• Adolescents' Understanding of What Causes Emotional Distress: A Qualitative Exploration in a Non-clinical Sample Using Ideal-Type Analysis

      O'Neill, Alisha; email: alisha.oneill@Manchester.ac.uk; Stapley, Emily; Stock, Sarah; Merrick, Hannah; Humphrey, Neil (Frontiers Media S.A., 2021-05-24)
      Background: There is increased interest in early intervention and prevention of mental health difficulties during adolescence; thus, we are seeing increased efforts to optimize well-being during this epoch. Positive emotional experiences are a central component of overall well-being. However, research exploring what adolescents perceive to be the cause(s) of their emotional difficulties is lacking. Improving understanding of this issue within non-clinical adolescent groups may provide useful insight into how to develop strategies to support young people as they navigate emotional difficulties. Objectives: The aim of this research was to explore if meaningful categories of perceived cause(s) for emotional distress exist for non-clinical adolescent groups. Methods: The data for this study were drawn from interviews across 6 sites in England conducted as part of the 5-year national evaluation of the HeadStart Learning Programme. The sample comprised of 32 young people aged 11–12 years from the first annual wave of qualitative data collection in 2017. Ideal type analysis—a qualitative form of person-centered analysis—was used to construct a typology of adolescents perceived cause(s) for emotional distress. Findings: We identified five distinct categories of perceived cause: (1) perceived lack of control; (2) unfair treatment; (3) others, their actions and judgements as the catalyst; (4) concerns for self and others; and, (5) self as cause. Conclusions: Our findings illustrate that distinct categories for perceived cause of emotional distress exist among adolescents considered to be “at risk” of developing mental health difficulties, which provides a foundation for future necessary work seeking to investigate the possible link between perceived cause for emotional distress and help-seeking behavior among sub-clinical groups.
    • Autosomal Recessive Cutis Laxa 1C Mutations Disrupt the Structure and Interactions of Latent TGFβ Binding Protein-4

      Alanazi, Yasmene F.; Lockhart-Cairns, Michael P.; Cain, Stuart A.; Jowitt, Thomas A.; Weiss, Anthony S.; Baldock, Clair; email: clair.baldock@manchester.ac.uk (Frontiers Media S.A., 2021-09-03)
      Latent TGFβ binding protein-4 (LTBP4) is a multi-domain glycoprotein, essential for regulating the extracellular bioavailability of TGFβ and assembly of elastic fibre proteins, fibrillin-1 and tropoelastin. LTBP4 mutations are linked to autosomal recessive cutis laxa type 1C (ARCL1C), a rare congenital disease characterised by high mortality and severely disrupted connective tissues. Despite the importance of LTBP4, the structure and molecular consequences of disease mutations are unknown. Therefore, we analysed the structural and functional consequences of three ARCL1C causing point mutations which effect highly conserved cysteine residues. Our structural and biophysical data show that the LTBP4 N- and C-terminal regions are monomeric in solution and adopt extended conformations with the mutations resulting in subtle changes to their conformation. Similar to LTBP1, the N-terminal region is relatively inflexible, whereas the C-terminal region is flexible. Interaction studies show that one C-terminal mutation slightly decreases binding to fibrillin-1. We also found that the LTBP4 C-terminal region directly interacts with tropoelastin which is perturbed by both C-terminal ARCL1C mutations, whereas an N-terminal mutation increased binding to fibulin-4 but did not affect the interaction with heparan sulphate. Our results suggest that LTBP4 mutations contribute to ARCL1C by disrupting the structure and interactions of LTBP4 which are essential for elastogenesis in a range of mammalian connective tissues.
    • Continuous Magnitude Production of Loudness

