A call to action: increasing health providers in underrepresented populations through the military.

The state of the nation's health and healthcare disparities looms large and is currently at crisis proportions, so much so, that these issues have been advanced as a national priority. These disparities are known to disproportionately afflict minorities and disadvantaged groups who become predisposed to certain risks. However, in light of the ever increasing racial and ethnic diversity of the American population, the visible absence of underrepresented minorities (URMs) in the health professions needed to meet these growing needs continues to fuel these crises. The purpose of this paper is thus fourfold. First, to examine the reason (s) for the persistent shortage of underrepresented minorities in the health professions and the associated barriers they encounter in pursuing opportunities in these professions. Second, to determine the degree to which the shortage of URMs contributes to the current state of health and healthcare disparities among certain groups. Third, to identify nontraditional mechanisms like the military as a medium to help increase the number of URMs in the health professions pipeline. Finally, the authors discuss the role of cultural competence as an essential skill set in rendering quality healthcare to minority patients; the strengths and limitations of their findings; and the implications of these findings for future research.

Reducing healthcare disparities in the military through cultural competence.

Healthcare disparities are fast encroaching upon equal access healthcare systems like the military. While this growth has been attributed to the same antecedents as those found in the general civilian population, four additional assumptions are posited as contributing factors to healthcare disparities that are peculiar to the military. Research on certain segments of the veteran population in the Veterans Administration (VA) is profiled as the most analogous healthcare system to that of the military's and a meta-analysis of studies on similar populations in the military are also examined. Like the general civilian population, cultural competence is viewed as an imperative component of healthcare delivery to help to narrow the healthcare disparities gap between majority (men and whites) and minority (women and nonwhites) populations in the military.

Cultural competence: its promise for reducing healthcare disparities.

Healthcare disparities have reached such disproportionate levels of disease burden for certain groups that the issue has become a national priority. This article examines the most recent iteration of the healthcare disparities movement, the aggressive legislative steps by the federal government to disrupt its destructive path and the promise that cultural competence holds for healthcare providers and the healthcare industry as a whole in placing the patient back at the center of healthcare treatment. Such efforts, it is argued, will be instrumental in helping to reduce healthcare disparities and make the healthcare delivery experience a more positive outcome for all patients.

Inactivation of olfactory sensilla of a single morphological type differentially affects the response of Drosophila to odors.

The olfactory organs on the head of Drosophila, antennae and maxillary palps, contain several hundred olfactory hairs, each with one or more olfactory receptor neurons. Olfactory hairs belong to one of three main morphological types, trichoid, basiconic, and coeloconic sensilla, and show characteristic spatial distribution patterns on the surface of the antenna and maxillary palps. Here we show that targeting expression of the cell-death gene reaper to basiconic sensilla (BS) causes the specific inactivation of most olfactory sensilla of this type with no detectable effect on other types of olfactory sensilla or the structure of the antennal lobe. Our data suggest that BS are required for a normal sensitivity to many odorants with a variety of chemical structures, through a wide range of concentrations. Interestingly, however, in contrast to other odorants tested, the behavioral response of ablated flies to intermediate concentrations of propionic and butyric acids is normal, suggesting the involvement of sensilla unaffected by ectopic reaper expression, probably coeloconic sensilla that respond strongly to these two organic acids. As inactivation of BS causes an underestimation of the concentration of both acids detectable at both the highest and lowest odorants concentrations, our results suggest that concentration coding for these two odorants relies on the integration of signals from different subsets of sensilla, most likely of different morphological types.

NIST Mechanisms for Disseminating Measurements.

The national responsibilities assigned to the National Bureau of Standards (NBS) early in the last century for providing measurement assistance and service are carried out today by the four programs that comprise the National Institute of Standards and Technology (NIST) Office of Measurement Services (OMS). They are the Calibration Program (CP), the Standard Reference Materials Program (SRMP), the Standard Reference Data Program (SRDP), and the Weights and Measures Program (W&MP). Organized when the U.S. Congress changed the NBS name to NIST, the OMS facilitates access to the measurement and standards activities of NIST laboratories and programs through the dissemination of NIST products, data, and services. A brief historical introduction followed by a perspective of pivotal measurement developments from 1901 to the present and concluding with a look to the future of NIST measurement services in the next decade of the new millennium are presented for each OMS program.

