Ethnogenetic layering (EL): an alternative to the traditional race model in human variation and health disparity studies.

BACKGROUND: Traditionally, studies in human biodiversity, disease risk, and health disparities have defined populations in the context of typological racial models. However, such racial models are often imprecise generalizations that fail to capture important local patterns of human biodiversity. AIM: More explicit, detailed, and integrated information on relevant geographic, environmental, cultural, genetic, historical, and demographic variables are needed to understand local group expressions of disease inequities. This paper details the methods used in ethnogenetic layering (EL), a non-typological alternative to the current reliance of the biological racial paradigm in public health, epidemiology, and biomedicine. SUBJECTS AND METHODS: EL is focused on geographically identified microethnic groups or MEGs, a more nuanced and sensitive level of analysis than race. Using the MEG level of analysis, EL reveals clinical variations, details the causes of health disparities, and provides a foundation for bioculturally effective intervention strategies. EL relies on computational approaches by using GIS-facilitated maps to produce horizontally stratified geographical regional profiles which are then stacked and evaluated vertically. Each horizontal digital map details local geographic variation in the attributes of a particular database; usually this includes data on local historical demography, genetic diversity, cultural patterns, and specific chronic disease risks (e.g. dietary and toxicological exposures). Horizontal visual display of these layered maps permits vertical analysis at various geographic hot spots. RESULTS AND CONCLUSIONS: From these analyses, geographical areas and their associated MEGs with highly correlated chronic disease risk factors can be identified and targeted for further study.

Changes in brain and spinal cord water content during recurrent experimental autoimmune encephalomyelitis in female Lewis rats.

Regional changes in percent water content, a measure of regional levels of edema, were determined in female Lewis rats during key stages of recurrent experimental autoimmune encephalomyelitis (rEAE). The changes in percent water content of the spinal cord and brainstem closely paralleled the clinical and, to a lesser extent, histological course of rEAE (increasing during exacerbations and decreasing during remissions), whereas the percent water content of the forebrain, thalamus/midbrain, hypothalamus, and cerebellum remained constant and equal to control levels at all stages of the disease process. These results suggest that edema formation and resolution in the brainstem and spinal cord may be significant determinants of the transient and recurrent course of neurological dysfunction exhibited by rats with rEAE.

The bioanthropological context of disease.

Apparent differences in susceptibility to disease continue to be major delineators between human groups. From the vantage of human evolutionary biology, disease is the biocultural product of the interactions of human biology, culture, and ecology. These interactions are graphically represented in a working model and the characteristics of their interactions are discussed. The variability observed in contemporary African Americans is seen as having its roots in Africa and in the collective history of human origins. Thus, identifying simple factors contributing to disease susceptibilities in African Americans is considerably problematic given the high rate of inherent heterogeneity in this group and their retention and expression of various African ecogenetic variants. By focusing more intensively on comparisons among "US blacks," researchers may be able to better identify specific anatomic, physiochemical, or molecular "markers" that will clarify the diversity in clinical response of many African Americans to disease.

Race and ethnicity as biological constructs.

For some time, biologists and anthropologists have overwhelmingly rejected the partitioning of modern humans into biological "races." An examination of recent human evolutionary history suggests that the zoological definition of race, based on significant genetic differences, cannot be legitimately applied to contemporary humans. Extensive past hybridization, plasticity of the human phenotype, the presence of ecotypes, the lack of extensive molecular information, and the lack of longitudinal multigenerational evaluations of diverse groups contribute to ambiguity in taxonomic assignment. Although biological aggregates do exist, they represent variation below the subspecies level, and, as such, are much more tenuous over evolutionary time. The persistent reference to quasibiological constructs such as ethnicity and race in the lay and scientific literatures requires that ethnicity be scrutinized for possible biological dimensions. The Diop model of ethnicity suggests that at least three components contribute to its formation: a historical factor, a linguistic factor, and a psychological factor, each of which can be examined for possible biological dimensions. Presumed biological affinities may allow certain groups to expand and extend their collective history and amplify their kin networks, possibly improving group biological fitness. Individual and group initial language of acquisition may influence brain physiology and organize the template for interpretation and behavior, creating greater consistency of response across otherwise divergent biological aggregates. Psychological continuity in particular behavioral traits, particularly repetitive multigenerational responses, may have an adaptive aspect at the group level. While ethnicity remains primarily a sociocultural category, it has biological precursors, parameters, and consequences for both individuals and groups. The genetic components of these biological dimensions remain to be identified and quantified.

