Statistical effects of varying sample sizes on the precision of percentile estimates

The present study evaluates the precision of outlying percentile estimates, with age- and sex-associated variations and facilitates decisions needed to revise the current NCHS 1977 Growth Charts with regard to 1) the inclusion of 3^rd and 97^th percentiles and 2) the selection of survey data for the construction of the revised growth charts. Simulation was performed to obtain data with distribution characteristics similar to those of The Third National Health and Nutritional Examination Survey (NHANES III) (1988–1991) data. NHANES III consists of a two-phase, 6-year, complex stratified multistage probability cluster, cross-sectional survey conducted from 1988 through 1994 to represent the US noninstitutionalized population. Phase I of the survey consisted of 679 boys and 622 girls in age groups 3, 8, 13, and 18 years. Weight and stature, the body mass index (BMI) (weight/stature²; kg/m²) was calculated. The results show that 1) the precision of the percentile estimates is greater for stature than for weight and BMI, 2) percentiles during the pubertal period are less precise than those during the prepubertal and postpubertal periods for weight and BMI but there is little difference for stature, and 3) percentile estimates are more precise for girls than boys for weight and BMI, but not for stature. The present findings suggest that pooling of NHANES III and earlier National Center for Health Statistics (NCHS) survey data is necessary to achieve reasonable precision for the 3^rd and 97^th percentile estimates. Am. J. Hum. Biol. 12:64–74, 2000. © 2000 Wiley-Liss, Inc.     

EphrinB2/EphB4 inhibition in the osteoblast lineage modifies the anabolic response to parathyroid hormone

Previous reports indicate that ephrinB2 expression by osteoblasts is stimulated by parathyroid hormone (PTH) and its related protein (PTHrP) and that ephrinB2/EphB4 signaling between osteoblasts and osteoclasts stimulates osteoblast differentiation while inhibiting osteoclast differentiation. To determine the role of the ephrinB2/EphB4 interaction in the skeleton, we used a specific inhibitor, soluble EphB4 (sEphB4), in vitro and in vivo. sEphB4 treatment of cultured osteoblasts specifically inhibited EphB4 and ephrinB2 phosphorylation and reduced mRNA levels of late markers of osteoblast/osteocyte differentiation (osteocalcin, dentin matrix protein‐1 [DMP‐1], sclerostin, matrix‐extracellular phosphoglycoprotein [MEPE]), while substantially increasing RANKL. sEphB4 treatment in vivo in the presence and absence of PTH increased osteoblast formation and mRNA levels of early osteoblast markers (Runx2, alkaline phosphatase, Collagen 1α1, and PTH receptor [PTHR1]), but despite a substantial increase in osteoblast numbers, there was no significant change in bone formation rate or in late markers of osteoblast/osteocyte differentiation. Rather, in the presence of PTH, sEphB4 treatment significantly increased osteoclast formation, an effect that prevented the anabolic effect of PTH, causing instead a decrease in trabecular number. This enhancement of osteoclastogenesis by sEphB4 was reproduced in vitro but only in the presence of osteoblasts. These data indicate that ephrinB2/EphB4 signaling within the osteoblast lineage is required for late stages of osteoblast differentiation and, further, restricts the ability of osteoblasts to support osteoclast formation, at least in part by limiting RANKL production. This indicates a key role for the ephrinB2/EphB4 interaction within the osteoblast lineage in osteoblast differentiation and support of osteoclastogenesis. © 2013 American Society for Bone and Mineral Research.     

