Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Personalized Depression Prevention: A Randomized Controlled Trial to Optimize Effects Through Risk-Informed Personalization

Objective: To evaluate whether evidence-based depression prevention programs can be optimized by matching youths to interventions that address their psychosocial vulnerabilities. Method: This randomized controlled trial included 204 adolescents (mean [SD] age ¼ 14.26 [1.65] years; 56.4% female). Youths were categorized as high or low on cognitive and interpersonal risks for depression and randomly assigned to Coping With Stress (CWS), a cognitive-behavioral program, or Interpersonal Psychotherapy–Adolescent Skills Training (IPT-AST), an interpersonal program. Some participants received a match between risk and prevention (eg, high cognitive–low interpersonal risk teen in CWS, low cognitive–high interpersonal risk teen in IPT-AST), others received a mismatch (eg, low cognitive-high interpersonal risk teen in CWS). Outcomes were depression diagnoses and symptoms through 18 months postintervention (21 months total). Results: Matched adolescents showed significantly greater decreases in depressive symptoms than mismatched adolescents from postintervention through 18-month follow-up and across the entire 21-month study period (effect size [d] ¼ 0.44, 95% CI ¼ 0.02, 0.86). There was no significant difference in rates of depressive disorders among matched adolescents compared with mismatched adolescents (12.0% versus 18.3%, t193 ¼ .78, p ¼ .44). Conclusion: This study illustrates one approach to personalizing depression prevention as a form of precision mental health. Findings suggest that risk-informed personalization may enhance effects beyond a one-size-fits-all approach. Clinical trial registration information: Bending Adolescent Depression Trajectories Through Personalized Prevention; https://www.clinicaltrials. gov/; NCT01948167

Long-Term Effects From A School-Based Trial Comparing Interpersonal Psychotherapy-Adolescent Skills Training To Group Counseling

Adolescence represents a vulnerable developmental period for depression and an opportune time for prevention efforts. In this study, 186 adolescents with elevated depressive symptoms (M age = 14.01, SD = 1.22; 66.7% female; 32.2% racial minority) were randomized to receive either Interpersonal Psychotherapy–Adolescent Skills Training (IPT-AST; n = 95) delivered by research clinicians or group counseling (GC; n = 91) delivered by school counselors. We previously reported the short-term outcomes of this school-based randomized controlled trial: IPT-AST youth experienced significantly greater improvements in depressive symptoms and overall functioning through 6-month follow-up. Here, we present the long-term outcomes through 24 months postintervention. We examined differences in rates of change in depressive symptoms and overall functioning and differences in rates of depression diagnoses. Youth in both conditions showed significant improvements in depressive symptoms and overall functioning from baseline to 24-month follow-up, demonstrating the efficacy of school-based depression prevention programs. However, the two groups did not differ in overall rates of change or in rates of depression diagnoses from baseline to 24-month follow-up. Although IPT-AST demonstrated advantages over GC in the short term, these effects dissipated over long-term follow-up. Specifically, from 6- to 24-month follow-up, GC youth showed continued decreases in depressive symptoms, whereas IPT-AST youth showed a nonsignificant increase in symptoms. GC youth remained relatively stable in overall functioning, whereas IPT-AST youth experienced a small but statistically significant worsening in functioning. This study highlights the potential of school-based depression prevention efforts and the need for further research

Pain coping skills training for African Americans with osteoarthritis (STAART): study protocol of a randomized controlled trial

Background: African Americans bear a disproportionate burden of osteoarthritis (OA), with higher prevalence rates, more severe pain, and more functional limitations. One key barrier to addressing these disparities has been limited engagement of African Americans in the development and evaluation of behavioral interventions for management of OA. Pain Coping Skills Training (CST) is a cognitive-behavioral intervention with shown efficacy to improve OA-related pain and other outcomes. Emerging data indicate pain CST may be a promising intervention for reducing racial disparities in OA symptom severity. However, there are important gaps in this research, including incorporation of stakeholder perspectives (e.g. cultural appropriateness, strategies for implementation into clinical practice) and testing pain CST specifically among African Americans with OA. This study will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA. Methods/Design: This is a randomized controlled trial among 248 participants with symptomatic hip or knee OA, with equal allocation to a pain CST group and a wait list (WL) control group. The pain CST program incorporated feedback from patients and other stakeholders and involves 11 weekly telephone-based sessions. Outcomes are assessed at baseline, 12 weeks (primary time point), and 36 weeks (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include self-efficacy, pain coping, pain interference, quality of life, depressive symptoms, and global assessment of change. Linear mixed models will be used to compare the pain CST group to the WL control group and explore whether participant characteristics are associated with differential improvement in the pain CST program. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, Durham Veterans Affairs Medical Center, East Carolina University, and Duke University Health System. Discussion: This culturally enhanced pain CST program could have a substantial impact on outcomes for African Americans with OA and may be a key strategy in the reduction of racial health disparities.Funded by Patient-Centered Outcomes Research Institute (PCORI) Award (AD-1408-19519)

Physical therapy vs. internet-based exercise training (PATH-IN) for patients with knee osteoarthritis: study protocol of a randomized controlled trial

