A research center's experience of T-cell-redirecting therapies in triple-class refractory multiple myeloma.

ABSTRACT: The efficacies of chimeric antigen receptor T cells (CAR-Ts) and bispecific monoclonal antibodies (BiAbs) for triple-class refractory (TCR) myeloma have not previously been compared, and clinical data on how to rescue patients after relapse from these immunotherapies are limited. A retrospective study of 73 TCR patients included in trials was conducted: 36 received CAR-Ts and 37 received BiAbs. CAR-Ts produced a higher overall response rate (ORR) than BiAbs (97.1% vs 56.8%, P = .002). After a median of follow-up of 18.7 months, no significant difference in progression-free survival (PFS) was observed between the CAR-T and BiAbs groups (16.6 vs 10.8 months; P = .090), whereas overall survival (OS) was significantly longer in the CAR-T than in the BiAbs group (49.2 vs 22.6 months; P = .021). BiAbs after CAR-Ts yielded a higher ORR and longer PFS2 than did nonredirecting T-cell therapies after CAR-Ts (ORR: 87.5% vs 50.0%; PFS2: 22.9 vs 12.4 months). By contrast, BiAbs after BiAbs resulted in an ORR of 33% and PFS2 of 8.4 months, which was similar to that produced by the nonredirecting T-cell therapies (ORR: 28.6%; PFS2: 8.1 months). Although this is a pooled analysis of different trials with different products and the patient profile is different for CAR-Ts and BiAbs, both were effective therapies for TCR myeloma. However, in our experience, although the PFS was similar with the 2 approaches, CAR-T therapy resulted in better OS, mainly because of the efficacy of BiAbs as rescue therapy. Our results highlight the importance of treatment sequence in real-word experience.

Experiencia sobre el proceso de salud-enfermedad-atención en pacientes con artritis reumatoidea pertenecientes a la comunidad Wichí de Misión Chaqueña "El Algarrobal", Salta / Experience on the health-disease-care process in patients with rheumatoid arthritis belonging to the Wichí community of Mission Chaqueña "El Algarrobal", Salta

Introducción: se ha reportado que la prevalencia de artritis reumatoidea (AR) en la comunidad Wichí representa la más alta informada por el Grupo Latinoamericano para el Estudio de las Enfermedades Reumáticas en los Pueblos Originarios (GLADERPO). El objetivo de este estudio fue describir la experiencia sobre el proceso de salud-enfermedad-atención de pacientes con AR de la comunidad Wichí de Misión Chaqueña "El Algarrobal", Salta. Materiales y métodos: estudio narrativo. Diseño de corte etnográfico. Se realizaron entrevistas semi-estructuradas y observaciones registradas. Se utilizaron guías de entrevistas y observación. Los aspectos incluidos fueron: concepción del proceso salud-enfermedad, percepción de la AR en la vida diaria, el acceso al sistema de salud, utilización de recursos tradicionales y de medicina tradicional. Resultados: se realizaron 10 entrevistas. Los aspectos más relevantes fueron la concepción del proceso salud-enfermedad asociado al trauma social pasado y al concepto de voluntad Wichí. Se evidenció la combinación de estrategias para mejorar el dolor (biomedicina, medicina tradicional y acompañamiento religioso). Además, se observó una relación unidireccional con el sistema de salud. Conclusiones: la AR es una enfermedad con un impacto negativo en la comunidad Wichí. Se requieren otras actividades, desde otras disciplinas, para mejorar el acceso al sistema de salud y la continuidad de los tratamientos.

Introduction: the prevalence of rheumatoid arthritis (RA) in the Wichí community has already been published, representing the highest reported by the Grupo Latinoamericano para el Estudio de las Enfermedades Reumáticas en los Pueblos Originarios (GLADERPO). The objective was to describe the experience of the health-disease-care process of patients with RA from the Wichí community of Misión Chaqueña "El Algarrobal", Salta. Materials and methods: study with ethnographic design. Semi-structured interviews and recorded observations were conducted. Interview and observation guides were used. The aspects included were: conception of the health-disease process; perception of RA in daily life, access to the health system, use of traditional resources and traditional medicine. Results: ten interviews were conducted. The most relevant aspects were the conception of the health-disease process, associated with past social trauma and the concept of "Wichí good will". The combination of strategies to improve pain (biomedicine, traditional medicine and religious accompaniment) was evidenced. In addition, a unidirectional relationship with the health system was observed. Conclusions: RA is a disease with a negative impact on the Wichí community. Other activities from other disciplines are necessary to improve access to the health system and continuity of treatment.

