NASA SPRINT exercise program efficacy for vastus lateralis and soleus skeletal muscle health during 70 days of simulated microgravity.

The efficacy of the NASA SPRINT exercise countermeasures program for quadriceps (vastus lateralis) and triceps surae (soleus) skeletal muscle health was investigated during 70 days of simulated microgravity. Individuals completed 6° head-down-tilt bedrest (BR, n = 9), bedrest with resistance and aerobic exercise (BRE, n = 9), or bedrest with resistance and aerobic exercise and low-dose testosterone (BRE + T, n = 8). All groups were periodically tested for muscle (n = 9 times) and aerobic (n = 4 times) power during bedrest. In BR, surprisingly, the typical bedrest-induced decrements in vastus lateralis myofiber size and power were either blunted (myosin heavy chain, MHC I) or eliminated (MHC IIa), along with no change (P > 0.05) in %MHC distribution and blunted quadriceps atrophy. In BRE, MHC I (vastus lateralis and soleus) and IIa (vastus lateralis) contractile performance was maintained (P > 0.05) or increased (P < 0.05). Vastus lateralis hybrid fiber percentage was reduced (P < 0.05) and energy metabolism enzymes and capillarization were generally maintained (P > 0.05), while not all of these positive responses were observed in the soleus. Exercise offsets 100% of quadriceps and approximately two-thirds of soleus whole muscle mass loss. Testosterone (BRE + T) did not provide any benefit over exercise alone for either muscle and for some myocellular parameters appeared detrimental. In summary, the periodic testing likely provided a partial exercise countermeasure for the quadriceps in the bedrest group, which is a novel finding given the extremely low exercise dose. The SPRINT exercise program appears to be viable for the quadriceps; however, refinement is needed to completely protect triceps surae myocellular and whole muscle health for astronauts on long-duration spaceflights.NEW & NOTEWORTHY This study provides unique exercise countermeasures development information for astronauts on long-duration spaceflights. The NASA SPRINT program was protective for quadriceps myocellular and whole muscle health, whereas the triceps surae (soleus) was only partially protected as has been shown with other programs. The bedrest control group data may provide beneficial information for overall exercise dose and targeting fast-twitch muscle fibers. Other unique approaches for the triceps surae are needed to supplement existing exercise programs.

Effects of aging and lifelong aerobic exercise on expression of innate immune components in skeletal muscle of women.

This study examined the effects of aging and lifelong aerobic exercise on innate immune system components in the skeletal muscle of healthy women in the basal state and after an unaccustomed resistance exercise (RE) challenge. We also made exploratory between-sex comparisons with our previous report on men. Three groups of women were studied: young exercisers (YE, n = 10, 25 ± 1 yr, V̇o2max: 44 ± 2 mL/kg/min), lifelong aerobic exercisers with a 48 ± 2 yr training history (LLE, n = 7, 72 ± 2 yr, V̇o2max: 26 ± 2 mL/kg/min), and old healthy nonexercisers (OH, n = 10, 75 ± 1 yr, V̇o2max: 18 ± 1 mL/kg/min). Ten Toll-like receptors (TLRs)1-10, TLR adaptors (Myd88, TRIF), and NF-κB pathway components (IκBα, IKKß) were assessed at the mRNA level in vastus lateralis biopsies before and 4 h after RE [3×10 repetitions, 70% 1-repetition maximum (1RM)]. Basal TLR1-10 expression was minimally influenced by age or LLE in women (TLR9 only; OH > YE, +43%, P < 0.05; OH > LLE, +30%, P < 0.10) and was on average 24% higher in women versus men. Similarly, basal adaptor expression was not influenced (P > 0.05) by age or LLE in women but was on average 26% higher (myeloid differentiation primary response 88, Myd88) and 23% lower [Toll interleukin (IL)-1 receptor-containing adaptor-inducing interferon-γ, TRIF] in women versus men. RE-induced changes in women, independent of the group, in TLR3, TLR4, TLR6 (∼2.1-fold, P < 0.05), Myd88 (∼1.2-fold, P < 0.10), and IκBα (∼0.3-fold, P < 0.05). Although there were some similar RE responses in men (TLR4: 2.1-fold, Myd88: 1.2-fold, IκBα: 0.4-fold), several components responded only in men to RE (TLR1, TLR8, TRIF, and IKKß). Our findings support the sexual dimorphism of immunity, with women having greater basal skeletal muscle TLR expression and differential response to unaccustomed exercise than men.NEW & NOTEWORTHY We recently reported that aging increases basal expression of many Toll-like receptors (TLRs) in men and lifelong aerobic exercise does not prevent this effect. In addition, a resistance exercise (RE) challenge increased the expression of many TLRs. Here we show that basal TLR expression is minimally influenced by aging in women and findings support the sexual dimorphism of immunity, with women having greater basal skeletal muscle TLR expression and a differential response to unaccustomed exercise than men.

