Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins

Sirt1 is an NAD(+)-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD's ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site. ATP, but not NAD(+), causes a conformational shift to a less compact structure. Mutations that prevent ATP binding increase Sirt1's ability to promote stress resistance and inhibit adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to other proteins, thereby converting them into energy-regulated proteins. These discoveries provide insight into how extreme energy deprivation can impact Sirt1 activity and underscore the complex nature of Sirt1 structure and regulation

Magnetic Resonance Imaging Assessment of the Femoral Tunnel Position in Medial Patellofemoral Ligament Reconstruction

Background/Purpose: Correct femoral tunnel position in medial patellofemoral ligament (MPFL) reconstruction is essential to maintain proper biomechanics of the patellofemoral joint throughout the range of movement. Several techniques have been described for MPFL reconstruction, however, there are few reports describing the accuracy of femoral tunnel positioning assessed postoperatively. Methods: Ten patients having recurrent patellar dislocation with MPFL reconstruction performed in our centre from 2009 to 2013 were analysed. Femoral tunnel position was guided by intraoperative X-ray with landmarks described by Schottle et al, 2007. Postoperative magnetic resonance imaging (MRI) was performed on both knees, and femoral tunnel was assessed with reference to the femoral origin of the MPFL in the nonoperated side. Results: All cases showed an intact MPFL graft, with the majority demonstrating satisfactory femoral tunnel position based on postoperative MRI. Conclusion: MPFL reconstruction with anatomic positioning of the femoral tunnel guided by intraoperative X-ray showed satisfactory accuracy in postoperative MRI results, indicating that a well-positioned MPFL graft results in better clinical outcomes

Thoracic imaging of coronavirus disease 2019 (COVID-19) in children: a series of 91 cases

Background: Pulmonary infection with SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2; COVID-19) has rapidly spread worldwide to become a global pandemic. Objective: To collect paediatric COVID-19 cases worldwide and to summarize both clinical and imaging findings in children who tested positive on polymerase chain reaction testing for SARS-CoV-2. Materials and methods: Data were collected by completion of a standardised case report form submitted to the office of the European Society of Paediatric Radiology from March 12 to April 8, 2020. Chest imaging findings in children younger than 18 years old who tested positive on polymerase chain reaction testing for SARS-CoV-2 were included. Representative imaging studies were evaluated by multiple senior paediatric radiologists from this group with expertise in paediatric chest imaging. Results: Ninety-one children were included (49 males; median age: 6.1 years, interquartile range: 1.0 to 13.0 years, range: 9 days–17 years). Most had mild symptoms, mostly fever and cough, and one-third had coexisting medical conditions. Eleven percent of children presented with severe symptoms and required intensive unit care. Chest radiographs were available in 89% of patients and 10% of them were normal. Abnormal chest radiographs showed mainly perihilar bronchial wall thickening (58%) and/or airspace consolidation (35%). Computed tomography (CT) scans were available in 26% of cases, with the most common abnormality being ground glass opacities (88%) and/or airspace consolidation (58%). Tree in bud opacities were seen in 6 of 24 CTs (25%). Lung ultrasound and chest magnetic resonance imaging were rarely utilized. Conclusion: It seems unnecessary to perform chest imaging in children to diagnose COVID-19. Chest radiography can be used in symptomatic children to assess airway infection or pneumonia. CT should be reserved for when there is clinical concern to assess for possible complications, especially in children with coexisting medical conditions

Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes

Poly(ADP-ribose) polymerases (PARPs) are NAD(+) dependent enzymes that were identified as DNA repair proteins, however, today it seems clear that PARPs are responsible for a plethora of biological functions. Sirtuins (SIRTs) are NAD(+)-dependent deacetylase enzymes involved in the same biological processes as PARPs raising the question whether PARP and SIRT enzymes may interact with each other in physiological and pathophysiological conditions. Hereby we review the current understanding of the SIRT-PARP interplay in regard to the biochemical nature of the interaction (competition for the common NAD(+) substrate, mutual posttranslational modifications and direct transcriptional effects) and the physiological, or pathophysiological consequences of the interactions (metabolic events, oxidative stress response, genomic stability and ageing). Finally, we give an overview of the possibilities of pharmacological intervention to modulate PARP and SIRT enzymes either directly, or through modulating NAD(+) homeostasis

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease