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Background: Evidence supports establishing a continuum of care from stroke rehabilitation (SR) to cardiac rehabilitation programs (CRPs). It is not known to what extent people poststroke are being integrated. This study aimed to determine the proportion of CRPs that accept referrals poststroke, barriers/facilitators, and eligibility criteria. Methods: A web-based questionnaire was sent to CRPs across Canada. Results: Of 160 questionnaires sent, 114 representatives (71%) of 130 CRPs responded. Of respondents, 65% (n = 74) reported accepting people with a diagnosis of stroke and doing so for a median of 11 years, 11 offering stroke-specific classes and an additional 6 planning inclusion. However, 62.5% of CRPs reported that < 11 patients participated in the last calendar year despite 88.5% reporting no limit to the number they could enroll. Among CRPs, 25% accepted only patients with concurrent cardiac diagnoses, living in the community (47.8%), and without severe mobility (70.1%), communication (80.6%), or cognitive (85.1%) deficits. The 2 most influential barriers and facilitators among all CRPs were funding and staffing. The fourth greatest barrier was lack of poststroke referrals, and third to sixth facilitators were SR/CRP collaboration to ensure appropriate referrals (third) and to increase referrals (sixth), toolkits for prescribing resistance (fourth), and aerobic training (fifth). CRP characteristics associated with accepting stroke were a hybrid program model, a medium program size, and having a falls prevention component. Conclusions: Most CRPs accept patients poststroke, but few participate. Therefore, establishing SR/CRP partnerships to increase appropriate referrals, using a toolkit to help operationalize exercise components, and allocating funding/resources to CRPs may significantly increase access to secondary prevention strategies. Résumé: Contexte: Les données recueillies appuient la continuité des soins entre les programmes de réadaptation après un accident vasculaire cérébral (PR-AVC) et les programmes de réadaptation cardiaque (PRC). On ne sait toutefois pas dans quelle mesure les patients qui ont subi un accident vasculaire cérébral (AVC) sont intégrés à un PRC. L’étude visait donc à déterminer la proportion de PRC admettant les patients ayant subi un AVC, les obstacles à l’intégration de ces derniers et les éléments qui la facilitent, ainsi que les critères d’admissibilité. Méthodologie: Des responsables de PRC de partout au Canada ont été invités à répondre à un questionnaire en ligne. Résultats: Au total, 160 invitations ont été envoyées et 114 (71 %) responsables rattachés à 130 PRC y ont répondu. Parmi ces répondants, 65 % (n = 74) ont dit que leur programme admettait depuis un nombre médian de 11 ans les patients ayant reçu un diagnostic d’AVC; 11 programmes offraient des cours spécialement destinés aux patients ayant subi un AVC et 6 autres prévoyaient de le faire. Toutefois, 62,5 % des répondants ont souligné que moins de 11 patients avaient participé à leur programme au cours de l’année qui précédait, malgré le fait que dans 88,5 % des cas, il n’y avait pas de limite au nombre de participants admis. Parmi les PRC, 25 % n’admettaient que des patients ayant aussi reçu un diagnostic d’atteinte cardiaque, vivant dans la collectivité (47,8 %) et n’ayant pas de déficit sévère sur les plans de la mobilité (70,1 %), de la communication (80,6 %) ou de la fonction cognitive (85,1 %). Dans tous les cas, les deux facteurs influant le plus (positivement ou négativement, selon le cas) sur l’intégration des patients ayant subi un AVC étaient les ressources financières et les ressources humaines. Le quatrième obstacle en importance était le faible nombre de patients ayant subi un AVC orientés vers les programmes; les autres éléments facilitateurs également recensés étaient la collaboration entre les PR-AVC et les PRC afin d’assurer l’orientation des patients concernés (3e place), l’augmentation du nombre de ces orientations (6e place), ainsi que les outils permettant de prescrire un programme d’entraînement musculaire (4e place) et un programme d’entraînement aérobique (5e place). Les PRC admettant des patients ayant subi un AVC avaient en commun les caractéristiques suivantes : ils reposaient sur un modèle hybride, ils étaient de taille moyenne et ils comprenaient un volet sur la prévention des chutes. Conclusions: Si la plupart des PRC admettent les patients qui ont subi un AVC, ces derniers sont peu nombreux à y participer. L’établissement de partenariats entre les PR-AVC et les PRC afin d’augmenter le nombre de patients orientés, la mise en place d’outils facilitant l’exécution de programmes d’exercice physique et l’affectation de fonds et de ressources aux PRC pourraient donc augmenter considérablement l’accès aux stratégies de prévention secondaire.

