Exploring palliative care practice and learning needs of allied health professionals in the Loddon Mallee region of Victoria: a cross-sectional survey.

ObjectivesThe objectives of this study were to examine the roles and needs of allied health professionals (AHPs) working in public healthcare settings in rural and regional Victoria, Australia in providing components of palliative care in their routine practice.MethodsA cross-sectional study was conducted between March and May 2023. Surveys were collected from AHPs working in public healthcare settings in the Loddon Mallee region of Victoria, Australia. Clinicians reported on the frequency of provision of care to patients with terminal illness, and their self-reported skill and confidence in providing interventions to patients with palliative care needs.ResultsIn total, 121 clinicians completed the survey. Almost every respondent reported they had provided care to patients with a terminal illness, with 41% of clinicians providing this care daily or weekly. The respondents were confident carrying out generalist interventions such as maintaining physical function but reported lower confidence in managing common symptoms of terminal illness such as loss of appetite, swallowing difficulties and changing communication needs. Two-thirds of respondents had not undertaken any training specific to palliative care, with many unaware of how to access palliative care-specific training.ConclusionAHPs in rural and remote areas regularly provide care to patients with terminal illness. As the number of patients seen in non-specialist palliative care settings is likely to increase in rural and regional areas, the low self-reported confidence in providing common components of care, and the low uptake of palliative care-specific training must be addressed to ensure AHPs can provide high-quality care to people with terminal illness.

Telehealth-Delivered Allied Health Interventions: A Rapid Umbrella Review of Systematic Reviews.

Introduction: Telehealth is used by allied health professionals to deliver health care remotely. This umbrella review addressed the following questions: (1) What telehealth interventions have been implemented to deliver allied health care? (2) What are the reported clinical benefits, and challenges of the implementation of telehealth delivered allied health interventions? (3) What are the reported experiences of patients and clinicians? Methods: A rapid umbrella systematic review method was utilized. Following a search of five electronic databases, only systematic reviews reporting on telehealth-delivery allied health interventions published in the past 10 years were included. Reported outcomes included clinical effectiveness, implementation factors, and patient/clinician experiences. Methodological quality was established using the A MeaSurement Tool to Assess systematic Reviews 2. Results: After applying eligibility criteria to 571 studies, 26 studies were included. Findings indicate that telehealth-delivered allied health interventions may obtain similar clinical outcomes as compared with face-to-face appointments. Patients reported less stress and valued the reduced need to travel when telehealth was used. Patient satisfaction with telehealth delivered care was equal to face-to-face care, and no differences were noted in the capacity to build therapeutic alliance when using telehealth. Difficulties with technology use were reported by clinicians and patients. Clinicians were identified as needing increased time management skills. Cautious interpretation of findings is recommended due to the quality rating of low to critical low for the majority of individual reviews. Conclusions: Telehealth-delivered care might obtain similar clinical outcomes to face-to-face care; however, difficulties may arise during broad implementation. It is recommended that health services be strategic to overcome implementation barriers and provide targeted support to enable effective, equitable, and sustained allied health service delivery via telehealth.

Management of stable proximal interphalangeal joint volar plate injuries with figure-of-8 orthoses: A parallel-group randomized controlled trial.

BACKGROUND: Volar plate injuries of the proximal interphalangeal (PIP) finger joint are common. Conservative treatment involves orthoses to limit hyperextension at the PIP joint yet allow movement of the joints to prevent joint stiffness and deformity. Custom-made dorsal blocking orthoses are recommended treatments. Previous research also supports the use of a figure-of-8 orthosis, although the comparative effectiveness of these orthoses is not currently known. PURPOSE: This study aimed to compare the figure-of-8 orthosis and dorsal blocking orthosis for changes in the range of movement, pain, and function following stable volar plate PIP joint injuries and to compare the number of hand therapy appointments required. STUDY DESIGN: A parallel-group pilot randomized controlled trial. This trial was registered with the Australian and New Zealand Clinical Trials Registry (Trial ID: CTRN12619000449134). METHODS: Participants aged 13-65 years were recruited from an outpatient hand therapy service and randomly assigned to experimental or control groups. The experimental group of 20 participants received a custom-made thermoplastic figure-of-8 orthosis limiting the extension to 15-20 degrees. The control group of 22 participants had a dorsal blocking orthosis, which was serially extended by 10 degrees weekly starting at 30 degrees flexion. Participants were blinded to their group allocation. Outcome measures included range of movement, edema, pain, function, and number of hand therapy appointments. Data collection was completed by the treating therapist who was not blinded to group assignment. Data analysis included a series of mixed-model analyses of variance to examine changes over time. RESULTS: Forty-two participants were recruited and had their data analyzed. No significant between-group differences were observed for DIP flexion, PIP flexion, pain, and function from baseline to follow-up. Both groups exhibited significant improvements in these outcomes over time (p < 0.001); effect sizes ranged from small to large (0.28-0.79). On average, the intervention group required 4 (±1.5) appointments compared to 6 (±1.5) in the control group over the same period representing a significant difference (p < 0.001). CONCLUSIONS: Both dorsal blocking and figure-of-8 orthoses provide similar outcomes. The use of a figure-of-8 orthosis, or a dorsal block orthosis fabricated in maximal comfortable extension depending on severity, could reduce the number of appointments and increase convenience for patients.