      Schlittenlacher, Josef; email: josef.schlittenlacher@manchester.ac.uk; Ellermeier, Wolfgang (Frontiers Media S.A., 2021-05-11)
      Continuous magnitude estimation and continuous cross-modality matching with line length can efficiently track the momentary loudness of time-varying sounds in behavioural experiments. These methods are known to be prone to systematic biases but may be checked for consistency using their counterpart, magnitude production. Thus, in Experiment 1, we performed such an evaluation for time-varying sounds. Twenty participants produced continuous cross-modality matches to assess the momentary loudness of fourteen songs by continuously adjusting the length of a line. In Experiment 2, the resulting temporal line length profile for each excerpt was played back like a video together with the given song and participants were asked to continuously adjust the volume to match the momentary line length. The recorded temporal line length profile, however, was manipulated for segments with durations between 7 to 12 s by eight factors between 0.5 and 2, corresponding to expected differences in adjusted level of −10, −6, −3, −1, 1, 3, 6, and 10 dB according to Stevens’s power law for loudness. The average adjustments 5 s after the onset of the change were −3.3, −2.4, −1.0, −0.2, 0.2, 1.4, 2.4, and 4.4 dB. Smaller adjustments than predicted by the power law are in line with magnitude-production results by Stevens and co-workers due to “regression effects.” Continuous cross-modality matches of line length turned out to be consistent with current loudness models, and by passing the consistency check with cross-modal productions, demonstrate that the method is suited to track the momentary loudness of time-varying sounds.
    • Dance at Home for People With Parkinson's During COVID-19 and Beyond: Participation, Perceptions, and Prospects

      Bek, Judith; email: judith.bek@manchester.ac.uk; Groves, Michelle; Leventhal, David; Poliakoff, Ellen (Frontiers Media S.A., 2021-05-31)
      Emerging evidence shows that dance can provide both physical and non-physical benefits for people living with Parkinson's disease (PD). The suspension of in-person dance classes during the COVID-19 pandemic necessitated a transition to remote provision via live and recorded digital media. An online survey explored accessibility of and engagement with home-based dance programs, as well as potential benefits and processes involved in participation. The survey was co-developed by researchers and dance program providers, with input from people with PD and physiotherapists. Responses were collected from 276 individuals, including 178 current users of home-based programs, the majority of whom were participating at least once per week. Among respondents not currently using digital resources, lack of knowledge and motivation were the primary barriers. Most participants (94.9%) reported that home based practise provided some benefits, including physical (e.g., balance, posture) and non-physical (e.g., mood, confidence) improvements. Participants valued the convenience and flexibility of digital participation, but noted limitations including reductions in social interaction, support from instructors and peers, and motivation. There was a strong preference (70.8%) for continuing with home-based practise alongside in-person classes in the future. The results indicate that at-home dance is accessible and usable for people with PD, and that some of the previously-reported benefits of dance may be replicated in this context. Digital dance programs will likely remain a key element of future provision for people with PD, and the present findings will inform further development of resources and research into mechanisms and outcomes of home-based dance participation.
    • Differences in Characteristics and Ambulance Pathway Adherence Between Strokes and Mimics Presenting to a Large UK Centralized Hyper Acute Stroke Unit (HASU)