Effects of acute aerobic exercise on circulating sTLR and sRAGE profiles in normal- and abnormal-glucose-tolerant individuals.

BMI-matched normal- (NGT, n = 10, 41 ± 4y, 35.6 ± 3.0 kg/m2 ) and abnormal-glucose-tolerant (AGT, n = 16, 51 ± 3y, 34.3 ± 1.5 kg/m2 ) participants were evaluated for body composition, metabolic health (oral glucose tolerance test [OGTT]), and VO2 max. Participants also completed a treadmill walking test at 65% VO2 max for 30 min. Total sRAGE, esRAGE, sTLR2, and sTLR4 were assessed via ELISA, and cRAGE was calculated. AGT exhibited greater (p < 0.05) body fat % (+24%), fasting plasma glucose (+37%), OGTT AUC (+59%), and HOMA-IR (+55%) and lower (p < 0.05) VO2 max (-24%). sTLR2 was 33% lower in AGT than NGT (main effect, p = 0.034). However, sTLR2 did not change (p > 0.05) following AE. sTLR4 tended to be 36% lower in AGT than NGT (main effect, p = 0.096) and did not change following AE (p > 0.05). Total sRAGE and isoforms were similar (p > 0.05) between groups and did not change following AE (p > 0.05). sTLR2 was correlated with (p < 0.05) basal BG (r = -0.505) and OGTT AUC (r = -0.687). sTLR4 was correlated with basal BG (p < 0.10, r = -0.374) and OGTT AUC (p < 0.05, r = -0.402). Linear regressions were predictive of sTLRs in the basal state (sTLR2: R2 = 0.641, p = 0.01; sTLR4: R2 = 0.566, p = 0.037) and after acute exercise state (sTLR2: R2 = 0.681, p = 0.004, sTLR4: R2 = 0.568, p = 0.036).These findings show circulating sTLR profiles are disrupted in AGT and acute AE minimally modulates their levels.

Soluble RAGE and skeletal muscle tissue RAGE expression profiles in lean and obese young adults across differential aerobic exercise intensities.

