Validation of the psychosocial consequences of screening in lung cancer questionnaire in the international lung screen trial Australian cohort.

BACKGROUND: Evaluation of psychosocial consequences of lung cancer screening with LDCT in high-risk populations has generally been performed using generic psychometric instruments. Such generic instruments have low coverage and low power to detect screening impacts. This study aims to validate an established lung cancer screening-specific questionnaire, Consequences Of Screening Lung Cancer (COS-LC), in Australian-English and describe early results from the baseline LDCT round of the International Lung Screen Trial (ILST). METHODS: The Danish-version COS-LC was translated to Australian-English using the double panel method and field tested in Australian-ILST participants to examine content validity. A random sample of 200 participants were used to assess construct validity using Rasch item response theory models. Reliability was assessed using classical test theory. The COS-LC was administered to ILST participants at prespecified timepoints including at enrolment, dependent of screening results. RESULTS: Minor linguistic alterations were made after initial translation of COS-LC to English. The COS-LC demonstrated good content validity and adequate construct validity using psychometric analysis. The four core scales fit the Rasch model, with only minor issues in five non-core scales which resolved with modification. 1129 Australian-ILST participants were included in the analysis, with minimal psychosocial impact observed shortly after baseline LDCT results. CONCLUSION: COS-LC is the first lung cancer screening-specific questionnaire to be validated in Australia and has demonstrated excellent psychometric properties. Early results did not demonstrate significant psychosocial impacts of screening. Longer-term follow-up is awaited and will be particularly pertinent given the announcement of an Australian National Lung Cancer Screening Program. TRIAL REGISTRATION: NCT02871856.

Factors predicting the progression from paroxysmal to persistent atrial fibrillation despite an index catheter ablation.

INTRODUCTION: Despite undergoing an index ablation, some patients progress from paroxysmal atrial fibrillation (PAF) to persistent AF (PersAF), and the mechanism behind this is unclear. The aim of this study was to investigate the predictors of progression to PersAF after catheter ablation in patients with PAF. METHODS: This study included 400 PAF patients who underwent an index ablation between 2015 and 2019. The patients were classified into three groups based on their outcomes: Group 1 (PAF to sinus rhythm, n = 226), Group 2 (PAF to PAF, n = 146), and Group 3 (PAF to PersAF, n = 28). Baseline and procedural characteristics were collected, and predictors for AF recurrence and progression were evaluated. RESULTS: The mean age of the patients was 58.4 ± 11.1 years, with 272 males. After 3 years of follow-up, 7% of the PAF cases recurred and progressed to PersAF despite undergoing an index catheter ablation. In the multivariable analysis, a larger left atrial (LA) diameter and the presence of non-pulmonary vein (PV) triggers during the index procedure independently predicted recurrence. Moreover, a larger LA diameter, the presence of non-PV triggers, and a history of thyroid disease independently predicted AF progression. CONCLUSION: The progression from PAF to PersAF after catheter ablation is associated with a larger LA diameter, history of thyroid disease, and the presence of non-PV triggers. Meticulous preprocedural evaluation, patient selection, and comprehensive provocation tests during catheter ablation are recommended.

Oral Cladribine Impairs Intermediate, but Not Conventional, Monocyte Transmigration in Multiple Sclerosis Patients across a Model Blood-Brain Barrier.

Multiple sclerosis (MS) is a disease in which the immune system damages components of the central nervous system (CNS), leading to the destruction of myelin and the formation of demyelinating plaques. This often occurs in episodic "attacks" precipitated by the transmigration of leukocytes across the blood-brain barrier (BBB), and repeated episodes of demyelination lead to substantial losses of axons within and removed from plaques, ultimately leading to progressive neurological dysfunction. Within leukocyte populations, macrophages and T and B lymphocytes are the predominant effectors. Among current immunotherapies, oral cladribine's impact on lymphocytes is well characterised, but little is known about its impact on other leukocytes such as monocytes and dendritic cells (DCs). The aim of this study was to determine the transmigratory ability of monocyte and DC subsets in healthy subjects and untreated and cladribine-treated relapse-remitting MS (RRMS) patients using a well-characterised model of the BBB. Peripheral blood mononuclear cells from subjects were added to an in vitro transmigration assay to assess cell migration. Our findings show that while prior treatment with oral cladribine inhibits the migration of intermediate monocytes, it has no impact on the transmigration of DC subsets. Overall, our data indicate a previously unrecognised role of cladribine on intermediate monocytes, known to accumulate in the brain active MS lesions.

