To determine the timing of peak bone mass and density, we conducted a cross-sectional study of bone mass measurements in 265 premenopausal Caucasian females, aged 8-50 yr. Bone mass and bone mineral density were measured using dual X-ray absorptiometry and single-photon absorptiometry at the spine (anteroposterior, lateral), proximal femur, radius shaft, distal forearm, and the whole body. Bone mass parameters were analyzed using a quadratic regression model and segmented regression models with quadratic-quadratic or quadratic-linear form. The results show that most of the bone mass at multiple skeletal locations will be accumulated by late adolescence. This is particularly notable for bone mineral density of the proximal femur and the vertebral body. Bone mass of the other regions of interest is either no different in women between the age of 18 yr and the menopause or it is maximal in 50-yr-old women, indicating slow but permanent bone accumulation continuing at some sites up to the time of menopause. This gain in bone mass in premenopausal adult women is probably the result ofcontinuous periosteal expansion with age. Since rapid skeletal mineral acquisition at all sites occurs relatively early in life, the exogenous factors which might optimize peak bone mass need to be more precisely identified and characterized. (J. Clin. Invest.

On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees.

The significance of KRAS mutant allele-specific imbalance (MASI) in lung adenocarcinomas is unknown. KRAS MASI was defined as predominance of the mutant allele over the wild-type allele. We assessed the frequency of KRAS MASI by comparing peak heights of mutant and wild-type alleles on sequencing electropherograms and by KRAS fluorescence in situ hybridization (FISH). A review of sequencing electropherograms of 207 KRAS-mutated lung adenocarcinomas demonstrated 23 (11%) cases with the mutant allele peak higher than the wild-type allele peak and 15 (7%) cases with the mutant allele peak equal to the wild-type allele peak. Of 17 cases with the mutant allele peak higher or equal to the wild-type allele peak, 8 (47%) showed KRAS amplification by FISH. KRAS FISH analysis of 36 KRAS-mutated lung adenocarcinomas with the mutant allele peak lower than the wild-type allele peak, 21 KRAS and EGFR wild-type and 16 EGFR-mutated adenocarcinomas showed no KRAS amplification. KRAS MASI was associated with selective amplification of the KRAS mutant allele (Po0.001). Patients with KRAS MASI showed worse overall survival. The cumulative proportion surviving at 17 months for KRAS MASI group was 35% compared with 84.1% for patients with KRAS mutant allele peak lower than wild-type allele peak (P ¼ 0.012). The adverse prognostic significance of KRAS MASI was independent of clinical stage and was maintained among stage I patients. The detection of KRAS MASI in lung adenocarcinomas by sequencing electropherograms may identify patients with more aggressive disease.

T he coronavirus disease 2019 (COVID-19) pandemic is the largest public health crisis in over a century. 1 As of Jan. 15, 2021, COVID-19 has resulted in over 113 million infections and almost 2.5 million deaths globally. 2 The global crude mortality rate among patients diagnosed with COVID-19 is about 3%, but some countries have reported rates that are up to 3 times higher. 2,3 Factors explaining these variations include population differences in demographics, health status and socioeconomics, as well as system factors such as the availability of testing, pandemic preparedness and response, with others yet to be uncovered. 4,5 There is an urgent need for high-quality, populationlevel data to understand modifiable risks for disease severity

We have found that nanobacteria, recently discovered Gram-negative atypical bacteria, can cause local calciphylaxis on the mitral valve in a setting of high-calcium X phosphorous product in the blood. We present the case of a 33-year-old man with diabetic renal failure on continuous ambulatory peritoneal dialysis who died as a result of multiple brain infarcts due to embolizations from mitral valve vegetations. Systemic calciphylaxis was not present. Spectrometric analysis of the mitral valve vegetations showed that they were composed of calcium phosphate, carbonate apatite form, and fibrin. The electron microscopy of the thrombotic vegetation demonstrated nanobacterium as a nidus for carbonate apatite formation. Investigation for the presence of nanobacteria in the multiple organs involved in systemic calciphylaxis may be of help in elucidating the pathogenesis of this frequently fatal disorder.

Adolescence is characterized by rapid skeletal development and high demands for bone minerals. Though the stimulative effect of calcitriol on intestinal calcium and phosphorus absorption is well understood, its effect on bone development is not completely clear. It may be directly involved in the facilitation of calcium economy during this critical phase of skeletal development. Therefore, we evaluated the serum concentrations of calcitriol in relation to skeletal development in a cross-sectional study of 178 healthy Caucasian females during different pubertal stages, extending from childhood to young adulthood. In addition, a subsample of 57 younger girls was followed for a 1-year period to evaluate the association among serum calcitriol, nutrition parameters (dietary calcium, phosphorus, and vitamin D), bone mass accumulation, and biochemical markers of bone turnover. The serum calcitriol concentration in a cross-sectional sample was the highest during pubertal growth spurt (sexual maturity index 3-4, age 11-13 years) (ANOVA; F = 2.4945; P = 0.0329). This correlated to the peak skeletal calcium accretion (g/year) and bone mass accumulation in total body and forearm. In a longitudinal sample, there was a positive association between annual change in TBBMC (P = 0.0255); TBBMD (P = 0.0168); proximal radius (1/3 distance from styloid process) BMC (P = 0.0096); BMD (P = 0.0541), and baseline calcitriol level in forward stepwise regression analyses. The results of the forward stepwise regression analyses with serum calcitriol as a dependent variable and different serum, urinary, and dietary parameters measured at baseline (age 11 years, n = 114) and after 1 year (age 12 years, n = 57) showed that osteocalcin was positively associated with calcitriol in both years; more so in a second year (P = 0.0514, P < 0.001, respectively). Dietary vitamin D and phosphorus showed negative association with serum calcitriol at age 11, and dietary Ca and P were selected at age 12. The results of this study show that calcitriol is a significant correlate of bone mass accumulation during pubertal growth, presumably in response to the high requirements for calcium during this critical phase of skeletal development.

ObjectivesThis study sought to establish by expert review a consensus‐based, focused ultrasound curriculum, consisting of a foundational set of focused ultrasound skills that all Canadian medical students would be expected to attain at the end of the medical school program.MethodsAn expert panel of 21 point‐of‐care ultrasound and educational leaders representing 15 of 17 (88%) Canadian medical schools was formed and participated in a modified Delphi consensus method. Experts anonymously rated 195 curricular elements on their appropriateness to include in a medical school curriculum using a 5‐point Likert scale. The group defined consensus as 70% or more experts agreeing to include or exclude an element. We determined a priori that no more than 3 rounds of voting would be performed.ResultsOf the 195 curricular elements considered in the first round of voting, the group reached consensus to include 78 and exclude 24. In the second round, consensus was reached to include 4 and exclude 63 elements. In our final round, with 1 additional item added to the survey, the group reached consensus to include an additional 3 and exclude 8 elements. A total of 85 curricular elements reached consensus to be included, with 95 to be excluded. Sixteen elements did not reach consensus to be included or excluded.ConclusionsBy expert opinion‐based consensus, the Canadian Ultrasound Consensus for Undergraduate Medical Education Group recommends that 85 curricular elements be considered for inclusion for teaching in the Canadian medical school focused ultrasound curricula.

Examination of 125 insulin pens used in hospitals revealed hemoglobin in 1 pen and at least one cell in another 6 pens. The nine detected cells consisted of four squamous epithelial cells, four macrophages, and one RBC.