HLA-C expression in extravillous trophoblasts is determined by an ELF3-NLRP2/NLRP7 regulatory axis.

The distinct human leukocyte antigen (HLA) class I expression pattern of human extravillous trophoblasts (EVT) endows them with unique tolerogenic properties that enable successful pregnancy. Nevertheless, how this process is elaborately regulated remains elusive. Previously, E74 like ETS transcription factor 3 (ELF3) was identified to govern high-level HLA-C expression in EVT. In the present study, ELF3 is found to bind to the enhancer region of two adjacent NOD-like receptor (NLR) genes, NLR family pyrin domain-containing 2 and 7 (NLRP2, NLRP7). Notably, our analysis of ELF3-deficient JEG-3 cells, a human choriocarcinoma cell line widely used to study EVT biology, suggests that ELF3 transactivates NLRP7 while suppressing the expression of NLRP2. Moreover, we find that NLRP2 and NLRP7 have opposing effects on HLA-C expression, thus implicating them in immune evasion at the maternal-fetal interface. We confirmed that NLRP2 suppresses HLA-C levels and described a unique role for NLRP7 in promoting HLA-C expression in JEG-3. These results suggest that these two NLR genes, which arose via gene duplication in primates, are fine-tuned by ELF3 yet have acquired divergent functions to enable proper expression levels of HLA-C in EVT, presumably through modulating the degradation kinetics of IkBα. Targeting the ELF3-NLRP2/NLRP7-HLA-C axis may hold therapeutic potential for managing pregnancy-related disorders, such as recurrent hydatidiform moles and fetal growth restriction, and thus improve placental development and pregnancy outcomes.

Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia.

Sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli to the central nervous system. Single-cell RNA sequencing has provided insights into the diversity of sensory ganglia cell types in rodents, nonhuman primates, and humans, but it remains difficult to compare cell types across studies and species. We thus constructed harmonized atlases of the DRG and TG that describe and facilitate comparison of 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. We then performed single-cell/nucleus RNA sequencing of DRG from both human and the highly regenerative axolotl and found that the harmonized atlas also improves cell type annotation, particularly of sparse neuronal subtypes. We observed that the transcriptomes of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The resources presented here can guide future studies in comparative transcriptomics, simplify cell-type nomenclature differences across studies, and help prioritize targets for future analgesic development.

Fluorescence-guided surgical system using holographic display: from phantom studies to canine patients.

Significance: Holographic display technology is a promising area of research that can lead to significant advancements in cancer surgery. We present the benefits of combining bioinspired multispectral imaging technology with holographic goggles for fluorescence-guided cancer surgery. Through a series of experiments with 43D-printed phantoms, small animal models of cancer, and surgeries on canine patients with head and neck cancer, we showcase the advantages of this holistic approach. Aim: The aim of our study is to demonstrate the feasibility and potential benefits of utilizing holographic display for fluorescence-guided surgery through a series of experiments involving 3D-printed phantoms and canine patients with head and neck cancer. Approach: We explore the integration of a bioinspired camera with a mixed reality headset to project fluorescent images as holograms onto a see-through display, and we demonstrate the potential benefits of this technology through benchtop and in vivo animal studies. Results: Our complete imaging and holographic display system showcased improved delineation of fluorescent targets in phantoms compared with the 2D monitor display approach and easy integration into the veterinarian surgical workflow. Conclusions: Based on our findings, it is evident that our comprehensive approach, which combines a bioinspired multispectral imaging sensor with holographic goggles, holds promise in enhancing the presentation of fluorescent information to surgeons during intraoperative scenarios while minimizing disruptions.

Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia.

Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli including touch, temperature, and pain to the central nervous system. Recent advances in single-cell RNA-sequencing (scRNA-seq) have provided new insights into the diversity of sensory ganglia cell types in rodents, non-human primates, and humans, but it remains difficult to compare transcriptomically defined cell types across studies and species. Here, we built cross-species harmonized atlases of DRG and TG cell types that describe 18 neuronal and 11 non-neuronal cell types across 6 species and 19 studies. We then demonstrate the utility of this harmonized reference atlas by using it to annotate newly profiled DRG nuclei/cells from both human and the highly regenerative axolotl. We observe that the transcriptomic profiles of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The new resources and data presented here can guide future studies in comparative transcriptomics, simplify cell type nomenclature differences across studies, and help prioritize targets for future pain therapy development.

Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models.

Real-time guidance through fluorescence imaging improves the surgical outcomes of tumor resections, reducing the chances of leaving positive margins behind. As tumors are heterogeneous, it is imperative to interrogate multiple overexpressed cancer biomarkers with high sensitivity and specificity to improve surgical outcomes. However, for accurate tumor delineation and ratiometric detection of tumor biomarkers, current methods require multiple excitation wavelengths to image multiple biomarkers, which is impractical in a clinical setting. Here, we have developed a biomimetic platform comprising near-infrared fluorescent semiconducting polymer nanoparticles (SPNs) with red blood cell membrane (RBC) coating, capable of targeting two representative cell-surface biomarkers (folate, αυß3 integrins) using a single excitation wavelength for tumor delineation during surgical interventions. We evaluate our single excitation ratiometric nanoparticles in in vitro tumor cells, ex vivo tumor-mimicking phantoms, and in vivo mouse xenograft tumor models. Favorable biological properties (improved biocompatibility, prolonged blood circulation, reduced liver uptake) are complemented by superior spectral features: (i) specific fluorescence enhancement in tumor regions with high tumor-to-normal tissue (T/NT) ratios in ex vivo samples and (ii) estimation of cell-surface tumor biomarkers with single wavelength excitation providing insights about cancer progression (metastases). Our single excitation, dual output approach has the potential to differentiate between the tumor and healthy regions and simultaneously provide a qualitative indicator of cancer progression, thereby guiding surgeons in the operating room with the resection process.

Bioinspired color-near infrared endoscopic imaging system for molecular guided cancer surgery.

Significance: Fluorescently guided minimally invasive surgery is improving patient outcomes and disease-free survival, but biomarker variability hinders complete tumor resection with single molecular probes. To overcome this, we developed a bioinspired endoscopic system that images multiple tumor-targeted probes, quantifies volumetric ratios in cancer models, and detects tumors in ex vivo samples. Aim: We present a new rigid endoscopic imaging system (EIS) that can capture color images while simultaneously resolving two near-infrared (NIR) probes. Approach: Our optimized EIS integrates a hexa-chromatic image sensor, a rigid endoscope optimized for NIR-color imaging, and a custom illumination fiber bundle. Results: Our optimized EIS achieves a 60% improvement in NIR spatial resolution when compared to a leading FDA-approved endoscope. Ratio-metric imaging of two tumor-targeted probes is demonstrated in vials and animal models of breast cancer. Clinical data gathered from fluorescently tagged lung cancer samples on the operating room's back table demonstrate a high tumor-to-background ratio and consistency with the vial experiments. Conclusions: We investigate key engineering breakthroughs for the single-chip endoscopic system, which can capture and distinguish numerous tumor-targeting fluorophores. As the molecular imaging field shifts toward a multi-tumor targeted probe methodology, our imaging instrument can aid in assessing these concepts during surgical procedures.

Associations between the Dietary Inflammatory Index and Sleep Metrics in the Energy Balance Study (EBS).