Incidencia del mindfulness en el estrés académico en estudiantes universitarios: un estudio controlado / Incidence of mindfulness in academic stress in university students: a controlled study

Resumen El mindfulness es un método cognitivo que consiste en prestar atención plena al cuerpo, respiración, pensamientos, emociones, y conductas, que se utiliza para reducir el estrés, dolor, ansiedad y depresión, el cual cuenta con algunas evidencias clínicas. Recientemente se está evaluando sus aplicaciones en el ámbito universitario, con resultados aún no concluyentes. El propósito del estudio fue evaluar la incidencia de un programa de ocho semanas del mindfulness en la reducción del estrés académico en una muestra de 54 estudiantes universitarios, con grupo de control aleatorio, y con medidas de pre-posprueba utilizando el Inventario CISCO de Estrés Académico. Se encontró que no existe diferencias estadísticamente significativas en los niveles de estrés del grupo que recibió el programa de mindfulness comparado con los que no recibieron el entrenamiento. El resultado es congruente con algunos hallazgos que no atribuyen eficacia de la atención plena en el manejo del estrés académico.

Abstract Mindfulness is a cognitive method that consists of giving full attention to the body, breathing, thoughts, emotions, and behaviors, which is used to reduce stress, pain, anxiety and depression, which has some clinical evidence. Recently, its applications in the university field are being evaluated, with results that are not yet conclusive. The purpose of the study is to evaluate the incidence of an eight-week program of mindfulness in reducing academic stress in a group of 54 university students, with a randomized control group, and with pre-post-test measures using the CISCO Academic Stress Inventory. It was found that there are no statistically significant differences in the stress levels of the group that received the der mindfulnes program compared to those who did not receive the training. The result is congruent with some findings that do not attribute efficiency of mindfulness in the management of academic stress.

Behavioral thermoregulation and critical thermal limits of giant keyhole limpet Megathura crenulata(Sowerby 1825) (Mollusca; Vetigastropoda).

The thermoregulatory behavior of the giant keyhole limpet Megathura crenulata was determined in a horizontal thermal gradient during the day at 18.9 °C and 18.3 °C for the night. The final preferendum determined for giant keyhole limpets was of 18.6±1.2 °C. Limpets' displacement velocity was 10.0±3.9 cm h(-1) during the light phase and 8.4±1.6 cm h(-1) during the dark phase. The thermotolerance (measured as CTMax at 50%) was determined in a keyhole limpet in three acclimation temperatures 17, 20, and 23 °C. Limpets were subjected to water increasing temperatures at a rate of 1 °C every 30 min, until they detached from the substrate. The critical thermal maximum at 50% was 27.2, 27.9 and 28.3 °C respectively.

Modifications in lipid levels are independent of serum TNF-α in rheumatoid arthritis: results of an observational 24-week cohort study comparing patients receiving etanercept plus methotrexate or methotrexate as monotherapy.

OBJECTIVE: To compare the modifications in lipids between patients with rheumatoid arthritis (RA) receiving etanercept plus methotrexate (ETA + MTX) versus methotrexate (MTX) and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α). METHODS: In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and TNF-α. RESULTS: Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, P < 0.001, and to 56.0 mg/dL at 24 weeks, a 25.1% increase, P < 0.001), while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P < 0.001). The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P = 0.04) and also in TNF-α (P = 0.01). CONCLUSION: HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α.

