Long Distance Runners Present Upregulated Sweating Responses than Sedentary Counterparts

Relatively few studies have investigated peripheral sweating mechanisms of long-distance runners. The aim of this study was to compare peripheral sweating mechanisms in male long-distance runners, and sedentary counterparts. Thirty six subjects, including 20 sedentary controls and 16 long-distance runners (with 7–12 years of athletic training, average 9.2±2.1 years) were observed. Quantitative sudomotor axon reflex testing (QSART) with iontophoresis (2 mA for 5 min) and 10% acetylcholine (ACh) were performed to determine axon reflex-mediated and directly activated (DIR, muscarinic receptor) sweating. Sweat onset time, sweat rate, number of activated sweat glands, sweat output per gland and skin temperature were measured at rest while maximum oxygen uptake (VO₂max) were measured during maximal cycling. Sweat rate, activated sweat glands, sweat output per gland, skin temperature and VO₂max were significantly higher in the trained runners than in the sedentary controls. Sweat onset time was significantly shorter for the runners. In the group of long-distance runners, significant correlations were found between VO₂max and sweat onset time (r² = 0.543, P<0.01, n = 16), DIR sweat rate (r² = 0.584, P<0.001, n = 16), sweat output per gland (r² = 0.539, P<0.01, n = 16). There was no correlation between VO₂max and activated sweat glands. These findings suggest that habitual long-distance running results in upregulation of the peripheral sweating mechanisms in humans. Additional research is needed to determine the molecular mechanism underlying these changes. These findings complement the existing sweating data in long-distance runners.     

Knee muscle forces during walking and running in patellofemoral pain patients and pain-free controls

One proposed mechanism of patellofemoral pain, increased stress in the joint, is dependent on forces generated by the quadriceps muscles. Describing causal relationships between muscle forces, tissue stresses, and pain is difficult due to the inability to directly measure these variables in vivo. The purpose of this study was to estimate quadriceps forces during walking and running in a group of male and female patients with patellofemoral pain (n=27, 16 female; 11 male) and compare these to pain-free controls (n=16, 8 female; 8 male). Subjects walked and ran at self-selected speeds in a gait laboratory. Lower limb kinematics and electromyography (EMG) data were input to an EMG-driven musculoskeletal model of the knee, which was scaled and calibrated to each individual to estimate forces in 10 muscles surrounding the joint. Compared to controls, the patellofemoral pain group had greater co-contraction of quadriceps and hamstrings (p=0.025) and greater normalized muscle forces during walking, even though the net knee moment was similar between groups. Muscle forces during running were similar between groups, but the net knee extension moment was less in the patellofemoral pain group compared to controls. Females displayed 30–50% greater normalized hamstring and gastrocnemius muscle forces during both walking and running compared to males (p<0.05). These results suggest that some patellofemoral pain patients might experience greater joint contact forces and joint stresses than pain-free subjects. The muscle force data are available as supplementary material.     

Alveolar-Membrane Diffusing Capacity Limits Performance in Boston Marathon Qualifiers

Purpose(1) to examine the relation between pulmonary diffusing capacity and marathon finishing time, and (2), to evaluate the accuracy of pulmonary diffusing capacity for nitric oxide (DLNO) in predicting marathon finishing time relative to that of pulmonary diffusing capacity for carbon monoxide (DLCO).Methods28 runners [18 males, age = 37 (SD 9) years, body mass = 70 (13) kg, height = 173 (9) cm, percent body fat = 17 (7) %] completed a test battery consisting of measurement of DLNO and DLCO at rest, and a graded exercise test to determine running economy and aerobic capacity prior to the 2011 Steamtown Marathon (Scranton, PA). One to three weeks later, all runners completed the marathon (range: 2∶22:38 to 4∶48:55). Linear regressions determined the relation between finishing time and a variety of anthropometric characteristics, resting lung function variables, and exercise parameters.ResultsIn runners meeting Boston Marathon qualification standards, 74% of the variance in marathon finishing time was accounted for by differences in DLNO relative to body surface area (BSA) (SEE = 11.8 min, p<0.01); however, the relation between DLNO or DLCO to finishing time was non-significant in the non-qualifiers (p = 0.14 to 0.46). Whereas both DLCO and DLNO were predictive of finishing time for all finishers, DLNO showed a stronger relation (r² = 0.30, SEE = 33.4 min, p<0.01) compared to DLCO when considering BSA.ConclusionDLNO is a performance-limiting factor in only Boston qualifiers. This suggests that alveolar-capillary membrane conductance is a limitation to performance in faster marathoners. Additionally, DLNO/BSA predicts marathon finishing time and aerobic capacity more accurately than DLCO.     

Prevalence of Consensual Male–Male Sex and Sexual Violence,and Associations with HIV in South Africa: A Population-Based Cross-Sectional Study

Background

In sub-Saharan Africa the population prevalence of men who have sex with men (MSM) is unknown, as is the population prevalence of male-on-male sexual violence, and whether male-on-male sexual violence may relate to HIV risk. This paper describes lifetime prevalence of consensual male–male sexual behavior and male-on-male sexual violence (victimization and perpetration) in two South African provinces, socio-demographic factors associated with these experiences, and associations with HIV serostatus.

Methods and Findings

In a cross-sectional study conducted in 2008, men aged 18–49 y from randomly selected households in the Eastern Cape and KwaZulu-Natal provinces provided anonymous survey data and dried blood spots for HIV serostatus assessment. Interviews were completed in 1,737 of 2,298 (75.6%) of enumerated and eligible households. From these households, 1,705 men (97.1%) provided data on lifetime history of same-sex experiences, and 1,220 (70.2%) also provided dried blood spots for HIV testing. 5.4% (n = 92) of participants reported a lifetime history of any consensual sexual activity with another man; 9.6% (n = 164) reported any sexual victimization by a man, and 3.0% (n = 51) reported perpetrating sexual violence against another man. 85.0% (n = 79) of men with a history of consensual sex with men reported having a current female partner, and 27.7% (n = 26) reported having a current male partner. Of the latter, 80.6% (n = 21/26) also reported having a female partner. Men reporting a history of consensual male–male sexual behavior are more likely to have been a victim of male-on-male sexual violence (adjusted odds ratio [aOR] = 7.24; 95% CI 4.26–12.3), and to have perpetrated sexual violence against another man (aOR = 3.10; 95% CI 1.22–7.90). Men reporting consensual oral/anal sex with a man were more likely to be HIV+ than men with no such history (aOR = 3.11; 95% CI 1.24–7.80). Men who had raped a man were more likely to be HIV+ than non-perpetrators (aOR = 3.58; 95% CI 1.17–10.9).

Conclusions

In this sample, one in 20 men (5.4%) reported lifetime consensual sexual contact with a man, while about one in ten (9.6%) reported experience of male-on-male sexual violence victimization. Men who reported having had sex with men were more likely to be HIV+, as were men who reported perpetrating sexual violence towards other men. Whilst there was no direct measure of male–female concurrency (having overlapping sexual relationships with men and women), the data suggest that this may have been common. These findings suggest that HIV prevention messages regarding male–male sex in South Africa should be mainstreamed with prevention messages for the general population, and sexual health interventions and HIV prevention interventions for South African men should explicitly address male-on-male sexual violence. Please see later in the article for the Editors'' Summary     

Shoe midsole hardness, sex and age effects on lower extremity kinematics during running

Previous studies investigating the effects of shoe midsole hardness on running kinematics have often used male subjects from within a narrow age range. It is unknown whether shoe midsole hardness has the same kinematic effect on male and female runners as well as runners from different age categories. As sex and age have an effect on running kinematics, it is important to understand if shoe midsole hardness affects the kinematics of these groups in a similar fashion. However, current literature on the effects of sex and age on running kinematics are also limited to a narrow age range distribution in their study population. Therefore, this study tested the influence of three different midsole hardness conditions, sex and age on the lower extremity kinematics during heel-toe running. A comprehensive analysis approach was used to analyze the lower-extremity kinematic gait variables for 93 runners (male and female) aged 16-75 years. Participants ran at 3.33±0.15 m/s on a 30 m-long runway with soft, medium and hard midsoles. A principal component analysis combined with a support vector machine showed that running kinematics based on shoe midsole hardness, sex, and age were separable and classifiable. Shoe midsole hardness demonstrated a subject-independent effect on the kinematics of running. Additionally, it was found that age differences affected the more dominant movement components of running compared to differences due to the sex of a runner.     

