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A comprehensive review on the risks assessment and treatment options for Sarcopenia in people with diabetesThis comprehensive review aims to examine the reciprocal interplay between Type 2 diabetes mellitus (T2DM) and sarcopenia, identify prevailing research gaps, and discuss therapeutic approaches and measures to enhance healthcare practices within hospital settings. A thorough literature review was conducted to gather relevant studies and articles on the relationship between T2DM and sarcopenia. Various databases were searched, including Google Scholar, PubMed, Scopus, and Science Direct databases. The search terms included T2DM, sarcopenia, inflammation, insulin resistance, advanced glycation end products, oxidative stress, muscle dimensions, muscle strength, muscle performance, aging, nutrition, hormone levels, and physical activity. The collected articles were critically analysed to extract key findings and identify gaps in current research. The prevalence and incidence of metabolic and musculoskeletal disorders, notably T2DM and sarcopenia, have surged in recent years. T2DM is marked by inflammation, insulin resistance, accumulation of advanced glycation end products, and oxidative stress, while sarcopenia involves a progressive decline in skeletal muscle mass and function. The review underscores the age-related correlation between sarcopenia and adverse outcomes like fractures, falls, and mortality. Research gaps regarding optimal nutritional interventions for individuals with T2DM and sarcopenia are identified, emphasizing the necessity for further investigation in this area. The reciprocal interplay between T2DM and sarcopenia holds significant importance. Further research is warranted to address knowledge gaps, particularly in utilizing precise measurement tools during clinical trials. Lifestyle modifications appear beneficial for individuals with T2DM and sarcopenia. Additionally, practical nutritional interventions require investigation to optimize healthcare practices in hospital settings. The online version contains supplementary material available at 10.1007/s40200-023-01262-w. [Abstract copyright: © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.]
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Coupled information networks drive honeybee (Apis mellifera) collective foragingCollective behaviour by eusocial insect colonies is typically achieved through multiple communication networks that produce complex behaviour at the group level but often appear to provide redundant or even competing information. A classic example occurs in honeybee (Apis mellifera) colonies, where both the dance communication system and robust scent‐based mechanisms contribute to the allocation of a colony's workforce by regulating the flow of experienced foragers among known food sources. Here we analysed social connectivity patterns during the reactivation of experienced foragers to familiar feeding sites to show that these social information pathways are not simply multiple means to achieve the same end but intersect to play complementary roles in guiding forager behaviour. Using artificial feeding stations, we mimicked a natural scenario in which two forager groups were simultaneously collecting from distinct patches containing different flowering species. We then observed the reactivation of these groups at their familiar feeding sites after interrupting their foraging. Social network analysis revealed that temporarily unemployed individuals interacted more often and for longer with foragers that advertised a familiar versus unfamiliar foraging site. Due to such resource‐based assortative mixing, network‐based diffusion analysis estimated that reactivation events primarily resulted from interactions among bees that had been trained to the same feeding station and less so from different‐feeder interactions. Both scent‐ and dance‐based interactions strongly contributed to reactivation decisions. However, each bout of dance‐following had an especially strong effect on a follower's likelihood of reactivation, particularly when dances indicated locations familiar to followers. Our findings illustrate how honeybee foragers can alter their social connectivity in ways that are likely to enhance collective outcomes by enabling foragers to rapidly access up‐to‐date information about familiar foraging sites. In addition, our results highlight how reliance on multiple communication mechanisms enables social insect workers to utilise flexible information‐use strategies that are robust to variation in the availability of social information.
