Evaluation of a New Integrative Health and Wellness Clinic for Veterans at the San Francisco VA Health Care System: A Mixed-Methods Pilot Study.

Objective: The Integrative Health and Wellness Clinic (IHWC), established in 2019 at the San Francisco VA Health Care System, is an interdisciplinary clinic consisting of a medical provider, dietician, physical therapist, and psychologist trained in complementary and integrative health (CIH) following the VA Whole Health model of care. Veterans with complex chronic conditions seeking CIH and nonpharmacologic approaches are referred to the IHWC. This study evaluated the clinic's acceptability and feasibility among veteran patients and its preliminary impact on health and wellbeing, health-related goals, and use of CIH approaches. Methods: Mixed methods were used to assess patient-reported outcomes and experiences with the IHWC. Participants completed surveys administered at baseline and 6-months and a subset completed a qualitative interview. Pre- and post-scores were compared using t-tests and chi-square tests. Results: Thirty-five veterans completed baseline and 6-month follow up surveys. Of these, 13% were women; 24% < 50 years of age, and 44% identified as racial/ethnic minorities. Compared to baseline, at 6 months, there were significant (P < .05) improvements in overall health, physical health, perceived stress, and perceived helpfulness of clinicians in assisting with goal attainment; there was a trend toward improved mental health (P = .057). Interviews (n = 25) indicated satisfaction with the interdisciplinary clinical model, support of IHWC providers in goal attainment, and positive impact on physical and mental health. Areas for improvement included logistics related to scheduling of multiple IHWC providers and referrals to other CIH services. Conclusion: Results revealed significant improvement in important clinical domains and satisfaction with interprofessional IHWC clinic providers, but also opportunities to improve clinic processes and care coordination. An interdisciplinary clinic focused on CIH and Whole Health is a feasible and acceptable model of care for veterans with complex chronic health conditions in the VA healthcare system.

Correlation of Professional Antigen-Presenting Tbet+CD11c+ B Cells With Bone Destruction in Untreated Rheumatoid Arthritis.

OBJECTIVE: Subsets of CD21-/low memory B cells (MBCs), including double-negative (DN, CD27-IgD-) and Tbet+CD11c+ cells, are expanded in chronic inflammatory diseases. In rheumatoid arthritis (RA), CD21-/low MBCs correlate with joint destruction. However, whether this is due to the Tbet+CD11c+ subset, its function and pathogenic contribution to RA are unknown. This study aims to investigate the association between CD21-/lowTbet+CD11c+ MBCs and joint destruction as well as other clinical parameters and to elucidate their functional properties in patients with untreated RA (uRA). METHODS: Clinical observations were combined with flow cytometry (n = 36) and single-cell RNA sequencing (scRNA-seq) and V(D)J sequencing (n = 4) of peripheral blood (PB) MBCs from patients with uRA. The transcriptome of circulating Tbet+CD11c+ MBCs was compared with scRNA-seq data of synovial B cells. In vitro coculture of Tbet+CD11c+ B cells with T cells was used to assess costimulatory capacity. RESULTS: CD21-/lowTbet+CD11c+ MBCs in PB correlated with bone destruction but no other clinical parameters analyzed. The Tbet+CD11c+ MBCs have undergone clonal expansion and express somatically mutated V genes. Gene expression analysis of these cells identified a unique signature of more than 150 up-regulated genes associated with antigen presentation functions, including B cell receptor activation and clathrin-mediated antigen internalization; regulation of actin filaments, endosomes, and lysosomes; antigen processing, loading, presentation, and costimulation; a transcriptome mirrored in their synovial tissue counterparts. In vitro, Tbet+CD11c+ B cells induced retinoic acid receptor-related orphan nuclear receptor γT expression in CD4+ T cells, thereby polarizing to Th17 cells, a T cell subset critical for osteoclastogenesis and associated with bone destruction. CONCLUSION: This study suggests that Tbet+CD11c+ MBCs contribute to the pathogenesis of RA by promoting bone destruction through antigen presentation, T cell activation, and Th17 polarization.

Cartilage destruction in early rheumatoid arthritis patients correlates with CD21-/low double-negative B cells.

BACKGROUND: Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21-/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21-/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. METHODS: Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry. RESULTS: Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21-/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21-/low double-negative (DN, CD27-IgD-) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21-/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). CONCLUSIONS: Cartilage destruction in eRA patients was associated with an expanded proportion of CD21-/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21-/low DN in RA pathogenesis.

Density and population size estimates of the endangered northern yellow-cheeked crested gibbon Nomascus annamensis in selectively logged Veun Sai-Siem Pang National Park in Cambodia using acoustic spatial capture-recapture methods.

Many gibbon species are threatened with extinction, including the endangered northern yellow-cheeked crested gibbon, Nomascus annamensis. Assessing gibbon populations and understanding how human disturbances and environmental factors impact these populations is vital for effective conservation planning. In 2010, auditory surveys revealed that Veun Sai-Siem Pang National Park (VSSP) in Cambodia contains one of the largest known N. annamensis populations in the world, with an estimated 456 (95% CI 421-490) gibbon groups. Illegal selective logging is common in the park, but the impact of continued logging on the gibbon population has not been investigated. To determine any change in the N. annamensis population since 2010, between January and April 2019 we conducted auditory surveys at 13 sites that were at least 4 km apart. We surveyed each site for three days, each day recording the gibbon calls heard over 3.25 hours from three listening posts located 500 m apart. At the same sites, we assessed the logging intensity using transects and ecological plots. Gibbon densities can be influenced by various environmental factors such as canopy height and forest type. Therefore, in addition to investigating the relationship between the density of N. annamensis groups and logging, we included five additional environmental variables in our acoustic spatial capture-recapture models. Our best fit model with the lowest AIC value included canopy height, forest type, distance to villages, and logging. We estimate that there are 389 (95% CI 284-542) N. annamensis groups currently in VSSP. Selective logging is widespread in the park, primarily targeting four tree species. The estimated felling time of these logged trees, together with previous reports, indicate that the species most targeted in VSSP varies over time. To conserve the N. annamensis population in VSSP, it is crucial that action is taken to reduce illegal logging.

Virtual Worlds Technology to Enhance Training for Primary Care Providers in Assessment and Management of Posttraumatic Stress Disorder Using Motivational Interviewing: Pilot Randomized Controlled Trial.

BACKGROUND: Many individuals with posttraumatic stress disorder (PTSD) first present to primary care rather than specialty mental health care. Primary care providers often lack the training required to assess and treat patients with PTSD. Virtual trainings have emerged as a convenient and effective way of training primary care providers in PTSD assessment and communication methods (ie, motivational interviewing [MI]). OBJECTIVE: The aim of this study was to conduct a pilot randomized controlled trial of a synchronous Virtual Worlds (VW; a virtual world where learners were immersed as avatars) training versus an asynchronous web-based training on PTSD and MI, comparing the feasibility, acceptability, usability, and preliminary efficacy of 2 different training platforms among primary care providers. METHODS: Participating primary care providers were randomized to a VW and a web-based PTSD training. Outcomes were collected at baseline, posttraining, and 90-days follow-up. Standardized patient interviews measured participants' communication skills in assessing and managing patients with PTSD symptoms. RESULTS: Compared to the web-based training, the VW training platform achieved larger learning gains in MI (ie, partnership and empathy) and in discussing pharmacotherapy and psychotherapy for PTSD. Both VW and web-based trainings led to increases in PTSD knowledge and primary care providers' self-confidence. CONCLUSIONS: The asynchronous web-based PTSD training improved PTSD-related knowledge and self-confidence but was not as effective as the VW immersive experience in teaching MI or clinical management. Because VW training is synchronous and new for many learners, it required more time, facilitation, and technical support. As computer technology improves, VW educational interventions may become more feasible, particularly in teaching clinical skills. TRIAL REGISTRATION: ClinicalTrials.gov NCT03898271; https://tinyurl.com/mu479es5.

Integration of Health Coaches in a Whole Health Team Model of Chronic Pain Care: a Qualitative Study.