Utilidad de la ultrasonografía endoscópica en el diagnóstico de los linfomas / The use of endoscopic ultrasound for lymphoma diagnosis

La ecoendoscopia digestiva es una herramienta de gran utilidad para el diagnóstico y estadificación de las neoplasias digestivas, así como para aquellas que comprometen estructuras cercanas al tracto digestivo. Los linfomas son neoplasias que albergan una elevada dificultad diagnóstica, y ello se debe a la íntima relación entre el subtipo histológico y la respuesta al tratamiento quimioterapéutico. De esta forma, un diagnóstico preciso es fundamental en el manejo de la enfermedad. Mientras que la mayoría de los linfomas gastrointestinales pueden ser diagnosticados y subclasificados a partir de biopsias endoscópicas, los que afectan órganos o adenopatías de difícil acceso requieren con frecuencia maniobras invasivas para la obtención de una muestra histológica adecuada. La ecoendoscopia ha demostrado su utilidad en la estadificación de linfomas gastrointestinales y, además, puede ser útil en el diagnóstico de linfomas localizados en órganos o adenopatías de difícil acceso cuando se acompaña del análisis citológico obtenido mediante punción aspiración con aguja fina o biopsia. En este artículo se revisa el papel de la ecoendoscopia digestiva en linfomas gastrointestinales, pancreáticos, esplénicos o ganglionares...

Thermopreference, tolerance and metabolic rate of early stages juvenile Octopus maya acclimated to different temperatures.

Thermopreference, tolerance and oxygen consumption rates of early juveniles Octopus maya (O. maya; weight range 0.38-0.78g) were determined after acclimating the octopuses to temperatures (18, 22, 26, and 30°C) for 20 days. The results indicated a direct relationship between preferred temperature (PT) and acclimated temperature, the PT was 23.4°C. Critical Thermal Maxima, (CTMax; 31.8±1.2, 32.7±0.9, 34.8±1.4 and 36.5±1.0) and Critical Thermal Minima, (CTMin; 11.6±0.2, 12.8±0.6, 13.7±1.0, 19.00±0.9) increased significantly (P<0.05) with increasing acclimation temperatures. The endpoint for CTMax was ink release and for CTMin was tentacles curled, respectively. A thermal tolerance polygon over the range of 18-30°C resulted in a calculated area of 210.0°C(2). The oxygen consumption rate increased significantly α=0.05 with increasing acclimation temperatures between 18 and 30°C. Maximum and minimum temperature quotients (Q10) were observed between 26-30°C and 22-26°C as 3.03 and 1.71, respectively. These results suggest that O. maya has an increased capability for adapting to moderate temperatures, and suggest increased culture potential in subtropical regions southeast of México.

Effect of Extraction Conditions on the Antioxidant Activity of Olive Wood Extracts.

An investigation to optimize the extraction yield and the radical scavenging activity from the agricultural by-product olive tree wood (Olea europaea L., cultivar Picual) using six different extraction protocols was carried out. Four olive wood samples from different geographical origin, and harvesting time have been used for comparison purposes. Among the fifty olive wood extracts obtained in this study, the most active ones were those prepared with ethyl acetate, either through direct extraction or by successive liquid-liquid partitioning procedures, the main components being the secoiridoids oleuropein and ligustroside. An acid hydrolysis pretreatment of olive wood samples before extractions did not improve the results. In the course of this study, two compounds were isolated from the ethanolic extracts of olive wood collected during the olives' harvesting season and identified as (7''R)-7''-ethoxyoleuropein (1) and (7''S)-7''-ethoxyoleuropein (2).

Structure-activity relationship study of nitrosopyrimidines acting as antifungal agents.

The design, synthesis, in vitro evaluation, and conformational study of nitrosopyrimidine derivatives acting as antifungal agents are reported. Different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines have displayed a significant antifungal activity against human pathogenic strains. In this paper, we report a new group of nitrosopyrimidines acting as antifungal agents. Among them, compounds 2a, 2b and 15, the latter obtained from a molecular modeling study, exhibited antifungal activity against Candida albicans, Candida tropicalis and Cryptococcus neoformans. We have performed a conformational and electronic analysis on these compounds by using quantum mechanics calculations in conjunction with Molecular Electrostatic Potentials (MEP) obtained from B3LYP/6-31G(d) calculations. Our experimental and theoretical results have led us to identify a topographical template which may provide a guide for the design of new nitrosopyrimidines with antifungal effects.

Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents.

