Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus

BACKGROUND: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy. METHODS AND RESULTS: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period. CONCLUSIONS: A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions

The influence of caffeine on energy content of sugar-sweetened beverages : the caffeine–calorie effect

Background/Objectives: Caffeine is a mildly addictive psychoactive chemical and controversial additive to sugar-sweetened beverages (SSBs). The objective of this study is to assess if removal of caffeine from SSBs allows co-removal of sucrose (energy) without affecting flavour of SSBs, and if removal of caffeine could potentially affect population weight gain. Subjects/Methods: The research comprised of three studies; study 1 used three-alternate forced choice and paired comparison tests to establish detection thresholds for caffeine in water and sucrose solution (subjects, n ¼ 63), and to determine if caffeine suppressed sweetness. Study 2 (subjects, n ¼ 30) examined the proportion of sucrose that could be co-removed with caffeine from SSBs without affecting the flavour of the SSBs. Study 3 applied validated coefficients to estimate the impact on the weight of the United States population if there was no caffeine in SSBs. Results: Detection threshold for caffeine in water was higher (1.09±0.08 mM) than the detection threshold for caffeine in sucrose solution (0.49 ± 0.04 mM), and a paired comparison test revealed caffeine significantly reduced the sweetness of sucrose (Po0.001). Removing caffeine from SSBs allowed co-removal of 10.3% sucrose without affecting flavour of the SSBs, equating to 116 kJ per 500 ml serving. The effect of this on body weight in adults and children would be 0.600 and 0.142 kg, which are equivalent to 2.08 and 1.10 years of observed existing trends in weight gain, respectively. Conclusion: These data suggest the extra energy in SSBs as a result of caffeine's effect on sweetness may be associated with adult and child weight gain

Nitrate Radical Facilitates Indirect Benzyl Alcohol Oxidation on Bismuth(III) Vanadate Photoelectrodes

Bismuth(III) vanadate (BiVO4) films show activity for direct benzyl alcohol (PhCH2OH) oxidation to benzaldehyde (PhCHO) in acetonitrile solvent. Introducing tetrabutylammonium nitrate (Bu4NNO3) drastically reduces the overpotential required to generate the PhCHO product while maintaining a high faradaic efficiency (FE) >90 %. BiVO4 corrosion accompanies PhCH2OH oxidation. However, the presence of nitrate ions (NO3−) results in significantly less bismuth‐ and vanadium‐ion leaching (determined by ICP‐MS analysis), as well as reduced surface roughening (determined by SEM imaging). In this reaction, it is proposed that rate‐determining NO3− oxidation generates a highly reactive nitrate radical (NO3⋅) that reacts with PhCH2OH by hydrogen‐atom abstraction (HAT). NO3− is stoichiometrically consumed by the irreversible formation of electrochemically inert HNO3, characterized by an ECi mechanism, rather than a catalytic EC′ mechanism. In the presence of PhCH2OH, NO3− oxidation on BiVO4 becomes more facile; every order of magnitude increase in PhCH2OH concentration shifts the NO3−/ NO3⋅ equilibrium potential negatively by 200 mV. The shift results from the introduction of a consumption pathway for the nitrate radical intermediate via a coupled chemical step with benzyl alcohol. This report is the first example of photoelectrochemical NO3⋅ generation to initiate indirect PhCH2OH oxidation.Initiate to generate: Bismuth(III) vanadate (BiVO4) films show activity for direct benzyl alcohol (PhCH2OH) oxidation to benzaldehyde (PhCHO) in acetonitrile solvent. Introducing tetrabutylammonium nitrate (Bu4NNO3) drastically reduces the overpotential required to generate the PhCHO product while maintaining a high faradaic efficiency. BiVO4 corrosion accompanies PhCH2OH oxidation. Moreover, the presence of nitrate ions (NO3−) results in significantly less bismuth‐ and vanadium‐ion leaching as well as reduced surface roughening.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162788/3/celc202000911.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162788/2/celc202000911-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162788/1/celc202000911_am.pd

Molybdenum Complexes of Chiral C2-symmetric Picchxn-type Ligands: Synthesis, Characterization, and Structural Studies

A series of molybdenum complexes based on chiral C2-symmetric picchxn-type ligands (N4 ligands, defined as trans-N,N′-bis(heterocycl-2-ylmethyl)-1,2-diaminocyclohexanes) has been synthesized and characterized. Reported and novel picchxn-type ligands form (κ3-N4)Mo(CO)3, [(κ4-N4)Mo(NO)(CO)]PF6, and [(κ4-N4)Mo(NO)X]PF6 (X = Br, I) compounds. Multiple tridentate (κ3) and tetradentate (κ4) ligand configurations were observed, and the favored κ4 configuration was found to vary with N4 heterocycle identity. Heterocycle variation allowed for directed modification of the molybdenum electronic characteristics, but none of the studied {(κ4-N4)Mo(NO)}+ fragments was found to be a suitable π-base for dearomatization chemistry. The crystal structures of eight molybdenum complexes with picchxn-type ligands were determined

Acute Effects of Enteral Nutrition on Protein Turnover in Adolescents with Crohn Disease

ABSTRACT: Adults with inactive Crohn disease have been shown to have normal rates of protein turnover when compared with healthy adults. It is not known whether this is true for adolescents with inactive Crohn disease, when rate of protein synthesis must be greater than that of breakdown for normal development. The objective of this study was to determine whether enteral nutrition acutely suppresses proteolysis and increases protein synthesis in adolescents with inactive Crohn disease. Six adolescents (five males/one female; mean age, 15.8 Ϯ 1.9 y; range, 13.2-17.6 y; mean bone age, 14.6 Ϯ 1.8 y; range, 12.5-17 y) participated. Leucine (Leu) and phenylalanine (Phe) kinetics were measured using stable isotopes under fasted and fed conditions during a single study visit. In response to enteral nutrition, the endogenous rates of appearance (R a ) of Leu and Phe (reflecting proteolysis) decreased significantly by 40%. The percentages of splanchnic uptake of Leu and Phe were 35 Ϯ 10% and 13 Ϯ 12%, respectively. Under fed conditions, utilization of Phe for protein synthesis increased significantly. We conclude that in clinically stable adolescents with Crohn disease, enteral nutrition promotes anabolism by suppressing proteolysis and increasing protein synthesis. Rates of suppression of proteolysis were similar to those reported previously in normal children

Predicting growth and curve progression in the individual patient with adolescent idiopathic scoliosis: design of a prospective longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Scoliosis is present in 3-5% of the children in the adolescent age group, with a higher incidence in females. Treatment of adolescent idiopathic scoliosis is mainly dependent on the progression of the scoliotic curve. There is a close relationship between curve progression and rapid (spinal) growth of the patient during puberty. However, until present time no conclusive method was found for predicting the timing and magnitude of the pubertal growth spurt in total body height, or the curve progression of the idiopathic scoliosis.</p> <p>The goal of this study is to determine the predictive value of several maturity indicators that reflect growth or remaining growth potential, in order to predict timing of the peak growth velocity of total body height in the individual patient with adolescent idiopathic scoliosis. Furthermore, different parameters are evaluated for their correlation with curve progression in the individual scoliosis patient.</p> <p>Methods/design</p> <p>This prospective, longitudinal cohort study will be incorporated in the usual care of patients with adolescent idiopathic scoliosis. All new patients between 8 and 17 years with adolescent idiopathic scoliosis (Cobb angle >10 degrees) visiting the outpatient clinic of the University Medical Center Groningen are included in this study. Follow up will take place every 6 months. The present study will use a new ultra-low dose X-ray system which can make total body X-rays. Several maturity indicators are evaluated like different body length dimensions, secondary sexual characteristics, skeletal age in hand and wrist, skeletal age in the elbow, the Risser sign, the status of the triradiate cartilage, and EMG ratios of the paraspinal muscle activity.</p> <p>Correlations of all dimensions will be calculated in relationship to the timing of the pubertal growth spurt, and to the progression of the scoliotic curve. An algorithm will be made for the optimal treatment strategy in the individual patient with adolescent idiopathic scoliosis.</p> <p>Discussion</p> <p>This study will determine the value of many maturity indicators and will be useful as well for other clinicians treating children with disorders of growth. Since not all clinicians have access to the presented new 3D X-ray system or have the time to make EMG's, for example, all indicators will be correlated to the timing of the peak growth velocity of total body height and curve progression in idiopathic scoliosis. Therefore each clinician can chose which indicators can be used best in their practice.</p> <p>Trial registration number</p> <p>NTR2048</p

Natural history of perinatal and infantile hypophosphatasia: A retrospective study

Objective: To report clinical characteristics and medical history data obtained retrospectively for a large cohort of pediatric patients with perinatal and infantile hypophosphatasia. Study design: Medical records from academic medical centers known to diagnose and/or treat hypophosphatasia were reviewed. Patients born between 1970 and 2011 with hypophosphatasia and any of the following signs/symptoms at age &lt;6 months were eligible: vitamin B6–dependent seizures, respiratory compromise, or rachitic chest deformity (NCT01419028). Patient demographics and characteristics, respiratory support requirements, invasive ventilator–free survival, and further complications of hypophosphatasia were followed for up to the first 5 years of life. Results: Forty-eight patients represented 12 study sites in 7 countries; 13 patients were alive, and 35 were dead (including 1 stillborn). Chest deformity, respiratory distress, respiratory failure (as conditioned by the eligibility criteria), failure to thrive, and elevated calcium levels were present in &gt;70% of patients between birth and age 5 years. Vitamin B6–dependent seizures and respiratory distress and failure were associated significantly (P &lt;.05)with the risk of early death. Serum alkaline phosphatase activity in all 41 patients tested (mean [SD]: 18.1 [15.4]U/L)was below the mean lower limit of normal of the reference ranges of the various laboratories (88.2 U/L). Among the 45 patients with relevant data, 29 had received respiratory support, of whom 26 had died at the time of data collection. The likelihood of invasive ventilator–free survival for this cohort decreased to 63% at 3 months, 54% at 6 months, 31% at 12 months, and 25% at 5 years. Conclusions: Patients with perinatal or infantile hypophosphatasia and vitamin B6–dependent seizures, with or without significant respiratory distress or chest deformities, have high morbidity and mortality in the first 5 years of life. Trial registration: ClinicalTrials.gov: NCT01419028