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Non‐invasive sampling reveals low mitochondrial genetic diversity for an island endemic species: The critically endangered Grenada Dove Leptotila wellsiAs an island endemic with a decreasing population, the critically endangered Grenada Dove Leptotila wellsi is threatened by accelerated loss of genetic diversity resulting from ongoing habitat fragmentation. Small, threatened populations are difficult to sample directly but advances in molecular methods mean that non‐invasive samples can be used. We performed the first assessment of genetic diversity of populations of Grenada Dove by (a) assessing mtDNA genetic diversity in the only two areas of occupancy on Grenada, (b) defining the number of haplotypes present at each site and (c) evaluating evidence of isolation between sites. We used non‐invasively collected samples from two locations: Mt Hartman (n = 18) and Perseverance (n = 12). DNA extraction and PCR were used to amplify 1751 bps of mtDNA from two mitochondrial markers: NADH dehydrogenase 2 (ND2) and Cytochrome b (Cyt b). Haplotype diversity (h) of 0.4, a nucleotide diversity (π) of 0.00023 and two unique haplotypes were identified within the ND2 sequences; a single haplotype was identified within the Cyt b sequences. Of the two haplotypes identified, the most common haplotype (haplotype A = 73.9%) was observed at both sites and the other (haplotype B = 26.1%) was unique to Perseverance. Our results show low mitochondrial genetic diversity and clear evidence for genetically isolated populations. The Grenada Dove needs urgent conservation action, including habitat protection and potentially augmentation of gene flow by translocation in order to increase genetic resilience and diversity with the ultimate aim of securing the long‐term survival of this critically endangered species.
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An assessment of interventions following moderate and high scores on the dynamic appraisal of situational aggression risk assessment tool in a forensic mental health unitThe Dynamic Appraisal of Situational Aggression (DASA) provides a quick and systematic assessment of short-term violence risk. Risk assessment should be closely aligned to management and result in interventions aimed to reduce risk. The aim of this study was to investigate what interventions followed a moderate/high DASA score and whether they reduced risk. The impact of staff training was also assessed. The study was a retrospective analysis of health records within a medium secure hospital over 6 months. Data was gathered on tool adherence and interventions that were used to reduce risk following a moderate/high score. The change in DASA score following the intervention was recorded. There were 70 patients covering 8224 bed days. There were 24 occasions where a moderate score led to an intervention (n = 24/40%), and 26 occasions for a high score (n = 26/87%). A moderate score was mostly followed by no intervention (n = 35/59%), a high score was mostly followed by seclusion (n = 9/29%). The intervention that led to the largest reduction in DASA score was pro re nata medication following a moderate score and seclusion following a high score. The training of staff led to a reduction in tool adherence and increased intervention use. These results support the need for combining the DASA assessment with operationalised systems to link assessment with risk prevention to help reduce aggression and restrictive practices.
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Asthma and COPD as co-morbidities in patients hospitalised with Covid-19 disease: a global systematic review and meta-analysisBackground: Factors predisposing to increased mortality with COVID-19 infection have been identified as male sex, hypertension, obesity, and increasing age. Early studies looking at airway diseases gave some contradictory results. The purpose of our study was to determine global variation in studies in patients hospitalized with COVID-19 in the prevalence of COPD and asthma; and to determine whether the presence of asthma or COPD affected mortality in the same hospital population. Methods: A systematic review and meta-analysis of the published literature of COPD and asthma as co-morbidities in patients hospitalized with COVID-19 was performed, looking firstly at the prevalence of these diseases in patients hospitalized with COVID-19, and secondly at the relative risk of death from any cause for patients with asthma or COPD. Results: Prevalence of both airway diseases varied markedly by region, making meaningful pooled global estimates of prevalence invalid and not of clinical utility. For individual studies, the interquartile range for asthma prevalence was 4.21 to 12.39%, and for COPD, 3.82 to 11.85%. The relative risk of death with COPD for patients hospitalized with COVID-19 was 1.863 (95% CI 1.640–2.115), while the risk with asthma was 0.918 (95% CI 0.767 to 1.098) with no evidence of increased mortality. Conclusions: For asthma and COPD, prevalence in patients hospitalized with COVID-19 varies markedly by region. We found no evidence that asthma predisposed to increased mortality in COVID-19 disease. For COPD, there was clear evidence of an association with increased mortality. Trial registration: The trial was registered with PROSPERO: registration number CRD42021289886.