Objective . Chemotherapy-induced peripheral neuropathy (CIPN) syndrome causes significant pain as an adverse effect of treatment, with few nonpharmacological interventions tested. A somatic yoga and meditation (SYM) intervention on functional outcomes and quality of life (QOL) was investigated. Design and methods . Individuals diagnosed with CIPN were enrolled in an open-label, single-arm, mixed-methods feasibility trial. Participants and Setting . In an outpatient rehabilitation center, ten participants with median age 64.4 years (47-81) attended 61% of the sessions with no adverse events. Intervention . SYM twice a week for 8 weeks for 1.5 hours, with home program and journaling. Main outcome measures . Primary functional outcomes included Sit and Reach (SR), Functional Reach (FR), and Timed Up and Go (TUG). Self-reported Patient Neurotoxicity Questionnaire (PNQ) and Functional Assessment of Cancer Therapy—Neurotoxicity (FACT-GOG-NTX) were secondary CIPN outcomes. Biomarkers included salivary cortisol (stress) and bioesthesiometer (vibration). Results: Quantitative findings . Significant improvements were found in flexibility (SR; P = .006); balance (FR; P = .001) and fall risk (TUG; P = .004). PNQ improved significantly ( P = .003) with other measures improving non-significantly. Qualitative findings . Five themes emerged: (1) vacillation of CIPN pain perception over time; (2) transferability of skills to daily activities; (3) improvement in physical function; (4) perceived relaxation as an effect of SYM; and (5) group engagement provided a social context for not feeling isolated with CIPN. Conclusion . Preliminary data suggest SYM may improve QOL, flexibility, and balance in cancer survivors with CIPN, with a fully powered randomized controlled trial indicated. Trial registration: NCT03786055

Introduction: Overweight and obesity are linked to increased hospitalization and mortality in COVID-19 patients. This study aimed to characterize induced immune responses and deep immune cell profiles stratified by BMI in hospitalized COVID-19 patients., Methods and Results: This observational multicenter cohort pilot study included 122 adult patients with PCR-confirmed COVID-19 in Denmark, stratified by BMI (normal weight, overweight, obese). Inflammation was assessed using TruCulture® and immune cell profiles by flow cytometry with a customized antibody panel (DuraClone®). Patients with obesity had a more pro-inflammatory phenotype with increased TNF-α, IL-8, IL-17, and IL-10 levels post-T cell stimulation, and altered B cell profiles. Patients with obesity showed higher concentrations of naïve, transitional, and non-isotype switched memory B cells, and plasmablasts compared to normal weight patients and healthy controls., Conclusions: Obesity in hospitalized COVID-19 patients may correlate with elevated pro-inflammatory cytokines, anti-inflammatory IL-10, and increased B cell subset activation, highlighting the need for further studies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Vaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19., Methods: A nested case-control study on adults (≥ 18 years) who received at least two doses of a mRNA-COVID-19 vaccine and were hospitalized with SARS-CoV-2 breakthrough infections and severe COVID-19 between January 7, 2021, and February 1, 2022, were eligible for inclusion. Age- and sex-matched non-vaccinated controls were identified. Immunophenotyping was performed using a custom-designed 10-color flow cytometry prefabricated freeze-dried antibody panel (DuraClone, Beckman Coulter (BC), Brea, Calif). TruCulture (Myriad RBM, Austin, USA) was used to assess induced immune response in whole blood, revealing different critical signaling pathways as a proxy for immune function. All samples were obtained within 48 hours of admission., Results: In total, 20 hospitalized patients with severe COVID-19 and a breakthrough SARS-CoV-2 infection were included, ten vaccinated and ten non-vaccinated patients. Vaccinated patients had lower concentrations of CD19 B cells (p = 0.035), naïve CD4 T cells (p = 0.015), a higher proportion of γδ1 T cells (p = 0.019), and higher unstimulated immune cell release of IL-10 (p = 0.015)., Conclusion: We observed immunological differences between vaccinated and non-vaccinated patients hospitalized due to severe COVID-19 that indicate that vaccinated patients had lower B cell concentrations, lower concentrations of CD4 naïve T cells, a skewed gamma-delta V1/V2 ratio, and an exaggerated IL-10 response at admission. These results could indicate a suboptimal immune response involved in SARS-CoV-2 breakthrough infections that cause severe COVID-19 in vaccinated adults. However, the sample size was small, and further research is needed to confirm these results., Competing Interests: CN received research funding and/or consultancy fees outside this study from Abbvie, Janssen, AstraZeneca, Takeda, Octapharma, CSL Behring, Beigene and Genmab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sejdic, Hartling, Holler, Klingen Gjærde, Lindegaard, Dungu, Gnesin, Møller, Teglgaard, Niemann, Brooks, Jørgensen, Franck, Fischer, Marquart, Harboe and Ostrowski.)

Competing Interests: Kirsten Grønbæk has received research funding and/or consultancy fees from Janssen Pharma and GSK. Carsten Utoft Niemann has received research funding and/or consultancy fees from Abbvie, AstraZeneca, Janssen, Octapharma, Beigene, Genmab, CSL Behring, Takeda, Lilly, and MSD. Anne‐Mette Lebech has received unrestricted research grant from Gilead and consultancy fees from GSK, MSD, and Pfizer.

