The Cost of Loneliness: Assessing the Social Relationships of the Elderly via an Abbreviated Sociotype Questionnaire for inside and outside the Clinic

Gauging the social relationships of the elderly is a significant sociometric research subject and a deep biomedical concern-particularly after the COVID-19 pandemic. It is imperative for facultatives in primary care, for geriatric clinics, and for social care services. In this respect, this article explores the validity of an abbreviated version of the Sociotype Questionnaire (SOCQ), a tool previously developed by the authors for assessing the social relationships of the general population, now specifically addressed to the elderly population. The aim is to construct a 4-item dichotomous scale (SOCG-4) out of the 12 items of the original scale of the SOCQ, so that it can serve to discriminate among the patients in primary care and the geriatric clinic, helping the facultative to find those in need of social care or of psychosocial intervention. The population data have been obtained from a series of previous studies on social relationships in different segments of the elderly population (Ntotal = 915). The resulting abbreviated version of SOCG-4 was extracted by means of confirmatory factor analysis, with the congruence, validity, and relationship with the determinants as close to optimal. The significant correlations with SOCQ (0.82), UCLA (-0.55), Barthel (0.40), and other relevant tests are obtained. The test was also put to trial in a pilot study, being applied to 150 subjects via phone surveys, home visiting, and geriatric clinic-it becomes particularly useful for assessing the social relationships in geriatric clinic use. The 4-item Geriatric Sociotype scale (SOCG-4) appears as a valid measurement instrument for use in the clinic and in other social care instances

Observational study of HR+/HER2− metastatic breast cancer patients treated with abemaciclib in Spain in the Named Patient Use Program (AbemusS)

Metastatic breast cancer; Abemaciclib; EffectivenessCàncer de mama metastàtic; Abemaciclib; EficàciaCáncer de mama metastásico; Abemaciclib; EficaciaIntroduction/objectives To describe abemaciclib use in patients with hormone receptor-positive, human epidermal growth factor receptor-negative (HR+/HER2−) metastatic breast cancer (mBC) who participated in the Named Patient Use program (NPU) in Spain. Material and methods This retrospective study was based on medical record review of patients across 20 centers during 2018/2019. Patients were followed up until death, enrolment in a clinical trial, loss of follow-up or study end. Clinical and demographic characteristics, treatment patterns and abemaciclib effectiveness were analyzed; time-to-event and median times were estimated using the Kaplan–Meier (KM) method. Results The study included 69 female patients with mBC (mean age 60.4 ± 12.4 years), 86% of whom had an initial diagnosis of early BC and 20% had an ECOG ≥ 2. Median follow-up was 23 months (range 16–28). Metastases were frequently observed in bone (79%) and visceral tissue (65%), with 47% having metastases in > 2 sites. Median number of treatment lines before abemaciclib was 6 (range 1–10). Abemaciclib monotherapy was received by 72% of patients and combination therapy with endocrine therapy by 28% of patients; 54% of patients required dose adjustments, with a median time to first adjustment of 1.8 months. Abemaciclib was discontinued in 86% of patients after a median of 7.7 months (13.2 months for combination therapy and 7.0 months for monotherapy) mainly due to disease progression (69%). Conclusion These results suggest that abemaciclib is effective, as monotherapy and in combination, for patients with heavily pretreated mBC, consistent with clinical trial results.Sponsorship for this study was funded by Lilly. It was conducted with the support of the Clinical Research Organization IQVIA for the following activities: protocol development, site monitoring and statistical analysis

Palbociclib with Fulvestrant or Letrozole in Endocrine-Sensitive Patients with HR-Positive/HER2-Negative Advanced Breast Cancer: A Detailed Safety Analysis of the Randomized PARSIFAL Trial

Endocrine therapy; Neutropenia; Venous thromboembolismTerapia endocrina; Neutropenia; Tromboembolismo venosoTeràpia endocrina; Neutropènia; Tromboembolisme venósBackground Palbociclib has gained a central role in the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC). Despite its manageable toxicity profile, venous thromboembolism (VTE) or interstitial lung disease (ILD)/pneumonitis may infrequently occur. Therefore, we provide a comprehensive summary of the safety and tolerability of the combination of endocrine therapy and palbociclib among patients included in the randomized phase 2 PARSIFAL study. Materials and Methods Patients with endocrine-sensitive HR+/HER2- ABC and no prior therapy in an advanced setting (n = 486) were randomly assigned 1:1 to receive fulvestrant–palbociclib (FP) or letrozole–palbociclib (LP). Laboratory tests and the incidence of adverse events (AEs) were recorded at baseline and day 1 of each cycle. Progression-free survival (PFS) was estimated for patients with and without VTE. Results A total of 483 patients were analyzed. Neutropenia, leukopenia, anemia, asthenia, arthralgia, fatigue, and diarrhea were the most frequent AEs in both groups. Febrile neutropenia occurred in 3 (1.2%) patients of the FP group and in 1 (0.4%) patient in the LP group. Six (2.5%; 0.4% grade 3) patients in the FP group and 6 patients (2.5%; 0.4% grade 3) in the LP group experienced ILD/pneumonitis. Pulmonary embolism was reported in 12 (5.0%) patients in the FP group and 6 (2.5%) patients in the LP group. Advanced age at baseline was the only factor significantly associated with an increased risk of pulmonary embolism (P < .01). Conclusion The PARSIFAL data confirmed the favorable safety profile of both palbociclib regimens. VTE and ILD/pneumonitis were occasionally reported, and their early detection allowed patients to continue treatment effectively without detriment to efficacy.The PARSIFAL study was sponsored by Medica Scientia Innovation Research S.L. (MEDSIR) and funded by Pfizer, who had no role in the design and conduct of this study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Fulvestrant was provided by AstraZeneca

Synthesis of Combretastatin A-4 and 3 0 -Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tubulin and as Downregulators of the VEGF, hTERT and c-Myc Gene Expression

Natural product combretastatin A-4 (CA-4) and its nitrogenated analogue 3 0 -aminocombretastatin A-4 (AmCA-4) have shown promising antitumor activities. In this study, a range of CA-4 and AmCA-4 derivatives containing amino acid pendants have been synthesized in order to compare their biological actions with those of their parent compounds. Thus, inhibition of cell proliferation on tumor cell lines HT-29, MCF-7 and A-549, as well as on the nontumor cell line HEK-273; in vitro tubulin polymerization; mitotic cell arrest; action on the microtubule cell network and inhibition of VEGF, hTERT, and c-Myc genes have been evaluated. Some AmCA-4 derivatives bearing L-amino acids exhibited inhibition of cell proliferation at low nanomolar levels exceeding the values shown by AmCA-4. Furthermore, while CA-4 and AmCA-4 derivatives do not show significant effects on the in vitro tubulin polymerization and cell cycle arrest, some selected CA-4 and AmCA-4 derivatives are able to cause total depolymerization of the microtubule network on A-549 cells. The best results were obtained in the inhibition of gene expression, particularly on the VEGF gene, in which some AmCA-4 derivatives greatly exceeded the inhibition values achieved by the parent compound

Palbociclib Rechallenge for Hormone Receptor-Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial

Hormone receptor; Advanced breast cancerCàncer de mama avançat; Receptor hormonalCáncer de mama avanzado; Receptor hormonalPurpose: To assess the efficacy and exploratory biomarkers of continuing palbociclib plus endocrine therapy (ET) beyond progression on prior palbociclib-based regimen in patients with hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer (ABC). Patients and Methods: The multicenter, open-label, phase II BioPER trial included women who had experienced a progressive disease (PD) after having achieved clinical benefit on the immediately prior palbociclib plus ET regimen. Palbociclib (125 mg, 100 mg, or 75 mg daily orally for 3 weeks and 1 week off as per prior palbociclib-based regimen) plus ET of physician's choice were administered in 4-week cycles until PD or unacceptable toxicity. Coprimary endpoints were clinical benefit rate (CBR) and percentage of tumors with baseline loss of retinoblastoma (Rb) protein expression. Additional endpoints included safety and biomarker analysis. Results: Among 33 patients enrolled, CBR was 34.4% [95% confidence interval (CI), 18.6–53.2; P < 0.001] and 13.0% of tumors (95% CI, 5.2–27.5) showed loss of Rb protein expression, meeting both coprimary endpoints. Median progression-free survival was 2.6 months (95% CI, 1.8–6.7). No new safety signals were reported. A signature that included baseline mediators of therapeutic resistance to palbociclib and ET (low Rb score, high cyclin E1 score, ESR1 mutation) was independently associated with shorter median progression-free survival (HR, 22.0; 95% CI, 1.71–282.9; P = 0.018). Conclusions: Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients. A composite biomarker signature predicts a subset of patients who may not derive a greater benefit from palbociclib rechallenge, warranting further validation in larger randomized controlled trials.This work was supported by Pfizer. The authors would like to thank the patients, their caregivers, and their families for participating in this study and all investigators and site personnel. The BioPER study was conceived and designed by Medica Scientia Innovation Research (MEDSIR) in collaboration with Pfizer Inc., which funded the study and provided palbociclib. J. Albanell acknowledges CIBERONC CB16/12/00241, PI21/00002, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, Generalitat de Catalunya (2017 SGR 507)

