A Biomathematical Model of Tumor Response to Radioimmunotherapy with PDL1 and CTLA4

There is evidence of synergy between radiotherapy and immunotherapy. Radiotherapy can increase liberation of tumor antigens, causing activation of antitumor T-cells. This effect can be boosted with immunotherapy. Radioimmunotherapy has potential to increase tumor control rates. Biomathematical models of response to radioimmunotherapy may help on understanding of the mechanisms affecting response, and assist clinicians on the design of optimal treatment strategies. In this work we present a biomathematical model of tumor response to radioimmunotherapy. The model uses the linear-quadratic response of tumor cells to radiation (or variation of it), and builds on previous developments to include the radiation-induced immune effect. We have focused this study on the combined effect of radiotherapy and PDL1/CTLA4 therapies. The model can fit preclinical data of volume dynamics and control obtained with different dose fractionations and PDL1/CTLA4. A biomathematical study of optimal combination strategies suggests that a good understanding of the involved biological delays, the biokinetics of the immunotherapy drug, and the interplay between them, may be of paramount importance to design optimal radioimmunotherapy schedules. Biomathematical models like the one we present can help to interpret experimental data on the synergy between radiotherapy and immunotherapy, and to assist in the design of more effective treatments

Integral field spectroscopy of nitrogen overabundant blue compact dwarf galaxies

We study the spatial distribution of the physical properties and of oxygen and nitrogen abundances in three Blue Compact Dwarf Galaxiess (HS 0128+2832, HS 0837+4717 and Mrk 930) with a reported excess of N/O in order to investigate the nature of this excess and, particularly, if it is associated with Wolf-Rayet (WR) stars We have observed these BCDs by using PMAS integral field spectroscopy in the optical spectral range (3700 - 6900 {\AA}), mapping their physical-chemical properties, using both the direct method and appropriate strong-line methods. We make a statistical analysis of the resulting distributions and we compare them with the integrated properties of the galaxies. Our results indicate that outer parts of the three galaxies are placed on the "AGN-zone" of the [NII]/H{\alpha} vs. [OIII]/H{\beta} diagnostic diagram most likely due to a high N/O combined with the excitation structure in these regions. From the statistical analysis, it is assumed that a certain property can be considered as spatially homogeneous (or uniform) if a normal gaussian function fits its distribution in several regions of the galaxy. Moreover, a disagreement between the integrated properties and the mean values of the distribution usually appears when a gaussian does not fit the corresponding distribution. We find that for Mrk 930, the uniformity is found for all parameters, except for electron density and reddening. The rotation curve together with the H{\alpha} map and UV images, reveal a perturbed morphology and possible interacting processes. The N/O is found to be constant in the three studied objects at spatial scales of the order of several kpc so we conclude that the number of WR stars estimated from spectroscopy is not sufficient to pollute the ISM and to produce the observed N/O excess in these objectsComment: 17 pages, 14 figures, accepted for publication in Astronomy & Astrophysic

Intercellular Trafficking of Gold Nanostars in Uveal Melanoma Cells for Plasmonic Photothermal Therapy

Efficient plasmonic photothermal therapies (PPTTs) using non-harmful pulse laser irradiation at the near-infrared (NIR) are a highly sought goal in nanomedicine. These therapies rely on the use of plasmonic nanostructures to kill cancer cells while minimizing the applied laser power density. Cancer cells have an unsettled capacity to uptake, retain, release, and re-uptake gold nanoparticles, thus offering enormous versatility for research. In this work, we have studied such cell capabilities for nanoparticle trafficking and its impact on the effect of photothermal treatments. As our model system, we chose uveal (eye) melanoma cells, since laser-assisted eye surgery is routinely used to treat glaucoma and cataracts, or vision correction in refractive surgery. As nanostructure, we selected gold nanostars (Au NSs) due to their high photothermal efficiency at the near-infrared (NIR) region of the electromagnetic spectrum. We first investigated the photothermal effect on the basis of the dilution of Au NSs induced by cell division. Using this approach, we obtained high PPTT efficiency after several cell division cycles at an initial low Au NS concentration (pM regime). Subsequently, we evaluated the photothermal effect on account of cell division upon mixing Au NS-loaded and non-loaded cells. Upon such mixing, we observed trafficking of Au NSs between loaded and non-loaded cells, thus achieving effective PPTT after several division cycles under low irradiation conditions (below the maximum permissible exposure threshold of skin). Our study reveals the ability of uveal melanoma cells to release and re-uptake Au NSs that maintain their plasmonic photothermal properties throughout several cell division cycles and re-uptake. This approach may be readily extrapolated to real tissue and even to treat in situ the eye tumor itself. We believe that our method can potentially be used as co-therapy to disperse plasmonic gold nanostructures across affected tissues, thus increasing the effectiveness of classic PPTT

