Switching people who smoke to unfiltered cigarettes: Effects on smoking topography.

Introduction: Smoking topography (ST) describes smoking behavior and patterns. Removal of the cigarette filter and subsequent impact on ST has not been investigated. This is the first clinical trial comparing ST for filtered and unfiltered cigarettes in a naturalistic experiment. Methods: We conducted a crossover clinical trial following established people who smoke cigarettes (n = 32) for two weeks under filtered and unfiltered smoking experimental conditions. Participants (50 % female, mean age 38.3 yr.) smoked in each experimental condition followed by a 3-week post-washout period. ST (puff count, volume, duration, peak and average flow) was measured at six time-points. Statistical analysis included a linear repeated mixed-effects model of smoking experimental conditions by visit number and sex. Results: Average flow (ml/sec) was significantly less for filtered smoking (-6.92 lower (95 % CI: -13.44 to -0.39), p < 0.05), thus demonstrating more resistance on inhalation. No significant differences were found between filtered or unfiltered experimental conditions for other ST variables. However, average volume and average peak flow were somewhat higher in unfiltered smoking, and lower mean puff counts/cigarette were observed for unfiltered compared to filtered smoking. Conclusion: Lower average flow rates were associated with filtered cigarette smoking. No significant differences were found for other ST variables between smoking experimental conditions. ST measurements comparing cigarette smoking conditions may determine if product regulatory changes, such as removing the cigarette filter could impact smoking behavioral patterns among people who smoke. This proof-of-principle study measuring ST may be replicated in larger trials to determine potential behavioral changes in smoking unfiltered cigarettes.

Biphasic Kinetics of IGF-I and IGFBP-3 in Response to Military Field Training in Brazilian Air Force Recruits.

INTRODUCTION: Insulin-like growth factor type I (IGF-I) has gained considerable notoriety in military training, primarily because it is responsible for energy deficits and sensitive to an inadequate protein intake, which are situations that are commonly experienced in specific military operations. Therefore, this study aimed to assess the kinetics of IGF-I and insulin-like growth factor binding protein type 3 (IGFBP-3) in a 4-day military field training exercise. MATERIALS AND METHODS: The sample comprised 12 male soldiers (21.71 ± 1.64 years). Changes were assessed at 3 times: time 1-basal (control week); time 2-after specific military field training; and time 3-1 week after the specific training (control week). Changes in body composition and serum levels of IGF-I and IGFBP-3 were observed. RESULTS: The main finding of this study was it verified the biphasic kinetics of both IGF-I and IGFBP-3 at the 3 times observed, that is, a significant drop from time 1 (basal-IGF-I: 189 ng/mL and IGFBP-3: 4.71 mg/L) to time 2 (immediately after military training-IGF-I: 162 ng/mL and IGFBP-3: 4.08 mg/L) and a subsequent recovery of these markers, with a significant increase from time 2 (immediately after military training) to time 3 (a week after military training-IGF-I: 199 ng/mL and IGFBP-3: 4.96 mg/L). CONCLUSIONS: It can be concluded that IGF-I and IGFBP-3 levels respond quickly to the stimuli caused by military training, especially after specific field training. However, the same markers quickly return to their basal values after this type of training finishes, simply by following the daily routine of the battalion in the control weeks, with no specific intervention being necessary.

Blood pressure variability supersedes heart rate variability as a real-world measure of dementia risk.

Blood pressure variability (BPV) and heart rate variability (HRV) have been associated with Alzheimer's Disease and Related Dementias (ADRD) in rigorously controlled studies. However, the extent to which BPV and HRV may offer predictive information in real-world, routine clinical care is unclear. In a retrospective cohort study of 48,204 adults (age 54.9 ± 17.5 years, 60% female) receiving continuous care at a single center, we derived BPV and HRV from routinely collected clinical data. We use multivariable Cox models to evaluate the association of BPV and HRV, separately and in combination, with incident ADRD. Over a median 3 [2.4, 3.0] years, there were 443 cases of new-onset ADRD. We found that clinically derived measures of BPV, but not HRV, were consistently associated with incident ADRD. In combined analyses, only patients in both the highest quartile of BPV and lowest quartile of HRV had increased ADRD risk (HR 2.34, 95% CI 1.44-3.81). These results indicate that clinically derived BPV, rather than HRV, offers a consistent and readily available metric for ADRD risk assessment in a real-world patient care setting. Thus, implementation of BPV as a widely accessible tool could allow clinical providers to efficiently identify patients most likely to benefit from comprehensive ADRD screening.

