A unified call to action from Australian nursing and midwifery leaders: ensuring that Black lives matter.

Nurses and midwives of Australia now is the time for change! As powerfully placed, Indigenous and non-Indigenous nursing and midwifery professionals, together we can ensure an effective and robust Indigenous curriculum in our nursing and midwifery schools of education. Today, Australia finds itself in a shifting tide of social change, where the voices for better and safer health care ring out loud. Voices for justice, equity and equality reverberate across our cities, our streets, homes, and institutions of learning. It is a call for new songlines of reform. The need to embed meaningful Indigenous health curricula is stronger now than it ever was for Australian nursing and midwifery. It is essential that nursing and midwifery leadership continue to build an authentic collaborative environment for Indigenous curriculum development. Bipartisan alliance is imperative for all academic staff to be confident in their teaching and learning experiences with Indigenous health syllabus. This paper is a call out. Now is the time for Indigenous and non-Indigenous nurses and midwives to make a stand together, for justice and equity in our teaching, learning, and practice. Together we will dismantle systems, policy, and practices in health that oppress. The Black Lives Matter movement provides us with a 'now window' of accepted dialogue to build a better, culturally safe Australian nursing and midwifery workforce, ensuring that Black Lives Matter in all aspects of health care.

All's well that ends well.

A recent Cold Spring Harbour meeting(*) reviewed the latest progress on telomeres (the specialized structures that form the ends of chromosomes) and telomerase (the enzyme primarily responsible for their replication). Among the many aspects of telomere biology covered were strong sessions elaborating telomere replication and length regulation, telomerase structure and function, end-binding and telomere-associated proteins, DNA-damage-response proteins and telomerase-independent telomere maintenance.

Qualitative analysis of domestic violence detection and response in a tertiary hospital.

INTRODUCTION Domestic and family violence is a public health problem of epidemic proportions and a significant issue facing the Australian community. It knows no boundaries, is indiscriminate to geographical location, social class, age, religious or cultural background. AIM This study aimed to analyse the processes currently used to identify and respond to domestic and family violence in a large tertiary hospital in Australia, and to classify the benefits and weaknesses of these existing systems. METHODS A qualitative method used semistructured, face-to-face and telephone interviews with key informants in 16 key areas across the hospital. Thematic analysis of the interviews was used to define the key issues and areas of interest identified by participants. RESULTS There was a dearth of existing guidelines or pathways of care for patients experiencing domestic violence. Several strengths and weaknesses were identified in relation to the protocols and systems used by the hospital, including limited training for staff and a lack of standardisation of processes, workplace instructions and clinical guidelines. With the exception of maternity services, no clinical service area used a guideline or work instruction. Most interviewees highlighted the need for the safety and protection of staff and victims as a priority. DISCUSSION Domestic and family violence is an enormous burden on the health system. However, many staff have little or no guidance on dealing with it or are unaware of existing protocols or guidelines for detection or response. Participants recommended further education and training for staff, consistent guidelines, specialist liaison and more educational and information resources for staff and patients. Further investigation and discussions with patients affected by violence is warranted to provide robust recommendations for policy change.

Effects of autoantibodies to the insulin receptor on isolated adipocytes. Studies of insulin binding and insulin action.

Autoantibodies to the insulin receptor have been detected in the sera of several patients with the Type B syndrome of insulin resistance and acanthosis nigricans. In this study we have used three of these sera (B-1, B-2, and B-3) as probes of the insulin receptor in isolated rat adipocytes. Preincubation of adipocytes with each of the three sera resulted in an inhibition of subsequent [(125)I]insulin binding. 50% inhibition of binding occurred with serum dilutions of 1:5 to 1:7,500. As in our previous studies with other tissues, Scatchard analysis of the insulin-binding data was curvilinear consistent with negative cooperativity. Computer analysis suggested that in each case the inhibition of binding was due to a decrease in receptor affinity rather than a change in available receptor number. In addition to the effects on insulin binding, adipocytes pretreated with antireceptor sera also showed alterations in biological responses. All three sera produced some stimulation of basal glucose oxidation. With serum B-3, maximal stimulation of glucose oxidation occurred at a serum concentration that inhibited binding by only 10-15%, whereas with serum B-2 the dilution curves for inhibition of binding and stimulation of glucose oxidation were superimposable. Serum B-1 behaved as a partial agonist; that is, it inhibited binding more effectively than it stimulated glucose oxidation. Cells pretreated with this serum in a concentration which inhibited binding by 80% also showed a five-fold shift to the right in the dose response of insulin-stimulated glucose oxidation, whereas spermine-stimulated glucose oxidation was unaffected. Serum B-2, which contained the highest titer of antireceptor antibodies, also stimulated 2-deoxy-glucose transport, as well as glucose incorporation into lipid and glycogen. Both the ability of the serum to inhibit binding and stimulate glucose utilization were enriched in purified immunoglobulin fractions and retained in the F(ab')(2) fragment of the IgG. In addition, the bioactivity was blocked by antihuman IgG but not by anti-insulin antibodies. Enzymatic digestion of adipocytes with trypsin resulted in a complete loss of insulin-stimulated bioactivity of serum B-3, but had only minor effects on the glucose oxidation produced by serum B-1 or B-2.These data suggest that the antibodies present in these three sera bind to different determinants on the insulin receptor. Thus, these antibodies may be useful probes of receptor structure and function.