Evaluación del impacto de una intervención para mejorar las coberturas de vacunación frente a neumococo en pacientes con VIH

Fundamentos: Las personas infectadas por el vi-rus de la inmunodeficiencia humana (VIH) presentan riesgo elevado de sufrir la enfermedad neumocócica invasiva, motivo por el que se recomienda su vacuna-ción frente al neumococo. El objetivo de este trabajo fue evaluar el impacto de implementar una consulta hospitalaria de vacunas en las coberturas de vacuna-ción de estos pacientes. Métodos: Se elaboró un estudio cuasiexperimental sin grupo control, de tipo antes/después, en el que se realizó un muestreo de casos consecutivos de pacientes con VIH remitidos a nuestra consulta entre el 1 noviembre de 2014 y el 30 junio de 2018. Las coberturas en el momento de la fecha de la cita para la valoración de su estado vacunal (en nuestra consulta) y después de ser atendido se compararon usando la prueba chi-cuadrado. Como referencia se utilizaron las del momento de la fecha de la primera cita. Resultados: Se analizaron 209 pacientes, en los que se obtuvieron mejoras estadísticamente signifi-cativas en sus coberturas vacunales: 2, 9% en el mo-mento de la fecha de la cita para la valoración en nuestra consulta y 88% después de ser atendidos en nuestra consulta (RR [IC95%]= 30, 7 [13, 92-67, 58]) para la vacuna antineumocócica conjugada 13-valen-te, y 16, 3% en el momento de la primera cita y 83, 7% después de ser atendidos en nuestra consulta (RR [IC95%]=5, 2 [3, 76-7, 04]) para la vacuna antineumo-cócica polisacárida 23-valente. Conclusiones: Implementar una consulta hospitalaria de vacunas representa una intervención efectiva para mejorar las coberturas de vacunación frente al neumococo en pacientes con VIH. Background: People affected by the human immunodeficiency virus (HIV) have a higher risk of invasive pneumococcal disease. Therefore, vaccination against streptococcus pneumoniae is recommended for that group. The objective of this study was to analyze the impact of implementing a hospital appointment to assess vaccination status as part of the vaccination schedule of HIV patients. Methods: We carried out a quasi-experimental uncontrolled before and after study with a sampling of consecutive cases of HIV patients referred to our department from November 1, 2014 to June 30, 2018. The study compared the vaccination coverage on the date of the appointment for an assessment of their vaccination status in our department and after the appointment. The analysis used the chi-squared test and the values on the date of the first appointment were taken as a reference. Results: 209 patients were analyzed, and a statistically significant improvement was observed regarding their vaccination coverage: 2.9% of the patients had been vaccinated on the date in which they made an appointment for assessment by our department, and 88.0% were vaccinated after they left (OR [95%CI]: 30.7 [13.92-67.58]) with the 13-valent pneumococcal conjugate vaccine; and 16.3% had been vaccinated on the date they made the first appointment vs. 83.7% after they came to the appointment (OR [95%CI]: 5.2 [3.76-7.04]) with the 23-valent polysaccharide pneumococcal vaccine. Conclusions: Implementing a hospital appointment for vaccination is an effective intervention to improve vaccination coverage against streptococcus pneumoniae in HIV patients

Diet and lifestyle changes during the COVID-19 pandemic in Ibero-American countries: Argentina, Brazil, Mexico, Peru, and Spain