Nearly 40% of Americans have obesity and are at increased risk for developing type 2 diabetes. Skeletal muscle is responsible for >80% of insulin-stimulated glucose uptake that is attenuated by the inflammatory milieu of obesity and augmented by aerobic exercise. The receptor for advanced glycation endproducts (RAGE) is an inflammatory receptor directly linking metabolic dysfunction with inflammation. Circulating soluble isoforms of RAGE (sRAGE) formed either by proteolytic cleavage (cRAGE) or alternative splicing (esRAGE) act as decoys for RAGE ligands, thereby counteracting RAGE-mediated inflammation. We aimed to determine if RAGE expression or alternative splicing of RAGE is altered by obesity in muscle, and whether acute aerobic exercise (AE) modifies RAGE and sRAGE. Young (20-34 yr) participants without [n = 17; body mass index (BMI): 22.6 ± 2.6 kg/m2] and with obesity (n = 7; BMI: 32.8 ± 2.9 kg/m2) performed acute aerobic exercise (AE) at 40%, 65%, or 80% of maximal aerobic capacity (V̇o2max; mL/kg/min) on separate visits. Blood was taken before and 30 min after each AE bout. Muscle biopsy samples were taken before, 30 min, and 3 h after the 80% V̇o2max AE bout. Individuals with obesity had higher total RAGE and esRAGE mRNA and RAGE protein (P < 0.0001). In addition, RAGE and esRAGE transcripts correlated to transcripts of the NF-κB subunit P65 (P < 0.05). There was no effect of AE on total RAGE or esRAGE transcripts, or RAGE protein (P > 0.05), and AE tended to decrease circulating sRAGE in particular at lower intensities of exercise. RAGE expression is exacerbated in skeletal muscle with obesity, which may contribute to muscle inflammation via NF-κB. Future work should investigate the consequences of increased skeletal muscle RAGE on the development of obesity-related metabolic dysfunction and potential mitigating strategies.NEW & NOTEWORTHY This study is the first to investigate the effects of aerobic exercise intensity on circulating sRAGE isoforms, muscle RAGE protein, and muscle RAGE splicing. sRAGE isoforms tended to diminish with exercise, although this effect was attenuated with increasing exercise intensity. Muscle RAGE protein and gene expression were unaffected by exercise. However, individuals with obesity displayed nearly twofold higher muscle RAGE protein and gene expression, which positively correlated with expression of the P65 subunit of NF-κB.

Exercise-induced changes to the fiber type-specific redox state in human skeletal muscle are associated with aerobic capacity.

The benefits of exercise involve skeletal muscle redox state alterations of nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD). We determined the fiber-specific effects of acute exercise on the skeletal muscle redox state in healthy adults. Muscle biopsies were obtained from 19 participants (11 M, 8 F; 26 ± 4 yr) at baseline (fasted) and 30 min and 3 h after treadmill exercise at 80% maximal oxygen consumption (V̇o2max). Muscle samples were probed for autofluorescence of NADH (excitation at 340-360 nm) and oxidized flavoproteins (Fp; excitation at 440-470 nm) and subsequently, fiber typed to quantify the redox signatures of individual muscle fibers. Redox state was calculated as the oxidation-to-reduction redox ratio: Fp/(Fp + NADH). At baseline, pair-wise comparisons revealed that the redox ratio of myosin heavy chain (MHC) I fibers was 7.2% higher than MHC IIa (P = 0.023, 95% CI: 5.2, 9.2%) and the redox ratio of MHC IIa was 8.0% higher than MHC IIx (P = 0.035, 95% CI: 6.8, 9.2%). MHC I fibers also displayed greater NADH intensity than MHC IIx (P = 0.007) and greater Fp intensity than both MHC IIa (P = 0.019) and MHC IIx (P < 0.0001). Fp intensities increased in all fiber types (main effect, P = 0.039) but redox ratios did not change (main effect, P = 0.483) 30 min after exercise. The change in redox ratio was positively correlated with capillary density in MHC I (rho = 0.762, P = 0.037), MHC IIa fibers (rho = 0.881, P = 0.007), and modestly in MHC IIx fibers (rho = 0. 771, P = 0.103). These findings support the use of redox autofluorescence to interrogate skeletal muscle metabolism.NEW & NOTEWORTHY This study is the first to use autofluorescent imaging to describe differential redox states within human skeletal muscle fiber types with exercise. Our findings highlight an easy and efficacious technique for assessing skeletal muscle redox in humans.

Advanced Glycation End Products and Inflammatory Cytokine Profiles in Maintenance Hemodialysis Patients After the Ingestion of a Protein-Dense Meal.