Energy prices in Europe. Evidence of persistence across markets

This paper deals with the behavior of energy price changes and how their shocks exert an impact on suppliers and consumers in different markets. For this purpose, a fractional integration model is used to evaluate the persistence and mean reversion in prices across the major European markets (Germany, France, Italy, UK, Spain). We compare the results with other major players as the US and Japan, to understand, first, if the European behavior is different, and second, if geopolitical shocks that are affecting this market are expected to be permanent. Empirical results show evidence of mean reversion properties in European prices, though some minor differences arise from market to market that apparently, are not associated with the energy generation strategies followed by each country. Thus, it will likely be expected following the current energy shocks the series will recover due to natural market forces, without the need for additional policies

Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants

The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELISA, qPCR and Western blot. The highest EtOH concentration used stimulated a large increase in ROS levels, upregulating the cytochrome P450-2E1 (CYP2E1) and promoting cell death. The use of antioxidants such as N-acetylcysteine (NAC) and diallyl sulfide (DAS), which is also a CYP2E1 inhibitor, reverted cell death and oxidative stress, modulating also the upstream angiogenesis and inflammation regulators. Because oxidative stress plays a central role in most frequent ocular diseases, the results herein support the proposal that CYP2E1 upregulation could aggravate retinal degeneration, especially in those patients with high baseline oxidative stress levels due to their ocular pathology and should be considered as a risk factor.LVG was recipient of a pre-doctoral fellowship (EDUCV-PRE-2015-006). Financial support by grant #94/2016 from the PROMETEO program from the Generalitat Valenciana, Valencia, Spain, to FJR

The planetary nebula IC 4776 and its post-common-envelope binary central star

We present a detailed analysis of IC 4776, a planetary nebula displaying a morphology believed to be typical of central star binarity. The nebula is shown to comprise a compact hourglass-shaped central region and a pair of precessing jet-like structures. Time-resolved spectroscopy of its central star reveals periodic radial velocity variability consistent with a binary system. While the data are insufficient to accurately determine the parameters of the binary, the most likely solutions indicate that the secondary is probably a low-mass main sequence star. An empirical analysis of the chemical abundances in IC 4776 indicates that the common-envelope phase may have cut short the AGB evolution of the progenitor. Abundances calculated from recombination lines are found to be discrepant by a factor of approximately two relative to those calculated using collisionally excited lines, suggesting a possible correlation between low abundance discrepancy factors and intermediate-period post-common-envelope central stars and/or Wolf-Rayet central stars. The detection of a radial velocity variability associated with binarity in the central star of IC 4776 may be indicative of a significant population of (intermediate-period) post-common-envelope binary central stars which would be undetected by classic photometric monitoring techniques.Comment: Accepted for publication in MNRA

Experimental analysis of slabs foundation by scale models: lightweight slabs by expanded polystyrene blocks opposite solid slabs

El objetivo del presente artículo es confirmar el distinto comportamiento que presenta la solución tradicional de losa maciza frente a una aligerada, empleando bloques de poliestireno expandido (EPS) como material aligerante, uniéndose las zonas macizas bajo pilares mediante nervios. Se mantienen por tanto, dos placas, superior e inferior, alrededor de los bloques aligerantes de EPS. Para ello se ha realizado dos modelos a escala, sometiendo cada uno de ellos a una serie de ensayos. Esto se ha podido analizar comparativamente con otros modelos hechos en ordenador, empleando para ello programas de Elementos Finitos. Los resultados obtenidos permiten afirmar que, en situaciones de suelos blandos, con posibles problemas de asientos, la solución planteada presenta importantes ventajas, al disminuir esos asientos en un porcentaje que variará en función de las condiciones particulares. Además de esto, se reducen en gran medida los asientos diferenciales entre apoyos, por lo que la alternativa planteada presenta un comportamiento más uniforme, así como ventajas constructivas.The aim of this work is to confirm the different behavior of traditional solid slab versus lightened solution, using expanded polystyrene (EPS) blocks as a lightening material, joining solid areas under pillars with grating beams. Therefore there are two plates, one of them on the top and the other one on the bottom, covering the EPS blocks. For this purpose, two scale models have been performed, each of them being subjected to a series of tests. These have been able to comparatively analyze with models made in computer, using Finite Element programs. The results obtained allow us to assert that in situations of soft soils, with possible problems of settlements, the proposed solution has significant advantages by reducing this settlement on a percentage it will vary depending on specific conditions. Besides this, it significantly reduces the differential settlements among supports, so this alternative has a more uniform behavior, as well as constructive advantages