Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.

Mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms. Male C57BL/6J mice (10 wk old) were randomly assigned to one of the three experimental groups: nonimmobilization control group (sterilized water injection), immobilization control group (sterilized water injection), and immobilization and MOTS-c-treated group (15 mg/kg/day MOTS-c injection). We used casting tape for the immobilization experiment. After 8 days of the experimental period, skeletal muscle samples were collected and used for Western blotting, RNA sequencing, and lipid and collagen assays. Immobilization reduced ∼15% of muscle mass, whereas MOTS-c treatment attenuated muscle loss, with only a 5% reduction. MOTS-c treatment also normalized phospho-AKT, phospho-FOXO1, and phospho-FOXO3a expression levels and reduced circulating inflammatory cytokines, such as interleukin-1b (IL-1ß), interleukin-6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), and monocyte chemoattractant protein 1 (MCP-1), in immobilized mice. Unbiased RNA sequencing and its downstream analyses demonstrated that MOTS-c modified adipogenesis-modulating gene expression within the peroxisome proliferator-activated receptor (PPAR) pathway. Supporting this observation, muscle fatty acid levels were lower in the MOTS-c-treated group than in the casted control mice. These results suggest that MOTS-c treatment inhibits skeletal muscle lipid infiltration by regulating adipogenesis-related genes and prevents immobilization-induced muscle atrophy.NEW & NOTEWORTHY MOTS-c, a mitochondrial microprotein, attenuates immobilization-induced skeletal muscle atrophy. MOTS-c treatment improves systemic inflammation and skeletal muscle AKT/FOXOs signaling pathways. Furthermore, unbiased RNA sequencing and subsequent assays revealed that MOTS-c prevents lipid infiltration in skeletal muscle. Since lipid accumulation is one of the common pathologies among other skeletal muscle atrophies induced by aging, obesity, cancer cachexia, and denervation, MOTS-c treatment could be effective in other muscle atrophy models as well.

Mitochondrial DNA variation in Alzheimer's disease reveals a unique microprotein called SHMOOSE.

Mitochondrial DNA variants have previously associated with disease, but the underlying mechanisms have been largely elusive. Here, we report that mitochondrial SNP rs2853499 associated with Alzheimer's disease (AD), neuroimaging, and transcriptomics. We mapped rs2853499 to a novel mitochondrial small open reading frame called SHMOOSE with microprotein encoding potential. Indeed, we detected two unique SHMOOSE-derived peptide fragments in mitochondria by using mass spectrometry-the first unique mass spectrometry-based detection of a mitochondrial-encoded microprotein to date. Furthermore, cerebrospinal fluid (CSF) SHMOOSE levels in humans correlated with age, CSF tau, and brain white matter volume. We followed up on these genetic and biochemical findings by carrying out a series of functional experiments. SHMOOSE acted on the brain following intracerebroventricular administration, differentiated mitochondrial gene expression in multiple models, localized to mitochondria, bound the inner mitochondrial membrane protein mitofilin, and boosted mitochondrial oxygen consumption. Altogether, SHMOOSE has vast implications for the fields of neurobiology, Alzheimer's disease, and microproteins.

Pedicle screw insertion into infected vertebrae reduces operative time and range of fixation in minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis: a multicenter retrospective cohort study.

BACKGROUND: Minimally invasive posterior fixation surgery for pyogenic spondylitis is known to reduce invasiveness and complication rates; however, the outcomes of concomitant insertion of pedicle screws (PS) into the infected vertebrae via the posterior approach are undetermined. This study aimed to assess the safety and efficacy of PS insertion into infected vertebrae in minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis. METHODS: This multicenter retrospective cohort study included 70 patients undergoing minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis across nine institutions. Patients were categorized into insertion and skip groups based on PS insertion into infected vertebrae, and surgical data and postoperative outcomes, particularly unplanned reoperations due to complications, were compared. RESULTS: The mean age of the 70 patients was 72.8 years. The insertion group (n = 36) had shorter operative times (146 versus 195 min, p = 0.032) and a reduced range of fixation (5.4 versus 6.9 vertebrae, p = 0.0009) compared to the skip group (n = 34). Unplanned reoperations occurred in 24% (n = 17) due to surgical site infections (SSI) or implant failure; the incidence was comparable between the groups. Poor infection control necessitating additional anterior surgery was reported in four patients in the skip group. CONCLUSIONS: PS insertion into infected vertebrae during minimally invasive posterior fixation reduces the operative time and range of fixation without increasing the occurrence of unplanned reoperations due to SSI or implant failure. Judicious PS insertion in patients with minimal bone destruction in thoracolumbar pyogenic spondylitis can minimize surgical invasiveness.