Exercise Training in Transgenic Mice Is Associated with Attenuation of Early Breast Cancer Growth in a Dose-Dependent Manner

Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence. It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved. We investigated the effects of voluntary wheel running on tumor progression and cytokine gene expression in the transgenic polyoma middle T oncoprotein (PyMT) mouse model of invasive breast cancer. Runners showed significantly reduced tumor sizes compared with non-runners after 3 weeks of running (p≤0.01), and the greater the running distance the smaller the tumor size (Pearson''s r = −0.61, p≤0.04, R² = 0.38). Mice running greater than 150 km per week had a significantly attenuated tumor size compared with non-runners (p≤0.05). Adipose tissue mass was inversely correlated with tumor size in runners (Pearson''s r = −0.77, p = 0.014) but not non-runners. Gene expression of CCL22, a cytokine associated with recruitment of immunosuppressive T regulatory cells, was decreased in tumors of runners compared to non-runners (p≤0.005). No differences in tumor burden or metastatic burden were observed between runners and non-runners after ten weeks of running when the study was completed. We conclude that voluntary wheel running in PyMT mice correlates with an attenuation in tumor progression early during the course of invasive breast cancer. This effect is absent in the later stages of overwhelming tumor burden even though cytokine signaling for immunosuppressive regulatory T cells was down regulated. These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.     

Longer Leukocyte Telomeres Are Associated with Ultra-Endurance Exercise Independent of Cardiovascular Risk Factors

Telomere length is recognized as a marker of biological age, and shorter mean leukocyte telomere length is associated with increased risk of cardiovascular disease. It is unclear whether repeated exposure to ultra-endurance aerobic exercise is beneficial or detrimental in the long-term and whether it attenuates biological aging. We quantified 67 ultra-marathon runners’ and 56 apparently healthy males’ leukocyte telomere length (T/S ratio) using real-time quantitative PCR. The ultra-marathon runners had 11% longer telomeres (T/S ratio) than controls (ultra-marathon runners: T/S ratio = 3.5±0.68, controls: T/S ratio = 3.1±0.41; β = 0.40, SE = 0.10, P = 1.4×10⁻⁴) in age-adjusted analysis. The difference remained statistically significant after adjustment for cardiovascular risk factors (P = 2.2×10⁻⁴). The magnitude of this association translates into 16.2±0.26 years difference in biological age and approximately 324–648bp difference in leukocyte telomere length between ultra-marathon runners and healthy controls. Neither traditional cardiovascular risk factors nor markers of inflammation/adhesion molecules explained the difference in leukocyte telomere length between ultra-marathon runners and controls. Taken together these data suggest that regular engagement in ultra-endurance aerobic exercise attenuates cellular aging.     

Is the COL5A1 rs12722 Gene Polymorphism Associated with Running Economy?

The COL5A1 rs12722 polymorphism is considered to be a novel genetic marker for endurance running performance. It has been postulated that COL5A1 rs12722 may influence the elasticity of tendons and the energetic cost of running. To date, there are no experimental data in the literature supporting the relationship between range of motion, running economy, and the COL5A1 rs12722 gene polymorphism. Therefore, the main purpose of the current study was to analyze the influence of the COL5A1rs12722 polymorphism on running economy and range of motion. One hundred and fifty (n = 150) physically active young men performed the following tests: a) a maximal incremental treadmill test, b) two constant-speed running tests (10 km•h⁻¹ and 12 km•h⁻¹) to determine the running economy, and c) a sit-and-reach test to determine the range of motion. All of the subjects were genotyped for the COL5A1 rs12722 single-nucleotide polymorphism. The genotype frequencies were TT = 27.9%, CT = 55.8%, and CC = 16.3%. There were no significant differences between COL5A1 genotypes for running economy measured at 10 km•h⁻¹ (p = 0.232) and 12 km•h⁻¹ (p = 0.259). Similarly, there were no significant differences between COL5A1 genotypes for range of motion (p = 0.337). These findings suggest that the previous relationship reported between COL5A1 rs12722 genotypes and running endurance performance might not be mediated by the energetic cost of running.     

