Migration of vascular smooth muscle cells (VSMCs) contributes to vascular pathology. PDGF induces VSMC migration by a Nox1-based NADPH oxidase mediated mechanism. We have previously shown that PDGF-induced migration in VSMCs requires Slingshot-1L (SSH1L) phosphatase activity. In the present work, the mechanism of SSH1L activation by PDGF is further investigated. We identified a 14-3-3 consensus binding motif encompassing Ser-834 in SSH1L that is constitutively phosphorylated. PDGF induces SSH1L auto-dephosphorylation at Ser-834 in wild type (wt), but not in Nox1−/y cells. A SSH1L-S834A phospho-deficient mutant has significantly lower binding capacity for 14-3-3 when compared with the phospho-mimetic SSH1L-S834D mutant, and acts as a constitutively active phosphatase, lacking of PDGF-mediated regulation. Given that Nox1 produces reactive oxygen species, we evaluated their participation in this SSH1L activation mechanism. We found that H2O2 activates SSH1L and this is accompanied by SSH1L/14-3-3 complex disruption and 14-3-3 oxidation in wt, but not in Nox1−/y cells. Together, these data demonstrate that PDGF activates SSH1L in VSMC by a mechanism that involves Nox1-mediated oxidation of 14-3-3 and Ser-834 SSH1L auto-dephosphorylation.

Purpose of Review-Inadequate health literacy is common among American adults, but little is known about the impact of health literacy in rheumatic diseases. The purpose of this article is to review studies investigating health literacy and its association with clinical outcomes in systemic lupus erythematosus (SLE).Recent Findings-Several validated health literacy measures have been examined in SLE patients. Low health literacy is associated with worse patient-reported outcomes and lower numeracy with higher disease activity. Two studies found no association of low health literacy with medication adherence. One randomized controlled trial tested a medication decision aid among patients with low health literacy.Summary-We found a paucity of studies exploring health literacy in SLE. Low health literacy is associated with worse patient-reported outcomes and limited numeracy with higher disease activity in SLE. Further studies are needed exploring the impact of low health literacy on clinical outcomes and the effectiveness of literacy-sensitive interventions.

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ObjectiveWe have developed a new conceptual model to characterise the signs and symptoms of SLE: the Type 1 and 2 SLE Model. Within the original model, Type 1 SLE consists of inflammatory manifestations like arthritis, nephritis and rashes; Type 2 SLE includes symptoms of fatigue, myalgia, mood disturbance and cognitive dysfunction. Through in-depth interviews, we explored how the Type 1 and 2 SLE Model fits within the lived experience of patients with SLE, with a focus on the connection between Type 1 and Type 2 SLE symptoms.MethodsSemistructured in-depth interviews were conducted among adult participants meeting 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria for SLE. Participants were purposefully selected for age, race, sex and nephritis history. All interviews were audio-recorded and transcribed. Data were analysed through episode profile and thematic analysis.ResultsThrough interviews with 42 patients with SLE, two patterns of Type 2 SLE emerged: Intermittent (n=18) and Persistent (n=24). Participants with Intermittent Type 2 SLE described feeling generally well when Type 1 is inactive; these participants were younger and had more internal SLE manifestations. Participants with Persistent Type 2 described always experiencing Type 2 symptoms despite inactive Type 1, although the severity may fluctuate. Participants with Persistent Type 2 SLE experienced traditional lupus symptoms of joint pain, hair loss and rash, but less often had severe organ system involvement.ConclusionsBy listening to the stories of our patients, we found two underlying patterns of Type 2 SLE: Intermittent Type 2 symptoms that resolve in synchrony with Type 1 inflammatory symptoms, and Persistent Type 2 symptoms that continue despite remission of Type 1 symptoms.

Objective Evidence suggests low health literacy is prevalent in the United States and associated with worse clinical outcomes, yet few studies have investigated health literacy in systemic lupus erythematosus (SLE). The objective of this study was to determine the prevalence of low health literacy and numeracy in lupus patients and to examine its association with disease characteristics. Methods Patients with SLE were recruited from an academic center clinic. Participants completed in-person assessments of health literacy (Rapid Estimate of Adult Literacy in Medicine, REALM) and numeracy (Numeracy Understanding in Medicine Instrument Shortened Version, S-NUMi). Clinical disease activity measures were obtained, including urine protein to creatinine ratio (UPC), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician global assessment (PhGA) scores. Results Ninety-five SLE patients participated in the study; 13% had low health literacy and 73% had limited health numeracy. Patients with lower health literacy and numeracy were more likely to be Black, have Medicaid insurance, and earn income <$50 K annually. In linear regression models, patients with limited health numeracy had, on average, PhGA scores 0.31 points higher (95% CI: 0.02, 0.60) than patients with adequate numeracy, after adjusting for race and age. No clinical outcomes were associated with health literacy. Conclusion In this exploratory study, we found SLE patients with low numeracy had higher disease activity. Our findings indicate that lower health literacy and numeracy are more common among Black and socioeconomically disadvantaged patients. Additional research will be needed to investigate the impact of health literacy on other outcomes and racial disparities in SLE.

In this article, we describe the case of a 61-year-old woman who presented with altered mental status and was found to have Klebsiella pneumoniae meningitis, bacteremia, and hepatic abscess. Despite intravenous antibiotic therapy and percutaneous drainage of the hepatic abscess, the patient developed worsening meningitis with ventriculitis, which led to her death. This invasive Klebsiella syndrome is characterized by metastatic infections with a hypervirulent strain and a poor clinical prognosis. Important elements of this patient’s case—including the widespread and highly aggressive course—and of those reported in the literature are reviewed. Although the invasive Klebsiella syndrome is an increasingly recognized clinical entity, most often in the Eastern hemisphere, it remains rare in the United States with approximately 20 cases reported in the literature, and given its high morbidity, it is vitally important for clinicians to recognize.

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Objective Limited health literacy and numeracy are associated with worse patient-reported outcomes and higher disease activity in systemic lupus erythematosus (SLE), but which factors may mediate this association is unknown. We sought to determine the association of health literacy and numeracy with lupus knowledge. Methods Patients with SLE were recruited from an academic center clinic. Participants completed validated assessments of health literacy (Newest Vital Sign, NVS) and numeracy (Numeracy Understanding in Medicine Instrument Shortened Version, S-NUMi) and answered four questions to assess lupus knowledge (Lupus Knowledge Assessment Test, LKAT) determined through consensus expert opinion of wide applicability and importance related to self-management. Descriptive statistics and multivariable logistic regression modeling were used to analyze results. Results In our lupus cohort (n=125), 33% had limited health literacy and 76% had limited numeracy. The majority correctly identified that hydroxychloroquine prevented lupus flares (91%); however, only 23% of participants correctly answered a numeracy question assessing which urine protein to creatinine (UPC) ratio was greater than 1000 mg/g. The mean LKAT score was 2.7 out of 4.0. Limited health literacy, but not numeracy, was associated with lower knowledge about SLE as measured by the LKAT, even after adjusting for education. Conclusion Patients with SLE with limited health literacy had lower knowledge about SLE. The LKAT could be further refined and/or used as a screening tool to identify patients with knowledge gaps. Further work is needed to improve understanding of proteinuria and investigate whether literacy-sensitive education can improve care.