Effect of platelet-rich plasma on the acceleration of graft bone catabolism in lateral lumbar interbody fusion in a short-term assessment.

This study aimed to demonstrate whether impregnating the graft bone with platelet-rich plasma (PRP) accelerates graft bone catabolism in lateral lumbar interbody fusion (LLIF). Consecutive patients who underwent LLIF were assessed. Of the two spaces for bone grafts in the intervertebral cage, one space was filled with graft bone impregnated with PRP, and the other was filled with graft bone without PRP, which divided the graft bones into PRP and non-PRP groups. The mean Hounsfield units (HU) of the graft bone at the center of the cage space in the coronal and axial slices were measured using computed tomography (CT) images 1 week and 6 months after surgery. The delta value of HU from 1 week to 6 months after surgery was calculated for the PRP and non-PRP groups. We compared the delta values of the HU between the two groups. The PRP and non-PRP groups comprised 16 bone grafts. In the coronal slices, the HU value in the PRP group (delta value: 526.1 ± 352.2) tended to have a greater decrease at 6 months after surgery compared with that in the non-PRP group (delta value: 217.6 ± 240.4) (p = 0.065). In the axial slices, the HU value in the PRP group (delta value: 501.3 ± 319.6) was significantly decreased at 6 months after surgery compared with that in the non-PRP group (delta value: 159.2 ± 215.3) (p = 0.028). Impregnating the graft-bone with PRP accelerated graft bone catabolism in LLIF within 6 months after surgery.

Unidirectional porous beta-tricalcium phosphate as a potential bone regeneration material for infectious bony cavity without debridement in pyogenic spondylitis.

An 81-year-old man was initially diagnosed with T11 osteoporotic vertebral fracture. The fractured vertebral body was filled with unidirectional porous beta-tricalcium phosphate (ß-TCP) granules, and posterior spinal fixation was conducted using percutaneous pedicle screws. However, the pain did not improve, the inflammatory response increased, and bone destructive changes extended to T10. The correct diagnosis was pyogenic spondylitis with concomitant T11 fragility vertebral fracture. Revision surgery was conducted 2 weeks after the initial surgery, the T10 and T11 pedicle screws were removed, and refixation was conducted. After the revision surgery, the pain improved and mobilization proceeded. The infection was suppressed by the administration of sensitive antibiotics. One month after surgery, a lateral bone bridge appeared at the T10/11 intervertebral level. This increased in size over time, and synostosis was achieved at 6 months. Resorption of the unidirectional porous ß-TCP granules was observed over time and partial replacement with autologous bone was evident from 6 months after the revision surgery. Two years and 6 months after the revision surgery, although there were some residual ß-TCP and bony defect in the center of the vertebral body, the bilateral walls have well regenerated. This suggested that given an environment of sensitive antibiotic administration and restricted local instability, unidirectional porous ß-TCP implanted into an infected vertebral body may function as a resorbable bone regeneration scaffold without impeding infection control even without debridement of the infected bony cavity.

Summary of the clinical practice manual for late-onset hypogonadism.

Testosterone plays an important role in maintaining both physical and mental function. Age-related testosterone depletion contributes to the development of angina, arteriosclerosis, obesity, metabolic syndrome, dementia, frailty, and a range of other conditions. A condition involving age-related testosterone depletion and the associated clinical symptoms is defined as late-onset hypogonadism (LOH). LOH is treated by testosterone replacement therapy. Indications for testosterone replacement therapy are determined by evaluating symptoms and signs.

An exploratory clinical trial for concentrated autologous bone marrow aspirate transplantation in the treatment of osteonecrosis of the femoral head.