Alterations in Postural Control during the World's Most Challenging Mountain Ultra-Marathon

We investigated postural control (PC) effects of a mountain ultra-marathon (MUM): a 330-km trail run with 24000 m of positive and negative change in elevation. PC was assessed prior to (PRE), during (MID) and after (POST) the MUM in experienced ultra-marathon runners (n = 18; finish time = 126±16 h) and in a control group (n = 8) with a similar level of sleep deprivation. Subjects were instructed to stand upright on a posturographic platform over a period of 51.2 seconds using a double-leg stance under two test conditions: eyes open (EO) and eyes closed (EC). Traditional measures of postural stability (center of pressure trajectory analysis) and stabilogram-diffusion analysis (SDA) parameters were analysed. For the SDA, a significantly greater short-term effective diffusion was found at POST compared with PRE in the medio-lateral (ML; Dxs) and antero-posterior (AP) directions (Dys) in runners (p<0.05) The critical time interval (Ctx) in the ML direction was significantly higher at MID (p<0.001) and POST (p<0.05) than at PRE in runners. At MID (p<0.001) and POST (p<0.05), there was a significant difference between the two groups. The critical displacement (Cdx) in the ML was significantly higher at MID and at POST (p<0.001) compared with PRE for runners. A significant difference in Cdx was observed between groups in EO at MID (p<0.05) and POST (p<0.005) in the ML direction and in EC at POST in the ML and AP directions (p<0.05).Our findings revealed significant effects of fatigue on PC in runners, including, a significant increase in Ctx (critical time in ML plan) in EO and EC conditions. Thus, runners take longer to stabilise their body at POST than at MID. It is likely that the mountainous characteristics of MUM (unstable ground, primarily uphill/downhill running, and altitude) increase this fatigue, leading to difficulty in maintaining balance.     

Relation of Pulse Pressure to Long-Distance Gait Speed in Community-Dwelling Older Adults: Findings from the LIFE-P Study

Background

Reduced gait speed is associated with falls, late-life disability, hospitalization/institutionalization and cardiovascular morbidity and mortality. Aging is also accompanied by a widening of pulse pressure (PP) that contributes to ventricular-vascular uncoupling. The purpose of this study was to test the hypothesis that PP is associated with long-distance gait speed in community-dwelling older adults in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study.

Methods

Brachial blood pressure and 400-meter gait speed (average speed maintained over a 400-meter walk at “usual” pace) were assessed in 424 older adults between the ages of 70–89 yrs at risk for mobility disability (mean age = 77 yrs; 31% male). PP was calculated as systolic blood pressure (BP) – diastolic BP.

Results

Patients with a history of heart failure and stroke (n = 42) were excluded leaving 382 participants for final analysis. When categorized into tertiles of PP, participants within the highest PP tertile had significantly slower gait speed than those within the lowest PP tertile (p<0.05). Following stepwise multiple regression, PP was significantly and inversely associated with 400-meter gait speed (p<0.05). Other significant predictors of gait speed included: handgrip strength, body weight, age and history of diabetes mellitus (p<0.05). Mean arterial pressure, systolic BP and diastolic BP were not predictors of gait speed.

Conclusions

Pulse pressure is associated long-distance gait speed in community-dwelling older adults. Vascular senescence and altered ventricular-vascular coupling may be associated with the deterioration of mobility and physical function in older adults.     

