Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
856
result(s) for
"Sweet, David"
Sort by:
Baabwaa & Wooliam
\"Baabwaa is a sheep who loves to knit. Wooliam is a sheep who loves to read. It sounds a bit boring, but they like it. Then, quite unexpectedly, a third sheep shows up. A funny-looking sheep who wears a tattered wool coat and has long, dreadfully decaying teeth. Wooliam, being well-read, recognizes their new acquaintance: the Wolf in Sheep's Clothing! The wolf is so flattered to discover his literary reputation precedes him that he stops trying to eat Baabwaa and Wooliam. And a discovery by the sheep turns the encounter into an unexpected friendship\"--Amazon.
Book
When to treat with surfactant?
Correspondence to Dr David G Sweet, Neonatal Unit, Royal Maternity Hospital, Belfast, Belfast, UK; david.sweet@belfasttrust.hscni.net Synthesis of available data by different expert groups has resulted in differing fraction of inspired oxygen (FiO2) thresholds for surfactant therapy in babies with respiratory distress syndrome (RDS). Branagan et al attempt through network meta-analysis to determine if there is an optimal FiO2 cut-off for surfactant therapy to reduce any of the important negative outcomes of prematurity including mortality and bronchopulmonary dysplasia (BPD). Cochrane meta-analysis of six randomised trials show a reduction in mortality (RR 0.69; 95% CI 0.55 to 0.86) and the combined outcome of death or BPD (RR 0.83; 95% CI 0.75 to 0.91) for the babies treated earlier; however, the included studies randomised infants according to time after birth, rather than by FiO2 thresholds.1 For preterm babies managed on CPAP, Verder and coworkers showed us 20 years ago that surfactant at an earlier time point compared with later would reduce the need for mechanical ventilation or death before 7 days. Lung ultrasound, with appropriate training, may offer an alternative way of diagnosing significant RDS best treated at an earlier stage, without apparently resulting in more infants overall being treated.5 Rapid point-of-care testing for surfactant components in gastric aspirate is also now available, and clinical trials will hopefully determine if these tests can predict who should receive surfactant before the infant becomes very unwell.
Journal Article
The Krüppel-Like Factors and Control of Energy Homeostasis
Abstract
Nutrient handling by higher organisms is a complex process that is regulated at the transcriptional level. Studies over the past 15 years have highlighted the critical importance of a family of transcriptional regulators termed the Krüppel-like factors (KLFs) in metabolism. Within an organ, distinct KLFs direct networks of metabolic gene targets to achieve specialized functions. This regulation is often orchestrated in concert with recruitment of tissue-specific transcriptional regulators, particularly members of the nuclear receptor family. Upon nutrient entry into the intestine, gut, and liver, KLFs control a range of functions from bile synthesis to intestinal stem cell maintenance to effect nutrient acquisition. Subsequently, coordinated KLF activity across multiple organs distributes nutrients to sites of storage or liberates them for use in response to changes in nutrient status. Finally, in energy-consuming organs like cardiac and skeletal muscle, KLFs tune local metabolic programs to precisely match substrate uptake, flux, and use, particularly via mitochondrial function, with energetic demand; this is achieved in part via circulating mediators, including glucocorticoids and insulin. Here, we summarize current understanding of KLFs in regulation of nutrient absorption, interorgan circulation, and tissue-specific use.
Journal Article
KLF2 regulates neutrophil activation and thrombosis in cardiac hypertrophy and heart failure progression
It is widely recognized that inflammation plays a critical role in cardiac hypertrophy and heart failure. However, clinical trials targeting cytokines have shown equivocal effects, indicating the need for a deeper understanding of the precise role of inflammation and inflammatory cells in heart failure. Leukocytes from human subjects and a rodent model of heart failure were characterized by a marked reduction in expression of Klf2 mRNA. Using a mouse model of angiotensin II-induced nonischemic cardiac dysfunction, we showed that neutrophils played an essential role in the pathogenesis and progression of heart failure. Mechanistically, chronic angiotensin II infusion activated a neutrophil KLF2/NETosis pathway that triggered sporadic thrombosis in small myocardial vessels, leading to myocardial hypoxia, cell death, and hypertrophy. Conversely, targeting neutrophils, neutrophil extracellular traps (NETs), or thrombosis ameliorated these pathological changes and preserved cardiac dysfunction. KLF2 regulated neutrophil activation in response to angiotensin II at the molecular level, partly through crosstalk with HIF1 signaling. Taken together, our data implicate neutrophil-mediated immunothrombotic dysregulation as a critical pathogenic mechanism leading to cardiac hypertrophy and heart failure. This neutrophil KLF2-NETosis-thrombosis mechanism underlying chronic heart failure can be exploited for therapeutic gain by therapies targeting neutrophils, NETosis, or thrombosis.
