The antibody response of pregnant swine to transmissible gastroenteritis (TGE) virus was studied, with special reference to the titers and the immunoglobulin (Ig) class of TGE neutralizing antibodies in colostrum and milk. Animals vaccinated twice intramuscularly or intramammarily with live attenuated TGE virus developed high levels of antibodies in serum and colostrum, but the levels in milk declined markedly within a few days post-farrowing. In contrast, animals naturally or experimentally infected with virulent virus generally developed lower levels of antibodies in serum and colostrum but maintained higher levels in milk, as compared to the vaccinated animals. Gel filtration studies indicated that antibodies in milk from vaccinated animals were primarily of the IgG class, whereas those

Sexual dimorphism exists in energy balance, but the underlying mechanisms remain unclear. Here we show that the female mice have more pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus than males, and female POMC neurons display higher neural activities, compared to male counterparts. Strikingly, deletion of the transcription factor, TAp63, in POMC neurons confers “male-like” diet-induced obesity (DIO) in female mice associated with decreased POMC neural activities; but the same deletion does not affect male mice. Our results indicate that TAp63 in female POMC neurons contributes to the enhanced POMC neuron functions and resistance to obesity in females. Thus, TAp63 in POMC neurons is one key molecular driver for the sexual dimorphism in energy homeostasis.

Germline manipulation using CRISPR/Cas9 genome editing has dramatically accelerated the generation of new mouse models. Nonetheless, many metabolic disease models still depend upon laborious germline targeting, and are further complicated by the need to avoid developmental phenotypes. We sought to address these experimental limitations by generating somatic mutations in the adult liver using CRISPR/Cas9, as a new strategy to model metabolic disorders. As proof-of-principle, we targeted the low-density lipoprotein receptor (Ldlr), which when deleted, leads to severe hypercholesterolemia and atherosclerosis. Here we show that hepatic disruption of Ldlr with AAV-CRISPR results in severe hypercholesterolemia and atherosclerosis. We further demonstrate that co-disruption of Apob, whose germline loss is embryonically lethal, completely prevented disease through compensatory inhibition of hepatic LDL production. This new concept of metabolic disease modeling by somatic genome editing could be applied to many other systemic as well as liver-restricted disorders which are difficult to study by germline manipulation.

Background Although giant cell tumors (GCTs) are benign, their aggressiveness and tendency to recur locally challenge the orthopaedic surgeon's ability to perform joint-preserving intralesional surgery with an acceptably low risk of local recurrence. Denosumab has emerged as a possible medical treatment of GCT because it seems to halt the progression of GCT, alleviate pain, and increase perilesional bone formation, but its exact role has been questioned, and specifically its efficacy and associated complications are not well characterized. Questions/purposes (1) Does denosumab reduce the risk of recurrence after resection or intralesional surgery? (2) What are the complications associated with the use of denosumab? Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/ licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution waived approval for the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

Six months of cholecalciferol and calcium supplementation results in enhanced skeletal muscle strength and physical performance despite no change in muscle energy parameters. Cholecalciferol supplementation of 60,000 IU per month could not maintain 25(OH)D levels in the sufficient range.