Molecular magnetic resonance imaging of liver inflammation using an oxidatively activated probe.

Background & Aims: Many liver diseases are driven by inflammation, but imaging to non-invasively diagnose and quantify liver inflammation has been underdeveloped. The inflammatory liver microenvironment is aberrantly oxidising owing in part to reactive oxygen species generated by myeloid leucocytes. We hypothesised that magnetic resonance imaging using the oxidatively activated probe Fe-PyC3A will provide a non-invasive biomarker of liver inflammation. Methods: A mouse model of drug-induced liver injury was generated through intraperitoneal injection of a hepatoxic dose of acetaminophen. A mouse model of steatohepatitis was generated via a choline-deficient, l-amino acid defined high-fat diet (CDAHFD). Images were acquired dynamically before and after intravenous injection of Fe-PyC3A. The contrast agent gadoterate meglumine was used as a non-oxidatively activated negative control probe in mice fed CDAHFD. The (post-pre) Fe-PyC3A injection change in liver vs. muscle contrast-to-noise ratio (ΔCNR) recorded 2 min post-injection was correlated with liver function test values, histologic scoring assigned using the NASH Clinical Research Network criteria, and intrahepatic myeloid leucocyte composition determined by flow cytometry. Results: For mice receiving i.p. injections of acetaminophen, intrahepatic neutrophil composition correlated poorly with liver test values but positively and significantly with ΔCNR (r = 0.64, p <0.0001). For mice fed CDAHFD, ΔCNR generated by Fe-PyC3A in the left lobe was significantly greater in mice meeting histologic criteria strongly associated with a diagnosis NASH compared to mice where histology was consistent with likely non-NASH (p = 0.0001), whereas no differential effect was observed using gadoterate meglumine. In mice fed CDAHFD, ΔCNR did not correlate strongly with fractional composition of any specific myeloid cell subpopulation as determined by flow cytometry. Conclusions: Magnetic resonance imaging using Fe-PyC3A merits further evaluation as a non-invasive biomarker for liver inflammation. Impact and implications: Non-invasive tests to diagnose and measure liver inflammation are underdeveloped. Inflammatory cells such as neutrophils release reactive oxygen species which creates an inflammatory liver microenvironment that can drive chemical oxidation. We recently invented a new class of magnetic resonance imaging probe that is made visible to the scanner only after chemical oxidation. Here, we demonstrate how this imaging technology could be applied as a non-invasive biomarker for liver inflammation.

The role of ultrasound-guided perineural injection of the tibial nerve with a sub-anesthetic dosage of lidocaine for the diagnosis of tarsal tunnel syndrome.

Background: Tarsal tunnel syndrome (TTS) involves entrapment of the tibial nerve at the medial ankle beneath the flexor retinaculum and its branches, the medial and lateral plantar nerves, as they course through the porta pedis formed by the deep fascia of the abductor hallucis muscle. TTS is likely underdiagnosed, because diagnosis is based on clinical evaluation and history of present illness. The ultrasound-guided lidocaine infiltration test (USLIT) is a simple approach that may aid in the diagnosis of TTS and predict the response to neurolysis of the tibial nerve and its branches. Traditional electrophysiological testing cannot confirm the diagnosis and only adds to other findings. Methods: We performed a prospective study of 61 patients (23 men and 38 women) with a mean age of 51 (29-78) years who were diagnosed with idiopathic TTS using the ultrasound guided near-nerve needle sensory technique (USG-NNNS). Patients subsequently underwent USLIT of the tibial nerve to assess the effect on pain reduction and neurophysiological changes. Results: USLIT led to an improvement in symptoms and nerve conduction velocity. The objective improvement in nerve conduction velocity can be used to document the pre-operative functional capacity of the nerve. USLIT may also be used as a possible quantitative indicator of whether the nerve has the potential to improve in neurophysiological terms and ultimately inform prognosis after surgical decompression. Conclusion: USLIT is a simple technique with potential predictive value that can help the clinician to confirm the diagnosis of TTS before surgical decompression.