OBJECTIVE: The goal of this investigation was to evaluate circulating and skeletal muscle inflammatory biomarkers between maintenance hemodialysis (MHD) and demographic-matched control subjects (CON) before and after ingestion of a protein-rich meal. DESIGN AND METHODS: CON (n = 8; 50 ± 2 years; 31 ± 1 kg/m2) and MHD patients (n = 8; 56 ± 5 years; 32 ± 2 kg/m2) underwent a basal blood draw and muscle biopsy and serial blood draws after the ingestion of a mixed meal on a nondialysis day. Plasma advanced glycation end products (AGEs) and markers of oxidation were assessed via liquid chromatography-tandem mass spectrometry before and after the meal (+240 min). Circulating inflammatory cytokines and soluble receptors for AGE (sRAGE) isoforms (endogenous secretory RAGEs and cleaved RAGEs) were determined before and after the meal (+240 min). Basal muscle was probed for inflammatory cytokines and protein expression of related signaling components (RAGE, Toll-like receptor 4, oligosaccharyltransferase subunit 48, TIR-domain-containing adapter-inducing interferon-ß, total IκBα, and pIκBα). RESULTS: Basal circulating AGEs were 7- to 343-fold higher (P < .001) in MHD than those in CON, but only MG-H1 increased in CON after the meal (P < .001). There was a group effect (MHD > CON) for total sRAGEs (P = .02) and endogenous secretory RAGEs (P < .001) and a trend for cleaved RAGEs (P=.09), with no meal effect. In addition, there was a group effect (MHD < CON; P < .05) for circulating fractalkine, interleukin (IL)10, IL17A, and IL1ß and a trend (P < .10) for IL6 and macrophage inflammatory protein 1 alpha, whereas tumor necrosis factor alpha was higher in MHD (P < .001). In muscle, Toll-like receptor 4 (P = .03), TIR-domain-containing adapter-inducing interferon-ß (P = .002), and oligosaccharyltransferase subunit 48 (P = .02) expression was lower in MHD than that in CON, whereas IL6 was higher (P = .01) and IL8 (P = .08) tended to be higher in MHD. CONCLUSION: Overall, MHD exhibited an exaggerated, circulating, and skeletal muscle inflammatory biomarker environment, and the meal did not appreciably affect the inflammatory status.

An Anterior Cruciate Ligament (ACL) Injury Risk Screening and Reduction Program for High School Female Athletes: A Pilot Study.

Background: Anterior cruciate ligament (ACL) injury causes physical, mental, and financial burdens. Therefore, it is imperative to screen, identify, and educate athletes who are at high-risk. The combination of screening and education could identify those at risk and potentially reduce future injuries. Purpose: The purpose was to conduct a feasible community pre-season screening program for high school female athletes for the presence of known modifiable risk factors that predispose them to sustaining a non-contact ACL injury. Study Design: Non-experimental prospective study. Methods: A convenience sample of 15 healthy female athletes were recruited from local high schools, consisting of 11 soccer players and four basketball players.  A pre-season screening program was designed encompassing four stations that addressed modifiable neuromuscular and biomechanical risk factors including range of motion (ROM), jump-landing technique, strength, and balance. Athletes were categorized into high-risk versus low-risk groups based on cutoff scores previously established in the literature. Results: Every athlete met the high-risk cutoff score for at least one extremity during the ROM screening, and some met high-risk cutoff scores for more than one ROM. Out of all four categories tested, lower extremity ROM demonstrated the greatest deficits. Conclusion: This study identified athletes as having multiple modifiable risk factors that can be addressed with training and exercises. This supports implementing a pre-season program aimed at screening for injury risk factors. Level of Evidence: Level 3.

Age-Related Changes in Skeletal Muscle Oxygen Utilization.

The cardiovascular and skeletal muscle systems are intrinsically interconnected, sharing the goal of delivering oxygen to metabolically active tissue. Deficiencies within those systems that affect oxygen delivery to working tissues are a hallmark of advancing age. Oxygen delivery and utilization are reflected as muscle oxygen saturation (SmO2) and are assessed using near-infrared resonance spectroscopy (NIRS). SmO2 has been observed to be reduced by ~38% at rest, ~24% during submaximal exercise, and ~59% during maximal exercise with aging (>65 y). Furthermore, aging prolongs restoration of SmO2 back to baseline by >50% after intense exercise. Regulatory factors that contribute to reduced SmO2 with age include blood flow, capillarization, endothelial cells, nitric oxide, and mitochondrial function. These mechanisms are governed by reactive oxygen species (ROS) at the cellular level. However, mishandling of ROS with age ultimately leads to alterations in structure and function of the regulatory factors tasked with maintaining SmO2. The purpose of this review is to provide an update on the current state of the literature regarding age-related effects in SmO2. Furthermore, we attempt to bridge the gap between SmO2 and associated underlying mechanisms affected by aging.