Avian Cephalic Vascular Anatomy,Sites of Thermal Exchange,and the Rete Ophthalmicum

The general anatomy of avian cephalic blood vessels is well known and there are published details of their role in physiological thermoregulation. Unfortunately, the finer details of vascular pathways to and from sites of thermal exchange are not well known. Additionally, the role of the rete ophthalmicum (RO), a vascular heat exchanger in the temporal region, has been investigated in terms of brain temperature regulation, yet only the arteries have received substantial attention. Without anatomical details of both the arterial and venous pathways, the role of blood vessels in physiological thermoregulation is incomplete. Cephalic vascular anatomy of multiple avian taxa was investigated using a differential‐contrast, dual‐vascular injection technique and high‐resolution X‐ray microcomputed tomography. Sites of thermal exchange (oral, nasal, and orbital regions) and the RO were given special attention due to their known roles in cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and their ability to deliver cooled blood to the RO and dural venous sinus. Sites of thermal exchange were supplied by arteries directly and through collateral pathways. Veins were found to offer multiple pathways that could influence the temperature of neurosensory tissues, as well as pathways that would bypass neurosensory tissues. These results question the paradigm that arterial blood from the RO is the primary method of brain cooling in birds. A shift in the primary role of the RO from brain cooling to regulating and maintaining the temperature of the avian eye should be further investigated. Anat Rec, 299:1461–1486, 2016. © 2016 Wiley Periodicals, Inc.     

Recurrent nightly ketosis after prolonged exercise in type 1 diabetes – the need for glycogen replacement strategies. Case report and review of literature

Exercise in diabetes patients has many benefits but also several risks, of which hypoglycemia is most often discussed. We present a case with recurrent keto‐acidosis post‐exercise, in which we hypothesize that glycogen replacement strategies were insufficient. Our experience in this case and review of the literature emphasize the importance of discussing glycogen replacement strategies with your diabetic athletes.     

Potent antitumor activity of cabozantinib,a c‐MET and VEGFR2 inhibitor,in a colorectal cancer patient‐derived tumor explant model

Antiangiogenic therapy is commonly used for the treatment of colorectal cancer (CRC). Although patients derive some clinical benefit, treatment resistance inevitably occurs. The MET signaling pathway has been proposed to be a major contributor of resistance to antiangiogenic therapy. MET is upregulated in response to vascular endothelial growth factor pathway inhibition and plays an essential role in tumorigenesis and progression of tumors. In this study, we set out to determine the efficacy of cabozantinib in a preclinical CRC patient‐derived tumor xenograft model. We demonstrate potent inhibitory effects on tumor growth in 80% of tumors treated. The greatest antitumor effects were observed in tumors that possess a mutation in the PIK3CA gene. The underlying antitumor mechanisms of cabozantinib consisted of inhibition of angiogenesis and Akt activation and significantly decreased expression of genes involved in the PI3K pathway. These findings support further evaluation of cabozantinib in patients with CRC. PIK3CA mutation as a predictive biomarker of sensitivity is intriguing and warrants further elucidation. A clinical trial of cabozantinib in refractory metastatic CRC is being activated.     

Studying the human oral microbiome: challenges and the evolution of solutions

Since the pioneering work of van Leeuwenhoek in 1684, subsequently built upon by other renowned microbiologists Robert Koch, Willoughby Miller and GV Black, oral microbiology has developed innovative techniques to study the oral microflora (now termed the ‘oral microbiome’). The advent of molecular techniques such as DNA–DNA hybridization, polymerase chain reaction and DNA sequencing has created an array of opportunities to construct a comprehensive picture of the diversity and composition of the oral microbiome. Approximately 700 oral bacterial species have been identified, of which 50% have yet to be cultivated, and some of these are known only by their signature DNA sequences. The synergism of ever‐evolving culture‐based and state‐of‐the‐art culture‐independent molecular techniques has facilitated in‐depth understanding of the dynamics, acquisition and transfer of oral bacteria, along with their role in oral and general health and disease. Further research is needed to not only analyse but also to make sense of the ever‐increasing volumes of data which these molecular techniques (especially high‐throughput DNA sequencing) are generating, as well as why particular bacteria are present and what they are ‘actually doing’ there. This review presents a comprehensive literature search of oral microbiology‐related methods currently used to study the oral microbiome.