Novel Biotinylated Cu(II)-Phenanthroline Complexes: 2D and 3D Cytotoxic Activity and Mechanistic Insight.

The interest in the use of copper as a metal scaffold for the development of novel chemotherapeutics has considerably grown in recent years. This is mainly due to the relatively lower toxicity of copper complexes with respect to platinum drugs (i.e., cisplatin), the different mechanisms of action, and the cheaper cost. In the last decades, hundreds of copper-based complexes were developed and screened as anticancer agents, with the antesignanus of all compounds being copper bis-phenanthroline [Cu(phen)2]2+ developed by D.S. Sigman in the late 1990s. In particular, copper(phen) derivatives have been shown high interest in their capacity to interact with DNA by nucleobase intercalation. Here, we report the synthesis and chemical characterization of four novel copper(II) complexes functionalised with phenanthroline derivatives containing biotin. Biotin, also known as Vitamin B7, is involved in a series of metabolic processes, and its receptors are often overexpressed in many tumour cells. A detailed biological analysis including cytotoxicity in 2D and 3D, cellular drug uptake, DNA interaction, and morphological studies are discussed.

The effect of motivational interviewing and/or cognitive behaviour therapy techniques on gestational weight gain - a systematic review and meta-analysis.

BACKGROUND: Women with gestational weight gain (GWG) that is below or above recommendations are at risk of adverse perinatal outcomes. Motivational interviewing and/or cognitive behaviour therapy have demonstrated efficacy in initiating and sustaining behaviour change, including weight control. The objective of this review was to investigate the effect of antenatal interventions that include components of motivational interviewing and/or cognitive behaviour therapy on gestational weight gain. METHODS: This review was designed and reported in accordance with guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Five electronic databases were systematically searched to March 2022. Randomised controlled trials evaluating interventions with identified components of motivational interviewing and/or cognitive behaviour therapies were included. Pooled proportions of appropriate GWG and GWG above or below guidelines, and standardised mean difference for total gestational weight gain, were calculated. Risk of bias in included studies was evaluated using the Risk of Bias 2 tool, and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence. RESULTS: Twenty-one studies (8030 participants) were included. Overall, MI and/or CBT interventions had a small effect on the total gestational weight gain (SMD: -0.18, 95% confidence interval: -0.27 to -0.09, p < 0.001) and improved the proportion of women achieving recommended gestational weight gain (29% versus 23% in the comparison, p < 0.001). The GRADE assessment indicated that overall quality of evidence is very uncertain, however sensitivity analyses to account for high risk of bias produced similar results to original meta-analyses. The magnitude of effect was greater in women with overweight or obesity when compared to women with BMI < 25 kg/m2. CONCLUSION: Motivational interviewing and/or cognitive behaviour therapy techniques may be effective for promoting healthy gestational weight gain. Nevertheless, a high proportion of women do not achieve recommended gestational weight gain. Future interventions should consider factors, including clinician and consumer perspectives, in the design and delivery of psychosocial interventions that aim to support healthy gestational weight gain. TRIAL REGISTRATION: The protocol for this review was registered with the PROSPERO International register of systematic reviews (registration number CRD42020156401).

Fast detection of liver fibrosis with collagen-binding single-nanometer iron oxide nanoparticles via T1-weighted MRI.