Characterization of Individuals With Apparent Resistant Hypertension Using Contemporary Guidelines: Insights From CV-QUIC.

BACKGROUND: Apparent resistant hypertension (aRH) carries excess cardiovascular risk beyond nonresistant forms of hypertension; however, our understanding of this at-risk population, as defined by current US practice guidelines, is limited. Accordingly, we sought to evaluate the prevalence, clinical characteristics, and pharmacotherapeutic patterns of patients with aRH using contemporary blood pressure guidance. METHODS: We classified patients at 3 large healthcare systems by hypertensive status using contemporary hypertension guidelines. We subsequently described the demographic and clinical characteristics of patients with aRH and compared these factors among hypertensive patients without aRH and between those with controlled and uncontrolled aRH. RESULTS: A total of 2 420 468 patients were analyzed, of whom 1 343 489 (55.6%) were hypertensive according to contemporary guidelines. Among hypertensive patients, 11 992 (8.5%) met criteria for aRH, with nearly all assessed comorbid conditions, particularly diabetes and heart failure, being more common in those with aRH. When compared with patients with uncontrolled aRH, those with controlled aRH were more frequently prescribed a beta-blocker, diuretic, and nitrate, with the largest standardized difference observed for a mineralocorticoid receptor antagonist (35.4% versus 10.4%, Cohen D 0.62). Consistent findings were noted in sensitivity analyses using the blood pressure threshold of 140/90 mm Hg. CONCLUSIONS: In an analysis of over 2.4 million individuals, a lower prevalence of aRH was observed than previously reported (12%-15%), but with a high burden of comorbidities. Identification of differences in pharmacotherapy between patients with controlled and uncontrolled aRH, particularly lower rates of mineralocorticoid receptor antagonist use, help define potential opportunities to improve care and lower cardiovascular risk.

Changing positive and negative affects through music experiences: a study with university students.

BACKGROUND: Currently, there are few empirical studies that demonstrate the effects of music on specific emotions, especially in the educational context. For this reason, this study was carried out to examine the impact of music to identify affective changes after exposure to three musical stimuli. METHODS: The participants were 71 university students engaged in a music education course and none of them were musicians. Changes in the affective state of non-musical student teachers were studied after listening to three pieces of music. An inter-subject repeated measures ANOVA test was carried out using the Positive and Negative Affect Schedule (PANAS) to measure their affective state. RESULTS: The results revealed that: (i) the three musical experiences were beneficial in increasing positive affects and reducing negative affects, with significant differences between the interaction of Music Experiences × Moment (pre-post); (ii) listening to Mahler's sad fifth symphony reduced more negative affects than the other experimental conditions; (iii) performing the blues had the highest positive effects. CONCLUSIONS: These findings provide applied keys aspects for music education and research, as they show empirical evidence on how music can modify specific affects of personal experience.

Switching people who smoke to unfiltered cigarettes: perceptions, addiction and behavioural effects in a cross-over randomised controlled trial.