The K+ channel gene ether a go-go is required for the transduction of a subset of odorants in adult Drosophila melanogaster.

The functional identity of an olfactory receptor neuron is determined in part by its repertoire of responses to odorants. As an approach toward understanding the contributions of particular conductances to olfactory neuron excitability and odor discrimination, we have investigated the role of the putative cyclic nucleotide-modulated K+ channel subunit encoded by the ether a go-go (eag) gene in odorant responsiveness in Drosophila melanogaster. Four independent mutant eag alleles exhibited reduced antennal sensitivity to a subset of nine odorants, all having short aliphatic side chains: ethyl butyrate (EB), propionic acid, 2-butanone, and ethyl acetate. Significantly fewer eag antennal neurons responded to EB compared with control neurons; the proportion sensitive to 2-heptanone was similar to controls. Two aspects of the character of EB-induced excitability were affected by mutations in eag. First, fewer EB-induced inhibitory responses were observed in eag mutants, and second, fewer excitatory odorant responses dependent on extracellular Ca2+ were observed. Furthermore, modulation of neuronal excitability by membrane-permeant cyclic nucleotide analogs was largely eag dependent. Focal application of high K+ saline to sensillae altered the excitability of the majority of neurons from wild-type but not eag antennae, suggesting that Eag may have a dendritic localization.

Involvement of genes encoding a K+ channel (ether a go-go) and a Na+ channel (smellblind) in Drosophila olfaction.

We have investigated the roles of the putative cyclic nucleotide-modulated K+ channel subunit encoded by the ether a go-go (eag) gene and a voltage-gated Na+ channel, smellblind (sbl), encoded by the paralytic (para) locus in odorant responsiveness and cell excitability in Drosophila melanogaster. Three independent mutant alleles of eag revealed reduced antennal responsiveness in adult flies to a subset of odorants, all having short aliphatic side chains: ethyl butyrate (EB), propionic acid, 2-butanone and ethyl acetate (manuscript submitted). Loose patch recordings revealed that significantly fewer eag antennal neurons responded to EB compared to control neurons. As expected if Eag were involved in odor transduction, fewer EB-induced inhibitory responses were observed in eag mutants and focal application of high K+ saline to sensillae altered the excitability of the majority of neurons from wild-type, but not eag, antennae. Interestingly, there were fewer excitatory odorant responses dependent on extracellular Ca2+ in eag neurons. In contrast to the involvement of Eag in adult olfactory neuron odorant transduction, we found no evidence that adult sbl and allelic olfactory D (olfD) gene mutants were defective in their behavioral response to a complex attractive odor. Furthermore, electrophysiological analyses of adult sbl and olfD mutants revealed normal electroantennogram responses to a broad range of individual pure odorants and no changes in the excitable properties of olfactory neurons as determined by loose patch recordings.

Voltage-activated and odor-modulated conductances in olfactory neurons of Drosophila melanogaster.

Voltage-activated currents and odor-modulated conductances were studied in cells in semi-intact Drosophila third antennal segments (the main olfactory organ) using patch-clamp techniques. All neurons expressed outward currents, and most expressed labile fast transient inward currents with kinetics similar to Na+ currents in other systems. Action potentials were detected as bipolar capacitative current transients in cell-attached or loose patches from the soma of both odor-sensitive (97%) and insensitive neurons. A mixture of odorants from five chemical classes caused an increase (approximately 70%), decrease (approximately 10%), or no effect on firing frequency in pharate adult neurons. The development of chemosensitivity was examined and odor-induced changes in action potential firing frequency were recorded in pupal antennal neurons as early as P8, a stage after completion of sensillar development. The character of odor-induced responses was more profound and complex later in development; small, tonic increases in firing frequency were observed at pupal stages P8 through P11 (ii), while in older pupae and young adults approximately 25% of the increased responses were phasic-tonic. The apical dendrite was the site of odor modulation in approximately 90% and 100% of responsive adult and early pupal neurons, respectively. Whole-cell recordings revealed that apparent nonselective cation and chloride conductances were modulated by a mixture of odorants in separate antennal neurons.

TNF alpha receptor expression in rat cardiac myocytes: TNF alpha inhibition of L-type Ca2+ current and Ca2+ transients.

Tumor necrosis factor-alpha (TNF alpha) is a potentially powerful anti-neoplastic agent; however, its therapeutic usefulness is limited by its cardiotoxic and negative inotropic effects. Accordingly, studies were undertaken to gain a better understanding of the mechanisms of TNF alpha-mediated cardiodepression. Single cell RT-PCR, [125I]TNF alpha ligand binding and Western immunoblotting experiments demonstrated that rat cardiac cells predominantly express type I TNF alpha receptors (TNFRI or p60). TNF alpha inhibited cardiac L-type Ca2+ channel current (ICa) and contractile Ca2+ transients. Thus, it is possible that the negative inotropic effects of TNF alpha are the result of TNFRI-mediated blockade of cardiac excitation-contraction coupling.

Scutoid mutation of Drosophila melanogaster specifically decreases olfactory responses to short-chain acetate esters and ketones.

A molecular-genetic approach has been taken to identify genes involved in olfactory transduction in Drosophila melanogaster. Two independent lines of research led to the finding that the dominant Scutoid (Sco) mutation causes a diminished extracellular electroantennogram response to the odorants ethyl acetate (EtAC) and acetone (AC). Sco flies showed about 4- and 2.5-fold reduced responses to EtAC and AC, respectively, compared to Canton-S wild-type and sibling control flies lacking the Sco mutation when electroantennogram recordings were made from the proximal anterior third antennal segment. The responses to five other odors from three different chemical classes were unaltered. The maximum response to either EtAC or AC was decreased with no change in apparent affinity. Responses to short-chain (but not long-chain) acetate esters and ketones were dramatically affected at all antennal locations tested. Only in the proximal quadrants were responses to ethyl acetoacetate also reduced. Most Sco revertants tested had a normal olfactory response; duplications of the region including no-ocelli partially suppress the Sco bristle as well as olfactory phenotypes. Sco adults had an impaired behavioral response to EtAC but not to banana or propionate. There was no effect of the mutation on larval chemosensory behavior or extracellularly recorded adult compound eye and ocellar visual responses. These findings suggest the involvement of Sco in an olfactory pathway in adults which is specific for short-chain acetate esters and ketones.

A Drosophila mutant defective in extracellular calcium-dependent photoreceptor deactivation and rapid desensitization.

CALCIUM is involved in the adaptation of vertebrate photoreceptors to light and may have a similar role in invertebrate phototransduction. But the molecular mechanisms mediating this stimulus-dependent regulation are not well understood in any G protein-coupled transduction system. We have developed a preparation of isolated Drosophila photoreceptors that has allowed us to carry out an electrophysiological characterization of the light-activated response in these sensory neurons using patch-clamp techniques. We report here that extracellular calcium entering through the light-activated conductance is a key regulator of both the activation and deactivation phases of the phototransduction cascade, and that inaC mutant photoreceptors are specifically defective in the calcium-dependent deactivation mechanism. These data suggest that the light-dependent calcium influx inactivates this cascade through a biochemical pathway that requires the inaC gene product, and that this mechanism represents a molecular basis for stimulus-dependent regulation of visual transduction in Drosophila photoreceptors.

The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins.

Mutations in the Drosophila ninaA gene cause dramatic reductions in rhodopsin levels, leading to impaired visual function. The ninaA protein is a homolog of peptidyl-prolyl cis-trans isomerases. We find that ninaA is unique among this family of proteins in that it is an integral membrane protein, and it is expressed in a cell type-specific manner. We have used transgenic animals misexpressing different rhodopsins in the major class of photoreceptor cells to demonstrate that ninaA is required for normal function by two homologous rhodopsins, but not by a less conserved member of the Drosophila rhodopsin gene family. This demonstrates in vivo substrate specificity in a cyclophilin-like molecule. We also show that vertebrate retina contains a ninaA-related protein and that ninaA is a member of a gene family in Drosophila. These data offer insights into the in vivo role of this important family of proteins.

Allergic contact dermatitis potential of 3 pyridostigmine bromide transdermal drug delivery formulations.