SNIO-CBP, a single-nanometer iron oxide (SNIO) nanoparticle functionalized with a type I collagen-binding peptide (CBP), was developed as a T1-weighted MRI contrast agent with only endogenous elements for fast and noninvasive detection of liver fibrosis. SNIO-CBP exhibits 6.7-fold higher relaxivity compared to a molecular gadolinium-based collagen-binding contrast agent CM-101 on a per CBP basis at 4.7 T. Unlike most iron oxide nanoparticles, SNIO-CBP exhibits fast elimination from the bloodstream with a 5.7 min half-life, high renal clearance, and low, transient liver enhancement in healthy mice. We show that a dose of SNIO-CBP that is 2.5-fold lower than that for CM-101 has comparable imaging efficacy in rapid (within 15 min following intravenous injection) detection of hepatotoxin-induced liver fibrosis using T1-weighted MRI in a carbon tetrachloride-induced mouse liver injury model. We further demonstrate the applicability of SNIO-CBP in detecting liver fibrosis in choline-deficient L-amino acid-defined high-fat diet mouse model of nonalcoholic steatohepatitis. These results provide a platform with potential for the development of high relaxivity, gadolinium-free molecular MRI probes for characterizing chronic liver disease.

Molecular MRI quantification of extracellular aldehyde pairs for early detection of liver fibrogenesis and response to treatment.

Liver fibrosis plays a critical role in the evolution of most chronic liver diseases and is characterized by a buildup of extracellular matrix, which can progress to cirrhosis, hepatocellular carcinoma, liver failure, or death. Now, there are no noninvasive methods available to accurately assess disease activity (fibrogenesis) to sensitively detect early onset of fibrosis or to detect early response to treatment. Here, we hypothesized that extracellular allysine aldehyde (LysAld) pairs formed by collagen oxidation during active fibrosis could be a target for assessing fibrogenesis with a molecular probe. We showed that molecular magnetic resonance imaging (MRI) using an extracellular probe targeting these LysAld pairs acts as a noninvasive biomarker of fibrogenesis and demonstrated its high sensitivity and specificity in detecting fibrogenesis in toxin- and dietary-induced mouse models, a cholestasis rat model of liver fibrogenesis, and in human fibrotic liver tissues. Quantitative molecular MRI was highly correlated with fibrogenesis markers and enabled noninvasive detection of early onset fibrosis and response to antifibrotic treatment, showing high potential for clinical translation.

Inhibition of microbial deconjugation of micellar bile acids protects against intestinal permeability and liver injury.

Altered host-microbe interactions and increased intestinal permeability have been implicated in disease pathogenesis. However, the mechanisms by which intestinal microbes affect epithelial barrier integrity remain unclear. Here, we investigate the impact of bacterial metabolism of host-produced bile acid (BA) metabolites on epithelial barrier integrity. We observe that rats fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) exhibit reduced intestinal abundance of host-produced conjugated BAs at early time points, coinciding with increased gut permeability. We show that in vitro, conjugated BAs protect gut epithelial monolayers from damage caused by bacterially produced unconjugated BAs through micelle formation. We then demonstrate that inhibition of bacterial BA deconjugation with a small-molecule inhibitor prevents the development of pathologic intestinal permeability and hepatic inflammation in CDAHFD-fed rats. Our study identifies a signaling-independent, physicochemical mechanism for conjugated BA-mediated protection of epithelial barrier function and suggests that rational manipulation of microbial BA metabolism could be leveraged to regulate gut barrier integrity.

Dual Hydrazine-Equipped Turn-On Manganese-Based Probes for Magnetic Resonance Imaging of Liver Fibrogenesis.

Liver fibrogenesis is accompanied by upregulation of lysyl oxidase enzymes, which catalyze oxidation of lysine ε-amino groups on the extracellular matrix proteins to form the aldehyde containing amino acid allysine (LysAld). Here, we describe the design and synthesis of novel manganese-based MRI probes with high signal amplification for imaging liver fibrogenesis. Rational design of a series of stable hydrazine-equipped manganese MRI probes gives Mn-2CHyd with the highest affinity and turn-on relaxivity (4-fold) upon reaction with LysAld. A dynamic PET-MRI study using [52Mn]Mn-2CHyd showed low liver uptake of the probe in healthy mice. The ability of the probe to detect liver fibrogenesis was then demonstrated in vivo in CCl4-injured mice. This study enables further development and application of manganese-based hydrazine-equipped probes for imaging liver fibrogenesis.

Factors influencing adults who participate in a physical activity coaching intervention: a theoretically informed qualitative study.