Bilateral Bronchoscopic Lung Volume Reduction After Surgical Fissure Completion.

Although bilateral lung volume reduction surgery has been shown to be safe and effective in carefully selected patients with upper lobe-predominant emphysema and hyperinflation, bronchoscopic lung volume reduction via placement of endobronchial valves is conventionally performed only unilaterally. Furthermore, it is not offered to patients with interlobar collateral ventilation because of the lack of clinical efficacy. We describe two novel management approaches including (1) bilateral bronchoscopic lung volume reduction, and (2) a combined thoracic surgical and interventional pulmonary procedure involving surgical fissure completion followed by endobronchial valve placement, which culminated in safe and effective lung volume reduction of both lungs along with an excellent patient outcome.

Genetic diagnosis of immune dysregulation can lead to targeted therapy for interstitial lung disease: A case series and single center approach.

In recent years, a growing number of monogenic disorders have been described that are characterized by immune dysregulation. A subset of these "primary immune regulatory disorders" can cause severe interstitial lung disease, often recognized in late childhood or adolescence. Patients presenting to pulmonary clinic may have long and complex medical histories, but lack a unifying genetic diagnosis. It is crucial for pulmonologists to recognize features suggestive of multisystem immune dysregulation and to initiate genetic workup, since targeted therapies based on underlying genetics may halt or even reverse pulmonary disease progression. Through such an approach, our center has been able to diagnose and treat a cohort of patients with interstitial lung disease from gene defects that affect immune regulation. Here we present representative cases related to pathogenic variants in three distinct pathways and summarize disease manifestations and treatment approaches. We conclude with a discussion of our perspective on the outstanding challenges for diagnosing and managing these complex life-threatening and chronic disorders.

Perceptions of Social Media Use to Augment Health Care Among Adolescents and Young Adults With Cystic Fibrosis: Survey Study.

BACKGROUND: For individuals with cystic fibrosis (CF), adolescence and young adulthood are times of significant vulnerability and have been associated with clinical and psychosocial challenges. Social media may offer innovative care delivery solutions to address these challenges. OBJECTIVE: This study explored motivations and attitudes regarding current social media use and preferences for a social media platform in a sample of adolescents and young adults (AYA) with CF. METHODS: A cross-sectional survey was administered to 50 AYA with CF followed at a large pediatric-adult CF center. The survey included questions regarding social media platform utilization, attitudes toward general and CF-specific online activities, and preferences for a CF-specific care delivery platform. RESULTS: YouTube, Snapchat, and Instagram were the most commonly used social media platforms. AYA with CF do not report routinely using social media for health-related information acquisition, social support, or help with adherence. However, their perceptions of social media utilization and preferences for platform development suggest interest in doing so in the future. CONCLUSIONS: AYA with CF use social media and expressed interest in the development of a social media platform. Platform development will allow for gaps in health care delivery to be addressed by improving social support and adherence while augmenting current methods of health information acquisition.

Rapid Implementation of Telehealth Services in a Pediatric Pulmonary Clinic During COVID-19.

