Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies

AbstractAutologous stem cell transplantation (ASCT) is indicated in a number of hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Relapse, however, remains 1 of the main causes of post-ASCT failure, and several strategies are being investigated to decrease the risk of relapse of progression. Recent advances in the treatment of hematological malignancies have included adoptive transfer of genetically modified T cells that express chimeric antigen receptors or T cell receptors, as well the use of checkpoint inhibitors. Early clinical results in nontransplantation patients have been very promising. This review will focus on the use of gene-modified T cells and checkpoint inhibitors in stem cell transplantation

Allogeneic Stem Cell Transplantation with CD34+ Cell Selection

PB received funding a PERIS 2018-2020 grant from the Generalitat de Catalunya (BDNS357800). MAP received funding from the National Institutes of Health (Grant P01 CA23766 and NIH/NCI cancer Center Support Grant P30 CA008748).The success of allogeneic stem cell transplant is hampered by the development of acute and chronic graft- versus -host disease (GvHD) which has direct impact on treatment-related mortality and morbidity. As a result, T cell depletion through positive selection of CD34+ cells has emerged as a promising strategy to reduce acute and chronic GvHD in these patients. In this review, we summarize the main characteristics of allogeneic stem cell transplant with CD34+ cell selection including risks of graft failure, GvHD, infection, organ toxicity, and long-term survival. Moreover, we highlight future strategies to improve the results of this platform and to consolidate its use in clinical practice

Social Media and the Adolescent and Young Adult (AYA) Patient with Cancer

Over 70,000 adolescent and young adults aged 15 to 39 years (AYA) are diagnosed with cancer each year in the US. The National Cancer Institute (NCI) has identified AYA cancer patients as a unique population. The most common cancers in this age group include tumors typically seen in pediatric patients such as acute lymphoblastic leukemia (ALL) and brain tumors, as well as cancers more typically seen in adult patients such as breast cancer and melanoma. In addition, some cancers have their highest incidence in AYA patients, such as Hodgkin Lymphoma, testicular cancer and bone tumors. AYA patients face additional unique issues due to their age, not just questions about treatment choices due to lack of data, but also questions about fertility, relationships, loss of autonomy, and interruptions in school/work with potentially significant financial complications. This age group also has very high rates of social media usage with up to 90% of adults aged 18 to 29 using social networking sites. In this review, we will describe the use of social media in AYAs with cancer and highlight some of the online resources for AYAs

Ecotoxicity and biodegradability of an alkyl ethoxysulphate surfactant in coastal waters.

Alkyl ethoxysulphates (AES) are anionic surfactants widely used in numerous commercial and industrial applications. In spite of the high AES volume consumption a few data concerning the occurrence, fate and effects of AES in marine environments are reported in literature. The objective of this study is to evaluate the biodegradability and toxicity of AES in pristine sea water. Ultimate biodegradation was studied according to the guideline 835.3160 “Biodegradability in sea water” proposed by the United States Environmental Protection Agency (USEPA). Acute toxicity of AES was studied to the microalgae Nannochloropsis gaditana, Isochrysis galbana, Chaetoceros gracilis, Dunaliella salina and Tetraselmis chuii and the invertebrate Artemia franciscana, using culture growth inhibition and death, respectively, as effect criteria. During the degradative process two different stages were observed, which were better described with the first order and logistic kinetic models, respectively. Lag times were 3.3 (stage A) and 26.5 (stage B) days whereas half-lives were 18.6 (stage A) and 49.8 (stage B) days. AES inhibited the microalgae growth, with 96-h EC50 values ranging from 4.68 g L− 1 for D. salina to 24.02 mg L− 1 for I. galbana. Mean 48- and 72-h LC50 values for A. franciscana were 38.30 and 23.92 mg L− 1, respectively. The results indicate an extensive biodegradability of AES in sea water, although at a very slow rate. Acute toxicity was highly dependent on the species tested, being the green alga D. salina the most affected organism. The present study provides relevant data concerning the biodegradability and adverse effects of an AES surfactant on marine organisms, which are useful to establish water quality criteria in a regulatory framework

Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation for Adults with Relapsed and Refractory Mantle Cell Lymphoma: A Single Center Retrospective Analysis in the Rituximab Era

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Perception of bullying in sixth year students of a Lima public university school of medicine 2015