Novel (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones 5/6 (pyrazolic chalcones) were synthesized from a Claisen-Schmidt reaction of 3-aryl-1-phenylpyrazol-4-carboxaldehydes 4 with several acetophenone derivatives 1. Subsequently, the microwave-assisted cyclocondensation reaction of chalcones 5/6 with hydrazine afforded the new racemic 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazoles 7 or their N-acetyl derivatives 8 and 9 when reactions where carried out in DMF or acetic acid, respectively. Several of these compounds were screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where 5c and 9g showed remarkable activity mainly against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell lung cancer (HOP-92) cell lines, with the most important GI50 values ranging from 0.04 to 11.4 microM, from the in vitro assays.

Synthesis and olfactory evaluation of bulky moiety-modified analogues to the sandalwood odorant Polysantol.

Five new bulky moiety-modified analogues of the sandalwood odorant Polysantol have been synthesized by aldol condensation of appropriate aldehydes with butanone, deconjugative alpha-methylation of the resulting alpha,beta-unsaturated ketones, and reduction of the corresponding beta,gamma-unsaturated ketones. The final compounds were evaluated organoleptically and one of them seemed to be of special interest for its natural sandalwood scent.

Hyperhomocysteinemia in ankylosing spondylitis: prevalence and association with clinical variables.

We evaluated the prevalence and characteristics associated with hyperhomocysteinemia in ankylosing spondylitis (AS). Ninety-seven patients with AS were compared with 97 controls. The assessment included clinical characteristics, disease activity (BASDAI), functioning (BASFI), history of drugs, and erythrocyte sedimentation rate (ESR). Total serum homocysteine (tHcy) was determined by fluorescence polarization immunoassay. A higher frequency of hyperhomocysteinemia (>15 micromol/L) was observed in AS (12 vs. 1%, P = 0.002). In the multivariate analysis the risk for hyperhomocysteinemia was increased in patients with higher score of HAQ-S (OR = 5.27, 95% CI: 1.29-21.44) and higher ESR (OR = 1.09, 95% CI: 1.02-1.18). No statistical associations was observed between hyperhomocysteinemia with other variables including methotrexate or sulfasalazine utilization. In conclusion, this study found a significant prevalence of hyperhomocysteinemia in Mexican patients with AS mainly associated to a worst functional impairment. Further follow-up studies are required to evaluate the risk of cardiovascular disease in these patients.

Quiste hidatídico esplénico gigante / Giant splenic hydatid cyst

La hidatidosis es una parasitosis relativamente frecuente en determinadas áreas geográficas, y hace referencia al desarrollo en el organismo humano de tumoraciones quísticas que corresponden a la fase larvaria del Echinococcus granulosus. Los órganos más frecuentemente afectados son el hígado y los pulmones. La afectación esplénica única es rara y suele cursar con dolor abdominal y una masa palpable en el hipocondrio izquierdo. El tratamiento de elección es quirúrgico. Se recomienda la cirugía radical (esplenectomía), sobre todo en los quistes grandes, y la cirugía conservadora se deja para los pacientes en edad pediátrica o con quistes irresecables. La cirugía laparoscópica de esta patología tiene algunas limitaciones (AU)

Hydatidosis is a relatively frequent parasitic disease in some geographical areas and is caused by infection with Echinococcus granulosus larvae leading to the development of cysts. The most frequently affected organs are the liver and lungs. Splenic involvement alone is rare and produces mild abdominal discomfort and a palpable mass in the left hypochondriac region. The treatment of choice is surgery. Radical surgery (splenectomy) is recommended, especially in large cysts. Conservative procedures are employed in pediatric patients or unresectable cysts. Laparoscopic techniques have had limited success (AU)

Isolation and identification of radical scavengers in olive tree (Olea europaea) wood.

Several extracts of Olea europaea wood (Picual olive cultivar) were obtained with solvents of different polarity and their antioxidant activities determined. The active compounds were detected in fractions of an ethyl acetate extract using HPLC with on-line radical scavenging detection. After applying different separation techniques, hydroxytyrosol, tyrosol, cycloolivil, 7-deoxyloganic acid, oleuropein and ligustroside were isolated and characterized. Hydroxytyrosol showed a higher activity than the natural antioxidant rosmarinic acid in scavenging the DPPH model radical. Cycloolivil and oleuropein showed stronger activities than the synthetic antioxidant BHT against the same radical. Ligustroside, tyrosol and 7-deoxyloganic acid showed little activity. The latter compound has not been previously identified in the genus Olea.

