The axial skeleton of Tiktaalik roseae.

The axial columns of the earliest limbed vertebrates show distinct patterns of regionalization as compared to early tetrapodomorphs. Included among their novel features are sacral ribs, which provide linkage between the vertebral column and pelvis, contributing to body support and propulsion by the hindlimb. Data on the axial skeletons of the closest relatives of limbed vertebrates are sparce, with key features of specimens potentially covered by matrix. Therefore, it is unclear in what sequence and under what functional context specializations in the axial skeletons of tetrapods arose. Here, we describe the axial skeleton of the elpistostegalian Tiktaalik roseae and show that transformations to the axial column for head mobility, body support, and pelvic fin buttressing evolved in finned vertebrates prior to the origin of limbs. No atlas-axis complex is observed; however, an independent basioccipital-exoccipital complex suggests increased mobility at the occipital vertebral junction. While the construction of vertebrae in Tiktaalik is similar to early tetrapodomorphs, its ribs possess a specialized sacral domain. Sacral ribs are expanded and ventrally curved, indicating likely attachment to the expanded iliac blade of the pelvis by ligamentous connection. Thus, the origin of novel rib types preceded major alterations to trunk vertebrae, and linkage between pelvic fins and axial column preceded the origin of limbs. These data reveal an unexpected combination of post-cranial skeletal characters, informing hypotheses of body posture and movement in the closest relatives of limbed vertebrates.

Humans plan for the near future to walk economically on uneven terrain.

Humans experience small fluctuations in their gait when walking on uneven terrain. The fluctuations deviate from the steady, energy-minimizing pattern for level walking and have no obvious organization. But humans often look ahead when they walk, and could potentially plan anticipatory fluctuations for the terrain. Such planning is only sensible if it serves some an objective purpose, such as maintaining constant speed or reducing energy expenditure, that is also attainable within finite planning capacity. Here, we show that humans do plan and perform optimal control strategies on uneven terrain. Rather than maintaining constant speed, they make purposeful, anticipatory speed adjustments that are consistent with minimizing energy expenditure. A simple optimal control model predicts economical speed fluctuations that agree well with experiments with humans (N = 12) walking on seven different terrain profiles (correlated with model [Formula: see text] , [Formula: see text] all terrains). Participants made repeatable speed fluctuations starting about six to eight steps ahead of each terrain feature (up to ±7.5 cm height difference each step, up to 16 consecutive features). Nearer features matter more, because energy is dissipated with each succeeding step's collision with ground, preventing momentum from persisting indefinitely. A finite horizon of continuous look-ahead and motor working space thus suffice to practically optimize for any length of terrain. Humans reason about walking in the near future to plan complex optimal control sequences.

Lifestyle Walking Intervention for Patients With Heart Failure With Reduced Ejection Fraction: The WATCHFUL Trial.

BACKGROUND: Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS: The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS: Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS: Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.

Walking is like slithering: A unifying, data-driven view of locomotion.

Legged movement is ubiquitous in nature and of increasing interest for robotics. Most legged animals routinely encounter foot slipping, yet detailed modeling of multiple contacts with slipping exceeds current simulation capacity. Here we present a principle that unifies multilegged walking (including that involving slipping) with slithering and Stokesian (low Reynolds number) swimming. We generated data-driven principally kinematic models of locomotion for walking in low-slip animals (Argentine ant, 4.7% slip ratio of slipping to total motion) and for high-slip robotic systems (BigANT hexapod, slip ratio 12 to 22%; Multipod robots ranging from 6 to 12 legs, slip ratio 40 to 100%). We found that principally kinematic models could explain much of the variability in body velocity and turning rate using body shape and could predict walking behaviors outside the training data. Most remarkably, walking was principally kinematic irrespective of leg number, foot slipping, and turning rate. We find that grounded walking, with or without slipping, is governed by principally kinematic equations of motion, functionally similar to frictional swimming and slithering. Geometric mechanics thus leads to a unified model for swimming, slithering, and walking. Such commonality may shed light on the evolutionary origins of animal locomotion control and offer new approaches for robotic locomotion and motion planning.

Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose-response associations from the Prospective Physical Activity, Sitting and Sleep Consortium.

AIMS/HYPOTHESIS: The aim of this study was to examine the dose-response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] -0.14 [-0.25, -0.02]) and 5 min/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification.

Physical inactivity causes exercise resistance of fat metabolism: harbinger or culprit of disease?

Physical inactivity is the fourth leading cause of death in the world. It is associated with myriad diseases and premature death. Two possible contributing factors are postprandial lipidaemia (PPL), which accelerates atherosclerosis, and impaired whole-body fat oxidation, which contributes to obesity. Acute exercise in physically active people is effective for increasing whole body fat oxidation and lowering PPL the next morning. However, in people who have low physical activity (<8000 steps/day), an acute bout of exercise (1 h at 62% maximal oxygen consumption) has no effect on increasing fat oxidation or reducing PPL ('exercise resistance'). The acute harms of inactivity are not due to the lack of exercise and are more powerful than the benefits of exercise, at least regarding fat metabolism. The increase in mortality with reduced daily steps is remarkably steep. Low background steps/day also impair the metabolic adaptations to short-term endurance training, suggesting that the ills of inactivity extend beyond fat metabolism. 'Exercise resistance' with inactivity could be a culprit, causing atherosclerosis, or maybe also a harbinger (impaired fat oxidation) of more widespread diseases. Recommendations regarding the amount of moderate to vigorous exercise needed for health should factor in the amount of background activity (i.e. ∼8000 steps/day) necessary to avoid 'exercise resistance'.

Morning exercise and pre-breakfast metformin interact to reduce glycaemia in people with type 2 diabetes: a randomized crossover trial.

Exercise is recommended in the treatment of type 2 diabetes and can improve insulin sensitivity. However, previous evidence suggests that exercise at different times of the day in people with type 2 diabetes may have opposing outcomes on glycaemia. Metformin is the most commonly prescribed initial pharmacological intervention in type 2 diabetes, and may alter adaptions to exercise. It is unknown if there is an interaction between metformin and diurnal exercise outcomes. We aimed to investigate glycaemic outcomes of moderate intensity morning vs. evening exercise in people with type 2 diabetes being prescribed metformin monotherapy. In this study, nine males and nine females with type 2 diabetes undergoing metformin monotherapy (age 61 ± 8.2 years, mean ± SD) completed a 16-week crossover trial including 2-week baseline recording, 6 weeks randomly assigned to a morning exercise (07.00-10.00 h) or evening exercise (16.00-19.00 h) and a 2-week wash-out period. Exercise arms consisted of 30 min of walking at 70% of estimated max heart rate every other day. Glucose levels were measured with continuous glucose monitors and activity measured by wrist-worn monitors. Food-intake was recorded by 4-day food diaries during baseline, first and last 2 weeks of each exercise arm. There was no difference in exercise intensity, total caloric intake or total physical activity between morning and evening arms. As primary outcomes, acute (24 h) glucose area under the curve (AUC), was lower (P = 0.02) after acute morning exercise (180.6 ± 68.4 mmol/l) compared to baseline (210.3 ± 76.7 mmol/l); and there were no differences identified for glucose (mmol/l) between baseline, morning and evening exercise at any specific time point when data were analysed with two-way ANOVA. As secondary outcomes, acute glucose AUC was significantly lower (P = 0.01) in participants taking metformin before breakfast (152.5 ± 29.95 mmol/l) compared with participants taking metformin after breakfast (227.2 ± 61.51 mmol/l) only during the morning exercise arm; and during weeks 5-6 of the exercise protocol, glucose AUC was significantly lower (P = 0.04) for participants taking metformin before breakfast (168.8 ± 15.8 mmol/l), rather than after breakfast (224.5 ± 52.0 mmol/l), only during morning exercise. Our data reveal morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. This beneficial effect upon glucose levels of combined morning exercise and pre-breakfast metformin persisted through the final 2 weeks of the trial. Our findings suggest that morning moderate intensity exercise combined with pre-breakfast metformin intake may benefit the management of glycaemia in people with type 2 diabetes. KEY POINTS: Morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. Morning exercise combined with pre-breakfast metformin persistently reduced glucose compared to morning exercise combined with post-breakfast metformin through the final week (week 6) of the intervention. Our study suggests it may be possible to make simple changes to the time that people with type 2 diabetes take metformin and perform exercise to improve their blood glucose.

Acute Intermittent Hypoxia With High-Intensity Gait Training in Chronic Stroke: A Phase II Randomized Crossover Trial.

BACKGROUND: Studies in individuals with chronic stroke indicate high-intensity training (HIT) focused on walking improves locomotor function, which may be due to repeated activation of locomotor circuits and serotonin-dependent modulation of motor output. Separate studies in animals and individuals with spinal cord injury suggest acute intermittent hypoxia (AIH) can augment the effects of locomotor interventions through similar serotonin-dependent mechanisms, although no studies have coupled AIH with HIT in individuals poststroke. The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke. METHODS: This phase II double-blind randomized, crossover trial recruited individuals between 18 and 85 years old, >6 months poststroke, and self-selected speeds <1.0 m/s. Participants received up to 15 sessions of AIH for 30 minutes using 15 cycles of hypoxia (60-90 seconds; 8%-9% O2) and normoxia (30-60 seconds; 21% O2), followed by 1 hour of HIT targeting >75% heart rate reserve. The control condition received normoxia for 30 minutes before HIT. Following the first training phase, participants performed the second phase >1 month later. The primary outcomes were self-selected speed and fastest speed, a 6-minute walk test, and peak treadmill speed. A 3-way mixed-model ANOVA assessed the effects of time, training, and order of interventions. RESULTS: Of 55 individuals screened, 35 were randomized to AIH+HIT or normoxia+HIT first, and 28 individuals completed both interventions, revealing greater gains in self-selected speeds (0.14 [0.08-0.18] versus 0.05 [0.01-0.10] m/s), fastest speed (0.16 [0.10-0.21] versus 0.06 [0.02-0.10] m/s), and peak treadmill speed (0.21 [0.14-0.29] versus 0.11 [0.06-0.16] m/s) following AIH+HIT versus normoxia+HIT (P<0.01) with no order effects. Greater gains in spatiotemporal symmetry were observed with AIH+HIT, with worse outcomes for those prescribed serotonin-mediated antidepressant medications. CONCLUSIONS: AIH+HIT resulted in greater gains in locomotor function than normoxia+HIT. Subsequent phase III trials should further evaluate the efficacy of this intervention. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT04472442.

Increasing Activity After Stroke: A Randomized Controlled Trial of High-Intensity Walking and Step Activity Intervention.

BACKGROUND: Physical inactivity in people with chronic stroke profoundly affects daily function and increases recurrent stroke risk and mortality, making physical activity improvements an important target of intervention. We compared the effects of a high-intensity walking intervention (FAST), a step activity monitoring behavioral intervention (SAM), or a combined intervention (FAST+SAM) on physical activity (ie, steps/day). We hypothesized the combined intervention would yield the greatest increase in steps/day. METHODS: This assessor-blinded multisite randomized controlled trial was conducted at 4 university/hospital-based laboratories. Participants were 21 to 85 years old, walking without physical assistance following a single, unilateral noncerebellar stroke of ≥6 months duration, and randomly assigned to FAST, SAM, or FAST+SAM for 12 weeks (2-3 sessions/week). FAST training consisted of walking-related activities at 70% to 80% heart rate reserve, while SAM received daily feedback and goal setting of walking activity (steps/day). Assessors and study statistician were masked to group assignment. The a priori-determined primary outcome and end point was a comparison of the change in steps/day between the 3 intervention groups from pre- to post-intervention. Adverse events were tracked after randomization. All randomized participants were included in the intent-to-treat analysis. RESULTS: Participants were enrolled from July 18, 2016, to November 16, 2021. Of 2385 participants initially screened, 250 participants were randomized (mean [SE] age, 63 [0.80] years; 116 females/134 males), with 89 assigned to FAST, 81 to SAM, and 80 to FAST+SAM. Steps/day significantly increased in both the SAM (mean [SE], 1542 [267; 95% CI, 1014-2069] P<0.001) and FAST+SAM group (1307 [280; 95% CI, 752-1861] P<0.001) but not in the FAST group (406 [238; 95% CI, -63 to 876] P=0.09). There were no deaths or serious study-related adverse events. CONCLUSIONS: Only individuals with chronic stroke who completed a step activity monitoring behavioral intervention with skilled coaching and goal progression demonstrated improvements in physical activity (steps/day). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02835313.