OBJECTIVES: The coronavirus pandemic created significant, abrupt challenges to the delivery of ambulatory health care. Because tertiary medical centers limited elective in-person services, telehealth was rapidly enacted in settings with minimal previous experience to allow continued access to care. With this quality improvement (QI) initiative, we aimed to achieve a virtual visit volume of at least 75% of our prepandemic volume. We also describe patient and provider experience with telehealth services. METHODS: Our QI team identified the primary drivers contributing to low telehealth volume and developed a telehealth scheduling protocol and data tracking system using QI-based strategies. Patients and providers were surveyed on their telehealth experience. RESULTS: At the onset of the pandemic, weekly visit volume dropped by 65% (99 weekly visits; historical average of 281). Over the subsequent 3 weeks, using rapid Plan-Do-Study-Act cycles, we achieved our goal volume. In surveys, it was indicated that most participants had never before used telehealth (71% of patients; 82% of providers) yet reported high satisfaction (90% of patients; 81% of providers). Both groups expressed concern over the lack of in-person assessments. Most respondents were interested in future use of telehealth. CONCLUSIONS: With a QI-based approach, we successfully maintained access to care via telehealth services for pediatric pulmonary patients during the coronavirus pandemic and found high rates of satisfaction among patients and providers. Telehealth will likely continue to be a part of our health care delivery platform, expanding the reach of our services. Further work is needed to understand the effects on clinical outcomes.

An evaluation of healthcare utilization and clinical charges in children and adults with cystic fibrosis.

BACKGROUND: Prior studies have estimated healthcare costs for cystic fibrosis (CF) of $8000-$131,000, but do not account for impacts of CF modulator therapy. This study aims to assess utilization patterns and cost of CF care in a center in the United States. METHODS: Care utilization patterns and costs at a large pediatric-adult CF center were examined from November 2017 to November 2018. Subjects were stratified by age and cost (excluding pharmacy costs) were calculated based on hospital-derived utilization charges. RESULTS: A total of 166 patients were reviewed with mean clinical charges of $28,755. Lower lung function ($23,032 normal lung function, $62,293 moderate reduction, $186,786 severe reduction; p = .05), hospitalizations ($85,452 yes, $6362 no; p = .0001), Pseudomonas positive culture ($48,660 positive, $22,013 negative, p = .0001), and CF-related diabetes ($161,892 CFRD, $22,153 no CFRD; p = .001) were associated with increased charges. Patients utilizing Ivacaftor had lower charges compared to lumacaftor-ivacaftor ($6633 vs. $33,039; p = .05) and tezacaftor-ivacaftor ($6633 vs. $64,434; p = .002). CONCLUSION: Our study characterized utilization and care charges among a CF cohort. Lower lung function, hospitalizations, and CFRD were associated with increased charges.

Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation in women.

Low muscle mass and frailty are especially prevalent in older women and may be accelerated by age-related inflammation. Habitual physical activity throughout the life span (lifelong exercise) may prevent muscle inflammation and associated pathologies, but this is unexplored in women. This investigation assessed basal and acute exercise-induced inflammation in three cohorts of women: young exercisers (YE, n = 10, 25 ± 1 yr, [Formula: see text]: 44 ± 2 mL/kg/min, quadriceps size: 59 ± 2 cm2), old healthy nonexercisers (OH, n = 10, 75 ± 1 yr, [Formula: see text]: 18 ± 1 mL/kg/min, quadriceps size: 40 ± 1 cm2), and lifelong aerobic exercisers with a 48 ± 2 yr aerobic training history (LLE, n = 7, 72 ± 2 yr, [Formula: see text]: 26 ± 2 mL/kg/min, quadriceps size: 42 ± 2 cm2). Resting serum IL-6, TNF-α, C-reactive protein (CRP), and IGF-1 were measured. Vastus lateralis muscle biopsies were obtained at rest (basal) and 4 h after an acute exercise challenge (3 × 10 reps, 70% 1-repetition maximum) to assess gene expression of cytokines (IL-6, TNF-α, IL-1ß, IL-10, IL-4, IL-1Ra, TGF-ß), chemokines (IL-8, MCP-1), cyclooxygenase enzymes (COX-1, COX-2), prostaglandin E2 synthases (mPGES-1, cPGES) and receptors (EP3-4), and macrophage markers (CD16b, CD163), as well as basal macrophage abundance (CD68+ cells). The older cohorts (LLE + OH combined) demonstrated higher muscle IL-6 and COX-1 (P ≤ 0.05) than YE, whereas LLE expressed lower muscle IL-1ß (P ≤ 0.05 vs. OH). Acute exercise increased muscle IL-6 expression in YE only, whereas the older cohorts combined had the higher postexercise expression of IL-8 and TNF-α (P ≤ 0.05 vs. YE). Only LLE had increased postexercise expression of muscle IL-1ß and MCP-1 (P ≤ 0.05 vs. preexercise). Thus, aging in women led to mild basal and exercise-induced inflammation that was unaffected by lifelong aerobic exercise, which may have implications for long-term function and adaptability.NEW & NOTEWORTHY We previously reported a positive effect of lifelong exercise on skeletal muscle inflammation in aging men. This parallel investigation in women revealed that lifelong exercise did not protect against age-related increases in circulating or muscle inflammation and that preparedness to handle loading stress was not preserved by lifelong exercise. Further investigation is necessary to understand why lifelong aerobic exercise may not confer the same anti-inflammatory benefits in women as it does in men.