PURPOSE: This study evaluated the efficacy and safety of a novel treatment for osteonecrosis, in which concentrated autologous bone marrow aspirate transplantation (CABMAT) is followed by low-intensity pulsed ultrasound (LIPUS) stimulation for 3 months. The study was designed as a prospective, uncontrolled, open-label phase II clinical study. METHODS: This study included 16 cases of osteonecrosis of the femoral head (ONFH), including 26 hips. Patients were transplanted with concentrated bone marrow and periodically evaluated for infection and neoplasm development. Moreover, clinical and radiological examinations were conducted to confirm the treatment efficacy. RESULTS: No infections were observed during the course of this study nor tumours developed at the treatment site 24 months after transplantation. At a mean 48 (30-56) months post-transplantation, the onset or progression of collapse was noted in four hips, of which one hip underwent total hip arthroplasty. CONCLUSION: Treatment with CABMAT combined with 3-month LIPUS stimulation was safe, and further randomised clinical studies are needed to determine the efficacy and feasibility of this treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000020940, 9/2/2016).

A rs936306 C/T Polymorphism in the CYP19A1 Is Associated With Stress Fractures.

ABSTRACT: Kumagai, H, Miyamoto-Mikami, E, Kikuchi, N, Kamiya, N, Zempo, H, and Fuku, N. A rs936306 C/T polymorphism in the CYP19A1 is associated with stress fractures. J Strength Cond Res 36(8): 2322-2325, 2022-A stress fracture (SF) is an overuse injury, and low bone mineral density (BMD) is the risk factor for the SF. Estrogen is suggested to have a crucial role in bone metabolism, and estrogen-related genetic polymorphisms are associated with BMD. However, the possible association between SF and estrogen-related genetic polymorphisms has not been clarified yet. Therefore, we aimed to clarify whether estrogen-related genetic polymorphisms are associated with a history of SFs in Japanese athletes. A total of 1,311 (men: n = 868, women: n = 443) top-level Japanese athletes who participated in various sports and at different levels were analyzed. The history of SFs was assessed using a questionnaire, and the cytochrome P450 aromatase gene ( CYP19A1 ) rs936306 C/T and estrogen receptor α gene ( ESR1 ) rs2234693 T/C polymorphisms were analyzed using the TaqMan genotyping assay. The genotype frequency of the CYP19A1 C/T polymorphism was significantly different between the injured group and noninjured group under the C allele additive genetic model (odds ratio = 1.31, 95% confidence interval = 1.01-1.70), especially in men and in women with irregular menstruation. On the other hand, there were no significant differences with the ESR1 T/C polymorphism. This study demonstrated that the C allele in the CYP19A1 rs936306 polymorphism is a risk factor for SFs in top-level Japanese athletes.

The association of ACTN3 R577X polymorphism with sports specificity in Japanese elite athletes.

The α-actinin-3 proteins regulate muscle function and are located in the Z-line of the fast skeletal muscle. A common null polymorphism of R577X in α-actinin-3 gene (ACTN3) results in its complete absence in fast-twitch muscles. The ACTN3 R577X polymorphism is associated with sprint/power performance in athletes. However, little is known about how this polymorphism impacts sports other than sprint/power-oriented sports in Japanese elite athletes. The aim of our study was to examine the association between ACTN3 R577X polymorphism and elite athlete status in various sports categorized as power/sprint, endurance, artistic, martial arts, and ball game sports. The subjects included 906 Japanese elite athletes and 649 Japanese controls. We analysed the genotype frequency of the ACTN3 R577X polymorphism in sprint/power (n = 120), endurance (n = 150), artistic (n = 45), martial arts (n = 94), and ball game (n = 497) sports athletes. A higher number of sprint/power athletes were R allele carriers compared to the controls, and the endurance and artistic athletes (OR = 1.69, 1.83, and 2.36, 95% CI: 1.02-2.79, 1.02-3.31, and 1.08-5.13, respectively). The frequency of RR genotype was higher in sprint/power, martial arts, and ball game sports athletes (OR = 1.61, 1.84, and 1.39, 95% CI: 1.04-2.50, 1.11-2.95, and 1.05-1.83, respectively) compared to control. Furthermore, there is a significant linear trend with increasing R allele according to athletic status (P for trend < 0.05). The ACTN3 R allele is positively associated with sports performance requiring explosive power such as sprint/power, martial arts, and ball game sports categories.

