Calcium handling precedes cardiac differentiation to initiate the first heartbeat

The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca2+-oscillations (SACOs) in the forming cardiac crescent (stage E7.75) prior to overt beating. Nascent contraction initiated at around E8.0 and was associated with sarcomeric assembly and rapid Ca2+ transients, underpinned by sequential expression of the Na+-Ca2+ exchanger (NCX1) and L-type Ca2+ channel (LTCC). Pharmacological inhibition of NCX1 and LTCC revealed rapid development of Ca2+ handling in the early heart and an essential early role for NCX1 in establishing SACOs through to the initiation of beating. NCX1 blockade impacted on CaMKII signalling to down-regulate cardiac gene expression, leading to impaired differentiation and failed crescent maturation

The role of thymosin-β4 in kidney disease

Therapies that modulate inflammation and fibrosis have the potential to reduce the morbidity and mortality associated with chronic kidney disease (CKD). A promising avenue may be manipulating thymosin-β4, a naturally occurring peptide, which is the major G-actin sequestering protein in mammalian cells and a regulator of inflammation and fibrosis. Thymosin-β4 is already being tested in clinical trials for heart disease and wound healing. This editorial outlines the evidence that thymosin-β4 may also have therapeutic benefit in CKD

High-Resolution Magnetic Resonance Imaging of the Regenerating Adult Zebrafish Heart

The adult zebrafish is a well-established model for studying heart regeneration, but due to its tissue opaqueness, repair has been primarily assessed using destructive histology, precluding repeated investigations of the same animal. We present a high-resolution, non-invasive in vivo magnetic resonance imaging (MRI) method incorporating a miniature respiratory and anaesthetic perfusion set-up for live adult zebrafish, allowing for visualization of scar formation and heart regeneration in the same animal over time at an isotropic 31 µm voxel resolution. To test the method, we compared well and poorly healing cardiac ventricles using a transgenic fish model that exhibits heat-shock (HS) inducible impaired heart regeneration. HS-treated groups revealed persistent scar tissue for 10 weeks, while control groups were healed after 4 weeks. Application of the advanced MRI technique allowed clear discrimination of levels of repair following cryo- and resection injury for several months. It further provides a novel tool for in vivo time-lapse imaging of adult fish for non-cardiac studies, as the method can be readily applied to image wound healing in other injured or diseased tissues, or to monitor tissue changes over time, thus expanding the range of questions that can be addressed in adult zebrafish and other small aquatic species

Enhancing Distorted Metal Organic Framework Derived ZnO as Anode Material for Lithium Storage by the Addition of Ag2S Quantum Dots.

The lithium storage properties of the distorted metal-organic framework (MOF) derived nanosized ZnO@C are significantly improved by the introduction of Ag2S quantum dots (QDs) during the processing of the material. In the thermal treatment, the Ag2S QDs react to produce Ag nanoparticles and ZnS. The metal nanoparticles act to shorten electron pathways and improve the connectivity of the matrix and the partial sulfidation of the ZnO surface improves the cycling stability of the material. The electrochemical properties of ZnO@C, Ag2S QDs treated ZnO@C and the amorphous carbon in ZnO@C have been compared. The small weight ratio of Ag2S QDs to ZnO@C at 1:180 shows the best performance in lithium storage. The exhibited specific capacities are improved and retained remarkably in the cycling at high current rates. At low current densi-ties (200 mA g-1) treatment of ZnO@C with Ag2S QDs results in a 38% increase in the specific capacity

PCA-induced respiratory depression simulating stroke following endoluminal repair of abdominal aortic aneurysm: a case report

<p>Abstract</p> <p>Aim</p> <p>To report a case of severe respiratory depression with PCA fentanyl use simulating stroke in a patient who underwent routine elective endoluminal graft repair for abdominal aortic aneurysm (AAA)</p> <p>Case presentation</p> <p>A 78-year-old obese lady underwent routine endoluminal graft repair for AAA that was progressively increasing in size. Following an uneventful operation postoperative analgesia was managed with a patient-controlled analgesia (PCA) device with fentanyl. On the morning following operation the patient was found to be unusually drowsy and unresponsive to stimuli. Her GCS level was 11 with plantars upgoing bilaterally. A provisional diagnosis of stroke was made. Urgent transfer to a high-dependency unit (HDU) was arranged and she was given ventilatory support with a BiPap device. CT was performed and found to be normal. Arterial blood gas (ABG) analysis showed respiratory acidosis with PaCO₂81 mmHg, PaO₂140 mmHg, pH 7.17 and base excess -2 mmol/l. A total dose of 600 mcg of fentanyl was self-administered in the 16 hours following emergence from general anaesthesia. Naloxone was given with good effect. There was an increase in the creatinine level from 90 μmol/L preoperatively to 167 μmol/L on the first postoperative day. The patient remained on BiPap for two days that resulted in marked improvement in gas exchange. Recovery was complete.</p

Exercise therapy for chronic low back pain:protocol for an individual participant data meta-analysis

<p>Abstract</p> <p>Background</p> <p>Low back pain (LBP) is one of the leading causes of disability and has a major socioeconomic impact. Despite a large amount of research in the field, there remains uncertainty about the best treatment approach for chronic LBP, and identification of relevant patient subgroups is an important goal. Exercise therapy is a commonly used strategy to treat chronic low back pain and is one of several interventions that evidence suggests is moderately effective.</p> <p>In parallel with an update of the 2005 Cochrane review, we will undertake an individual participant data (IPD) meta-analysis, which will allow us to standardize analyses across studies and directly derive results, and to examine differential treatment effects across individuals to estimate how patients’ characteristics modify treatment benefit.</p> <p>Methods/design</p> <p>We will use standard systematic review methods advocated by the Cochrane Collaboration to identify relevant trials. We will include trials evaluating exercise therapy compared to any or no other interventions in adult non-specific chronic LBP. Our primary outcomes of interest include pain, functional status, and return-to-work/absenteeism. We will assess potential risk of bias for each study meeting selection criteria, using criteria and methods recommended by the Cochrane BRG.</p> <p>The original individual participant data will be requested from the authors of selected trials having moderate to low risk of bias. We will test original data and compile a master dataset with information about each trial mapped on a pre-specified framework, including reported characteristics of the study sample, exercise therapy characteristics, individual patient characteristics at baseline and all follow-up periods, subgroup and treatment effect modifiers investigated. Our analyses will include descriptive, study-level meta-analysis and meta-regression analyses of the overall treatment effect, and individual-level IPD meta-analyses of treatment effect modification. IPD meta-analyses will be conducted using a one-step approach where the IPD from all studies are modeled simultaneously while accounting for the clustering of participants with studies.</p> <p>Discussion</p> <p>We will analyze IPD across a large number of LBP trials. The resulting larger sample size and consistent presentation of data will allow additional analyses to explore patient-level heterogeneity in treatment outcomes and prognosis of chronic LBP.</p

Belowground DNA-based techniques: untangling the network of plant root interactions

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