Passive immunotherapy with convalescent plasma may be the only available agent during the early phases of a pandemic. Here, we report safety and efficacy of high-titer convalescent plasma for COVID-19 pneumonia. Double-blinded randomized multicenter placebo-controlled trial of adult patients hospitalized with COVID-19 pneumonia. The intervention was COVID-19 convalescent plasma and placebo was saline allocated 2:1. The primary outcome was clinical status 14 days after the intervention evaluated on a clinical ordinal scale. The trial was registered at ClinicalTrials.Gov, NCT04345289, 14/04/2020. The CCAP-2 trial was terminated prematurely due to futility. Of 147 patients randomized, we included 144 patients in the modified intention-to-treat population. The ordinal clinical status 14 days post-intervention was comparable between treatment groups (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.72-2.09). Results were consistent when evaluating clinical progression on an individual level 14 days after intervention (OR 1.09; 95% CI 0.46-1.73). No significant differences in length of hospital stay, admission to ICU, frequency of severe adverse events or all-cause mortality during follow-up were found between the intervention and the placebo group. Infusion of convalescent plasma did not influence clinical progression, survival or length of hospitalization in patients with COVID-19 pneumonia., (© 2022. The Author(s).)

Background: The immune pathogenesis underlying the diverse clinical course of COVID-19 is poorly understood. Currently, there is an unmet need in daily clinical practice for early biomarkers and improved risk stratification tools to help identify and monitor COVID-19 patients at risk of severe disease., Methods: We performed longitudinal assessment of stimulated immune responses in 30 patients hospitalized with COVID-19. We used the TruCulture whole-blood ligand-stimulation assay applying standardized stimuli to activate distinct immune pathways, allowing quantification of cytokine responses. We further characterized immune cell subsets by flow cytometry and used this deep immunophenotyping data to map the course of clinical disease within and between patients., Results: Here we demonstrate impairments in innate immune response pathways at time of COVID-19 hospitalization that are associated with the development of severe disease. We show that these impairments are transient in those discharged from hospital, as illustrated by functional and cellular immune reconstitution. Specifically, we identify lower levels of LPS-stimulated IL-1β, and R848-stimulated IL-12 and IL-17A, at hospital admission to be significantly associated with increasing COVID-19 disease severity during hospitalization. Furthermore, we propose a stimulated immune response signature for predicting risk of developing severe or critical COVID-19 disease at time of hospitalization, to validate in larger cohorts., Conclusions: We identify early impairments in innate immune responses that are associated with subsequent COVID-19 disease severity. Our findings provide basis for early identification of patients at risk of severe disease which may have significant implications for the early management of patients hospitalized with COVID-19., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Virus neutralization assays provide a means to quantitate functional antibody responses that block virus infection. These assays are instrumental in defining vaccine and therapeutic antibody potency, immune evasion by viral variants, and post-infection immunity. Here we describe the development, optimization and evaluation of a live virus microneutralization assay specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this assay, SARS-CoV-2 clinical isolates are pre-incubated with serial diluted antibody and added to Vero E6 cells. Replicating virus is quantitated by enzyme-linked immunosorbent assay (ELISA) targeting the SARS-CoV-2 nucleocapsid protein and the standardized 50% virus inhibition titer calculated. We evaluated critical test parameters that include virus titration, assay linearity, number of cells, viral dose, incubation period post-inoculation, and normalization methods. Virus titration at 96 hours was determined optimal to account for different growth kinetics of clinical isolates. Nucleocapsid protein levels directly correlated with virus inoculum, with the strongest correlation at 24 hours post-inoculation. Variance was minimized by infecting a cell monolayer, rather than a cell suspension. Neutralization titers modestly decreased with increasing numbers of Vero E6 cells and virus amount. Application of two different normalization models effectively reduced the intermediate precision coefficient of variance to <16.5%. The SARS-CoV-2 microneutralization assay described and evaluated here is based on the influenza virus microneutralization assay described by WHO, and are proposed as a standard assay for comparing neutralization investigations., Competing Interests: The authors have declared that no competing interests exist.

Campylobacter jejuni causes foodborne gastroenteritis and may trigger acute autoimmune sequelae including Guillain Barré Syndrome. Onset of neuromuscular paralysis is associated with exposure to C. jejuni lipooligosaccharide (LOS) classes A, B, C, D, and E that mimic and evoke antibodies against gangliosides on myelin and axons of peripheral nerves. Family members managing a Michigan dairy operation reported recurring C. jejuni gastroenteritis. Because dairy cattle are known to shed C. jejuni , we hypothesized that calves in the sick pen were the source of human infections. Fecal samples obtained from twenty-five calves, one dog, and one asymptomatic family member were cultured for Campylobacter . C. jejuni isolates were obtained from thirteen calves and the family member: C. coli from two calves, and C. hyointestinalis from two calves. Some calves had diarrhea; most were clinically normal. Typing of lipooligosaccharide biosynthetic loci showed that eight calf C. jejuni isolates fell into classes A, B, and C. Two calf isolates and the human isolate possessed LOS class E, associated mainly with enteric disease and rarely with Guillain Barré Syndrome. Multi-locus sequence typing, por A and fla A typing, and whole genome comparisons of the thirteen C. jejuni isolates indicated that the three LOS class E strains that included the human isolate were closely related, indicating zoonotic transmission. Whole-genome comparisons revealed that isolates differed in virulence gene content, particularly in loci encoding biosynthesis of surface structures. Family members experienced diarrheal illness repeatedly over 2 years, yet none experienced GBS despite exposure to calves carrying invasive C. jejuni with LOS known to elicit antiganglioside autoantibodies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 St. Charles, Brooks, Bell, Ahmed, Van Allen, Manning and Mansfield.)

