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Background: Miro is a mitochondrial protein involved in mitochondrial trafficking.Results: Mitochondrial damage drives rapid Miro ubiquitination in a manner dependent on Ser-65 in Parkin; however, Miro degradation is delayed.Conclusion: Ubiquitination of Miro, rather than its degradation, could act as a signal for mitochondrial arrest and clearance.Significance: Disruption of the mitochondrial transport machinery could be implicated in Parkinson disease.

SummaryValosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family. VCP mutations are the cause of inclusion body myopathy, Paget’s disease of the bone, and frontotemporal dementia (IBMPFD) and they account for 1%–2% of familial amyotrophic lateral sclerosis (ALS). Using fibroblasts from patients carrying three independent pathogenic mutations in the VCP gene, we show that VCP deficiency causes profound mitochondrial uncoupling leading to decreased mitochondrial membrane potential and increased mitochondrial oxygen consumption. This mitochondrial uncoupling results in a significant reduction of cellular ATP production. Decreased ATP levels in VCP-deficient cells lower their energy capacity, making them more vulnerable to high energy-demanding processes such as ischemia. Our findings propose a mechanism by which pathogenic VCP mutations lead to cell death.

A total of 161 patients with lobar or segmental consolidation were examined by realtime ultrasound and Doppler ultrasound. Air bronchograms were detected in 141 patients, fluid bronchograms in 27 patients, and parapneumonic effusion in 74 patients. In 36 patients with necrotizing pneumonia, ultrasound detected microabscesses in 33 (91.7%) compared with the air-fluid levels detected by standard chest radiographs in 20 patients (55.6%; p less than 0.05). Of 31 patients with tumors causing obstructive pneumonitis, 29 (93.5%) had tumors detected by chest ultrasound, whereas only 11 patients (35.5%) had chest radiographs that suggested a tumor was causing the obstructive pneumonitis (p less than 0.05). Chest ultrasound was used to guide thoracentesis for parapneumonic effusion in 65 patients, with a 100% success rate. Twenty-six patients with necrotizing pneumonia underwent ultrasound-guided needle aspiration of microabscesses. The procedure was successful in 24 patients (92.3%), and 21 patients (80.8%) had microbiologic confirmation. Twenty patients with tumor-associated obstructive pneumonitis received needle aspiration biopsy under ultrasound guidance; 19 patients (95.0%) had the histology confirmed. Five patients with malignancy manifesting as pulmonary consolidation underwent a diagnostic ultrasound-guided needle aspiration biopsy. Five patients (3.8%) developed complications of minimal pneumothorax or mild hemoptysis in 132 episodes of needle aspiration. We conclude that ultrasonography is useful for the evaluation of pulmonary consolidation. It can also be used for needle aspiration guidance for etiologic diagnosis of patients with complicated pneumonia.

NIV may be applied to those patients with a low APACHE II score and a lesser degree of metabolic compensation for respiratory acidosis. For patients undergoing invasive mechanical ventilation, extubation failure is associated with significant in-hospital morbidity in myasthenic crisis. Adequate levels of Pemax and cough strength correlate significantly with extubation success.

IntroductionInhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. Safety concerns regarding iNO and renal dysfunction have been reported; however, there are currently no systematic reviews on this issue. Our objective was to evaluate published randomized controlled trials (RCTs) to ascertain the risk of renal dysfunction associated with iNO therapy in patients with and without ARDS.MethodsA systematic review of databases was performed to identify RCTs which compared iNO with controls up to September 2014. Effect estimates for risk ratio (RR) of acute kidney injury (AKI) were pooled using a random-effects model.ResultsTen RCTs involving 1363 participants were included. Inhaled nitric oxide significantly increased the risk of AKI compared with controls (RR, 1.4, 95%CI, 1.06 to 1.83, p = 0.02). In the stratified analysis, a high cumulative-dose of iNO significantly increased the risk of AKI (RR, 1.52, 95%CI, 1.14 to 2.02, p = 0.004), whereas medium and low cumulative-doses did not (RR, 0.64, 95%CI, 0.23 to 1.81 and RR, 0.56, 95%CI, 0.11 to 2.86 respectively). In subgroup analysis by study population, an increased risk of AKI was observed in patients with ARDS (RR, 1.55, 95%CI, 1.15 to 2.09, p = 0.005) but not in those without (RR, 0.90, 95%CI, 0.49 to 1.67, p = 0.75).ConclusionsThe available data show that iNO therapy may increase the risk of renal dysfunction, especially with prolonged use and in patients with ARDS. The risk in pediatric population is unknown owing to limited data. We suggest monitoring renal function during iNO therapy, and that future trials of iNO should evaluate renal safety.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0880-2) contains supplementary material, which is available to authorized users.

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Purpose of the Report In vivo tau PET imaging could help clarify the spatial distribution of tau deposition in Alzheimer disease (AD) and aid in the differential diagnosis of tauopathies. To date, there have been no in vivo 18F-APN1607 tau PET studies in patients with AD. Methods We applied tau tracer in 12 normal controls (NCs) and 10 patients in the mild to moderate stage of probable AD. Detailed clinical information, cognitive measurements, and disease severity were documented. Regional SUV ratios (SUVRs) from 18F-AV-45 (florbetapir), 18F-APN1607 PET images, and regional gray matter (GM) atrophic ratios were calculated for further analysis. Results Quantitative analyses showed significantly elevated SUVRs in the frontal, temporal, parietal, occipital lobes, anterior and posterior cingulate gyri, precuneus, and parahippocampal region (all P’s < 0.01) with medium to large effect sizes (0.44–0.75). The SUVRs from 18F-APN1607 PET imaging showed significant correlations with the Alzheimer’s Disease Assessment Scale (ADAS-cog) scores (all P’s < 0.01) and strong correlation coefficients (R 2 ranged from 0.54 to 0.68), even adjusted for age and sex effects. Finally, the SUVRs from 18F-APN1607 PET imaging of the parahippocampal region showed rapid saturation as the ADAS-cog scores increased, and the SUVRs of the posterior cingulate gyrus and the temporal, frontal, parietal, and occipital regions slowly increased. The combined SUVRs from amyloid, tau PET, and regional GM atrophic ratio showed regional specific patterns as the ADAS-cog scores increased. Conclusions Our findings suggest that the 18F-APN1607 tau tracer correlated well with cognitive changes and demonstrated the spatial pattern of amyloid, tau deposition, and GM atrophy in the progression of AD.