Autophagy is a promising target for promoting neural regeneration, which is essential for sensorimotor recovery following traumatic brain injury (TBI). Whether neuronal heat shock protein B2 (HSPB2), a small molecular heat shock protein, reduces injury and promotes recovery following TBI remains unclear. In this study, we demonstrated that HSPB2 was significantly increased in the neurons of a TBI mouse model, patients, and primary neuron cultures subjected to oxygen/glucose deprivation and reperfusion treatment. Upon creating a tamoxifen-induced neuron-specific HSPB2 overexpression transgenic mouse model, we found that elevated HSPB2 levels promoted long-term sensorimotor recovery and alleviated tissue loss after TBI. We also demonstrated that HSPB2 enhanced white matter structural and functional integrity, promoted central nervous system (CNS) plasticity, and accelerated long-term neural remodeling. Moreover, we found that autophagy occurred around injured brain tissues in patients, and the pro-regenerative effects of HSPB2 relied on its autophagy-promoting function. Mechanistically, HSPB2 may regulate autophagy possibly by forming the HSPB2/BCL2-associated athanogene 3/sequestosome-1 complex to facilitate the clearance of erroneously accumulated proteins in the axons. Treatment with the autophagy inhibitor chloroquine during the acute stage or delayed induction of HSPB2 remarkably impeded HSPB2’s long-term reparative function, indicating the importance of acute-stage autophagy in long-term neuro-regeneration. Our findings highlight the beneficial role of HSPB2 in neuro-regeneration and functional recovery following acute CNS injury, thereby emphasizing the therapeutic potential of autophagy regulation for enhancing neuro-regeneration.  Traumatic brain injury (TBI) is a prevalent neurosurgical disease of the central nervous system (CNS) resulting in a significant number of disabilities and mortality worldwide, thereby imposing a substantial burden on both the family and society , 2. TBI Autophagy plays a vital role in clearing aberrant proteins and damaged organelles, as well as maintaining cellular homeostasis . IncreasHeat shock protein B2 (HSPB2) is an important small heat shock protein (sHSP) . Cells eHowever, whether neuronal HSPB2 reduces injury and promotes recovery following TBI remains unclear. In this study, we found that HSPB2 potentially participates in autophagy possibly through the HSPB2/BAG3/sequestosome-1 (SQSTM1) complex, guiding the clearance of erroneously accumulated axonal proteins, such as βAPP, to facilitate neural regeneration following TBI, thereby revealing the importance of acute-stage autophagy in long-term neuro-repair. This study provides valuable information concerning neuronal HSPB2’s neuroprotective and pro-recovery effects on TBI and aims to develop a potentially novel therapeutic target for acute CNS injuries.https://doi.org/10.1172/jci.insight.168919DS1), which was consistent with a previous study in rats  and significantly increased 3 days post-TBI in the neurons of the cortical layer 5 (L5), accompanied by a decrease in neuronal density  , Western density , C and D density , E and F density , C–F. Thpression . Changespost-TBI .Next, we assessed the HSPB2 levels in the glial cells. Although the HSPB2 levels increased in the microglia and astrocytes 3 days post-TBI, the neurons revealed a much higher HSPB2 level than glial cells, indicating that neurons were the major contributors to the surge in the HSPB2 levels . As antiFurthermore, we collected damaged brain tissues that were surgically removed from patients with brain contusion and laceration who underwent emergency neurosurgery. Importantly, we also found that HSPB2 was significantly upregulated in the neurons of the damaged tissue specimens of patients with acute brain contusion . Taken tAn in vitro primary neuron culture model verified alterations in neuronal HSPB2 expression in response to acute injury . NeuronsMap2-CreERT2 mice, selectively expressing Cre in neurons, to generate R26-e(CAG-LSL-Hspb2) Map2-CreERT2, N-HSPB2, termed TG  HSPB2 in a Cre-dependent manner. We initially overexpressed HSPB2 in the neurons by crossing mice with ermed TG , A and Bermed TG , E–H, wiermed TG . AdditioNA level . The exppression . A previpression . In our The long-term effects of HSPB2 on neurofunction were assessed using a series of behavioral tests 3 to 35 days following TBI . No signNo significant differences in the swim velocity were observed between the groups in the Morris water maze (MWM) test , C and DNumerous preclinical studies have failed to demonstrate clinical translation because they used only male animals. Although men have a higher incidence of TBI, women experience equivalent consequences . Sex dimWe also evaluated whether HSPB2 protected against brain tissue loss. In the acute stage (3 days after TBI), no significant differences were found between the genotypes . HoweverWe investigated the structural integrity of the white matter using diffusion tensor imaging–MRI (DTI-MRI) in vivo on days 7 and 28 and ex vivo on day 49 , A–E. FrTo assess the functional integrity of the white matter, we performed electrophysiological recordings by detecting the compound action potentials (CAPs) in the CC 35 days following TBI  39). CA. CA39). Additionally, we assessed the synaptic density in the peri-injury cortex. The density of synaptophysin, a presynaptic protein, significantly decreased following TBI. However, HSPB2 overexpression partially reversed this reduction in TG mice , H and I+ fibers crossing the midline was used to quantify CST crossing and compensatory axon sprouting. Our results demonstrated that the natural cross-connection between the CC in the cerebrum and medulla oblongata FN was reduced 49 days post-TBI, whereas HSPB2 recovered the decrease in the connection at the FN  vesicles transported along the BDA-labeled axons increased on the compensatory side of C7 in TG-TBI mice  corticospinal tract (CST) . BDA is t the FN , B and Ct the FN , which wt the FN . Moreovemodeling . We alsoTBI mice . SynaptiTBI mice , therebyTo investigate cortical remapping and assess the function of the compensatory CST in vivo, we recorded the neuronal activity in the contralateral S1FL in response to tactile stimulation applied to each forepaw, following stereotactic injection of AAV-hSyn-GCaMP6m at the S1FL and optical fiber implantation . At 2 anIn summary, these results suggest that neuronal HSPB2 promotes CNS plasticity and facilitates the neural remodeling processes, including axon sprouting and cortical remapping, which contribute to the sensorimotor function recovery.P = 0.071, Previous studies have demonstrated that neuronal autophagy peaks at 3 days post-TBI , which iElevated SQSTM1and LC3-II protein levels may also result from blockage of autophagic flux . TBI canTo better validate HSPB2’s role in enhancing autophagy without harming autophagic flux, we injected AAV-CMV-mCherry-EGFP-LC3 virus to label and differentiate the autophagosomes and autolysosomes based on the instability of enhanced green fluorescent protein (EGFP) in the acidic lysosomal environment and quantified the autophagic flux , 43 Fig. Three-dWe attempted to determine the signaling pathways involved in the regulation of autophagy by HSPB2. HSPB1 interacts directly with Akt , which aAccumulating evidence indicates that chaperones remove misfolded or aggregated proteins via macroautophagy in cooperation with co-chaperones . To furtNext, we assessed the interaction of HSPB2 with BAG3 and SQSTM1 by in vivo immunostaining. We found that HSPB2 colocalized with BAG3, the cargo protein SQSTM1, and the autophagosome membrane protein LC3 in AAV-LC3–injected WT mice . Plot pr+ neurofilament following OGD/r, potentially due to axonal transport malfunction . All efforts were made to minimize animal suffering and the number of animals used. For patients, written informed consent was obtained. Patients’ tissue was obtained and used in a manner compliant with the Declaration of Helsinki, and all procedures were approved by the China Human Genetic Resources Management Office of the Huashan Hospital, approval number: GKYBSZ (year 2017) No. 256.All relevant data are available in the For other methods, please see YG designed the study. YH, SM, BW, HS, YW, JX, ZS, YL, and XJ performed the experiments. YH, JX, and JL analyzed the data. YG, ZXX, GW, and JH validated the data. YH wrote the manuscript. YG and ZXX critically edited the manuscript.