OBJECTIVE: Health coaching has shown promise in helping patients manage their chronic disease and in improving health outcomes, yet the implementation of health coaching in healthcare systems is understudied. Further, evidence suggests that interdisciplinary care teams may be more effective in treating chronic pain than usual care. As such, we sought to examine the benefits and drawbacks to embedding health coaches within interdisciplinary pain care teams ("Whole Health Teams"). DESIGN: As part of a multisite clinical trial (at five Veterans Health Administration sites) investigating the effectiveness of a Whole Health Team (WHT) approach to care for patients with chronic pain, qualitative interviews gathered data on how the experience of treating patients in the WHT differed from the experience treating patients outside the WHT, as well as provider experiences coordinating patient care within the WHT. PARTICIPANTS: Twenty-two WHT members, study investigators, and study coordinators. APPROACH: Data were analyzed using a rapid analysis approach. RESULTS: Overall, stakeholders perceived considerable synergy within the interdisciplinary pain care team. Each provider brought a different perspective to the patient's health concerns, which stakeholders felt was valuable and increased patient progress towards goals. The team model was also viewed as efficient because everyone was committed to working together and communicating as a team. Logistically, however, stakeholders noted challenges to working as a team, especially regarding patient goal setting. Furthermore, multiple stakeholders believed the care team model required a high degree of dedication to teamwork and communication among its members to be successful. CONCLUSIONS: Embedding health coaches within interdisciplinary pain care teams may improve care processes and accelerate patient progress. Successful implementation would require adequate training, role clarification, and expectation setting to facilitate good communication across all care team members. Additional research is needed to evaluate the clinical outcomes of integrating health coaches on WHTs versus other implementation approaches.

Early Increase of Circulating Transitional B Cells and Autoantibodies to Joint-Related Proteins in Patients With Metastatic Melanoma Developing Checkpoint Inhibitor-Induced Inflammatory Arthritis.

OBJECTIVE: To investigate potential associations between B cell-related immunologic changes and development of inflammatory arthritis (IA) after treatment with immune checkpoint inhibitors (ICIs). METHODS: Patients who developed ICI-induced IA (ICI-IA) and patients who did not develop immune-related adverse events (non-IRAE) after receiving ICIs to treat metastatic melanoma were consecutively recruited. Blood samples were collected at the time of ICI-IA occurrence and at different time points during treatment. Peripheral blood B cell subsets during ICI treatment were analyzed by flow cytometry. Rheumatoid factor, anti-citrullinated protein antibodies, and antibodies against joint-related proteins were measured. RESULTS: Proportions of CD19+ B cells were higher in patients with ICI-IA (n = 7) compared to patients with non-IRAE (n = 15) (median 11.7% [interquartile range (IQR) 9.7-16.2%] versus 8.1% [IQR 5.7-11.0%]; P = 0.03). The proportion and absolute numbers of transitional CD19+CD10+CD24high CD38high B cells were increased in patients with ICI-IA compared to non-IRAE patients (median 8.1% [IQR 4.9-12.1%] versus 3.6% [IQR 1.9-4.9%]; median 10.7 cells/µl [IQR 8.9-19.6] versus 4.4 cells/µl [IQR 2.3-6.6]; P < 0.01 for both). In addition, higher levels of transitional B cells were associated with development of ICI-IA (odds ratio 2.25 [95% confidence interval 1.03-4.9], P = 0.04). Transitional B cells increased before the onset of overt ICI-IA and decreased between the active and quiescent stages of ICI-IA (P = 0.02). Autoantibodies to type II collagen epitopes were detected in up to 43% of ICI-IA patients compared to none of the non-IRAE patients (P = 0.02). CONCLUSION: Development of ICI-IA is accompanied by an increase in transitional B cells and by production of autoantibodies to joint-related proteins. Monitoring of B cell-driven abnormalities upon ICI treatment may help earlier recognition of ICI-IA.

A close-up on the expanding landscape of CD21-/low B cells in humans.

Memory B cells (MBCs) are an essential part of our immunological memory. They respond fast upon re-encountering pathogens and can differentiate into plasma cells that secrete protective antibodies. The focus of this review is on MBCs that lack, or express low levels of, CD21, hereafter referred to as CD21-/low. These cells are expanded in peripheral blood with age and during chronic inflammatory conditions such as viral infections, malaria, common variable immunodeficiency, and autoimmune diseases. CD21-/low MBCs have gained significant attention; they produce disease-specific antibodies/autoantibodies and associate with key disease manifestations in some conditions. These cells can be divided into subsets based on classical B-cell and other markers, e.g. CD11c, FcRL4, and Tbet which, over the years, have become hallmarks to identify these cells. This has resulted in different names including age-associated, autoimmune-associated, atypical, tissue-like, tissue-resident, tissue-restricted, exhausted, or simply CD21-/low B cells. It is however unclear whether the expanded 'CD21-/low' cells in one condition are equivalent to those in another, whether they express an identical gene signature and whether they have a similar function. Here, we will discuss these issues with the goal to understand whether the CD21-/low B cells are comparable in different conditions.

Annexin-A1: The culprit or the solution?