(1) Background: Sleep, a physiological necessity, has strong inflammatory underpinnings. Diet is a strong moderator of systemic inflammation. This study explored the associations between the Dietary Inflammatory Index (DII®) and sleep duration, timing, and quality from the Energy Balance Study (EBS). (2) Methods: The EBS (n = 427) prospectively explored energy intake, expenditure, and body composition. Sleep was measured using BodyMedia's SenseWear® armband. DII scores were calculated from three unannounced dietary recalls (baseline, 1-, 2-, and 3-years). The DII was analyzed continuously and categorically (very anti-, moderately anti-, neutral, and pro-inflammatory). Linear mixed-effects models estimated the DII score impact on sleep parameters. (3) Results: Compared with the very anti-inflammatory category, the pro-inflammatory category was more likely to be female (58% vs. 39%, p = 0.02) and African American (27% vs. 3%, p < 0.01). For every one-unit increase in the change in DII score (i.e., diets became more pro-inflammatory), wake-after-sleep-onset (WASO) increased (ßChange = 1.00, p = 0.01), sleep efficiency decreased (ßChange = −0.16, p < 0.05), and bedtime (ßChange = 1.86, p = 0.04) and waketime became later (ßChange = 1.90, p < 0.05). Associations between bedtime and the DII were stronger among African Americans (ßChange = 6.05, p < 0.01) than European Americans (ßChange = 0.52, p = 0.64). (4) Conclusions: Future studies should address worsening sleep quality from inflammatory diets, leading to negative health outcomes, and explore potential demographic differences.

Associations of cardiorespiratory fitness and body mass index with incident restrictive spirometry pattern.

OBJECTIVES: Restrictive spirometry pattern (RSP) suggests an impairment of lung function associated with a significantly increased risk of premature mortality. We evaluated the independent and joint associations of cardiorespiratory fitness (CRF) and body mass index with incident RSP. METHODS: Data from the Aerobics Centre Longitudinal Study included 12 360 participants (18-82 years). CRF was assessed by maximal treadmill test and categorised into five groups. Body mass index was categorised into normal weight (<25.0 kg/m2), overweight (25.0-29.9 kg/m2) or obesity (≥30.0 kg/m2). RSP was defined as the simultaneous occurrence of forced expiratory volume in 1 s/force vital capacity ≥lower limit of normal and forced vital capacity

Causal mediation analysis between resistance exercise and reduced risk of cardiovascular disease based on the Aerobics Center Longitudinal Study.

Health benefits of resistance exercise (RE), particularly in lowering cardiovascular disease (CVD) risks, are less understood in comparison to aerobic exercise (AE). Motivated by big data from the Aerobics Center Longitudinal Study (ACLS), we study the direct and indirect effects of RE on CVD risks. The primary outcome in our study, total CVD events (CVD morbidity and mortality combined), is modeled as a survival outcome. To investigate the pathway from RE to CVD outcome through potential mediators, we first conduct causal mediation analysis based on marginal structural models (MSMs). To fully account the information from repeated measurements of the mediators, we also adopt a joint model of the CVD survival outcome and multiple longitudinal trajectories of the mediators. Results show statistically significant direct effects of RE and AE on lowering the risk of total CVD events under each pathway. The causal effect of RE and AE on CVD risk is also studied across different age and gender groups. Furthermore, we produce a ranking for the relative importance of the potential risk factors for CVD, with total cholesterol ranking the highest.

Interpolant-based demosaicing routines for dual-mode visible/near-infrared imaging systems.

Dual-mode visible/near-infrared imaging systems, including a bioinspired six-channel design and more conventional four-channel implementations, have transitioned from a niche in surveillance to general use in machine vision. However, the demosaicing routines that transform the raw images from these sensors into processed images that can be consumed by humans or computers rely on assumptions that may not be appropriate when the two portions of the spectrum contribute different information about a scene. A solution can be found in a family of demosaicing routines that utilize interpolating polynomials and splines of different dimensionalities and orders to process images with minimal assumptions.

Protease-activated indocyanine green nanoprobes for intraoperative NIR fluorescence imaging of primary tumors.

