Outcomes for Pressure Ulcer Trials (OUTPUTs) project: review and classification of outcomes reported in pressure ulcer prevention research.

In order to overcome inconsistencies in the reporting of outcomes in clinical trials, core outcome sets (COSs) have been developed in many clinical areas and the awareness of this concept is growing steadily. The Outcomes for Pressure Ulcer Trials (OUTPUTs) project aims to improve the quality of evidence from pressure ulcer prevention trials by developing a COS. As an initial step in the COS process we aimed to identify and classify both outcomes and concepts that represent potential outcomes for future trials that have been reported in pressure ulcer prevention research. A review was conducted in 12 major databases covering the literature indexed until 2016. Outcomes and relevant concepts reported in primary studies and/or reviews on pressure ulcer prevention in adult patients were extracted as presented in the articles, and afterwards inductively grouped into outcome domains. The domains were then categorized according to the outcome domain taxonomy recently proposed by the COMET group. In total 332 studies were included and 68 outcome domains were identified, covering multiple aspects of pressure ulcer prevention. Pressure ulcer occurrence was reported in 71% of all included studies, representing the most frequent outcome, followed by costs (22% of all studies) and acceptability of intervention and comfort (18% of all studies). A plethora of different outcomes are applied in pressure ulcer prevention research and substantial variations in definitions and reporting of similar outcomes were observed. A COS for pressure ulcer prevention trials is needed to overcome the noncomparability of outcomes.

High fat diet increases cognitive decline and neuroinflammation in a model of orexin loss.

Midlife obesity is a risk factor for cognitive decline and is associated with the earlier onset of Alzheimer's disease (AD). Diets high in saturated fat potentiate the onset of obesity, microglial activation, and neuroinflammation. Signaling deficiencies in the hypothalamic peptide orexin and/or orexin fiber loss are linked to neurodegeneration, cognitive impairment, and neuroinflammation. Prior studies show that orexin is neuroprotective, suppresses neuroinflammation, and that treatment with orexin improves cognitive processes in orexin/ataxin-3 (O/A3) mice, a transgenic mouse model of orexin neurodegeneration. Our overall hypothesis is that loss of orexin contributes to high fat diet (HFD)-induced hippocampal neuroinflammation and cognitive decline. To examine this, we tested male O/A3 mice (7-8 mo. of age) in a two-way active avoidance (TWAA) hippocampus-dependent memory task. We tested whether (1) orexin loss impaired cognitive function; (2) HFD worsened cognitive impairment; and (3) HFD increased microglial activation and neuroinflammation. O/A3 mice showed significant impairments in TWAA task learning vs. wild type (WT) mice (increased escapes p < 0.05, reduced avoidances p < 0.0001). Mice were then placed on HFD (45% total fat, 31.4% saturated fat) or remained on normal chow (NC; 4% total fat and 1% saturated fat), and TWAA was retested at 2 and 4 weeks. Learning impairment was evident at both 2 and 4 weeks in O/A3 mice fed HFD for following diet exposure vs. WT mice on normal chow or HFD (increased escapes, reduced avoidances p < 0.05). Additionally, O/A3 mice had increased gene expression of the microglial activation marker Iba-1 (measured via qRT-PCR, p < 0.001). Further characterization of the microglial immune response genes in hippocampal tissue revealed a significant increase in CX3 chemokine receptor 1 (CX3CR1), tumor necrosis factor-alpha (TNF-α) and the mitochondria-associated enzyme immune responsive gene-1 (Irg1). Collectively, our results indicate that orexin loss impairs memory, and that HFD accelerates hippocampus-dependent learning deficits and the onset of neuroinflammation.

Prognosis of the infected diabetic foot ulcer: a 12-month prospective observational study.

