Interpreting the functional role of a novel interaction motif in prokaryotic sodium channels

Voltage-gated sodium channels enable the translocation of sodium ions across cell membranes and play crucial roles in electrical signaling by initiating the action potential. In humans, mutations in sodium channels give rise to several neurological and cardiovascular diseases, and hence they are targets for pharmaceutical drug developments. Prokaryotic sodium channel crystal structures have provided detailed views of sodium channels, which by homology have suggested potentially important functionally related structural features in human sodium channels. A new crystal structure of a full-length prokaryotic channel, NavMs, in a conformation we proposed to represent the open, activated state, has revealed a novel interaction motif associated with channel opening. This motif is associated with disease when mutated in human sodium channels and plays an important and dynamic role in our new model for channel activation

Anca-associated vasculitis: a comparison of cases presenting to nephrology and rheumatology services

Background: Anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV) is a disease characterized by inflammation of small vessels and detectable ANCA in the circulation. Patients may develop a broad spectrum of clinical features ranging from indolent sino-nasal disease and rashes to fulminant renal failure or acute life-threatening pulmonary haemorrhage. Consequently, patients with AAV present to a variety of specialties including nephrology and rheumatology, whose training and approaches to management of such patients may differ. There is little literature comparing patients presenting to different specialties and their outcomes. Methods: We compared two cohorts of patients with ANCA-positive AAV presenting to either the rheumatology or nephrology department at Galway University Hospitals from June 2002 to July 2011. A standardized data collection form was used to collect information regarding baseline demographics, manifestations of AAV, initial management, relapses and complications. Results: Forty-five patients were included in this study (15 rheumatology/30 nephrology). The nephrology cohort was older, had a higher C-reactive protein, Birmingham Vascular Activity Score and ANCA titer at presentation compared to the rheumatology group. Induction treatment varied between the cohorts with rheumatology patients most commonly receiving a combination of oral corticosteroids (73%) and methotrexate (60%) and nephrology patients receiving a combination of intravenous corticosteroids (93%) and cyclophosphamide (90%). Fifty-three percent of the rheumatology patients who completed induction therapy relapsed compared to 30% of the nephrology patients. Conclusion: This study presents two different cohorts of patients with the same disease that were managed by two different disciplines. It highlights the heterogeneity of AAV and the importance of interdisciplinary communication and cooperation when managing these patients

Anca-associated vasculitis: a comparison of cases presenting to nephrology and rheumatology services

Background: Anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV) is a disease characterized by inflammation of small vessels and detectable ANCA in the circulation. Patients may develop a broad spectrum of clinical features ranging from indolent sino-nasal disease and rashes to fulminant renal failure or acute life-threatening pulmonary haemorrhage. Consequently, patients with AAV present to a variety of specialties including nephrology and rheumatology, whose training and approaches to management of such patients may differ. There is little literature comparing patients presenting to different specialties and their outcomes. Methods: We compared two cohorts of patients with ANCA-positive AAV presenting to either the rheumatology or nephrology department at Galway University Hospitals from June 2002 to July 2011. A standardized data collection form was used to collect information regarding baseline demographics, manifestations of AAV, initial management, relapses and complications. Results: Forty-five patients were included in this study (15 rheumatology/30 nephrology). The nephrology cohort was older, had a higher C-reactive protein, Birmingham Vascular Activity Score and ANCA titer at presentation compared to the rheumatology group. Induction treatment varied between the cohorts with rheumatology patients most commonly receiving a combination of oral corticosteroids (73%) and methotrexate (60%) and nephrology patients receiving a combination of intravenous corticosteroids (93%) and cyclophosphamide (90%). Fifty-three percent of the rheumatology patients who completed induction therapy relapsed compared to 30% of the nephrology patients. Conclusion: This study presents two different cohorts of patients with the same disease that were managed by two different disciplines. It highlights the heterogeneity of AAV and the importance of interdisciplinary communication and cooperation when managing these patients

Impact of Early Acute Kidney Injury on Management and Outcome in Patients With Acute Respiratory Distress Syndrome: A Secondary Analysis of a Multicenter Observational Study