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Effects of a transoceanic rowing challenge on cardiorespiratory function and muscle fitnessUltra-endurance sports and exercise events are becoming increasingly popular for older age groups. We aimed to evaluate changes in cardiac function and physical fitness in males aged 50-60 years who completed a 50-day transoceanic rowing challenge. This case account of four self-selected males included electro- and echo-cardiography (ECG, echo), cardiorespiratory and muscular fitness measures recorded nine-months prior to and three weeks after a transatlantic team-rowing challenge. No clinically significant changes to myocardial function were found over the course of the study. The training and race created expected functional changes to left ventricular and atrial function; the former associated with training, the latter likely due to dehydration, both resolving towards baseline within three weeks post-event. From race-start to finish all rowers lost 8.4-15.6 kg of body mass. Absolute cardiorespiratory power and muscular strength were lower three weeks post-race compared to pre-race, but cardiorespiratory exercise economy improved in this same period. A structured programme of moderate-vigorous aerobic endurance and muscular training for >6 months, followed by 50-days of transoceanic rowing in older males proved not to cause any observable acute or potential long-term risks to cardiovascular health. Pre-event screening, fitness testing, and appropriate training is recommended, especially in older participants where age itself is an increasingly significant risk factor.
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SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AMLKMT2A-rearranged (KMT2A-R) is an aggressive and chemo-refractory acute leukemia which mostly affects children. Transcriptomics-based characterization and chemical interrogation identified kinases as key drivers of survival and drug resistance in KMT2A-R leukemia. In contrast, the contribution and regulation of phosphatases is unknown. In this study we uncover the essential role and underlying mechanisms of SET, the endogenous inhibitor of Ser/Thr phosphatase PP2A, in KMT2A-R-leukemia. Investigation of SET expression in acute myeloid leukemia (AML) samples demonstrated that SET is overexpressed, and elevated expression of SET is correlated with poor prognosis and with the expression of MEIS and HOXA genes in AML patients. Silencing SET specifically abolished the clonogenic ability of KMT2A-R leukemic cells and the transcription of KMT2A targets genes HOXA9 and HOXA10. Subsequent mechanistic investigations showed that SET interacts with both KMT2A wild type and fusion proteins, and it is recruited to the HOXA10 promoter. Pharmacological inhibition of SET by FTY720 disrupted SET-PP2A interaction leading to cell cycle arrest and increased sensitivity to chemotherapy in KMT2A-R-leukemic models. Phospho-proteomic analyses revealed that FTY720 reduced the activity of kinases regulated by PP2A, including ERK1, GSK3β, AURB and PLK1 and led to suppression of MYC, supporting the hypothesis of a feedback loop among PP2A, AURB, PLK1, MYC, and SET. Our findings illustrate that SET is a novel player in KMT2A-R leukemia and they provide evidence that SET antagonism could serve as a novel strategy to treat this aggressive leukemia. [Abstract copyright: © 2023. The Author(s).]
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Monitoring wildlife population trends with sample counts: a case study on the Alpine ibex (Capra ibex)Monitoring population dynamics is of fundamental importance in conservation but assessing trends in abundance can be costly, especially in large and rough areas. Obtaining trend estimations from counts performed in only a portion of the total area (sample counts) can be a cost‐effective method to improve the monitoring and conservation of species difficult to count. We tested the effectiveness of sample counts in monitoring population trends of wild animals, using as a model population the Alpine ibex Capra ibex in the Gran Paradiso National Park (Italy), both with computer simulations and using historical count data collected over the last 65 years. Despite sample counts failed to correctly estimate the true population abundance, sampling half of the target area could reliably monitor the trend of the target population. In case of strong changes in abundance, an even lower proportion of the total area could be sufficient to identify the direction of the population trend. However, when there is a high yearly trend variability, the required number of samples increases and even counting in the entire area can be ineffective to detect population trends. The effect of other parameters, such as which portion of the area is sampled and detectability, was lower, but these should be tested case by case. Sample counts could therefore constitute a viable alternative to assess population trends, allowing for important, cost‐effective improvements in the monitoring of wild animals of conservation interest.