AIMS: To determine clinical outcomes and explore prognostic factors related to ulcer healing in people with a clinically infected diabetic foot ulcer. METHODS: This multicentre, prospective, observational study reviewed participants' data at 12 months after culture of a diabetic foot ulcer requiring antibiotic therapy. From participants' notes, we obtained information on the incidence of wound healing, ulcer recurrence, lower extremity amputation, lower extremity revascularization and death. We estimated the cumulative incidence of healing at 6 and 12 months, adjusted for lower extremity amputation and death using a competing risk analysis, and explored the relationship between baseline factors and healing incidence. RESULTS: In the first year after culture of the index ulcer, 45/299 participants (15.1%) had died. The ulcer had healed in 136 participants (45.5%), but recurred in 13 (9.6%). An ipsilateral lower extremity amputation was recorded in 52 (17.4%) and revascularization surgery in 18 participants (6.0%). Participants with an ulcer present for ~2 months or more had a lower incidence of healing (hazard ratio 0.55, 95% CI 0.39 to 0.77), as did those with a PEDIS (perfusion, extent, depth, infection, sensation) perfusion grade of ≥2 (hazard ratio 0.37, 95% CI 0.25 to 0.55). Participants with a single ulcer on their index foot had a higher incidence of healing than those with multiple ulcers (hazard ratio 1.90, 95% CI 1.18 to 3.06). CONCLUSIONS: Clinical outcomes at 12 months for people with an infected diabetic foot ulcer are generally poor. Our data confirm the adverse prognostic effect of limb ischaemia, longer ulcer duration and the presence of multiple ulcers.

'Loneliness in the city': examining socio-economics, loneliness and poor health in the North East of England.

OBJECTIVES: The aim of this study was to discover whether lower socio-economic status is associated with increased experiences of loneliness and isolation. The research subsequently determined whether this relationship impacted health inequalities. STUDY DESIGN: The study used a cross-sectional, self-reported survey collecting information on loneliness, isolation and poor health (n = 680). The survey was administered through Sunderland District Council in 2016-2017, and data were analysed at The University of Sunderland. METHODS: The study used a quantitative approach, and data were analysed using descriptive statistics, engaging in univariate, bivariate and multivariate levels of analysis. RESULTS: A number of significant findings emerged from the data analysis, linking lower socio-economic status to experiences of loneliness (P = 0.000) and social isolation (P = 0.000). When determining if social isolation and socio-economics had a detrimental impact on a person's health, no statistical association was discovered (P = 0.098). Yet, there was a significant relationship concerning socio-economic status, loneliness and poor health (P = 0.026). CONCLUSIONS: The authors have identified a number of associations within the data with reference to isolation, loneliness and poor health. Therefore, participants from a lower socio-economic group experienced disproportionately high levels of social isolation and emotional loneliness when compared with other socio-economic groups. The data also demonstrate that participants who experienced loneliness, and who were from a lower socio-economic background, were consistently more likely to report poor health than those from other socio-economic backgrounds.

Treatment of severe, chronic hand eczema: results from a UK-wide survey.

Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain information about their usual treatment pathways to inform the choice of the comparator in a trial of alitretinoin in severe HE (ALPHA trial); the results indicated that the treatment approaches favoured by UK dermatologists differ. Psoralen combined with ultraviolet A (PUVA) and alitretinoin were identified as the most frequent first-line treatment options for hyperkeratotic HE, whereas oral corticosteroids were identified as the most frequent first-line treatment for vesicular HE, followed by PUVA and alitretinoin. In terms of potential adverse effects of long-term or repeated use, oral steroids and ciclosporin A were reported to cause most concern. There is uncertainty about which treatment gives the best short and long-term outcomes, because of a lack of definitive randomised controlled trials evaluating the effectiveness of different treatment pathways in severe HE.

Using cognitive pre-testing methods in the development of a new evidenced-based pressure ulcer risk assessment instrument.

BACKGROUND: Variation in development methods of Pressure Ulcer Risk Assessment Instruments has led to inconsistent inclusion of risk factors and concerns about content validity. A new evidenced-based Risk Assessment Instrument, the Pressure Ulcer Risk Primary Or Secondary Evaluation Tool - PURPOSE-T was developed as part of a National Institute for Health Research (NIHR) funded Pressure Ulcer Research Programme (PURPOSE: RP-PG-0407-10056). This paper reports the pre-test phase to assess and improve PURPOSE-T acceptability, usability and confirm content validity. METHODS: A descriptive study incorporating cognitive pre-testing methods and integration of service user views was undertaken over 3 cycles comprising PURPOSE-T training, a focus group and one-to-one think-aloud interviews. Clinical nurses from 2 acute and 2 community NHS Trusts, were grouped according to job role. Focus group participants used 3 vignettes to complete PURPOSE-T assessments and then participated in the focus group. Think-aloud participants were interviewed during their completion of PURPOSE-T. After each pre-test cycle analysis was undertaken and adjustment/improvements made to PURPOSE-T in an iterative process. This incorporated the use of descriptive statistics for data completeness and decision rule compliance and directed content analysis for interview and focus group data. Data were collected April 2012-June 2012. RESULTS: Thirty-four nurses participated in 3 pre-test cycles. Data from 3 focus groups, 12 think-aloud interviews incorporating 101 PURPOSE-T assessments led to changes to improve instrument content and design, flow and format, decision support and item-specific wording. Acceptability and usability were demonstrated by improved data completion and appropriate risk pathway allocation. The pre-test also confirmed content validity with clinical nurses. CONCLUSIONS: The pre-test was an important step in the development of the preliminary PURPOSE-T and the methods used may have wider instrument development application. PURPOSE-T proposes a new approach to pressure ulcer risk assessment, incorporating a screening stage, the inclusion of skin status to distinguish between those who require primary prevention and those who require secondary prevention/treatment and the use of colour to support pathway allocation and decision making. Further clinical evaluation is planned to assess the reliability and validity of PURPOSE-T and it's impact on care processes and patient outcomes.

A systematic narrative review of support groups for people with dementia.

BACKGROUND: Provision of non-pharmacological interventions is a common policy objective for people with dementia, and support groups are an increasingly common intervention. However, there have been few attempts to synthesize evidence on the effectiveness of support groups for people with dementia. This review investigated the outcomes of support groups for people with dementia, explored participant characteristics and reviewed group formats. METHODS: A systematic review was undertaken and a narrative synthesis of data from 29 papers (reporting on 26 groups and a survey of a range of groups) was conducted. RESULTS: Support groups seem acceptable to people with dementia. Qualitative studies report subjective benefits for participants but there is limited evidence of positive outcomes based on quantitative data. Samples have tended to be homogenous and this may limit the generalizability of findings. CONCLUSIONS: Although qualitative studies will remain important in this area, further mixed-methods randomized controlled trials (RCTs)or comparison group studies with longer follow-up periods are needed to strengthen the evidence base.

Microbiome-induced Increases and Decreases in Bone Tissue Strength can be Initiated After Skeletal Maturity.

Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n=143 total, n=12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected from geometry in mice from the Continuous (p= 0.001), Delayed (p= 0.005), and Initial (p=0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota, however, led to a bone matrix strength similar to Unaltered animals (p=0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating sex-related differences in the response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed (Raman spectroscopy). Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) is small; however, this suggests that microbiome-induced changes in bone matrix occur without osteoblast/osteoclast turnover using an, as of yet unidentified mechanism. These findings add to evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.

A systematic review of risk factors for the development and recurrence of pressure ulcers in people with spinal cord injuries.

STUDY DESIGN: A systematic review was undertaken, based upon methods recommended for effectiveness questions but adapted to identify observational risk factor (RF) studies. OBJECTIVES: The literature identifies many RFs for pressure ulcer (PU) recurrence and development; however, RFs independently predictive of PU development in adults with spinal cord injury (SCI) have not been determined. A systematic review was undertaken to identify RFs for PUs for people with SCI. SETTING: Acute hospital, community and rehabilitation settings. METHODS: Electronic searches of MEDLINE, EMbase and Cochrane databases from 1980 to 2011 were completed. Retrieved studies were assessed for eligibility and quality criteria applied by two independent reviewers. Identified RFs were categorised into themes and compared and contrasted with RFs identified for the general PU population. RESULTS: The five studies included 18 RFs. These were classified into six themes: sociodemographic, neurological, functional, clinical, biological and medical care management. RFs for both the general and SCI-specific populations were similar, however, clinical, functional and hospital management emerged as specific RF domains for the SCI population. CONCLUSION: We identified SCI-specific RFs for the development and recurrence of PUs. However, these findings are based on a small number of studies; highlighting the need for further confirmatory work to reduce PU development and recurrence, and provide a foundation for SCI risk assessment development.