Relation between reproductive, physiological, and immunological condition of Litopenaeus setiferus pre-adult males fed different dietary protein levels (Crustacea; Penaeidae).

The present study was designed to evaluate the effect of amount of dietary protein levels on blood indicators of protein metabolism and immune condition (blood protein, hemocyanin, osmotic pressure, and hemocytes concentrations), and reproductive capacity of pre-adult Litopenaeus setiferus males (F0). Assessments were made of the relationship between amount of dietary protein, immune condition, and reproductive condition of the shrimp during the maturation process. Three different diets, with different amounts of protein (DP; 35, 45, and 55%), were evaluated over 55 days and compared with shrimp that were from a baseline group before treatments were administrated. Osmotic pressure, hemocyanin, blood protein, and hemocytes were greater in shrimp from control ponds than those obtained of shrimp fed 35 and 45% DP and similar to that obtained in shrimp fed 55% DP, demonstrating that food in the control pond had a nutritional value to that obtained by feeding amounts of dietary protein beyond 45%. Osmotic pressure, hemocyanin (Hc), blood protein (BP), and hemocytes were influenced by amount of DP with the physiology and immune system of shrimp being influenced by diet. At the same time, a maximum reproductive condition (measured as a proportion of normal cells of the total sperm cells) of shrimp males was observed in shrimp fed 45% DPL with lesser normal cells being present in shrimp fed 35 and 55% DPL. These results indicate that an immune reaction can occur in response to dietary protein with excess DP affecting several physiological functions included the sperm synthesis and sperm quality. Influence on hemocytes concentration in shrimp fed protein in excess could activate an attack on sperm cells in the vas deferens provoking lose of sperm quality in such conditions. Results indicate an optimal DP of 45 for maintaining the broodstock bank of L. setiferus.

Preliminary assay on the radical scavenging activity of olive wood extracts.

The dichloromethane and ethanol extracts of Olea europaea wood (picual olive cultivar) were screened for antioxidant activity, determined by the DPPH free radical scavenging assay. The ethanol extract displayed potent antioxidant activity.

Potential for use of synthetic sex pheromone for mating disruption of the olive pyralid moth, Euzophera pinguis.

The potential for pheromone-based mating disruption of the olive pyralid moth (OPM), Euzophera pinguis, in olive groves was investigated during the second flight period in small-plot trials in 2002. The female of this species emits a blend of (9Z,12E)-tetradecadien-1-ol and (9Z,12E)-tetradecadienyl acetate, which were synthesized for field tests. Mating disruption efficacy in 0.8-ha trials was evaluated using two parameters: reduction of male capture in pheromone traps and reduction of infestation in infestation-prone sites. White rubber septa containing 10 mg of pheromone blend as disruptant were applied at a density of 50 septa/ha for each treatment. Mean catches of E. pinguis males in pheromone traps were greatly reduced (> 95%) in pheromone-treated plots relative to similar traps placed in control plots. In addition, significant reductions were recorded (35-40%) in the oviposition and infestation levels during pheromone treatment. The total amount of pheromone blend released from disruption dispensers during the field trials was estimated to average 5.4 mg/ha/day, over 56 days.

2-amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile.

The supramolecular structure of the title compound, C(18)H(17)ClN(2)O(2), is determined by the intersection of two chains formed by N-H...O and N-H...N hydrogen bonds, forming a two-dimensional sheet.

Ethyl N-(2-benzylamino-6-benzyloxy-5-nitrosopyrimidin-4-yl)glycinate: sheets built from a three-centre N[bond]H...(N,O), and two-centre C[bond]H...O and C[bond]H...pi(arene) hydrogen bonds.

In the title compound, C(22)H(23)N(5)O(4), the molecules are linked into chains by a three-centre N[bond]H...(N,O) hydrogen bond, reinforced by a two-centre C[bond]H...O hydrogen bond, and the chains are further linked into sheets by a combination of C[bond]H...O and C[bond]H...pi(arene) hydrogen bonds.