Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of daily co-occurrence of affect on older adults’ reactivity to health stressors

Objectives: The present study examined age differences among older adults in the daily co-occurrence of affect and its potential role in buffering the negative effects of health stressors. Design: Participants were from the Veterans Affairs Normative Aging Study and included 249 young-old adults (age = 60–79 years, M = 71.6) and 64 old-old adults (age = 80–89, M = 82.9) who completed questionnaires assessing stressors, physical health symptoms, and positive and negative affect for eight consecutive days. Results: An independent samples t-test showed young-old and old-old adults did not significantly differ in their mean levels of daily co-occurrence of affect. The between-person relationships among stressors, health and daily co-occurrence of affect revealed that neither stressors nor health were significantly related to daily co-occurrence of affect. However, results from a multilevel model revealed a three-way cross-level interaction (health stressor × age group × co-occurrence of affect) where old-old adults with higher levels of co-occurrence of affect were less emotionally reactive to health stressors than young-old adults. Conclusion: These findings provide support for the assertion that co-occurrence of affect functions in an adaptive capacity and highlight the importance of examining domain-specific stressors.
Autophagy, Myocardial Protection, and the Metabolic Syndrome

Abstract: Autophagy is a housekeeping process that helps to maintain cellular energy homeostasis and remove damaged organelles. In the heart, autophagy is an adaptive process that is activated in response to stress including acute and chronic ischemia. Given the evidence that autophagy is suppressed in energy-rich conditions, the objective of this review is to examine autophagy and cardioprotection in the setting of the metabolic syndrome. Clinical approaches that involve the induction of cardiac autophagy pharmacologically to enhance the heart's tolerance to ischemia are also discussed.
Graft outcomes influenced by co‐expression of Pax7 in graft and host tissue

Cell replacement therapies offer promise in the treatment of neurotrauma and neurodegenerative disorders and have concentrated on the use of primary fetal brain tissue. However, there is a growing promise of using neural stem cells, in which case other factors may be important in their successful engraftment. We therefore investigated whether the co‐expression of the major developmental transcription factor (Pax7 in this study) of donor tissue to graft site influences transplant survival and differentiation in the rat midbrain. Neural progenitor cells were prepared from either the Pax7‐expressing dorsal (DM) or non‐Pax7‐expressing ventral mesencephalon (VM) of embryonic EGFP+/+ rats. Cells were dissociated and grafted into the adult rat superior colliculus (SC) lesioned with quinolinic acid 3 days previously, a time shown to be associated with the up‐regulation of Pax7. Grafts were then examined 4 weeks later. Our results suggest the origin of the graft tissue did not alter graft survival in the SC; however, dorsal grafts appear to have a higher incidence of neuronal survival, whereas ventral grafts have a higher incidence of astrocytic survivors.
Measuring illness representations in breast cancer survivors (BCS) prescribed tamoxifen: Modification and validation of the Revised Illness Perceptions Questionnaire (IPQ-BCS)

Objective: The Revised Illness Perceptions Questionnaire (IPQ-R), widely used to assess illness perceptions, may fail to measure unique characteristics of different illnesses. This study modified and validated the IPQ-R for breast cancer survivors to provide detailed understanding of the specific illness perceptions held by these patients. Design: Initial modifications were made following qualitative interviews and were revised in a think-aloud study. The modified scale was tested in 753 breast cancer survivors prescribed tamoxifen. Modifications included adding a tamoxifen consequences scale and adapting the timeline scales to measure beliefs around risk of recurrence and cure. A confirmatory factor analysis was conducted on the modified questionnaire and an exploratory factor analysis on the causal beliefs scale. Test–retest reliability, internal consistency and construct validity were also examined. Results: The proposed eight-factor structure showed acceptable model fit, with high loadings and good reliability for all subscales. Correlations between subscales were consistent with theory and previous research. Conclusions: The IPQ-BCS is valid and reliable, and provides unique understanding of specific perceptions held by this population, including beliefs surrounding risk of recurrence and consequences of ongoing hormonal treatment. Identifying these perceptions will aid development of interventions targeting depression, fear of recurrence and medication non-adherence.
Influence of Simvastatin on the Thromboxane and Prostacyclin Pathways, In Vitro and In Vivo

Abstract: 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) are believed to exert beneficial effects against cardiovascular disease beyond correction of dyslipidemia. The aim of this combined in vitro and in vivo study was to investigate the influence of the commonly used simvastatin on prostacyclin and thromboxane A2, 2 prostaglandins with different cardiovascular effects, normally in homeostatic balance in the circulatory system. Single-dose administration of simvastatin significantly decreased urinary prostacyclin excretion of healthy volunteers (P < 0.01) and increased the ratio between thromboxane A2 and prostacyclin (2-fold increase, P < 0.01), as assessed by enzyme immunoassays of the corresponding metabolites in urine. Human vascular endothelial cells, exposed to corresponding concentrations of simvastatin and assayed in the same way, reduced the release of prostacyclin about 40% (P < 0.05), altered the transcriptional expression of cyclooxygenase and prostacyclin synthase as analyzed by real-time polymerase chain reaction, and reduced the prostacyclin synthase promoter activity by 50% (P < 0.05), evaluated in a luciferase reporter system. We speculate that simvastatin shifts the balance between thromboxane A2 and prostacyclin in favor of the thromboxane pathway in vivo, and after exposure to clinically relevant concentrations in vitro. This may have pathophysiological implications by promoting a prothrombotic state in the blood vessels.
Developing and validating a theoretical measure of modifiable influences on hormonal therapy medication taking behaviour in women with breast cancer

Objective: Taking adjuvant hormonal therapy for 5–10 years is recommended to prevent breast cancer recurrence in those with oestrogen positive disease. Despite proven clinical efficacy many women do not take their hormonal therapy as prescribed. This study reports the development and initial validation of a questionnaire measuring the behavioural determinants of hormonal therapy medication taking behaviour (MTB) based on the theoretical domains framework (TDF). Design: Women with Stage I-III breast cancer (N = 223) completed the questionnaire based on the TDF. The TDF is an integrative framework consisting of 14 domains of behaviour change determinants to inform intervention design. Main outcome measures: Items were developed from previous research, in-depth patient interviews and consultation with health professionals. Confirmatory factor analysis (CFA) was undertaken to generate the model of best fit. Results: The final questionnaire consisted of eight domains and CFA produced a reasonable fit (χ2(810) = 942, p < . 001; RMSEA = . 03; CFI = . 93 and WRMR = . 91) as well as internal consistency (r = .16 to .64). There were adequate levels of discriminant validity for the majority of the domains. Conclusions: A TDF-based measure of the behavioural determinants of MTB was developed. Further research is needed to confirm the reliability and validity of this measure.
Functional and RNA Expression Profile of Adenosine Receptor Subtypes in Mouse Mesenteric Arteries

Abstract: Concentration–response curves (CRCs) of adenosine receptor (AR) agonists, NECA (nonspecific), CCPA (A1 specific), CGS-216870 (A2A specific), BAY 60-6583 (A2B specific), and Cl-IB-MECA (A3 specific) for mesenteric arteries (MAs) from 4 AR knockout (KO) mice (A1, A2A, A2B, and A3) and their wild type (WT) were constructed. The messenger RNA expression of MAs from KO mice and WT were also studied. Adenosine (10−5 to 10−4 M) and NECA (10−6 to 10−5 M) induced relaxation in all mice except A2B KO mice, which only showed constriction by adenosine at 10−6 to 10−4 and NECA at 10−8 to 10−5 M. The CCPA induced a significant constriction at 10−8 and 10−7 M in all mice, except A1KO. BAY 60-6583 induced relaxation (10−7 to 10−5 M) in WT and no response in A2BKO except at 10−5 M. The CRCs for BAY 60-6583 in A1, A2A, and A3 KO mice shifted to the left when compared with WT mice, suggesting an upregulation of A2B AR. No responses were noted to CGS-21680 in all mice. Cl-IB-MECA only induced relaxation at concentration greater than 10−7 M, and no differences were found between different KO mice. The CRC for Bay 60-6583 was not significantly changed in the presence of 10−5 M of L-NAME, 10−6 M of indomethacin, or both. Our data suggest that A2B AR is the predominant AR subtype and the effect may be endothelial independent, whereas A1 AR plays a significant modulatory role in mouse MAs.
The mediating and moderating role of planning on mothers’ decisions for early childhood dietary behaviours

