Mitigating sTNF/TNFR1 activation on VGluT2+ spinal cord interneurons improves immune function after mid-thoracic spinal cord injury.

Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual's outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-κB dependent in VGluT2+ INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.

Incidence, demographics, characteristics and management of acute Achilles tendon rupture: An epidemiological study.

BACKGROUND: Achilles tendon rupture (ATR) account for 10.7% of all tendon and ligament injuries and causes lasting muscular deficits and have a profound impact on patients' quality of life. The incidence, characteristics and management of ATR in the United Kingdom (UK) is poorly understood. This investigation aims to understand the incidence of ATR in the UK. METHODS: Prospective data collection of ATR incidence from a United Kingdom Emergency department. Retrospective review of management protocols and immobilisation duration from electronic medical records. RESULTS: ATR incidence is 8 per 100,000 people per annum. Participants were predominately male (79.2%) and primarily reported a sporting mechanism of injury (65.2%). Mean immobilisation duration was 63.1 days. 97.1% were non-surgically managed post ATR. 46.2% of participants had experienced a previous ATR or Achilles tendinopathy prior to their current ATR. CONCLUSION: The incidence of ATR found was 8. cases per 100,000 people per annum. Most ATR were managed non-surgically in this cohort. The majority of ruptures occurred during sporting activity. Almost one quarter (23.3%) of individuals report Achilles pain prior to ATR.

Variability in weather and site properties affect fuel and fire behavior following fuel treatments in semiarid sagebrush-steppe.

Fuel-treatments targeting shrubs and fire-prone exotic annual grasses (EAGs) are increasingly used to mitigate increased wildfire risks in arid and semiarid environments, and understanding their response to natural factors is needed for effective landscape management. Using field-data collected over four years from fuel-break treatments in semiarid sagebrush-steppe, we asked 1) how the outcomes of EAG and sagebrush fuel treatments varied with site biophysical properties, climate, and weather, and 2) how predictions of fire behavior using the Fuel Characteristic Classification System fire model related to land-management objectives of maintaining fire behavior expected of low-load, dry-climate grasslands. Generalized linear mixed effect modeling with build-up model selection was used to determine best-fit models, and marginal effects plots to assess responses for each fuel type. EAG cover decreased as antecedent-fall precipitation increased and increased as antecedent-spring temperatures and surface soil clay contents increased. Herbicides targeting EAGs were less effective where pre-treatment EAG cover was >40 % and antecedent spring temperatures were >9.5 °C. Sagebrush cover was inversely related to soil clay content, especially where clay contents were >17 %. Predicted fire behavior exceeded management objectives under 1) average fire weather conditions when EAG or sagebrush cover was >50 % or >26 %, respectively, or 2) extreme fire weather conditions when EAG or sagebrush cover was >10 % or >8 %, respectively. Consideration of the strong effects of natural variability in site properties and antecedent weather can help in justifying, planning and implementing fuel-treatments.

Resistance Training in Post-COVID Recovery: Rationale and Current Evidence.

During hospitalisation with COVID-19, individuals may experience prolonged periods of immobilisation. Combined with the inflammatory effects of the virus, this may lead to a significant reduction in both muscle mass and strength. Data from several long-term studies suggest that these symptoms may not fully resolve within one year. Owing to its effectiveness at inducing muscle fibre hypertrophy and improving neuromuscular efficiency, resistance training is of great interest in the rehabilitation of this population. This narrative review aims to identify the rationale and potential efficacy of resistance training for restoring physical function following infection with SARS-CoV-2, as well as evidence of its use in clinical practice. The studies included in this narrative review consisted mostly of multi-component rehabilitation trials. Of these, widespread improvements in muscle strength were reported using intensities of up to 80% of participants' 1-repetition-maximum. Evidence thus far indicates that resistance training may be safe and effective in patients following COVID-19, although its individual contribution is difficult to discern. Future exercise intervention studies investigating the efficacy of resistance training as a sole modality are needed.

Effects of combining electrical stimulation of the calf and thigh muscles in patients with osteoarthritis of the knee: protocol for a double-blind, randomised, sham-controlled trial.