This study aimed to evaluate changes in dietary and lifestyle habits during the period of confinement due to the first wave of the COVID-19 pandemic in Ibero-American countries. A cross-sectional investigation was conducted with 6,325 participants of both genders (68% women), over 18 years of age and from five countries: Brazil (N = 2,171), Argentina (N = 1,111), Peru (N = 1,174), Mexico (N = 686), and Spain (N = 1,183). Data were collected during the year 2020, between April 01 and June 30 in Spain and between July 13 and September 26, in the other countries studied using a self-administered online survey designed for the assessment of sociodemographic, employment, physical activity, health status, and dietary habits changes. Most participants (61.6%), mainly those from Spain, remained constant, without improving or worsening their pattern of food consumption. Among those who changed, a pattern of better eating choices prevailed (22.7%) in comparison with those who changed toward less healthy choices (15.7%). Argentina and Brazil showed the highest proportion of changes toward a healthier pattern of food consumption. Peruvians and Mexicans were less likely to make healthy changes in food consumption (OR: 0.51; 95% CI: 0.4–0.6 and OR: 0.69; 95% CI: 0.4–0.8, respectively), when compared to Argentinians. Most respondents did not change their pattern of meal consumption, but those who did reduced their consumption of main meals and increased intake of small meals and snacks. Although most participants affirmed to be doing physical activity at home, about one-half reported perception of weight gain. Individuals with alterations in sleep pattern (either by increasing or decreasing sleep time) were more likely to change their diets to a healthier pattern. In contrast, individuals with confirmed diagnosis of COVID-19 and those who reported feeling anxious were more likely to perform changes to a less healthy eating pattern (OR: 1.72; 95% CI: 1.2–2.3 and OR: 1.21; 95% CI: 1.1–1.4, respectively). In conclusion, although most participants remained constant in their eating habits, lifestyle changes and anxiety feelings were reported. Among those who changed patterns of food consumption, healthier choices prevailed, with differences between countries. However, there were alterations in the distribution of meals, with higher consumption of snacks and small meals. These results can be used to guide policies to prevent deleterious consequences that may affect the incidence of chronic diseasesWe acknowledge the National Council for Scientific and Technological Development (CNPq) which provided MCBM a productivity fellowship and the Coordination for the Improvement of Higher Education Personnel (CAPES) which granted OE-M a Ph.D. scholarship. The project developed in Spain was supported by the Program of R&D activities between research groups of the Community of Madrid in Social Sciences and Humanities, co-financed with the European Social Fund (H2019/HUM-5802

Prospective study of changes in sugar-sweetened beverages consumption and incidence of metabolic syndrome and its components

The incidence of the metabolic syndrome (MetS) is increasing and lifestyle behaviours may play a role. The aim of the present study was to prospectively assess the association between changes in the consumption of sugar-sweetened beverages (SSB) and the incidence of the MetS and its components in a Spanish cohort of university graduates. We included 8157 participants initially free of the MetS and followed up during at least 6 years. SSB consumption was collected by a FFQ previously validated in Spain. The change in SSB consumption was calculated as the difference between SSB consumption at a 6-year follow-up and baseline consumption. The MetS was defined according to the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute's new definition of the MetS that had harmonised previous definitions. The associations between changes in SSB intake and the MetS were examined using multiple logistic regression. We observed 361 incident cases of the MetS. Participants who increased their consumption of SSB (upper v. lower quintile) had a significantly higher risk of developing the MetS (adjusted OR 2·2, 95 % CI 1·4, 3·5; P for trend = 0·003). Similarly, they presented a significantly higher risk of developing high blood pressure (adjusted OR 1·6, 95 % CI 1·3, 2·1), central obesity (adjusted OR 2·3, 95 % CI 1·9, 2·7), hypertriacylglycerolaemia (adjusted OR 1·7, 95 % CI 1·1, 2·6) or impaired fasting glucose (adjusted OR 1·6, 95 % CI 1·1, 2·2). In conclusion, an increase in SSB consumption was associated with a higher risk of developing the MetS and other metabolic disorders after 6 years of follow-up in a Mediterranean cohort of university graduates

Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma

PURPOSE: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG). PATIENTS AND METHODS: In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1, 100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial. RESULTS: Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%. CONCLUSION: The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM

Dual-tasking and gait in people with Mild Cognitive Impairment. The effect of working memory

<p>Abstract</p> <p>Background</p> <p>Cognition and mobility in older adults are closely associated and they decline together with aging. Studies evaluating associations between cognitive factors and gait performance in people with Mild Cognitive Impairment (MCI) are scarce. In this study, our aim was to determine whether specific cognitive factors have a more identifiable effect on gait velocity during dual-tasking in people with MCI.</p> <p>Methods</p> <p>Fifty-five participants, mean age 77.7 (SD = 5.9), 45% women, with MCI were evaluated for global cognition, working memory, executive function, and attention. Gait Velocity (GV) was measured under a single-task condition (single GV) and under two dual-task conditions: 1) while counting backwards (counting GV), 2) while naming animals (verbal GV). Multivariable linear regression analysis was used to examine associations with an alpha-level of 0.05.</p> <p>Results</p> <p>Participants experienced a reduction in GV while engaging in dual-task challenges (p < 0.005). Low executive function and working memory performances were associated with slow single GV (p = 0.038), slow counting GV (p = 0.017), and slow verbal GV (p = 0.031). After adjustments, working memory was the only cognitive factor which remained significantly associated with a slow GV.</p> <p>Conclusion</p> <p>In older adults with MCI, low working memory performance was associated with slow GV. Dual-task conditions showed the strongest associations with gait slowing. Our findings suggest that cortical control of gait is associated with decline in working memory in people with MCI.</p