Effects of multicomponent exercise training on muscle oxygenation in young and older adults.

Objective: Though multicomponent exercise training was found beneficial in improving the physical functionality, the effects of multicomponent exercise training on muscle oxygenation are still unclear. The purpose of this study was to investigate the effects of multicomponent exercise training on muscle oxygenation in young and older participants. Methods: In this study, 17 young adults (Y) and 18 healthy older adults (E) were recruited to receive a multicomponent exercise training for 12 weeks, 2-3 sessions per week. Muscle oxygenation, muscle strength, and electromyography data were collected and compared pre- and post-training. Muscle oxygen saturation (SpO2) during isometric knee extension tests involving voluntary contraction (VOL) and electrical stimulation (ES) was measured by near-infrared spectroscopy. The SpO2 kinetics in the contraction and recovery phases were calculated using a tangential model to extract ΔSpO2 and inflection time (IF). Results: Muscle strength significantly increased in the post-training (234.31 ± 83.2 N·m, p < 0.05). The post-training ΔSpO2 of the ES in the Y (8.43 ± 5.35%) significantly increased and was higher than that in the E (2.78 ± 3.03%, p < 0.05). In the recovery phase, the post-training IF of VOL (7.07 ± 3.31s) was significantly shorter than that of the pre-training period (8.73 ± 4.46s, p < 0.05). Additionally, the median frequency of electromyography significantly decreased in the post-training period (103.84 ± 21.75 Hz, p < 0.05). Conclusion: The multicomponent exercise training improved the muscle strength, neuromuscular performance, and muscle aerobic function irrespective of age. The primary adaptation of the muscles to the multicomponent exercise training between the two groups varied.

Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.

An i-motif is a non-canonical DNA structure implicated in gene regulation and linked to cancers. The C-rich strand of the HRAS oncogene, 5'-CGCCCGTGCCCTGCGCCCGCAACCCGA-3' (herein referred to as iHRAS), forms an i-motif in vitro but its exact structure was unknown. HRAS is a member of the RAS proto-oncogene family. About 19 % of US cancer patients carry mutations in RAS genes. We solved the structure of iHRAS at 1.77 Šresolution. The structure reveals that iHRAS folds into a double hairpin. The two double hairpins associate in an antiparallel fashion, forming an i-motif dimer capped by two loops on each end and linked by a connecting region. Six C-C+ base pairs form each i-motif core, and the core regions are extended by a G-G base pair and a cytosine stacking. Extensive canonical and non-canonical base pairing and stacking stabilizes the connecting region and loops. The iHRAS structure is the first atomic resolution structure of an i-motif from a human oncogene. This structure sheds light on i-motifs folding and function in the cell.

Application of Ensite™ LiveView function for identification of scar-related ventricular tachycardia isthmus.

INTRODUCTION: Dynamic display of real-time wavefront activation pattern may facilitate the recognition of reentrant circuits, particularly the diastolic path of ventricular tachycardia (VT). OBJECTIVE: We aimed to evaluate the feasibility of LiveView Dynamic Display for mapping the critical isthmus of scar-related reentrant VT. METHODS: Patients with mappable scar-related reentrant VT were selected. The characteristics of the underlying substrates and VT circuits were assessed using HD grid multielectrode catheter. The VT isthmuses were identified based on the activation map, entrainment, and ablation results. The accuracy of the LiveView findings in detecting potential VT isthmus was assessed. RESULTS: We studied 18 scar-related reentrant VTs in 10 patients (median age: 59.5 years, 100% male) including 6 and 4 patients with ischemic and nonischemic cardiomyopathy, respectively. The median VT cycle length was 426 ms (interquartile range: 386-466 ms). Among 590 regional mapping displays, 92.0% of the VT isthmus sites were identified by LiveView Dynamic Display. The accuracy of LiveView for isthmus identification was 84%, with positive and negative predictive values of 54.8% and 97.8%, respectively. The area with abnormal electrograms was negatively correlated with the accuracy of LiveView Dynamic Display (r = -.506, p = .027). The median time interval to identify a VT isthmus using LiveView was significantly shorter than that using conventional activation maps (50.5 [29.8-120] vs. 219 [157.5-400.8] s, p = .015). CONCLUSION: This study demonstrated the feasibility of LiveView Dynamic Display in identifying the critical isthmus of scar-related VT with modest accuracy.