An evolutionary perspective on salt, hypertension, and human genetic variability.

Natural selection for electrolyte conservation has likely been the norm throughout human evolutionary history. However, the current patterns of excessive dietary salt intake create the potential for salt overload. Under these conditions, hypertension may be considered an expected pathological response to an evolutionarily new constraint. The transatlantic Middle Passage may have created a genetic bottleneck for salt conservation in African-Americans. Although the initial consequences of this important historical event probably constricted genetic variability and further magnified the potential for salt-sensitive hypertension, the Middle Passage undoubtedly also served as a more generalized major source of environmental stress and may have stimulated subsequent hereditary diversity in the survivors of this holocaust and their descendants. Accelerated rates of mutation, genetic recombination, and transposable genetic elements in conjunction with enhanced opportunities for gene flow, new selective pressures, and drift have all contributed to the tremendous heterogeneity of contemporary African-Americans. It is unlikely that a single genetic event, even of the severity of the Middle Passage, can account comprehensively for the apparent susceptibility of this macroethnic group to high blood pressure and hypertension.

Reassessing 'hereditary' interethnic differences in anemia status.

The widely accepted hypothesis that significant differences in hemoglobin levels exist between African Americans and European Americans is critically evaluated. Most studies implying hereditary interethnic differences are derived from analyses of national cross-sectional surveys or smaller nonprobability samples. Yet those studies give inadequate consideration to the important nutritional and genetic variables that must be controlled for in acceptable comparative assessments of the heritable component of anemia. Missing but vital nutritional variables include reliable parameters of intake, absorption, and utilization of nutrients, and preexisting nutrient stores. Actual measures of confounding genetic conditions such as alpha-thalassemia and hemoglobin variants are also absent, although pronounced within-group diversity has been observed in both macroethnic groups. The likelihood that significant interethnic differences exist in the structural genes coding for hemoglobin level is nil given our species' molecular genetics and evolutionary history. Common recent African origins for all modern humans, as suggested by the fossil and molecular data, as well as our close biochemical affinities with chimpanzees and gorillas, suggest that biologically significant differences among populations of contemporary humans are unlikely. When the proper control of relevant epigenetic and genetic variables is maintained, the reported discrepancies tend to disappear.

Attenuation of experimental autoimmune encephalomyelitis by Compound 48/80 in Lewis rats.

The appearance of increased levels of histamine in the central nervous system (CNS) concomitant with the development of clinically significant acute experimental autoimmune encephalomyelitis (EAE) in male Lewis rats suggests that CNS-associated mast cells may mediate acute EAE in Lewis rats. We now report that, compared to controls, rats with acute EAE exhibit fewer detectable mast cells in their dura mater and velum interpositum. In addition, intracisternal, but not intraperitoneal administration of Compound 48/80 just prior to the appearance of clinical signs of acute or recurrent EAE in male and female rats, respectively, significantly attenuates the clinical severity of both forms of EAE. These results further support the hypothesis that CNS-associated, but not peripheral mast cells are mediators or modulators of acute and recurrent EAE in Lewis rats.

Larvicidal effects of grain sorghum (Sorghum bicolor) seedling extracts upon Culex pipiens larvae.

A study of laboratory and field reared 2nd and 3rd instar Culex pipiens larvae suggests that extracts from 2 varieties of Sorghum bicolor seedlings are significant (P less than 0.05) larvicides under laboratory conditions. These plant extracts contain the organic cyanogen dhurrin and were calibrated to produce 90% mortality in 2nd instar Culex pipiens larvae at 0.82 ppm and 90% mortality in 3rd instar larvae at 1.12 ppm. A preliminary behavioral assessment of late 3rd instar larvae exposed to 1.42 ppm suggests that these plant extracts produce 80% mortality after only 4-5 h of contact. Plant extracts appear stable when stored at up to 32 degrees C in a closed container. Once the extracts are infused in water and exposed to air, however, they biodegrade after 24 h. These laboratory results emphasize the need for field tests against natural populations of Culex pipiens and nontarget organisms.

Sensitivity to diethylstilbestrol-(DES)-induced abortions is influenced by the Whitten effect.