MOTS-c reduces myostatin and muscle atrophy signaling.

Obesity and type 2 diabetes are metabolic diseases, often associated with sarcopenia and muscle dysfunction. MOTS-c, a mitochondrial-derived peptide, acts as a systemic hormone and has been implicated in metabolic homeostasis. Although MOTS-c improves insulin sensitivity in skeletal muscle, whether MOTS-c impacts muscle atrophy is not known. Myostatin is a negative regulator of skeletal muscle mass and also one of the possible mediators of insulin resistance-induced skeletal muscle wasting. Interestingly, we found that plasma MOTS-c levels are inversely correlated with myostatin levels in human subjects. We further demonstrated that MOTS-c prevents palmitic acid-induced atrophy in differentiated C2C12 myotubes, whereas MOTS-c administration decreased myostatin levels in plasma in diet-induced obese mice. By elevating AKT phosphorylation, MOTS-c inhibits the activity of an upstream transcription factor for myostatin and other muscle wasting genes, FOXO1. MOTS-c increases mTORC2 and inhibits PTEN activity, which modulates AKT phosphorylation. Further upstream, MOTS-c increases CK2 activity, which leads to PTEN inhibition. These results suggest that through inhibition of myostatin, MOTS-c could be a potential therapy for insulin resistance-induced skeletal muscle atrophy as well as other muscle wasting phenotypes including sarcopenia.NEW & NOTEWORTHY MOTS-c, a mitochondrial-derived peptide reduces high-fat-diet-induced muscle atrophy signaling by reducing myostatin expression. The CK2-PTEN-mTORC2-AKT-FOXO1 pathways play key roles in MOTS-c action on myostatin expression.

Peptides derived from small mitochondrial open reading frames: Genomic, biological, and therapeutic implications.

Mitochondrial-derived peptides (MDPs) are a novel class of bioactive microproteins that modify cell metabolism. The the eight MDPs that been characterized (e.g., humanin, MOTS-c, SHLPs1-6) attenuate disease pathology including Alzheimer's disease, prostate cancer, macular degeneration, cardiovascular disease, and diabetes. The association between disease and human genetic variation in MDPs is underexplored, although two polymorphisms in humanin and MOTS-c associate with cognitive decline and diabetes, respectively, suggesting a precise role for MDPs in disease-modification. There could be hundreds of additional MDPs that have yet to be discovered. Altogether, MDPs could explain unanswered biological and metabolic questions and are part of a growing field of novel microproteins encoded by small open reading frames. In this review, the current state of MDPs are summarized with an emphasis on biological and therapeutic implications.

Unidirectional porous beta-tricalcium phosphate and hydroxyapatite artificial bone: a review of experimental evaluations and clinical applications.

In Japan, where allograft bone transplantation is not widespread, prospects for artificial bones are very high. Therefore, artificial bones with various compositions, porous structures, and porosities have been developed and employed for clinical use. Both Affinos® and Regenos® (made of beta-tricalcium phosphate and hydroxyapatite, respectively) are artificial bones with a unique unidirectional porous structure, in which pores with a diameter suitable for tissue penetration (25-300 µm) are aligned in one direction. The unidirectional porous structure allows rapid penetration of blood deep into the materials by a capillary effect. In animal experiments, Affinos® showed well-balanced resorption and was replaced with the host's own bone from an early stage after implantation and new bone formation and remodeling were observed in the cortical bone and medullary cavity. When implanted for clinical situation, resorption from an early stage and good replacement with the patient's own bone were also observed. Regenos® has an internal osteon-like material and a vascular-like structure that is maintained within the pores even after long-term implantation, as noted in an animal experiment. When implanted for clinical situation, good osteoconductivity was observed from an early stage of implantation. In addition, the material was observed to be slowly absorbed over time in some cases. We have discussed the beneficial effects of combining teriparatide and platelet-rich plasma impregnation and the potential prospects of these artificial bones.

eQTL variants in COL22A1 are associated with muscle injury in athletes.