OBJECTIVE: Behaviour change interventions targeting changes in physical activity (PA) can benefit by examining the underlying mechanisms that promote change. This study explored the use of the Capability, Opportunity, Motivation and Behaviour (COM-B) model and the Theoretical Domains Framework (TDF) to code and contextualise the experiences of participants who completed a PA coaching intervention underpinned by motivational interviewing and cognitive-behavioural therapy. DESIGN: Semistructured interviews were conducted with a purposive sample of participants. SETTING: Interviews were conducted in a tertiary hospital in regional Victoria, Australia. PARTICIPANTS: Eighteen participants who completed a PA coaching intervention were interviewed. The participants were recruited into the coaching intervention because they were insufficiently physically active at the time of recruitment. RESULTS: Thirteen (72%) participants were women and the average age of participants was 54 (±5) years. Four participant themes mapped directly onto five components of the COM-B model, and ten of the TDF domains. Increases in PA were influenced by changes in motivation and psychological capability. The autonomy-supportive PA coaching intervention helped to evoke participants' own reasons (and motives) for change and influenced PA behaviours. Participants reflected on their own social and/or professional strengths, and used these skills to set appropriate PA goals and action plans. The structure of the PA coaching intervention provided clarity on session determinants and a framework from which to set an appropriate agenda. Relational components (eg, non-judgemental listening, collaboration) were continually highlighted as influential for change, and should be considered in future behaviour change intervention design. CONCLUSIONS: We demonstrate the beneficial effect of using theory-informed behaviour change techniques, and delivering them in a style that promotes autonomy and relatedness. The views of participants should be a key consideration in the design and implementation of PA coaching interventions TRIAL REGISTRATION NUMBER: ACTRN12619000036112. Post-results analysis.

Hepatocellular carcinoma chemoprevention by targeting the angiotensin-converting enzyme and EGFR transactivation.

Hepatocellular carcinoma (HCC) is a leading cause of death among cirrhotic patients, for which chemopreventive strategies are lacking. Recently, we developed a simple human cell-based system modeling a clinical prognostic liver signature (PLS) predicting liver disease progression and HCC risk. In a previous study, we applied our cell-based system for drug discovery and identified captopril, an approved angiotensin converting enzyme (ACE) inhibitor, as a candidate compound for HCC chemoprevention. Here, we explored ACE as a therapeutic target for HCC chemoprevention. Captopril reduced liver fibrosis and effectively prevented liver disease progression toward HCC development in a diethylnitrosamine (DEN) rat cirrhosis model and a diet-based rat model for nonalcoholic steatohepatitis-induced (NASH-induced) hepatocarcinogenesis. RNA-Seq analysis of cirrhotic rat liver tissues uncovered that captopril suppressed the expression of pathways mediating fibrogenesis, inflammation, and carcinogenesis, including epidermal growth factor receptor (EGFR) signaling. Mechanistic data in liver disease models uncovered a cross-activation of the EGFR pathway by angiotensin. Corroborating the clinical translatability of the approach, captopril significantly reversed the HCC high-risk status of the PLS in liver tissues of patients with advanced fibrosis. Captopril effectively prevents fibrotic liver disease progression toward HCC development in preclinical models and is a generic and safe candidate drug for HCC chemoprevention.

Physical activity telephone coaching intervention for insufficiently physically active ambulatory hospital patients: Economic evaluation of the Healthy 4U-2 randomised controlled trial.

The Healthy 4U-2 randomised controlled trial demonstrated that a physical activity (PA) telephone coaching intervention was effective for improving objectively-measured PA and health-related outcomes. The current study reports on an economic evaluation performed alongside the trial to determine whether this effective intervention is also cost-effective from a healthcare funder perspective. Participants (N = 120) were insufficiently physically active adults recruited from an ambulatory care clinic in a public hospital in regional Australia. The primary outcome was change in moderate-to-vigorous physical activity (MVPA) measured using accelerometers. Changes in quality-adjusted life-years (QALYs) were derived from the 12-Item Short Form Health Survey Questionnaire (SF-12). Incremental cost-effectiveness ratios (ICERs) were calculated for each outcome. Uncertainty of cost-effectiveness results were estimated using non-parametric bootstrapping techniques and sensitivity analyses. The mean intervention cost was $132 per person. The control group incurred higher overall costs compared to intervention ($2,465 vs. $1,743, respectively). Relative to control, the intervention resulted in incremental improvements in MVPA and QALYs and was deemed cost-effective. Probabilistic sensitivity analysis indicated that compared to control, the intervention would be cost-effective for improving MVPA and QALYs at very low willingness to pay thresholds. Sensitivity analyses indicated that results were robust to varied assumptions. This study shows that PA telephone coaching was a low-cost strategy for increasing MVPA and QALYs in insufficiently active ambulatory hospital patients. Findings of health benefits and overall cost-savings are uncommon and PA telephone coaching offers a potentially cost-effective investment to produce important public health outcomes.