Acute pain impairs retention of locomotor learning.

Despite abundant evidence that pain alters movement performance, considerably less is known about the potential effects of pain on motor learning. Some of the brain regions involved in pain processing are also responsible for specific aspects of motor learning, indicating that the two functions have the potential to interact, yet it is unclear if they do. In experiment 1, we compared the acquisition and retention of a novel locomotor pattern in young, healthy individuals randomized to either experience pain via capsaicin and heat applied to the lower leg during learning or no stimulus. On day 1, participants learned a new asymmetric walking pattern using distorted visual feedback, a paradigm known to involve mostly explicit re-aiming processes. Retention was tested 24 h later. Although there were no differences in day 1 acquisition between groups, individuals who experienced pain on day 1 demonstrated reduced retention on day 2. Furthermore, the degree of forgetting between days correlated with pain ratings during learning. In experiment 2, we examined the effects of a heat stimulus alone, which served as a control for (nonpainful) cutaneous stimulation, and found no effects on either acquisition or retention of learning. Thus, pain experienced during explicit, strategic locomotor learning interferes with motor memory consolidation processes and does so most likely through a pain mechanism and not an effect of distraction. These findings have important implications for understanding basic motor learning processes and for clinical rehabilitation, in which painful conditions are often treated through motor learning-based interventions.NEW & NOTEWORTHY Pain is a highly prevalent and burdensome experience that rehabilitation practitioners often treat using motor learning-based interventions. Here, we showed that experimental acute pain, but not a heat stimulus, during locomotor learning impaired 24-h retention of the newly learned walking pattern. The degree of retention loss was related to the perceived pain level during learning. These findings suggest important links between pain and motor learning that have significant implications for clinical rehabilitation.

Mechanosensory encoding of forces in walking uphill and downhill: force feedback can stabilize leg movements in stick insects.

Force feedback could be valuable in adapting walking to diverse terrains, but the effects of changes in substrate inclination on discharges of sensory receptors that encode forces have rarely been examined. In insects, force feedback is provided by campaniform sensilla, mechanoreceptors that monitor forces as cuticular strains. We neurographically recorded responses of stick insect tibial campaniform sensilla to "naturalistic" forces (joint torques) that occur at the hind leg femur-tibia (FT) joint in uphill, downhill, and level walking. The FT joint torques, obtained in a previous study that used inverse dynamics to analyze data from freely moving stick insects, are quite variable during level walking (including changes in sign) but are larger in magnitude and more consistent when traversing sloped surfaces. Similar to vertebrates, insects used predominantly extension torque in propulsion on uphill slopes and flexion torques to brake forward motion when going downhill. Sensory discharges to joint torques reflected the torque direction but, unexpectedly, often occurred as multiple bursts that encoded the rate of change of positive forces (dF/dt) even when force levels were high. All discharges also showed hysteresis (history dependence), as firing substantially decreased or ceased during transient force decrements. These findings have been tested in simulation in a mathematical model of the sensilla (Szczecinski NS, Dallmann CJ, Quinn RD, Zill SN. Bioinspir Biomim 16: 065001, 2021) that accurately reproduced the biological data. Our results suggest the hypothesis that sensory feedback from the femoro-tibial joint indicating force dynamics (dF/dt) can be used to counter the instability in traversing sloped surfaces in animals and, potentially, in walking machines.NEW & NOTEWORTHY Discharges of sensory receptors (campaniform sensilla) in the hind legs of stick insects can differentially signal forces that occur in walking uphill versus walking downhill. Unexpectedly, sensory firing most closely reflects the rate of change of force (dF/dt) even when the force levels are high. These signals have been replicated in a mathematical model of the receptors and could be used to stabilize leg movements both in the animal and in a walking robot.

Human brain dynamics dissociate early perceptual and late motor-related stages of affordance processing.

Affordances, the opportunities for action offered by the environment to an agent, are vital for meaningful behaviour and exist in every interaction with the environment. There is an ongoing debate in the field about whether the perception of affordances is an automated process. Some studies suggest that affordance perception is an automated process that is independent from the visual context and bodily interaction with the environment, whereas others argue that it is modulated by the visual and motor context in which affordances are perceived. The present paper aims to resolve this debate by examining affordance automaticity from the perspective of sensorimotor time windows. To investigate the impact of different forms of bodily interactions with an environment, that is, the movement context (physical vs. joystick movement), we replicated a previous study on affordance perception in which participants actively moved through differently wide doors in an immersive 3D virtual environment. In the present study, we displayed the same environment on a 2D screen with participants moving through doors of different widths using the keys on a standard keyboard. We compared components of the event-related potential (ERP) from the continuously recorded electroencephalogram (EEG) that were previously reported to be related to affordance perception of architectural transitions (passable and impassable doors). Comparing early sensory and later motor-related ERPs, our study replicated ERPs reflecting early affordance perception but found differences in later motor-related components. These results indicate a shift from automated perception of affordances during early sensorimotor time windows to movement context dependence of affordance perception at later stages, suggesting that affordance perception is a dynamic and flexible process that changes over sensorimotor stages.

Primer extension refractory PCR: an efficient and reliable genome walking method.

Genome walking, a molecular technique for obtaining unknown flanking genomic sequences from a known genomic sequence, has been broadly applied to determine transgenic sites, mine new genetic resources, and fill in chromosomal gaps. This technique has advanced genomics, genetics, and related disciplines. Here, an efficient and reliable genome walking technique, called primer extension refractory PCR (PER-PCR), is presented. PER-PCR uses a set of primary, secondary, and tertiary walking primers. The middle 15 nt of the primary walking primer overlaps with the 3' parts of the secondary and tertiary primers. The 5' parts of the three primers are heterologous to each other. The short overlap allows the walking primer to anneal to its predecessor only in a relaxed-stringency PCR cycle, resulting in a series of single-stranded DNAs; however, the heterologous 5' part prevents the creation of a perfect binding site for the walking primer. In the next stringent cycle, the target single strand can be extended into a double-stranded DNA molecule by the sequence-specific primer and thus can be exponentially amplified by the remaining stringent cycles. The nontarget single strand fails to be enriched due to the lack of a perfect binding site for any primer. PER-PCR was validated by extension into unknown flanking regions of the hyg gene in rice and the gadR gene in Levilactobacillus brevis CD0817. In summary, in this study, a new practical PER-PCR method was constructed as a potential alternative to existing genome walking methods.

Neuronal mechanisms regulating locomotion in adult Drosophila.