Clinical disorders associated with autoantibodies to the insulin receptor. Simulation by passive transfer of immunoglobulins to rats.

Patients with autoantibodies to the insulin receptor (Anti-R) may exhibit either fasting hypoglycemia or hyperglycemia and extreme insulin resistance. Occasionally, both these phenomena are observed in the same patient at different times in the clinical course. In an effort to understand what determines the patient's response to Anti-R, we developed an animal model of these clinical disorders by passive transfer of Anti-R IgG to rats. IgG fractions from the plasma of Anti-R patients and control subjects were prepared by affinity chromatography with staphylococcal protein A-Sepharose. Anti-R IgG, injected into fasting rats, induced severe and persistent hypoglycemia (plasma glucose 30-60 mg/dl). Rats injected with control IgG maintained a plasma glucose within the range of 75 (fasting) to 165 mg/dl (feeding). In comparison with the effects of insulin, the hypoglycemic response to Anti-R IgG had a slower onset (2-4 h) and lasted longer (8-24 h). Similar, dose-dependent hypoglycemic responses were observed in rats whether the Anti-R IgG was derived from an insulin-resistant or hypoglycemic patient. When Anti-R IgG was administered in sufficiently high doses for several days to fed rats, persistent hyperglycemia (plasma glucose 200-400 mg/dl) developed. Based on these in vivo and previous in vitro studies, we attribute the hypoglycemic response to an insulin-like effect of Anti-R, and the hyperglycemic response to a desensitization of host tissues to the effects of insulin, with more prolonged exposure to higher levels of Anti-R.

Prevalence and determinants of fatigue in patients with moderate to severe chronic GvHD.

Although fatigue is common after allogeneic hematopoietic cell transplantation, little is known about fatigue in patients with chronic GvHD (cGvHD). The aim of this study was to explore factors associated with fatigue in cGvHD. Data were drawn from a sequentially recruited, cross-sectional study of adults with moderate or severe cGvHD (n=263). Respondents were classified as fatigued or not fatigued based on their response to a single item regarding loss of energy from the Lee cGvHD Symptom Scale. In univariate analysis, factors significantly associated with fatigue included performance status, number of prior cGvHD therapies, cGvHD symptom bother, self-assessed physical and mental health, nutritional status, walk velocity and self-reported physical activity. There were no significant associations between fatigue and disease-related cGvHD variables. Multivariable logistic regression demonstrated that being less active and having pulmonary and/or muscle/joint symptoms were independently associated with fatigue. In conclusion, clinically significant fatigue was prevalent in more than one-third of subjects with cGvHD, and was disabling. Absence of association with measures of cGvHD severity underscores the need to elucidate the pathogenesis of fatigue and its relationship with inflammatory activity. Pulmonary and muscle/joint symptoms and physical inactivity represent potential targets for intervention in clinical studies.

Oral disease profiles in chronic graft versus host disease.

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials.

Abnormal growth factor and cytokine expression in Dupuytren's contracture.