INTRODUCTION: Knee osteoarthritis (KOA) is a leading cause of disability and is characterised by degenerative changes causing pain and loss of function. Neuromuscular electrical stimulation (NMES) has been shown to influence muscle size and strength in healthy subjects. A novel self-administered NMES device has been developed to help manage the symptoms of KOA. This study aims to investigate the effects of combining NMES of the calf and quadriceps on individuals with KOA. METHODS AND ANALYSIS: 193 individuals with KOA will be recruited to a single-centre, double-blind, randomised, sham-controlled trial at the Respiratory Biomedical Research Centre, Leicester, UK. Participants will be randomised (1:1) to follow an 8-week home-based intervention using a NMES device or sham device. The NMES device consists of footplate electrodes and two quadriceps electrodes. Footplate stimulation will be completed daily for 30 min and quadriceps stimulation for 20 min, five times a week (compliance is recorded in a self-reported participant diary). The primary outcome is the Western Ontario and McMaster Universities Arthritis Index pain domain, taken at 8 weeks follow-up. Secondary outcomes will explore quadriceps muscle strength, swelling, health-related quality of life, exercise capacity, anxiety and depression, sleep, physical activity and self-reported compliance. A powered subgroup analysis for compliance to the active device will be complete for the primary outcome. Participant focus groups will be completed following recruitment of half of the participants and after all participants have been recruited. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North-West Preston ethics committee (17/NW/0081). Participants are required to provide informed consent following review of the participant information sheet and discussion regarding study procedures with a member of the research team. The study results will be disseminated to the appropriate stakeholders through presentations, conferences and peer-reviewed journals. Results will be presented to participants following study completion at the Biomedical Research Centre-Respiratory, Glenfield Hospital, Leicester. TRIAL REGISTRATION NUMBER: ISRCTN registry, ISRCTN12112819 (date registered 1 May 2019). IRAS registry 219 693. University Hospitals of Leicester registry 91 017. Protocol Version 8.

Exploring the prevalence and impact of hip and knee pain in pulmonary rehabilitation: a propensity-matched cohort study.

BACKGROUND: Musculoskeletal pain is more common in individuals with chronic respiratory diseases than the aged-matched general population. This investigation aimed to understand the prevalence and impact of hip and knee pain on pulmonary rehabilitation outcomes and completion rates. METHODS: Participants who experienced hip/knee pain in the 4 weeks prior to pulmonary rehabilitation completed an Oxford Hip and/or Knee Score alongside a routine pulmonary rehabilitation assessment. Participants engaged in a twice-weekly, 6-week outpatient pulmonary rehabilitation programme. A 1:1 propensity score match for age, sex, BMI, sessions attended and MRC score was completed prior to group comparison for a pulmonary rehabilitation cohort without hip/knee pain. RESULTS: 6.5% (n = 97) of pulmonary rehabilitation participants reported pain: hip (n = 27), knee (n = 40) or hip and knee pain (n = 30). 75 participants with hip/knee pain provided sufficient data for pre pulmonary rehabilitation matching and were propensity matched with a pulmonary rehabilitation group without hip/knee pain. The average Oxford Score across all reported joints was 28.7 (8.5) indicating moderate/severe pain at baseline. Statistically significant improvements were made in Oxford Scores for the left hip, left knee and right knee (P < 0.01) but not the right hip following pulmonary rehabilitation. There was no statistically significant difference between groups for improvements in quadriceps strength, walking tests or depression scores, both groups achieved within group significance. There were no significant differences in pulmonary rehabilitation completion rates between groups. CONCLUSIONS: Prevalence of hip/knee pain in individuals presenting to pulmonary rehabilitation is 6.5%. Pain improved in the majority of joints following pulmonary rehabilitation and pain did not impact the effectiveness or completion of the programme. TRIAL REGISTRATION: This trial was an evaluation of a clinical service and has not been registered in a public domain.

A proof of concept for continuous, non-invasive, free-living vital signs monitoring to predict readmission following an acute exacerbation of COPD: a prospective cohort study.