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'I just need to know what they are and if you can help me': Medicalization and the search for legitimacy in people diagnosed with non-epileptic attack disorderThis paper focuses on the struggles for legitimacy expressed by people with non-epileptic attack disorder (NEAD), one of the most common manifestations of functional neurological disorder presenting to emergency and secondary care services. Nonepileptic attacks are episodes of altered experience, awareness, and reduced self-control that superficially resemble epileptic seizures or other paroxysmal disorders but are not associated with physiological abnormalities sufficient to explain the semiological features. "Organic" or medicalized explanations are frequently sought by patients as the only legitimate explanation for symptoms, and consequently, a diagnosis of NEAD is often contested. Drawing on narrative interviews with patients from a small exploratory study and using a sociological perspective, we propose that a psychological account of NEAD does not provide a sufficiently legitimate path into a socially sanctioned sick role. This is a reflection of the dominance of biomedicine and the associated processes of medicalization. These processes are, we argue, the sole route to achieving legitimacy. The stress-based or psychologically oriented explanations offered to patients in contemporary medical models of the etiology of NEAD engender an uncertain identity and social position and fail to provide many patients with an account of the nature or origin of their symptoms that they find satisfactory or convincing. These struggles for legitimacy (shared by others with functional or somatoform conditions) are sharpened by key features of the contemporary healthcare landscape, such as the increasing framing of health through a lens of 'responsibilization'. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.]
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Cucumeropsis mannii seed oil protects against bisphenol A-induced hepatotoxicity by mitigating inflammation and oxidative stress in ratsOBJECTIVES This study looked at how CMSO affected male Wistar albino rats' liver damage caused by bisphenol A. METHODS The standard HPLC method was used to assess the CMSO's phenolic content. Then, six (n = 8) groups of forty-eight (48) male Wistar rats (150 20 g) each received either CMSO or olive oil before being exposed to BPA for 42 days. Groups: A (one milliliter of olive oil, regardless of weight), B (BPA 100 mg/kg body weight (BW)), C (CMSO 7.5 mg/kg BW), D (CMSO 7.5 mg/kg BW + BPA 100 mg/kg BW), E (CMSO 5.0 mg/kg BW + BPA 100 mg/kg BW), and F (CMSO 2.5 mg/kg BW + BPA 100 mg/kg BW). KEY FINDINGS A surprising abundance of flavonoids, totaling 17.8006 10.95 g/100 g, were found in the HPLC data. Malondialdehyde, liver enzymes, reactive oxygen species, total bilirubin, and direct bilirubin levels were all significantly elevated by BPA (p 0.05). Additionally, nuclear factor-B, interleukin-6, interleukin-1, tumor necrosis factor, and histological alterations were all considerably (p 0.05) caused by BPA. The altered biochemical markers and histology were, however, noticeably recovered by CMSO to a level that was comparable to the control. CONCLUSION Due to the abundance of flavonoid components in the oil, CMSO protects the liver from BPA-induced hepatotoxicity by lowering oxidative stress and inflammatory reactions.
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Causation, historiographic approaches and the investigation of serious adverse incidents in mental health settingsTo improve the safety of healthcare systems, it is necessary to understand harm-related events that occur in these systems. In mental health services, particular attention is paid to harm arising from the actions of patients against themselves or others. The primary intention of examining these adverse events is to inform changes to care provision so as to reduce the likelihood of the recurrence of such events. The predominant approach to investigating adverse incidents has relied on the cause-and-effect conceptualisation of past events. Whilst the merits of approaches which are reliant on cause-and-effect narratives have been questioned, alternatives models to explain adverse incidents in health settings have not been theoretically or empirically tested. This novel article (i) examines the notion of causation (and the related notion of omission) in the context of explaining adverse events in mental health settings, and (ii) draws on a long-established discipline devoted to the study of how the past is interpreted (namely historiography) to theoretically investigate the innovative application of two historiographical approaches (i.e. counterfactual analysis and historical materialism) to understanding adverse events in mental health settings.
