Enhancing undergraduate education and research in aging to eliminate health disparities (ENGAGED) - A pipeline program to advance diversity in aging research.

The Enhancing Undergraduate Education and Research in Aging to Eliminate Health Disparities (ENGAGED) program takes advantage of the broad, multidisciplinary research established in the area of aging at Wake Forest University School of Medicine and its partner institutions, Wake Forest University and Winston-Salem State University. The ENGAGED program is designed to provide undergraduate students who are underrepresented in the biomedical sciences an opportunity to participate in educational and research training in aging and health disparities. Funded since August 2019, ENGAGED has provided 73 academic year internships and 46 summer internships, with another 8 internships starting in Fall 2023. A total of 61 students (67% female, 64% African American, 21% Hispanic) have participated in the ENGAGED program, reflecting the fact that 49% participate in more than one session or program offering. To date, 38 of the ENGAGED trainees have graduated (100% with a science, technology, engineering, or math degree), 84% of whom are working or pursuing advanced degrees in the biomedical sciences. Given the unique strengths, existing infrastructure, and long-standing collaborations among the partner institutions, the ENGAGED program is helping advance diversity in aging and health disparities research by creating a pipeline for well-trained underrepresented students interested in biomedical research careers.

Cost-Effectiveness of Community-Based Diet and Exercise for Patients with Knee Osteoarthritis and Obesity or Overweight.

OBJECTIVE: Obesity exacerbates pain and functional limitation in persons with knee osteoarthritis (OA). In the Weight Loss and Exercise for Communities with Arthritis in North Carolina (WE-CAN) study, a community-based diet and exercise (D + E) intervention led to an additional 6 kg weight loss and 20% greater pain relief in persons with knee OA and body mass index (BMI) >27 kg/m2 relative to a group-based health education (HE) intervention. We sought to determine the incremental cost-effectiveness of the usual care (UC), UC + HE, and UC + (D + E) programs, comparing each strategy with the "next-best" strategy ranked by increasing lifetime cost. METHODS: We used the Osteoarthritis Policy Model to project long-term clinical and economic benefits of the WE-CAN interventions. We considered three strategies: UC, UC + HE, and UC + (D + E). We derived cohort characteristics, weight, and pain reduction from the WE-CAN trial. Our outcomes included quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). RESULTS: In a cohort with mean age 65 years, BMI 37 kg/m2, and Western Ontario and McMaster Universities Osteoarthritis Index pain score 38 (scale 0-100, 100 = worst), UC leads to 9.36 QALYs/person, compared with 9.44 QALYs for UC + HE and 9.49 QALYS for UC + (D + E). The corresponding lifetime costs are $147,102, $148,139, and $151,478. From the societal perspective, UC + HE leads to an ICER of $12,700/QALY; adding D + E to UC leads to an ICER of $61,700/QALY. CONCLUSION: The community-based D + E program for persons with knee OA and BMI >27kg/m2 could be cost-effective for willingness-to-pay thresholds greater than $62,000/QALY. These findings suggest that incorporation of community-based D + E programs into OA care may be beneficial for public health.

Clinical, Health-Related Quality of Life, and Gait Differences Among Obesity Classes in Adults With Knee Osteoarthritis.

OBJECTIVE: The purpose of this study was to determine whether clinical, health-related quality of life (HRQL), and gait characteristics in adults with knee osteoarthritis (OA) differed by obesity category. METHODS: This cross-sectional analysis of 823 older adults (mean age 64.6 years, SD 7.8 years) with knee OA and overweight or obesity compared clinical, HRQL, and gait outcomes among obesity classifications (overweight or class I, body mass index [BMI] 27.0-34.9; class II, BMI 35.0-39.9; class III BMI ≥40.0). RESULTS: Patients with class III obesity had worse Western Ontario McMasters Universities Arthritis Index knee pain (0-20) than the overweight or class I (mean 8.6 vs 7.0; difference 1.5; 95% confidence interval [CI] 1.0-2.1; P < 0.0001) and class II (mean 8.6 vs 7.4; difference 1.1; 95% CI 0.6-1.7; P = 0.0002) obesity groups. The Short Form 36 physical HRQL measure was lower in the class III obesity group compared to the overweight or class I (mean 31.0 vs 37.3; difference -6.2; 95% CI -7.8 to -4.7; P < 0.0001) and class II (mean 31.0 vs 35.0; difference -3.9; 95% CI -5.6 to -2.2; P < 0.0001) obesity groups. The class III obesity group had a base of support (cm) during gait that was wider than that for the overweight or class I (mean 14.0 vs 11.6; difference 3.3; 95% CI 2.6-4.0; P < 0.0001) and class II (mean 14.0 vs 11.6; difference 2.4; 95% CI 1.6-3.2; P < 0.0001) obesity groups. CONCLUSION: Among adults with knee OA, those with class III obesity had significantly higher pain levels and worse physical HRQL and gait characteristics compared to adults with overweight or class I or class II obesity.

