The processing of brain diffusion tensor imaging (DTI) data for large cohort studies requires fully automatic pipelines to perform quality control (QC) and artifact/outlier removal procedures on the ...raw DTI data prior to calculation of diffusion parameters. In this study, three automatic DTI processing pipelines, each complying with the general ENIGMA framework, were designed by uniquely combining multiple image processing software tools. Different QC procedures based on the RESTORE algorithm, the DTIPrep protocol, and a combination of both methods were compared using simulated ground truth and artifact containing DTI datasets modeling eddy current induced distortions, various levels of motion artifacts, and thermal noise. Variability was also examined in 20 DTI datasets acquired in subjects with vascular cognitive impairment (VCI) from the multi-site Ontario Neurodegenerative Disease Research Initiative (ONDRI). The mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated in global brain grey matter (GM) and white matter (WM) regions. For the simulated DTI datasets, the measure used to evaluate the performance of the pipelines was the normalized difference between the mean DTI metrics measured in GM and WM regions and the corresponding ground truth DTI value. The performance of the proposed pipelines was very similar, particularly in FA measurements. However, the pipeline based on the RESTORE algorithm was the most accurate when analyzing the artifact containing DTI datasets. The pipeline that combined the DTIPrep protocol and the RESTORE algorithm produced the lowest standard deviation in FA measurements in normal appearing WM across subjects. We concluded that this pipeline was the most robust and is preferred for automated analysis of multisite brain DTI data.
In some cooperatively breeding groups, individuals have distinct behavioral characteristics that are often stable and predictable across time. However, in others, as in the eusocial naked mole-rat, ...evidence for behavioral phenotypes is ambiguous. Here, we study whether the naked mole-rat can be divided into discrete phenotypes and if circulating hormone concentrations underpin these differences. Naked mole-rat colonies consist of a single breeding female and large numbers of non-reproductive subordinates that in some cases can exceed several hundred in a colony. The subordinates can potentially be divided into soldiers, who defend the colony; workers, who maintain it; and dispersers, who want to leave it. We established six colonies de novo, tracked them over three years, and assessed the behavior and hormone concentrations of the subordinates. We found that soldiers tended to be from earlier litters and were higher ranked compared to workers, whereas dispersers were distributed throughout litters and rankings. There was no difference in estradiol, testosterone, or dehydroepiandrosterone (DHEA) concentrations among phenotypes. Progesterone concentrations were higher in soldiers, but this difference appeared to be driven by a few individuals. Principal component analysis demonstrated that soldiers separated into a discrete category relative to workers/dispersers, with the highest ranked loadings being age, body mass, and testosterone concentrations. However, the higher testosterone in soldiers was correlated with large body size instead of strictly behavioral phenotype. Workers and dispersers have more overlap with each other and no hormonal differences. Thus the behavioral variation in subordinate naked mole-rats is likely not driven by circulating steroid hormone concentrations, but rather it may stem from alternative neural and/or neuroendocrine mechanisms.
•Naked mole-rat subordinates are classified into workers, dispersers and soldiers.•Soldiers tend to be born in earlier litters and rank higher in dominance.•Soldiers have higher levels of circulating progesterone.•Workers and dispersers have overlapping biological correlates.•Behavioral phenotypes are not driven by circulating hormones.
•ACT informed physical therapy (PACT) is acceptable for people with CLBP•PACT participants reported significantly better functioning at 3 months’ follow-up•Improvements compared to standard physical ...therapy were not maintained at 12 months•PACT can be delivered with high fidelity by trained physical therapists
Chronic low back pain (CLBP) is a major cause of global disability and improving management is essential. Acceptance and commitment therapy (ACT) is a promising treatment for chronic pain but has not been modified for physical therapy. This randomized controlled trial (RCT) compared physical therapy informed by ACT (PACT) against standard care physical therapy for patients with CLBP. Patients with CLBP (duration ≥12 weeks, mean 3 years) were recruited from physical therapy clinics in 4 UK public hospitals. The Roland-Morris Disability Questionnaire (RMDQ) at 3 months’ post-randomization was the primary outcome. Two hundred forty-eight participants (59% female, mean age = 48) were recruited and 219 (88.3%) completed measures at 3 and/or 12 months’ follow-up. At 3 months, PACT participants reported better outcomes for disability (RMDQ mean difference = 1.07, p = .037, 95% CI = −2.08 to −.07, d = .2), Patient Specific Functioning (p = .008), SF12 physical health (p = .032), and treatment credibility (p < .001). At 12 months’ follow-up, there were no significant differences between groups. PACT was acceptable to patients and clinicians and feasible to deliver. Physical therapists incorporated psychological principles successfully and treatment was delivered with high (≥80%) fidelity. Our results may inform the management of CLBP, with potential benefits for patients, health care providers, and society.