Introducción: Las conductas agresivas y discriminatorias afectan la salud física y mental incluso de quienes las cometen. Los estudiantes están sometidos a situaciones de estrés, las cuales aumentan el riesgo de desarrollar dichas conductas y a sufrir sus consecuencias. Por otro lado, la Escuela de Medicina tiene como propósito formar integralmente profesionales médicos, con capacidad de evitar situaciones de violencia y convivir pacíficamente. Es por ello el interés de describir este problema en la Escuela de Medicina de la Universidad Nacional Mayor de San Marcos, Lima, Perú. Objetivo: Abordar la situación de violencia (bullying) en estudiantes de Medicina Humana del 6° año que no habían participado en el Programa de Formación Integral en la UNMSM. Diseño: Estudio descriptivo-transversal. Lugar: Sede docente “Instituto Nacional de Salud del Niño”, Lima, Perú. Participantes: Muestra conformada por 93 (63%) estudiantes matriculados en el sexto año de la Facultad de Medicina que llevaron el curso de Pediatría durante los meses de julio a noviembre de 2015. Intervenciones: Se utilizó un instrumento desarrollado y validado por la Defensoría del Pueblo de España, modificado y corregido por Hoyos y col. Se calcularon las frecuencias y porcentajes de las respuestas. Resultados: Las conductas de violencia fueron más prevalentes entre estudiantes, entre ellas la conducta de agresión verbal más practicada fue la de expresarse de mala manera (40,8%). Conclusiones: La existencia de violencia se presenta en un alto porcentaje de la población estudiada y están implicados en ella docentes y estudiantes.Introduction. Aggressive and discriminatory behavior affects physical and mental health even on those who commit them. Students are subjected to stress, which increases the risk of those behaviors and makes them likely to suffer from its consequences. On the other hand, the Medical School aims to educate medical professionals integrally, with abilities to avoid violence and live peacefully. That is why the interest of describing this problem in Universidad Nacional Mayor de San Marcos, Lima, Peru’s Medical School. Objective. To address violence in students from the sixth year of Human Medicine who had not participated in the Integral Formation Program in UNMSM. Design: Descriptive, transversal study. Setting. "Instituto Nacional del Niño", Lima, Peru, teaching hospital. Participants. Sample consisted in 93 (63%) students enrolled in the sixth year of the Faculty of Medicine who took the course of Pediatrics during the months of July to November 2015. Interventions. An instrument developed and validated by the Spanish Office of the Ombudsman, modified and corrected by Hoyos et al was used. Frequencies and percentages of responses were calculated. Results. Violent behaviors were more prevalent among students; the most practiced behavior was to express badly (40.8%). Conclusions. The existence of violence occurs in a high percentage of the studied population; teachers and students are involved

Functional connectivity in mild cognitive impairment during a memory task: implications for the disconnection hypothesis.

Mild cognitive impairment (MCI) has been considered an intermediate state between healthy aging and dementia. The early damage in anatomical connectivity and progressive loss of synapses that characterize early Alzheimer's disease suggest that MCI could also be a disconnection syndrome. Here, we compare the degree of synchronization of brain signals recorded with magnetoencephalography from patients (22) with MCI with that of healthy controls (19) during a memory task. Synchronization Likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. During the memory task patients showed higher interhemispheric synchronization than healthy controls between left and right -anterior temporo-frontal regions (in all studied frequency bands) and in posterior regions in the γ band. On the other hand, the connectivity pattern from healthy controls indicated two clusters of higher synchronization, one among left temporal sensors and another one among central channels. Both of them were found in all frequency bands. In the γ band, controls showed higher Synchronization Likelihood values than MCI patients between central-posterior and frontal-posterior channels and a high synchronization in posterior regions. The inter-hemispheric increased synchronization values could reflect a compensatory mechanism for the lack of efficiency of the memory networks in MCI patients. Therefore, these connectivity profiles support only partially the idea of MCI as a disconnection syndrome, as patients showed increased long distance inter-hemispheric connections but a decrease in antero-posterior functional connectivit

Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP.

Mechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an essential step for mechanotransduction. However, how mechanical forces regulate the nuclear import process is not understood. Here, we identify a highly mechanoresponsive nuclear transport receptor (NTR), Importin-7 (Imp7), that drives the nuclear import of YAP, a key regulator of mechanotransduction pathways. Unexpectedly, YAP governs the mechanoresponse of Imp7 by forming a YAP/Imp7 complex that responds to mechanical cues through the Hippo kinases MST1/2. Furthermore, YAP behaves as a dominant cargo of Imp7, restricting the Imp7 binding and the nuclear translocation of other Imp7 cargoes such as Smad3 and Erk2. Thus, the nuclear import process is an additional regulatory layer indirectly regulated by mechanical cues, which activate a preferential Imp7 cargo, YAP, which competes out other cargoes, resulting in signaling crosstalk.We thank Miguel Sánchez for text editing. We thank Erika R. Geisbrecht, Kenneth Irvine, and Ariberto Fassati for kindly providing reagents. This study was supported by grants from the Spanish Ministry of Science and Innovation (MICIIN)/Agencia Estatal de Investigación (AEI)/European Regional Development Fund (ARDF/FEDER) “A way to make Europe” (PID2020-118658RB-I00, SAF2017-83130-R, IGP-SO grant MINSEV1512-07-2016, CSD2009-0016 and BFU2016-81912-REDC), Comunidad Autónoma de Madrid (Tec4Bio-CM, S2018/NMT¬4443), Fundació La Marató de TV3 (201936-30-31), “La Caixa” Foundation (HR20-00075) and AECC (PROYE20089DELP) all to M.A.d.P. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 641639. M.G.G. and L.S. are sponsored by FPU fellowships (FPU15/ 03776 and FPU18/05394, respectively). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MICIIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence CEX2020- 001041-S.S