AIM: To analyse patterns of gene expression for peptide regulatory factors in patients with Dupuytren's contracture. METHODS: Tissue samples (palmer fascia) from 12 patients with Dupuytren's contracture and 12 controls were studied using the reverse transcription/polymerase chain reaction (RT/PCR) technique. RESULTS: Tissue from patients with Dupuytren's contracture expressed a higher percentage of peptide regulatory factors than that of controls: interleukin-1 alpha (83% v 16%; p < 0.01); interleukin-1 beta (66% v 8%; p < 0.01); transforming growth factor beta (75% v 25%; p < 0.02); and basic fibroblast growth factor (66% v 25%; p < 0.05). Platelet derived growth factors alpha and beta were also expressed more commonly (66% v 33% and 25% v 16%, respectively), but these differences were not significant. CONCLUSIONS: The increased prevalence of expression for the above mRNAs in Dupuytren's tissue is relevant as interleukin-1, basic fibroblast growth factor, and transforming growth factor beta stimulate the growth of fibroblasts and transforming growth factor beta also enhances production of collagen and other extracellular matrix proteins. Excessive local release of these peptide regulatory factors may have an important role in the pathogenesis of Dupuytren's contracture.

Pathways of insulin degradation in isolated adipocytes: evaluation by gel filtration and differential precipitation.

Insulin degradation by isolated rat adipocytes was evaluated using gel filtration and a new technique of differential precipitation to fractionate the sample by molecular size using polyethylene glycol and trichloracetic acid. At 37 degrees C, 125I-insulin bound to adipocytes was rapidly degraded into small fragments or iodotyrosine. 125I-insulin in the medium was also degraded into iodotyrosine, as well as fragments intermediate in molecular weight between insulin and iodotyrosine. Lowering the temperature to 15 degrees C or adding bacitracin to the medium inhibited degradation in the medium but had little effect on cell-associated degradation. Methylamine, on the other hand, inhibited cell-associated degradation, but had little effect on the insulin degradation in the medium. Addition of methylamine or bacitracin or lowering of the temperature increased the amount of 125I-insulin bound to the cell and prolonged the steady-state of binding. Bacitracin also produced a slight shift to the left in the dose response curve for insulin-stimulated glucose oxidation. Methylamine increased basal glucose oxidation, but had no effect on insulin sensitivity as measured in the glucose oxidation bioassay. These data suggest that isolated adipocytes in vitro exhibit at least two distinct pathways of insulin degradation, a cell-associated pathway which can be inhibited by methylamine and a medium pathway which can be inhibited by bacitracin. Neither pathway, however, appears to be closely linked to insulin's ability to stimulate glucose metabolism in these cells.

The regulations of renal ammoniagenesis in the rat by extracellular factors. I. The combined effects of acidosis and physiologic fuels.

Substrate oxidation by rat kidney slices regulates renal ammoniagenesis from glutamine. At concentrations close to those expected in plasma, lactate alone, or combined with other renal fuels, inhibits ammoniagenesis markedly; glucose and citrate decrease ammoniagenesis slightly. However, lactate, citrate, and glucose inhibit ammoniagenesis of kidney slices from acidotic rats less than ammoniagenesis of kidney slices from control rats. Lesser inhibition of ammoniagenesis is seen also when acidotic slices rather than control slices are incubated in the presence of all the tested substrates combined in the same medium. In addition to decreasing the ammoniagenesis of renal slices from control rats, the presence of lactate causes an augmented accumulation of glutamate. In contrast, adding lactate to acidotic slices does not increase glutamate accumulation nearly as much. When glutamate is substituted for glutamine in the medium, lactate still decreases ammonia production, but to a lesser extent with acidotic slices. Changes in medium pH from 7.0 to 7.8 have no, or only small, overall effects on net renal slice ammonia production from glutamine under any of the circumstances tested. We conclude that lactate alone and combined with other substrates decreases ammoniagenesis primarily at the glutamate dehydrogenase step and that slices from acidotic rats are relatively resistant to substrate mediated inhibition.

Expression of growth factors, cytokines and matrix metalloproteinases in frozen shoulder.

Frozen shoulder is a chronic fibrosing condition of the capsule of the joint. The predominant cells involved are fibroblasts and myofibroblasts which lay down a dense matrix of type-I and type-III collagen within the capsule. This subsequently contracts leading to the typical features of pain and stiffness. Cytokines and growth factors regulate the growth and function of the fibroblasts of connective tissue and remodelling of the matrix is controlled by the matrix metalloproteinases (MMPs) and their inhibitors. Our aim was to determine whether there was an abnormal expression or secretion of cytokines, growth factors and MMPs in tissue samples from 14 patients with frozen shoulder using the reverse transcription/polymerase chain reaction (RT/PCR) technique and to compare the findings with those in tissue from four normal control shoulders and from five patients with Dupuytren's contracture. Tissue from frozen shoulders demonstrated the presence of mRNA for a large number of cytokines and growth factors although the frequency was only slightly higher than in the control tissue. The frequency for a positive signal for the proinflammatory cytokines Il-beta and TNF-alpha and TNF-beta, was not as great as in the Dupuytren's tissue. The presence of mRNA for fibrogenic growth factors was, however, more similar to that obtained in the control and Dupuytren's tissue. This correlated with the histological findings which in most specimens showed a dense fibrous tissue response with few cells other than mature fibroblasts and with very little evidence of any active inflammatory cell process. Positive expressions of the mRNA for the MMPs were also increased, together with their natural inhibitor TIMP. The notable exception compared with control and Dupuytren's tissue was the absence of MMP-14, which is known to be a membrane-type MMP required for the activation of MMP-2 (gelatinase A). Understanding the control mechanisms which play a part in the pathogenesis of frozen shoulder may lead to the development of new regimes of treatment for this common, protracted and painful chronic fibrosing condition.