The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis: Design and rationale.

Background: Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control. Methods/design: The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) â€‹≥ â€‹30 â€‹kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention. Discussion: This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA. Trial registration: ClinicalTrials.gov Identifier: NCT05946044.

Impact on Cardiovascular Health of Using Phentermine/Topiramate in Combination With Laparoscopic Sleeve Gastrectomy in Super Obesity.

INTRODUCTION: Management of patients with BMI≥50 kg/m2 is challenging. In previous work, pre and postoperative pharmacotherapy with phentermine/topiramate plus laparoscopic sleeve gastrectomy (PT + SG) promoted greater weight loss than sleeve gastrectomy (SG) alone at 24 mo postoperatively. This current secondary analysis studied the impact of PT + SG on blood pressure (BP), heart rate, and antihypertensive usage. METHODS: Patients with BMI≥50 kg/m2 planning to have SG (n = 13) were recruited from 2014 to 2016, at an academic medical center in Winston-Salem, North Carolina, for this open-label trial. Participants took phentermine/topiramate (PT; 7.5/46-15/92 mg/d) for ≥3 mo preoperatively and 24 mo postoperatively. The control group (n = 40) underwent SG during the same time frame. We used mixed models for BP and heart rate to compare PT + SG versus SG alone over time, adjusted for age, sex, and initial BP. RESULTS: By 24 mo postoperatively the model adjusted changes in systolic blood pressure/diastolic blood pressure (SBP/DBP) (mm Hg) were -24.44 (-34.46,-14.43)/-28.60 (-40.74,-16.46) in the PT + SG group versus -11.81 (-17.58,-6.05)/-13.89 (-21.32,-6.46) in the control group (SBP P = 0.02; DBP P = 0.03). At baseline 8 (61.5%) participants in the PT + SG arm and 22 (55.0%) in the control group used antihypertensives. Excluding patients lost to follow-up (n = 3), by 24 mo postoperatively, none of the PT + SG participants were on antihypertensives compared to 14 (41.2%) in the control group (P = 0.01). CONCLUSIONS: Patients with BMI≥50 kg/m2 treated with PT + SG had greater improvement in BP with no use of antihypertensive medication at 24 mo postoperatively versus SG alone, where 41% continued medication use. Larger trials are required to evaluate this.

Efficacy and Variability in Plasma Nitrite Levels during Long-Term Supplementation with Nitrate Containing Beetroot Juice.

Long-term consumption of beetroot juice on efficacy of converting dietary nitrate to plasma nitrate and nitrite was investigated. Adults were randomized to consume either beetroot juice with 380 mg of nitrate (BR) or a beetroot juice placebo (PL) for 12-weeks. Plasma nitrate and nitrite were measured before and 90-minutes after consuming their intervention beverage. Percent change in nitrite across the 90 min was greater in BR (273.2 ± 39.9%) vs. PL (4.9 ± 36.9%). Long-term consumption of nitrate containing beetroot juice increased fasting nitrate and nitrite plasma levels compared to baseline.

Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial.

Importance: Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings. Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Interventions: Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. Main Outcomes and Measures: The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Results: Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, -0.6; 95% CI, -1.0 to -0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was -7.7 kg (8%) in the diet and exercise group (n = 289) and -1.7 kg (2%) in the attention control group (n = 273) (mean difference, -6.0 kg; 95% CI, -7.3 kg to -4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Conclusions and Relevance: Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02577549.

The Effects of Graded Protein Intake in Conjunction with Progressive Resistance Training on Skeletal Muscle Outcomes in Older Adults: A Preliminary Trial.