Classification accuracy of a single tri-axial accelerometer for training background and experience level in runners

Accelerometers are increasingly used tools for gait analysis, but there remains a lack of research on their application to running and their ability to classify running patterns. The purpose of this study was to conduct an exploratory examination into the capability of a tri-axial accelerometer to classify runners of different training backgrounds and experience levels, according to their 3-dimensional (3D) accelerometer data patterns. Training background was examined with 14 competitive soccer players and 12 experienced marathon runners, and experience level was examined with 16 first-time and the same 12 experienced marathon runners. Discrete variables were extracted from 3D accelerations during a short run using root mean square, wavelet transformation, and autocorrelation procedures. A principal component analysis (PCA) was conducted on all variables, including gait speed to account for covariance. Eight PCs were retained, explaining 88% of the variance in the data. A stepwise discriminant analysis of PCs was used to determine the binary classification accuracy for training background and experience level, with and without the PC of Speed. With Speed, the accelerometer correctly classified 96% of runners for both training background and experience level. Without Speed, the accelerometer correctly classified 85% of runners based on training background, but only 68% based on experience level. These findings suggest that the accelerometer is effective in classifying athletes of different training backgrounds, but is less effective for classifying runners of different experience levels where gait speed is the primary discriminator.     

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Stroke: A Systematic Review and Meta-Analysis

Background

The PlA1/A2 polymorphism of glycoprotein IIIa (GPIIIa) has been reported to be associated with risk of stroke in some studies, although other studies suggest no such association. This meta-analysis and systematic review was conducted to investigate the hypothesis that carriage of the PlA2 allele is a risk factor for stroke.

Methods

Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating carriage of the PlA2 allele and the incidence of stroke. Pooled odds ratios (ORs) were calculated using fixed-effect and random-effect models.

Findings

A total of 35 articles were eligible for inclusion, of which 25 studies were suitable for statistical analysis. For carriage of the PlA2 allele, OR 1.12 (n = 11,873; 95% CI = 1.03–1.22; p = 0.011) was observed for the incidence of stroke in adults, with subgroup analyses identifying the association driven by stroke of an ischaemic (n = 10,494; OR = 1.15, 95% CI = 1.05–1.27; p = 0.003) but not haemorrhagic aetiology (n = 2,470; OR = 0.90, 95% CI = 0.71–1.14; p = 0.398). This association with ischaemic stroke was strongest in individuals homozygous for the PlA2 allele compared to those homozygous for wild-type PlA1 (n = 5,906; OR = 1.74, 95% CI = 1.34–2.26; p<0.001). Subgroup analysis of ischaemic stroke subtypes revealed an increased association with stroke of cardioembolic (n = 1,271; OR 1.56, 95% CI 1.14–2.12; p = 0.005) and large vessel (n = 1,394; OR = 1.76, 95% CI 1.34–2.31; p<0.001) aetiology, but not those of small vessel origin (n = 1,356; OR = 0.99, 95% CI 0.74–1.33; p = 0.950). Egger''s regression test suggested a low probability of publication bias for all analyses (p>0.05).

Conclusions

The totality of published data supports the hypothesis that carriage of the PlA2 polymorphism of GPIIIa is a risk factor for ischaemic strokes, and specifically those of cardioembolic and large vessel origin.     

Identifying Gender-Preferred Communication Styles within Online Cancer Communities: A Retrospective,Longitudinal Analysis

Background

The goal of this research is to determine if different gender-preferred social styles can be observed within the user interactions at an online cancer community. To achieve this goal, we identify and measure variables that pertain to each gender-specific social style.

Methods and Findings

We perform social network and statistical analysis on the communication flow of 8,388 members at six different cancer forums over eight years. Kruskal-Wallis tests were conducted to measure the difference between the number of intimate (and highly intimate) dyads, relationship length, and number of communications. We determine that two patients are more likely to form an intimate bond on a gender-specific cancer forum (ovarian P = <0.0001, breast P = 0.0089, prostate P = 0.0021). Two female patients are more likely to form a highly intimate bond on a female-specific cancer forum (Ovarian P<0.0001, Breast P<0.01). Typically a male patient communicates with more members than a female patient (Ovarian forum P = 0.0406, Breast forum P = 0.0013). A relationship between two patients is longer on the gender-specific cancer forums than a connection between two members not identified as patients (ovarian forum P = 0.00406, breast forum P = 0.00013, prostate forum P = .0.0003).