Prevalence and site specificity of Sarcocystis greineri sarcocysts in Virginia opossum (Didelphis virginiana) in Florida.

Sarcocysts of Sarcocystis greineri in the Virginia opossum (Didelphis virginiana) were observed for documenting sarcocyst prevalence, seasonal prevalence, and muscle specificity. Characteristics of sarcocysts found in striated muscle were recorded, as were light microscopy measurements. Overall prevalence of sarcocysts in striated muscle was 10.0% (24/240). No statistical difference (P = 0.156) in prevalence was detected between summer (13.1%; 16/122) and fall (6.7%; 8/118). Sarcocysts were found in muscles of the diaphragm, leg, breast, tongue, back, and esophagus. Diaphragm had the highest specificity of 72.7% (8/11), which was significantly different (P = 0.05) when compared with tongue and esophagus at 16.6% (1/6). Breast and leg muscle had a specificity of sarcocysts of 54.5% (6/11), whereas 27.2% (3/11) of back muscles contained sarcocysts.

From hospital to community: a follow up of community placement of the long term mentally ill.

AIM: To evaluate the planned movement of long stay patients with chronic mental disorders from Sunnyside Hospital into staffed residential accommodation in the community. METHOD: Sixty-nine long stay psychiatric patients were followed up over 18 months to assess their social functioning, psychiatric symptomatology, resource use, relapse rate, satisfaction with their care, and impact on the community. RESULTS: Social functioning and psychiatric symptomatology scores on the social behaviour schedule remained stable overall. Relapse rates were low, and rehospitalisation rare. Use of community and area health board resources tended to decrease. Over 90% of patient responses indicated satisfaction with their new living arrangements. Over 50% reported no contact with outside friends, though over the follow up period about 70% maintained at least monthly contact with relatives. CONCLUSION: Careful community placement of the long term mentally ill, with ongoing supervision, can have a successful outcome from clinical, patient and community perspectives.

Adherence to cardiac therapy for men with coronary artery disease.

A study developed and executed within Orem's (1995) Self-Care Deficit Theory of Nursing uncovered factors that influence men's adherence to cardiac therapy. Data obtained from individual audiotaped interviews with five men 60 to 70 years of age in northwestern Ohio were analyzed using Colaizzi's (1978) method. Specific self-care factors, possessed by all the men and responsible for facilitating and inhibiting adherence to cardiac therapy, were found within the components for self-care agency and basic conditioning factors. Identification of these factors is critical, as the completion of the requirements of the prescribed cardiac therapy regimen can assist persons in achieving maximal cardiac efficiency while promoting independence, which ultimately affects their self-care agency. This study makes valuable contributions by (a) becoming aware of factors that influence men's adherence to cardiac therapy, (b) offering direction for interventions focused on self-care, and (c) serving as an impetus for further research.

Malnutrition in patients with chronic GVHD.

Malnutrition is a known complication of chronic GVHD (cGVHD), but has not been well described in the context of organ-specific manifestations and the recent National Institutes of Health (NIH) criteria. Here, 210 cGVHD patients were analyzed, in a cross-sectional study design, for demographics, transplant-related history, clinical assessments, symptoms, function, quality-of-life, laboratory values and survival in order to determine their associations with nutritional status. Most patients had long-standing, moderate or severe cGVHD and had failed many lines of therapy. Twenty-nine percent (60/210) of subjects were malnourished, using the subjective Patient-Generated Subjective Global Assessment (PG-SGA) questionnaire and evaluation. No demographic or transplant characteristics were associated with malnutrition; cGVHD of the lungs, gastrointestinal (GI) tract and mouth, NIH global score, cGVHD symptoms, worse functioning, low albumin, poorer survival and low BMI were associated with malnutrition. A predictive model was developed from all variables of significance: cGVHD of the lungs, GI tract, mouth and BMI accurately predicted 84.2% of malnourished patients as well as 87.2% of well-nourished patients. The PG-SGA questionnaire may be a useful tool in diagnosing nutritional deficits in cGVHD patients undergoing one-time evaluations. Longitudinal prospective studies should assess the utility of nutritional support interventions in cGVHD.