BACKGROUND: The use of vital signs monitoring in the early recognition of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) post-hospital discharge is limited. This study investigated whether continuous vital signs monitoring could predict an AECOPD and readmission. METHODS: 35 people were recruited at discharge following hospitalisation for an AECOPD. Participants were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks and to complete the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item symptom diary, daily. The Equivital LifeMonitor recorded respiratory rate (RR), heart rate (HR), skin temperature (ST) and physical activity (PA) every 15-s. An AECOPD was classified as mild (by EXACT score), moderate (prescribed oral steroids/antibiotics) or severe (hospitalisation). RESULTS: Over the 6-week period, 31 participants provided vital signs and symptom data and 14 participants experienced an exacerbation, of which, 11 had sufficient data to predict an AECOPD. HR and PA were associated with EXACT score (p < 0.001). Three days prior to an exacerbation, RR increased by mean ± SD 2.0 ± 0.2 breaths/min for seven out of 11 exacerbations and HR increased by 8.1 ± 0.7 bpm for nine of these 11 exacerbations. CONCLUSIONS: Increased heart rate and reduced physical activity were associated with worsening symptoms. Even with high-resolution data, the variation in vital signs data remains a challenge for predicting AECOPDs. Respiratory rate and heart rate should be further explored as potential predictors of an impending AECOPD. TRIAL REGISTRATION: ISRCTN registry; ISRCTN12855961. Registered 07 November 2018-Retrospectively registered, https://www.isrctn.com/ISRCTN12855961.

Usability of Wearable Multiparameter Technology to Continuously Monitor Free-Living Vital Signs in People Living With Chronic Obstructive Pulmonary Disease: Prospective Observational Study.

BACKGROUND: Vital signs monitoring (VSM) is routine for inpatients, but monitoring during free-living conditions is largely untested in chronic obstructive pulmonary disease (COPD). OBJECTIVE: This study investigated the usability and acceptability of continuous VSM for people with COPD using wearable multiparameter technology. METHODS: In total, 50 people following hospitalization for an acute exacerbation of COPD (AECOPD) and 50 people with stable COPD symptoms were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks (42 days). The device recorded heart rate (HR), respiratory rate (RR), skin temperature, and physical activity. Adherence was defined by the number of days the vest was worn and daily wear time. Signal quality was examined, with thresholds of ≥85% for HR and ≥80% for RR, based on the device's proprietary confidence algorithm. Data quality was calculated as the percentage of wear time with acceptable signal quality. Participant feedback was assessed during follow-up phone calls. RESULTS: In total, 84% of participants provided data, with average daily wear time of 11.8 (SD 2.2) hours for 32 (SD 11) days (average of study duration 76%, SD 26%). There was greater adherence in the stable group than in the post-AECOPD group (≥5 weeks wear: 71.4% vs 45.7%; P=.02). For all 84 participants, the median HR signal quality was 90% (IQR 80%-94%) and the median RR signal quality was 93% (IQR 92%-95%). The median HR data quality was 81% (IQR 58%-91%), and the median RR data quality was 85% (IQR 77%-91%). Stable group BMI was associated with HR signal quality (rs=0.45, P=.008) and HR data quality (rs=0.44, P=.008). For the AECOPD group, RR data quality was associated with waist circumference and BMI (rs=-0.49, P=.009; rs=-0.44, P=.02). In total, 36 (74%) participants in the Stable group and 21 (60%) participants in the AECOPD group accepted the technology, but 10 participants (12%) expressed concerns with wearing a device around their chest. CONCLUSIONS: This wearable multiparametric technology showed good user acceptance and was able to measure vital signs in a COPD population. Data quality was generally high but was influenced by body composition. Overall, it was feasible to continuously measure vital signs during free-living conditions in people with COPD symptoms but with additional challenges in the post-AECOPD context.

COPD assessment test for the evaluation of COVID-19 symptoms.

There is evidence to demonstrate the ongoing symptoms of COVID-19; however, there are currently no agreed outcomes to assess these symptoms. This study examined the use of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) for patients recovering from COVID-19. 131 patients who were admitted with COVID-19 were followed up over the phone to assess symptoms. The median (IQR) CAT score was 10 (5-16). Cough, phlegm and chest tightness domains were within range for healthy people, but there was evidence of significant breathlessness, loss of energy, and activity and sleep disturbance. The CAT is a useful tool to assess symptoms of COVID-19 recovery.

Pepsin-pancreatin hydrolysis reduced the ability of lunasin-enriched material to inhibit activation of the inflammasomes in THP-1 human macrophages.

Inflammation caused by the NLRP3 inflammasome has been linked to many diseases. Lunasin is a bioactive peptide from soybeans with reported anti-inflammatory properties. The objective of this work was to determine the effect of pepsin-pancreatin hydrolysis (PPH) on the ability of lunasin-enriched preparation (LEP) to inhibit inflammasome activation in differentiated THP-1 human macrophages. THP-1 macrophages were treated with different concentrations of LEP (0.0625 to 0.25 mg mL-1), primed with 1 µg mL-1 lipopolysaccharide for 6 h and activated by 5 mM adenosine triphosphate for 1 h. LEP reduced secretion of IL-1ß and IL-18. In addition, LEP treatment inhibited the production of intracellular reactive oxygen species (ROS) in THP-1 human macrophages without affecting the expressions of NLRP3 and ASC proteins involved in inflammasomes. PPH reduced the ability of LEP to inhibit production of intracellular ROS. Our results showed that LEP inhibited activation of inflammasomes by reducing intracellular ROS in vitro which was reduced by PPH.