      Sammut-Powell, Camilla; email: Camilla.sammut-powell@manchester.ac.uk; Ashton, Christopher; Paroutoglou, Kyriaki; Parry-Jones, Adrian (Frontiers Media S.A., 2021-05-10)
      Background: In Greater Manchester (GM), prehospital clinicians use the Face Arm Speech Test (FAST) to identify suspected stroke patients alongside pathway exclusions. Within the centralized stroke service, patients with a suspected stroke are taken directly to a Hyper Acute Stroke Unit (HASU), often bypassing their local emergency department (ED). However, many of these patients are experiencing an illness that looks like a stroke but is not a stroke. The data collected in the prehospital setting is rarely used in research yet could give valuable insights into the performance of the pathway. Aim: To evaluate the presenting symptoms and final diagnoses of prehospital suspected strokes and to evaluate the adherence of prehospital stroke pathway exclusions. Methods: We analyzed data from all patients brought in by ambulance and admitted on the stroke pathway between 01/09/15 and 28/02/17. Patient demographics and all data recorded in the prehospital setting were evaluated to identify differences in stroke, TIA, and mimic patients. Pathway adherence was assessed according to whether the patient was local or out-of-area (OOA) and bypassed their local ED. Results: A total of 4,216 suspected strokes were identified: 2,213 (52.5%) had a final diagnosis of stroke, 492 (11.7%) experienced a transient ischemic attack (TIA), and 1,511 (35.8%) were stroke mimics. There were 714 (16.9%) patients that were identified as having at least one pathway exclusion or were FAST negative, of which 270 (37.8%) experienced a stroke. The proportion of strokes was significantly lower in those with a pathway exclusion (41.8 vs. 53.5%; p < 0.001) and the proportion of breaches tended to be comparable or higher in the local population. Discussion: There are high volumes of stroke mimics but identified differences indicate there is an opportunity to better utilize prehospital data. Ambulance clinicians were able to correctly overrule FAST negative results and the volume of these suggest that FAST alone may be too restrictive.
    • Editorial: Cooperation and Coordination in the Family

      Savage, James L.; email: james.savage@cantab.net; Hinde, Camilla A.; Johnstone, Rufus A. (Frontiers Media S.A., 2020-12-07)
    • Editorial: New Drug Targets for Proteotoxicity in Cardiometabolic Diseases

      Ren, Jun; email: jren@uw.edu; Wang, Xin; email: xin.wang@manchester.ac.uk; Zhang, Yingmei; email: zhangym197951@126.com (Frontiers Media S.A., 2021-09-16)
    • Effects of Radiation sterilization Dose on the Molecular Weight and Gelling Properties of Commercial Alginate Samples

      Mollah, M. Z. I.; email: zahirul1973@yahoo.com; Rahaman, M S.; Faruque, M R I.; Khandaker, M U.; Osman, Hamid; Alamri, Sultan; Al-Assaf, Saphwan (Frontiers Media S.A., 2021-12-20)
      To estimate the molecular weight (Mw) and gelling properties, a total of 26 alginate samples consisting of control (n = 13) and 15 kGy γ-irradiated (n = 13) samples were characterized through viscometric and gel permeation chromatography (GPC-MALLS) methods. Based on the observations, a remarkable decrease in the intrinsic viscosity of all samples of alginates was evident due to the effects of radiation, with a linear relationship between viscosity and concentration in 0.01 M NaCl solution. The correlation among the Mw, percentage mass recovery, radii of gyration (Rz/Rg), and percentage reduction of Mw assessed by GPC was significant. The Mw decreased dramatically (from 3.1 × 105 to 0.49 × 105 mole/g in sample no. 12) by the effect of radiation with momentous relation to the % reduction of the molecular weight. The highest molecular weight reduction (84%), which is the most sensitive to γ-radiation, and the average reduction rate was ≥50%. The mass recovery was 100% obtained from samples no. 1,3,4,5,7,12, and 13, while the rest of the samples’ recovery rate was significantly higher. The reduction rate of mass molecular weight (Mw) is higher than the average molecular weight (Mv), but they showed a sensitivity towards radiation, consequently their performance are different from each other. The stability test was performed as a critical behaviour in the control, recurrently same as in the irradiated samples. Thus, the sterilization dose of 15 kGy for the Mw distribution, and subsequently for the characterization, was significantly effective.
    • Equivalence, Justice, Injustice – Health and Social Care Decision Making in Relation to Prison Populations