NHANES III equations enhance early detection and mortality prediction of bronchiolitis obliterans syndrome after hematopoietic SCT.

Bronchiolitis obliterans syndrome (BOS) is a serious complication of chronic GVHD (cGVHD) following HSCT (hematopoietic SCT). The clinical diagnosis of BOS is based on pulmonary function test (PFT) abnormalities including: FEV1<75% predicted and obstructive FEV1/VC ratio, calculated using reference equations. We sought to determine if the frequency of clinical diagnoses and severity of BOS would be altered by using the recommended NHANES III vs older equations (Morris/Goldman/Bates, MGB) in 166 cGVHD patients, median age 48 (range: 12-67). We found that NHANES III equations significantly increased the prevalence of BOS, with an additional 11% (18/166) meeting diagnostic criteria by revealing low FEV1 (<75%) (P<0.0001), and six additional patients by obstructive ratio (vs MBG). Collectively, this led to an increase of BOS incidence from 17 (29/166) to 29% (41/166). For patients with severe BOS, (FEV1<35%), NHANES III equations correctly predicted death 71.4% vs 50% using MGB. In conclusion, the use of NHANES III equations markedly increases the proportion of cases meeting diagnostic criteria for BOS and improves prediction of survival.

Validation of the National Institutes of Health chronic GVHD Oral Mucosal Score using component-specific measures.

Oral chronic GVHD (cGVHD) is a common, late complication of alloSCT that is associated with significant patient morbidity. The NIH Oral Mucosal Score (NIH OMS) was developed to assess oral cGVHD therapeutic response, but has not been fully validated. This study's purpose was to conduct a rigorous construct validity and internal consistency analysis of this score and its components (erythema, lichenoid, ulcers, mucoceles) using established measures of oral pain, oral function, oral-related quality-of-life, nutrition and laboratory parameters in 198 patients with cGVHD. The construct validity of the NIH OMS was supported: a moderate correlation was observed between NIH OMS and mouth pain (rho=0.43), while a weaker correlation was observed with low albumin (rho=-0.26). Total NIH OMS, erythema and lichenoid components were associated with malnutrition, oral pain and impaired oral QOL, while ulcers were only associated with oral pain. No associations were found between mucoceles and any indicator evaluated, including salivary function or xerostomia. Kappa determined between scale components was low overall (all 0.35), supporting a conclusion that each component measures a distinct manifestation of oral cGVHD. This study supports the use of the NIH OMS and its components (erythema, lichenoid and ulcerations) to measure clinician-reported severity of oral cGVHD.

Active thrombopoiesis is associated with worse severity and activity of chronic GVHD.

Chronic GVHD (cGVHD) is a major complication of allogeneic hematopoietic SCT. Post transplant thrombocytopenia in patients with cGVHD has been associated with poor outcome and its etiology is unclear. We investigated whether thrombopoiesis, assessed via measurement of the absolute immature platelet number (AIPN) in the blood, is impaired in cGVHD, and whether the level of thrombopoiesis correlates with the severity and activity of cGVHD as assessed via the National Institutes of Health (NIH) organ scoring system. We used a cohort of 110 well-characterized cGVHD patients, including 83 (75%) with severe cGVHD per NIH global score. Higher AIPN was associated with active therapeutic intent (P=0.026), lower Karnofsky score (P=0.0013), worse joint/fascia cGVHD (P=0.0005) and worse skin cGVHD (P=0.0044). AIPN correlated with platelet counts and was not correlated with ANC, WBC, C-reactive protein (CRP), absolute lymphocyte count (ALC), albumin, total and average NIH scores, or number of prior systemic therapies. AIPN values for cGVHD patients substantially overlapped those of the normal population. Higher AIPN, as marker of active thrombopoiesisis, was associated with worse severity and activity of cGVHD, especially skin and joints/fascia manifestations. Among patients with stable moderate or severe cGVHD, there was no evidence of hypoproduction of platelets. Future studies should further investigate the role of thrombopoiesis in cGVHD.

Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity.

Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.