Afforestation and reforestation (AR) are nature-based solutions to climate change. However, the greenhouse gas (GHG) mitigation efficacy of protection or commercial AR is under debate. This study develops a dynamic life cycle assessment to quantify the GHG mitigation potential of protection and commercial AR on marginal land in the southeastern United States. We found that commercial AR with cross-laminated timber and biochar production generally mitigates more GHGs across 100 y than protection AR and commercial AR with traditional lumber production. Protection AR could mitigates more GHGs in a shorter timeframe (≤50 y). These results highlight the role of synergizing protection AR, innovative wood utilization, and strategic forest plantation management in supporting short- and long-term climate change mitigation goals. 2 equivalent (Gt CO2e)) through cross-laminated timber (CLT) and biochar than protection AR (3.35 to 3.69 Gt CO2e) and commercial AR with traditional lumber production (3.17 to 3.51 Gt CO2e), especially in moderately cooler and dryer regions in this study with higher forest carbon yield, soil clay content, and CLT substitution. In a shorter timeframe (≤50 y), protection AR is likely to deliver higher GHG mitigation. On average, for the same wood product, low-density plantations without thinning and high-density plantations with thinning mitigate more life cycle GHGs and result in higher carbon stock than that of low-density with thinning plantations. Commercial AR increases the carbon stock of standing plantations, wood products, and biochar, but the increases have uneven spatial distributions. Georgia (0.38 Gt C), Alabama (0.28 Gt C), and North Carolina (0.13 Gt C) have the largest carbon stock increases that can be prioritized for innovative commercial AR projects on marginal land.Afforestation and reforestation (AR) on marginal land are nature-based solutions to climate change. There is a gap in understanding the climate mitigation potential of protection and commercial AR with different combinations of forest plantation management and wood utilization pathways. Here, we fill the gap using a dynamic, multiscale life cycle assessment to estimate one-century greenhouse gas (GHG) mitigation delivered by  commercial and protection AR with different planting density and thinning regimes on marginal land in the southeastern United States. We found that innovative commercial AR generally mitigates more GHGs across 100 y (3.73 to 4.15 Giga tonnes of CO The Intergovernmental Panel on Climate Change highlights afforestation and reforestation (AR) as a critical land-based greenhouse gas (GHG) mitigation strategy to limit global warming to 1.5 to 2 °C above preindustrial levels 1. However4514The GHG mitigation potential of commercial and protection AR has been highlighted in the literature , 18–25, 182714There is a gap in understanding the role of synergizing different, innovative wood uses from AR and forest plantation management strategies in mitigating climate change. Previous studies have compared protection and commercial forest plantations for traditional wood products  or compa3336SI Appendix, Fig. S1) that links process-scale LCA for wood products and biochar with regional-scale modeling of forest ecosystems on an annual basis for 100 y. Spatially explicit climate and soil conditions were modeled for loblolly pine AR (Pinus taeda L.) on marginal land in the southeastern United States at 1 km resolution, including Virginia (VA), Tennessee (TN), North Carolina (NC), Mississippi (MS), Alabama (AL), Georgia (GA), South Carolina (SC), and Florida (FL). The cradle-to-grave LCA includes GHG emissions of forest operations, manufacturing, EOL, carbon sequestration of forests, and material substitution credits for replacing steel and concrete in the construction industry. Emissions from SOC with spatial heterogeneity were simulated in the RothC model  and the use of harvested wood  and forest plantation residues . Two baselines were established for protection AR without forest plantation management at low (450 trees/acre) and high plantation densities (900 trees/acre). Nine scenarios were simulated as a combination of three scenarios for different wood and residue uses and three scenarios of varying forest plantation management strategies. This study estimated the carbon stock change as the change from year zero on marginal land where the aboveground and soil carbon stock is assumed to be zero and current state, respectively. Carbon stock changes were estimated for different locations and years to understand their temporal–spatial distributions.2 sequestrated by high-density plantations are primarily canceled out by greater emissions from biochar manufacturing and soil and ground surface respiration is associated with more biomass generated in high-density plantations  with lower temperature, precipitation, and landfill decay rate and higher forest carbon yield (Mg C/ha), mill waste recovery rate, soil clay content, and steel usage for traditional buildings  . Under the pessimistic conditions, protection AR mitigates slightly more GHGs than those of commercial AR in the high-density plantations but not low-density plantations . However, protection AR may have larger uncertainties because it is more prone to exposure for longer periods of time to natural disturbances such as insects, diseases, wind, and fire  and decay emissions are minor (Discussion Section).The largest GHG mitigation of S2 and S3 is mainly attributed to CLT substitution and biochar, e.g., CLT substitution accounts for 11% of the total GHG mitigation potential in S2 and S3 A. Biogenre minor B. Biochare minor C. CLT anre minor B; howeveSI Appendix, Fig. S2 C and D). Three density scenarios are 1) low-density plantation (450 trees/acre) without thinning, 2) low-density plantation (450 trees/acre) with thinning 25% of standing in year 10, and 3) high-density (900 trees/acre) with thinning 50% of standing in year 10. On average, without substitution credits, high-density protection AR across 100 y has similar GHG mitigation potentials with innovative commercial AR in S2 and S3 . These comparative trends are similar for low-density plantations with thinning; however, innovative commercial AR without thinning in S2 and S3 mitigates more GHG than that of the baseline protection AR on average, even without substitution credits . Considering uncertainty, without CLT substitution, all commercial AR in S2 and S3 still mitigate more GHG than that of protection AR regardless of densities under optimistic conditions, while this is not the case under pessimistic conditions .Another key factor is CLT substitution, one of the uncertainty sources. Without CLT substitution credits, the comparative conclusions depend on plantation density and thinning practices . Thinning low-density plantations delays the time when commercial AR reaches similar GHG mitigation potential as the low-density baseline . The total carbon stock change shows similar trends as the net GHG balances  and pessimistic conditions in warmer and more humid climates within our study region with lower forest carbon yield, soil clay content, and CLT substitution, protection AR is likely to be climate favorable. In general and optimistic conditions in climates that are moderately cooler and dryer within the region of our study with higher forest carbon yield, soil clay content, and CLT substitution, innovative commercial AR is likely to achieve greater GHG mitigation than that of protection AR and commercial AR with lumber production in the long term (100 y). Without CLT material substitution benefits, compared to protection AR with the same plantation density, low-density commercial AR without thinning is still climate favorable on average and optimistic conditions, while high-density commercial AR with thinning is preferred only under optimistic conditions.The carbon stock results in SI Appendix, Fig. S2E). This finding is consistent with other studies indicating that thinning can lower the total standing volume in low-density plantations . From years 55 and 85, a portion of wood product carbon moves to landfills when lumber and CLT reach their lifetime . A small portion of carbon in litterfall, root, and plantation residues moves to SOC. The remaining sequestered carbon in plantation residues under S2 and S3 goes to biochar. Compared to protection AR, commercial AR for traditional lumber production has limited capacity to increase carbon storage further, as demonstrated by similar 100-y carbon stock results of S1 and baselines . The total amount of carbon stored in CLT and landfill is slightly higher than the carbon stored in lumber and its landfill over 100 y due to the shorter lifetime of lumber . It indicates that higher residue removal rate for biochar production results in an overall greater carbon stock increase in soil.In general, high-density plantations with thinning and 100% residue removal yield the highest carbon stock. Commercial plantations demonstrate stable growth in carbon stock every 25 y, whereas protection plantations experience a slowing increase in carbon stock after year 50 D–F. Carbaselines C. CLT scf lumber C. The mof lumber . Howeverf lumber  because SI Appendix, Figs. S2 and S5 for more details).Overall, innovative commercial AR with CLT and biochar demonstrate considerably more carbon stock increases than those of protection AR and commercial AR with traditional lumber production over 100 y on average and optimistic conditions . Protection AR has similar or lower carbon stock increase as innovative commercial AR on pessimistic conditions  across 100 y, but greater carbon stock increase in general within a shorter timeframe. This conclusion is consistent across all scenarios and timeframes . The impacts of site index and marginal land availability differ by region. Eastern SC  has a higher site index than its western areas  , but western SC yields more carbon stock increases because of the greater availability of marginal land . Another example is the piedmont of southwestern VA and eastern TN where marginal lands have similar availability, suggesting similar distributions of their site index and carbon stock increases. At the state level, GA achieves the highest 100-y total carbon stock increase (0.38 Gt C) in high-planting density with thinning scenarios, followed by AL (0.28 Gt C) and NC (0.13 Gt C) . These three states account for 70.5% of the total carbon stock increase of the entire study region. At the regional level, southern GA, southern AL, and southwestern VA (dark purple) demonstrate substantial 100-y carbon stock increase because of their high marginal land availability and high site index . These regions can be priorities for commercial AR on marginal land.The spatial pattern of carbon stock increase  is driveSI Appendix, Table S6). This additional timber can meet future demands of wood products without converting natural forests to plantations or more intensive management and without losing productive agricultural farmland.This study highlights the importance of strategically considering the combination of available marginal land, AR management, and sustainable wood products as a valid nature-based solution. Our dynamic LCA results suggest that commercial AR on marginal land offers benefits in supplying timber for wood products, mitigating climate change, and establishing a long-term carbon sink. Based on our analysis, commercial AR on marginal land in the southeastern United States can supply up to 485.2 million oven dry metric tons of loblolly pine logs for a 25-y rotation. This amount is around nine times of the total annual harvested loblolly pine timber provided by the region   for protection AR. Commercial AR for traditional lumber production shows lower or similar average values of GHG mitigation potential and carbon stock increase with larger uncertainty ranges compared to protection AR, although this study does not model natural disturbances and possible carbon losses resulting from greater exposure to natural disturbances with prolonged forest stocking in protection AR. Commercial AR with CLT and biochar using high-density plantations with thinning and low-density without thinning are more likely to achieve higher long-term GHG mitigation potential than that of protection AR, especially in moderately cooler and dryer regions in this study with higher forest carbon yield (higher site index region); soil clay content; CLT substitution benefit; and less GHG emissions from soil, forest floor, and landfill. But, this is not the case in the shorter term  or warmer and more humid regions with lower forest carbon yield and soil clay content in this study. Given the urgency of GHG mitigation, a mix of protection and innovative AR could be useful to meet near-term climate change mitigation goals while providing a propeller for driving longer-term GHG reduction and carbon storage through innovative wood products and biochar. Considering variations of net GHG balances, commercial AR is more climate favorable than protection AR in moderately cooler and less moist regions with higher site index and soil clay content. Additionally, this study pinpoints the regions where innovative AR can deliver higher carbon stock increase than traditional commercial AR and protection AR in general conditions, including most of Alabama and the Piedmont of North Carolina, South Carolina, Georgia, and central southern Virginia, and the Red Hills and Sandhill regions of Georgia and South Carolina. Other economic and social factors related to protection and commercial AR should also be considered for region-specific decision-making.The extent of GHG mitigation benefits depends on wood product, planting density, thinning practices, time, and climate and environmental conditions. Protection AR was estimated to have 10.1 Gt COper Mha) . Our finOur results demonstrate the critical contribution that material substitution can make to maximizing the GHG mitigation potential of innovative wood products. Securing the replacement of carbon-intensive materials such as steel and concrete is essential to reduce GHG and increase carbon stock in buildings –17. Alth48Interestingly, higher plantation residue removal  for biochar production contributes to negligible greater GHG mitigation potentials (1.5 to 1.9% more), although higher carbon stock (4.4 to 8.7% more) over 100 y is achived by the 100% removal rate compared with the 50% removal rate. One hundred percent removal is an extreme conceptual scenario to explore the maximum possibility, and the actual forest removal ratio should be lower given ecological considerations of maintaining soil carbon stocks and associated productivity –53. Prev54One limitation of this study is the exclusion of the potential social and economic aspects discussed in prior marginal land literature , 8. The 57592 concentration , which integrated the Geographic Information System (GIS) model, the forest growth model, SOC model, and process-based models of producing wood products . A 100-y cutoff time horizon was adopted to be consistent with climate change literature  were processed and visualized by ArcMap 10.8.1  out of ten opportunity classes identified by the study . Other lp 10.8.1 .Pinus taeda L.) plantations in the three prominent physiographic regions in the southern United States: piedmont, upper coastal plain, and lower coastal plain. The reliability of the model has been demonstrated . We adopted a method  , which h79SI Appendix, SI Note 4) . CLT has a similar life cycle with lumber but differs in production and EOL. The life cycle inventory data of CLT production are documented in SI Appendix, SI Note 6 and Table S12. Fifty percent of CLT panel is assumed to be recycled . Logging residues and snags are chipped and sent to a pyrolysis plant for biochar production that was simulated in Aspen Plus . The end-of-life GHG emissions of biochar applied as soil amendment are documented in SI Appendix, SI Note 8. The life cycle carbon balances are shown in SI Appendix, Fig. S4. This study deploys a two-step uncertainty analysis for wood product systems .Harvested logs are transported to saw mills that include processes such as debarking, sawing, kiln drying, planing, and power generation ( Note 4) , 94. The Note 4) . SI Appedatabase  and GREEdatabase . The landatabase , 97 withrecycled , while trecycled  (SI AppeAppendix 01 (PDF)Click here for additional data file.