The coordinated action of multiple leg joints and muscles is required even for the simplest movements. Understanding the neuronal circuits and mechanisms that generate precise movements is essential for comprehending the neuronal basis of the locomotion and to infer the neuronal mechanisms underlying several locomotor-related diseases. Drosophila melanogaster provides an excellent model system for investigating the neuronal circuits underlying motor behaviors due to its simple nervous system and genetic accessibility. This review discusses current genetic methods for studying locomotor circuits and their function in adult Drosophila. We highlight recently identified neuronal pathways that modulate distinct forward and backward locomotion and describe the underlying neuronal control of leg swing and stance phases in freely moving flies. We also report various automated leg tracking methods to measure leg motion parameters and define inter-leg coordination, gait and locomotor speed of freely moving adult flies. Finally, we emphasize the role of leg proprioceptive signals to central motor circuits in leg coordination. Together, this review highlights the utility of adult Drosophila as a model to uncover underlying motor circuitry and the functional organization of the leg motor system that governs correct movement.

An integrated strategy involving high-throughput sequencing to characterize an unknown GM wheat event in Canada.

Glyphosate-resistant wheat plants were discovered in southern Alberta in 2017, representing an unauthorized GM release in Canada. The Canadian Food Inspection Agency undertook a series of experiments to characterize and identify this unknown GM wheat, as well as to develop and validate construct-specific and event-specific qPCR assays. Results of PCR-based assays and Sanger sequencing indicated the presence of CaMV 35S promoter (p35S), Rice Actin 1 intron (RactInt1), CP4-EPSPS gene and nopaline synthase terminator (tNOS) elements in the unknown GM wheat. Genome walking and bead capture strategies, combined with high-throughput sequencing, were used to identify the 5' and 3' wheat junctions and the subsequent mapping of the insert to chromosome 3B of the wheat genome. A probable transformation vector, pMON25497, was recognized, and further testing identified the unknown GM wheat as MON71200 event, one of two events obtained with the pMON25497 vector. The two construct-specific assays targeted the junctions of the RactInt1 and the CP4-EPSPS elements and the CP4-EPSPS and tNOS elements, while the event-specific assay was located at the 3' junction into the wheat genome. Both construct-specific and event-specific assays had limits of detection of 0.10% of MON71200 in a seed pool. As expected, the two construct-specific assays cross-reacted with other wheat and corn events containing the same elements in the same order. No cross-reactivity was observed for the event-specific assay. The integrated strategy employed in this study can serve as a model for other cases when facing similar challenges involving unknown GM events.

Home-Based Trimodal Prehabilitation in Patients with Peritoneal Carcinomatosis Undergoing Cytoreductive Surgery: Effect on Functional Walking Capacity and Skeletal Muscle Mass.

BACKGROUND: Patients with peritoneal carcinomatosis often suffer from loss of skeletal muscle mass and require extensive surgery. Multimodal prehabilitation may improve physical status but its benefits for these specific patients remain unknown. This study aimed to evaluate the effect of prehabilitation on functional walking capacity and skeletal muscle mass, as well as its association with postoperative complications. PATIENTS AND METHODS: A prospective study of patients with peritoneal carcinomatosis following a home-based trimodal prehabilitation program was carried out. Functional walking capacity was assessed with the 6-min walk test (T6MWT), and by the appendicular skeletal muscle index (ASMI) estimated by bioelectrical impedance analysis. Data were collected at the first medical appointment and on the day before surgery. A 90-day postoperative morbidity was registered according to the Clavien-Dindo classification. RESULTS: A total of 62 patients were included in the analysis. Women were more prevalent (77.4%) and peritoneal metastasis from ovarian origin accounted for 48.4%. Clavien II-V grades occurred in 30 (57.7%) patients. After prehabilitation, functional walking capacity improved by 42.2 m (39.62-44.72 m) compared with baseline data (p < 0.001), but no improvement was observed in the ASMI (p = 0.301). Patients able to walk at least 360 m after prehabilitation suffered fewer Clavien-Dindo II-V postoperative complications (p = 0.016). A T6MWT of less than 360 m was identified as an independent risk factor in the multivariable analysis (OR 3.99; 1.01-15.79 p = 0.048). CONCLUSIONS: This home-based trimodal prehabilitation program improved functional walking capacity but not ASMI scores in patients with peritoneal metastasis before surgery. A T6MWT of less than 360 m was found to be a risk factor for postoperative complications.

Real-world walking behaviors are associated with early-stage heart failure: a Project Baseline Health Study.

BACKGROUND: Data collected via wearables may complement in-clinic assessments to monitor subclinical heart failure (HF). OBJECTIVES: Evaluate the association of sensor-based digital walking measures with HF stage and characterize their correlation with in-clinic measures of physical performance, cardiac function and participant reported outcomes (PROs) in individuals with early HF. METHODS: The analyzable cohort included participants from the Project Baseline Health Study (PBHS) with HF stage 0, A, or B, or adaptive remodeling phenotype (without risk factors but with mild echocardiographic change, termed RF-/ECHO+) (based on available first-visit in-clinic test and echocardiogram results) and with sufficient sensor data. We computed daily values per participant for 18 digital walking measures, comparing HF subgroups vs stage 0 using multinomial logistic regression and characterizing associations with in-clinic measures and PROs with Spearman's correlation coefficients, adjusting all analyses for confounders. RESULTS: In the analyzable cohort (N=1265; 50.6% of the PBHS cohort), one standard deviation decreases in 17/18 walking measures were associated with greater likelihood for stage-B HF (multivariable-adjusted odds ratios [ORs] vs stage 0 ranging from 1.18-2.10), or A (ORs vs stage 0, 1.07-1.45), and lower likelihood for RF-/ECHO+ (ORs vs stage 0, 0.80-0.93). Peak 30-minute pace demonstrated the strongest associations with stage B (OR vs stage 0=2.10; 95% CI:1.74-2.53) and A (OR vs stage 0=1.43; 95% CI:1.23-1.66). Decreases in 13/18 measures were associated with greater likelihood for stage-B HF vs stage A. Strength of correlation with physical performance tests, echocardiographic cardiac-remodeling and dysfunction indices and PROs was greatest in stage B, then A, and lowest for 0. CONCLUSIONS: Digital measures of walking captured by wearable sensors could complement clinic-based testing to identify and monitor pre-symptomatic HF.

Outdoor walking, genetic predisposition, and the risk of incident osteoporosis among older adults: A prospective large population-based cohort study.

This large-scale prospective study showed that a significant association between longer duration of daily outdoor walking and reduced osteoporosis risk was found among older adults, particularly among those with a low genetic predisposition to osteoporosis, which highlighted the importance of outdoor walking as a simple, cost-effective adjunct for preventing osteoporosis. PURPOSE: The available cross-sectional data and small-scale studies indicate that outdoor walking benefits bone metabolism. Nevertheless, there is a scarcity of comprehensive prospective research investigating the enduring correlation between outdoor walking and osteoporosis. This study aims to conduct a prospective analysis of the correlation between outdoor walking and osteoporosis while also examining potential variations influenced by genetic susceptibility to osteoporosis. METHODS: 24,700 older adults without osteoporosis at baseline were enrolled. These individuals were followed up until December 31, 2021, during which data on outdoor walking was gathered. The genetic risk score for osteoporosis was comprised of 14 single-nucleotide polymorphisms. RESULTS: 4,586 cases of osteoporosis were identified throughout a median follow-up period of 37.3 months. Those who walked outside for > 30 but ≤ 60 min per day had a hazard ratio (HR) of 0.83 (95% confidence interval (CI): 0.72-0.95) for incident osteoporosis, whereas those who walked outside for > 60 min per day had an HR of 0.60 (95% CI: 0.39-0.92). We found that osteoporosis risk exhibited a declining trend in individuals with low genetic risk. Individuals walking outside for > 60 min per day tended to have the lowest overall osteoporosis risk among those with high genetic risk. CONCLUSIONS: A significant negative correlation exists between an extended period of daily outdoor walking and osteoporosis incidence risk. This correlation is particularly pronounced among individuals with low genetic risk. The results above underscore the significance of outdoor walking as a simple and economical adjunct to public health programs to prevent osteoporosis.