Pyridostigmine bromide (PB) delivered transdermally may be a useful pretreatment for organophosphate poisoning. PB transdermal formulations were developed since this route has the potential to provide a more constant, prolonged and therapeutically-effective drug level in the body. Guinea pig skin sensitization studies, using a variation of the split adjuvant technique, were conducted with various PB transdermal formulations as part of a safety evaluation profile. 3 gel matrix formulations were tested. The 3 formulations contained 50% PB, 30% PB with 0.198% sodium lauryl sulfate (SLS) and 30% PB with 0.21% of a proprietary surfactant (PS), respectively. SLS and the proprietary surfactant were added to the formulations as dermal penetration enhancers. 9 groups of 10 animals were induced and challenged with 1 of the 3 PB or PB/surfactant formulations (3 groups per formulation). In addition, 2 groups of 10 animals were included in the study as positive controls that were induced and challenged with 2,4-dinitrochlorobenzene (DNCB). 44% of the animals responded positively at challenge to 50% PB. 80% of the animals responded positively at challenge to 30% PB/0.198% SLS and 82% of the animals had positive responses at challenge to 30% PB/0.21% PS. This study demonstrates that PB is a potential contact sensitizer that shows a potentiated response in the presence of surfactants.

Intracellular chloride and the mechanism for its accumulation in rat lumbrical muscle.

1. Double-barrelled Cl(-)-sensitive microelectrodes have been used to measure the intracellular Cl- activity (aCli) and membrane potential (Em) in rat lumbrical muscles. The mean Cl- equilibrium potential (ECl), calculated from the measured aCli in sixty fibres, was 2.9 +/- 2.5 mV (S.D. of an observation) less negative than Em. The value of aCli was higher than would be expected for a passive distribution, by a mean 1.4 +/- 1.2 mM. The mean Em was -59.5 +/- 8.2 mV. 2. Removal of external Cl- (Cl-(o)) resulted in a rapid fall in aCli and a transient depolarization. aCli stabilized at an apparent level of 1.7 +/- 1.0 mM (n = 24) while Em became substantially more negative than in normal Krebs solution (mean, -80.1 +/- 12.4 mV). Readdition of Cl-(o) caused a rapid rise in aCli and transient hyperpolarization. ECl quickly became less negative than Em and both then fell in parallel towards the levels previously recorded in normal Krebs solution. 3. If lack of selectivity of the Cl(-)-sensitive ion exchanger and the intracellular presence of interfering anions, assumed to be responsible for the apparent aCli recorded in Cl(-)-depleted fibres, were also responsible for the apparently non-passive Cl- distribution recorded under normal conditions, the difference between the calculated ECl and Em would increase at more negative potentials. This was not observed over a range of Em values between -46 and -84 mV. 4. Inhibition of the Cl- permeability by application of 9-anthracene carboxylic acid (9-AC) resulted in an immediate rise in aCli and hyperpolarization. An aCli up to 40 mM higher, or eleven times higher, than that predicted by a passive distribution was recorded. Application of 9-AC after depletion of intracellular Cl- in Cl(-)-free solution had no effect on either the apparent aCli or Em. 5. It is concluded that Cl- ions are actively accumulated by the skeletal muscle fibre and that the Cl- distribution therefore normally exerts a depolarizing influence. 6. In the presence of 9-AC and nominal absence of CO2 and HCO3-, readdition of Cl-(o) to Cl(-)-depleted fibres resulted in a substantial rise in aCli and a small, maintained depolarization. This clear demonstration of active accumulation was used to investigate the mechanism responsible for inward transport of Cl- ions. 7. Neither application of CO2 and HCO3- nor application of DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) had any effect on the accumulation of Cl- ions. This suggests that Cl(-)-HCO3- exchange is not involved.(ABSTRACT TRUNCATED AT 400 WORDS)

The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein.

Mutations of the Drosophila melanogaster ninaA gene affect phototransduction: ninaA mutant flies have a 10-fold reduction in the levels of rhodopsin in the R1-R6 photoreceptor cells. The ninaA gene was isolated and found to encode a 237-amino-acid protein that has over 40% amino-acid sequence identity with the vertebrate cyclosporin A-binding protein, cyclophilin, a protein that seems to be involved in T-lymphocyte activation. The remarkable evolutionary conservation of cyclophilin in two phylogenetically distant organisms and its involvement in diverse transduction processes suggests that this protein plays an important role in cellular metabolism. Indeed, cyclophilin has recently been shown to be a prolyl cis-trans isomerase that catalyses, in vitro, rate-limiting steps in the folding of a number of proteins. Here, we present evidence for the involvement of cyclophilin-like molecules in a defined cellular process. The availability of mutations in a cyclophilin gene provides a new model system for the study of cyclophilin and cyclosporin action.