This research aimed to explore the serum high-mobility group box 1 (HMGB1) and high-mobility group box 2 (HMGB2) levels in allergic rhinitis (AR) children and its correlation with clinical results. This present prospective observational study enrolled 179 AR children and 100 healthy children who came to our hospital during October 2020 to August 2022. The serum HMGB1, HMGB2, interleukin (IL)-6, IL-1β, interferon-γ, and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay. Demographic and clinical statistics including age, body mass index (BMI), sex, diastolic blood pressure, SBP, family history of allergy, Visual Analogue Score (VAS) and Rhinoconjunctivitis Quality of Life Questionnaire were collected. All data used SPSS 18.0 to statistical analyses. The proportion of family history of allergy was obviously higher in the AR group than that in the healthy group. The serum levels of HMGB1, HMGB2 and cytokines were remarkably enhanced in the AR patients. Spearman analysis supported that positive correlation existed among the HMGB1, HMGB2, CRP, IL-6 and IL-1β levels. Serum IL-6, CRP, HMGB2, IL-1β, VAS score and Rhinoconjunctivitis Quality of Life Questionnaire score levels were significantly higher and serum interferon-γ levels were significantly lower in the HMGB1 high expression group. Similar results were found in in the HMGB2 high group compared to the HMGB2 low group. In addition, HMGB1 and HMGB2 could be potential diagnostic biomarkers of AR patients. Finally, we found that HMGB1, HMGB2, IL-6, IL-1β, and family history of allergy were the risk factors for AR. This study showed that the serum HMGB1 and HMGB2 levels was remarkably enhanced in AR patients and closely associated with cytokines. This study may provide new targets and a comprehensive approach for the treatment of AR patients. With the growing worldwide prevalence of AR, about 10% to 20% of people in the world are affected by AR. According to recent estimates from the Agency for Healthcare Research and Quality, the prevalence of AR in adults ranges from 10% to 30%, but its prevalence in children is already approaching 40%. The pathological mechanism of AR is complex, and risk factors for AR have been reported to be related to genetic, environmental, psychological, and regional differences, etc.,9 AR predisposes or exacerbates patients to fatigue, headaches, cognitive impairment, and sleep disturbances and is a risk factor for asthma. However, the diagnosis of AR still relies on observation of patients’ symptoms, allergen skin testing, and lack of specific serum markers.Allergic rhinitis (AR) is one of the common immunological disorders with clinical symptoms such as frequent episodes of sneezing, clear nasal discharge, and significant nasal congestion. HMGB1 can be released into the extracellular space from neurons or glial cells to induce immune cell activation and cause inflammatory response. While the amino acid sequence of HMGB2 is highly similar to that of HMGBl, more than 80% of its amino acid sequences are identical. HMGB2 is present in large numbers in immune cells, which can damage the intima and lead to hyperplasia of the intima. Previous reports had demonstrated that overexpression of HMGB1 and HMGB2 is associated with the severity and poor prognosis of a number of inflammatory diseases and cancer.,16 HMGB1 has been found to play an important mechanism in the pathogenesis of AR in animal studies.,18 However, so far, no clinical studies focus on the role of HMGB1 and HMGB2 in AR development.High-mobility group box 1 (HMGB1) is a nonhistone DNA-binding protein widely found in the nucleus of eukaryotic cells.In the present prospective observational research, we aimed to explore the expression of HMGB1 and HMGB2 in AR patients and its correlation with clinical results. This study might reveal the clinical significance of HMGB1 and HMGB2 in AR patients, as well as provide novel research targets for ischemic stroke treatment. with specific inclusion criteria: (1) Sneezing, clear watery nose, nasal itching, and nasal congestion present for 2 or more times. Symptoms persist or accumulate for more than 1 hour per day with other concomitant disease symptoms such as respiratory symptoms  and ocular symptoms ; (2) pale and edematous nasal mucosa with watery nasal discharge is common; (3) allergen testing for at least 1 allergen with positive serum-specific IgE; (4) allergen skin test showing dust mite punctate wind cluster ≥ 3 mm in diameter; (5) age < 14. The exclusion criteria included: (1) persons with other allergic diseases or autoimmune diseases; (2) patients with a history of chronic diseases such as diabetes and hypertension; (3) patients who had used hormones, immunosuppressive or enhancing, anti-inflammatory drugs etc within 7 days prior to enrollment; (4) patients with seriously infection, severe liver, renal, malignancy, cardiovascular dysfunctions; (5) patients with a history of nasal masses, nasal polyps, sinusitis, etc. In addition, we collected serum samples and clinical data from 100 healthy children. All participants signed a written informed consent and were followed up for 3 months. The study was approved by the Ethics Committee of the author’s hospital.This present prospective observational study enrolled 179 allergic rhinitis (AR) children who came to our hospital during October 2020 to August 2022. All patients were diagnosed AR according to BSACI guidelines for the diagnosis and management of allergic and nonallergic rhinitis,The serum HMGB1, HMGB2, interleukin (IL)-6, IL-1β, interferon-γ (IFN-γ), and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Blood samples of fasting cubital venous (5 mL) were collected within 24 hours after admission for all cases. Samples were centrifuged at 2000 g for 15 minutes, following with ELISA tested using commercially available kits .Demographic and clinical statistics including age, BMI, sex, diastolic blood pressure, systolic blood pressure, family history of allergy, etc were collected. Visual Analogue Score (VAS) and Rhinoconjunctivitis Quality of Life Questionnaire were used to assess the patient’s symptom profile.t test was used for comparison between 2 groups. Chi square test was used for rates. Spearman rank correlation was used for correlation analysis. ROC curves were used to analyze the diagnostic value of HMGB1 for AR. Logistic regression was performed for risk factors of AR. P < .05 regarded significant difference. All data used SPSS 18.0 to statistical analyses.The normal distribution of data was confirmed by Kolmogorov–Smirnov analysis. Normal distribution data were expressed by mean ± SD while non-normal distribution data median (range). Mann–Whitney test or Student P < .05). No other significantly difference was found in age, sex, BMI, SBP, and diastolic blood pressure.This study enrolled 179 AR patients and 100 healthy children. The basic information was shown in Table To further investigate the relationship between HMGB1, HMGB2, and inflammatory in AR patients, we measured the serum levels of HMGB1, HMGB2, IL-6, IFN-γ, IL-1β, and CRP by ELISA. As shown in Figure P < .05). In addition, the serum IFN-γ levels in HMGB1 high expression group were obviously decreased (P < .05). Besides, compared with HMGB1 high expression group, the VAS scores and Rhinoconjunctivitis Quality of Life Questionnaire scores were significantly higher than that patients in the HMGB1 low expression group(P < .05), suggesting that HMGB1 was associated with the clinical outcomes and severity in AR patients. We also divided all patients into HMGB2 high expression group and low expression group according to the median HMGB2 value (195.92 pg/mL) to compare the clinical data. As shown in Table Further, all patients were divided into HMGB1 high expression group and low expression group according to its mean value (350.65 pg/mL) and the clinical characteristics were compared. As summarized in Table We draw ROC curves to assess the diagnostic value of HMGB1 and HMGB2 for AR patients. The result showed that HMGB1 and HMGB2 could be potential diagnostic biomarkers of AR patients and HMGB1 had better diagnostic value  were also found to be closely associated with disease development in AR in their study. In the last 2 years of research, the clinical significance of some new biomarkers in AR has also been noticed. Wen et al supported that serum nitric oxide synthase levels were elevated in AR patients and could be used to predict the treatment of AR. Ramin et al suggested that serum levels of resolvin E1 and leukotriene B4 were significantly higher in AR patients than healthy persons. However, up to now, there are no specific biomarker for the diagnosis of AR.Several studies have similarly focused on serum biomarkers in AR patients. A clinical study by Han et al confirmed that serum IL-1β could be a biomarker of AR and correlated with disease severity.–27 In autoimmune diseases, Tsakalidou et al demonstrated that serum HMGB1 levels correlated with disease activity and severity in systemic lupus erythematosus patients. A review by Taniguchi et al found that multiple functions of the HMGB protein family  play a complex role as intrinsic and endogenous regulators in rheumatoid arthritis. Several previous studies have also focused on the relationship between HMGB1 and AR. Yue et al found that inhibition of HMGB1 improved allergic rhinitis as well as inflammatory factor expression in mice model. Yuan et al suggested that SIRT1 administration attenuated HMGB1 protein expression and regulated the production of pro-inflammatory mediators to reduce allergic symptoms in AR mice. A clinical study by Zhu et al found high expression of HMGB1 levels in nasal lavage fluid samples from AR patients. However, there are no more clinical studies on the role of HMGB1 and HMGB2 in patients with AR. In our study, we found that serum HMGB1 and HMGB2 levels were declined in AR patients and were associated with other inflammatory factors.HMGB protein family has been confirmed to be involved in cellular proliferation, apoptosis, oxidative stress and inflammatory responses in a variety of diseases.This present research also has some limitations. First, we only included a small size of study population. Secondly, we only checked a small number of inflammatory factors. Thirdly, the molecular mechanism of HMGB1 and HMGB2 affecting AR development is unclear.This study showed that the serum HMGB1 and HMGB2 levels was remarkably enhanced in AR patients. In addition, HMGB1 and HMGB2 were closely associated with cytokines and clinical outcomes in AR patients. This study may provide new targets and a comprehensive approach for the treatment of AR patients.Data curation: Hai wang.Formal analysis: Xinxin Xing.Writing – original draft: Xinxin Xing, Hai Wang.Writing – review & editing: Hai Wang.