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Predicted Structure and Potential Binding of the Nematode Tetraspanin 7 Protein (tsp-7) With Human Tissue Inhibitor Metalloprotease 1 (TIMP-1): a Possible Role In Parasite- Host InteractionsHuman parasitic nematodes evade the host immune system through cross communication by unknown mechanisms. The proteins of the parasitic nematodes are still poorly annotated. CD63 is a human tetraspanin and binds to TIMP-1 a metalloproteinase inhibitor, which has recently been found to play an active role in inflammation by acting as a cytokine when bound to CD63. Caenorhabditis elegans is a free-living nematode, a model organism for both human and parasitic nematodes. C. elegans tetraspanin protein -7 (tsp-7) is an orthologue of human CD63. The model organism used can provide information about potential tetraspanin proteins from parasitic nematodes, which are believed to play a role in the cross communication between parasite and host. The tsp-7 protein sequence from C. elegans shares a high percentage similarity, identity, and homology with a variety of human parasitic nematode proteins. Using a number of computer-based programmes including ‘Alpha-Fold,’ which is currently the most powerful Artificial Intelligence protein structure prediction programme, the structure of the C. elegans tsp-7 was determined. From the predicted structure, the tsp-7 protein has one highly likely, membrane exposed tyrosine phosphorylation site, with implications of its potential involvement in signalling pathways and immune responses. Using multiple protein docking databases and programmes, tsp-7 has been shown to theoretically bind to human TIMP-1. Two mutant strains of C. elegans were obtained from Caenorhabditis Genetics Centre, University of Minnesota, USA, with amino acid deletions within the tsp-7 protein (mutant tm5046 and mutant tm5761). These tsp-7 mutant strains were shown to have an overall longer life span than the wild type C. elegans (N2). The mutant tm5761 showed a greater stress response compared to the N2 wild-type, when exposed to various chemical stimuli, however, mutant tm5046 was more similar to wild type C. elegans. Under heat stress, mutant tm5761 and wild type N2, were less tolerant to heat compared to the tm5046 mutant. In general, mutant tm5046 was more stable and displayed a reduced stress behavioural response compared to mutant tm5761. A primary polyclonal antibody was produced against the tsp-7 large extracellular loop domain, believed to be the key active site in protein-protein interactions. The expression of tsp-7 in mutant tm5761 was detected at lower concentrations than the wild type and mutant tm5046 in an ELISA assay and it also could not be detected by western blotting. Mutant tm5046 was detected weakly by western blotting. Cos-7 cells transfected with the tsp-7 protein-GFP tagged plasmid were incubated with active human TIMP-1. The tsp-7 tagged cells showed co-localisation with TIMP-1, using immuno-fluorescence microscopy, thus adding to the evidence that tsp-7 could interact with human TIMP-1. Such an interaction may well play a role in parasite-host interactions and its effects on the immune response. As C. elegans tsp-7 shares high similarity with many parasitic nematodes that are known to infect humans, it is a good protein candidate to further explore the potential interactions of parasitic nematodes with humans, in terms of cross communication and interaction with the host immune system.
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Technical validation and a comparison of two methods to quantify individual levels of glucocorticoids in Alpine marmot hairQuantification of cortisol concentration in hair has become a promising conservation tool for non-invasive monitoring of “stress” in wild populations, yet this method needs to be carefully validated for each species. The goals of the study were: • Immunologically validate two methods (study 1 and 2 respectively) to extract and quantify cortisol in the hair of wild Alpine marmots. • Compare the amount of cortisol extracted from hair samples using two methods i.e. cut into fine pieces (study 1) and hair samples pulverized using a ball mill (study 2). • Determine the extent to which methods in study 2 could provide individual specific hair cortisol (HC) measures when samples were taken from the same body location. Within and between individual variations in HC levels were examined from multiple hair samples from 14 subjects in study 2. We evaluated if inter-individual variations in HC levels could be explained by sex and age. At least twice the amount of cortisol was obtained per g/hair when samples were pulverized in a ball mill prior to extraction compared to when cut into pieces. Our methods demonstrated intra-individual consistency in HC at a given time point: inter-individual variation in HC was three times larger than within individual variance. Sex and age did not impact HC levels.