Annexin-A1 has a well-defined anti-inflammatory role in the innate immune system, but its function in adaptive immunity remains controversial. This glucocorticoid-induced protein has been implicated in a range of inflammatory conditions and cancers, as well as being found to be overexpressed on the T cells of patients with autoimmune disease. Moreover, the formyl peptide family of receptors, through which annexin-A1 primarily signals, has also been implicated in these diseases. In contrast, treatment with recombinant annexin-A1 peptides resulted in suppression of inflammatory processes in murine models of inflammation. This review will focus on what is currently known about annexin-A1 in health and disease and discuss the potential of this protein as a biomarker and therapeutic target.

Herb-drug Interactions in Neuropsychiatric Pharmacotherapy - A Review of Clinically Relevant Findings.

The management of neuropsychiatric disorders relies heavily on pharmacotherapy. The use of herbal products as complimentary medicine, often concomitantly, is common among patients taking prescription neuropsychiatric drugs. Herb-drug interaction, a clinical consequence of this practice, may jeopardize the success of pharmacotherapy in neuropsychiatry. Besides the wellknown ability of phytochemicals to inhibit and/or induce drug-metabolizing enzymes and transport proteins, several phytoconstituents are capable of exerting pharmacological effects on the central nervous system. This study reviewed the relevant literature and identified 13 commonly used herbal products - celery, echinacea, ginkgo, ginseng, hydroxycut, kava, kratom, moringa, piperine, rhodiola, St. John's wort, terminalia/commiphora ayurvedic mixture and valerian - which have shown clinically relevant interactions with prescription drugs used in the management of neuropsychiatric disorders. The consequent pharmacokinetic and pharmacodynamic interactions with orthodox medications often result in deleterious clinical consequences. This underscores the importance of caution in herb-drug co-medication.

Suppression of inflammatory arthritis by the parasitic worm product ES-62 is associated with epigenetic changes in synovial fibroblasts.

ES-62 is the major secreted protein of the parasitic filarial nematode, Acanthocheilonema viteae. The molecule exists as a large tetramer (MW, ~240kD), which possesses immunomodulatory properties by virtue of multiple phosphorylcholine (PC) moieties attached to N-type glycans. By suppressing inflammatory immune responses, ES-62 can prevent disease development in certain mouse models of allergic and autoimmune conditions, including joint pathology in collagen-induced arthritis (CIA), a model of rheumatoid arthritis (RA). Such protection is associated with functional suppression of "pathogenic" hyper-responsive synovial fibroblasts (SFs), which exhibit an aggressive inflammatory and bone-damaging phenotype induced by their epigenetic rewiring in response to the inflammatory microenvironment of the arthritic joint. Critically, exposure to ES-62 in vivo induces a stably-imprinted CIA-SF phenotype that exhibits functional responses more typical of healthy, Naïve-SFs. Consistent with this, ES-62 "rewiring" of SFs away from the hyper-responsive phenotype is associated with suppression of ERK activation, STAT3 activation and miR-155 upregulation, signals widely associated with SF pathogenesis. Surprisingly however, DNA methylome analysis of Naïve-, CIA- and ES-62-CIA-SF cohorts reveals that rather than simply preventing pathogenic rewiring of SFs, ES-62 induces further changes in DNA methylation under the inflammatory conditions pertaining in the inflamed joint, including targeting genes associated with ciliogenesis, to programme a novel "resolving" CIA-SF phenotype. In addition to introducing a previously unsuspected aspect of ES-62's mechanism of action, such unique behaviour signposts the potential for developing DNA methylation signatures predictive of pathogenesis and its resolution and hence, candidate mechanisms by which novel therapeutic interventions could prevent SFs from perpetuating joint inflammation and destruction in RA. Pertinent to these translational aspects of ES-62-behavior, small molecule analogues (SMAs) based on ES-62's active PC-moieties mimic the rewiring of SFs as well as the protection against joint disease in CIA afforded by the parasitic worm product.

Remote and local drivers of Pleistocene South Asian summer monsoon precipitation: A test for future predictions.