Tumor-targeted fluorescent probes in the near-infrared spectrum can provide invaluable information about the location and extent of primary and metastatic tumors during intraoperative procedures to ensure no residual tumors are left in the patient's body. Even though the first fluorescence-guided surgery was performed more than 50 years ago, it is still not accepted as a standard of care in part due to the lack of efficient and non-toxic targeted probes approved by regulatory agencies around the world. Herein, we report protease-activated cationic gelatin nanoparticles encapsulating indocyanine green (ICG) for the detection of primary breast tumors in murine models with high tumor-to-background ratios. Upon intravenous administration, these nanoprobes remain optically silent due to the energy resonance transfer among the bound ICG molecules. As the nanoprobes extravasate and are exposed to the acidic tumor microenvironment, their positive surface charges increase, facilitating cellular uptake. The internalized nanoprobes are activated upon proteolytic degradation of gelatin to allow high contrast between the tumor and normal tissue. Since both gelatin and ICG are FDA-approved for intravenous administration, this activatable nanoprobe can lead to quick clinical adoption and improve the treatment of patients undergoing image-guided cancer surgery.

Decoupling channel count from field of view and spatial resolution in single-sensor imaging systems for fluorescence image-guided surgery.

Significance: Near-infrared fluorescence image-guided surgery is often thought of as a spectral imaging problem where the channel count is the critical parameter, but it should also be thought of as a multiscale imaging problem where the field of view and spatial resolution are similarly important. Aim: Conventional imaging systems based on division-of-focal-plane architectures suffer from a strict relationship between the channel count on one hand and the field of view and spatial resolution on the other, but bioinspired imaging systems that combine stacked photodiode image sensors and long-pass/short-pass filter arrays offer a weaker tradeoff. Approach: In this paper, we explore how the relevant changes to the image sensor and associated image processing routines affect image fidelity during image-guided surgeries for tumor removal in an animal model of breast cancer and nodal mapping in women with breast cancer. Results: We demonstrate that a transition from a conventional imaging system to a bioinspired one, along with optimization of the image processing routines, yields improvements in multiple measures of spectral and textural rendition relevant to surgical decision-making. Conclusions: These results call for a critical examination of the devices and algorithms that underpin image-guided surgery to ensure that surgeons receive high-quality guidance and patients receive high-quality outcomes as these technologies enter clinical practice.

Are flexibility and muscle-strengthening activities associated with functional limitation?

This retrospective cohort study examined the relationship between self-reported participation in flexibility and muscular strengthening activities and the development of functional limitation (i.e., once an individual has difficulty with or becomes unable to perform activities of daily living). Data were obtained from 1318 adults (mean age 49.5 â€‹± â€‹9.7 years; 98.7% Caucasian; 14.9% female) enrolled in the Aerobics Center Longitudinal Study from 1979 to 2004 and free of functional limitation at baseline. Mail-back health surveys were used to prospectively determine incident functional limitation. Participation in muscle-strengthening and flexibility activities was assessed via self-report. Adjusted logistic regression analyses were used to determine the odds ratios (OR) and corresponding 95% confidence intervals for developing functional limitation during follow-up based on participation in general and specific categories of flexibility ('Stretching', 'Calisthenics', or 'Exercise Class') and muscle-strengthening activities ('Calisthenics', 'Free Weights', 'Weight Training Machines', or 'Other'). Overall, 42.6% of the sample reported incident functional limitation. After adjusting for potential confounders (e.g., age, sex, cardiometabolic risk factors), those who reported performing muscle-strengthening activities in general (n â€‹= â€‹685) were at lower risk of developing functional limitation [OR â€‹= â€‹0.79 (0.63-1.00)]. In addition, the specific flexibility activities of stretching (n â€‹= â€‹491) and calisthenics (n â€‹= â€‹122) were associated with 24% and 38% decreased odds of incident functional limitation, respectively. General muscle-strengthening, stretching, and calisthenics activities are prospectively associated with decreased risk of incident functional limitation in generally healthy, middle-aged and older adults. Thus, both public health and rehabilitation programs should highlight the importance of flexibility and muscle-strengthening activities during adulthood to help preserve functional capacity.