Operationally defining physical literacy in Chinese culture: Results of a meta-narrative synthesis and the Panel's recommendations.

Purpose: The definition of physical literacy (PL) needs to be explored by researchers from educational, public health, and sports organisations in Chinese culture; an adequate definition and theoretical framework of PL can then be embraced within different contexts and according to cultural influences. Methods: This meta-narrative synthesis of literature in this area included a series of planning, search, mapping, appraisal, synthesis, and recommendation phases. The literature was translated into English and circulated among international experts to seek suggestions. A total of 74 articles were included in the PL definition synthesis and 28 were included for philosophical synthesis in this study. Results: Based on three rounds of discussions, the final agreement was reached among panel members regarding the defining statements and practical and theoretical models of PL in Chinese culture. According to consensus, PL is the integration of physical, perceptual, cognitive, psychological, and behavioural capabilities, echoing with the need for an active, healthy, and fulfilling lifestyle, which involves continuous positive interactions with the environment and embodied engagement in physical activities for life. The framework addressed five domains (physical, sensory-perceptual, cognitive, psychological, and behavioural) and one important overlapping factor (dynamic environment). A further explanation was provided in the defining statement to assist in understanding the concept. Conclusion: It is suggested that the cultural interpretation and historical background of PL in Chinese discourse should be addressed and respected. The development of a specific cultural definition statement of PL in one country could provide implications for PL researchers worldwide.

Identification and Characterization of a B-Raf Kinase α-Helix Critical for the Activity of MEK Kinase in MAPK Signaling.

In the MAPK pathway, an oncogenic V600E mutation in B-Raf kinase causes the enzyme to be constitutively active, leading to aberrantly high phosphorylation levels of its downstream effectors, MEK and ERK kinases. The V600E mutation in B-Raf accounts for more than half of all melanomas and ∼3% of all cancers, and many drugs target the ATP binding site of the enzyme for its inhibition. Because B-Raf can develop resistance against these drugs and such drugs can induce paradoxical activation, drugs that target allosteric sites are needed. To identify other potential drug targets, we generated and kinetically characterized an active form of B-RafV600E expressed using a bacterial expression system. In doing so, we identified an α-helix on B-Raf, found at the B-Raf-MEK interface, that is critical for their interaction and the oncogenic activity of B-RafV600E. We assessed the binding between B-Raf mutants and MEK using pull downs and biolayer interferometry and assessed phosphorylation levels of MEK in vitro and in cells as well as its downstream target ERK to show that mutating certain residues on this α-helix is detrimental to binding and downstream activity. Our results suggest that this B-Raf α-helix binding site on MEK could be a site to target for drug development to treat B-RafV600E-induced melanomas.

Quadruplexes in 'Dicty': crystal structure of a four-quartet G-quadruplex formed by G-rich motif found in the Dictyostelium discoideum genome.

Guanine-rich DNA has the potential to fold into non-canonical G-quadruplex (G4) structures. Analysis of the genome of the social amoeba Dictyostelium discoideum indicates a low number of sequences with G4-forming potential (249-1055). Therefore, D. discoideum is a perfect model organism to investigate the relationship between the presence of G4s and their biological functions. As a first step in this investigation, we crystallized the dGGGGGAGGGGTACAGGGGTACAGGGG sequence from the putative promoter region of two divergent genes in D. discoideum. According to the crystal structure, this sequence folds into a four-quartet intramolecular antiparallel G4 with two lateral and one diagonal loops. The G-quadruplex core is further stabilized by a G-C Watson-Crick base pair and a A-T-A triad and displays high thermal stability (Tm > 90°C at 100 mM KCl). Biophysical characterization of the native sequence and loop mutants suggests that the DNA adopts the same structure in solution and in crystalline form, and that loop interactions are important for the G4 stability but not for its folding. Four-tetrad G4 structures are sparse. Thus, our work advances understanding of the structural diversity of G-quadruplexes and yields coordinates for in silico drug screening programs and G4 predictive tools.