Cytokine-specific autoantibodies (c-aAbs) represent an emerging field in endogenous immunodeficiencies, and the immunomodulatory potential of c-aAbs is now well documented. Here, we investigated the hypothesis that c-aAbs affects inflammatory, immunoregulatory and injury-related processes and hence the clinical outcome of haematopoietic stem cell transplantation (HSCT). C-aAbs against IL-1α, IL-6, IL-10, IFNα, IFNγ and GM-CSF were measured in 131 HSCT recipients before and after (days + 7, + 14, + 28) HSCT and tested for associations with 33 different plasma biomarkers, leukocyte subsets, platelets and clinical outcomes, including engraftment, GvHD and infections. We found that c-aAb levels were stable over the course of HSCT, including at high titres, with few individuals seeming to acquire high-titre levels of c-aAbs. Both patients with stable and those with acquired high-titre c-aAb levels displayed significant differences in biomarker concentrations and blood cell counts pre-HSCT and at day 28, and the trajectories of these variables varied over the course of HSCT. No clinical outcomes were associated with high-titre c-aAbs. In this first study of c-aAbs in HSCT patients, we demonstrated that high-titre levels of c-aAb may both persist and emerge in patients over the course of HSCT and may be associated with altered immune biomarkers and cell profiles., (© 2021. The Author(s).)

Quantitative methods for assessing differentiative potency of adipose-derived stem/stromal cells may lead to improved clinical application of this multipotent stem cell, by advancing our understanding of specific processes such as adipogenic differentiation. Conventional cell staining methods are used to determine the formation of adipose areas during adipogenesis as a qualitative representation of adipogenic potency. Staining methods such as oil-red-O are quantifiable using absorbance measurements, but these assays are time and material consuming. Detection methods for cell characteristics using advanced image analysis by machine learning are emerging. Here, live-cell imaging was combined with a deep learning-based detection tool to quantify the presence of adipose areas and lipid droplet formation during adipogenic differentiation of adipose-derived stem/stromal cells. Different detection masks quantified adipose area and lipid droplet formation at different time points indicating kinetics of adipogenesis and showed differences between individual donors. Whereas CEBPA and PPARG expression seems to precede the increase in adipose area and lipid droplets, it might be able to predict expression of ADIPOQ . The applied method is a proof of concept, demonstrating that deep learning methods can be used to investigate adipogenic differentiation and kinetics in vitro using specific detection masks based on algorithm produced from annotation of image data.

We aimed to use a novel standardized whole-blood stimulation system to evaluate differences in the functional immune reconstitution in patients early after allogeneic haematopoietic cell transplantation (HCT). Between April and September 2018, 30 patients undergoing HCT had whole blood samples collected around day -21 (day 0 being the day of haematopoietic cell infusion) and day +28. Whole blood was transferred to TruCulture assays comprising prefilled incubation tubes with cell culture medium and a standardized stimulus. We used a panel of four stimuli (lipopolysaccharide, resiquimod, heat-killed Candida albicans and polyinosinic:polycytidylic acid) and a blank, designed to evaluate the function of critical extra- and intracellular immunological signalling pathways. For each stimulus, the cytokine response was assessed by the concentration of interferon-γ, interleukin (IL)-12p40, IL-10, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A and tumour necrosis factor-α using a multiplex Luminex assay. Pre-HCT cytokine responses were globally decreased across several different stimuli. Despite patients receiving immunosuppressive prophylaxis at the time, post-HCT cytokine responses were higher and less intercorrelated than pre-HCT responses, also after adjusting for differences in the leukocyte differential counts. For the resiquimod and heat-killed Candida albicans stimuli, we identified a cluster of patients in whom post-HCT responses were lower than average across several cytokines, indicating a possible functional immune deficiency. Our findings suggest that the standardized whole blood stimulation system can be used to reveal heterogeneity in the in vitro cytokine responses to various stimuli after HCT. Larger studies are needed to address if the functional immune reconstitution after HCT can predict the risk of infections., (© 2021 The Scandinavian Foundation for Immunology.)