Objective: Examine the roles of action and coping planning on the intention–behaviour relationship for mothers’ decisions for their young children’s dietary behaviours. Design: Prospective design with two waves of data collection, one week apart. Main outcome measures: Mothers (N = 197, Mage = 34.39, SD = 5.65) of children aged 2–3 years completed a main questionnaire assessing planning constructs and intentions, and a one-week follow-up of the target behaviours – ‘healthy eating’ and ‘discretionary choices’. Results: Intention was the strongest predictor of behaviour for both dietary behaviours. For healthy eating, intention moderated the indirect relationship between intention–behaviour via planning; coping planning was less important when intention was strong. Further, intention was not a direct predictor of behaviour when intention was relatively low. Action planning was not a direct predictor of either behaviour after accounting for intention and coping planning; action planning on behaviour was mediated by coping planning (only for healthy eating). Intention was not a direct predictor of coping planning; intention on coping planning was mediated by action planning. Neither type of planning predicted discretionary choices. Conclusion: Current findings contribute novel information on the mechanisms underpinning the effect of action and coping planning on the intention–behaviour relationship.
Inner ear of a notoungulate placental mammal: anatomical description and examination of potentially phylogenetically informative characters

We provide the first detailed description of the inner ear of a notoungulate, an extinct group of endemic South American placental mammals, based on a three‐dimensional reconstruction extracted from CT imagery of a skull of Notostylops murinus. This description provides new anatomical data that should prove to be phylogenetically informative, an especially significant aspect of this research given that both the interrelationships of notoungulates and the position of Notoungulata within Placentalia are still unresolved. We also assess the locomotor agility of Notostylops based on measurements of the semicircular canals. This is the best available data on the locomotion of a notostylopid because significant postcranial remains for this group have not been described. The cochlea of Notostylops has 2.25 turns, and the stapedial ratio is 1.6. The stapedial ratio is one of the lowest recorded for a eutherian, which typically have ratios greater than 1.8. The fenestra cochleae is located posterior to the fenestra vestibuli, a condition previously only reported for some stem primates. The separation of the saccule and utricule of the vestibule is visible on the digital endocast of the bony labyrinth. The posterior arm of the LSC and the inferior arm of the PSC are confluent, but these do not form a secondary crus commune, and the phylogenetic or functional significance of this confluence is unclear at this time. Locomotor agility scores for Notostylops suggest a medium or ‘average’ degree of agility of motion compared to extant mammals. In terms of its locomotion, we tentatively predict that Notostylops was a generalized terrestrial mammal, with cursorial tendencies, based on its agility scores and the range of locomotor patterns inferred from postcranial analyses of other notoungulates.
I’m still standing: A longitudinal study on the effect of a default nudge

Objective: This study assessed the effect of a default nudge to reduce sedentary behaviour at work over time. Design and main outcome measures: A field study was conducted at a governmental organisation. In the present study, the default setting of sit–stand desks (SSDs) was changed from sitting to standing height during a two-week intervention. Stand-up working rates were calculated based on observations that were done prior to, during, two weeks after and two months after the intervention. Additionally, a pre-measure survey (n = 606) and post-measure survey (n = 354) were completed. Intention and social norms concerning stand-up working were compared for the 183 employees who completed both pre- and post-assessments (45.4% female, Mage = 44.21). Results: Stand-up working rates raised from 1.82% in the baseline to 13.13% during the intervention. After the nudge was removed the percentage was 10.01% after two weeks and 7.78% after two months. A multilevel analysis indicated a significant increase in both intention and social norms after the nudge intervention. Conclusions: This study shows that a default nudge can increase stand-up working rates in offices with SSDs at least until two months after the nudge intervention.
POSTTRAUMATIC STRESS DISORDER AND RISK FACTORS IN PARENTS OF CHILDREN WITH A CANCER DIAGNOSIS