Functional Neurological Disorders (FNDs) are one of the most common and disabling neurological disorders, affecting approximately 10–30% of patients in neurology clinics. FNDs manifest as a range of motor, sensory, and cognitive symptoms that are not explained by organic disease. This narrative review aims to assess the current state of knowledge in physical-based rehabilitation for motor/movement FNDs in the adult population, with the goal of improving research and medical care for this patient population. To ensure optimal outcomes for patients, it is critical to consider several domains pertaining to FNDs, including which field of discipline they should belong to, how to investigate and test, methods for rating outcome measures, and optimal courses of treatment. In the past, FNDs were primarily treated with psychiatric and psychological interventions. However, recent literature supports the inclusion of physical rehabilitation in the treatment of FNDs. Specifically, physical-based approaches tailored to FNDs have shown promising results. This review utilized a comprehensive search of multiple databases and inclusion criteria to identify relevant studies. One of the oldest and most recognized functional disorders is Functional Neurological (Symptom) Disorder (FNSD or FND). Despite the advancement in knowledge and treatment of FNDs within the last 10 to 15 years, clear guidelines for physical-based rehabilitation for this common and debilitating disorder are lacking. This narrative review aims to assess the current knowledge in physical-based rehabilitation for specifically motor/movement FNDs, recognized as FMDs, within the adult population.A narrative review of the current literature on physical rehabilitation in FMDs was conducted using the PubMed database. The search terms “Functional Movement Disorder”, “Functional Motor Disorder”, “Motor Functional Neurological Disease”, “Movement Functional Neurological Disease”, “Rehabilitation”, and “Physical Rehabilitation” were used to identify relevant literature published from 2014 to September 2022. Additional publications were identified from the references cited in the initial papers. Only literature in English was included, and clinical trials were prioritized. The focus was on the most current literature related to the DSM-V’s revised definition of FND, specifically FMDs.After a thorough review, 48 sources were included, comprising 6 review articles, 4 recommendation articles, 11 clinical trials and case studies, 1 overview-case study, and information gathered from the FND-COM  and the Functional Neurological Disorder Society. The sources included articles reporting current overviews of FMDs physical rehabilitation, clinical trials, case series, and recommendations.hysteria [Corpus Hippocraticum of Greece, are the first sources to describe FNDs in detail, defining the uterus as the organ of origin [hysteria is linked to the uterus in various ways; therefore, the clinical term coined was hysteria [hysteria became attributed to witchcraft and supernatural sources [hysteria, became classified as a neurosis, a disorder of the nervous system [conversion, (psycho)somatization, and dissociation became directly associated with the condition and later labeled terms. In the first edition of the Diagnostic and Statistical Manual for Mental Disorders by the American Psychiatric Association, the disorder appears in psychophysiologic autonomic and visceral disorders. The conversion reactions of psychosomatic disorders were a result of the autonomic nervous system, which innervates organs, and according to this, it did not involve perception or voluntary control and required a psychological stressor [FND has a rich historical past and was first documented over 4000 years ago in Egyptian writings, recognized then as hysteria . In FND,hysteria . Throughhysteria ,4. As thf origin ,6. The Ghysteria . Additio sources . The diss system ,8. Charcs system . The apphysteria was replaced with somatoform disorder, body dysmorphic disorder, dissociative disorder, and conversion disorder [Toward the end of the 20th century, the focus that had been on etiology and the theory behind the disease turned toward symptomatic descriptions. The term disorder . The mosdisorder .International Classification of Diseases (ICD-11) functional disorders, these disorders appear in both neurological and psychiatric categories [FND is a common and disabling condition associated with motor and sensory symptoms which are incompatible with a recognized neurological or medical condition ,10 but wtegories .Substance abuse (including medications) must be ruled out, clinical and laboratory findings cannot be explained by recognizable neurological or medical conditions, and FNDs should not be accompanied by distress and/or excessive thoughts, feelings, or behaviors and should be distinct from intentionally produced or contrived symptoms . This haSince the revision of FNDs’ terms and definitions in the DSM-V, the condition’s description has become significantly clearer, thereby substantially improving the accuracy of rates and risks in the most current literature . Recent There is a significantly higher occurrence of FNDs in women 3:1 ratio) :1 ratio ,15. DiagFND was once considered a somatic or conversive disorder, believed to result from precipitating stressors of trauma or psychiatric disorders . Recent Following these findings, one may conclude that it is difficult to explicate a specific model of the neural paradigm of functional motor disorders due to the broad and various brain regions involved. One may summarize that FND patient experiences misinterpretation of sensory input, which thus interferes with motor planning ,12. DepeMany FND patients have negative experiences during treatment within the healthcare system. The negative experiences are generally the result of a combination of poor knowledge on the part of healthcare providers and a tendency to disbelieve, blame, or shame patients suffering from FND. The approach adopted by physicians often results in statements that the symptoms do not exist or accusations that the patient has voluntarily created the symptoms, and the course taken thereafter is psychiatric care . In the The balance of treatments in motor FNDs is complex for the following reasons: physical and psychological symptoms are comingled, symptoms vary significantly between patients, and unique aspects point towards relating to subjective measures  .Limitations also derive from the fact that comparatively little research has been conducted in the past. However, this has significantly changed within the last 10 to 15 years as increasing awareness of FNDs has compelled further research ,15. CurrOne may draw the conclusion that the literature regarding physical rehabilitation for FMD has significantly increased within the last decade. Research on FMDs has increased, and the establishment of the Functional Neurological Disorder Society (FNDS) in 2019 has signified critical markings with regard to the condition . From thConsensus recommendations have been published; however, due to the heterogeneity of symptoms in FMD patients, it is challenging to recommend uniform interventions ,34. Therhttp://www.comet-initiative.org (accessed on 8 May 2023)). Additional commonly measured domains are life impact, health economics/utility costs, and physical and psychological symptoms ).Another aspect that was lacking in the field of motor FNDs, due to the complexity and heterogeneity of the disorders, was a clear set of outcome measures . Over thPhysical rehabilitation for motor FNDs can be in an outpatient, inpatient, or telehealth setting, depending on the nature of symptom onset ,41,42. WThe main principles for the physical rehabilitation of FMDs are concluded in FNDs are complex neurological disorders that require a multidisciplinary approach to management. While the traditional approach of psychological and psychiatric interventions has been the norm, recent literature suggests that physical rehabilitation should be a crucial part of the management of FNDs. The literature reviewed in this narrative review provides evidence of the effectiveness of physical rehabilitation in improving motor function and quality of life in individuals with FNDs. However, further research is needed to establish optimal rehabilitation protocols, including the intensity, frequency, and duration of physical therapy interventions. In addition, the development of standardized outcome measures and the implementation of interdisciplinary care will help improve the accuracy of FND diagnosis and management. Despite these challenges, the integration of physical rehabilitation in FND management provides hope for individuals with FMDs, particularly those who are limited in their daily activities due to the disorder.In addition, the study identifies three settings for physical rehabilitation: inpatient rehabilitation, outpatient care, and telehealth, which can be tailored to the specific needs of individual patients. As research and literature continue to emerge on the topic, it is important to explore and identify more specific and effective interventions in physical rehabilitation. This will lead to better outcomes and higher quality of life for patients with FNDs. Ultimately, the most effective treatment approach for FNDs is one that includes physical rehabilitation with a unique and tailored approach.