"Exercise Is My Medicine": A Qualitative Study Exploring the Experiences of Non-admitted Patients Receiving Physical Activity Promotion From Hospital Surgeons.

Background: Hospital clinicians are increasingly encouraged to use outpatient consultations as an avenue to deliver opportunistic health promotion. There is a dearth of evidence regarding the acceptance of health promotion initiatives from hospital patients themselves. Methods: We explored the experiences of non-admitted patients who, during a routine consultation with a hospital surgeon received a recommendation to increase physical activity (PA) and a recommendation to engage in a PA telephone coaching program. Twenty-two semi-structured interviews were conducted with individuals who had received the recommendation and proceeded to enroll in a telephone coaching intervention to identify factors that influenced behavior change. Data were analyzed thematically. Results: Participants' age ranged between 42 and 66 years, with the average age being 54 years. Of the participants, 15 (68%) were women and 7 (32%) were men. Three major themes were identified: (1) the hospital visit represented an opportunity for behavior change that is not to be missed; (2) surgeons were influential in promoting PA change contemplation; and (3) patients welcomed a communication style that promoted autonomy. Conclusions: Almost all patients considered receiving the recommendation to engage with the telephone coaching as acceptable and helpful toward PA change. Although working in time-restricted consultations, surgeons delivered the recommendation in a patient-centered, autonomy-supportive way, which influenced behavior change. Hospitals should explore avenues to integrate health promotion into routine care, confident of the acceptability and appropriateness of health promotion practice to hospital patients.

Peroxidasin Deficiency Re-programs Macrophages Toward Pro-fibrolysis Function and Promotes Collagen Resolution in Liver.

BACKGROUND & AIMS: During liver fibrosis, tissue repair mechanisms replace necrotic tissue with highly stabilized extracellular matrix proteins. Extracellular matrix stabilization influences the speed of tissue recovery. Here, we studied the expression and function of peroxidasin (PXDN), a peroxidase that uses hydrogen peroxide to cross-link collagen IV during liver fibrosis progression and regression. METHODS: Mouse models of liver fibrosis and cirrhosis patients were analyzed for the expression of PXDN in liver and serum. Pxdn-/- and Pxdn+/+ mice were either treated with carbon tetrachloride for 6 weeks to generate toxin-induced fibrosis or fed with a choline-deficient L-amino acid-defined high-fat diet for 16 weeks to create nonalcoholic fatty liver disease fibrosis. Liver histology, quantitative real-time polymerase chain reaction, collagen content, flowcytometry and immunostaining of immune cells, RNA-sequencing, and liver function tests were analyzed. In vivo imaging of liver reactive oxygen species (ROS) was performed using a redox-active iron complex, Fe-PyC3A. RESULTS: In human and mouse cirrhotic tissue, PXDN is expressed by stellate cells and is secreted into fibrotic areas. In patients with nonalcoholic fatty liver disease, serum levels of PXDN increased significantly. In both mouse models of liver fibrosis, PXDN deficiency resulted in elevated monocyte and pro-fibrolysis macrophage recruitment into fibrotic bands and caused decreased accumulation of cross-linked collagens. In Pxdn-/- mice, collagen fibers were loosely organized, an atypical phenotype that is reversible upon macrophage depletion. Elevated ROS in Pxdn-/- livers was observed, which can result in activation of hypoxic signaling cascades and may affect signaling pathways involved in macrophage polarization such as TNF-a via NF-kB. Fibrosis resolution in Pxdn-/- mice was associated with significant decrease in collagen content and improved liver function. CONCLUSION: PXDN deficiency is associated with increased ROS levels and a hypoxic liver microenvironment that can regulate recruitment and programming of pro-resolution macrophages. Our data implicate the importance of the liver microenvironment in macrophage programming during liver fibrosis and suggest a novel pathway that is involved in the resolution of scar tissue.

Quantifying the Peak Physical Match-Play Demands of Professional Soccer Substitutes Following Pitch-Entry: Assessing Contextual Influences.