      Shepherd, Andrew; email: andrew.shepherd-2@manchester.ac.uk; Hewson, Tom; Hard, Jake; Green, Russell; Shaw, Jennifer (Frontiers Media S.A., 2021-07-14)
      Prisons represent sites of singular healthcare need–characterized by high levels of distress and disorder. In many jurisdictions, practitioners are ethically charged with delivering healthcare that is “equivalent” to that available in the wider community. This claim has been much debated–yet the emergence of a global coronavirus pandemic has highlighted the arguments in a particularly stark manner. In the following conceptual analysis, we explore the emergent discourse of the coronavirus and consider its particular significance for prison healthcare decision making and the concept of equivalence. For example, both the coronavirus pandemic and practice of prison incarceration induce a sense of varied temporality: The discourse of prison is replete in this area–such as the concept of “hard time.” Alongside this, the discourse in relation to coronavirus has highlighted two competing modes of temporal understanding: The political–where the pandemic is conceptualized as has having a discrete “beginning and end”, and the scientific–where the “new normal” reflects the incorporation of the “novel” coronavirus into the wider ecology. The impact of these disparate understandings on the prison population is complex: “Locking down” prisoners–to safeguard the vulnerable against infection–is relatively simple, yet it has traumatic repercussions with respect to liberty and psychosocial health. Easing lockdown, by contrast, is a difficult endeavor and risks collision between the temporalities of prison–where “hard time” is accentuated by separation from the “real world”–the political and the scientific. Whither then the concept of equivalence in relation to a field that is definitively non-equivalent? How can practitioners and policy makers maintain a just ethical stance in relation to the allocation of resources when it comes to a politically marginalized yet manifestly vulnerable population? We argue that further debate and consideration are required in this field–and propose a framework for such discussion.
    • Extrinsic and Existential Mortality Risk in Reproductive Decision-Making: Examining the Effects of COVID-19 Experience and Climate Change Beliefs

      Gordon, David S.; email: david.gordon@chester.ac.uk (Frontiers Media S.A., 2021-06-11)
      While the COVID-19 pandemic has presented an immediate risk to human life around the world, climate change poses an arguably greater—although less immediate—threat to our species’ survival. Within the framework of life-history theory (LHT), this pre-registered study investigated whether extrinsic risk (i.e., external factors that pose a risk to an individual’s life, e.g., COVID-19) and existential risk (i.e., risks with outcomes that threaten the existence of humans as a species, e.g., climate change) had similar or different relationships with reproductive decision-making. A UK representative sample of 325 participants between 18 and 35 years of age was asked to indicate their ideal number of children, ideal age to start having children, and whether their desire for a child had recently changed. Participants were asked about their experiences of COVID-19 and given a series of scales with which to assess their beliefs about climate change. In support of LHT, the study found evidence that knowing people who had been hospitalized with or died of COVID-19 was associated with a greater ideal number of children. Conversely, there was no clear evidence of a relationship between climate change beliefs and reproductive decision-making. The repercussions for understanding how we interpret and respond to different forms of mortality risk are discussed.
    • Heart's Ease: Eudaimonia, Musicking in the Pandemic, and Its Implications for Music Education

      Boyce-Tillman, June; email: june.boyce-tillman@winchester.ac.uk (Frontiers Media S.A., 2021-09-09)
      This article will review the themes found in the literature on eudaimonia: ethical behaviour, a sense of meaning and purpose, autonomy – being able to make wise decisions and manage behaviour, contemplation, relationship with spirits of the ancestors and celestial beings and relationships of mutuality, respect. It will use these to critique various events online during the pandemic, such as the Embodiment conference, the SHIFT conference and the ZOOM peace choir. These developments related to music and wellbeing will be used to interrogate the purposes of music education and what might be learned from these new developments in relation to technology in relation to themes, such as values, orality and literacy, process and product.
    • Iron Is Filtered by the Kidney and Is Reabsorbed by the Proximal Tubule