This study’s objective is to evaluate retrograde reperfusion (RR) compared to sequential anterograde reperfusion (AR), with and without the washout technique (WO).  this prospective cohort study collected data from 94 deceased donor orthotopic liver transplants and divided it into three groups: RR with WO (RR+WO), AP with WO (AR+WO), and AP without WO (AR). This study did not assign the reperfusion technique to the participants. The primary outcome considered the early graft dysfunction, and secondary outcomes included post-reperfusion syndrome (PRS), post-reperfusion lactate, surgery fluid balance, and vasoactive drug dose during the surgery. 87 patients were submitted to the final analysis-29 in the RR+WO group, 27 in the AR+WO group, and 31 in the AR group. Marginal grafts prevalence was not significantly different between the groups  and early graft dysfunction occurred at the same rate . RR+WO reduced serum post-reperfusion lactate (p=0.034) and the incidence of significant PRS , but norepinephrine dosing >0.5mcg/kg/min were not different during the surgery . primary outcome was not significantly different between the groups; however, intraoperative hemodynamic management was safer using the RR+WO technique. We theorized that the RR+WO technique could reduce the incidence of PRS and benefit marginal graft survival following diseased donor orthotopic liver transplantation. Liver transplantation (LT) is the most effective treatment for end liver disease. The outcome of this procedure has significantly improved over the past decade; however, the reperfusion phase remains a weak spot of this procedureMany revascularization techniques in LT have been described to alleviate the PRS and favor graft survivalThe portal vein (PV) unclamping with anterograde reperfusion (AR) was the first technique developed by Starzl et al. using conventional surgery with venovenous bypass. It has been widely used in transplant centers. It is based on physiological precepts of liver vascularizationHowever, the first idea of anterograde portal reperfusion may oppose another complex pathomechanism of the PRS that has yet to be understood. Abrupt high blood flow can, paradoxically, aggravate organ perfusion. It is called ‘paradoxical reperfusion’ and yields massive reactive oxygen species that cause endothelial inflammation and capillary occlusionThe retrograde revascularization (RR) technique was proposed in 2003; it constitutes a reperfusion technique that provides low and gradual backflow of blood to the graft,,,,Few studies have proposed to understand RR techniques and their effects on intraoperative hemodynamicsThis prospective cohort study followed deceased donor LT from December 2018 to January 2020 at the University Hospital Oswaldo Cruz Pernambuco, Brazil. We divided the patients into three groups: retrograde reperfusion with washout technique (RR+WO), anterograde reperfusion with washout technique (AR+WO), and anterograde reperfusion without washout technique (AR). This study method did not assign the reperfusion technique. Instead, it was an intraoperative decision of the assistant surgeon based on his technical experience and clinical judgment. The team of this investigation recorded, prospectively, pre-defined data until the seventh-day post-transplant. The primary outcome was early graft dysfunction, and secondary outcomes included post-reperfusion syndrome, post-reperfusion lactate, surgery fluid balance, and vasoactive drug dose during the surgery. Adult patients with end-stage liver disease were included. We excluded patients with: fulminant liver failure, combined transplantation, or split graft. No other criteria were applied to exclude any participant. Comorbidities , PV thrombosis, and MELD-Na were considered risk factors for the recipient.The conventional hepatectomy technique was performed and both portal flow and vena cava flow were interrupted, whereas the piggyback approach only occluded portal flow. The surgeon’s preference defined it. No bypass was used in the conventional technique. Modified retrograde reperfusion was performed by IVC supra and infra-hepatic anastomoses and, as soon as it was completed, backward unclamping. During the anastomosis of the infra-hepatic IVC, the wash-out technique was carried out by the infusion of 1000ml of frozen saline 0,9% solution through the PV. Following retrograde reperfusion, 100ml of blood was released through the PV into the cavity. Next, PV anastomosis was performed and then unclamped. Then, hepatic artery anastomosis was done. Anterograde reperfusion was carried out by the following steps: conventional (or piggyback) hepatectomy; IVC supra (and infra-hepatic) anastomoses; PV anastomosis; portal and IVC supra (and infra-hepatic) unclamp; hepatic artery anastomosis and hepatic artery unclamp. Wash-out in anterograde reperfusion was performed in the same way as in retrograde reperfusion and blood release was done throughout the infra-hepatic IVC after PV unclampWarm ischemia was defined as the interval from removal from cold storage to the establishment of reperfusion of the liver graft either through hepatic veins or portal vein. While portal ischemia was defined as the interval from removal from cold storage to establishing portal vein unclamp. We used the Histidine-Tryptophan-Ketoglutarate (HTK) solution at 4ºC to preserve the graft. The deceased donor was defined as expanded criteria liver donor - marginal grafts - with at least one of: age over 60 years, length of ICU stay over four days, bilirubin over 2,0mg/dl, AST over 170U/I, ALT over 140U/I, bloodstream sodium over 155mEq/l and macrosteatosis over 30%, need for vasopressor drugs .2 (mmHg), lactate (mmol/L) and potassium (mmol/L)] were used to measure microvascular dysfunction the first, 30 minutes before reperfusion, and the second, 30 minutes after reperfusion. Finally, the macrohemodynamic evaluated the need to maintain vasoactive amines at the end of the surgery and the fluid intake during the surgery. The hemodynamic outcome was evaluated in three domains: ischemia-reperfusion syndrome, microvascular hemodynamic, and macrovascular hemodynamic. Mild PRS was defined by a decrease of mean arterial pressure or heart rate fewer than 30% of baseline value that lasts for less than 5 minutes and that responsive to an intravenous bolus dose of Calcium Chloride (1g) or epinephrine (≤100mcg). Significant PRS was defined by a drop of mean arterial pressure or increase of heart rate greater than 30% of baseline, asystole, or hemodynamically significant arrhythmias; or the need to start the infusion of vasopressors that persist throughout the postoperative period. Absent PRS was assigned when none of these alterations were observedEarly graft dysfunction (EGD) was defined within at least two of the following criteria during the first seven days: ALT over 2000U/l, bilirubin over 10mg/dl, or INR over 2,0. Primary non-function (PNF) was defined within EGD associated with retransplantation or death after hepatic thrombosis artery was excluded. ® Statistics 13.0 (IBM® Inc.). The data values were presented as absolute frequency plus relative frequency and median plus interquartile range. All inferential tests performed were two-tailed. All conclusions were taken at the 5% significance level.Statistical data analysis was done in SPSSThis study was approved by the Human Research Ethics Committee of the institution where it was conducted , following the principles of the Brazilian National Health Council.During the studied period, 87 patients were submitted to the final analysis 29 in the RR+WO group, 27 in the AR+WO group, and 31 in the AR group. Seven patients were excluded: four patients were excluded because they did not undergo the washout technique combined with RR and three patients were excluded from lack of postoperative data.We summarized receptor and donor baseline characteristics in RR+WO technique minimized the prevalence of significant PRS compared to AR+WO and AR . .Intraoperative arterial gasometry before reperfusion and after reperfusion of the graft showed: 1) an increase of post-reperfusion acidemia in AR+WO (p=0.004) and AR (p=0.026) and hypercapnia in AR+WO (p≤0.001) and AR (p≤0.001); 2) lower serum post-reperfusion lactate in RR+WO (p=0.034), 3) reduction of kalemia in the RR+WO  and the AR+WO  . Post-reThe statistical method showed no significant difference in post-transplant liver enzymes and INR. Both parameters converged on the seventh-day post-transplant. The serum bilirubin level in the RR+WO group increased .The data of this study associate RR with lower PRS incidence. PRS is a critical moment and can affect up to 32% of the patients submitted to LT,However, no definitive consensus exists that RR could produce better graft function and recipient survival outcomes. Since the first large case series of RR in 2003, this technique downgrade liver transaminases in early post-transplantationOur study did not observe differences in the early graft function between the groups. We imply this finding to the unbalanced sample submitted to different reperfusion techniques. A senior liver surgeon carried the reperfusion technique option. RR and WO techniques were used in qualitative inferior grafts and donors. It quantitatively explains marginal prevalence in the RR+WO group (34%). The unbalance of the sample limits the comparative analysis of this research; however, it highlights the role of RR+WO in sparse contexts of ideal grafts: in our sample, RR showed similar outcomes compared to AR despite the inferior graft scenario. However, the benefits of the hepatocytes occur at the expense of biliary ducts. Ischemia-type biliary lesions were higher in the group submitted to RR in the Heidenhain et al. study,,,Intraoperative management of LT is complex and exposes the patient to hemodynamic and biochemical changes. It represents a significant cause of cardiac arrest and might be evitable by the RR. In many investigations, RR was associated with a better post-reperfusion hemodynamic profile and better short-term outcomesThe WO technique is another way to improve post-reperfusion hemodynamics. Kalemia was reduced in the RR+WO and the AR+WO groups, and it was not observed in the AR group. It resembles to be associated with washing out the solution in the graft before revascularization. However, the HTK solution has a relatively low potassium concentration compared to other preservative solutions employed in the transplant. The systemic spread of cytokines and eicosanoids can also be minimized by this techniqueThe conventional technique without venovenous bypass using AR is the standard technique performed at this transplant center. Surgery duration was still lower in the RR+WO. We do not justify it based only on the surgery technique. Other factors not pre-emptively hypothesized by this study could explain it, such as biliary reconstruction, hepatectomy technique , portal vein thrombosis, obesity and post-reperfusion coagulopathy. Indeed, the applicability of RR was workable and did not jeopardize the surgical performance of this transplantation group.This study’s primary and secondary outcomes should not vary depending on the surgical technique . A previous study at this center showed equivalent results between the two surgical techniques, and both have been carried out since without differing overall morbimortalityWe could perform RR with no delay to portal reperfusion. According to the definitions of this work, warm ischemia time and portal ischemia time are different. However, both are the same when performing sequential AR. The warm ischemia time is inherently reduced when RR is carried out; however, the portal ischemia time, which could have been compromised, was also reduced. The allocation criteria of the reperfusion technique impose important limitations on the study. This analysis observes different reperfusion techniques applied by a specific team of transplant surgeons and does not randomly assign them. Therefore, the implication of these results must be taken with due merit of the methodology. The small number of patients also implies limitations; however, the sample is appropriate for the literature in terms of liver transplantation.RR+WO technique combined physiopathological mechanisms that might reduce the impact of reperfusion-ischemia injury in the LT. The primary outcome was not different between RR+WO, RA+WO and RA. Secondary outcomes showed that intraoperative hemodynamic management was safer using the RR+WO. This observational study enlightens the RR+WO for marginal grafts in LT. However, ischemia-type biliary lesions may limit the feasibility of RR+WO. Further randomised studies should address these hypotheses.