Background: The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and to calculate the infection fatality rate (IFR). These measures may help the authorities make informed decisions and adjust the current societal interventions. The objective was to perform nationwide real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population-based IFR., Methods: Danish blood donors aged 17-69 years giving blood 6 April to 3 May were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between geographical areas, and an estimate of the IFR was calculated. Seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CIs)., Results: The first 20 640 blood donors were tested, and a combined adjusted seroprevalence of 1.9% (95% CI, .8-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers, a combined IFR in patients <70 years is estimated at 89 per 100 000 (95% CI, 72-211) infections., Conclusions: The IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR is likely severalfold lower than the current estimate. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

As the scale of biological data generation has increased, the bottleneck of research has shifted from data generation to analysis. Researchers commonly need to build computational workflows that include multiple analytic tools and require incremental development as experimental insights demand tool and parameter modifications. These workflows can produce hundreds to thousands of intermediate files and results that must be integrated for biological insight. Data-centric workflow systems that internally manage computational resources, software, and conditional execution of analysis steps are reshaping the landscape of biological data analysis and empowering researchers to conduct reproducible analyses at scale. Adoption of these tools can facilitate and expedite robust data analysis, but knowledge of these techniques is still lacking. Here, we provide a series of strategies for leveraging workflow systems with structured project, data, and resource management to streamline large-scale biological analysis. We present these practices in the context of high-throughput sequencing data analysis, but the principles are broadly applicable to biologists working beyond this field., (© The Author(s) 2021. Published by Oxford University Press GigaScience.)

Mesenchymal stromal/stem cells (MSCs) derived from bone marrow, umbilical cord and especially adipose tissue are increasingly being explored for their therapeutic potential to treat a wide variety of diseases. A prerequisite for most allogeneic off-the-shelf and some autologous MSC therapies is the ability to safely and efficiently cryopreserve cells during production or for storage prior to treatment. Dimethyl sulfoxide (Me 2 SO) is still the commonly used gold standard cryoprotectant (CPA). However, undesirable cellular impacts and side effects of Me 2 SO have led to an increasing demand for the development of safe and effective alternatives. This study investigated the effect of pentaisomaltose as a CPA for cryopreservation of adipose-derived stromal/stem cells (ASCs). We compared pentaisomaltose-based freezing media containing 1% Me 2 SO (PIM1) or 2% Me 2 SO (PIM2) to our in-house freezing media formulation containing 10% Me 2 SO (STD10) and to CryoStor freezing media containing 2% or 10% Me 2 SO (CS2 and CS10). We assessed the recovery of viable ASCs, their phenotype, differentiation potential, proliferation potential, and migratory potential. Further, their immunomodulatory potential was assessed by measuring their ability to suppress T cell proliferation and express immunomodulatory markers. The results showed that the post-thaw viability of ASCs cryopreserved with STD10, CS10 and PIM2 was improved compared to that of CS2. The recovery of ASCs with PIM1 and PIM2 was also improved compared to that of CS2. Proliferation and migration were comparable among the tested freezing media. The results showed no difference in the induction of PDL1, PDL2 or IDO1 expression. Nevertheless, the potential of cryopreserved ASCs to suppress T cell proliferation was reduced when the Me 2 SO concentration was reduced (CS10>STD10>CS2 and PIM2>PIM1). Altogether, the migratory and immunomodulatory potential combined with improved recovery indicate that the addition of pentaisomaltose in the freezing media may allow for the reduction of the Me 2 SO concentration to 2% while retaining a more potent cell product that what is recovered using comparable freezing media. With the desire to reduce the amount of Me 2 SO, these results suggest that 2% and potentially even 1% Me 2 SO in combination with 10% pentaisomaltose could be an effective and less toxic alternative to comparable freezing media., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pain is a common problem for patients receiving home care, often limiting mobility and contributing to functional decline. Pharmacological pain management is common, but all drugs bring some risk of side effects and adverse reactions. The opioid epidemic has brought into question analgesic prescribing patterns across all care settings. This study, which used data collected between 2012 and 2014, examines the pain medications used by older adults with activity-limiting pain receiving home care physical therapy in a large metropolitan home care agency. Eighty-five percent of subjects took at least one analgesic medication on admission to home care, and of these, 51.3% were using an opioid, 33.1% used acetaminophen, and 23.2% used nonsteroidal anti-inflammatory drugs (NSAIDs). At the 60-day follow-up, the most common medication classes taken by participants included acetaminophen (38%), opioids (35.9%), and NSAIDs (31.6%). We found racial/ethnic differences in analgesic use at baseline but not at follow-up. At baseline, analgesic use differed by pain type, but there were no differences at follow-up. The high use of medications to control pain by patients receiving home care, particularly opioid use, underscores the importance of providers being alert to potential adverse drug reactions.

Adipose-derived stromal/stem cells (ASCs) are being tested as a possible treatment for a wide range of diseases to exploit the immunomodulatory and regenerative potential demonstrated in vitro. Pooled human platelet lysate (pHPL) has replaced fetal bovine serum (FBS) as the preferred growth supplement because of its xeno-free origin and improved cell proliferation. Much has been done toward reducing the concentration of pHPL required when expanding ASCs. However, little is known on how increasing the concentration of pHPL affects ASC potency, which could lead to changes with possible beneficial applications. This study investigated the effect of 5, 10, or 20% pHPL in culture media on ASC proliferation and phenotypic marker expression, including chemokine receptors CXCR2, CXCR3, CXCR4, and VLA-4. Adipogenic and osteogenic properties, as well as immunosuppressive properties, including the ability to induce indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) and suppress T cell proliferation, were also examined. We observed a significant increase in cell yield (approximately 2-fold) and a corresponding reduction in population doubling time and cell volume when doubling the concentration of pHPL in the growth media. ASCs maintained expression of phenotypic surface markers CD73, CD90, and CD105 and were negative for CD45 and CD31. The ability to induce IDO1 and suppress T cell proliferation was observed as well. Adipogenesis and osteogenesis, however, seem to be increased at higher concentrations of pHPL (20% > 10% > 5%), while expression of chemokine receptors CXCR2 and CXCR3 was lower. In conclusion, increasing the pHPL concentration to 20% could be used to optimize culture conditions when producing cells for clinical treatments and may even be used to enhance beneficial ASC properties depending on the desired therapeutic effect., (© 2021 S. Karger AG, Basel.)