      Wareing, Mark; Smith, Craig P.; email: craig.smith@manchester.ac.uk (Frontiers Media S.A., 2021-09-30)
      The aim of this study was to determine the iron (Fe) concentration profile within the lumen of the S2 renal proximal convoluted tubule (PCT) and to resolve whether this nephron segment transported Fe. To do this, we performed in vivo renal micropuncture on Wistar rats, collected PCT tubular fluid from superficial nephrons, and measured Fe concentration. The Fe concentration profile along the S2 PCT suggested significant Fe reabsorption. Proximal tubules were also microperfused in vivo with physiological solutions containing Fe and Zn, Cu, Mn, or Cd. PCTs perfused with 12μmol.l−1 55FeCl3 reabsorbed 105.2±12.7 fmol.mm−1.min−1 Fe, 435±52pmol.mm-1.min−1 Na, and 2.7±0.2nl.mm−1.min−1 water (mean ± SEM; n=19). Addition of ascorbate (1mmol.l−1) to the perfusate did not significantly alter Fe, Na, or water reabsorption. Supplementing the control perfusate with 60μmol.l−1 FeSO4 significantly decreased 55Fe uptake. Recalculating for the altered molar activity following addition of unlabeled Fe revealed a three-fold increase in Fe flux. Addition to the perfusate 12μmol.l−1 CuSO4, MnSO4, CdSO4, or ZnSO4 did not affect Fe, Na, or water flux. In conclusion, (1) in vivo, S2 PCTs of rat reabsorb Fe and (2) Fe is reabsorbed along the PCT via a pathway that is insensitive to Cu, Mn, Cd, or Zn. Together, these data demonstrate for the first time the hitherto speculated process of renal Fe filtration and subsequent tubular Fe reabsorption in a living mammal.
    • Learning Actions From Natural Language Instructions Using an ON-World Embodied Cognitive Architecture

      Giorgi, Ioanna; email: ioanna.giorgi@manchester.ac.uk; Cangelosi, Angelo; Masala, Giovanni L. (Frontiers Media S.A., 2021-05-13)
      Endowing robots with the ability to view the world the way humans do, to understand natural language and to learn novel semantic meanings when they are deployed in the physical world, is a compelling problem. Another significant aspect is linking language to action, in particular, utterances involving abstract words, in artificial agents. In this work, we propose a novel methodology, using a brain-inspired architecture, to model an appropriate mapping of language with the percept and internal motor representation in humanoid robots. This research presents the first robotic instantiation of a complex architecture based on the Baddeley's Working Memory (WM) model. Our proposed method grants a scalable knowledge representation of verbal and non-verbal signals in the cognitive architecture, which supports incremental open-ended learning. Human spoken utterances about the workspace and the task are combined with the internal knowledge map of the robot to achieve task accomplishment goals. We train the robot to understand instructions involving higher-order (abstract) linguistic concepts of developmental complexity, which cannot be directly hooked in the physical world and are not pre-defined in the robot's static self-representation. Our proposed interactive learning method grants flexible run-time acquisition of novel linguistic forms and real-world information, without training the cognitive model anew. Hence, the robot can adapt to new workspaces that include novel objects and task outcomes. We assess the potential of the proposed methodology in verification experiments with a humanoid robot. The obtained results suggest robust capabilities of the model to link language bi-directionally with the physical environment and solve a variety of manipulation tasks, starting with limited knowledge and gradually learning from the run-time interaction with the tutor, past the pre-trained stage.
    • Like Father Like Son: Cultural and Genetic Contributions to Song Inheritance in an Estrildid Finch

