional publicada en recientes guías de distintos países, tales como Estados Unidos, Reino Unido y Canadá. En este consenso, se recomiendan los requisitos mínimos que un laboratorio de Anatomía Patológica debe cumplir para garantizar la adecuada determinación de HER2 en la práctica diaria. Aquellos laboratorios que carezcan de los estándares mínimos expuestos en esta guía deberían trabajar en alcanzarlos y durante este proceso remitir a laboratorios de referencia las muestras en las que la determinación de HER2 tenga implicaciones clínicas para las pacientes.Breast cancers with HER2 alterations are critical to identify because such tumors require unique treatment, including the use of targeted therapies. HER2 alterations at the DNA (amplification) and protein (overexpression) level usually occur in concert, and both in situ hybridization and immunohistochemistry can be accurate methods to assess these alterations. However, recent studies including those conducted by the Association for Quality Assessment of the Spanish Society of Pathology and the experience of several national reference centres for HER2 testing have suggested that serious reproducibility issues exist with both techniques. To address this, a joint committee of both the Spanish Society of Pathology and the Spanish Society of Medical Oncology has met to review guidelines for HER2 testing. Consensus recommendation are based not only on panellist’s experience but also in those consensus guidelines previously reported in several countries, such as United Stated, United Kingdom and Canada. These guidelines include minimal requirements that Pathology Department must meet in order to guarantee appropriate HER2 testing in breast cancer. Pathology laboratories that do not meet these standards must put effort to reach them and, in the meantime, send clinical cases to reference centres.Vera Sempere, Fco Jose, [email protected] ; Lluch Hernandez, Ana, [email protected]

BOMET-QoL-10 questionnaire for breast cancer patients with bone metastasis: the prospective MABOMET GEICAM study

Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0–1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patientsThis work was sponsored by GEICAM and Novartis. Roche funded the publication fees for this articl

Treatment of cancer with oral drugs: a position statement by the Spanish Society of Medical Oncology (SEOM)

Cancer treatment involves the participation of multiple medical specialties and, as our knowledge of the disease increases, this fact becomes even more apparent. The degree of multidisciplinarity is determined by several factors, which include the severity and type of disease, the increasing diversity in the available pharmacological and non-pharmacological therapies, and the range of specialists involved in cancer therapy, such as medical oncologists, radiotherapists, gynecologists, gastroenterologists, urologists, surgeons, and pneumologists, among others. Across Europe, the situation of cancer care can be variable due to the diversity of health systems, differences in drug reimbursement, and the degree of establishment of Medical Oncology as a medical specialty in the European Union states

Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N= 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel