Parental Adverse Childhood Experiences and Pediatric Healthcare Use by 2 Years of Age.

OBJECTIVE: To determine whether maternal and paternal exposure to adverse childhood experiences (ACEs) has an association with offspring healthcare use by 2 years of age. STUDY DESIGN: A retrospective cohort study was performed on 454 patients at a large suburban pediatric primary care practice whose mother (n = 374) or father (n = 156) or both (n = 123) completed an ACE survey between October 2012 and June 2014. The association between self-reported parental ACEs and healthcare use by 2 years of age, including number of missed well-child visits, sick visits, and delayed or missed immunizations, was modeled using multivariable negative binomial regression. All analyses adjusted for child sex, payer source, and preterm birth. RESULTS: Maternal, but not paternal, ACE exposure was significantly associated with missed well-child visits by 2 years of age. For each additional maternal ACE, there was a significant 12% increase in the incidence rate of missed well-child visits (relative risk, 1.12; 95% CI, 1.03-1.22; P = .010). Maternal and paternal ACE scores were not significantly associated with increased sick visits or delayed or missed immunizations. CONCLUSIONS: The ACE exposure of mothers is negatively associated with adherence to preventive healthcare visits among their children early in life. Future research is needed to elucidate the mechanisms of this association and to develop and implement family-based intervention strategies.

The national improvement partnership network: state-based partnerships that improve primary care quality.

Improvement partnerships (IPs) are a model for collaboration among public and private organizations that share interests in improving child health and the quality of health care delivered to children. Their partners typically include state public health and Medicaid agencies, the local chapter of the American Academy of Pediatrics, and an academic health care organization or children's hospital. Most IPs also engage other partners, including a variety of public, private, and professional organizations and individuals. IPs lead and support measurement-based, systems-focused quality improvement (QI) efforts that primarily target primary care practices that care for children. Their projects are most often conducted as learning collaboratives that involve a team from each of 8 to 15 participating practices over 9 to 12 months. The improvement teams typically include a clinician, office manager, clinical staff (nurses or medical assistants), and, for some projects, a parent; the IPs provide the staff and local infrastructure. The projects target clinical topics, chosen because of their importance to public health, local clinicians, and funding agencies, including asthma, attention-deficit/hyperactivity disorder, autism, developmental screening, obesity, mental health, medical home implementation, and several others. Over the past 13 years, 19 states have developed (and 5 are exploring developing) IPs. These organizations share similar aims and methods but differ substantially in leadership, structure, funding, and longevity. Their projects generally engage pediatric and family medicine practices ranging from solo private practices to community health centers to large corporate practices. The practices learn about the project topic and about QI, develop specific improvement strategies and aims that align with the project aims, perform iterative measures to evaluate and guide their improvements, and implement systems and processes to support and sustain those improvements. Since 2008, IPs have offered credit toward Part 4 of Maintenance of Certification for participants in some of their projects. To date, IPs have focused on achieving improvements in care delivery through individual projects. Rigorous measurement and evaluation of their efforts and impact will be essential to understanding, spreading, and sustaining state/regional child health care QI programs. We describe the origins, evolution to date, and hopes for the future of these partnerships and the National Improvement Partnership Network (NIPN), which was established to support existing and nurture new IPs.

Gender differences in the anatomy of the distal femur.

Recently, gender-specific designs of total knee replacement have been developed to accommodate anatomical differences between males and females. We examined a group of male and female distal femora matched for age and height, to determine if there was a difference in the aspect ratio (mediolateral distance versus anteroposterior distance) and the height of the anterior flange between the genders. The Hamann-Todd Collection provided 1207 skeletally mature cadaver femora. The femoral length, the anteroposterior height, height of the lateral and medial flanges and the mediolateral width were measured in all the specimens. The mechanical axis of the femur, the cut articular width and the aspect ratio were assessed. Statistical analysis of the effect of gender upon the aspect ratio and the lateral and medial flanges was undertaken, controlling for age, height and race. The mean aspect ratio of male femora was 1.21 (SD 0.07) and of female femora it was 1.16 (SD 0.06) (p < 0.001). There was no significant difference between male and female specimens in the mean size of the lateral flange (6.57 mm (SD 2.57) and 7.02 mm (SD 2.36), respectively; p = 0.099) or of the medial flange (3.03 mm (SD 2.47) and 3.56 mm (SD 2.32), respectively; p = 0.67). Future work in the design of knee prostheses should take into account the overall variability of the anatomy of the distal femur.

Idiopathic post-traumatic dermatitis at the site of recent joint replacement.

Idiopathic dermatitis over the site of previous trauma is a recognized but infrequently reported phenomenon that provides a diagnostic dilemma. Careful investigation is needed in order to exclude other rare and/or treatable causes.

Gilbert N. Lewis and the chemical bond: the electron pair and the octet rule from 1916 to the present day.

We describe the development of Lewis's ideas concerning the chemical bond and in particular the concept of the electron pair bond and the octet rule. We show that the concept of the electron pair bond has endured to the present day and is now understood to be a consequence of the Pauli principle. In contrast the octet rule is now regarded as much less important than was originally generally believed, although Lewis himself knew several exceptions and regarded it as less important than what he called the rule of two (the electron pair). The octet rule was more strongly promoted by Langmuir who is also responsible for the term covalent bond. However, many more exceptions to the octet rules than were known to Lewis are now known and the terms hypervalent and hypovalent used to describe such molecules are no longer particularly useful. Today it is realized that bonding electron pairs in many molecules are not as well localized as Lewis believed, nevertheless resonance structures, i.e., plausible alternative Lewis structures, are still often used to describe such molecules. Moreover electrons are not always found in pairs, as for example in linear molecules, which can, however, be satisfactorily described by Linnett's double quartet theory. The electron density distribution in a molecule can now be analyzed using the ELF and other functions of the electron density to show where electron pairs are most probably to be found in a molecule.

The geometry of nonmetal hydrides and the ligand radius of hydrogen.

The aim of this paper was to investigate why the geometries of nonmetal hydrides are often not in accordance with the VSEPR model. From a consideration of interligand distances in a variety of BX(4), CX(4), and NX(4) molecules where X is a ligand or a lone pair and in which there are at least two H ligands we have shown that the hydrogen ligands are essentially close-packed. For each of the central atoms we have obtained a value for the ligand radius of hydrogen. These radii decrease with decreasing negative charge and increasing positive charge of the hydrogen ligand as the electronegativity of the central atom increases, as has been found previously for other ligands such as F and Cl. We show that ligand-ligand intractions are an important factor in determining bond angles in hydrides and that the ligand close-packing (LCP) model gives a better explanation of bond angles than the VSEPR model according to which bond angles depend on the electronegativity of the ligand rather than on its size. For example, although the very small angles in PH(3) and SH(2) are not in accord with the VSEPR model, they are consistent with the LCP model in that they are a consequence of the small size of hydrogen ligands which are pushed together by the lone pairs until they are almost close-packed.

Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease.

During a program to investigate the biochemical basis of side effects associated with the antimalarial drug mefloquine, the authors made the unexpected discovery that the (-)-(R,S)-enantiomer of the drug is a potent adenosine A2A receptor antagonist. Although the compound was ineffective in in vivo animal models of central adenosine receptor function, it provided a unique nonxanthine adenosine A2A receptor antagonist lead structure and encouraged the initiation of a medicinal chemistry program to develop novel adenosine A2A antagonists for the management of Parkinson's disease (PD). The authors have synthesized and screened more than 2,000 chemically diverse and novel adenosine A(2A antagonists. Early examples from two distinct chemical series are the thieno[3,2-dy]pyrimidine VER-6623 and the purine compounds VER-6947 and VER-7835, which have high affinity at adenosine A2A receptors (K(i) values 1.4, 1.1, and 1.7 nmol/L, respectively) and act as competitive antagonists. In particular, VER-6947 and VER-7835 demonstrate potent in vivo activity reversing the locomotor deficit caused by the D2 receptor antagonist haloperidol, with minimum effective doses comparable with that of KW6002 (0.3 to 1 mg/kg). In conclusion, the authors have discovered potent, selective, and in vivo active nonxanthine adenosine A2A antagonists that have considerable promise as a new therapy for PD.

Ligand close packing and the geometry of the fluorides of the nonmetals of periods 3, 4, and 5.

This paper discusses the geometry of the fluorides of the nonmetals of periods 3, 4, and 5 in terms of the ligand close packing (LCP) model according to which molecular geometry is determined primarily by ligand-ligand repulsions (Pauli closed shell repulsions) rather than by the bonding and lone pair Pauli repulsions of the VSEPR model. The LCP model becomes the dominant factor in determing geometry when the ligands are sufficiently crowded that they may be regarded as essentially incompressible. Ligand close packing is a modification of the VSEPR model in which ligand-ligand repulsion (Pauli closed shell repulsion) is given more emphasis than bonding and nonbonding electron pair Pauli repulsion. The nonmetals of period 3 are large enough to form octahedral six coordinated molecules in which the ligands are close packed. The larger nonmetals of period 4 also have a maximum coordination number of six and an octahedral geometry although the ligands are not close packed. Ligand radii derived from the interligand distances in the molecules of period 3 depend only on the charge of the fluorine ligands and are consistent with the previously derived radii obtained from the fluorides of the close packed tetrahedral molecules of the period 2 elements. Although the ligands in the molecules of the period 4 nonmetals are not close packed, these elements are not large enough to form molecules with a higher coordination number. However, the larger period 5 nonmetals may have coordination numbers of seven and eight. The seven coordinated molecules have a pentagonal bipyramidal geometry in which the equatorial ligands are close packed. The eight coordinated molecules have a square antiprism geometry, which is not a close packed geometry although the fluorine interligand distances are only a little larger than expected for close packing. The difference between the axial and equatorial bond lengths in the trigonal bipyramidal pentafluorides and the pentagonal bipyramidal pentafluorides can be understood on the basis of ligand close packing. Ligand packing prevents the lone pair in AF(6)E molecules from fully entering the valence shell and thereby exerting its full stereochemical effect so that these molecules have a C(3)(v)() distorted octahedral geometry rather than a geometry based on pentagonal bipyramidal seven coordination.

RSC-SCI--tenth medicinal chemistry symposium. 5-8 September 1999, Churchill College, Cambridge, UK.

This meeting was part of a biennial series focusing upon topics at the forefront of medicinal chemistry. There was no single therapeutic focus for the meeting, but the 24 lectures were spread between various themes: enzyme inhibitors; drug-receptor/ion channel interactions; enabling technologies; and, new topics in drug research. Several of the lectures featured structure-activity relationships of new drugs, outlining the rationale for the selection of drug candidates. It was clear that many pharmaceutical companies now routinely employ in vivo studies of distribution and pharmacokinetics early in the drug discovery process, thereby adding to the traditional criteria of affinity, selectivity and in vivo effect when potential drugs are selected for development. Likelihood of success during later clinical investigation phases is thereby enhanced.

Primary cryptococcal cellulitis caused by Cryptococcus neoformans var. gattii in an immunocompetent host.

Primary cutaneous cryptococcal infection is uncommon. The cutaneous manifestations are most often the result of dissemination from the central nervous system or lung, usually in an immunocompromised host; cellulitis is regarded as the rarest cutaneous form. Primary cutaneous cryptococcosis has occasionally been reported in the immunocompetent, the causative organism being Cryptococcus neoformans var. neoformans. We present a case of cellulitis of the right arm in a 75-year-old man caused by Cryptococcus neoformans var. gattii, a fungus which is endemic in Australia and an important cause of infection in the immunocompetent. This is the first case described of a primary cutaneous infection due to Cryptococcus neoformans var. gattii. The interesting ecology of this organism is discussed.

Pitfalls and opportunities for environmental marketers.

Issues such as global warming, ozone depletion, insufficient landfill capacity, and excess packaging are foremost on the minds of consumers. Companies face a myriad of environmental challenges, but they also recognize the opportunities to be gained by implementing responsible marketing action plans.

2-(oxadiazolyl)- and 2-(thiazolyl)imidazo[1,2-a]pyrimidines as agonists and inverse agonists at benzodiazepine receptors.

Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivated conflict test thought to predict anxiolytic properties. Compounds 4, 5, and 13 were equipotent with chlordiazepoxide but showed little or no myorelaxant effects. Replacing the oxadiazole group by thiazole gave compounds such as 23 which binds to the benzodiazepine receptor but exhibits the intrinsic activity of a partial inverse agonist in vivo.