The peripheral neuropathy Guillain-Barré Syndrome can follow Campylobacter jejuni infection when outer core lipooligosaccharides induce production of neurotoxic anti-ganglioside antibodies. We hypothesized that gut microbiota depletion with an antibiotic would increase C. jejuni colonization, severity of gastroenteritis, and GBS. Microbiota depletion increased C. jejuni colonization, invasion, and colitis with Type 1/17 T cells in gut lamina propria. It also stimulated Type 1/17 anti-C. jejuni and -antiganglioside-antibodies, Type 2 anti-C. jejuni and -antiganglioside antibodies, and neurologic phenotypes. Results indicate that both C. jejuni strain and gut microbiota affect development of inflammation and GBS and suggest that probiotics following C. jejuni infection may ameliorate inflammation and autoimmune disease., (Copyright © 2019. Published by Elsevier B.V.)

We investigated Portuguese physiotherapy students' and physiotherapists' (1) perceptions of cardiorespiratory physiotherapy (CRP); (2) factors that influenced their decision to pursue a career in CRP; and (3) suggestions to develop CRP. Online surveys were disseminated to final year students and physiotherapists. A number of 189 students (mean age 23 [SD 6] years; 78% ♀) and 375 physiotherapists (mean age 31 [SD 8] years; 78% ♀) participated. Students' opinions about CRP were positively influenced by lecturers ( n  = 112, 69%), clinical experiences ( n  = 110, 68%), and scientific evidence ( n  = 93, 57%). Only 13% of students were "extremely interested" in specializing in CRP. Interest in the area and clinical exposure were the main factors influencing students to pursue a career in CRP. A percentage of 15 of responding physiotherapists were working in CRP. Their decision to pursue a CRP career was most influenced by their interest in the area ( n  = 37, 67%) and opportunity to work in acute settings ( n  = 31; 56%). Main suggestions to develop CRP were (1) include placements in CRP; (2) emphasize health promotion within the curriculum; and (3) develop CRP skills in broader contexts and training. Strategies focusing on changing the curriculum, increasing exposure to CRP, providing good mentorship, developing health promotion activities, and creating postgraduate courses may increase the attractiveness for CRP.

Campylobacter jejuni is an important zoonotic pathogen recently designated a serious antimicrobial resistant (AR) threat. While most patients with C. jejuni experience hemorrhagic colitis, serious autoimmune conditions can follow including inflammatory bowel disease (IBD) and the acute neuropathy Guillain Barré Syndrome (GBS). This review examines inter-relationships among factors mediating C. jejuni diarrheal versus autoimmune disease especially AR C. jejuni and microbiome shifts. Because both susceptible and AR C. jejuni are acquired from animals or their products, we consider their role in harboring strains. Inter-relationships among factors mediating C. jejuni colonization, diarrheal and autoimmune disease include C. jejuni virulence factors and AR, the enteric microbiome, and host responses. Because AR C. jejuni have been suggested to affect the severity of disease, length of infections and propensity to develop GBS, it is important to understand how these interactions occur when strains are under selection by antimicrobials. More work is needed to elucidate host-pathogen interactions of AR C. jejuni compared with susceptible strains and how AR C. jejuni are maintained and evolve in animal reservoirs and the extent of transmission to humans. These knowledge gaps impair the development of effective strategies to prevent the emergence of AR C. jejuni in reservoir species and human populations.