The myotendinous junction (MTJ) is at high risk of muscle injury, and collagen XXII is strictly expressed at tissue junctions, specifically at the MTJ. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) related to collagen type XXII α-1 chain gene (COL22A1) mRNA expression are associated with susceptibility to muscle injury in athletes. History of muscle injury was assessed in 3,320 Japanese athletes using a questionnaire, and two expression quantitative trait loci (eQTL) SNPs for COL22A1 (rs11784270 A/C and rs6577958 T/C) were analyzed using the TaqMan SNP Genotyping Assay. rs11784270 [odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.27-2.62, P = 0.0006] and rs6577958 (OR = 1.45, 95% CI = 1.10-1.94, P = 0.0083) were significantly associated with muscle injury under A and T allele additive genetic models, respectively. These results suggest that the expression level of COL22A1 at the MTJ influences muscle injury risk in athletes.

Mitochondrial-derived peptides in energy metabolism.

Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by short open-reading frames (sORF) in mitochondrial DNA that do not necessarily have traditional hallmarks of protein-coding genes. To date, eight MDPs have been identified, all of which have been shown to have various cyto- or metaboloprotective properties. The 12S ribosomal RNA (MT-RNR1) gene harbors the sequence for MOTS-c, whereas the other seven MDPs [humanin and small humanin-like peptides (SHLP) 1-6] are encoded by the 16S ribosomal RNA gene. Here, we review the evidence that endogenous MDPs are sensitive to changes in metabolism, showing that metabolic conditions like obesity, diabetes, and aging are associated with lower circulating MDPs, whereas in humans muscle MDP expression is upregulated in response to stress that perturbs the mitochondria like exercise, some mtDNA mutation-associated diseases, and healthy aging, which potentially suggests a tissue-specific response aimed at restoring cellular or mitochondrial homeostasis. Consistent with this, treatment of rodents with humanin, MOTS-c, and SHLP2 can enhance insulin sensitivity and offer protection against a range of age-associated metabolic disorders. Furthermore, assessing how mtDNA variants alter the functions of MDPs is beginning to provide evidence that MDPs are metabolic signal transducers in humans. Taken together, MDPs appear to form an important aspect of a retrograde signaling network that communicates mitochondrial status with the wider cell and to distal tissues to modulate adaptative responses to metabolic stress. It remains to be fully determined whether the metaboloprotective properties of MDPs can be harnessed into therapies for metabolic disease.

Regular aerobic exercise improves sexual function assessed by the Aging Males' Symptoms questionnaire in adult men.

The leading cause of aging-induced male-specific disorders such as physical, mental and/or sexual symptoms is testosterone deficiency. Although aerobic exercise is suggested to improves circulating testosterone levels, physical fitness, depressive symptoms, and sexual function, the effect of regular aerobic exercise on aging-induced disorders has not yet been clarified. Here we performed cross-sectional and interventional studies to identify the effect of aerobic exercise on aging-induced disorders assessed by the Aging Males' Symptoms questionnaire (AMS). In study 1, the relationship between aerobic exercise capacity (i.e. peak oxygen consumption) and AMS scores were cross-sectionally examined in 169 adult men. In study 2, the effect of a 12-week regular aerobic exercise on AMS scores was longitudinally investigated in 18 adult men. In study 1, the AMS-total, AMS-somatic, AMS-psychological, and AMS-sexual scores were significantly correlated to aerobic exercise capacity even after considering age and testosterone levels. In study 2, 12-week aerobic exercise training significantly improved AMS-sexual and tended to improve AMS-total scores. Additionally, an increase in vigorous physical activity was correlated to improve in the AMS-sexual score. These results suggest that regular aerobic exercise is an effective strategy to improve aging-induced disorders in men.

Incremental short maximal exercise increases urinary liver-type fatty acid-binding protein in adults without CKD.