South Asian precipitation amount and extreme variability are predicted to increase due to thermodynamic effects of increased 21st-century greenhouse gases, accompanied by an increased supply of moisture from the southern hemisphere Indian Ocean. We reconstructed South Asian summer monsoon precipitation and runoff into the Bay of Bengal to assess the extent to which these factors also operated in the Pleistocene, a time of large-scale natural changes in carbon dioxide and ice volume. South Asian precipitation and runoff are strongly coherent with, and lag, atmospheric carbon dioxide changes at Earth's orbital eccentricity, obliquity, and precession bands and are closely tied to cross-equatorial wind strength at the precession band. We find that the projected monsoon response to ongoing, rapid high-latitude ice melt and rising carbon dioxide levels is fully consistent with dynamics of the past 0.9 million years.

"Then COVID happened ": Veterans' Health, Wellbeing, and Engagement in Whole Health Care During the COVID-19 Pandemic.

BACKGROUND: Little is known about the COVID-19 pandemic's impact on US military veterans' health, wellbeing, and care engagement. Healthcare systems like VA need additional information about the pandemic's biopsychosocial impacts and how a Whole Health approach may help to address them. OBJECTIVE: To examine how the pandemic has affected veterans' health, wellbeing, and engagement in the VA Whole Health System of Care. METHOD: We conducted qualitative interviews with 40 veterans at a large multicampus VA healthcare system during the pandemic. Informed by a Whole Health approach, interviews used open-ended questions to holistically explore pandemic impacts on mental and physical health, healthcare access and engagement, social support, coping strategies, and use of VA healthcare and wellness services. Interviews were conducted by telephone, audio-recorded, and analyzed using a matrix-based technique. Interviews were supplemented by an original survey assessing pandemic impacts; descriptive frequencies were calculated to describe and characterize the interviewed sample. INTERVIEW RESULTS: Nearly, all participating veterans described significant pandemic impacts on their wellbeing, especially loneliness and sorrow stemming from isolation and disruptions to ordinary routines. These emotional impacts-sometimes combined with new constraints on care access and personal mobility-disrupted veterans' health plans and sometimes deterred engagement in both routine and wellness care. Veterans already struggling with chronic mental and physical health conditions and those who experienced transitions or losses during the pandemic described the most severe impacts on their wellbeing. Virtual VA wellness services, especially health coaching and mind-body wellness groups, were a key source of support and connection for those who engaged in them. CONCLUSION: We discuss the implications of our findings for care systems attempting to implement a Whole Health System of Care, including how they can address postpandemic barriers to engagement in healthcare and wellness programs, and how wellness programs can be leveraged to support those most at risk after the COVID-19 pandemic and in future crises.

Tailored to Fit: How an Implementation Framework Can Support Pragmatic Pain Care Trial Adaptation for Diverse Veterans Affairs Clinical Settings.

BACKGROUND: Veterans Affairs (VA) has rolled out a holistic, multicomponent Whole Health care model nationwide, yet no pragmatic trials have been conducted in real-world clinical settings to compare its effectiveness against other evidence-based approaches for chronic pain management in veterans. OBJECTIVES: We describe the adaptation of the first large pragmatic randomized controlled trial of the Whole Health model for chronic pain care for diverse VA clinical settings. RESEARCH DESIGN: Informed by the Promoting Action on Research Implementation in Health Systems implementation framework, we conducted qualitative semistructured interviews to obtain feedback on trial design from VA leadership, frontline clinicians, and veterans with chronic pain at 5 VA enrollment sites. Next, we convened in-person evidence-based quality improvement (EBQI) meetings with study stakeholders (including frontline clinicians and administrators) at each site to discuss study design; review interview themes; and identify site-specific barriers, facilitators, and approaches to implementation. Ethnographic observations from EBQI meetings provided additional insight into implementation strategies. SUBJECTS: Seventy-four veteran and VA staff stakeholders were interviewed; 71 stakeholders participated in EBQI meetings. RESULTS: At each site, unique clinical contexts and varying resources for Whole Health and pain care delivery affected plans for trial implementation. We present examples of local adaptations that emerged through the formative evaluation process to facilitate implementation and yield a more pragmatic trial design. CONCLUSIONS: A systematic formative evaluation can facilitate engagement and buy-in of study stakeholders. Locally tailored pragmatic implementation strategies may improve the likelihood of successful trial execution as well as future implementation of evidence-based pain care approaches in real-world clinical settings.

Chanzyme TRPM7 protects against cardiovascular inflammation and fibrosis.

