Institution
Boston Children's Hospital
Healthcare•Boston, Massachusetts, United States•
About: Boston Children's Hospital is a healthcare organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 165409 authors who have published 215589 publications receiving 6885627 citations.
Topics: Population, Medicine, Transplantation, Poison control, Intensive care
Papers published on a yearly basis
Papers
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TL;DR: Three independent lines of evidence support the hypothesis that hypoxic microenvironments are an important feature of some lesions in these animal models of tuberculosis.
Abstract: Understanding the physical characteristics of the local microenvironment in which Mycobacterium tuberculosis resides is an important goal that may allow the targeting of metabolic processes to shorten drug regimens. Pimonidazole hydrochloride (Hypoxyprobe) is an imaging agent that is bioreductively activated only under hypoxic conditions in mammalian tissue. We employed this probe to evaluate the oxygen tension in tuberculous granulomas in four animal models of disease: mouse, guinea pig, rabbit, and nonhuman primate. Following infusion of pimonidazole into animals with established infections, lung tissues from the guinea pig, rabbit, and nonhuman primate showed discrete areas of pimonidazole adduct formation surrounding necrotic and caseous regions of pulmonary granulomas by immunohistochemical staining. This labeling could be substantially reduced by housing the animal under an atmosphere of 95% O2. Direct measurement of tissue oxygen partial pressure by surgical insertion of a fiber optic oxygen probe into granulomas in the lungs of living infected rabbits demonstrated that even small (3-mm) pulmonary lesions were severely hypoxic (1.6 ± 0.7 mm Hg). Finally, metronidazole, which has potent bactericidal activity in vitro only under low-oxygen culture conditions, was highly effective at reducing total-lung bacterial burdens in infected rabbits. Thus, three independent lines of evidence support the hypothesis that hypoxic microenvironments are an important feature of some lesions in these animal models of tuberculosis.
582 citations
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TL;DR: A first-in-humans pilot study sets the stage for clinical trials employing adoptive transfer in the context of minimal residual disease in children with recurrent/refractory neuroblastoma.
582 citations
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TL;DR: The inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage.
582 citations
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TL;DR: The objectives of GH therapy in short children who are SGA are catch-up growth in early childhood, maintenance of normal growth in childhood, and achievement of normal adult height.
Abstract: Objective. To provide pediatric endocrinologists, general pediatricians, neonatologists, and primary care physicians with recommendations for the management of short children born small for gestational age (SGA). Methods. A 13-member independent panel of pediatric endocrinologists was convened to discuss relevant issues with respect to definition, diagnosis, and clinical management of short children born SGA. Panel members convened over a series of 3 meetings to thoroughly review, discuss, and come to consensus on the identification and treatment of short children who are born SGA. Conclusions. SGA is defined as birth weight and/or length at least 2 standard deviations (SDs) below the mean for gestational age (≤−2 SD). Accurate gestational dating and measurement of birth weight and length are crucial for identifying children who are born SGA. Comprehensive pregnancy, perinatal, and immediate postnatal data may help to confirm the diagnosis. Maternal, placental, and fetal causes of SGA should be sought, although the cause is often not clear. Most children who are SGA experience catch-up growth and achieve a height >2 SD below the mean; this catch-up process is usually completed by the time they are 2 years of age. A child who is SGA and older than 3 years and has persistent short stature (ie, remaining at least 2 SD below the mean for chronologic age) is not likely to catch up and should be referred to a pediatrician who has expertise in endocrinology. Bone age is not a reliable predictor of height potential in children who are SGA. Nevertheless, a standard evaluation for short stature should be performed. A diagnosis of SGA does not exclude growth hormone (GH) deficiency, and GH assessment should be performed if there is clinical suspicion or biochemical evidence of GH deficiency. At baseline, insulin-like growth factor-I, insulin-like growth factor binding protein-3, fasting insulin, glucose, and lipid levels as well as blood pressure should be measured, and all aspects of SGA—not just stature—should be addressed with parents. The objectives of GH therapy in short children who are SGA are catch-up growth in early childhood, maintenance of normal growth in childhood, and achievement of normal adult height. GH therapy is effective and safe in short children who are born SGA and should be considered in those older than 2 to 3 years. There is long-term experience of improved growth using a dosage range from 0.24 to 0.48 mg/kg/wk. Higher GH doses (0.48 mg/kg/wk [0.2 IU/kg/d]) are more effective for the short term. Whether the higher GH dose is more efficacious than the lower dose in terms of adult height results is not yet known. Only adult height results of randomized dose-response studies will give a definite answer. Monitoring is necessary to ensure safety of medication. Children should be monitored for changes in glucose homeostasis, lipids, and blood pressure during therapy. The frequency and intensity of monitoring will vary depending on risk factors such as family history, obesity, and puberty.
582 citations
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Kyoto University1, Centre national de la recherche scientifique2, university of lille3, French Institute of Health and Medical Research4, Boston Children's Hospital5, University of Verona6, Sapienza University of Rome7, Imperial College London8, University of Oulu9, Leipzig University10, University of Antwerp11, University of Bern12, Aristotle University of Thessaloniki13, University of Duisburg-Essen14, McMaster University15, Jichi Medical University16
TL;DR: This study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.
Abstract: Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.
581 citations
Authors
Showing all 165661 results
Name | H-index | Papers | Citations |
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Walter C. Willett | 334 | 2399 | 413322 |
Frederick E. Shelton | 327 | 1485 | 295883 |
Robert Langer | 281 | 2324 | 326306 |
Graham A. Colditz | 261 | 1542 | 256034 |
Frank B. Hu | 250 | 1675 | 253464 |
George M. Whitesides | 240 | 1739 | 269833 |
Eugene Braunwald | 230 | 1711 | 264576 |
Ralph B. D'Agostino | 226 | 1287 | 229636 |
Mark J. Daly | 204 | 763 | 304452 |
Eric B. Rimm | 196 | 988 | 147119 |
Virginia M.-Y. Lee | 194 | 993 | 148820 |
Bernard Rosner | 190 | 1162 | 147661 |
Stuart H. Orkin | 186 | 715 | 112182 |
Mark Hallett | 186 | 1170 | 123741 |
Ralph Weissleder | 184 | 1160 | 142508 |