Hearing vs. engaging in negative body talk: an examination of adult men.

This study examined the negative body talk both engaged in and heard by adult men as separate constructs and how both constructs are related to men's body dissatisfaction and muscle dysmorphia. Data were collected from 260 adult men on negative body talk both engaged in and heard, body fat dissatisfaction, muscle dissatisfaction, and muscle dysmorphia. Results indicated that the muscle talk that men engaged in acted as a mediator between the relationship between the body talk men heard and muscle dissatisfaction. The same mediating relationship also existing for muscle dysmorphia symptoms. Similarly, the fat talk that men engaged in mediated the relationship between the fat talk that men heard from friends and body fat dissatisfaction. In addition, age was negatively related to muscle talk and body mass index was positively correlated with fat talk. These findings suggest that the relationship between the body talk that men hear from others and their body image may be explained by the body talk that men verbally engage in themselves.

Is listening to fat talk the same as participating in fat talk?

Our study examined whether verbally participating in fat talk conversations had a different effect on women's body image perception than merely listening to friends engage in fat talk conversations. Participants were 321 women who completed measures of listening to and participating in fat talk conversations, drive for thinness, body dissatisfaction, and dietary restraint. Results indicated that verbally participating in fat talk was a much stronger predictor of women's drive for thinness, body dissatisfaction, and dietary restraint than merely listening to friends engage in fat talk conversations.

Additive impact of pre-liver transplant metabolic factors on survival post-liver transplant.

BACKGROUND AND AIM: Diabetes at time of liver transplantation is associated with reduced post-transplant survival. We aimed to assess whether additional metabolic conditions such as obesity or hypertension had additive prognostic impact on post-transplantation survival. METHODS: A multi-center cohort study of 617 adult subjects undergoing liver transplantation between 2003 and 2009 has been used. Dry body mass index was calculated following adjustment for ascites. RESULTS: After a median follow-up of 5.8 years (range 0-10.5), 112 (18.2%) patients died. Diabetes was associated with reduced post-transplant survival (hazard ratio 1.89, 95% confidence interval [CI] 1.25-2.86, P = 0.003), whereas obesity, hypertension, dyslipidemia, and the metabolic syndrome itself were not (P > 0.3 for all). Patients with concomitant diabetes and obesity had lower survival (adjusted Hazard Ratio [aHR] 2.40, 95%CI 1.32-4.38, P = 0.004), whereas obese non-diabetic patients or diabetic non-obese patients had similar survival compared with non-diabetic, non-obese individuals. The presence of hypertension or dyslipidemia did not impact on survival in patients with diabetes (P > 0.1 for both). Obese diabetic patients had longer intensive care and hospital stays than non-obese diabetic or obese, non-diabetic patients (P < 0.05). The impact of concomitant obesity and diabetes on survival was greater in subjects aged 50+ years (52.6% 5-year survival, aHR 3.04, 95% CI 1.54-5.98) or those transplanted with hepatocellular carcinoma (34.1% 5-year survival, aHR 3.35, 95% CI 1.31-5.57). Diabetes without obesity was not associated with an increased mortality rate in these sub-groups. CONCLUSIONS: Concomitant diabetes and obesity but not each condition in the absence of the other is associated with reduced post-liver transplant survival. The impact of diabetes and obesity is greater in older patients and those with hepatocellular carcinoma.

Cognitive Function and Quality of Life in Community-Dwelling Seniors with Mild Cognitive Impairment in Taiwan.