Item does not contain fulltextOBJECTIVES: To understand the impact of mild-moderate and severe acute kidney injury in patients with acute respiratory distress syndrome. DESIGN: Secondary analysis of the "Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure", an international prospective cohort study of patients with severe respiratory failure. SETTING: Four-hundred fifty-nine ICUs from 50 countries across five continents. SUBJECTS: Patients with a glomerular filtration rate greater than 60 mL/min/1.73 m prior to admission who fulfilled criteria of acute respiratory distress syndrome on day 1 and day 2 of acute hypoxemic respiratory failure. INTERVENTIONS: Patients were categorized based on worst serum creatinine or urine output into: 1) no acute kidney injury (serum creatinine /= 0.5 mL/kg/hr), 2) mild-moderate acute kidney injury (serum creatinine 132-354 micromol/L or minimum urine output between 0.3 and 0.5mL/kg/hr), or 3) severe acute kidney injury (serum creatinine > 354 micromol/L or renal replacement therapy or minimum urine output < 0.3 mL/kg/hr). MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital mortality, whereas secondary outcomes included prevalence of acute kidney injury and characterization of acute respiratory distress syndrome risk factors and illness severity patterns, in patients with acute kidney injury versus no acute kidney injury. One-thousand nine-hundred seventy-four patients met inclusion criteria: 1,209 (61%) with no acute kidney injury, 468 (24%) with mild-moderate acute kidney injury, and 297 (15%) with severe acute kidney injury. The impact of acute kidney injury on the ventilatory management of patients with acute respiratory distress syndrome was relatively limited, with no differences in arterial CO2 tension or in tidal or minute ventilation between the groups. Hospital mortality increased from 31% in acute respiratory distress syndrome patients with no acute kidney injury to 50% in mild-moderate acute kidney injury (p </= 0.001 vs no acute kidney injury) and 58% in severe acute kidney injury (p </= 0.001 vs no acute kidney injury and mild-moderate acute kidney injury). In multivariate analyses, both mild-moderate (odds ratio, 1.61; 95% CI, 1.24-2.09; p < 0.001) and severe (odds ratio, 2.13; 95% CI, 1.55-2.94; p < 0.001) acute kidney injury were independently associated with mortality. CONCLUSIONS: The development of acute kidney injury, even when mild-moderate in severity, is associated with a substantial increase in mortality in patients with acute respiratory distress syndrome

Anca-associated vasculitis: a comparison of cases presenting to nephrology and rheumatology services

Background: Anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV) is a disease characterized by inflammation of small vessels and detectable ANCA in the circulation. Patients may develop a broad spectrum of clinical features ranging from indolent sino-nasal disease and rashes to fulminant renal failure or acute life-threatening pulmonary haemorrhage. Consequently, patients with AAV present to a variety of specialties including nephrology and rheumatology, whose training and approaches to management of such patients may differ. There is little literature comparing patients presenting to different specialties and their outcomes. Methods: We compared two cohorts of patients with ANCA-positive AAV presenting to either the rheumatology or nephrology department at Galway University Hospitals from June 2002 to July 2011. A standardized data collection form was used to collect information regarding baseline demographics, manifestations of AAV, initial management, relapses and complications. Results: Forty-five patients were included in this study (15 rheumatology/30 nephrology). The nephrology cohort was older, had a higher C-reactive protein, Birmingham Vascular Activity Score and ANCA titer at presentation compared to the rheumatology group. Induction treatment varied between the cohorts with rheumatology patients most commonly receiving a combination of oral corticosteroids (73%) and methotrexate (60%) and nephrology patients receiving a combination of intravenous corticosteroids (93%) and cyclophosphamide (90%). Fifty-three percent of the rheumatology patients who completed induction therapy relapsed compared to 30% of the nephrology patients. Conclusion: This study presents two different cohorts of patients with the same disease that were managed by two different disciplines. It highlights the heterogeneity of AAV and the importance of interdisciplinary communication and cooperation when managing these patients