AIMS: Transient Receptor Potential Melastatin 7 (TRPM7) cation channel is a chanzyme (channel + kinase) that influences cellular Mg2+ homeostasis and vascular signalling. However, the pathophysiological significance of TRPM7 in the cardiovascular system is unclear. The aim of this study was to investigate the role of this chanzyme in the cardiovascular system focusing on inflammation and fibrosis. METHODS AND RESULTS: TRPM7-deficient mice with deletion of the kinase domain (TRPM7+/Δkinase) were studied and molecular mechanisms investigated in TRPM7+/Δkinase bone marrow-derived macrophages (BMDM) and co-culture systems with cardiac fibroblasts. TRPM7-deficient mice had significant cardiac hypertrophy, fibrosis, and inflammation. Cardiac collagen and fibronectin content, expression of pro-inflammatory mediators (SMAD3, TGFß) and cytokines [interleukin (IL)-6, IL-10, IL-12, tumour necrosis factor-α] and phosphorylation of the pro-inflammatory signalling molecule Stat1, were increased in TRPM7+/Δkinase mice. These processes were associated with infiltration of inflammatory cells (F4/80+CD206+ cardiac macrophages) and increased galectin-3 expression. Cardiac [Mg2+]i, but not [Ca2+]i, was reduced in TRPM7+/Δkinase mice. Calpain, a downstream TRPM7 target, was upregulated (increased expression and activation) in TRPM7+/Δkinase hearts. Vascular functional and inflammatory responses, assessed in vivo by intra-vital microscopy, demonstrated impaired neutrophil rolling, increased neutrophil: endothelial attachment and transmigration of leucocytes in TRPM7+/Δkinase mice. TRPM7+/Δkinase BMDMs had increased levels of galectin-3, IL-10, and IL-6. In co-culture systems, TRPM7+/Δkinase macrophages increased expression of fibronectin, proliferating cell nuclear antigen, and TGFß in cardiac fibroblasts from wild-type mice, effects ameliorated by MgCl2 treatment. CONCLUSIONS: We identify a novel anti-inflammatory and anti-fibrotic role for TRPM7 and suggest that its protective effects are mediated, in part, through Mg2+-sensitive processes.

Rheumatic Disease: Protease-Activated Receptor-2 in Synovial Joint Pathobiology.

Protease-activated receptor-2 (PAR2) is one member of a small family of transmembrane, G-protein-coupled receptors. These receptors are activated via cleavage of their N terminus by serine proteases (e.g., tryptase), unveiling an N terminus tethered ligand which binds to the second extracellular loop of the receptor. Increasing evidence has emerged identifying key pathophysiological roles for PAR2 in both rheumatoid arthritis (RA) and osteoarthritis (OA). Importantly, this includes both pro-inflammatory and destructive roles. For example, in murine models of RA, the associated synovitis, cartilage degradation, and subsequent bone erosion are all significantly reduced in the absence of PAR2. Similarly, in experimental models of OA, PAR2 disruption confers protection against cartilage degradation, subchondral bone osteosclerosis, and osteophyte formation. This review focuses on the role of PAR2 in rheumatic disease and its potential as an important therapeutic target for treating pain and joint degradation.

Spin States of Homochiral and Heterochiral Isomers of [Fe(PyBox)2 ]2+ Derivatives.

The following iron(II) complexes of 2,6-bis(oxazolinyl)pyridine (PyBox; LH ) derivatives are reported: [Fe(LH )2 ][ClO4 ]2 (1); [Fe((R)-LMe )2 ][ClO4 ]2 ((R)-2; LMe =2,6-bis{4-methyloxazolinyl}pyridine); [Fe((R)-LPh )2 ][ClO4 ]2 ((R)-3) and [Fe((R)-LPh )((S)-LPh )][ClO4 ]2 ((RS)-3; LPh =2,6-bis{4-phenyloxazolinyl}pyridine); and [Fe((R)-LiPr )2 ][ClO4 ]2 ((R)-4) and [Fe((R)-LiPr )((S)-LiPr )][ClO4 ]2 ((RS)-4; LiPr =2,6-bis{4-isopropyloxazolinyl}pyridine). Solid (R)-3⋅MeNO2 exhibits an unusual very gradual, but discontinuous thermal spin-crossover with an approximate T1/2 of 350 K. The discontinuity around 240 K lies well below T1/2 , and is unconnected to a crystallographic phase change occurring at 170 K. Rather, it can be correlated with a gradual ordering of the ligand conformation as the temperature is raised. The other solid compounds either exhibit spin-crossover above room temperature (1 and (RS)-3), or remain high-spin between 5-300 K [(R)-2, (R)-4 and (RS)-4]. Homochiral (R)-3 and (R)-4 exhibit more twisted ligand conformations and coordination geometries than their heterochiral isomers, which can be attributed to steric clashes between ligand substituents [(R)-3]; or, between the isopropyl substituents of one ligand and the backbone of the other ((R)-4). In solution, (RS)-3 retains its structural integrity but (RS)-4 undergoes significant racemization through ligand redistribution by 1 H NMR. (R)-4 and (RS)-4 remain high-spin in solution, whereas the other compounds all undergo spin-crossover equilibria. Importantly, T1/2 for (R)-3 (244 K) is 34 K lower than for (RS)-3 (278 K) in CD3 CN, which is the first demonstration of chiral discrimination between metal ion spin states in a molecular complex.