The aims of this study were to examine the relationships between overall cognitive function and the quality of life (QOL) domains, and to compare the differences in these by age, gender, and educational level in community-dwelling seniors in Taiwan. A cross-sectional study was conducted, with the participants screened and recruited from Southern Tainan. The Saint Louis University Mental Status Examination was used to screen the cognitive status of the participants. A total of 144 seniors participated in this study were assessed using the Taiwanese version of WHOQOL-BREF. The results showed that the participants performed better in the cognitive domains of "figure identification" and "orientation" while they performed poor in "delayed recall" and "immediate paragraph recall". No significant relationship between cognitive function and overall QOL, but a positive relationship between cognitive function and the physical health domain of QOL was found. The findings of this study provide valuable information for community healthcare providers.

Comparative teratogenicity analysis of valnoctamide, risperidone, and olanzapine in mice.

OBJECTIVES: Based on the recent findings from animal studies, it has been proposed that the therapeutic use of valnoctamide, an anxiolytic drug developed in the early 1960s, be extended to treat other neurological disorders such as epilepsy and bipolar disease. Given the scarcity of adequate data on its prenatal toxicity, a comparative teratogenicity study of valnoctamide and two of the most commonly used drugs to treat bipolar disorder, risperidone and olanzapine, was carried out in a mouse model system. METHODS: Pregnant dams were treated with the aforementioned three drugs at the dose levels calculated as an equal proportion of the respective LD50 values of these drugs. The main reproductive indices examined included the numbers of implantations and resorptions, viable and dead fetuses, and fetal gross, visceral and skeletal abnormalities. RESULTS: The outcomes of the present study indicated that olanzapine was the most teratogenic of the three drugs, inducing maternal-, embryo-, and fetotoxicity. Risperidone also exerted a significant prenatal toxicity, but its adverse effect was less pronounced than that induced by olanzapine. Valnoctamide did not show any teratogenic effect, even when used in relatively higher dosages than olanzapine and risperidone. The observed increased skeletal abnormalities in one of the valnoctamide treatment groups were nonspecific and, as such, signaled a modest developmental delay rather than an indication that the compound could induce structural malformations. CONCLUSIONS: Under our experimental conditions, valnoctamide demonstrated the lowest prenatal toxicity of the three tested drugs.

Investigating the adaptation of muscle oxygenation to resistance training for elders and young men using near-infrared spectroscopy.

PURPOSE: The purpose of this study was to investigate the differences in resistance training adaptation on muscle oxygenation between young and elderly subjects. Groups of eleven trained young, untrained young, trained elderly, and untrained elderly (UTE) were recruited. METHODS: Muscle oxygenation of the vastus lateralis muscle during 20 % maximal voluntary isometric contraction was observed using near-infrared spectroscopy. The oxygen saturation (SpO2) kinetics in the contraction and recovery phases was modeled with a tangential model to extract ΔSpO2 and inflection time (IF). The median frequencies of SpO2 data representing the change of tissue oxygenation oscillation were compared. RESULTS: The ΔSpO2 values for the trained groups (12.00 ± 7.86%) were significantly higher than those for the untrained groups (5.91 ± 4.36%, P < 0.05), and those for the young groups (11.63 ± 7.52%) were significantly higher than those for the older groups (6.29 ± 4.70%, P < 0.05). In the recovery phase, the IF was significantly longer for the elderly groups (10.32 ± 4.39 s, P < 0.05) than that for the young groups (6.31 ± 3.69 s). The median frequency of tissue oxygenation oscillation was significantly lower for the TE group (0.41 ± 0.12 Hz, P < 0.05) than that for the UTE group (0.57 ± 0.13 Hz). CONCLUSIONS: The increased ΔSpO2 in trained groups during muscle contraction may be due to lower microvascular O2 pressure. The lower median frequency for the TE group indicates that tissue oxygenation oscillation significantly trended toward low-frequency oscillation, possibly resulting from the enhancement of vascular function.

A Prospective Observational Study of Physical Activity Levels and Physical Fitness of People at High Risk for Lung Cancer.