BACKGROUND: Behavioural research is needed to inform a ban on sales of filtered cigarettes that could reduce plastic waste due to discarded filters. This study reports on differences in perceptions, nicotine dependence and behaviour among participants in a cross-over randomised trial of filtered compared with unfiltered cigarettes. METHOD: This proof-of-concept study involved 43 people who smoke filtered cigarettes (41.9% women, mean age 36.7 years). Participants were provided 2 weeks' supply of filtered cigarettes, 2 weeks of the same brand of unfiltered cigarettes and randomly assigned to starting conditions. Measures included the Modified Cigarette Evaluation Questionnaire; single-item cigarette perception questions; Fagerström Test of Nicotine Dependence; 7-day cigarette consumption, urinary cotinine and intention to quit. Analyses included linear and ordinal repeated measures mixed-effects models and paired t-tests. RESULTS: Filtered cigarettes were perceived as better tasting, more satisfying, more enjoyable, less aversive, less harsh, less potent and less negatively reinforcing than unfiltered cigarettes. Filtered cigarettes were smoked at a higher rate during the trial than unfiltered cigarettes (p<0.05). There was no difference in cotinine, dependence or intention to quit between filtered versus unfiltered cigarette conditions (p>0.05). CONCLUSION: People who smoke perceived unfiltered cigarettes as having greater nicotine effects and less desirable sensory effects than filtered cigarettes, and they smoked fewer of these during the trial. Although cotinine, dependence and intention to quit were similar for smoking unfiltered and filtered cigarettes in this small trial, results suggest that banning the sale of filtered cigarettes might make smoking less attractive overall to people who smoke. TRIAL REGISTRATION NUMBER: NCT03749876.

Serum Hormone Concentrations and Body Composition in Brazilian Air Force Cadets During Rainforest Survival Training.

BACKGROUND: Physiological adaptations in military jungle survival training have not yet been studied. Knowledge about the relationship between the insulin-like growth factor type I (IGF-I)/insulin-like growth factor binding protein type 3 (IGFBP-3) system and survival activities in a jungle environment can improve readiness and prepare Brazilian Air Force cadets for this kind of battlefield. Our goal was to assess changes in body composition and serum concentrations of the IGF-I/IGFBP-3 system in Brazilian Air Force cadets during five-day Amazon rainforest survival training and whether differences in sex influence these variations. METHODS: In the five-day survival training, variations in body composition and serum levels of IGF-I and IGFBP-3 were observed. The sample consisted of 14 male cadets (21.71 ± 1.64 years) and 6 female cadets (22.00 ± 1.41 years). Changes were assessed before and immediately after the survival training. RESULTS: The male cadets' body mass (pre: 73.89 ± 8.79 kg; post: 69.57 ± 8.44 kg), body fat (pre: 11.43 ± 4.15%; post: 10.16 ± 4.19%), IGF-I serum concentrations (pre: 252 ± 72 ng/mL; post: 140 ± 42 ng/mL), and IGFBP-3 serum concentrations (pre: 4.90 ± 0.67 ng/mL; post: 4.22 ± 0.73 ng/mL) were significantly reduced (P < .01). In the female cadets, the mean body mass values (pre: 60.98 ± 8.82 kg; post: 57.91 ± 9.01 kg), body fat (pre: 19.20 ± 5.03%; post: 17.19 ± 4.77%), and IGF-I serum concentrations (pre: 202 ± 50 ng/mL; post: 108 ± 29 ng/mL) also decreased significantly (P < .01) after survival training. Finally, the cadet's sex does not affect the variations of IGF-I (P = .46) and IGFBP-3 (P = .205) serum concentrations. CONCLUSIONS: These findings all suggest that changes in body mass and body fat, as well as variations in the IGF-I/IGFBP-3 system, corroborate the need for military readiness preparation. Equivalent changes in both sexes indicate probable equal recovery intervals after survival training.

Apolipoprotein L1 (APOL1) cation current in HEK-293 cells and in human podocytes.