Association of Accelerometer-Measured Sedentary Time and Physical Activity With Risk of Stroke Among US Adults.

Importance: The amount and intensity of physical activity required to prevent stroke are yet to be fully determined because of previous reliance on self-reporting measures. Furthermore, the association between objectively measured time spent being sedentary as an independent risk factor for stroke is unknown. Objective: To investigate the associations of accelerometer-measured sedentary time and physical activity of varying intensity and duration with the risk of incident stroke. Design, Setting, and Participants: This cohort study involved participants who were enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from February 5, 2003, to October 30, 2007. Accelerometer data were collected from 7607 Black and White adults 45 years or older in the contiguous US between May 12, 2009, and January 5, 2013. Data on other races and ethnicities were not collected for scientific and clinical reasons. By design, Black adults and residents of the southeastern US stroke belt and stroke buckle were oversampled. Data were analyzed from May 5, 2020, to November 11, 2021. Exposures: Sedentary time, light-intensity physical activity (LIPA), and moderate- to vigorous-intensity physical activity (MVPA) were measured using a hip-mounted accelerometer worn for 7 consecutive days and stratified by tertile for the analyses. Main Outcomes and Measures: Incident stroke. Results: Among 7607 participants, the mean (SD) age was 63.4 (8.5) years; 4145 participants (54.5%) were female, 2407 (31.6%) were Black, and 5200 (68.4%) were White. A total of 2523 participants (33.2%) resided in the stroke belt, and 1638 (21.5%) resided in the stroke buckle. Over a mean (SD) of 7.4 (2.5) years of follow-up, 286 incident stroke cases (244 ischemic [85.3%]) occurred. The fully adjusted hazard ratios (HRs) for incident stroke in the highest tertile compared with the lowest tertile were 0.74 (95% CI, 0.53-1.04; P = .08) for LIPA and 0.57 (95% CI, 0.38-0.84; P = .004) for MVPA. Higher sedentary time was associated with a 44% greater risk of incident stroke (HR, 1.44; 95% CI, 0.99-2.07; P = .04). When comparing the highest with the lowest tertile, mean sedentary bout duration was associated with a significantly greater risk of incident stroke (HR, 1.53; 95% CI, 1.10-2.12; P = .008). After adjustment for sedentary time, the highest tertile of unbouted MVPA (shorter bouts [1-9 minutes]) was associated with a significantly lower risk of incident stroke compared with the lowest tertile (HR, 0.62; 95% CI, 0.41-0.94; P = .02); however, bouted MVPA (longer bouts [at least 10 minutes]) was not (HR, 0.78; 95% CI, 0.53-1.15; P = .17). When expressed as continuous variables, sedentary time was positively associated with incident stroke risk (HR per 1-hour/day increase in sedentary time: 1.14; 95% CI, 1.02-1.28; P = .02), and LIPA was negatively associated with incident stroke risk (HR per 1-hour/day increase in LIPA: 0.86; 95% CI, 0.77-0.97; P = .02). Conclusions and Relevance: In this cohort study, objectively measured LIPA, MVPA, and sedentary time were significantly and independently associated with incident stroke risk. Longer sedentary bout duration was also independently associated with an increased risk of incident stroke. These findings suggest that replacing sedentary time with LIPA, or even very short bouts of MVPA, may lower stroke risk, supporting the concept of moving more and sitting less as a beneficial stroke risk reduction strategy among adults.

Association Between Change in Nonexercise Estimated Cardiorespiratory Fitness and Mortality in Men.