Many studies have evaluated the effects of resistance training (RT) and protein intake to attenuate the age-related loss of skeletal muscle. However, the effects of graded protein intake with conjunctive RT in older adults are unclear. Older adults (n = 18) performed 10 weeks of whole-body RT with progressions to intensity and volume while consuming either a constant protein (CP) diet (0.8−1.0 g/kg/d) with no protein supplement or a graded protein (GP) diet progressing from 0.8 g/kg/d at week 1 to 2.2 g/kg/d at week 10 with a whey protein supplement. Data were collected prior to commencement of the RT protocol (PRE), after week 5 (MID), and after week 10 (POST). Dual Energy X-ray Absorptiometry derived lean/soft tissue mass, ultrasonography derived muscle thickness, and a proxy of muscle quality were taken at PRE and POST, while isokinetic dynamometry derived peak torque were taken at PRE, MID, and POST. This study demonstrated the feasibility of the RT protocol (attendance = 96%), and protein intake protocol (CP in range all weeks; GP deviation from prescribed = 7%). Peak torque, muscle quality scores, and appendicular lean/soft tissue mass demonstrated the main effects of time (p < 0.05) while no other main effects of time or group * time interactions were seen for any measure. In conclusion, RT improved appendicular lean/soft tissue mass, peak torque, and muscle quality, with no differential effects of graded or constant protein intake.

Effect of Vitamin C and Protein Supplementation on Plasma Nitrate and Nitrite Response following Consumption of Beetroot Juice.

Beetroot juice is a food high in nitrate and is associated with cardiometabolic health benefits and enhanced exercise performance through the production of nitric oxide in the nitrate−nitrite−nitric oxide pathway. Since various food components influence this pathway, the aim of this trial was to study the effect of beetroot juice alone and in conjunction with vitamin C or protein on the acute response to plasma nitrate and nitrite levels in healthy middle- to older-aged adults. In this cross-over trial, each participant received, in a randomized order, a single dose of Beet It Sport® alone; Beet It Sport®, plus a 200 mg vitamin C supplement; and Beet It Sport® plus 15 g of whey protein. Plasma levels of nitrate and nitrite were determined prior to and at 1 and 3 h after intervention. Log plasma nitrate and nitrite was calculated to obtain data that were normally distributed, and these data were analyzed using two-way within-factors ANOVA, with time and treatment as the independent factors. There were no statistically significant differences for log plasma nitrate (p = 0.308) or log plasma nitrite (p = 0.391) values across treatments. Log plasma nitrate increased significantly from pre-consumption levels after 1 h (p < 0.001) and 3 h (p < 0.001), but plasma nitrate was lower at 3 h than 1 h (p < 0.001). Log plasma nitrite increased from pre to 1 h (p < 0.001) and 3 h (p < 0.001) with log values at 3 h higher than at 1 h (p = 0.003). In this cohort, we observed no differences in log plasma nitrate and nitrite at 1 h and 3 h after co-ingesting beetroot juice with vitamin C or a whey protein supplement compared to beetroot juice alone. Further research needs to be undertaken to expand the blood-sampling time-frame and to examine factors that may influence the kinetics of the plasma nitrate to nitrite efficacy, such as differences in fluid volume and osmolarity between treatments employed.

Changes in Body Weight and Knee Pain in Adults With Knee Osteoarthritis Three-and-a-Half Years After Completing Diet and Exercise Interventions: Follow-Up Study for a Single-Blind, Single-Center, Randomized Controlled Trial.