Exercise-induced redistribution of tissue blood flow decreases the renal blood flow in an exercise intensity-dependent manner. However, the acute effects of incremental short maximal exercise on renal tubular conditions remain unknown. The purpose of this study was to investigate the acute effects of incremental short maximal exercise on the urinary liver-type fatty acid-binding protein, which is a highly sensitive tubular biomarker that correlates excellently with peritubular capillary blood flow. A total of 116 adults (aged 24-83 years) without chronic kidney disease performed the incremental short maximal exercise using a cycling ergometer, wherein the exercise sequence consisted of commencing with a 2-min workout period at 20 W (as a warm-up period) and then followed by a 10-20 W increase every 1 minute until termination criteria were reached. Urinary samples were gathered before and immediately after the exercise to evaluate the concentrations of urinary creatinine, albumin, and liver-type fatty acid-binding protein. Urinary excretion levels of albumin and liver-type fatty acid-binding protein were significantly increased post-exercise (P < .001 and P = .008, respectively). Furthermore, the % change in urinary liver-type fatty acid-binding protein levels after exercise was found to correlate independently with age, estimated glomerular filtration rate at baseline, and the % change in urinary albumin (Model R2  = 0.451, P < .001). Our findings suggest that incremental short maximal exercise may lead to acute slightly adverse effects on tubular conditions, especially in young adults or adults with lower renal function, even without chronic kidney disease.

The impact of aerobic fitness on arterial stiffness and adrenal cortex hormones in middle-aged and older adults.

An increase in arterial stiffness with advance aging is a risk for cardiovascular disease. Cardiovascular dysfunction is associated with the imbalance of adrenal cortex hormones, especially with the cortisol/dehydroepiandrosterone sulfate (DHEAs) ratio. However, the impact of aerobic fitness on arterial stiffness and cortisol/DHEAs ratio is unclear. The aim of this study was to investigate the relationship between aerobic fitness, arterial stiffness, and cortisol/DHEAs ratio. A total of 198 middle-aged and older adults (aged 50-79 years old) participated in this study. The aerobic fitness evaluated by peak oxygen consumption (VO2peak), carotid-femoral pulse wave velocity (cfPWV) as an indicator of arterial stiffness, and serum cortisol and DHEAs and their ratio were measured. The subjects were divided into the lower (n = 100) and the higher (n = 98) aerobic fitness groups based on the median value of VO2peak. There were no significant differences in serum cortisol and DHEAs concentration alone between the lower and higher fitness groups. However, the cortisol/DEHAs ratio and cfPWV in the higher fitness group was smaller than in the lower fitness group (p < 0.05). The cortisol/DHEAs ratio was significantly correlated with cfPWV (r = 0.159, p < 0.05). These findings suggest that the cortisol/DHEAs ratio is associated with aerobic fitness and arterial stiffness in middle-aged and older adults.

The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis.

PURPOSE: Iron is an important component of the oxygen-binding proteins and may be critical to optimal athletic performance. Previous studies have suggested that the G allele of C/G rare variant (rs1799945), which causes H63D amino acid replacement, in the HFE is associated with elevated iron indexes and may give some advantage in endurance-oriented sports. The aim of the present study was to investigate the association between the HFE H63D polymorphism and elite endurance athlete status in Japanese and Russian populations, aerobic capacity and to perform a meta-analysis using current findings and three previous studies. METHODS: The study involved 315 international-level endurance athletes (255 Russian and 60 Japanese) and 809 healthy controls (405 Russian and 404 Japanese). Genotyping was performed using micro-array analysis or by PCR. VO2max in 46 male Russian endurance athletes was determined using gas analysis system. RESULTS: The frequency of the iron-increasing CG/GG genotypes was significantly higher in Russian (38.0 vs 24.9%; OR 1.85, P = 0.0003) and Japanese (13.3 vs 5.0%; OR 2.95, P = 0.011) endurance athletes compared to ethnically matched controls. The meta-analysis using five cohorts (two French, Japanese, Spanish, and Russian; 586 athletes and 1416 controls) showed significant prevalence of the CG/GG genotypes in endurance athletes compared to controls (OR 1.96, 95% CI 1.58-2.45; P = 1.7 × 10-9). Furthermore, the HFE G allele was associated with high V̇O2max in male athletes [CC: 61.8 (6.1), CG/GG: 66.3 (7.8) ml/min/kg; P = 0.036]. CONCLUSIONS: We have shown that the HFE H63D polymorphism is strongly associated with elite endurance athlete status, regardless ethnicities and aerobic capacity in Russian athletes.