Objective: To examine the association between change in nonexercise estimated cardiorespiratory fitness (eCRF) and mortality risk in adult men. Patients and Methods: A total of 10,445 men (mean age, 44.6±9.3 years) from the Aerobics Center Longitudinal Study underwent 2 comprehensive medical examinations and peak work rate tests between January 1, 1979, and December 31, 2002, with an average time between measures of 5.7±4.9 years. Participants were observed for 11.6±6.4 years after their second examination until death or December 31, 2003. The eCRF was calculated with the Jackson et al (2012) and Nes et al (2011) published nonexercise estimation equations. Cox proportional hazards models were performed to examine the association between change in eCRF and all-cause and cardiovascular disease (CVD) mortality. Results: There were 601 deaths (192 CVD deaths) during the follow-up period. For both eCRF equations, a higher eCRF at baseline was associated with significant reductions in mortality risk from all causes and CVD (P<.001). Change in eCRF by the Jackson equation remained significantly associated with all-cause mortality (P<.001) and CVD mortality (P=.02) after multivariable adjustment. Every 1 metabolic equivalent (3.5 mL·kg-1·min-1) increase in eCRF was associated with a 21% and 22% reduction in mortality risk from all causes or CVD, respectively. No significant associations were observed between change in eCRF by the Nes equation and all-cause (P=.69) or CVD (P=.85) mortality risk after multivariable adjustment. Conclusion: The association between change in nonexercise eCRF and mortality risk may be equation dependent.

Effect of High-Intensity Power Training on Cognitive Function in Older Adults With Type 2 Diabetes: Secondary Outcomes of the GREAT2DO Study.

We sought to determine the effects of 12 months of power training on cognition, and whether improvements in body composition, muscle strength, and/or aerobic capacity (VO2peak) were associated with improvements in cognition in older adults with type 2 diabetes (T2D). Participants with T2D were randomized to power training or low-intensity sham exercise control condition, 3 days per week for 12 months. Cognitive outcomes included memory, attention/speed, executive function, and global cognition. Other relevant outcomes included VO2peak, strength, and whole body and regional body composition. One hundred and three adults with T2D (mean age 67.9 years; standard deviation [SD] 5.9; 50.5% women) were enrolled and analyzed. Unexpectedly, there was a nearly significant improvement in global cognition (p = .05) in the sham group relative to power training, although both groups improved over time (p < .01). There were significant interactions between group allocation and body composition or muscle strength in the models predicting cognitive changes. Therefore, after stratifying by group allocation, improvements in immediate memory were associated with increases in relative skeletal muscle mass (r = 0.38, p = .03), reductions in relative body fat (r = -0.40, p = .02), and increases in knee extension strength were directly related to changes in executive function (r = -0.41, p = .02) within the power training group. None of these relationships were present in the sham group (p > .05). Although power training did not significantly improve cognition compared to low-intensity exercise control, improvements in cognitive function in older adults were associated with hypothesized improvements in body composition and strength after power training.

Exercise effects on cardiovascular disease: from basic aspects to clinical evidence.

Cardiovascular (CV) disease (CVD) remains the leading cause of major morbidity and CVD- and all-cause mortality in most of the world. It is now clear that regular physical activity (PA) and exercise training (ET) induces a wide range of direct and indirect physiologic adaptations and pleiotropic benefits for human general and CV health. Generally, higher levels of PA, ET, and cardiorespiratory fitness (CRF) are correlated with reduced risk of CVD, including myocardial infarction, CVD-related death, and all-cause mortality. Although exact details regarding the ideal doses of ET, including resistance and, especially, aerobic ET, as well as the potential adverse effects of extreme levels of ET, continue to be investigated, there is no question that most of the world's population have insufficient levels of PA/ET, and many also have lower than ideal levels of CRF. Therefore, assessment and promotion of PA, ET, and efforts to improve levels of CRF should be integrated into all health professionals' practices worldwide. In this state-of-the-art review, we discuss the exercise effects on many areas related to CVD, from basic aspects to clinical practice.

Objectively Measured Physical Activity and Sedentary Time Among Adults With and Without Stroke: A National Cohort Study.