Six-minute walking distance and desaturation-distance ratio in allogeneic stem cell transplantation.

BACKGROUND: Most patients with haematological malignancies who undergo allogeneic haematopoietic stem cell transplant (HSCT) receive chemotherapy before the transplant to control the disease. Certain chemotherapy drugs can cause lung toxicity. Conversely, in patients with chronic respiratory conditions, the 6-min walking test (6MWT) and the desaturation-distance ratio (DDR) have demonstrated prognostic significance. Our objective was to determine whether the 6MWD and DDR, assessed prior to HSCT, have a prognostic impact on survival at 24 months post-HSCT. METHODS: A prospective experimental study was conducted in consecutive patients referred for allogeneic HSCT at Hospital Clinic, Barcelona, Spain. A complete functional respiratory study, including the 6MWT and DDR, was conducted prior to admission. The area under the curve (AUC) and cut-off points were calculated. Data on patients' characteristics, HSCT details, main events, with a focus on lung complications, and survival at 24 months were analysed. RESULTS: One hundred and seventy-five patients (39% women) with mean age of 48 ± 13 years old were included. Before HSCT, forced vital capacity and forced expiratory volume in the first second were 96% ± 13% predicted and 92% ± 14% predicted, respectively; corrected diffusing capacity for carbon monoxide 79% ± 15% predicted; 6MWD was 568 ± 83 m and DDR of .27 (.20-.41). The cut-off points for 6MWD and DDR were 566 m, [.58 95% CI (.51-.64)], p = .024 and .306, [.63 95% CI (.55-.70)], p = .0005, respectively. The survival rate at 24 months was 55%. CONCLUSION: Our results showed that individuals who exhibit a 6MWD shorter than 566 ms or a decline in DDR beyond .306 experienced reduced survival rates at 24 months after HSCT.

Blood Oxygen Level-Dependent MR Imaging of Lower Extremities in Peripheral Artery Disease and Its Correlation With Walking Performance.

BACKGROUND: A noninvasive and reliable approach to quantitatively measure muscle perfusion of lower extremity is needed to aid the diagnosis and treatment of peripheral artery disease (PAD). PURPOSE: To verify the reproductivity of using blood oxygen level-dependent (BOLD) imaging to evaluate perfusion in lower extremities, and explore its correlation with walking performance in patients with PAD. STUDY TYPE: Prospective observational study. SUBJECTS: Seventeen patients with lower extremity PAD (mean age: 67 ± 6 years, 15 males) and eight older adults (controls). FIELD STRENGTH/SEQUENCE: Dynamic multi-echo gradient echo T2* weighted imaging at 3T. ASSESSMENT: Perfusion was analyzed in regions of interest according to muscle groups. Perfusion parameters were measured, such as minimum ischemia value (MIV), time to peak (TTP), and gradient during reactive hyperemia (Grad) by two independent users. Walking performance experiments including short physical performance battery (SPPB) and 6-minute walk were tested in patients. STATISTICAL TESTS: BOLD parameters were compared using Mann-Whitney U test and Kruskal-Wallis test. Relations between parameters and walking performance were assessed by Mann-Whitney U test and Spearman's correlation coefficient. RESULTS: Good to perfect agreement was demonstrated for all perfusion parameters of interuser reproducibility, and the interscan reproducibility of MIV, TTP, and Grad was good. The TTP of the patients was longer than that of the controls (87.85 ± 38.85 s vs. 36.54 ± 7.27 s), while the Grad of patients was smaller (0.16 ± 0.12 msec/s vs. 0.24 ± 0.11 msec/s). Among PAD patients, the MIV was significantly lower in the low SPPB subgroup (score 6-8) than in the high SPPB group (score 9-12), and the TTP was negatively correlated with 6-minute walk distance (ρ = -0.549). DATA CONCLUSION: BOLD imaging method had overall good reproducibility for the perfusion assessment of calf muscles. The perfusion parameters were different between PAD patients and controls, and were correlated with lower extremity function. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.