Effects of aging and lifelong aerobic exercise on expression of innate immune components in human skeletal muscle.

The purpose of this investigation was to evaluate the effects of aging and lifelong exercise on skeletal muscle components of the innate immune system. Additionally, the effects of an acute resistance exercise (RE) challenge were explored. Three groups of men were studied: young exercisers (YE: n = 10, 25 ± 1 yr; V̇o2max: 53 ± 3 mL/kg/min; quadriceps size: 78 ± 3 cm2), lifelong aerobic exercisers with a 53 ± 1 yr training history (LLE; n = 21, 74 ± 1 yr; V̇o2max: 34 ± 1 mL/kg/min; quadriceps size: 67 ± 2 cm2), and old healthy nonexercisers (OH: n = 10, 75 ± 1 yr; V̇o2max: 22 ± 1 mL/kg/min, quadriceps size: 56 ± 3 cm2). Vastus lateralis muscle biopsies were obtained in the basal state and 4 h after RE (3 × 10 reps, 70% of 1 repetition maximum) to assess Toll-like receptors (TLR)1-10, TLR adaptors (Myd88 and TRIF), and NF-κB pathway components (IκΒα and IKKß) mRNA expression. Basal TLR3, TLR6, and TLR7 tended to be higher (P ≤ 0.10) with aging (LLE and OH combined). In general, RE increased expression of TLR1 and TLR8 (P ≤ 0.10) and TLR3 and TLR4 (P < 0.05), although TLR3 did not respond in OH. Both TLR adaptors also responded to the exercise bout; these were primarily (Myd88, main effect P ≤ 0.10) or exclusively (TRIF, P < 0.05) driven by the OH group. In summary, aging appears to increase basal expression of some innate immune components in human skeletal muscle, and lifelong aerobic exercise does not affect this age-related increase. An exercise challenge stimulates the expression of several TLRs, while the TLR adaptor response appears to be dysregulated with aging and maintained with lifelong exercise. Partially preserved muscle mass, coupled with a notable immunity profile, suggests lifelong exercisers are likely better prepared for a stress that challenges the immune system.NEW & NOTEWORTHY Findings from this investigation provide novel insight into the effect of aging and lifelong aerobic exercise on structural components of the innate immune system in skeletal muscle of humans. Data presented here suggest aging increases basal expression of select Toll-like receptors (TLRs), and lifelong exercise does not impact this age-related increase. Additionally, acute exercise stimulates gene expression of several TLRs, while the adaptor response is likely dysregulated with aging and maintained with lifelong exercise.

Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation.