Conclusion

The high level of interconnectedness among the prostate patients supports the hypothesis that men prefer to socialize in large, interconnected, less-intimate groups. A female patient is more likely to form a highly intimate connection with another female patient; this finding is consistent with the hypothesis that woman prefer fewer, more intimate connections. The relationships of same-gender cancer patients last longer than other relationships; this finding demonstrates homophily within these online communities. Our findings regarding online communication preferences are in agreement with research findings from person-to-person communication preference studies. These findings should be considered when designing online communities as well as designing and evaluating psychosocial and educational interventions for cancer patients.     

Support vector machines for detecting age-related changes in running kinematics

Age-related changes in running kinematics have been reported in the literature using classical inferential statistics. However, this approach has been hampered by the increased number of biomechanical gait variables reported and subsequently the lack of differences presented in these studies. Data mining techniques have been applied in recent biomedical studies to solve this problem using a more general approach. In the present work, we re-analyzed lower extremity running kinematic data of 17 young and 17 elderly male runners using the Support Vector Machine (SVM) classification approach. In total, 31 kinematic variables were extracted to train the classification algorithm and test the generalized performance. The results revealed different accuracy rates across three different kernel methods adopted in the classifier, with the linear kernel performing the best. A subsequent forward feature selection algorithm demonstrated that with only six features, the linear kernel SVM achieved 100% classification performance rate, showing that these features provided powerful combined information to distinguish age groups. The results of the present work demonstrate potential in applying this approach to improve knowledge about the age-related differences in running gait biomechanics and encourages the use of the SVM in other clinical contexts.     

Injectable and Oral Contraceptive Use and Cancers of the Breast,Cervix, Ovary,and Endometrium in Black South African Women: Case–Control Study

Background

Oral contraceptives are known to influence the risk of cancers of the female reproductive system. Evidence regarding the relationship between injectable contraceptives and these cancers is limited, especially in black South Africans, among whom injectable contraceptives are used more commonly than oral contraceptives.

Methods and Findings

We analysed data from a South African hospital-based case–control study of black females aged 18–79 y, comparing self-reported contraceptive use in patients with breast (n = 1,664), cervical (n = 2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported contraceptive use in 1,492 control patients diagnosed with cancers with no known relationship to hormonal contraceptive use. We adjusted for potential confounding factors, including age, calendar year of diagnosis, education, smoking, alcohol, parity/age at first birth, and number of sexual partners. Among controls, 26% had used injectable and 20% had used oral contraceptives. For current and more recent users versus never users of oral or injectable contraceptives, the odds ratios (ORs) for breast cancer were significantly increased in users of oral and/or injectable contraceptives (OR 1.66, 95% CI 1.28–2.16, p<0.001) and separately among those exclusively using oral (1.57, 1.03–2.40, p = 0.04) and exclusively using injectable (OR 1.83, 1.31–2.55, p<0.001) contraceptives; corresponding ORs for cervical cancer were 1.38 (1.08–1.77, p = 0.01), 1.01 (0.66–1.56, p = 0.96), and 1.58 (1.16–2.15, p = 0.004). There was no significant increase in breast or cervical cancer risk among women ceasing hormonal contraceptive use ≥10 y previously (p = 0.3 and p = 0.9, respectively). For durations of use ≥5 y versus never use, the ORs of ovarian cancer were 0.60 (0.36–0.99, p = 0.04) for oral and/or injectable contraceptive use and 0.07 (0.01–0.49, p = 0.008) for injectable use exclusively; corresponding ORs for endometrial cancer were 0.44 (0.22–0.86, p = 0.02) and 0.36 (0.11–1.26, p = 0.1).