Changes in densities and kinetics of delayed rectifier potassium channels during neuronal differentiation.

Single-channel K+ currents were recorded from young and mature spinal neurons cultured from Xenopus embryos to examine the bases of the developmental increases in density and in rate of activation of the macroscopic voltage-dependent delayed rectifier K+ current (IKv). K+ channels of three conductance classes (integral of 80, 30, and 15 pS) are present at both ages, but only the intermediate and small conductance classes are voltage-dependent and thus underlie IKv. The increase in the density of IKv is due to increases in the numbers of intermediate and small channels per cell, but not to changes in their open probabilities. The increase in rate of activation of IKv results from a change in the activation kinetics of the intermediate channel class alone.

Mental health care of black clients in two types of healthcare organizations.

This article compares the characteristics of black clients and their mental health treatment in two types of treatment facilities: an outpatient clinic of a community mental health center and a comprehensive medical facility. The comprehensive medical facility provides short-term case management to the less severely ill, while the community mental health center provides longer-term, individual psychotherapy and medications to those with more serious diagnoses. Given these findings and the current shift from traditional health insurance to prepaid healthcare, the evolving role of the community mental health center is discussed.

Evidence for active chloride accumulation in normal and denervated rat lumbrical muscle.

Intracellular Cl- activity (aiCl) was measured with Cl(-)-sensitive microelectrodes in normal and denervated rat lumbrical muscle. In normal muscle bathed in normal Krebs solution, aiCl lay close to that predicted by the Nernst equation. The addition of 9-anthracene carboxylic acid, which blocks Cl- conductance, caused aiCl to increase far above that predicted by a passive distribution. Furosemide (10 microM) reversibly blocked this accumulation. After muscle denervation, aiCl progressively increased for 1-2 wk. The rise occurred in two stages. The initial stage (1-3 d after denervation) reflected passive Cl- accumulation owing to membrane depolarization. At later times, aiCl continued to increase, with no further change in membrane potential, which suggests an active uptake mechanism. This rise approximately coincided with the natural reduction in membrane conductance to Cl- that occurs several days after denervation. Na+ replacement, K+ replacement, and furosemide each reversibly blocked the active Cl- accumulation in denervated muscle. Quantitative estimates suggested that there was little difference between Cl- flux rates in normal and denervated muscles. The results can be explained by assuming that, in normal muscle, an active accumulation mechanism operates, but that Cl- lies close to equilibrium owing to the high membrane conductance to Cl-. The rise in aiCl after denervation can be accounted for by the membrane depolarization, the reduction in membrane Cl- conductance, and the nearly unaltered action of an inwardly directed Cl- "pump."

Effect of denervation on a steady electric current generated at the end-plate region of rat skeletal muscle.

An electric current flows continuously out of the synaptic region of rat lumbrical muscle fibres. It is generated apparently as a result of a non-uniform Cl- conductance (GCl), with GCl being lowest at the end-plate. We investigated the effects of denervation on this current. The current persisted with little change after denervation. This was somewhat unexpected, since GCl falls dramatically after denervation, and in acute experiments on normal muscles, the steady current is greatly reduced by agents which block GCl. The steady current was blocked in denervated muscle, as in normal muscle, by low-Cl- solutions, Na+-free and K+-free solutions, and treatment with furosemide and 9-anthracene-carboxylic acid. The current in denervated muscle appears to be generated by the same general mechanism as in normal muscle. The results suggest that the [Cl-]i is significantly higher in denervated than in normal muscle fibres. Preliminary experiments with Cl- -selective micro-electrodes have confirmed this: [Cl-]i rises from about 12 mM to about 23 mM after denervation. This has the effect of moving the Cl- equilibrium potential (ECl) in a positive direction, so that the driving force for passive Cl- efflux is increased. The increased driving force compensates for the reduced GCl, allowing the steady current to persist in denervated fibres.