Age-associated chronic basal inflammation compromises muscle mass and adaptability, but exercise training may exert an anti-inflammatory effect. This investigation assessed basal and exercise-induced inflammation in three cohorts of men: young exercisers [YE; n = 10 men; 25 ± 1 yr; maximal oxygen consumption (V̇o2max), 53 ± 3 mL·kg-1·min-1; quadriceps area, 78 ± 3 cm2; means ± SE], old healthy nonexercisers (OH; n = 10; 75 ± 1 yr; V̇o2max, 22 ± 1 mL·kg-1·min-1; quadriceps area, 56 ± 3 cm2), and lifelong exercisers with an aerobic training history of 53 ± 1 yr (LLE; n = 21; 74 ± 1 yr; V̇o2max, 34 ± 1 mL·kg-1·min-1; quadriceps area, 67 ± 2 cm2). Resting serum IL-6, TNF-α, C-reactive protein, and IGF-1 levels were measured. Vastus lateralis muscle biopsies were obtained at rest (basal) and 4 h after an acute exercise challenge (3 × 10 repetitions, 70% 1-repetition maximum) to assess gene expression of cytokines [IL-6, TNF-α, IL-1ß, IL-10, IL-4, interleukin-1 receptor antagonist (IL-1Ra), and transforming growth factor-ß (TGF-ß)], chemokines [IL-8 and monocyte chemoattractant protein-1 (MCP-1)], cyclooxygenase enzymes [cyclooxygenase-1 and -2 (COX-1 and COX-2, respectively), prostaglandin E2 synthases [microsomal prostaglandin E synthase 1 (mPGES-1) and cytosolic prostaglandin E2 synthase (cPGES)] and receptors [prostaglandin E2 receptor EP3 and EP4 subtypes (EP3 and EP4, respectively), and macrophage markers [cluster of differentiation 16b (CD16b) and CD163], as well as basal macrophage abundance (CD68+ cells). Aging led to higher (P ≤ 0.05) circulating IL-6 and skeletal muscle COX-1, mPGES-1, and CD163 expression. However, LLE had significantly lower serum IL-6 levels (P ≤ 0.05 vs. OH) and a predominantly anti-inflammatory muscle profile [higher IL-10 (P ≤ 0.05 vs. YE), TNF-α, TGF-ß, and EP4 levels (P ≤ 0.05 vs. OH)]. In OH only, acute exercise increased expression of proinflammatory factors TNF-α, TGF-ß, and IL-8 (P ≤ 0.05). LLE had postexercise gene expression similar to YE, except lower IL-10 (P ≤ 0.10), mPGES-1, and EP3 expression (P ≤ 0.05). Thus, although aging led to a proinflammatory profile within blood and muscle, lifelong exercise partially prevented this and generally preserved the acute inflammatory response to exercise seen in young exercising men. Lifelong exercise may positively impact muscle health throughout aging by promoting anti-inflammation in skeletal muscle.NEW & NOTEWORTHY This study assessed a unique population of lifelong aerobic exercising men and demonstrated that their activity status exerts an anti-inflammatory effect in skeletal muscle and circulation. Furthermore, we provide evidence that the inflammatory response to acute exercise is dysregulated by aging but preserved with lifelong exercise, which might improve skeletal muscle resilience to unaccustomed loading and adaptability into late life.

Cerebrospinal fluid diversion versus bariatric surgery in the management of idiopathic intracranial hypertension.

Background: Idiopathic intracranial hypertension (IIH) is a condition affecting predominantly young women with increased body mass index (BMI). Obesity with the related metabolic and biochemical complications are thought to be involved in the pathogenesis of the condition. The aim of this study is to evaluate the safety, outcomes and economic implications of two treatment options for IIH.Methods: We retrospectively analysed cases of morbidly obese IIH patients treated by cerebrospinal fluid (CSF) shunting procedures between 2006 and 2016 in our department and compared their outcome with that of 69 patients undergoing bariatric surgery between 2015 and 2016.Results: A total of 42 female patients with IIH underwent de-novo shunting procedures during the study period. There was a high rate of shunt revisions (67%) and further weight gain in the majority of patients who had the insertion of CSF shunts. Of the 69 female patients undergoing bariatric surgery 4.3% required interventions related to their surgery with a significantly fewer number of hospital inpatient days. Furthermore, in the patients undergoing bariatric surgery, there was a significant improvement in all obesity-related complications.Conclusions: CSF shunting procedures do not address the aetiological factor of IIH and are associated with high rates of morbidity and further weight gain. Bariatric surgery is not only efficacious in the management of patients with IIH but is associated with significant improvements in other obesity-related comorbidities. Bariatric surgery is safe and more cost-effective than CSF shunting.