Abstract Background Physical activity improves pain and function among individuals with knee osteoarthritis (OA), but most people with this condition are inactive. Physical therapists play a key role in helping people with knee OA to increase appropriate physical activity. However, health care access issues, financial constraints, and other factors impede some patients from receiving physical therapy (PT) for knee OA. A need exists to develop and evaluate other methods to provide physical activity instruction and support to people with knee OA. This study is examining the effectiveness of an internet-based exercise training (IBET) program designed for knee OA, designed by physical therapists and other clinicians. Methods/Design This is a randomized controlled trial of 350 participants with symptomatic knee OA, allocated to three groups: IBET, standard PT, and a wait list (WL) control group (in a 2:2:1 ratio, respectively). The study was funded by the Patient Centered Outcomes Research Institute, which conducted a peer review of the proposal. The IBET program provides patients with a tailored exercise program (based on functional level, symptoms, and current activity), video demonstrations of exercises, and guidance for appropriate exercise progression. The PT group receives up to 8 individual visits with a physical therapist, mirroring standard practice for knee OA and with an emphasis on a home exercise program. Outcomes are assessed at baseline, 4 months (primary time point) and 12 months (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include objective physical function, satisfaction with physical function, physical activity, depressive symptoms and global assessment of change. Linear mixed models will be used to compare both the IBET and standard PT groups to the WL control group, examine whether IBET is non-inferior to PT (a treatment that has an established evidence base for knee OA), and explore whether participant characteristics are associated with differential effects of IBET and/or standard PT. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Board of the University of North Carolina at Chapel Hill. Discussion The IBET program could be disseminated widely at relatively low cost and could be an important resource for helping patients with knee OA to adopt and maintain appropriate physical activity. This trial will provide an important evaluation of the effectiveness of this IBET program for knee OA. Trial registration NCT0231271

Reference values for aerobic capacity estimated by cardiopulmonary exercise test on a cycle ergometer in a healthy Greek population

Objective: Aerobic capacity (AC) is inversely associated with a high risk of cardiovascular morbidity and mortality as well as all-cause mortality. Cardiopulmonary exercise testing (CPET) represents the gold standard for assessing exercise capacity based on maximum oxygen uptake (VO2max). The purpose of our study was to provide for the first time CPET-derived normative reference values in a Greek cohort of apparently healthy men and women on a cycle ergometer to evaluate their AC, and to compare our results with similar studies from other countries. Methods: A cohort of 194 apparently healthy subjects (118 males and 76 females, age range, 15-69 years) was submitted to CPET using a cycle ergometer. Mean ± SD values for several exercise parameters, VO2max included, were determined. We compared our results with existing data derived from USA and North Europe cohorts. Results: Male subjects achieved significantly higher levels of relative and absolute VO2max (p < 0.001) across all ages compared to female subjects. A decline in relative and absolute VO2max among older participants was observed in both sexes. Greek subjects had lower AC than the North Europe cohort and almost similar to the USA cohort. Conclusion: We provide the first reference data for AC in apparently healthy Greek subjects based on CPET using cycle ergometer. Our findings will allow for more accurate interpretation of CPET in several groups of healthy subjects or patients with CV diseases. The differences found between our reference values and those reported from the USA and northern European countries, underscore the need for individual countries to develop their own AC reference values. © 2019 Hellenic Society of Cardiolog

P804The significance of 24h blood pressure variability improvement regarding target organ damage indices three years after medical treatment initiation in essential hypertension

Abstract Background Blood pressure variability (BPV) has been associated with development, progression and severity of cardiac and vascular organ damage and with an increased risk of cardiovascular events and mortality, independently adding to cardiovascular risk, over and above the contribution of elevated mean BP levels. We aimed to explore any correlation between differences in BPV and target organ damage indices (TOD) in hypertensive patients three years after medical treatment initiation. Methods At baseline and before medical treatment initiation, we measured 24h average SBP and DBP as well as 24h systolic BPV after 24h ambulatory blood pressure monitoring (ABPM) in newly diagnosed and never treated hypertensive patients (n=171, mean age=52+12 years, 110 males, 24h average SBP/DBP=138+10/87+9 mmHg, 24h systolic BPV=15+3) who were also subjected to arterial stiffness by carotid-femoral pulse wave velocity (PWV), left ventricular hypertrophy by left ventricular mass index (LVMI) and coronary flow reserve (CFR) estimations. All the above tests were repeated approximately three years later after treatment initiation. Results Patients were characterized as controlled (n=113, mean age=54+12 years, 62 males, 24h average SBP/DBP=118+6/71+6 mmHg) or non-controlled hyperensives (n=58, mean age=48+11 years, 48 males, 24h average SBP/DBP=133+8/83+7 mmHg) based on ABPM results three years later (controlled BP=24h average BP&lt;130/80 mmHg). In the whole population, 24h average SBP/DBP, systolic BPV (p&lt;0.001) and LVMI (p=0.01) were decreased while systolic BPV difference was related with LVMI difference (r=0.27, p&lt;0.001). In controlled hypertensives, 24h average SBP/DBP, systolic BPV (p&lt;0.001) and LVMI (p=0.02) were decreased while systolic BPV difference was related with LVMI difference (r=0.35, p&lt;0.001). In non-controlled hypertensives, 24h average SBP (p=0.001), DBP p&lt;0.001) and systolic BPV (p=0.04) were decreased while PWV was increased (p=0.03) and no correlations were found between systolic BPV and TOD. Correlation between BPV and LVMI Conclusions It seems that antihypertensive-induced systolic BPV improvement relate with cardiovascular risk decrease occur only in the setting of blood pressure treated within normal limits and confirmed by ABPM. Our study confirms that left ventricular mass between other TOD primarily improves due to successful antihypertensive treatment. </jats:sec