Background: Campylobacter jejuni is the leading antecedent infection to the autoimmune neuropathy Guillain-Barré syndrome (GBS), which is accompanied by an autoimmune anti-ganglioside antibody attack on peripheral nerves. Previously, we showed that contrasting immune responses mediate C. jejuni induced colitis and autoimmunity in interleukin-10 (IL-10)-deficient mice, dependent upon the infecting strain. Strains from colitis patients elicited T helper 1 (T H 1)-dependent inflammatory responses while strains from GBS patients elicited T H 2-dependent autoantibody production. Both syndromes were exacerbated by antibiotic depletion of the microbiota, but other factors controlling susceptibility to GBS are unknown., Methods: Using 16S rRNA gene high-throughput sequencing, we examined whether structure of the gut microbial community alters host (1) gastrointestinal inflammation or (2) anti-ganglioside antibody responses after infection with C. jejuni strains from colitis or GBS patients. We compared these responses in C57BL/6 mice with either (1) stable human gut microbiota ( Hu microbiota) transplants or (2) conventional mouse microbiota ( Conv microbiota)., Results: Inoculating germ-free C57BL/6 wild-type (WT) mice with a mixed human fecal slurry provided a murine model that stably passed its microbiota over >20 generations. Mice were housed in specific pathogen-free (SPF) facilities, while extra precautions of having caretakers wear sterile garb along with limited access ensured that no mouse pathogens were acquired. Hu microbiota conferred many changes upon the WT model in contrast to previous results, which showed only colonization with no disease after C. jejuni challenge. When compared to Conv microbiota mice for susceptibility to C. jejuni enteric or GBS patient strains, infected Hu microbiota mice had (1) 10-100 fold increases in C. jejuni colonization of both strains, (2) pathologic change in draining lymph nodes but only mild changes in colon or cecal lamina propria, (3) significantly lower Th1/Th17-dependent anti-C. jejuni responses, (4) significantly higher IL-4 responses at 5 but not 7 weeks post infection (PI), (5) significantly higher Th2-dependent anti-C. jejuni responses, and (6) significantly elevated anti-ganglioside autoantibodies after C. jejuni infection. These responses in Hu microbiota mice were correlated with a dominant Bacteroidetes and Firmicutes microbiota., Conclusions: These data demonstrate that Hu microbiota altered host-pathogen interactions in infected mice, increasing colonization and Th-2 and autoimmune responses in a C. jejuni strain-dependent manner. Thus, microbiota composition is another factor controlling susceptibility to GBS.

Inhalation exposures to ozone commonly encountered in photochemical smog cause airway injury and inflammation. Elevated ambient ozone concentrations have been epidemiologically associated with nasal airway activation of neutrophils and eosinophils. In the present study, we elucidated the temporal onset and lymphoid cell dependency of eosinophilic rhinitis and associated epithelial changes in mice repeatedly exposed to ozone. Lymphoid cell-sufficient C57BL/6 mice were exposed to 0 or 0.5 parts per million (ppm) ozone for 1, 2, 4, or 9 consecutive weekdays (4 h/d). Lymphoid cell-deficient, Rag2(-/-)Il2rg(-/-) mice were similarly exposed for 9 weekdays. Nasal tissues were taken at 2 or 24 hours after exposure for morphometric and gene expression analyses. C57BL/6 mice exposed to ozone for 1 day had acute neutrophilic rhinitis, with airway epithelial necrosis and overexpression of mucosal Ccl2 (MCP-1), Ccl11 (eotaxin), Cxcl1 (KC), Cxcl2 (MIP-2), Hmox1, Il1b, Il5, Il6, Il13, and Tnf mRNA. In contrast, 9-day ozone exposure elicited type 2 immune responses in C57BL/6 mice, with mucosal mRNA overexpression of Arg1, Ccl8 (MCP-2), Ccl11, Chil4 (Ym2), Clca1 (Gob5), Il5, Il10, and Il13; increased density of mucosal eosinophils; and nasal epithelial remodeling (e.g., hyperplasia/hypertrophy, mucous cell metaplasia, hyalinosis, and increased YM1/YM2 proteins). Rag2(-/-)Il2rg(-/-) mice exposed to ozone for 9 days, however, had no nasal pathology or overexpression of transcripts related to type 2 immunity. These results provide a plausible paradigm for the activation of eosinophilic inflammation and type 2 immunity found in the nasal airways of nonatopic individuals subjected to episodic exposures to high ambient ozone.

Background: The use of standardized assessment tools is an element of evidence-informed rehabilitation, but physical therapists report administering these tools inconsistently poststroke. An in-depth understanding of physical therapists' approaches to walking assessment is needed to develop strategies to advance assessment practice., Objectives: The objective of this study was to explore the methods physical therapists use to evaluate walking poststroke, reasons for selecting these methods, and the use of assessment results in clinical practice., Design: A qualitative descriptive study involving semistructured telephone interviews was conducted., Methods: Registered physical therapists assessing a minimum of 10 people with stroke per year in Ontario, Canada, were purposively recruited from acute care, rehabilitation, and outpatient settings. Interviews were audiotaped and transcribed verbatim. Transcripts were coded line by line by the interviewer. Credibility was optimized through triangulation of analysts, audit trail, and collection of field notes., Results: Study participants worked in acute care (n=8), rehabilitation (n=11), or outpatient (n=9) settings and reported using movement observation and standardized assessment tools to evaluate walking. When selecting methods to evaluate walking, physical therapists described being influenced by a hierarchy of factors. Factors included characteristics of the assessment tool, the therapist, the workplace, and patients, as well as influential individuals or organizations. Familiarity exerted the primary influence on adoption of a tool into a therapist's assessment repertoire, whereas patient factors commonly determined daily use. Participants reported using the results from walking assessments to communicate progress to the patient and health care professionals., Conclusions: Multilevel factors influence physical therapists' adoption and daily administration of standardized tools to assess walking. Findings will inform knowledge translation efforts aimed at increasing the standardized assessment of walking poststroke., (© 2015 American Physical Therapy Association.)