Purpose: To quantify the peak post-pitch-entry physical responses of soccer substitutes while assessing contextual influences. Peak responses may be important performance indicators for substitutes introduced to provide a physical impact. Method: Thirty-three professional substitutes wore Microelectromechanical Systems during 44 matches (4 ± 3 observations·player-1). Post-pitch-entry relative peak values for total and high-speed (> 5.5 m·s-1) distances, average acceleration, and PlayerLoad™ were calculated using rolling averages over 60-s to 600-s. Linear mixed models assessed contextual influences (position, substitution timing, scoreline, and location). Results: Substitutes introduced during the final ~15 min of match-play covered less high-speed distance than first-half substitutes (~2.8-3.1 m·min-1) over 480-s to 600-s epochs, and less than 60:00-74:59 min substitutes (~1.7-1.8 m·min-1) during 540-s and 600-s epochs. Average acceleration during all except 180-s epochs was lower for 75:00+ min substitutes compared with first-half replacements (~0.27-0.43 m·s-2), and lower than 60:00-74:59 min substitutes during 60-s (~0.13 m·s-2). Substitutes introduced when their team was winning recorded greater distances over 120-s to 600-s (~6.2-7.7 m·min-1), and higher PlayerLoad™ values during 120-s, 180-s, 300-s, and 480-s epochs (~2.7-3.6 arbitrary units·min-1), compared with when scores were level at pitch-entry. Irrespective of substitution timing, substitute midfielders exceeded the total distance of substitute attackers (~5.9-16.2 m·min-1) for all except 360-s and 600-s epochs, and defenders (~13.3-26.7 m·min-1) during epochs < 300-s. Conclusions: This study provides benchmark data for practitioners tailoring training and recovery protocols, particularly "top-up" conditioning, to the competitive demands of soccer substitutes. Knowing how contextual factors influence substitutes' peak match-play responses may help managers/coaches assess the efficacy of substitution strategies.

The Effect of a Physical Activity Coaching Intervention on Accelerometer-Measured Sedentary Behaviours in Insufficiently Physically Active Ambulatory Hospital Patients.

Little is known about the impact that physical activity (PA) coaching interventions have on sedentary behaviours. The aim of this study was to investigate if a coaching intervention that increases PA coincidentally influences objectively measured sedentary time in insufficiently physically active adults. We recruited 120 insufficiently physically active ambulatory hospital patients and randomized them to either receive a PA coaching intervention designed to increase objectively measured moderate-to-vigorous-intensity PA (MVPA) or be part of a control group. Participants wore an accelerometer for seven days at baseline, post-intervention (three months) and follow-up (nine months). Changes in the average length of sedentary bouts, proportion of time in sedentary behaviours and number of sedentary bouts were evaluated using mixed-model ANOVAs. At baseline, both groups undertook 67 ± 13 sedentary bouts and spent 69% ± 6% of their time in sedentary behaviours. Compared with control, the intervention group decreased the number of sedentary bouts by 24% and the proportion of time in sedentary behaviours by 7% (p < 0.001). Significant changes were not observed between the groups for average length of sedentary bouts. The PA intervention led to a decrease in the number of sedentary bouts and proportion of time in sedentary behaviours. Future research should investigate PA coaching interventions designed to target simultaneous changes in MVPA and sedentary behaviours.

Midarch Foot Pain: Entrapment Neuropathy of the Distal Medial Plantar Nerve and Its Branches.

Medial forefoot pain, or midarch pain, is usually attributed to plantar fasciitis. The authors present their findings of a previously unreported nerve entrapment of the medial proper plantar digital nerve (MPPDN). Ten fresh-frozen cadaveric specimens were analyzed for anatomical variance in the nerve distribution of the MPPDN. In addition, clinical results from a retrospective review of nine patients who underwent surgical nerve decompression of the MPPDN are presented. Significant anatomical variance was found for the MPPDN in the cadaveric dissection of 10 fresh-frozen specimens. Nine patients with a clinical diagnosis of entrapment of the MPPDN all obtained excellent pain relief with surgical external neurolysis. Only one complication occurred: a hypertrophic scar formation that was successfully treated with intralesional steroid injections. The authors believe that this MPPDN entrapment is often overlooked or misdiagnosed as plantar fasciitis. Surgical peripheral nerve decompression of this nerve can provide positive outcomes for patients suffering from midarch foot pain caused by this pain generator.