OBJECTIVE: To determine whether long-term diet (D) and exercise (E) interventions, alone or in combination (D+E), have beneficial effects for older adults with knee osteoarthritis (OA) 3.5 years after the interventions end. METHODS: This is a secondary analysis of a subset (n = 94) of the first 184 participants who had successfully completed the Intensive Diet and Exercise in Arthritis (IDEA) trial (n = 399) and who consented to follow-up testing. Participants were older (age ≥55 years), overweight, and obese adults with radiographic and symptomatic knee OA in at least 1 knee who completed 1.5-year D+E (n = 27), D (n = 35), or E (n = 32) interventions and returned for 5-year follow-up testing an average of 3.5 years later. RESULTS: During the 3.5-years following the interventions, weight regain in D+E and D was 5.9 kg (7%) and 3.1 kg (4%), respectively, with a 1-kg (1%) weight loss in E. Compared to baseline, weight (D+E -3.7 kg [P = 0.0007], D -5.8 kg [P < 0.0001], E -2.9 kg [P = 0.003]) and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale scores (D+E -1.2 [P = 0.03], D -1.5 [P = 0.001], E -1.6 [P = 0.0008]) were lower in each group at the 5-year follow-up. The effect of group assignment at the 5-year follow-up was significant for body weight, with D being less than E (-3.5 kg; P = 0.04). CONCLUSION: Older adults with knee OA who completed 1.5-year D or D+E interventions experienced partial weight regain 3.5 years later; yet, relative to baseline, they preserved statistically significant changes in weight loss and reductions in knee pain.

Correction: A randomized controlled trial of nitrate supplementation in well-trained middle and older-aged adults.

[This corrects the article DOI: 10.1371/journal.pone.0235047.].

A randomized controlled trial of nitrate supplementation in well-trained middle and older-aged adults.

PURPOSE: Nitrate (NO3-), through its conversion to nitrite (NO2-) and nitric oxide, has been shown to increase exercise tolerance in healthy younger adults and older diseased patients. Nitrate's effect in well-trained middle to older-aged adults has not been studied. Therefore, the purpose of this investigation was to examine the effects of a NO3- rich beverage on submaximal constant work rate exercise time in well-trained middle to older-aged adults. METHODS: This was a randomized controlled cross-over trial with 15 well-trained middle to older-aged adults, 41-64 year-old, who received one of two treatments (NO3- rich beverage then placebo or placebo then NO3- rich beverage), after which an exercise test at 75 percent of the subject's maximal work rate was completed. RESULTS: The NO3- rich beverage increased plasma NO3- and NO2- levels by 260 µM and 0.47 µM, respectively (p<0.001). Exercise time was not significantly different (p = 0.31) between the NO3- rich versus placebo conditions (1130±151 vs 1060±132 sec, respectively). Changes in exercise time between the two conditions ranged from a 55% improvement to a 40% decrease with the NO3- rich beverage. Oxygen consumption and rating of perceived exertion were not significantly different between the two conditions. CONCLUSION: In middle to older-aged well-trained adults, NO3- supplementation has non-significant, albeit highly variable, effects on exercise tolerance. ClinicalTrials.gov Identifier: NCT03371966.

Evidence of Pathogen-Induced Immunogenetic Selection across the Large Geographic Range of a Wild Seabird.

Over evolutionary time, pathogen challenge shapes the immune phenotype of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between different clades. In this study, we examine the diversity in a key family of innate immune genes-the Toll-like receptors (TLRs)-across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7. We present evidence of positive selection in TLR4 and TLR5, which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world's most rapidly changing environments.

The effects of intensive dietary weight loss and exercise on gait in overweight and obese adults with knee osteoarthritis. The Intensive Diet and Exercise for Arthritis (IDEA) trial.

The Intensive Diet and Exercise for Arthritis (IDEA) trial was an 18-month randomized controlled trial that enrolled 454 overweight and obese older adults with symptomatic and radiographic knee osteoarthritis (OA). Participants were randomized to either exercise (E), intensive diet-induced weight loss (D), or intensive diet-induced weight loss plus exercise (D + E) interventions. We previously reported that the clinical benefits of D + E were significantly greater than with either intervention alone (e.g., greater pain reduction, and better function, mobility, and health-related quality of life). We now test the hypothesis that D + E has greater overall benefit on gait mechanics compared to either intervention alone. Knee joint loading was analyzed using inverse dynamics and musculoskeletal modeling. Analysis of covariance determined the interventions' effects on gait. The D + E group walked significantly faster at 18-month follow-up (1.35 m s-1) than E (1.29 m s-1, p = 0.0004) and D (1.31 m s-1, p = 0.0007). Tibiofemoral compressive impulse was significantly lower (p = 0.0007) in D (1069 N s) and D + E (1054 N s) compared to E (1130 N s). D had significantly lower peak hip external rotation moment (p = 0.01), hip abduction moment (p = 0.0003), and peak hip power production (p = 0.016) compared with E. Peak ankle plantar flexion moment was significantly less (p < 0.0001) in the two diet groups compared with E. There also was a significant dose-response to weight loss; participants that lost >10% of baseline body weight had significantly (p = 0.0001) lower resultant knee forces and lower muscle (quadriceps, hamstring, and gastrocnemius) forces than participants that had less weight loss. Compared to E, D produces significant load reductions at the hip, knee, and ankle; combining D with E attenuates these reductions, but most remain significantly better than with E alone.