Two heterozygous missense variants (G1 and G2) of Apolipoprotein L1 (APOL1) found in individuals of recent African ancestry can attenuate the severity of infection by some forms of Trypanosoma brucei. However, these two variants within a broader African haplotype also increase the risk of kidney disease in Americans of African descent. Although overexpression of either variant G1 or G2 causes multiple pathogenic changes in cultured cells and transgenic mouse models, the mechanism(s) promoting kidney disease remain unclear. Human serum APOL1 kills trypanosomes through its cation channel activity, and cation channel activity of recombinant APOL1 has been reconstituted in lipid bilayers and proteoliposomes. Although APOL1 overexpression increases whole cell cation currents in HEK-293 cells, the ion channel activity of APOL1 has not been assessed in glomerular podocytes, the major site of APOL1-associated kidney diseases. We characterize APOL1-associated whole cell and on-cell cation currents in HEK-293 T-Rex cells and demonstrate partial inhibition of currents by anti-APOL antibodies. We detect in primary human podocytes a similar cation current inducible by interferon-γ (IFNγ) and sensitive to inhibition by anti-APOL antibody as well as by a fragment of T. brucei Serum Resistance-Associated protein (SRA). CRISPR knockout of APOL1 in human primary podocytes abrogates the IFNγ-induced, antibody-sensitive current. Our novel characterization in HEK-293 cells of heterologous APOL1-associated cation conductance inhibited by anti-APOL antibody and our documentation in primary human glomerular podocytes of endogenous IFNγ-stimulated, APOL1-mediated, SRA and anti-APOL-sensitive ion channel activity together support APOL1-mediated channel activity as a therapeutic target for treatment of APOL1-associated kidney diseases.

Electronic cigarette use and perceptions during COVID-19.

This study was designed to examine how the COVID-19 pandemic changed e-cigarette user habits and risk perceptions. A nationally distributed 52-item questionnaire assessed nicotine e-cigarette use, perceptions, COVID-19 diagnosis, demographic data, and vaping habits among respondents aged 16-96 years (n = 565). Questions were developed in-house to assess vaping habits of users and risk perceptions of nicotine containing e-cigarette users and non-users both before and during the COVID-19 pandemic. Seventy-six percent of non-users believed that e-cigarette use would lead to worse COVID-19 symptoms, compared to 40% of e-cigarette users (P < 0.001). Twenty-eight percent of non-users also believed that e-cigarette users were more likely to be infected with SARS-CoV-2, versus 11% of e-cigarette users (P < 0.001). Fifty-eight percent of e-cigarette users described themselves as making no change in their e-cigarette usage, 10% decreased e-cigarette use, and 32% increased e-cigarette use during the pandemic. Twenty-five percent of users switched to vaping non-socially during the pandemic (P < 0.001). Sixty-seven percent of e-cigarette users replied that they would decrease or stop vaping if diagnosed with COVID and 31% said they would continue (P < 0.001). These findings reveal there are large differences in risk perception of e-cigarette use between users and non-users. Additionally, our findings characterize the habits of e-cigarette users during the COVID-19 pandemic, revealing users report steady to increased use, more caution in social settings, and would reduce usage if diagnosed with COVID-19.

DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk Variants.

BACKGROUND: Two variants in the gene encoding apolipoprotein L1 (APOL1) that are highly associated with African ancestry are major contributors to the large racial disparity in rates of human kidney disease. We previously demonstrated that recruitment of APOL1 risk variants G1 and G2 from the endoplasmic reticulum to lipid droplets leads to reduced APOL1-mediated cytotoxicity in human podocytes. METHODS: We used CRISPR-Cas9 gene editing of induced pluripotent stem cells to develop human-derived APOL1G0/G0 and APOL1G2/G2 kidney organoids on an isogenic background, and performed bulk RNA sequencing of organoids before and after treatment with IFN-γ. We examined the number and distribution of lipid droplets in response to treatment with inhibitors of diacylglycerol O-acyltransferases 1 and 2 (DGAT1 and DGAT2) in kidney cells and organoids. RESULTS: APOL1 was highly upregulated in response to IFN-γ in human kidney organoids, with greater increases in organoids of high-risk G1 and G2 genotypes compared with wild-type (G0) organoids. RNA sequencing of organoids revealed that high-risk APOL1G2/G2 organoids exhibited downregulation of a number of genes involved in lipogenesis and lipid droplet biogenesis, as well as upregulation of genes involved in fatty acid oxidation. There were fewer lipid droplets in unstimulated high-risk APOL1G2/G2 kidney organoids than in wild-type APOL1G0/G0 organoids. Whereas DGAT1 inhibition reduced kidney organoid lipid droplet number, DGAT2 inhibition unexpectedly increased organoid lipid droplet number. DGAT2 inhibition promoted the recruitment of APOL1 to lipid droplets, with associated reduction in cytotoxicity. CONCLUSIONS: Lipogenesis and lipid droplet formation are important modulators of APOL1-associated cytotoxicity. Inhibition of DGAT2 may offer a potential therapeutic strategy to attenuate cytotoxic effects of APOL1 risk variants.