Conclusions

In this study, use of oral and of injectable hormonal contraceptives was associated with a transiently increased risk of breast and cervical cancer and, for long durations of use, with a reduced risk of ovarian and endometrial cancer. The observed effects of injectable and of oral contraceptives on cancer risk in this study did not appear to differ substantially. Please see later in the article for the Editors'' Summary     

Running for Exercise Mitigates Age-Related Deterioration of Walking Economy

Introduction

Impaired walking performance is a key predictor of morbidity among older adults. A distinctive characteristic of impaired walking performance among older adults is a greater metabolic cost (worse economy) compared to young adults. However, older adults who consistently run have been shown to retain a similar running economy as young runners. Unfortunately, those running studies did not measure the metabolic cost of walking. Thus, it is unclear if running exercise can prevent the deterioration of walking economy.

Purpose

To determine if and how regular walking vs. running exercise affects the economy of locomotion in older adults.

Methods

15 older adults (69±3 years) who walk ≥30 min, 3x/week for exercise, “walkers” and 15 older adults (69±5 years) who run ≥30 min, 3x/week, “runners” walked on a force-instrumented treadmill at three speeds (0.75, 1.25, and 1.75 m/s). We determined walking economy using expired gas analysis and walking mechanics via ground reaction forces during the last 2 minutes of each 5 minute trial. We compared walking economy between the two groups and to non-aerobically trained young and older adults from a prior study.

Results

Older runners had a 7–10% better walking economy than older walkers over the range of speeds tested (p = .016) and had walking economy similar to young sedentary adults over a similar range of speeds (p = .237). We found no substantial biomechanical differences between older walkers and runners. In contrast to older runners, older walkers had similar walking economy as older sedentary adults (p = .461) and ∼26% worse walking economy than young adults (p<.0001).

Conclusion

Running mitigates the age-related deterioration of walking economy whereas walking for exercise appears to have minimal effect on the age-related deterioration in walking economy.     

Mildly Elevated Serum Bilirubin Levels Are Negatively Associated with Carotid Atherosclerosis among Elderly Persons

Serum bilirubin may have a beneficial role in preventing oxidative changes in atherosclerosis. Limited information is available on whether serum total bilirubin is an independent confounding factor for carotid atherosclerosis {for example, intima-media thickness (IMT), plaque} measured noninvasively by B-mode ultrasonography only among elderly persons. The study subjects were 325 men aged 79±8 (mean ± standard deviation) years and 509 women aged 81±8 years that were enrolled consecutively from patients aged ≥60 years in the medical department. Carotid IMT and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that in men age (β = 0.199, p = 0.002), smoking status (β = 0.154, p = 0.006), GGT (β = -0.139, p = 0.039), and GGT (β = -0.133, p = 0.022) were significantly and independently associated with carotid IMT, and in women age (β = 0.186, p<0.001), systolic blood pressure (β = 0.104, p = 0.046), diastolic blood pressure (β = -0.148, p = 0.004), prevalence of antihypertensive medication (β = 0.126, p = 0.004), fasting plasma glucose (β = 0.135, p = 0.003), GGT (β = -0.104, p = 0.032), estimated glomerular filtration rate, serum bilirubin (β = -0.119, p = 0.006), and prevalence of cardiovascular disease (CVD) (β = 0.103, p = 0.017) were also independently associated with carotid IMT. The odds ratios (ORs) {95% confidence interval (CI)} of increasing serum bilirubin category were negatively associated with carotid IMT ≥1.0 mm and plaque in both genders. Compared to subjects with a serum bilirubin of Quartile-1, the multivariate-OR (95% CI) of carotid plaque was 0.25 (0.11–0.57) in the Quartile-4 male group, and 0.41 (0.21–0.78) in the Quartile-2 female group, 0.51 (0.26–0.98) in the Quartile-3 female group, and 0.46 (0.24–0.89) in the Quartile-4 female group. Our data demonstrated an independently negative association between serum bilirubin and carotid atherosclerosis in both genders.     

