Chromosomal localization of 15 ion channel genes

As academic health center seek to address the changes in the health care system and in medical education, several approaches have been tried, some successfully, others not. The authors describe a successful approach that involves a close partnership between the health professions schools at two academic institutions, and agencies from the surrounding community. Specifically, the Center for Healthy Communities, begun in 1991 and formally institutionalized in 1994 in Dayton, Ohio, is a partnership among the schools of medicine, nursing, and professional psychology at Wright State University (WSU); the department of social work at WSU; the Allied Health Division of Sinclair Community College; more than 200 individuals (from grassroots neighborhood people to civic leaders); and 50 health and human services organizations in the Dayton area. The Center is recognized as a force for change in health professions education and health care delivery both in the community and in the academic settings. The authors explain how the Center was formed, list its goals (such as establishing strong partnerships among community educators and providers and educating students in the delivery of primary health care in the community), explain three principles that have been followed and that were crucial to the success of the Center (for example, individuals in the community must become empowered to capitalize on their strengths), and discuss the major difficulties that the community and the academic institutions encountered and strategies for meeting them (such as the importance of building trust and the importance of learning the needs identified by the community partners, not just those identified by the academic partners). The authors maintain that a successful community-academic partnership must be built on the foundation of community health development, a concept analogous to economic development, and that such a partnership can be a powerful tool for making a difference in the community's health.     

Altered secondary myogenesis in transgenic animals expressing the neural cell adhesion molecule under the control of a skeletal muscle alpha-actin promoter

The majority of skeletal muscle fibers are generated through the process of secondary myogenesis. Cell adhesion molecules such as NCAM are thought to be intricately involved in the cell-cell interactions between developing secondary and primary myotubes. During secondary myogenesis, the expression of NCAM in skeletal muscle is under strict spatial and temporal control. To investigate the role of NCAM in the regulation of primary-secondary myotube interactions and muscle fusion in vivo, we have examined muscle development in transgenic mice expressing the 125-kD muscle-specific, glycosylphosphatidylinositol-anchored isoform of human NCAM, under the control of a human skeletal muscle alpha-actin promoter that is active from about embryonic day 15 onward. Analysis of developing muscle from transgenic animals revealed a significantly lower number of myofibers encased by basal lamina at postnatal day 1 compared with nontransgenic littermates, although the total number of developing myofibers was similar. An increase in muscle fiber size and decreased numbers of VCAM-1-positive secondary myoblasts at postnatal day 1 was also found, indicating enhanced secondary myoblast fusion in the transgenic animals. There was also a significant decrease in myofiber number but no increase in overall muscle size in adult transgenic animals; other measurements such as the number of nuclei per fiber and the size of individual muscle fibers were significantly increased, again suggesting increased secondary myoblast fusion. Thus the level of NCAM in the sarcolemma is a key regulator of cell-cell interactions occurring during secondary myogenesis in vivo and fulfills the prediction derived from transfection studies in vitro that the 125-kD NCAM isoform can enhance myoblast fusion.     

Understanding why heterosexual adults do not practice safer sex: a comparison of two samples

This study evaluated the relationship between benzene exposure and low white blood cell (WBC) and red blood cell (RBC) counts. Hematologic screening data collected over a 35 year period at a rubber hydrochloride manufacturing plant were analyzed; an increased risk of leukemia had been demonstrated previously among workers at the plant [Infante et al. (1977).' Lancet 2:76-78; Rinsky et al. (1981): Am J Ind Med 2:217-45 (1987): NEJM 316:1044-1050/. Hematologic screening data were available for 657 of 1,037 (63.3%) individuals employed at the plant from 1939 through 1976. There was a total of 21. 710 blood test records (range per individual 1-354). The study utilized a case-control design and estimated benzene exposures using the job exposure matrix developed by Rinsky et al. (1987): NEJM 316:1044-1050]. The effects of benzene exposure in the 30, 90, and 180 days before the blood test date, as well as cumulative exposure up until the blood test date, were examined using conditional logistic regression. For WBCs there was a strong exposure response and all of the exposure metrics selected showed a significant relationship with low blood count. For RBCs there was a weak positive exposure-response, which was significant (p = 0.03) for one of the dose metrics. The finding of an exposure-response relationship in the range of exposures represented in this study, where the maximum daily benzene exposure estimate was 34 ppm, is consistent with findings of several animal studies demonstrating a decrease in peripheral lymphocyte counts at benzene exposures as low as 10 ppm, and a stronger effect of benzene exposure on lymphocytes (as reflected in total WBC count) than on red cells. There was no evidence for a threshold for the hematologic effects of benzene exposure, suggesting that even exposure to relatively low levels of benzene (e.g., <5 ppm) may result in hematologic suppression.     

The effects of midazolam or propofol followed by suxamethonium on the QT interval in humans

Atretic encephaloceles or myelomeningoceles are frequently solid due to hamartomatous proliferation of fibrous tissue and blood vessels. Because of the fibrous nature of the tumor with no cystic cavity and unusual location with no connection to CNS, they are frequently regarded as insignificant hamartomas. Apart from this terminology, they are also described as cutaneous meningiomas or hamartomas with ectopic meningothelial elements by the presence of meningothelial cells. We report a case of atretic encephalocele in the parietal scalp of an 8 year-old boy and a case of myelomeningocele in the posterior mediastinum of a 31 year-old woman. The terms atretic encephalocele and myelomeningocele are more appropriate for these cases because they include their pathogenesis and the non-neoplastic nature of the lesion.     

Fibroblast growth factor receptor function is required for the orderly projection of ganglion cell axons in the developing mammalian retina

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.     

First-principles insights on anion redox activity in NaxFe1/8Ni1/8Mn3/4O2: Toward efficient high-energy cathodes for Na-ion batteries

In the search for high-energy cathode materials for Na-ion batteries (NIBs), Fe-doped layered transition metal oxides have been recently proposed as promising systems that can ensure improved reversible capacity at high working voltage. Exploiting the anionic redox chemistry in this class of materials represents a great advance for the energy storage community, but uncontrolled oxidation process can lead to the formation of unbound molecular oxygen, with detrimental effects on overall capacity and stability upon cycling. The higher TM–O covalency provided by Fe doping seems to prevent oxygen loss and ensure full capacity recovery. Understanding anionic processes and the underlying mechanism with atomistic details can reinforce the experimental efforts and help to outline rational design strategies for novel high-performing NIB cathodes. To this end, we present a state-of-the-art first-principles study on the P2-type Na_xTMO₂ (TM = Fe, Ni, and Mn—NFNMO) oxide. We compare structural and electronic features of stoichiometric (Na_xFe_0.125Ni_0.125Mn_0.75O₂) and Mn-deficient (Na_xFe_0.125Ni_0.125Mn_0.68O₂) NFNMO to identify and discuss the contribution of each element sublattice on charge compensation processes. Although Mn deficiency is predicted to increase the cathode working voltage, we find the charge compensation being mostly exerted by the Ni and Fe sublattices. Oxygen redox is unfold via the formation of superoxide species at low Na loads with a preferential breaking of more labile Ni–O bonds and binding to Fe atoms. Our calculations predict no release of molecular O₂ upon desodiation, thus highlighting the key role of Fe dopant that provides a good TM–O bond strength, preventing oxygen loss while still enabling anionic redox reactions at high voltages with extra reversible capacity.