Microsatellites or simple sequence repeats (SSR) consist of 1–6 nucleotide motifs of DNA or RNA which are ubiquitously present in tandem repeated sequences across genome in viruses: prokaryotes and eukaryotes. They may be localized to both the coding and non-coding regions. SSRs play an important role in replication, gene regulation, transcription, and protein function. The Caliciviridae (CLV) family of viruses have ss-RNA, non-enveloped, icosahedral symmetry 27–35 nm in diameter in size. The size of the genome lies between 6.4 and 8.6 kb.https://www.ncbi.nlm.nih.gov), and microsatellites were extracted through MISA software. The average genome size is about 7538 bp ranging from 6273 (CLV61) to 8798 (CLV47) bp. The average GC content of the genomes was ~ 51%. There are a total of 1317 SSRs and 53 cSSRs in the studied genomes. CLV 41 and CLV 49 contain the highest and lowest value of SSRs with 32 and 10 respectively, while CLV16 had maximum cSSR incidence of 4. There were 29 species which do not contain any cSSR. The incidence of mono-, di-, and tri-nucleotide SSRs was 219, 884, and 206, respectively. The most prevalent mono-, di-, and tri-nucleotide repeat motifs were “C” (126 SSRs), AC/CA (240 SSRs), and TGA/ACT (23 SSRs), respectively. Most of the SSRs and cSSRs are biased toward the coding region with a minimum of ~ 90% incident SSRs in the genomes’ coding region. Viruses with similar host are found close to each other on the phylogenetic tree suggesting virus host being one of the driving forces for their evolution.The incidence, composition, diversity, complexity, and host range of different microsatellites in 62 representatives of the family of Caliciviridae were systematically analyzed. The full-length genome sequences were assessed from NCBI (The Caliciviridae genomes does not conform to any pattern of SSR signature in terms of incidence, composition, and localization. This unique property of SSR plays an important role in viral evolution. Clustering of similar host in the phylogenetic tree is the evidence of the uniqueness of SSR signature.The online version contains supplementary material available at 10.1186/s43141-023-00582-x. Norovirus, Sapovirus, Lagovirus, Vesivirus, Nebovirus, and Recovirus) and five more genera have been proposed . The virus members of the family Caliciviridae are known to have a wide range of hosts including human, geese, yellowfin seabream, greater green snake, arctic lamprey, frogs, and birds. These viruses are associated with several diseases like digestive tract infections, vesicular lesions, reproductive failure, stomatitis, upper respiratory tract and systemic diseases, and hemorrhagic disease [Norovirus and Sapovirus are the major causative agent for human epidemic acute gastroenteritis around the world. Their transmission happens through both direct contact as well as indirect means like fecal matter, vomitus or respiratory secretions, contaminated food, water, and fomites [The Caliciviridae family are non-enveloped viruses, about 27–35 nm in diameter with an icosahedral symmetry and ss-RNA 6.4–8.6 kb) as a genetic material. Their genomes contain multiple ORFs/genes encoding for structure and non-structure protein. The Caliciviridae family has six established genera . These are short tandem repeats of 1–6 bp repeat motif reportedly exhibiting ubiquitous presence in both the coding as well as non-coding regions of the prokaryotic and eukaryotic genomes , 10. SSRhttps://ictv.global/report_9th/RNApos/Caliciviridae) were retrieved from the NCBI database (http://www.ncbi.nlm.nih.gov/) and saved in GenBank information data and FASTA formats. The Virus-Host Database (https://www.genome.jp/virushostdb/note.html) was used for elucidating virus-host information. The summary of sequences analyzed in the study has been provided in Supplementary file The complete genome sequences of 62 Calicivirus (CLV) genomes of the family Caliciviridae which is listed in ICTV (https://webblast.ipk-gatersleben.de/misa/) with previously standardized parameters for viral genomes [The extraction of microsatellites was done using MISA software  tool was used for alignment and phylogenetic tree building as per standard protocols [ETE3 v3.1.1 GenomeNet  and RAWGraphs 2.0 (https://app.rawgraphs.io/), Gene structure display server (http://gsds.gao-lab.org/), and Microsoft PowerPoint 2016. All the tools are online webserver, and the figures are generated by default parameters. Gene structure display server required FASTA, GTF/GFF3, or BED format file for input data.All the figures are generated by Flourish  to 8798 (CLV47) bp. The average GC content of the genomes was ~ 51% with a range from 42.4% (CLV61) to 58.6% (CLV41). The genome size and GC% of the Calicivirus genomes have been shown in Fig.  to 8798 The extraction revealed a total of 1315 SSRs and 55 cSSRs from the Caliciviridae genomes. The SSR incidence ranged from 32 (CLV41) to 10 (CLV49) with an average of 21 SSRs per genome. Interestingly, there appears no linearity between genome size and SSR incidence as exemplified by CLV41 with genome length of 7365 bp having 32 SSRs, while CLV49 with 8741 bp genome had just 10 SSRs. The incidence of SSR and cSSR has been represented in Fig. r = 0.014075; p = 0.358409), cSSR , sRA , sRD , cRA , cRD , and cSSR%  while GC content also did not show positive and significance on any number, all the numbers show negative and non-significant correlation of SSR , cSSR , sRA , sRD , cRA , cRD , and cSSR% .We assessed the possible influence of genome size and GC content on number of SSR and cSSR incidence, RA, RD, of SSRs and cSSRs and cSSR% in SSR. Genome size of the assessed CLV type has no positive significance on any number. All are showing non-significant correlation of SSR (We further looked at the distribution of microsatellites and their iteration length. Relative abundance (RA) is defined as the number of microsatellites present per kb of the genome, whereas relative density (RD) is the number of bases present as SSR per kb of the genome. A higher RA value would denote greater SSR incident frequency, whereas a higher RD value would indicate a greater number of iterations and hence higher tract size of SSRs. The RA and RD for SSR in the Caliciviridae genomes ranged from 1.14 and 7.89 (CLV49) to 4.34 and 29.87 (CLV41) respectively. The cSSR incidence had a maximum of 4 in CLV16. A total of 29 species had no cSSR in their genomes  to 36.36 (CLV19). This implies that in CLV19, more than one-third of the incident SSRs have another SSR in their vicinity ; motif constitution (A/T/G/C) and tract size (number of repeats). In terms of motif length, the SSRs were predominantly composed of mono- to tri-nucleotide SSRs. There were only four  and two  tetra- and penta-nucleotide repeats observed across the genomes. No hexa-nucleotide repeats were observed  is localized in the polyprotein region followed by non-structural protein in the second position containing 10% of SSR (150) as represented in Fig.  is localIn order to understand the evolutionary relationship between the members of Caliciviridae, the phylogenetic tree was constructed and annotated with some specific aspects, which has been represented in Fig. Genome-wide scan study revealed genome size, GC content, occurrence, abundance, and composition of SSRs and cSSRs tracts across 62 Caliciviridae genomes. The average length of genome of Caliciviridae was about 7538 bp with a maximum and minimum of 6273 to 8798 bp. The average GC content of the genomes was ~ 51% with a range from 42.4 to 58.6%. This is one of the richer set of genomes in terms of GC% and would be interesting to observe the implications on microsatellite particularly in terms of motif composition. A total of 1315 SSRs and 55 cSSRs have been retrieved from the Caliciviridae genome. The average SSR per genome is 21 with a range from 32 to 10. The incidence of cSSR ranged from 0 to 4. The SSR incidence is independent from genome size. For instance, CLV13 has genome size (7338 bp) with 28 SSR incidence, while CLV31 contains (8450 bp) with 15 SSR incidence. The result indicates that there is no correlation between genome size and SSR incidence. RA and RD of SSR ranged from 1.14 to 4.34 and 7.89 to 29.87, while RA and RD of cSSR ranged from 0 to 0.5 and 0 to 8.23. Highly variation has been observed in RA and RD value of SSR and cSSR.The most abundant repeat motif is “C” comprising of around 58% (126 of 219) of the mono-nucleotide SSRs. “G” is the second most prevalent repeat motif (70) incidence. Similarly, among the di-nucleotide repeats, the most prevalent motif was AC/CA comprising around 27% (240 of 884) followed by GT/TG (202 of 884), while TGA/ACT is the most prevalent motif of tri-nucleotide repeat incidence. Poly C/G is predominant in all the types of SSR (mono-tri) because of a high percentage of GC content in the studied genome. These results when looked at in terms of host range are significant as it has been reported that viruses tend to have predominantly mono-nucleotide SSRs in the A/T region , 17. TheAs discussed above in the microsatellite composition section, genomes with the same microsatellite incidence may also have a totally unique microsatellite signature in terms of composition and number of iterations. This is in concordance with previous reports on other virus families , 19–21. We analyzed the distribution of SSR in the genome; ~ 90% of SSR incident were present in the coding regions, whereas only ~ 9% of SSR incident were found in the non-coding regions of the genome. SSR in the coding region are responsible for the genome diversity and evolution, while SSR in non-coding region are responsible for gene regulation and formation of a novel gene. In the genomes wherein there was no non-coding regions, rather than looking at absolute incidence of SSRs, we compared the SSR density therein with the coding regions. Interestingly, 18 genomes had a higher density of SSRs in the non-coding regions. This may be an indication of the non-coding regions equally contributing to the course of evolution and might be future genes in new viruses.We analyzed the distribution of SSR in the coding region. Polyprotein contains 65% of SSR (837) followed by non-structural protein in the second position with 10% of SSR (150). As evident, even in the members of the family, the genomes do not follow any pattern in SSR incidence across proteins, reinforcing the idea about a unique microsatellite signature for each genome. The location of incident SSRs in Caliciviridae genomes reiterates two important aspects. Firstly, the virus genome is mainly comprised of coding region, thus most of the SSR incident are present in the coding region of the genome. Secondly, as reported earlier, SSR plays an important role in gene expression and genome evolution, thus the position of SSR in the protein region is imperative which is approved by the data.As per the previous report, human and related species of viruses has A/T rich mono-nucleotide SSR repeats in their genome , 11, 17.The Caliciviridae genomes do not conform to any pattern of SSR signature in terms of incidence, composition, and localization. This unique property of SSRs plays an important role in viral evolution by acting as sites for genome diversity. Their presence in the different proteins means the microsatellite alterations can impact their function and thus aid evolution. The clustering of similar host in the phylogenetic tree is the evidence of the uniqueness of SSR signature. Though SSR signature plays a key role for all viral genome evolution, the mechanism through which it happens needs to be explored.Additional file 1. Genomes features and extracted microsatellites of Caliciviridae in the study.Additional file 2. SSRs and cSSRs extracted from Caliciviridae genomes.Additional file 3. SSR incidence, tract size, composition and location in Caliciviridae genomes.Additional file 4. SSR density range of genes of Caliciviridae genomes.


