Isolation and characterization of human apatite-inducing aortic proteolipid

A proteolipid, capable of inducing hydroxyapatite in vitro, can be isolated from human aortic calcified lesions, noncalcified lesions, and nonlesion tissue obtained at autopsy. Analysis of the amino acid composition after acid hydrolysis showed all nucleators to be high in the hydrophobic amino acids glycine and alanine. Estimation of the molecular weight of the nucleator, extracted from calcified lesions, by gel filtration and lipid content showed a minimum molecular weight of 469,000 Da. All nucleators were characterized by the presence of acidic phospholipids which may have a role in the mechanism of calcification.     

BACTERIAL VAGINOSIS AND PRETERM BIRTH: A COMPREHENSIVE REVIEW OF THE LITERATURE

Preterm low birth weight is the major determinant of infant morbidity and mortality. Numerous studies have linked bacterial vaginosis (BV) with preterm birth and low birth weight (LBW), especially among black women. This article reviews the published literature to provide clear evidence that BV is an independent risk factor for preterm birth and LBW. Pregnant black women are especially at risk, having nearly three times the level of BV as pregnant white women. Compounding the problem is the fact that half the population of women with BV are asymptomatic, and current standard antenatal procedures do not provide for screening for BV. By reviewing BV treatment literature, this article also provides evidence that treatment for BV is effective and that the identification and treatment of BV in pregnant women can lead to substantial reduction in the high rates of preterm birth and LBW.     

A practice-based intervention to enhance quality of care in the first 3 years of life: the Healthy Steps for Young Children Program

Context  There is growing concern regarding the quality of health care available in the United States for young children, and specific limitations have been noted in developmental and behavioral services provided for children in the first 3 years of life. Objective  To determine the impact of the Healthy Steps for Young Children Program on quality of early childhood health care and parenting practices. Design, Setting, and Participants  Prospective controlled clinical trial enrolling participants between September 1996 and November 1998 at 6 randomization and 9 quasi-experimental sites across the United States. Participants were 5565 children enrolled at birth and followed up through age 3 years. Intervention  Incorporation of developmental specialists and enhanced developmental services into pediatric care in participants' first 3 years of life. Main Outcome Measures  Quality of care was operationalized across 4 domains: effectiveness (eg, families received =" BORDER="0">4 Healthy Steps–related services or discussed >6 anticipatory guidance topics), patient-centeredness (eg, families were satisfied with care provided), timeliness (eg, children received timely well-child visits and vaccinations), and efficiency (eg, families remained at the practice for =" BORDER="0">20 months). Parenting outcomes included response to child misbehavior (eg, use of severe discipline) and practices to promote child development and safety (eg, mothers at risk for depression discussed their sadness with someone at the practice). Results  Of the 5565 enrolled families, 3737 (67.2%) responded to an interview at 30 to 33 months (usual care, 1716 families; Healthy Steps, 2021 families). Families who participated in the Healthy Steps Program had greater odds of receiving 4 or more Healthy Steps–related services (for randomization and quasi-experimental sites, respectively: odds ratio [OR], 16.90 [95% confidence interval {CI}, 12.78 to 22.34] and OR, 23.05 [95% CI, 17.38 to 30.58]), of discussing more than 6 anticipatory guidance topics (OR, 8.56 [95% CI, 6.47 to 11.32] and OR, 12.31 [95% CI, 9.35 to 16.19]), of being highly satisfied with care provided (eg, someone in the practice went out of the way for them) (OR, 2.06 [95% CI, 1.64 to 2.58] and OR, 2.11 [95% CI, 1.72 to 2.59]), of receiving timely well-child visits and vaccinations (eg, age-appropriate 1-month visit) (OR, 1.98 [95% CI, 1.08 to 3.62] and OR, 2.11 [95% CI, 1.16 to 3.85]), and of remaining at the practice for 20 months or longer (OR, 2.02 [95% CI, 1.61 to 2.55] and OR, 1.75 [95% CI, 1.43 to 2.15]). They also had reduced odds of using severe discipline (eg, slapping in face or spanking with object) (OR, 0.82 [95% CI, 0.54 to 1.26] and OR, 0.67 [95% CI, 0.46 to 0.97]). Among mothers considered at risk for depression, those who participated in the Healthy Steps Program had greater odds of discussing their sadness with someone at the practice (OR, 0.95 [95% CI, 0.56 to 1.63] and OR, 2.82 [95% CI, 1.57 to 5.08]). Conclusion  Universal, practice-based interventions can enhance quality of care for families of young children and can improve selected parenting practices.      

The voice evaluation after vertical hemilaryngectomy

The basic parameters of voice were estimated in 24 patients after vertical hemilaryngectomy. The results show deterioration of voice quality, but its social efficiency is still enough.     

Nonangiographic imaging of the pulmonary arteries: CT and MR

Computed tomography (CT) has provided a imaging modality by which the central pulmonary arteries can be studied noninvasively. CT provides cross-sectional images which accurately depict the pulmonary arteries and adjacent structures. Magnetic resonance (MR) imaging with its ability to image vessels without contrast media provides a potential truly noninvasive means of examining the pulmonary arteries. These modalities are well suited to evaluate pathology involving the central pulmonary arteries. Normal CT and MR anatomy is illustrated and discussed. The clinical presentation and appearance of pathological processes involving the pulmonary arteries are described.     