Thoracic kyphosis and pelvic anteversion in patients with adult spinal deformity increase while walking: analyses of dynamic alignment change using a three-dimensional gait motion analysis system.

PURPOSE: To determine dynamic changes of spinopelvic alignment while walking using a three-dimensional (3D) gait motion analysis in adult spinal deformity (ASD) patients. METHODS: This study included 20 ASD patients. The 3D gait motion analysis (Vicon) was performed during continuous walking to their limit. Dynamic parameters were obtained using reflective markers on the spinous processes, which were segmented into thoracic (T-), lumbar (L-), and whole spine (S-), sagittal spinal distance (SVA) and coronal one (CVA), sagittal spinal angle to the vertical axis (SA) and coronal one (CA), sagittal pelvic angle to the horizontal axis (P-SA) and coronal (P-CA), and thoracic limited spinal angle to the pelvic angle (T-P SA) and lumbar one (L-P SA). The dynamic variables at the final lap were compared with those at the first lap of an oval walkway. RESULTS: Spinal kyphotic deformity deteriorated significantly. As for pelvic angle, the mean P-SA parameters (first lap/final lap) were 3.2°/5.2°. Anteversion of pelvic sagittal angle increased significantly after continuous walking to their limit. In particular, regarding limited spinal angle to the pelvic angle, the mean T-P SA parameters were 30.5°/36.2° and L-P SA parameters were 6.4°/6.8°. Thoracic kyphotic angle increased significantly, but lumbar kyphotic angle did not change. CONCLUSION: Decrease of thoracic kyphosis and pelvic retroversion has been recognized as a compensation for ASD on standing radiograph. Our 3D gait motion analysis to determine spinal balance found thoracic kyphosis and pelvic anteversion increased significantly in patients with ASD after continuous walking to the limit of their endurance until they were fatigued, indicating a failure of compensation for ASD. These slides can be retrieved under Electronic Supplementary Material.

Posterolateral lumbar spine fusion with unidirectional porous beta-tricalcium phosphate in a canine model.

We investigated the use of the autologous iliac bone and unidirectional porous beta-tricalcium phosphate (UDPTCP) in posterolateral lumbar spine fusion (PLF). Ten canine PLF models were prepared. Using only the autologous bone as the control group, 100%, 75%, 50%, and 25% groups were prepared according to the mixing ratios of UDPTCP. Radiological evaluation and histological analysis were performed 12 weeks after surgery. Bone fusion was evaluated according to anteroposterior plain X-rays and coronal reconstruction CT views using four grades: 0 = no osteogenesis, 1 = only slight discontinuous osteogenesis between transverse processes, 2 = discontinuous osteogenesis between transverse processes, and 3 = continuous osteogenesis between transverse processes. Bone fusion determined by X-ray was 2.8 ± 0.5 in the control group, 0 in the 100% UDPTCP group (p = 0.02), 1.8 ± 0.5 (p = 0.03) in the 75% UDPTCP group, 2.5 ± 0.6 (p = 0.54) in the 50% UDPTCP group, and 2.8 ± 0.5 (p = 1.0) in the 25% UDPTCP group. The bone fusion score was significantly lower in the 75% and 100% UDPTCP groups than in the control group. Bone fusion determined by CT was 2.8 ± 0.5 in the control group, 1.0 ± 0.8 (p = 0.01) in the 100% UDPTCP group, 2.0 ± 0.0 (p = 0.02) in the 75% UDPTCP group, 2.5 ± 0.6 (p = 0.54) in the 50% UDPTCP group, and 2.8 ± 0.5 (p = 1.0) in the 25% UDPTCP group. Similar to the bone fusion determination by X-ray, the bone fusion score was significantly lower in the 75% and 100% UDPTCP groups. These data suggest that, in a canine PLF model, the appropriate mixing ratio of UDPTCP is 50% or less.