The Effect of Corrective Feedback in Basic Cognitive Tasks: A Study in Early Childhood.

The aim of this study was to examine the effect of trial-by-trial corrective feedback in a go-no-go task for children. A sample of 40 preschool students, divided into 4- and 5-year-olds, participated in the study, as well as a group of 20 university students. All the groups performed the task in a counterbalanced design of blocks with and without corrective feedback. Reaction time and accuracy rate were measured as dependent variables. Moreover, reaction time was also analyzed through an ex-Gaussian fit. Children were slightly more accurate and slower under the presence of corrective feedback, suggesting a more conservative pattern. University students were faster, but corrective feedback did not reach the statistical level. Regarding reaction time components, a reduction of the distribution tails, depicted by the τ parameter, was found for both groups under the corrective feedback condition. This suggests that parameterization of reaction time can be considered as a strategy for a more detailed analysis to examine the effect of corrective feedback, even at early ages. In this way, corrective feedback depicted beneficial effects in the τ parameter at early ages, suggesting its use in basic cognitive tasks based on go-no-go but not for older groups.

The Moderation Effects of Comparative Thinking Between Gratitude and Negative Affect During the COVID-19 Outbreak.

The aim of this research was to examine the moderation effects of comparative thinking (CT) across the relationship between gratitude and affect during the COVID-19 outbreak. To this purpose, multiple regression as well as moderation analyses were carried out. Age and sex were also addressed as variables of interest as described in previous literature. A sample of 306 north Americans was recruited by crowdsourcing platform ProA to obtain a representative sample based on age and gender. The participants filled in a questionnaire based on comparative thinking in relation to the emotional experience experienced before and during the COVID-19 outbreak, positive and negative affect schedule for positive and negative affect, as well as Gratitude Questionnaire - Six Items Form scores for gratitude. The main results of the current study related to the COVID-19 outbreak can be listed as follows: (i) no differences between CT groups in the gratitude trait, but differences in positive and negative affect did occur; (ii) regression models that included age, gratitude, and affect variables predicted negative and positive affects but gender did not reach the statistical level; (iii) two moderation models predicted affect from gratitude, with the CT variable moderating this effect; this moderation effect was also statistically significant in predicting negative affect but it was not statistically significant in predicting positive affect. These results might be of interest for training programs in applied levels and theoretical models of gratitude.

Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease.

People of recent sub-Saharan African ancestry develop kidney failure much more frequently than other groups. A large fraction of this disparity is due to two coding sequence variants in the APOL1 gene. Inheriting two copies of these APOL1 risk variants, known as G1 and G2, causes high rates of focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy and hypertension-associated end-stage kidney disease. Disease risk follows a recessive mode of inheritance, which is puzzling given the considerable data that G1 and G2 are toxic gain-of-function variants. We developed coisogenic bacterial artificial chromosome (BAC) transgenic mice harboring either the wild-type (G0), G1 or G2 forms of human APOL1. Expression of interferon gamma (IFN-γ) via plasmid tail vein injection results in upregulation of APOL1 protein levels together with robust induction of heavy proteinuria and glomerulosclerosis in G1/G1 and G2/G2 but not G0/G0 mice. The disease phenotype was greater in G2/G2 mice. Neither heterozygous (G1/G0 or G2/G0) risk variant mice nor hemizygous (G1/-, G2/-) mice had significant kidney injury in response to IFN-γ, although the heterozygous mice had a greater proteinuric response than the hemizygous mice, suggesting that the lack of significant disease in humans heterozygous for G1 or G2 is not due to G0 rescue of G1 or G2 toxicity. Studies using additional mice (multicopy G2 and a non-isogenic G0 mouse) supported the notion that disease is largely a function of the level of risk variant APOL1 expression. Together, these findings shed light on the recessive nature of APOL1-nephropathy and present an important model for future studies.