Applying mixed methods to pretest the Pressure Ulcer Quality of Life (PU-QOL) instrument.

PURPOSE: Pretesting is key in the development of patient-reported outcome (PRO) instruments. We describe a mixed-methods approach based on interviews and Rasch measurement methods in the pretesting of the Pressure Ulcer Quality of Life (PU-QOL) instrument. METHODS: We used cognitive interviews to pretest the PU-QOL in 35 patients with pressure ulcers with the view to identifying problematic items, followed by Rasch analysis to examine response options, appropriateness of the item series and biases due to question ordering (item fit). We then compared findings in an interactive and iterative process to identify potential strengths and weaknesses of PU-QOL items, and guide decision-making about further revisions to items and design/layout. RESULTS: Although cognitive interviews largely supported items, they highlighted problems with layout, response options and comprehension. Findings from the Rasch analysis identified problems with response options through reversed thresholds. CONCLUSIONS: The use of a mixed-methods approach in pretesting the PU-QOL instrument proved beneficial for identifying problems with scale layout, response options and framing/wording of items. Rasch measurement methods are a useful addition to standard qualitative pretesting for evaluating strengths and weaknesses of early stage PRO instruments.

Coronary artery pseudoaneurysm following blunt trauma.

A 42-year-old male was admitted with persistent atypical chest pain following a motorcycle accident six months previously. A pseudoaneurysm, diagnosed by transthoracic echocardiography and computed tomography, was excised and the right coronary artery underwent bypass grafting.

What influences the impact of pressure ulcers on health-related quality of life? A qualitative patient-focused exploration of contributory factors.

With the recognition of health-related quality of life (HRQL) as an important and relevant outcome in pressure ulceration, it is important to gain better understanding of the complex relationship among the various factors that affect it. A problem with existing literature in this area is that the impact of having a pressure ulcer on HRQL is combined conceptually with contributory factors which may influence outcome. This study identified contributory factors affecting pressure ulcer-related HRQL and explored interrelationships between factors based on views of adults with pressure ulcers. We obtained patient-reported qualitative data through semi-structured interviews with 30 patients with pressure ulcers recruited from hospital and community settings around England and Northern Ireland. Patients described how pressure ulcers affected their lives by recounting specific relevant events. Events (patient-reported issues) were sorted into categories and data framework analysed to produce a taxonomy of contributory factors. Inter-rater reliability established the extent of agreement between two independent raters. We identified 16 contributory factors, into two theme taxonomy: experience-of-care and individual-patient factors, defined by descriptive components. Our taxonomy is a comprehensive theoretical model of factors that contribute to pressure ulcer-related HRQL. We have also identified further research priorities to inform clinical practice.

Using multi-objective optimisation with ADM1 and measured data to improve the performance of an existing anaerobic digestion system.

This paper presents a method to model and optimise the substrate feeding rate of an anaerobic digestion (AD) system. The method is demonstrated for a case study plant in Bangalore, India, using onsite kitchen waste to provide biogas for cooking. The AD system is modelled using Anaerobic Digestion Model No. 1 (ADM1) and a genetic algorithm (GA) is applied to control the substrate feeding rate in order to simultaneously minimise the volume of flared biogas, unmet gas demand and energy cost. Our results show that ADM1 can predict biogas yield from a continuously operated digester well with mean percentage errors between daily predicted and measured data values of only 5.7% for March 2017 and 17.8% for July 2017. When biogas flaring and unmet gas demand were minimised, the amount of biogas flared reduced from 886.62 m3 to 88.87 m3 in March and from 73.79 m3 to 68.49 m3 in July. When the energy cost was also considered within the objective function, the biogas flared reduced from 886.62 m3 to 281.27 m3 for March, but increased from 73.79 m3 to 180.11 m3 for July. The amount of flaring increased in July as the energy cost function increased biogas yield without considering surplus gas production beyond demand and storage capacity. As AD systems are often operated to maximise biogas production, these results highlight the need for multi-objective optimisation, particularly for off-grid AD systems.