Kunitz trypsin inhibitor in addition to Bowman-Birk inhibitor influence stability of lunasin against pepsin-pancreatin hydrolysis.

Soybean contains several biologically active components and one of this belongs to the bioactive peptide group. The objectives of this study were to produce different lunasin-enriched preparations (LEP) and determine the effect of Bowman-Birk inhibitor (BBI) and Kunitz trypsin inhibitor (KTI) concentrations on the stability of lunasin against pepsin-pancreatin hydrolysis (PPH). In addition, the effect of KTI mutation on lunasin stability against PPH was determined. LEP were produced by calcium and pH precipitation methods of 30% aqueous ethanol extract from defatted soybean flour. LEP, lunasin-enriched commercially available products and KTI control and mutant flours underwent PPH and samples were taken after pepsin and pepsin-pancreatin hydrolysis. The concentrations of BBI, KTI, and lunasin all decreased after hydrolysis, but they had varying results. BBI concentration ranged from 167.5 to 655.8µg/g pre-hydrolysis and 171.5 to 250.1µg/g after hydrolysis. KTI concentrations ranged from 0.3 to 122.3µg/g pre-hydrolysis and 9.0 to 18.7µg/g after hydrolysis. Lunasin concentrations ranged from 8.5 to 71.0µg/g pre-hydrolysis and 4.0 to 13.2µg/g after hydrolysis. In all products tested, lunasin concentration after PPH significantly correlated with BBI and KTI concentrations. Mutation in two KTI isoforms led to a lower concentration of lunasin after PPH. This is the first report on the potential role of KTI in lunasin stability against PPH and must be considered in designing lunasin-enriched products that could potentially survive digestion after oral ingestion.

Highly conductive anion exchange membrane for high power density fuel-cell performance.

Anion exchange membrane fuel cells (AEMFCs) are regarded as a new generation of fuel cell technology that has the potential to overcome many obstacles of the mainstream proton exchange membrane fuel cells (PEMFCs) in cost, catalyst stability, efficiency, and system size. However, the low ionic conductivity and poor thermal stability of current anion exchange membranes (AEMs) have been the key factors limiting the performance of AEMFCs. In this study, an AEM made of styrenic diblock copolymer with a quaternary ammonium-functionalized hydrophilic block and a cross-linkable hydrophobic block and possessing bicontinuous phases of a hydrophobic network and hydrophilic conduction paths was found to have high ionic conductivity at 98 mS cm(-1) and controlled membrane swelling with water uptake at 117 wt % at 22 °C. Membrane characterizations and fuel cell tests of the new AEM were carried out together with a commercial AEM, Tokuyama A201, for comparison. The high ionic conductivity and water permeability of the new membrane reported in this study is attributed to the reduced torturosity of the ionic conduction paths, while the hydrophobic network maintains the membrane mechanical integrity, preventing excessive water uptake.

Development and revision of the Wittmann-Price Emancipated Decision-Making Scale.

BACKGROUND AND PURPOSE: The original Emancipated Decision-Making (EDM) scale was revised to test 3 subconcepts (flexible environment, personal knowledge, and awareness of social norms) of an emancipated decision-making process. METHODS: The original EDM scale was significantly related to the Satisfaction with Decision (SWD) scale in two separate studies (r = 0.79, r = 0.59). Two of the original 5 subconcepts showed a lack of contribution. The third study (N = 50) had good total scale reliability (r = 0.89). RESULTS: The revised EDM (EDM-r) scale was then leveled to the SWD scores and quantified into 2 categories and the subscales for the 3 subconcepts were reanalyzed for reliability and scale-if-item contribution. CONCLUSION: The final EDM-r is a generically worded, 20-item, 3-subscale instrument with good total and individual subscale reliability.

Relationships between Structure and Alkaline Stability of Imidazolium Cations for Fuel Cell Membrane Applications.