Effects of the Educational Use of Music on 3- to 12-Year-Old Children's Emotional Development: A Systematic Review.

Interest in the study of emotions in education has grown in recent years. Some of our modern challenges, such as constantly adapting to new scenarios or the need for team work have justified the introduction of emotional competence into educational systems, while diverse studies confirm the relationship between music and emotional intelligence, so that the former could be used as a tool to develop the latter. The aim of this work was to examine the evidence for positive effects of music on the emotions of 3- to 12-year-old children, to which end a systematic review was carried out. Two reviewers independently evaluated 424 studies that were identified in MEDLINE, Psycinfo, and CINAHL databases, in order to determine whether they met the stated inclusion criteria. A total of 26 articles were selected for review. The results suggest several beneficial effects of music on children's development, such as greater emotional intelligence, academic performance, and prosocial skills. It can therefore be concluded that music should be used in school settings, not only as an important subject in itself, but also as an educational tool within other subjects.

Gratitude Questionnaire-20 Items (G20): A Cross-Cultural, Psychometric and Crowdsourcing Analysis.

The use in psychology of crowdsourcing platforms as a method of data collection has been increasing in popularity because of its relative ease and versatility. Our goal is to adapt the Gratitude Questionnaire-20 Items (G20) to the English language by using data collected through a crowdsourcing platform. The G20 is a comprehensive instrument that takes in consideration the different basic processes of gratitude and assesses the construct's cognitive, evaluative, emotional, and behavioral processes. We test the psychometric properties of the English version of the G20 with a Prolific (ProA) user sample. We assess the adequacy of the G20 for the crowdsourcing population in its English version. A description of the characteristics of the participants is conducted. Reliability analyses reveal an optimal internal consistency of the adapted scale. The results are discussed from a cross-cultural vision of gratitude. We conclude that the Gratitude Questionnaire-20 Items (G20), adapted to English with an American sample, is a psychometrically strong instrument to measure gratitude using crowdsourcing platforms for data collection and, therefore, a reference and useful tool in future research.

Psychometric Properties of the Indebtedness Scale (IS-R) in Spanish University Students.

The importance of trait indebtedness in the context of the study of gratitude has been growing in recent years, since both constructs form complex dynamics in response to the reception of a gift. In this work, the disposition to feel indebtedness is studied, through analysis of convergence and divergence, exploratory, and confirmatory analysis in the Spanish population, with the most used measurement instrument, i.e. The Revised Indebtedness Scale, IS-R. This scale depicted a four factor solution interrelated with a high consistency of content, which allows their labeling and describing. To do this, two samples of university students were selected; one of the sample sizes had 229 participants and the other 200 participants. Results also indicated good internal consistency described as follows: Debt for material aspects (α = 0.81), Self-sufficiency and discomfort in receiving help (α = 0.82), Moral self-demand in the reception of help (α = 0.83) and Debt in the receipt of gifts (α = 0.75). Furthermore, it was suggested that the relationships between gratitude and indebtedness are complex: on the one hand, all the indebtedness factors are inversely correlated with gratitude, such as the GQ5, although only Self-sufficiency and discomfort in receiving help and Debt in the receipt of gifts are such to a significant extent. However, the Interpersonal Gratitude scale of the G-20 depicted low correlations only with the Self-sufficiency and discomfort. The results are discussed in relation to the need for conceptual definition of the constructs in Positive Psychology.