Psychologically informed physical therapy has great potential but there are challenges in implementation. The training and support included in the PACT trial enabled the intervention to be delivered as planned. This successfully reduced disability in the short but not long term. Findings could inform physical therapists’ treatment of CLBP.
Neuroendocrine mechanisms underlying social inhibition of puberty are not well understood. Here, we use a model exhibiting the most profound case of pubertal suppression among mammals to explore a ...role for RFamide-related peptide-3 RFRP-3; mammalian ortholog to gonadotropin-inhibitory hormone (GnIH) in neuroendocrine control of reproductive development. Naked mole rats (NMRs) live in sizable colonies where breeding is monopolized by two to four dominant animals, and no other members exhibit signs of puberty throughout their lives unless they are removed from the colony. Because of its inhibitory action on the reproductive axis in other vertebrates, we investigated the role of RFRP-3 in social reproductive suppression in NMRs. We report that RFRP-3 immunofluorescence expression patterns and RFRP-3/GnRH cross-talk are largely conserved in the NMR brain, with the exception of the unique presence of RFRP-3 cell bodies in the arcuate nucleus (Arc). Immunofluorescence comparisons revealed that central expression of RFRP-3 is altered by reproductive status, with RFRP-3 immunoreactivity enhanced in the paraventricular nucleus, dorsomedial nucleus, and Arc of reproductively quiescent NMRs. We further observed that exogenous RFRP-3 suppresses gonadal steroidogenesis and mating behavior in NMRs given the opportunity to undergo puberty. Together, our findings establish a role for RFRP-3 in preserving reproductive immaturity, and challenge the view that stimulatory peptides are the ultimate gatekeepers of puberty.
Recently, we described that in the naked mole rat ovary it is possible to study the ovarian reserve and the mitotic expansion of the germ cell postnatally. Herein, we show oocyte in vitro maturation ...and in vitro germ cell expansion using the same ovary.
In the long-lived naked mole-rat (NMR), the entire process of oogenesis occurs postnatally. Germ cell numbers increase significantly in NMRs between postnatal days 5 (P5) and P8, and germs cells ...positive for proliferation markers (Ki-67, pHH3) are present at least until P90. Using pluripotency markers (SOX2 and OCT4) and the primordial germ cell (PGC) marker BLIMP1, we show that PGCs persist up to P90 alongside germ cells in all stages of female differentiation and undergo mitosis both in vivo and in vitro. We identified VASA+ SOX2+ cells at 6 months and at 3-years in subordinate and reproductively activated females. Reproductive activation was associated with proliferation of VASA+ SOX2+ cells. Collectively, our results suggest that highly desynchronized germ cell development and the maintenance of a small population of PGCs that can expand upon reproductive activation are unique strategies that could help to maintain the NMR's ovarian reserve for its 30-year reproductive lifespan.
•Multi-segment foot model evaluated gait kinematics in PFP and healthy participants.•PFP participants did not demonstrate excessive dynamic pronation.•Kinematics was not associated with static foot ...posture in PFP participants.
Background Excessive pronation has been implicated in patellofemoral pain (PFP) aetiology and foot orthoses are commonly prescribed for PFP patients. Pronation can be assessed using foot posture tests, however, the utility of such tests depends on their association with foot and lower-limb kinematics.
Research questions Do PFP participants compared with healthy participants (1) have a more pronated foot measured with static foot tests and a kinematic multi-segmental foot model and (2) is there an association between static foot posture and foot and lower limb kinematics during walking?
Methods A case-control study including 22 participants (n = 11 PFP, 5 females per group, aged 24 ± 3 (mean ± SD) years) was conducted. Foot posture measures included Arch Height Ratio, Navicular Drop (ND), and Foot Posture Index. Between-group comparisons of foot posture, segment and joint angle magnitudes, and associations between foot posture and kinematic data during gait were evaluated.
Results There were no group differences in foot posture tests and mean joint angles. PFP participants had greater internal rotation of the shank and rearfoot segments, and adduction of the mid- and forefoot in the transverse plane (all p < 0.05). Greater ND was associated with increased forefoot abduction (rho=-0.68, p = 0.02) in healthy participants but no relationships were found between foot posture and kinematics in PFP participants.
Significance Foot posture and kinematic data did not indicate excessive pronation in PFP participants questioning the use of orthoses to correct pronation. Larger studies are needed to determine the utility of foot posture tests as indicators of gait abnormalities in PFP.
Walking is an effective but underused treatment for intermittent claudication. This qualitative study explored people’s experiences of and beliefs about their illness and walking with intermittent ...claudication. Using the Framework method, semi-structured in-depth interviews included 19 individuals with intermittent claudication, and were informed by the Theory of Planned Behaviour and Common Sense Model of Illness Representations. Walking was overlooked as a self-management opportunity, regardless of perceptions of intermittent claudication as severe or benign. Participants desired tailored advice, including purposeful and vigorous exercise, and the potential outcome of walking. Uncertainties about their illness and treatment may explain low walking participation among people with intermittent claudication.
In many social species, hierarchical status within the group is associated with differences in basal adrenocortical activity. We examined this relationship in naked mole-rats (Heterocephalus glaber), ...eusocial rodents with arguably the most extreme social hierarchies of all mammals. This species lives in colonies where breeding is restricted to one socially dominant ‘queen’ and her male consorts, and all other individuals are reproductively suppressed ‘subordinates’. The relationship between cortisol and social status in naked mole-rats has not fully been elucidated, as prior results on this topic have been contradictory. We used non-invasive feces sampling to measure baseline cortisol levels in eight laboratory colonies of naked mole-rats, to either replicate or reject rank differences. First, we successfully validated an assay to measure fecal cortisol metabolites (FCMs). Removal from the colony for the validation experiment, either alone or with an opposite sex conspecific, induced prolonged elevation of FCM levels on a scale of days to weeks. This increase in cortisol did not prevent the removed animals from sexually maturing. In colony-housed animals, we found no relationship between rank in the social hierarchy and FCM levels. Further, queens, breeding males, and reproductively suppressed subordinates all had equivalent FCM levels. We conclude that this species shows little evidence of the ‘stress of dominance’ or ‘stress of subordination’ and that reproductive suppression in naked mole-rats is not driven by elevated cortisol levels.
•Fecal cortisol levels do not differ in dominant and subordinate naked mole-rats.•Separation from the colony drives an increase in cortisol levels over days to weeks.•High cortisol is not associated with reproductive suppression in this species.
This study explored the experiences and acceptability of a novel, home-based, walking exercise behaviour-change intervention (MOtivating Structured walking Activity in people with Intermittent ...Claudication (MOSAIC)) in adults with Peripheral Arterial Disease (PAD).
Individual semi-structured audio-recorded interviews were conducted with adults with Peripheral Arterial Disease who had completed the MOSAIC intervention as part of a randomised clinical trial. Data were analysed using inductive reflexive thematic analysis and interpreted using the seven-construct theoretical framework of acceptability of healthcare interventions (TFA).
Twenty participants (mean age (range) 67(54−80) years, 70% male, 55% White British) were interviewed.
One central theme was identified: Acceptability of walking exercise as a treatment. This theme was explained by four linked themes: Exploring walking exercise with a knowledgeable professional, Building confidence with each step, Towards self-management-learning strategies to continue walking and The impact of walking exercise. These themes were interpreted using six of the seven TFA constructs: affective attitude, burden, perceived effectiveness, intervention coherence, opportunity costs, and self-efficacy.
Participants perceived MOSAIC as an effective, acceptable, and low burden intervention. Physiotherapists were regarded as knowledgeable and supportive professionals who helped participants understand PAD and walking exercise as a treatment. Participants developed confidence to self-manage their condition and their symptoms. As participants confidence and walking capacity improved, they expanded their activities and gained a more positive outlook on their future. MOSAIC is an acceptable intervention that may facilitate adoption of and access to exercise for people with PAD.
•The MOtivating Structured walking Activity in people with Intermittent Claudication (MOSAIC) intervention was perceived as an effective, low burden and acceptable intervention by participants.•Physiotherapists were regarded as knowledgeable and supportive professionals who helped participants understand PAD and walking exercise as a treatment.•MOSAIC helped participants improve their confidence to self-manage their condition and as their walking capacity improved participants expanded their activities and gained a more positive outlook on their future.•Implementation of MOSAIC may facilitate adoption of and access to exercise therapy for people with PAD.
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