This study aimed to identify priority self-management skills and behaviours in partnership with stroke survivors, and to co-create approaches to support self-management during inpatient stroke rehabilitation.Three stroke survivors and two communication partners participated in the three-stage Participatory Action Research project with embedded co-design processes after undertaking inpatient rehabilitation at a metropolitan tertiary hospital.Participants identified key factors influencing self-management during inpatient rehabilitation including motivation, emotional well-being, and fatigue. Three approaches to support people to self-manage post-stroke were co-created. (1) A health professional concierge and early family meeting. (2) A peer support person. (3) Adapting the hospital environment.Findings suggest post-stroke self-management support should commence during inpatient rehabilitation to optimise its research-informed benefits. This support should focus on empowering stroke survivors and their key support people through active involvement in decision-making, and provision of multi-modal individualised education. The impact of hospital environments on emotional-wellbeing and self-management post-stroke also requires further investigation.The identification of a health professional concierge as a co-designed solution to the current challenges with self-management support is an innovative recommendation for practice. The findings support changes to the traditional processes of rehabilitation towards a consumer and family-led practices. •A foundation of self-management support is required during inpatient stroke rehabilitation•Co-creation approaches are yet to be commonly used for the development of inpatient stroke rehabilitation practices.•Self-management support for stroke survivors during stroke rehabilitation requires individualised education and a family-centred approach.•Active, early involvement in should be prominent during inpatient stroke rehabilitation. Self-maSupport approaches to effectively develop self-management skills after stroke are yet to be conclusively identified and hospital-based self-management support approaches are currently underexplored . GreenwaStroke survivors experience frustration and disempowerment during inpatient rehabilitation , and the2A three-stage Participatory Action Research (PAR) approach adapted from Ogrin et al.  Fig. 1)Fig. 1) g2.1Ethical approval was granted from Metro South Human Research Ethics Committee [HREC/2021/QMS/70512] and Griffith University Research Ethics Committee [2021:194]. All participants received written and verbal information regarding the study purpose and procedures, and possible risks and benefits. Formal written consent was gained from all participants and verbal consent was gained at the commencement of each data collection event.2.2All potential participants received inpatient rehabilitation on a general rehabilitation ward for people with stroke and a range of other health conditions. The interprofessional team included dieticians, doctors, nurses, occupational therapists, pharmacists, physiotherapists, social workers, and speech pathologists with limited psychology or neuropsychology services available. People discharged from the inpatient unit are referred to an onsite outpatient day hospital or community-based transition care or rehabilitation services for continuing rehabilitation.2.3Convenience sampling aimed to recruit 6–8 stroke survivors discharged from the inpatient rehabilitation unit and/or accessing the outpatient day hospital clinic. The inclusion criteria were: diagnosis of stroke; ≥18 years of age; living in the community; ability to provide informed consent and participate in the qualitative data collection (with or without communication partners); no co-morbidities significantly altering stroke rehabilitation i.e., diagnosis of advanced dementia, severe mood disorder or chronic mental health condition.2.4Participants were involved in a series of three co-creation stages . Each co2.4.1The purpose of Stage One was to identify the priority issues post-stroke that could be addressed through self-management and propose potential approaches to support this skill and behaviour development. All participants received an information pack that introduced self-management prior to this stage. At the data collection event, participants and researchers introduced themselves, the aims and expectations of the research were clarified, and a shared understanding of self-management was established. Discussions were guided by open-ended and probing questions from the question guide  and the direction of the discussions. The discussions were audio-recorded and transcribed, and field notes were taken by the researchers.2.4.2Participants were emailed preparatory information including key issues identified for self-management support, service approaches and the aim of Stage Two. This information was reviewed at the beginning of the discussions to ensure they were an accurate reflection of participant perspectives. Guided discussions supported participants to further refine and develop these approaches including consideration of the timing of support, operationalisation of service provision, and pragmatics of the approaches in the inpatient rehabilitation environment. The discussions were audio-recorded and transcribed, and field notes were taken by the researchers.2.4.3Participants received a summary of the outcomes from Stage Two in preparation for the discussions to finalise and prioritise the approaches. Participants collaborated to make decisions regarding the importance of each approach and which approaches should be pursued further. Consensus was achieved through the discussions, which were audio-recorded, and field notes were taken by the researchers.2.5The data analysis was iterative in nature, using the knowledge created to inform action and the next stage of co-creation . Data an2.6The five criteria for qualitative methodological trustworthiness, credibility, transferability, dependability, confirmability, and authenticity, were considered through this study's design and implementation ,29. The 33.1n = 1), one was unable to commit to the data collection (n = 1) and two were unwilling with no reasons specified (n = 2). Three male stroke survivors participated and their pseudonyms and demographic details are outlined in Seven stroke survivors were invited to participate and three stroke survivors with two communication partners agreed. One stroke survivor was unable to be contacted (Two stroke survivors participated in the focus groups with communication partners and they were considered as dyads. Dyad one were: Thomas who had severe expressive aphasia and Eliza (spouse and communication partner) who spoke in the focus groups. Thomas was involved through yes/no questioning that allowed him to answer closed questions or agree/disagree with what had been conveyed by Eliza, Dyad two were Nathan who had a cognitive communication disorder and Christine (spouse and communication partner). Nathan would respond to questions and Christine would provide clarification or detail – as a result included quotes are often Christine representing what Nathan was wishing to convey. The third stroke survivor (Nicholas) was unable to attend the focus group due to work commitments and participated in an online individual interview, which always followed the focus group.3.2Participants identified sequelae of stroke that were challenging to self-manage, barriers to self-management during inpatient rehabilitation, and unmet needs that could be addressed through self-management. These included motivation, fatigue, emotional well-being, family engagement, individualised early education, and health professional relationships. Potential approaches to support this skill and behaviour development were introduced.3.2.1Motivation enabled or inhibited engagement in ongoing therapy, re-engagement with previous roles, and self-management. Motivation was difficult in the early stages of rehabilitation with Nathan preferring “to have my food in the bed” while the nurses “tried to get me to go into the dining room”. Christine added that the low motivation extended “Even down to the point where they [nurses] would say, right, you know it's time to go and have a shower, and he'd say, “No, not having a shower. No.” The turning point for Nathan was a meeting with a peer support person:I looked at this bloke, and I thought, I see what he's been through, you know, I'm not that bad. You know, get me finger out and, do something about, you know. After that, …..that's when I started to go into the dining room and, then start becoming pretty good after that.The challenges with motivation heightened on return to home without the structure of rehabilitation and impacted community re-engagement:It's like yes, you've got your other half there pushing you to do it so that you're going to get better and you're going to improve everyday … but when you're at home, it's like the wife's only nagging … I don't want to do it because you know, just leave me alone. (Eliza)3.2.2Participants highlighted the difficulties of managing fatigue. Nicholas described that “usually, it takes a couple of hours and then I just feel tired and want to go off [to sleep] and brain sort of goes into neutral as well”. Christine explained that she and Nathan had accepted that “You've got to work your way through it because you just don't know when the fatigue is going to be there, how long it is going to be there for.” The difficulties of managing this fatigue during occupational engagement were expressed, “On the weekend when I'm out walking around with my kids, I can't rest. I can't rest in the middle of a golf game.” (Nicholas) Strategies to self-manage fatigue ranged from the recognition that “If I'm tired, I know I have to sit down and have a break.” (Nicholas), through to Eliza who described a structured approach to managing Thomas's fatigue and therapy:We had sort of a roster set up because of fatigue and things like that … We had to have, he could do, have physio for an hour and then we had to have an hour break, and then we'd have speech and then he'd have a rest, and then lunch, and then ….3.2.3It was believed that emotional well-being was a crucial factor that limited the stroke survivors' capacity to self-manage. Emotional well-being was a significant factor from “the start of emergency all the way through [their hospital stay]” and was compounded by the hospital environment that is “just so foreign and confronting”. The transition to rehabilitation was described as entering “a whole new world” and Eliza stated,I know it's very busy, but it needs a little more humanisation… You've lost a lot of dignity. So, it's those hurdles as well as the emotional stuff that you've got to get past, I think, to even start to develop the concept that you have to do the therapies to get out.The impact of emotional well-being on self-management skills was highlighted. “I didn't have any goals to be started with because ….. I was down on myself. Even now I'm still down.” (Nicholas) Participants identified the need for additional support for emotional well-being “Especially if you're talking about the mental state, you need assistance, like the psychologist talking to them, rather than giving them a pill.” (Eliza) This was considered important to prepare for the transition to home, “Because I think if there's more the mental health [support] and that assistance at the beginning, by the time we get them home and have to deal with it, it's more an acceptance.” (Eliza)3.2.4The active involvement of the stroke survivor and key support people in therapy and decision-making would facilitate development of self-management skills. Eliza stated, “I think it would help their [stroke survivor] recovery because they're part of the process” further explaining that at the moment “The patient doesn't seem to be part of the process.” As an extension to this, the spouse was also not often included:I was not going to rehabilitation in the morning, because obviously that was peak therapy time, and … they don't encourage you to be there in those times. Which is fine to a degree. But I think for me personally, I missed out on a lot of learning. (Christine)Eliza explained this concept of active involvement in decision-making and therapy as essential for self-management:I think that's something that needs to be part of self-management but right from the beginning. Everything seems to be, let's wait until we get home to self-manage. We need to do it from here. If we're going to recover, we want it here as we're doing our recovery. We need to start self-management here.3.2.5Participants described the opportunity to facilitate self-management through “humanisation” of the education, “You know, that someone just to sit down and talk to you and run through [rehabilitation process].” (Eliza) The value of early and individualised education was considered important in contrast to what was received “The education that is given is very broad…But I think if there was something that was a little more targeted for different types of stroke.” (Christine). The incorporation of a family meeting early in the rehabilitation process to facilitate this active involvement of stakeholders and delivery of individualised education was discussed.A session to tell you what's going on, like we're all your therapists, we're going to do work to do blah with you, to get you to a stage to be able to go home and function…a family meeting sort of thing at the beginning…have other family members who are going to support you come along as well…So that you've got the buy-in by everyone else. That buy-in at the beginning, not at the end. (Eliza)3.2.6The positive influence of relationships with members of the healthcare team during the inpatient rehabilitation journey was noted. Participants discussed the perceived benefits of having familiar staff to approach if required. “The nurses, you get your team of nurses, and he likes routine and the familiarity.” (Eliza). Christine explained the importance of the first encounter with health care staff and the overall influence the interaction can have on the stroke survivor and family well-being:What I found was, your first nurse that you come in contact with is the one that has the greatest impact. She said to my son and I as a family, she said, “Don't be negative. It's going to be okay. Just keep the positive. All the good.”3.3The findings for stage one were discussed and informed further discussions of approaches to self-management support. The focus was on building a “foundation” with early and active involvement to develop self-management skills more effectively. The suggested approaches included a health professional concierge, family meeting, peer support, adapting the hospital environment, and implementing individualised education. These are illustrated in the themes below.3.3.1The importance of active involvement of the stroke survivor and key supports to facilitate self-management was confirmed. Participants detailed the need to address emotional well-being to catalyse motivation, “You don't get the motivation if you don't have the emotional well-being.” (Christine) Nicholas explained “I would have loved to plan my therapy session a little bit”. The impact of individualised education to actively involve people in the therapy was stressed “He had no great understanding why he was doing a particular task. And if it didn't interest him then motivation was low.” (Christine). Participants described the need for stroke survivors and supports to “become part of that journey, to help the therapists and everybody else.” (Eliza). Education and information were a motivator for Nicholas who explained that information about the importance of early therapy intervention encouraged him to take an active role in therapy and self-manage, “I did that [exercises] because I wanted to get better, and because I knew for a fact that the first six months … that's when you can become better.” However, Nicholas reinforced that “It's [education] got to be tailored to each specific need… I would tailor it [education] individually instead of just a blanket approach.”It was stressed that addressing emotional well-being, implementing individualised education, and supporting active involvement would build the foundation upon which the motivation and acquisition of self-management skills and behaviours would occur.Because once you know what you're looking for, you'll be motivated for the end goal. See, when you don't know, what have you got to look forward to, really? There's nothing to motivate you, because, yeah, you've got to get home, but how are you going to get home? (Eliza)3.3.2The opportunity to build this “foundation” started with the initial transition to rehabilitation. Participants introduced the idea of a “concierge”, someone who would meet with the person on admission to rehabilitation and guide them with individualised information about their stroke, the processes of rehabilitation, and what to expect. The importance of an early family meeting was reinforced:I think the whole thing [transition to rehabilitation] probably needs like, some guidelines, with everything, you know? … when they go in the stroke ward, it's explained to them what's going to happen and where you've got to go to rehab…have a family meeting, explain to everybody so they're all on the same page, know what's going on. (Eliza)The negative impact of the hospital environment on emotional well-being was identified as a barrier to this “foundation”. Adapting the physical and cultural environments of rehabilitation was encouraged:I just found the rooms were really depressing to be in … there was no lightness in the rooms. Like, I don't know how else to describe it as lightness, it is business, and it has to be business. (Christine)It needs to be a) let's encourage families in, let's encourage people to sessions, let's encourage family to bring pictures and paintings and things like that. Let's encourage family to bring food. (Eliza)Finally, meeting a peer support person early in rehabilitation to deliver individualised education, support emotional-well-being, and enable stroke survivor empowerment was suggested:Because I think if you can look at a person who's been through what [stroke survivors] have been through and then come out to a degree … maybe that interpersonal reaction would help to say well, you know, I've been at a bad place. But I was able to work through it and now I can do XYZ. (Christine)3.4Three approaches were refined, prioritised, and finalised during Stage Three: (1) A health professional concierge and early family meeting ; (2) A peer support person; (3) Adapting the hospital environment.These prioritised approaches are detailed in 44.1This PAR study sought to identify priority issues and develop approaches that support self-management skill and behaviour development during inpatient stroke rehabilitation. Through the operationalisation of co-creation, the participants identified that a “foundation” of active involvement, individualised education, and support for emotional well-being was required. Participants detailed three priority approaches to achieve this: a health professional concierge and early family meeting, peer support person, and adapting the hospital environment. This “foundation” of self-management support is consistent with the concept as described by Parke et al. . The finStroke survivors experience negative emotions during inpatient rehabilitation including disempowerment, frustration, feelings of lost control of their situation and environment, and isolation ,30. SelfIt is well established that there is a need for active and patient-specific information provision ,5,8,33 tA multi-modal approach to information provision harnesses the benefits of both peer supports and health professionals. Peer support positively influences self-efficacy and emotional well-being post-stroke  and is aFinally, the role of family, supports and carers in self-management post-stroke were highlighted. Family, carers, and support people face significant challenges and are intimately involved in supporting stroke survivors to adjust to the sudden life altering impacts of stroke . Self-maThis study was limited to participants from one inpatient rehabilitation unit, which supported the development of targeted recommendations, but a larger sample size from more services may yield different results. The COVID-19 pandemic may have influenced the participants rehabilitation experience and impacted the study, with the final data collection event occurring entirely online or via telephone. However, due to the prolonged engagement with participants and the relatively small sample size supporting increased rapport between participants and researchers, it is not considered that this significantly influenced data collection. The small sample size could be considered a limitation however the three participants were representative of the heterogeneous male stroke survivor population due to the range of stroke impacts that they experienced. It is unclear if the findings would have been different if female stroke survivors had been involved. The inclusion of two participants who required communication support partners is a strength of the study but may be considered to limit the findings to the perspectives of spouses. The data collection process was conducted to ensure that the discussions were representative of the stroke survivor and their experience. Finally, due to pragmatic reasons including COVID delays and transcription timelines, the informal analysis and discussion of the data collection episodes occurred prior to receipt of the transcript. Although we do not believe that this occurred, it may be considered that this process limited the prioritisation of the participants' voices during the analysis process.4.2Co-design of approaches for inpatient stroke rehabilitation is a novel field, with previous work predominantly for community- based context and frequently related to development of technology-based interventions . PrivileThe findings that link the introduction of a health professional concierge as a foundational requirement for self-management suggests an innovative solution for inpatient rehabilitation that has not been previously evaluated with respect to the development of self-management skills and behaviours.5An evidence base has rapidly developed over the last decade, identifying the benefits of stroke self-management but concluding that the optimal delivery and timing remain unrecognised. The findings suggest that the impact of integrating self-management support from the beginning of inpatient rehabilitation should be further investigated. It is proposed that to realise the benefits of self-management, stroke survivors must be firstly empowered, actively involved in therapy and emotionally supported through the provision of multi-modal individualised education, peer support, and carer involvement during inpatient rehabilitation. Furthermore, the rehabilitation environment must be adapted to support stroke survivor empowerment and emotional well-being to foster motivation, self-management skills and self-efficacy. Without this shift in rehabilitation environments and without building a “foundation” to support self-management, stroke survivors are not being optimally supported to manage the sudden, life-changing, and chronic impacts of their condition.10.13039/501100001791Griffith University Honours Funds.Study supported by Joshua Dobe: Conceptualization, Methodology, Formal analysis, Investigation, Writing – original draft, Visualization, Project administration. Louise Gustafsson: Conceptualization, Methodology, Formal analysis, Investigation, Writing – review & editing, Visualization, Supervision, Project administration. Kim Walder: Conceptualization, Methodology, Formal analysis, Writing – review & editing, Supervision. Kylie Bower: Conceptualization, Methodology, Formal analysis, Writing – review & editing. Rosa Lachman: Conceptualization, Formal analysis, Writing – review & editing.None.


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