A randomized pilot study of nitrate supplementation with beetroot juice in acute respiratory failure.

Nitrate rich beetroot juice (BRJ) can enhance nitric oxide signaling, leading to improved physical function in healthy and diseased populations, but its safety and biologic efficacy have not been evaluated in a critically ill population. We randomized 22 previously functional acute respiratory failure patients to either BRJ or placebo daily until day 14 or discharge. We measured blood nitrate and nitrite levels and quantified strength and physical function at intensive care unit (ICU) and hospital discharge. Participants were predominantly male (54%), aged 68.5 years with an APACHE III score of 62. BRJ increased plasma nitrate (mean 219.2 µM increase, p = 0.002) and nitrite levels (mean 0.144 µM increase, p = 0.02). We identified no adverse events. The unadjusted and adjusted effect sizes of the intervention on the short physical performance battery were small (d = 0.12 and d = 0.17, respectively). In this pilot trial, administration of BRJ was feasible and safe, increased blood nitrate and nitrate levels, but had a small effect on physical function. Future studies could evaluate the clinical efficacy of BRJ as a therapy to improve physical function in survivors of critical illness.

Appetite Regulation: Hormones, Peptides, and Neurotransmitters and Their Role in Obesity.

Understanding body weight regulation will aid in the development of new strategies to combat obesity. This review examines energy homeostasis and food intake behaviors, specifically with regards to hormones, peptides, and neurotransmitters in the periphery and central nervous system, and their potential role in obesity. Dysfunction in feeding signals by the brain is a factor in obesity. The hypothalamic (arcuate nucleus) and brainstem (nucleus tractus solitaris) areas integrate behavioral, endocrine, and autonomic responses via afferent and efferent pathways from and to the brainstem and peripheral organs. Neurons present in the arcuate nucleus express pro-opiomelanocortin, Neuropeptide Y, and Agouti Related Peptide, with the former involved in lowering food intake, and the latter two acutely increasing feeding behaviors. Action of peripheral hormones from the gut, pancreas, adipose, and liver are also involved in energy homeostasis. Vagal afferent neurons are also important in regulating energy homeostasis. Peripheral signals respond to the level of stored and currently available fuel. By studying their actions, new agents maybe developed that disable orexigenic responses and enhance anorexigenic signals. Although there are relatively few medications currently available for obesity treatment, a number of agents are in development that work through these pathways.

End-of-Trial Health Outcomes in Look AHEAD Participants who Elected to have Bariatric Surgery.

OBJECTIVE: This study examined end-of-trial health outcomes in participants in the Action for Health in Diabetes (Look AHEAD) trial who had bariatric surgery during the approximately 10-year randomized intervention. METHODS: Data were obtained from the Look AHEAD public access database of 4,901 individuals with type 2 diabetes and overweight/obesity who were assigned to intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) control group. Changes in outcomes in participants who had bariatric surgery were compared with those in participants with BMI ≥ 30 kg/m2 who remained in the ILI and DSE groups. RESULTS: A total of 99 DSE and 97 ILI participants had bariatric surgery. At randomization, these 196 participants were significantly younger and more likely to be female and to have higher BMI than the remaining ILI (N = 1,972) and DSE (N = 2,009) participants. At trial's end, surgically treated participants lost 19.3% of baseline weight, compared with 5.8% and 3.3% for the ILI and DSE groups, respectively, and were more likely to achieve partial or full remission of their diabetes. CONCLUSIONS: The large, sustained improvements in weight and diabetes observed in this self-selected sample of surgically treated participants are consistent with results of multiple randomized trials.

Effect of intensive diet and exercise on self-efficacy in overweight and obese adults with knee osteoarthritis: The IDEA randomized clinical trial.