Investigating the first outbreak of oriental theileriosis in cattle in South Australia using multiplexed tandem PCR (MT-PCR).

This study investigated the first outbreak of oriental theileriosis in a herd of beef cattle in South Australia using a newly established multiplexed tandem PCR (MT-PCR) to identify, differentiate and quantitate the four genotypes (buffeli, chitose, ikeda and type 5) of Theileria orientalis recognised to occur in Australasia. Following clinical diagnosis of oriental theileriosis (based on clinical signs, laboratory findings and post mortem examination), 155 blood samples were collected from individual cows (n = 85) and calves (n = 70), and tested by MT-PCR. In total, 117 (75.48%) cattle were shown to be test-positive for T. orientalis. All four genotypes were detected, and ikeda had the highest prevalence (90.6%; 106/117), followed by buffeli (83.8%; 98/117), chitose (18.8%; 22/117) and type 5 (5.1%; 6/117). Mixed infections with genotypes buffeli and ikeda had a higher prevalence (55.5%; 65/117) than any other combination of genotypes. The prevalences of buffeli and ikeda were significantly higher (P<0.005) than those of chitose and type 5. The average intensity of infection with genotype ikeda (329,775 DNA copies) was significantly higher (P<0.0001) than buffeli (212,843) and chitose (125,462). This study reinforces the utility of MT-PCR as a diagnostic tool for rapidly investigating oriental theileriosis outbreaks in cattle herds and as a pre-movement screening test for preventing the introduction of this disease into non-endemic regions.

Pneumococcus in Aboriginal and Torres Strait Islanders: the role of Aboriginal Health Workers and implications for nursing practice.

Abstract Background: Pneumonia is a common cause of hospitalization in Aboriginal and Torres Strait Islander men and women. Aim: This article seeks to describe the importance of immunizing against pneumonia in Aboriginal Australians and suggest strategies for screening and follow-up. Method: An integrative literature review, using both published and grey literature was undertaken to identify methods of screening and surveillance strategies for pneumococcus. Results: The literature was summarized under the following themes: pneumococcal disease; prevention strategies; access to care; improving access to vaccinations; culturally competent interventions and the role of Aboriginal health professionals. Conclusion: Community controlled conditions and the role of the Aboriginal Health Workers are seen as critical to reducing health disparities. Nurses can play a critical role in bridging the gap between mainstream and community controlled organizations. Working to increase the numbers of Aboriginal health professionals is a critical step in improving health outcomes for Aboriginal and Torres Strait Islander peoples.

Childhood disability in Aboriginal and Torres Strait Islander peoples: a literature review.

INTRODUCTION: Aboriginal and Torres Strait Islander children have higher rates of disability than non-Indigenous children and are considered doubly disadvantaged, yet there is very little data reflecting prevalence and service access to inform design and delivery of services. Failing to address physical, social, and psychological factors can have life-long consequences and perpetuate longstanding health disparities. METHODS: A narrative literature review was undertaken to identify peer reviewed literature describing factors impacting on the prevention, recognition, and access to support and management of disability in Indigenous Australian children. RESULTS: Twenty-seven peer-reviewed journal articles met inclusion criteria. The majority of articles focused on the hearing loss and learning disabilities consequent of otitis media. Few articles reported data on urban or metropolitan Indigenous populations or described interventions. Individual/community-, provider-, and systems level factors were identified as impacting on recognition and management of disability in young Indigenous children. CONCLUSIONS: Given the burden of childhood disability, the limited literature retrieved is concerning as this is a barometer of activity and investment. Solutions addressing childhood disability will require collaboration between health, social and educational disciplines as well as an increased investment in prevention, identification and promotion of access.