      Lewis, Rebecca N.; email: rebecca.lewis-3@manchester.ac.uk; Soma, Masayo; de Kort, Selvino R.; Gilman, R. Tucker (Frontiers Media S.A., 2021-06-04)
      Social learning of vocalizations is integral to song inheritance in oscine passerines. However, other factors, such as genetic inheritance and the developmental environment, can also influence song phenotype. The relative contributions of these factors can have a strong influence on song evolution and may affect important evolutionary processes such as speciation. However, relative contributions are well-described only for a few species and are likely to vary with taxonomy. Using archived song data, we examined patterns of song inheritance in a domestic population of Java sparrows (Lonchura oryzivora), some of which had been cross-fostered. Six-hundred and seventy-six songs from 73 birds were segmented and classified into notes and note subtypes (N = 22,972), for which a range of acoustic features were measured. Overall, we found strong evidence for cultural inheritance of song structure and of the acoustic characteristics of notes; sons’ song syntax and note composition were similar to that of their social fathers and were not influenced by genetic relatedness. For vocal consistency of note subtypes, a measure of vocal performance, there was no apparent evidence of social or genetic inheritance, but both age and developmental environment influenced consistency. These findings suggest that high learning fidelity of song material, i.e., song structure and note characteristics, could allow novel variants to be preserved and accumulate over generations, with implications for evolution and conservation. However, differences in vocal performance do not show strong links to cultural inheritance, instead potentially serving as condition dependent signals.
    • Mechanisms and Therapeutic Prospects of Diabetic Cardiomyopathy Through the Inflammatory Response

      Kaur, Namrita; Guan, Yingshu; Raja, Rida; Ruiz-Velasco, Andrea; Liu, Wei; email: wei.liu@manchester.ac.uk (Frontiers Media S.A., 2021-06-21)
      The incidence of heart failure (HF) continues to increase rapidly in patients with diabetes. It is marked by myocardial remodeling, including fibrosis, hypertrophy, and cell death, leading to diastolic dysfunction with or without systolic dysfunction. Diabetic cardiomyopathy (DCM) is a distinct myocardial disease in the absence of coronary artery disease. DCM is partially induced by chronic systemic inflammation, underpinned by a hostile environment due to hyperglycemia, hyperlipidemia, hyperinsulinemia, and insulin resistance. The detrimental role of leukocytes, cytokines, and chemokines is evident in the diabetic heart, yet the precise role of inflammation as a cause or consequence of DCM remains incompletely understood. Here, we provide a concise review of the inflammatory signaling mechanisms contributing to the clinical complications of diabetes-associated HF. Overall, the impact of inflammation on the onset and development of DCM suggests the potential benefits of targeting inflammatory cascades to prevent DCM. This review is tailored to outline the known effects of the current anti-diabetic drugs, anti-inflammatory therapies, and natural compounds on inflammation, which mitigate HF progression in diabetic populations.
    • Microbial Degradation of Citric Acid in Low Level Radioactive Waste Disposal: Impact on Biomineralization Reactions

      Byrd, Natalie; Lloyd, Jonathan R.; Small, Joe S.; Taylor, Frank; Bagshaw, Heath; Boothman, Christopher; Morris, Katherine; email: katherine.morris@manchester.ac.uk (Frontiers Media S.A., 2021-04-28)
      Organic complexants are present in some radioactive wastes and can challenge waste disposal as they may enhance subsurface mobility of radionuclides and contaminant species via chelation. The principal sources of organic complexing agents in low level radioactive wastes (LLW) originate from chemical decontamination activities. Polycarboxylic organic decontaminants such as citric and oxalic acid are of interest as currently there is a paucity of data on their biodegradation at high pH and under disposal conditions. This work explores the biogeochemical fate of citric acid, a model decontaminant, under high pH anaerobic conditions relevant to disposal of LLW in cementitious disposal environments. Anaerobic microcosm experiments were set up, using a high pH adapted microbial inoculum from a well characterized environmental site, to explore biodegradation of citrate under representative repository conditions. Experiments were initiated at three different pH values (10, 11, and 12) and citrate was supplied as the electron donor and carbon source, under fermentative, nitrate-, Fe(III)- and sulfate- reducing conditions. Results showed that citrate was oxidized using nitrate or Fe(III) as the electron acceptor at > pH 11. Citrate was fully degraded and removed from solution in the nitrate reducing system at pH 10 and pH 11. Here, the microcosm pH decreased as protons were generated during citrate oxidation. In the Fe(III)-reducing systems, the citrate removal rate was slower than in the nitrate reducing systems. This was presumably as Fe(III)-reduction consumes fewer moles of citrate than nitrate reduction for the same molar concentrations of electron acceptor. The pH did not change significantly in the Fe(III)-reducing systems. Sulfate reduction only occurred in a single microcosm at pH 10. Here, citrate was fully removed from solution, alongside ingrowth of acetate and formate, likely fermentation products. The acetate and lactate were subsequently used as electron donors during sulfate-reduction and there was an associated decrease in solution pH. Interestingly, in the Fe(III) reducing experiments, Fe(II) ingrowth was observed at pH values recorded up to 11.7. Here, TEM analysis of the resultant solid Fe-phase indicated that nanocrystalline magnetite formed as an end product of Fe(III)-reduction under these extreme conditions. PCR-based high-throughput 16S rRNA gene sequencing revealed that bacteria capable of nitrate Fe(III) and sulfate reduction became enriched in the relevant, biologically active systems. In addition, some fermentative organisms were identified in the Fe(III)- and sulfate-reducing systems. The microbial communities present were consistent with expectations based on the geochemical data. These results are important to improve long-term environmental safety case development for cementitious LLW waste disposal.
    • Mitochondrial Arrest on the Microtubule Highway—A Feature of Heart Failure and Diabetic Cardiomyopathy?