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Lysophosphatidic Acid Signalling in Diabetes MellitusDriven by obesity, the incidence of type 2 diabetes mellitus (T2DM) has escalated, reaching unprecedented levels worldwide. This has led to a change in approach from treatment to prevention or delaying the onset of the disease. While current treatment of the disease has been successful in increasing patients’ quality of life, it has substantially increased the financial burden on healthcare systems worldwide. In view of this, the NHS, in partnership with Diabetes UK and Public Health England, has launched a diabetes prevention programme to target people at risk of the disease and provide targeted support to prevent its development. A prelude to this strategy is to identify robust risk factors that will enable the capture of people at increased risk of developing the disease. The phospholipid lysophosphatidic acid (LPA), upregulated during obesity, has been shown to be a potent regulator of glucose homeostasis and insulin secretion in animal models. This thesis is the first to assess circulating levels of LPA in human T2DM patients versus non-DM control. The thesis aims to assess the usefulness of LPA as a biomarker for T2DM screening and has three major objectives: (1) to determine plasma LPA concentration in T2DM patients compared with non-diabetic controls and assess LPA correlation with current diagnostic markers for T2DM. (2) to determine LPA correlation with pathological markers known to lead to DM complications; (3) to develop an immunofluorescence assay to assess LPA signalling of glucose homoeostasis using a mammalian cell line. (4) to assess LPA regulations of GLUT4, PKC and α2a adrenergic receptor (α2aAR) using the developed assay.
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Prevalence of SARS-CoV-2 Omicron Sublineages and Spike Protein Mutations Conferring Resistance against Monoclonal Antibodies in a Swedish Cohort during 2022–2023Monoclonal antibodies (mAbs) are an important treatment option for COVID-19 caused by SARS-CoV-2, especially in immunosuppressed patients. However, this treatment option can become ineffective due to mutations in the SARS-CoV-2 genome, mainly in the receptor binding domain (RBD) of the spike (S) protein. In the present study, 7950 SARS-CoV-2 positive samples from the Uppsala and Örebro regions of central Sweden, collected between March 2022 and May 2023, were whole-genome sequenced using amplicon-based sequencing methods on Oxford Nanopore GridION, Illumina MiSeq, Illumina HiSeq, or MGI DNBSEQ-G400 instruments. Pango lineages were determined and all single nucleotide polymorphism (SNP) mutations that occurred in these samples were identified. We found that the dominant sublineages changed over time, and mutations conferring resistance to currently available mAbs became common. Notable ones are R346T and K444T mutations in the RBD that confer significant resistance against tixagevimab and cilgavimab mAbs. Further, mutations conferring a high-fold resistance to bebtelovimab, such as the K444T and V445P mutations, were also observed in the samples. This study highlights that resistance mutations have over time rendered currently available mAbs ineffective against SARS-CoV-2 in most patients. Therefore, there is a need for continued surveillance of resistance mutations and the development of new mAbs that target more conserved regions of the RBD.