Introduction: Physical activity (PA) is a potentially modifiable risk factor for lung cancer, with previous research revealing that people who engage in more PA have lower risk of developing lung cancer. PA levels of lung cancer screening participants have not previously been explored. Methods: Participants at a single Australian International Lung Screen Trial site were eligible for assessment of self-reported PA levels (International Physical Activity Questionnaire and Physical Activity Scale for the Elderly) and physical assessments (6-min walk distance, hand grip muscle strength, daily step count, and body composition) at a single time point during lung cancer screening. Statistics were predominantly descriptive, with parametric data presented as mean and SD and nonparametric data presented as median and interquartile range (IQR). Results: A total of 178 participants were enrolled in this study, with a median age of 61 years. Of the participants, 61% were men and 51% were people who currently smoke. The median total International Physical Activity Questionnaire score was 1756 MET/min/wk (IQR 689, 4049). Mean total Physical Activity Scale for the Elderly score was 160 (SD 72), higher than described in healthy sedentary adults. The median daily step count was 7237 steps (IQR 5353, 10,038) and mean 6-minute walk distance was 545 m (SD 92). Median grip strengths were within predicted normal range, with an elevated median percentage body fat and low skeletal muscle mass found on body composition. Conclusion: Almost a quarter of International Lung Screen Trial participants assessed reported low levels of PA and have a potentially modifiable risk factor to improve health outcomes. Larger studies are needed to characterize the burden of inactivity among high-risk lung cancer screening populations.

Pathways from fear of falling to quality of life: the mediating effect of the self-concept of health and physical independence.

OBJECTIVES: Fear of falling leads to many adverse consequences and may compromise the quality of life of older adults. Psychological factors are potential mediators between the fear of falling and quality of life, but have yet to be explored in detail. This study presents results from examining the mediating effect of the self-concept of health and physical independence. Data from Western and Eastern countries were compared. METHOD: Concerns about falling, the level of participation in physical activities, the self-concept of health and physical independence, and health-related quality of life were measured using samples from Taiwan (n = 193) and Germany (n = 182). Multiple regression models were used to test the mediating effects. RESULTS: The relationship between fear of falling and quality of life was partially mediated through participation in physical activities and the self-concept of health and physical independence in both the Taiwanese and German samples. In particular, the self-concept of health and physical independence of the Taiwanese sample resulted in the strongest mediating effect. CONCLUSION: Potential mediating mechanisms through both participation in physical activities and the self-concept of health and physical independence provide useful information for understanding related theories and for explicating interventions. Cultural factors should also be accounted for when conducting research and programs related to the fear of falling.

Translation and validation of a Chinese version of the body talk scale for women and men.

Body talk has received increasing research attention in recent years, with accumulating evidence supporting the link between body talk and eating and body image disturbances. However, research on body talk in China is still relatively scarce and generally focused on fat talk, especially in women, and much remains unknown about muscle talk and positive body talk for both Chinese women and men. To promote a better understanding of body talk in the Chinese context, the present study adapted the Body Talk Scale (BTS) into Chinese Mandarin (i.e., C-BTS) and evaluated the factor structure and psychometric properties of the C-BTS in Chinese adult women and men. The English version of the BTS was translated into Chinese Mandarin with standard procedures. With 300 Chinese women (Mage = 29.48 years, SD = 7.26) and 300 men (Mage = 29.36 years, SD = 6.81), we examined the factor structure and gender invariance of the C-BTS, as well as internal consistency reliability, test-retest reliability, and construct validity, including convergent, concurrent, and incremental validity of the C-BTS. The results indicated that, consistent with the development study of the BTS, the C-BTS had three subscales (i.e., Negative Fat Talk, Negative Muscle Talk, and Positive Body Talk) and good reliability and validity. The findings demonstrate that the C-BTS can be a useful measure of body talk in both Chinese women and men.

The Body Talk Scale (BTS) measures three types of body talk, including negative fat talk, negative muscle talk, and positive body talk. The present study adapted the English version of the BTS into Chinese Mandarin and examined its psychometric properties in Chinese adult women and men. Results showed that the BTS had adequate reliability and validity in Chinese adults and could be used to assess body talk in Chinese women and men.