Examining the quality of work-life of paramedics in northern Ontario, Canada: A cross-sectional study.

BACKGROUND: Paramedics are exposed to multiple stressors in the workplace. They are more likely to develop occupational-related stress conditions compared to other occupations. This study focused on understanding the factors affecting QoWL of paramedics in northern Ontario, Canada; a particular focus was on understanding the personal and organizational factors, such as practicing community paramedicine (CP), which may be associated with Quality of Work Life (QoWL). METHODS: Paramedic QoWL was assessed using an online survey that was distributed to approximately 879 paramedics across northern Ontario. The survey included the 23-Item Work- Related Quality of Work Life Scale. Data analysis involved linear regressions with nine predictor variables deemed to be related to QoWL for paramedics with QoWL and its six subscales as dependent variables. Multiple linear regressions were used to assess the personal and organizational factors, such as practicing of CP, which predicted QoWL. RESULTS: One hundred and ninety-seven paramedics completed the questionnaire. Overall, the mean QoWL score of all paramedic participants was 73.99, and this average compared to relevant published norms for other occupations. Factors that were most associated with higher QoWL were, experience practicing CP (p < 0.05), number of sick days/year (p < 0.01), and higher self- rated mental health (p < 0.001). CONCLUSIONS: Higher paramedic QoWL appears to be associated with many factors such as number of sick days per year, self-rated mental health, and participation in CP. EMS organizations should consider establishing necessary workplace health promotion strategies that are targeted at improving QoWL for paramedics.

Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: This guideline provides an overview of the evidence on established and emerging risk factors for stroke to provide evidence-based recommendations for the reduction of risk of a first stroke. METHODS: Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council Scientific Statement Oversight Committee and the AHA Manuscript Oversight Committee. The writing group used systematic literature reviews (covering the time since the last review was published in 2006 up to April 2009), reference to previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate recommendations using standard AHA criteria (Tables 1 and 2). All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. The guideline underwent extensive peer review by the Stroke Council leadership and the AHA scientific statements oversight committees before consideration and approval by the AHA Science Advisory and Coordinating Committee. RESULTS: Schemes for assessing a person's risk of a first stroke were evaluated. Risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented or less well documented). Nonmodifiable risk factors include age, sex, low birth weight, race/ethnicity, and genetic predisposition. Well-documented and modifiable risk factors include hypertension, exposure to cigarette smoke, diabetes, atrial fibrillation and certain other cardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution. Less well-documented or potentially modifiable risk factors include the metabolic syndrome, excessive alcohol consumption, drug abuse, use of oral contraceptives, sleep-disordered breathing, migraine, hyperhomocysteinemia, elevated lipoprotein(a), hypercoagulability, inflammation, and infection. Data on the use of aspirin for primary stroke prevention are reviewed. CONCLUSIONS: Extensive evidence identifies a variety of specific factors that increase the risk of a first stroke and that provide strategies for reducing that risk.

Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is commonly used for respiratory failure due to severe COVID-19 pneumonitis, including in patients deemed not likely to benefit from invasive mechanical ventilation (nIMV). Little evidence exists demonstrating superiority over conventional oxygen therapy, whilst ward-level delivery of CPAP presents practical challenges. We sought to compare clinical outcomes of oxygen therapy versus CPAP therapy in patients with COVID-19 who were nIMV. METHODS: This retrospective multi-centre cohort evaluation included patients diagnosed with COVID-19 who were nIMV, had a treatment escalation plan of ward-level care and clinical frailty scale ≤ 6. Recruitment occurred during the first two waves of the UK COVID-19 pandemic in 2020; from 1st March to May 31st, and from 1st September to 31st December. Patients given CPAP were compared to patients receiving oxygen therapy that required FiO2 ≥0.4 for more than 12 hours at hospitals not providing ward-level CPAP. Logistic regression modelling was performed to compare 30-day mortality between treatment groups, accounting for important confounders and within-hospital clustering. FINDINGS: Seven hospitals provided data for 479 patients during the UK COVID-19 pandemic in 2020. Overall 30-day mortality was 75.6% in the oxygen group (186/246 patients) and 77.7% in the CPAP group (181/233 patients). A lack of evidence for a treatment effect persisted in the adjusted model (adjusted odds ratio 0.84 95% CI 0.57-1.23, p=0.37). 49.8% of patients receiving CPAP-therapy (118/237) chose to discontinue it. INTERPRETATION: No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the current treatment guidance and widespread application of CPAP in this setting. FUNDING: L Pearmain is supported by the MRC (MR/R00191X/1). TW Felton is supported by the NIHR Manchester Biomedical Research Centre.

Elastase inhibitor. Characterization of the human elastase inhibitor molecule associated with monocytes, macrophages, and neutrophils.

A fast-acting inhibitor of serine elastase has been detected at high levels in human neutrophils, fresh monocytes, matured monocytes, and macrophages. The elastase inhibitor was isolated from large scale cultures of the monocyte-like cell line U937 by DNase chromatography, disulfide exchange, Phenyl-Sepharose, Red A-agarose, and DEAE HPLC chromatography with an average yield of 480 micrograms from 1.8 x 10(10) cells. The isolated polypeptide was verified as elastase inhibitor by its ability to (a) form a covalent complex with elastase; and (b) inhibit the elastinolytic activity of elastase. The purified elastase inhibitor molecule is unique, i.e., physiochemical and/or functional properties distinguish it from all other serine proteinase inhibitors. Treatment with iodoacetamide abrogates the ability of the molecule to form a complex with elastase, thereby providing evidence for the presence of an essential cysteine residue. Based on functional criteria, this elastase inhibitor has been grouped with the proteinase inhibitors of the serpin superfamily. The purified elastase inhibitor is a single polypeptide of Mr approximately 42,000. The NH2 terminus appears to be blocked. Compositional analyses indicates five cysteine residues per molecule of approximately 360 amino acid residues. Negligible levels of carbohydrate were detected on gas-liquid chromatography. This finding and the insensitivity of the molecule to peptide N-glycosidase F treatment strongly indicate that the elastase inhibitor is a nonglycosylated protein.

Dynamic interaction of PTPmu with multiple cadherins in vivo.

There is a growing body of evidence to implicate reversible tyrosine phosphorylation as an important mechanism in the control of the adhesive function of cadherins. We previously demonstrated that the receptor protein tyrosine phosphatase PTPmu associates with the cadherin-catenin complex in various tissues and cells and, therefore, may be a component of such a regulatory mechanism (Brady-Kalnay, S. M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977- 986). In this study, we present further characterization of this interaction using a variety of systems. We observed that PTPmu interacted with N-cadherin, E-cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We observed a direct interaction between PTPmu and E-cadherin after coexpression in Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v-Src, the complex between PTPmu and E-cadherin was dynamic, and conditions that resulted in tyrosine phosphorylation of E-cadherin were associated with dissociation of PTPmu from the complex. Furthermore, we have demonstrated that the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was required for association with PTPmu in WC5 cells. Zondag et al. (Zondag, G., W. Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513-1517) have asserted that the association we observed between PTPmu and the cadherin-catenin complex in immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity between BK2, our antibody to PTPmu, and cadherins. In this study we have confirmed our initial observation and demonstrated the presence of cadherin in immunoprecipitates of PTPmu obtained with three antibodies that recognize distinct epitopes in the phosphatase. In addition, we have demonstrated directly that the anti-PTPmu antibody BK2 that we used initially did not cross-react with cadherin. Our data reinforce the observation of an interaction between PTPmu and E-cadherin in vitro and in vivo, further emphasizing the potential importance of reversible tyrosine phosphorylation in regulating cadherin function.