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An Investigation of the Protein Quality and Temporal Pattern of Peripheral Blood Aminoacidemia following Ingestion of 0.33 g·kg−1 Body Mass Protein Isolates of Whey, Pea, and Fava Bean in Healthy, Young Adult MenAn increase in the intake of legumes is recommended in the promotion of plant-sourced (PSP) rather than animal-sourced (ASP) protein intake to produce a more sustainable diet. This study evaluated the quality of novel PSP isolates from pea (PEA) and fava bean (FAVA) and an ASP isolate of whey (WHEY) and compared the magnitude and temporal pattern of peripheral arterial aminoacidemia following ingestion of 0.33 g·kg−1 body mass of protein isolate in healthy young adult men (n = 9). Total indispensable amino acids (IAA) comprised 58% (WHEY), 46% (PEA), and 42% (FAVA) of the total amino acid (AA) composition, with the ingested protein providing 108% (WHEY), 77% (PEA), and 67% (FAVA) of the recommended per diem requirement of IAA. Reflecting the AA composition, the area under the curve (∆AUC0-180), post-ingestion increase in total IAA for WHEY was 41% (p < 0.001) and 57% (p < 0.001) greater than PEA and FAVA, respectively, with PEA exceeding FAVA by 28% (p = 0.003). As a sole-source, single-dose meal-size serving, the lower total IAA for PEA and FAVA would likely evoke a reduced post-prandial anabolic capacity compared to WHEY. Incorporated into a food matrix, the promotion of PSP isolates contributes to a more sustainable diet.
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Effect of movement‐evoked and tonic experimental pain on muscle force productionIntroduction: When performing an exercise or a functional test, pain that is evoked by movement or muscle contraction could be a stronger stimulus for changing how individuals move compared to tonic pain. We investigated whether the decrease in muscle force production is larger when experimentally‐induced knee pain is directly associated to the torque produced (movement‐evoked) compared to a constant painful stimulation (tonic). Methods: Twenty‐one participants performed three isometric knee extension maximal voluntary contractions without pain (baseline), during pain, and after pain. Knee pain was induced using sinusoidal electrical stimuli at 10 Hz over the infrapatellar fat pad, applied continuously or modulated proportionally to the knee extension torque. Peak torque and contraction duration were averaged across repetitions and normalized to baseline. Results: During tonic pain, participants reported lower pain intensity during the contraction than at rest (p < 0.001), whereas pain intensity increased with contraction during movement‐evoked pain (p < 0.001). Knee extension torque decreased during both pain conditions (p < 0.001), but a larger reduction was observed during movement‐evoked compared to tonic pain (p < 0.001). Participants produced torque for longer during tonic compared to movement‐evoked pain (p = 0.005). Conclusion: Our results indicate that movement‐evoked pain was a more potent stimulus to reduce knee extension torque than tonic pain. The longer contraction time observed during tonic pain may be a result of a lower perceived pain intensity during muscle contraction. Overall, our results suggest different motor adaptation to tonic and movement‐evoked pain and support the notion that motor adaptation to pain is a purposeful strategy to limit pain. This mechanistic evidence suggests that individuals experiencing prevalently tonic or movement‐evoked pain may exhibit different motor adaptations, which may be important for exercise prescription.
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Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterningComplex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf signalling makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenable ex vivo chick wing tissue explant system that faithfully replicates in vivo parameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis.
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Older adults’ experience of neuropsychological assessments for dementia screening in South India: a qualitative studyBackground: In community settings, neuropsychological assessment is the most commonly employed method for early recognition of dementia. However, little is known about the experience and perspectives of older adults when they undertake neuro psychological assessments in low-and middle-income countries (LMICs), including India. Methods: We conducted semi-structured interviews for 11 individuals (aged between 64 and 88 years) who had undergone cognitive assessment in the CST International (Cognitive Stimulation Therapy International) study and were free from dementia. The transcripts were analysed manually utilising Interpretative Phenomenological Analysis to develop key themes. Results: When data were analysed three super-ordinate themes (experiences related to the process, content and outcomes) each with a set of subordinate themes emerged. Conclusions: This study highlights the need for a thorough planning of pre-assessment briefing for equipping participants with adequate information related to the neuro psychological assessment: its indication, length of procedure, contents of the test, possible outcomes, medical implications of those outcomes, possible therapeutic options if diagnosed with lower cognitive function.We discuss our findings in relation to extant knowledge and explore issues clinicians should consider when conducting neuro psychological assessments in LMIC settings.