A role for DNA-mediated charge transport in regulating p53: Oxidation of the DNA-bound protein from a distance

Charge transport (CT) through the DNA base pairs provides a means to promote redox reactions at a remote site and potentially to effect signaling between molecules bound to DNA. Here we describe the oxidation of a cell-cycle regulatory protein, p53, from a distance through DNA-mediated CT. A consensus p53 binding site as well as three DNA promoters regulated by p53 were synthesized containing a tethered DNA photooxidant, anthraquinone. Photoinduced oxidation of the protein occurs from a distance; introduction of an intervening CA mismatch, which inhibits DNA-mediated CT, prevents oxidation of p53. DNA-mediated oxidation is shown to promote dissociation of p53 from only some promoters, and this sequence-selectivity in oxidative dissociation correlates with the biological regulation of p53. Under severe oxidative stress, effected here through oxidation at long range, p53 dissociates from a promoter that activates DNA repair as well as the promoter for the negative regulator of p53, Mdm2, but not from a promoter activating cell-cycle arrest. Mass spectrometry results are consistent with disulfide bond formation in p53 upon DNA-mediated oxidation. Furthermore, DNA-bound p53 oxidation is shown in vivo by up-regulation of p53 and subsequent irradiation in the presence of a rhodium photooxidant to give a new p53 adduct that can be reversed with thiol treatment. This DNA-mediated oxidation of p53 parallels that seen by treating cells with hydrogen peroxide. These results indicate a unique mechanism using DNA-mediated CT chemistry by which p53 activity on different promoters may be controlled globally under conditions of oxidative stress.     

Differential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis

Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer of thyroid C-cells, for which few treatment options are available. We have recently reported a role for cyclin-dependent kinase 5 (CDK5) in MTC pathogenesis. We have generated a mouse model, in which MTC proliferation is induced upon conditional overexpression of the CDK5 activator, p25, in C-cells, and arrested by interrupting p25 overexpression. Here, we identify genes and proteins that are differentially expressed in proliferating versus arrested benign mouse MTC. We find that downstream target genes of the tumor suppressor, retinoblastoma protein, including genes encoding cell cycle regulators such as CDKs, cyclins and CDK inhibitors, are significantly upregulated in malignant mouse tumors in a CDK5-dependent manner. Reducing CDK5 activity in human MTC cells down-regulated these cell cycle regulators suggesting that CDK5 activity is critical for cell cycle progression and MTC proliferation. Finally, the same set of cell cycle proteins was consistently overexpressed in human sporadic MTC but not in hereditary MTC. Together these findings suggest that aberrant CDK5 activity precedes cell cycle initiation and thus may function as a tumor-promoting factor facilitating cell cycle protein expression in MTC. Targeting aberrant CDK5 or its downstream effectors may be a strategy to halt MTC tumorigenesis.     

The effects of bullying

Bullying is a major problem for children. There are well-defined risk factors for bullying that are individual and social. Beyond the immediate trauma of experiencing bullying, victims are at high risk of later physical and emotional disorders. Bullies are the generators of this trauma but also suffer poor long-term effects as a result of their participation. Bystanders are also not immune from bullying's toxic effects nor innocent from its occurrence. While most often occurring at schools, paediatric clinicians can identify and support children suffering from bullying. They also have the unique opportunity to engage the schools and wider society on anti-bullying initiatives. This article will outline the risk, signs and symptoms of bullying to help clinicians identify and address these children in need.     

"Different is nice, but it sure isn't easy": differentiating the spectrum of autism from the spectrum of normalcy

CASE: Brian is a 15-year-old boy who has been just changed to your practice because of a change in insurance plans. When taking the social history, his parents note that he has "the hardest time relating to other kids." Sometimes he will be in the middle of a conversation with a friend and then discuss tangential topics. His father reports that Brian "...has always been an easy target. He has always been sort of bigger than other kids, but being bigger than other kids, he has a hard time standing up for himself." He seems to expect to be picked on in any new social situation. When Brian likes something, he really goes after it with a passion; for example, he is very interested in knowing all about the dynasties in China. His interests are dinosaurs and anime. He is described as "An all-or-nothing type kid" when it comes to his interests. If his father tries to explain to Brian why he would like something done in a particular way, Brian will explode, and at times, he has even tried to shove his father. He does not really have any friends. His mother finds it hard knowing that Brian cannot make friends because he "is the sweetest kid you will ever meet." Brian sometimes thinks he needs to master things right away. He is not very good at abstract thinking, and "he can't think outside of the box." Eye contact has always been something that has been difficult for Brian as well. He can sit in front of the TV watching a show and repeat the entire series word for word. His parents initially had concerns about Brian, when he was 3 or 4 years old. After a specialty evaluation, he was diagnosed with sensory integration disorder and attention-deficit hyperactivity disorder. He is currently starting the 10th grade this year. Brian was born at 9 months, weighing 7 pounds 10 ounces. There were no complications. He was treated with stimulants for attention-deficit hyperactivity disorder in the past, and he is currently on a long-acting amphetamine with equivocal efficacy. The parents are primarily here to refill his medication, but you wonder about their understanding about Brian's condition and where to head next during this visit.