Background: Exercise is recommended for people with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), yet there is little information to guide safe and effective mobilization and exercise for these patients., Objectives: The purpose of this study was to develop a clinical decision-making tool to guide health care professionals in the assessment, prescription, monitoring, and progression of mobilization and therapeutic exercise for patients with AECOPD., Design and Methods: A 3-round interdisciplinary Delphi panel identified and selected items based on a preselected consensus of 80%. These items were summarized in a paper-based tool titled Mobilization in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD-Mob). Focus groups and questionnaires were subsequently used to conduct a sensibility evaluation of the tool., Results: Nine researchers, 13 clinicians, and 7 individuals with COPD identified and approved 110 parameters for safe and effective exercise in AECOPD. These parameters were grouped into 5 categories: (1) "What to Assess Prior to Mobilization," (2) "When to Consider Not Mobilizing or to Discontinue Mobilization," (3) "What to Monitor During Mobilization for Patient Safety," (4) "How to Progress Mobilization to Enhance Effectiveness," and (5) "What to Confirm Prior to Discharge." The tool was evaluated in 4 focus groups of 18 health care professionals, 90% of whom reported the tool was easy to use, was concise, and would guide a health care professional who is new to the acute care setting and working with patients with AECOPD., Limitations: The tool was developed based on published evidence and expert opinion, so the applicability of the items to patients in all settings cannot be guaranteed. The Delphi panel consisted of health care professionals from Canada, so items may not be generalizable to other jurisdictions., Conclusions: The AECOPD-Mob provides practical and concise information on safe and effective exercise for the AECOPD population for use by the new graduate or novice acute care practitioner., (© 2015 American Physical Therapy Association.)

D-arginine dehydrogenase from Pseudomonas aeruginosa catalyzes the oxidation of D-arginine to iminoarginine, which is hydrolyzed in solution to ketoarginine and ammonia. In the present study, we have genetically engineered an untagged form of the enzyme that was purified to high levels and characterized in its kinetic properties. The enzyme is a true dehydrogenase that does not react with molecular oxygen. Steady-state kinetic studies with D-arginine or D-histidine as substrate and PMS as the electron acceptor established a ping-pong bi-bi kinetic mechanism. With the fast substrate D-arginine a dead-end complex of the reduced enzyme and the substrate occurs at high concentrations of D-arginine yielding substrate inhibition, while the overall turnover is partially limited by the release of the iminoarginine product. With the slow substrate D-histidine the initial Michaelis complex undergoes an isomerization involving multiple conformations that are not all equally catalytically competent for the subsequent oxidation reaction, while the overall turnover is at least partially limited by flavin reduction. The kinetic data are interpreted in view of the high-resolution crystal structures of the iminoarginine--and iminohistidine--enzyme complexes.

Objectives: To compare ultrasonography and abdominal radiography with intravenous urography in the investigation of urinary tract infection in men., Design: Prospective study in two hospital departments. Radiological procedures and urological assessments performed on different days by different clinicians, Setting: District general hospital., Participants: Consecutive series of men (n=114) referred to the department of urology for investigation of proved urinary tract infection., Interventions: Ultrasonography and intravenous urography of renal tract and assessment of urinary flow rate. Clinical assessment, cystoscopy, urodynamic studies, and transrectal ultrasonography with biopsy., Main Outcome Measures: Sensitivity and specificity of ultrasonography and abdominal radiography compared with intravenous urography., Results: Important abnormalities were seen in 53 of 100 fully evaluated patients, the most common being a poorly emptying bladder (34). The combination of plain radiographs of kidneys, ureter, and bladder and ultrasonography detected more abnormalities than intravenous urography alone. No important abnormality was missed by this combination (sensitivity 100% and specificity 93%)., Conclusions: Ultrasonography with abdominal radiography is as accurate as intravenous urography in detecting important urological abnormalities in men presenting with urinary tract infection. This combination is safer than intravenous urography and should be the initial investigation for such patients. Additional determination of urinary flow rate is useful for the assessment of an incompletely emptying bladder.

Two cases of large pneumoperitoneum are described following palliative laser therapy for inoperable oesophageal carcinoma. In both cases there was no constitutional upset and no perforation demonstrated on contrast examination of the oesophagus. The pneumoperitoneum is considered to be due to high pressure CO2, used to keep the tip of the laser clean, passing through the tumour and tracking into the peritoneum. The condition requires only conservative treatment.

Forty-one infants have been referred for thyroid scintigraphy following routine screening for congenital hypothyroidism: 14 (35%) were athyreotic, 19 (45%) had an ectopic thyroid, four (10%) were normal and four (10%) demonstrated other abnormalities. There was a female: male ratio of 4:1. Thyroid scintigraphy is a useful adjunct to biochemical screening.

A case of bladder involvement by Von Recklinghausen's disease with consequent hydronephrosis and hydroureters is presented. The intravenous urographic and ultrasonic appearances are correlated.