Physical activity decreases the risk of osteoarthritis (OA)-related disability; however, pain and lack of confidence represent barriers for older adults with knee OA. The purpose of this study was to examine (a) the baseline associations among self-efficacy and physical activity, function, and pain; (b) longitudinal changes in self-efficacy; and (c) whether self-efficacy mediates treatment effects on clinical outcomes. The Intensive Diet and Exercise for Arthritis (IDEA) trial was a single-blind, randomized controlled 18-month study including 454 overweight/obese older adults (M age = 66 years) with knee OA. Participants were randomized to one of three interventions: exercise (E), diet-induced weight loss (D), or both (D+E). Self-efficacy for gait, balance, and walking duration were assessed at baseline, 6 months, and 18 months. Baseline associations were tested using Pearson correlations, and group least squares means were compared using mixed linear models at follow-up. Participants with higher self-efficacy reported significantly better physical function and less knee pain at baseline, walked farther (6-min walk), and were more physically active (all |r| > 0.12, all p < .01). Significant differences between groups were detected for all self-efficacy measures at 18 months; the D+E group reported significantly (all p < .005) higher self-efficacy for gait, walking duration, and balance compared with the D- or E-only groups. Self-efficacy significantly (p < .05) mediated treatment effects on physical function and pain at 18 months. A combined intervention of diet-induced weight loss and exercise is the treatment of choice to maximize self-efficacy, improve physical function, and reduce pain in overweight/obese adults with knee OA.

Comparative population genomics reveals key barriers to dispersal in Southern Ocean penguins.

The mechanisms that determine patterns of species dispersal are important factors in the production and maintenance of biodiversity. Understanding these mechanisms helps to forecast the responses of species to environmental change. Here, we used a comparative framework and genomewide data obtained through RAD-Seq to compare the patterns of connectivity among breeding colonies for five penguin species with shared ancestry, overlapping distributions and differing ecological niches, allowing an examination of the intrinsic and extrinsic barriers governing dispersal patterns. Our findings show that at-sea range and oceanography underlie patterns of dispersal in these penguins. The pelagic niche of emperor (Aptenodytes forsteri), king (A. patagonicus), Adélie (Pygoscelis adeliae) and chinstrap (P. antarctica) penguins facilitates gene flow over thousands of kilometres. In contrast, the coastal niche of gentoo penguins (P. papua) limits dispersal, resulting in population divergences. Oceanographic fronts also act as dispersal barriers to some extent. We recommend that forecasts of extinction risk incorporate dispersal and that management units are defined by at-sea range and oceanography in species lacking genetic data.

Intentional Weight Loss in Overweight and Obese Patients With Knee Osteoarthritis: Is More Better?

OBJECTIVE: To determine the dose response effect of weight loss on clinical and mechanistic outcomes in overweight and obese adults with knee osteoarthritis (OA). METHODS: This is a secondary analysis of the diet-induced weight loss only (D) and diet-induced weight loss plus exercise (D + E) groups in the Intensive Diet and Exercise for Arthritis randomized controlled clinical trial. The 240 participants were overweight and obese older community-dwelling adults with pain and radiographic knee OA. Participants were assigned to 1 of 4 groups according to weight loss achieved over an 18-month period: <5% (<5% group), 5-10% (≥5% group), 10-20% (≥10% group), and >20% (≥20% group). RESULTS: There were significant dose responses to weight loss for pain (P = 0.01), function (P = 0.0006), 6-minute walk distance (P < 0.0001), physical (P = 0.0004) and mental (P = 0.03) health-related quality of life (HRQoL), knee joint compressive force (P < 0.0001), and interleukin-6 (P = 0.002). Greater weight loss resulted in superior clinical and mechanstic outcomes, with the highest weight loss group (≥20% group) distinguishing itself on all measures compared with the <5% and ≥5% groups; the ≥20% group had 25% less pain and better function compared with the ≥10% group and significantly (P = 0.006) better physical HRQoL. CONCLUSION: Long-term weight loss of 10-19.9% of baseline body weight has substantial clinical and mechanistic benefits compared with less weight loss. The value of an additional 10% weight loss includes significantly improved physical HRQoL and a clinically important reduction of pain and improvement in function.