Background and Purpose: We examined differences in the volume and pattern of physical activity (PA) and sedentary behavior between adults with and without stroke. Methods: We studied cohort members with an adjudicated or self-reported stroke (n=401) and age-, sex-, race-, region of residence-, and body mass index-matched participants without a history of stroke (n=1203) from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Sedentary behavior (total volume and bouts), light-intensity PA, and moderate-to-vigorous-intensity PA were objectively measured for 7 days via hip-worn accelerometer. Results: Sedentary time (790.5±80.4 versus 752.4±81.9 min/d) and mean sedentary bout duration (15.7±12.6 versus 11.9±8.1 min/d) were higher and PA (light-intensity PA: 160.5±74.6 versus 192.9±73.5 min/d and moderate-to-vigorous-intensity PA: 9.0±11.9 versus 14.7±17.0 min/d) lower for stroke survivors compared with controls (P<0.001). Stroke survivors also accrued fewer activity breaks (65.5±21.9 versus 73.31±18.9 breaks/d) that were shorter (2.4±0.7 versus 2.7±0.8 minutes) and lower in intensity (188.4±60.8 versus 217.9±72.2 counts per minute) than controls (P<0.001). Conclusions: Stroke survivors accrued a lower volume of PA, higher volume of sedentary time, and exhibited accrual patterns of more prolonged sedentary bouts and shorter, lower intensity activity breaks compared with persons without stroke.

Resistance exercise, alone and in combination with aerobic exercise, and obesity in Dallas, Texas, US: A prospective cohort study.

BACKGROUND: Obesity is a significant and growing public health problem in high-income countries. Little is known about the relationship between resistance exercise (RE), alone and in combination with aerobic exercise (AE), and the risk of developing obesity. The purpose of this prospective cohort study was to examine the associations between different amounts and frequencies of RE, independent of AE, and incident obesity. METHODS AND FINDINGS: Participants were 11,938 healthy adults ages 18-89 years with a BMI < 30 kg/m2 at baseline who completed at least 2 clinical examinations during 1987-2005 as part of the Aerobics Center Longitudinal Study. Self-reported RE participation in minutes/week and days/week was collected from a standardized questionnaire. Incident obesity was defined as a BMI ≥ 30 kg/m2 at follow-up. Incident obesity was also defined by waist circumference (WC) > 102/88 cm for men/women and percent body fat (PBF) ≥ 25%/30% for men/women at follow-up in participants who were not obese by WC (n = 9,490) or PBF (n = 8,733) at baseline. During the average 6-year follow-up, 874 (7%), 726 (8%), and 1,683 (19%) developed obesity defined by BMI, WC, or PBF, respectively. Compared with no RE, 60-119 min/wk of RE was associated with 30%, 41%, and 31% reduced risk of obesity defined by BMI (hazard ratio [95% CI], 0.70 [0.54-0.92], p = 0.008), WC (0.59 [0.44-0.81], p < 0.001), and PBF (0.69 [0.57-0.83], p < 0.001), respectively, after adjusting for confounders including age, sex, examination year, smoking status, heavy alcohol consumption, hypertension, hypercholesterolemia, diabetes, and AE. Compared with not meeting the RE guidelines of ≥2 d/wk, meeting the RE guidelines was associated with 18%, 30%, and 30% reduced risk of obesity defined by BMI (hazard ratio [95% CI], 0.82 [0.69-0.97], p = 0.02), WC (0.70 [0.57-0.85], p < 0.001), and PBF (0.70 [0.62-0.79], p < 0.001), respectively. Compared with meeting neither guideline, meeting both the AE and RE guidelines was associated with the smallest hazard ratios for obesity. Limitations of this study include limited generalizability as participants were predominantly white men from middle to upper socioeconomic strata, use of self-reported RE, and lack of detailed diet data for the majority of participants. CONCLUSIONS: In this study, we observed that RE was associated with a significantly reduced risk of obesity even after considering AE. However, meeting both the RE and AE guidelines was associated with the lowest risk of obesity.