Testing Motivational Theories in Music Education: The Role of Effort and Gratitude.

Acquiring musical skills requires sustained effort over long periods of time. This work aims to explore the variables involved in sustaining motivation in music students, including perceptions about one's own skills, satisfaction with achievements, effort, the importance of music in one's life, and perception of the sacrifice made. Two models were developed in which the variable of gratitude was included to integrate positive psychology into the motivational area of music education. The first predicts effort, while the second predicts gratitude. The models were tested using a sample of 84 music students. Both models were fitted using Bayesian analysis techniques to examine the relationship between variables and showed adequate goodness of fit. These models emphasize the role of cognition and motivation in music education and, more precisely, the relationship between effort and gratitude.

Recruitment of APOL1 kidney disease risk variants to lipid droplets attenuates cell toxicity.

Two coding variants in the apolipoprotein L1 (APOL1) gene (termed G1 and G2) are strongly associated with increased risk of nondiabetic kidney disease in people of recent African ancestry. The mechanisms by which the risk variants cause kidney damage, although not well-understood, are believed to involve injury to glomerular podocytes. The intracellular localization and function of APOL1 in podocytes remain unclear, with recent studies suggesting possible roles in the endoplasmic reticulum (ER), mitochondria, endosomes, lysosomes, and autophagosomes. Here, we demonstrate that APOL1 also localizes to intracellular lipid droplets (LDs). While a large fraction of risk variant APOL1 (G1 and G2) localizes to the ER, a significant proportion of wild-type APOL1 (G0) localizes to LDs. APOL1 transiently interacts with numerous organelles, including the ER, mitochondria, and endosomes. Treatment of cells that promote LD formation with oleic acid shifted the localization of G1 and G2 from the ER to LDs, with accompanying reduction of autophagic flux and cytotoxicity. Coexpression of G0 APOL1 with risk variant APOL1 enabled recruitment of G1 and G2 from the ER to LDs, accompanied by reduced cell death. The ability of G0 APOL1 to recruit risk variant APOL1 to LDs may help explain the recessive pattern of kidney disease inheritance. These studies establish APOL1 as a bona fide LD-associated protein, and reveal that recruitment of risk variant APOL1 to LDs reduces cell toxicity, autophagic flux, and cell death. Thus, interventions that divert APOL1 risk variants to LDs may serve as a novel therapeutic strategy to alleviate their cytotoxic effects.

Tbo-Filgrastim versus Filgrastim during Mobilization and Neutrophil Engraftment for Autologous Stem Cell Transplantation.

There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/µL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P < .01) and mean platelet transfusions (tbo-filgrastim, 1.7 units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated with cost savings of approximately $1406 per patient utilizing average wholesale price.

Evaluation of the quality of publications on randomized clinical trials using the Consolidated Standards of Reporting Trials (CONSORT) statement guidelines in a Spanish tertiary hospital.

The main reason for conducting a clinical trial (CT) is to test the effect of a drug or medical procedure to improve treatment of a disease. CTs contribute most when they are rigorously conducted and the results are published adequately. The aim of this study is to assess, using the CONSORT statement guidelines, the quality of reporting of completed CTs conducted at a tertiary hospital to determine which sections of the articles should be improved. CTs published between 2002 and 2008 were identified by searching the MEDLINE and Cochrane Library. Forty of 127 completed CTs were published. There was a marked increase in the number of articles and the quality of the journals that published the CTs over time. Although the articles were published in high-impact index journals, the Consolidated Standards of Reporting Trials (CONSORT) score reporting quality of the articles varied substantially, which indicates that they should be improved. The title, abstract, introduction, and discussion sections received the highest CONSORT scores and need little improvement. Poor reporting of methodological details and discussion on limitations and strengths were observed. In conclusion, much improvement remains to be made in the quality of reporting of CTs to allow reliable quality assessment of published trials.