A Functional Polymorphism in a Serotonin Transporter Gene (5-HTTLPR) Interacts with 9/11 to Predict Gun-Carrying Behavior

On September 11, 2001, one of the deadliest terrorist attacks in US history took place on American soil and people around the world were impacted in myriad ways. Building on prior literature which suggests individuals are more likely to purchase a gun for self-protection if they are fearful of being victimized, the authors hypothesized that the terrorist attacks of 9/11 would lead to an increase in gun carrying among US residents. At the same time, a line of research has shown that a polymorphism in the 5-HTT gene (i.e., 5-HTTLPR) interacts with environmental stressors to predict a range of psychopathologies and behaviors. Thus, it was hypothesized that 9/11 and 5-HTTLPR would interact to predict gun carrying. The results supported both hypotheses by revealing a positive association between 9/11 and gun carrying (b = .426, odds ratio = 1.531, standard error for b = .194, z = 2.196, p = .028) in the full sample of respondents (n = 15,052) and a statistically significant interaction between 9/11 and 5-HTTLPR in the prediction of gun carrying (b = −1.519, odds ratio = .219, standard error for b = .703, z = −2.161, p = .031) in the genetic subsample of respondents (n = 2,350). This is one of the first studies to find an association between 9/11 and gun carrying and, more importantly, is the first study to report a gene-environment interaction (GxE) between a measured gene and a terrorist attack.     

Are Treatments More Effective than Placebos? A Systematic Review and Meta-Analysis

BackgroundPlacebos are widely used in clinical practice in spite of ethical restrictions. Whether such use is justified depends in part on the relative benefit of placebos compared to ‘active’ treatments. A direct test for differences between placebo and ‘active’ treatment effects has not been conducted.ObjectivesWe aimed to test for differences between treatment and placebo effects within similar trial populations.ResultsIn trials with continuous outcomes (n = 115) we found no difference between treatment and placebo effects (MD = −0.29, 95% CI −0.62 to 0.05, P = 0.10). In trials with binary outcomes (n = 37) treatments were significantly more effective than placebos (RRR = 0.72, 95%CI = 0.61 to 0.86, P = 0.0003). Treatment and placebo effects were not different in 22 out of 28 predefined subgroup analyses. Of the six subgroups with differences treatments were more effective than placebos in five. However when all criteria for reducing bias were ruled out (continuous outcomes) placebos were more effective than treatments (MD = 1.59, 95% CI = 0.40 to 2.77, P = 0.009).

Conclusions and Implications

Placebos and treatments often have similar effect sizes. Placebos with comparatively powerful effects can benefit patients either alone or as part of a therapeutic regime, and trials involving such placebos must be adequately blinded.     

The Causal Effect of Vitamin D Binding Protein (DBP) Levels on Calcemic and Cardiometabolic Diseases: A Mendelian Randomization Study

Background

Observational studies have shown that vitamin D binding protein (DBP) levels, a key determinant of 25-hydroxy-vitamin D (25OHD) levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease.

Methods and Findings

We measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos). Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism) and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke) and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age- and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n = 2,254). DBP had a strong observational and causal association with 25OHD levels (p = 3.2×10⁻¹⁹). While DBP levels were observationally associated with calcium and body mass index (BMI), these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI −0.01, 0.01]; p = 1.00; n = 46,186); fasting insulin (0.01 pmol/l [95% CI −0.00, 0.01,]; p = 0.22; n = 46,186); BMI (0.00 kg/m² [95% CI −0.01, 0.01]; p = 0.80; n = 127,587); bone mineral density (0.01 g/cm² [95% CI −0.01, 0.03]; p = 0.36; n = 32,961); mean arterial pressure (−0.06 mm Hg [95% CI −0.19, 0.07]); p = 0.36; n = 28,775); ischemic stroke (odds ratio [OR] = 1.00 [95% CI 0.97, 1.04]; p = 0.92; n = 12,389/62,004 cases/controls); coronary artery disease (OR = 1.02 [95% CI 0.99, 1.05]; p = 0.31; n = 22,233/64,762); or type 2 diabetes (OR = 1.01 [95% CI 0.97, 1.05]; p = 0.76; n = 9,580/53,810).

Conclusions

DBP has no demonstrable causal effect on any of the diseases or traits investigated here, except 25OHD levels. It remains to be determined whether 25OHD has a causal effect on these outcomes independent of DBP. Please see later in the article for the Editors'' Summary