      Kassab, Sarah; Albalawi, Zainab; Daghistani, Hussam; Kitmitto, Ashraf; email: ashraf.kitmitto@manchester.ac.uk (Frontiers Media S.A., 2021-07-02)
      A pathophysiological consequence of both type 1 and 2 diabetes is remodelling of the myocardium leading to the loss of left ventricular pump function and ultimately heart failure (HF). Abnormal cardiac bioenergetics associated with mitochondrial dysfunction occurs in the early stages of HF. Key factors influencing mitochondrial function are the shape, size and organisation of mitochondria within cardiomyocytes, with reports identifying small, fragmented mitochondria in the myocardium of diabetic patients. Cardiac mitochondria are now known to be dynamic organelles (with various functions beyond energy production); however, the mechanisms that underpin their dynamism are complex and links to motility are yet to be fully understood, particularly within the context of HF. This review will consider how the outer mitochondrial membrane protein Miro1 (Rhot1) mediates mitochondrial movement along microtubules via crosstalk with kinesin motors and explore the evidence for molecular level changes in the setting of diabetic cardiomyopathy. As HF and diabetes are recognised inflammatory conditions, with reports of enhanced activation of the NLRP3 inflammasome, we will also consider evidence linking microtubule organisation, inflammation and the association to mitochondrial motility. Diabetes is a global pandemic but with limited treatment options for diabetic cardiomyopathy, therefore we also discuss potential therapeutic approaches to target the mitochondrial-microtubule-inflammatory axis.
    • Morphology and Mechanical Properties of Plantar Fascia in Flexible Flatfoot: A Noninvasive In Vivo Study

      Qian, Zhihui; Jiang, Zhende; Wu, Jianan; Chang, Fei; Liu, Jing; email: jingliu@jlu.edu.cn; Ren, Lei; email: lei.ren@manchester.ac.uk; Ren, Luquan (Frontiers Media S.A., 2021-09-15)
      Plantar fascia plays an important role in human foot biomechanics; however, the morphology and mechanical properties of plantar fascia in patients with flexible flatfoot are unknown. In this study, 15 flexible flatfeet were studied, each plantar fascia was divided into 12 positions, and the morphologies and mechanical properties in the 12 positions were measured in vivo with B-mode ultrasound and shear wave elastography (SWE). Peak pressures under the first to fifth metatarsal heads (MH) were measured with FreeStep. Statistical analysis included 95% confidence interval, intragroup correlation coefficient (ICC1,1), one-way analysis of variance (one-way ANOVA), and least significant difference. The results showed that thickness and Young’s modulus of plantar fascia were the largest at the proximal fascia (PF) and decreased gradually from the proximal end to the distal end. Among the five distal branches (DB) of the fascia, the thickness and Young’s modulus of the second and third DB were larger. The peak pressures were also higher under the second and third MH. This study found a gradient distribution in that the thickness and Young’s modulus gradient decreased from the proximal end to the distal end of plantar fascia in the longitudinal arch of flexible flatfeet. In the transverse arch, the thickness and Young’s modulus under the second and third DB were larger than those under the other three DB in flexible flatfoot, and the peak pressures under the second and third MH were also larger than those under the other three MH in patients with flexible flatfoot. These findings deepen our understanding of the changes of biomechanical properties and may be meaningful for the study of pathological mechanisms and therapy for flexible flatfoot.
    • Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle

      collab: Aldearee, H.; collab: Bisson, A.; collab: Bragg, L.; collab: Bridoux, V.; collab: Duelen, R.; collab: Farini, A.; collab: Gazzero, E.; collab: Giarratana, N.; collab: Giverne, C.; collab: Meggiolaro, L.; et al. (Frontiers Media S.A., 2021-08-02)
      This article will review myogenic cell transplantation for congenital and acquired diseases of skeletal muscle. There are already a number of excellent reviews on this topic, but they are mostly focused on a specific disease, muscular dystrophies and in particular Duchenne Muscular Dystrophy. There are also recent reviews on cell transplantation for inflammatory myopathies, volumetric muscle loss (VML) (this usually with biomaterials), sarcopenia and sphincter incontinence, mainly urinary but also fecal. We believe it would be useful at this stage, to compare the same strategy as adopted in all these different diseases, in order to outline similarities and differences in cell source, pre-clinical models, administration route, and outcome measures. This in turn may help to understand which common or disease-specific problems have so far limited clinical success of cell transplantation in this area, especially when compared to other fields, such as epithelial cell transplantation. We also hope that this may be useful to people outside the field to get a comprehensive view in a single review. As for any cell transplantation procedure, the choice between autologous and heterologous cells is dictated by a number of criteria, such as cell availability, possibility of in vitro expansion to reach the number required, need for genetic correction for many but not necessarily all muscular dystrophies, and immune reaction, mainly to a heterologous, even if HLA-matched cells and, to a minor extent, to the therapeutic gene product, a possible antigen for the patient. Finally, induced pluripotent stem cell derivatives, that have entered clinical experimentation for other diseases, may in the future offer a bank of immune-privileged cells, available for all patients and after a genetic correction for muscular dystrophies and other myopathies.
    • “No Way Out Except From External Intervention”: First-Hand Accounts of Autistic Inertia

      Buckle, Karen Leneh; email: karenleneh.buckle@manchester.ac.uk; Leadbitter, Kathy; Poliakoff, Ellen; Gowen, Emma (Frontiers Media S.A., 2021-07-13)
      This study, called for by autistic people and led by an autistic researcher, is the first to explore ‘autistic inertia,’ a widespread and often debilitating difficulty acting on their intentions. Previous research has considered initiation only in the context of social interaction or experimental conditions. This study is unique in considering difficulty initiating tasks of any type in real life settings, and by gathering qualitative data directly from autistic people. Four face-to-face and 2 online (text) focus groups were conducted with 32 autistic adults (19 female, 8 male, and 5 other), aged 23–64 who were able to express their internal experiences in words. They articulate in detail the actions they have difficulty with, what makes it easier or harder to act, and the impact on their lives. Thematic analysis of the transcripts found four overarching themes: descriptions of inertia, scaffolding to support action, the influence of wellbeing, and the impact on day-to-day activities. Participants described difficulty starting, stopping and changing activities that was not within their conscious control. While difficulty with planning was common, a subset of participants described a profound impairment in initiating even simple actions more suggestive of a movement disorder. Prompting and compatible activity in the environment promoted action, while mental health difficulties and stress exacerbated difficulties. Inertia had pervasive effects on participants’ day-to-day activities and wellbeing. This overdue research opens the door to many areas of further investigation to better understand autistic inertia and effective support strategies.