Journal Article
Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy
Nonischemic cardiomyopathy (NICM) resulting from long-standing hypertension, valvular disease, and genetic mutations is a major cause of heart failure worldwide. Recent observations suggest that myeloid cells can impact cardiac function, but the role of tissue-intrinsic vs. tissue-extrinsic myeloid cells in NICM remains poorly understood. Here, we show that cardiac resident macrophage proliferation occurs within the first week following pressure overload hypertrophy (POH; a model of heart failure) and is requisite for the heart’s adaptive response. Mechanistically, we identify Kruppel-like factor 4 (KLF4) as a key transcription factor that regulates cardiac resident macrophage proliferation and angiogenic activities. Finally, we show that blood-borne macrophages recruited in late-phase POH are detrimental, and that blockade of their infiltration improves myocardial angiogenesis and preserves cardiac function. These observations demonstrate previously unappreciated temporal and spatial roles for resident and nonresident macrophages in the development of heart failure.
Journal Article
Imaging of the acute scrotum: keys to a rapid diagnosis of acute scrotal disorders
Imaging of the scrotum in the setting of acute symptoms such as pain or swelling is commonly performed emergently to differentiate between patients who require immediate surgery and those that do not. Acute scrotal symptoms are generally caused by infectious, traumatic or vascular etiologies. Rapid diagnosis and initiation of treatment is vital for testicular salvage in cases of acute testicular torsion, testicular rupture, and Fournier gangrene. Epididymitis, epididymo-orchitis, torsed testicular appendage, segmental testicular infarction, scrotal hematomas, testicular neoplasms, and acute idiopathic scrotal edema can have similar clinical presentations, but these conditions do not require immediate surgery. Ultrasound is the well-established first-line imaging modality for the acute scrotum. Contrast-enhanced ultrasound and magnetic resonance imaging can be useful as problem-solving tools when ultrasound studies are inconclusive or equivocal. This review describes normal scrotal anatomy and a wide range acute scrotal disorders, with emphasis on the imaging and clinical features that can minimize the risk of misdiagnosis.
Journal Article
European Consensus Guidelines on the Management of Neonatal Respiratory Distress Syndrome in Preterm Infants - 2013 Update
Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report updated recommendations of a European Panel of expert neonatologists who developed consensus guidelines after critical examination of the most up-to-date evidence in 2007 and 2010. This second update of the guidelines is based upon published evidence up to the end of 2012. Strong evidence exists for the role of antenatal steroids in RDS prevention, but it is still not clear if the benefit of repeated courses on respiratory outcomes outweighs the risk of adverse outcomes in the short and long term. Many practices involved in preterm neonatal stabilization at birth are not evidence based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in the management of RDS but the best preparation, optimal dose and timing of administration at different gestations is not completely clear. In addition, use of very early continuous positive airway pressure (CPAP) has altered the indications for prophylactic surfactant administration. Respiratory support in the form of mechanical ventilation may be lifesaving but can cause lung injury, and protocols should be directed at avoiding mechanical ventilation where possible by using non-invasive respiratory support such as CPAP. For babies with RDS to have best outcomes, it is essential that they have optimal supportive care, including maintenance of normal body temperature, proper fluid management, good nutritional support, appropriate management of the ductus arteriosus and support of the circulation to maintain adequate tissue perfusion.
Journal Article
Three Seconds in Munich
One. Two. Three. That’s as long as it took to sear the souls of a dozen young American men, thanks to the craziest, most controversial finish in the history of the Olympics—the 1972 gold-medal basketball contest between the United States of America and the Union of Soviet Socialist Republics, the world’s two superpowers at the time. The U.S. team, whose unbeaten Olympic streak dated back to when Adolf Hitler reigned over the Berlin Games, believed it had won the gold medal that September in Munich—not once, but twice. But it was the third time the final seconds were played that counted. What happened? The head of international basketball—flouting rules he himself had created—trotted onto the court and demanded twice that time be put back on the clock. A referee allowed an illegal substitution and an illegal free-throw shooter for the Soviets while calling a slew of late fouls on the U.S. players. The American players became the only Olympic athletes in the history of the games to refuse their medals. Of course, the 1972 Olympics are remembered primarily for a far graver matter, when eleven Israeli team members were killed by Palestinian terrorists, stunning the world and temporarily stopping the games. One American player, Tommy Burleson, had a gun to his head as the hostages were marched past him before their deaths. Through interviews with many of the American players and others, the author relates the horror of terrorism, the pain of losing the most controversial championship game in sports history to a hated rival, and the consequences of the players’ decision to shun their Olympic medals to this day.
eBook
Taking KLF9 to “Cort” for crimes against metabolism
Glucocorticoids (GCs) are essential for proper glycemic control, but in excess, can lead to hyperglycemia and diabetes. In this issue of the JCI, Cui et al. elucidate a mechanism by which GCs regulate gluconeogenesis utilizing the transcription factor Krüppel-like factor 9 (KLF9) in physiology and disease settings. They report that KLF9 is a GC-inducible factor that ultimately increases the transcription of proliferator-activated receptor γ coactivator 1 α (PGC1α), resulting in gluconeogenesis. Given the high incidence of GC-induced diabetes, identification of this signaling axis provides, not only critical scientific insight, but also a foundation for preventative therapies for patients receiving chronic GC treatment.
Journal Article
Forensic dental identification
Identification of deceased persons is the most common role of the forensic dentist. Forensic physical comparison of antemortem and postmortem dental data is used to establish that a found body and a missing person are one and the same to a high degree of certainty. An overview of this role is presented as a review of dental identification.
Journal Article