Anion exchange membranes have substantial potential to be useful in methanol fuel cells due to the viability of non-noble metal electrocatalysts at high pH and increases in the oxidation rate of methanol in alkaline conditions. However, long-term stability of the cationic moiety has been an issue, and imidazoliums have recently attracted attention as candidates for stable cations. The prevailing strategy for increasing the stability of the imidazolium has involved adding sterically hindering groups at the 2 position. Surprisingly, the findings of this study show that steric hindrance is the least effective strategy for stabilizing imidazoliums. We propose that the most important stabilizing factor for an imidazolium is the ability to provide alternative, reversible deprotonation reactions with hydroxide and outline other structure-property relationships for imidazolium cations.

Structure-property optimizations in donor polymers via electronics, substituents, and side chains toward high efficiency solar cells.

Many advances in organic photovoltaic efficiency are not yet fully understood and new insight into structure-property relationships is required to push this technology into broad commercial use. The aim of this article is not to comprehensively review recent work, but to provide commentary on recent successes and forecast where researchers should look to enhance the efficiency of photovoltaics. By lowering the LUMO level, utilizing electron-withdrawing substituents advantageously, and employing appropriate side chains on donor polymers, researchers can elucidate further aspects of polymer-PCBM interactions while ultimately developing materials that will push past 10% efficiency.

Parallel-like bulk heterojunction polymer solar cells.

Here we demonstrate a conceptually new approach, the parallel-like bulk heterojunction (PBHJ), which maintains the simple device configuration and low-cost processing of single-junction BHJ cells while inheriting the major benefit of incorporating multiple polymers in tandem cells. In this PBHJ, free charge carriers travel through their corresponding donor-polymer-linked channels and fullerene-enriched domain to the electrodes, equivalent to a parallel-like connection. The short-circuit current (J(sc)) of the PBHJ solar cell is nearly identical to the sum of those of the individual "subcells", while the open-circuit voltage (V(oc)) is between those of the "subcells". Preliminary optimization of the PBHJ devices gives improvements of up to 40% in J(sc) and 30% in overall efficiency (η) in comparison with single-junction BHJ devices.

Solution-processed flexible polymer solar cells with silver nanowire electrodes.

The conventional anode for organic photovoltaics (OPVs), indium tin oxide (ITO), is expensive and brittle, and thus is not suitable for use in roll-to-roll manufacturing of OPVs. In this study, fully solution-processed polymer bulk heterojunction (BHJ) solar cells with anodes made from silver nanowires (Ag NWs) have been successfully fabricated with a configuration of Ag NWs/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/polymer:phenyl-C(61)-butyric acid methyl ester (PCBM)/Ca/Al. Efficiencies of 2.8 and 2.5% are obtained for devices with Ag NW network on glass and on poly(ethylene terephthalate) (PET), respectively. The efficiency of the devices is limited by the low work function of the Ag NWs/PEDOT:PSS film and the non-ideal ohmic contact between the Ag NW anode and the active layer. Compared with devices based on the ITO anode, the open-circuit voltage (V(oc)) of solar cells based on the Ag NW anode is lower by ~0.3 V. More importantly, highly flexible BHJ solar cells have been firstly fabricated on Ag NWs/PET anode with recoverable efficiency of 2.5% under large deformation up to 120°. This study indicates that, with improved engineering of the nanowires/polymer interface, Ag NW electrodes can serve as a low-cost, flexible alternative to ITO, and thereby improve the economic viability and mechanical stability of OPVs.

Fluorine substituted conjugated polymer of medium band gap yields 7% efficiency in polymer-fullerene solar cells.

Recent research advances on conjugated polymers for photovoltaic devices have focused on creating low band gap materials, but a suitable band gap is only one of many performance criteria required for a successful conjugated polymer. This work focuses on the design of two medium band gap (~2.0 eV) copolymers for use in photovoltaic cells which are designed to possess a high hole mobility and low highest occupied molecular orbital and lowest unoccupied molecular orbital energy levels. The resulting fluorinated polymer PBnDT-FTAZ exhibits efficiencies above 7% when blended with [6,6]-phenyl C(61)-butyric acid methyl ester in a typical bulk heterojunction, and efficiencies above 6% are still maintained at an active layer thicknesses of 1 µm. PBnDT-FTAZ outperforms poly(3-hexylthiophene), the current medium band gap polymer of choice, and thus is a viable candidate for use in highly efficient tandem cells. PBnDT-FTAZ also highlights other performance criteria which contribute to high photovoltaic efficiency, besides a low band gap.