The purpose of this study was to determine the prevalence of posttraumatic stress disorder (PTSD) in parents of children with cancer. Five questionnaires were administered to 104 parents, including a sociodemographic questionnaire, a traumatic events check list, the Structured Clinical Interview for DSM-IV PTSD and Major Depressive Disorder modules, and the self-rating instrument General Health Questionnaire-12. The prevalence of PTSD was 34.6%. The statistically significant tendency to develop PTSD were found in the female gender, better educational status, death of a loved one, previous history of psychiatric disorder, having a child with poorer prognosis, and the presence of radiotherapy in child's treatment. The vulnerable parents must receive psychosocial support.
Stereological assessment of pancreatic beta‐cell mass development in male Zucker Diabetic Fatty (ZDF) rats: correlation with pancreatic beta‐cell function

The present study was initiated to improve our understanding of pancreatic beta‐cell dynamics in male Zucker Diabetic Fatty (ZDF) rats and hence provide a framework for future diabetes studies in this animal model. Male ZDF rats from 6, 8, 10, 12, 14, 16, 20 and 26 weeks of age were subjected to an oral glucose tolerance test (OGTT). The animals were then euthanized and pancreases were removed for morphometric analyses of pancreatic beta‐cell mass. As evident by a marked fourfold increase in insulin secretion, insulin resistance developed rapidly from 6 to 8 weeks of age. Simultaneously, the pancreatic beta‐cell mass expanded from 6.17 ± 0.41 mg at 6 weeks of age, reaching a maximum of 16.5 ± 2.5 mg at 16 weeks of age, at which time pancreatic beta‐cell mass gradually declined. The corresponding changes in glucose/insulin homeostasis were analysed using a standard insulin sensitivity index (ISI), an area under the curve (AUC) glucose‐insulin index, or simple semi‐fasted glucose levels. The study demonstrated that male ZDF rats underwent rapid changes in pancreatic beta‐cell mass from the onset of insulin resistance to frank diabetes coupled directly to marked alterations in glucose/insulin homeostasis. The study underscores the need for a critical co‐examination of glucose homeostatic parameters in studies investigating the effects of novel anti‐diabetic compounds on pancreatic beta‐cell mass in the male ZDF rat. A simple assessment of fasting glucose levels coupled with information about age can provide a correct indication of the actual pancreatic beta‐cell mass and the physiological state of the animal.
Myocardial Postconditioning Is Lost in Vascular Nitrate Tolerance

Abstract: Organic nitrates play an important role in the therapy of ischemic heart disease; however, their clinical application is limited by the development of vascular nitrate tolerance. We have previously shown attenuation of the cardioprotective effect of preconditioning in vascular nitrate tolerance. Here, we studied whether the development of vascular nitrate tolerance affects the infarct size, limiting effect of ischemic postconditioning (IPost) in the myocardium, and whether the activation of survival kinases plays a role in the molecular mechanism of postconditioning in the presence or absence of vascular nitrate tolerance. Male Wistar rats were treated with nitroglycerin/vehicle for 3 days to induce vascular nitrate tolerance. On the fourth day, isolated hearts were subjected to 30-minute coronary occlusion followed by 120-minute reperfusion with or without IPost. In nontolerant hearts, postconditioning significantly decreased infarct size as compared with ischemia/reperfusion; however, postconditioning failed to decrease infarct size in hearts of nitrate tolerant rats. Phosphorylation of ERK 1/2, Akt, or endothelial nitric oxide synthetase showed no significant differences between the groups at the 10th minute of reperfusion. Vascular nitrate tolerance interferes with the infarct size limiting effect of IPost. Activation of survival kinases is not crucial in the molecular mechanism of postconditioning, which remains unaffected in nitrate tolerance.
ALLOGENEIC HEMOPOIETIC STEM CELL TRANSPLANTATION FOR CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN SECOND COMPLETE REMISSION—Similar Outcomes After Matched Related and Unrelated Donor Transplant: A Study of the Spanish Working Party for Blood and Marrow Transplantation in Children (Getmon)

The authors report the results of 58 children with ALL in 2CR after related (n = 31) or unrelated (n = 27) AHSCT. Characteristics at diagnosis and initial and after relapse antileukemic treatment were similar in the related donor (RD) and the unrelated donor (UD) groups. Conditioning consisted of TBI/CY ± VP-16 for patients ≥3 years old (n = 43) and Bu/CY for the rest. Median recipient age was 8 years (range 1–17) in the RD and 9 years (range 3–14) in the UD group. Median follow-up was 54 months (range 24–80) and 52 months (range 22–85) in the RD and the UD groups repectively.The 5-year EFS probability was 43 ± 9% for the RD group and 36 ± 9% in the UD group (p =. 25). The transplant-related mortality was 16% in the RD and 37% in the UD group (p =. 016). In the RD group 36.7% of patients relapsed versus 18.6% in the UD group (p =. 05). GvHD associated with organ failure or infection caused most of the transplant-related deaths in both groups. Survivor quality of life for both groups was good (Lansky score ≤ 90).
Progress in Gene Therapy for Heart Failure

Abstract: Recent advances in our understanding of the pathophysiology of myocardial dysfunction in the setting of congestive heart failure have created a new opportunity in developing nonpharmacological approaches to treatment. Gene therapy has emerged as a powerful tool in targeting the molecular mechanisms of disease by preventing the ventricular remodeling and improving bioenergetics in heart failure. Refinements in vector technology, including the creation of recombinant adeno-associated viruses, have allowed for safe and efficient gene transfer. These advancements have been coupled with evolving delivery methods that include vascular, pericardial, and direct myocardial approaches. One of the most promising targets, SERCA2a, is currently being used in clinical trials. The recent success of the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease phase 2 trials using adeno-associated virus 1-SERCA2a in improving outcomes highlights the importance of gene therapy as a future tool in treating congestive heart failure.
The implications for patients undergoing splenectomy: postsurgery risk management

Splenectomy has been performed for a heterogeneous group of hematologic diseases with a therapeutic or diagnostic purpose or as part of the staging process in Hodgkin's disease. Most patients undergoing therapeutic splenectomy are chronically ill with significant splenomegaly. This scenario can be associated with a high risk of postoperative morbidity and mortality due to the prolonged course of disease for patients with myelofibrosis; their susceptibility to infection, thrombosis, and hemorrhage; and the severe enlargement of their spleens. We have reviewed the main papers published about postoperative complications after splenectomy, analyzing the risk factors, prevention measures, and respective treatments. Great care must be taken in the management of patients presenting malignant diseases, splenomegaly, and hemostasis disorder. Moreover, despite the faster discharge that new surgical techniques now allow, close attention should be paid to symptoms reported by patients, in order to avoid potentially life-threatening complications such as portal vein thrombosis, pancreas injuries, and overwhelming postsplenectomy infection.
Identification of genetic variants associated with capecitabine-induced hand–foot syndrome through integration of patient and cell line genomic analyses

Objective A primary challenge in identifying replicable pharmacogenomic markers from clinical genomewide association study (GWAS) trials in oncology is the difficulty in performing a second large clinical trial with the same drugs and dosage regimen. We sought to overcome this challenge by incorporating GWAS results from cell-based studies using the same chemotherapy as a clinical cohort. Methods In this study, we test whether the overlap between genetic variants identified in a preclinical study and a clinical study on capecitabine is more than expected by chance. A GWAS of capecitabine-induced cytotoxicity was performed in 164 lymphoblastoid cell lines derived from the CEU HapMap population and compared with a GWAS of hand–foot syndrome (HFS), the most frequent capecitabine-induced adverse drug reaction, in Spanish breast and colorectal cancer patients (n=160) treated with capecitabine. Results We observed an overlap of 16 single nucleotide polymorphisms associated with capecitabine-induced cytotoxicity (P<0.001) in lymphoblastoid cell lines and HFS (P<0.05) in patients, which is a greater overlap than expected by chance (genotype–phenotype permutation empirical P=0.015). Ten tag single nucleotide polymorphisms, which cover the overlap loci, were genotyped in a second patient cohort (n=85) and one of them, rs9936750, was associated with capecitabine-induced HFS (P=0.0076). Conclusion The enrichment results imply that cellular models of capecitabine-induced cytotoxicity may capture components of the underlying polygenic architecture of related toxicities in patients.