Group-housed female mice, when introduced to a male, will undergo a synchronized estrous cycle with a characteristic pattern of mating where the majority of animals mate on the third day. This phenomenon is termed the Whitten effect. Exposure of pregnant mice to diethylstilbestrol (DES), a potent nonsteroidal estrogen, is capable of inducing premature parturition. The purpose of this study was to evaluate abortion induced by a single injection of DES on day 15 of gestation and compare the sensitivity depending on the day of mating. Initial observations confirmed that those animals that mated on day 3 were significantly more susceptible to DES-induced abortion than animals that mated on any other day. The possibility that this increase in sensitivity to abortion may be the result of differences in number or size of embryos at the time of DES exposure was examined. No significant difference was observed in the number of embryos at day 4 of gestation, at day 15 of gestation, or at birth. There was no difference in the weight of embryos at day 15 of gestation or at birth. A significant increase in the ratio of embryos between uterine horns was observed in the animals that mated on day 3 (ratio = 2.13) compared to animals mating on other days (ratio = 1.23 to 1.48). The cause of increased sensitivity to DES in animals that mated on day 3 is unclear. Our results may indicate that the induction of ovulation associated with the Whitten effect causes unequal embryo distribution leading to functional differences in sensitivity of the pregnancy to exogenous stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Superovulation and early embryo development in the adult mouse after prenatal exposure to diethylstilboestrol.

Pregnant mice were injected subcutaneously with diethylstilboestrol (DES: 10 micrograms/kg body weight in 0.1 ml corn oil) or corn oil alone on Day 15 or 16 of gestation (Day 1 = day of copulatory plug) and allowed to give birth. Female progeny from control and DES-exposed animals were superovulated with exogenous gonadotrophins at 6-8 weeks of age. In-vivo results indicated that the total number of ovulated ova, 2-cell embryos and blastocysts were significantly increased in DES-exposed progeny but that there was a decline in developmental potential from the ovulated ova stage to the blastocyst stage in these animals. However, there was no significant difference in the in-vitro development of 2-cell embryos to the blastocyst stage between control and DES-exposed animals. These results indicate that the ovaries of mice exposed in utero to DES are capable of responding to exogenous gonadotrophins and that second generation progeny have the potential for normal development to the early postblastocyst stage of embryogenesis. The in-vivo decline in developmental potential may be attributable to reproductive tract abnormalities rather than ova/embryo defects.

Biofilms on right heart flow-directed catheters.

This study was designed to detect biofilm and bacteria on right heart flow-directed catheters using scanning electron microscopy and culture following scraping and dispersion of biofilm by sonication. We examined 20 consecutive catheters removed from 18 critically ill patients, an average of 2.6 days after insertion. On scanning electron microscopy, all catheters were found to be covered by a biofilm, with bacteria visible on 50 percent of them. Cultures of specimens from 40 percent of the catheters grew skin organisms (Staphylococcus warneri, Diphtheroid), anaerobes (Propionibacterium), and other potential pathogens (Proteus vulgaris, Enterobacter cloacae). Combination of the two techniques produced a bacterial detection rate of 75 percent. This study demonstrates that the presence of biofilm with bacterial adherence is common on right heart flow-directed catheters. The phenomenon could play a significant role in endogenous infection in critically ill patients.

Effect of melatonin in vivo upon FSH and LH release from hamster pituitary glands.

The effect of chronic daily afternoon injections of melatonin upon basal and melatonin-modulated release of FSH and LH was investigated in superfused hamster anterior pituitary glands. The basal release rate of both FSH and LH began to decline following the beginning of melatonin injections, and reached a nadir after six weeks. Basal release rate of FSH and LH then began to spontaneously increase and reached a plateau at 13 weeks of injections. The inhibition by melatonin upon FSH and LH release in vitro gradually declined during the period of melatonin injections. After six weeks of melatonin injections the release rate of FSH was no longer suppressed by melatonin superfusion, while the release rate of LH became refractory to melatonin suppression in vitro after nine weeks of melatonin injections. These results demonstrate a change in the release rates of both basal and melatonin-inhibited gonadotropin release during melatonin-induced testicular regression and recrudescence in hamsters.

Implantation, deciduoma formation and live births in mast cell-deficient mice (W/Wv).

The intraluminal injection of oil produced deciduoma formation in ovariectomized, mast cell-normal (+/+) and mast cell-deficient (W/Wv) mice that were treated with exogenous steroids. Oil injection and trauma (e.g. sutures) also produced a deciduoma in ovariectomized +/+ and W/Wv mice that had received a single control (+/+) ovary transplanted under the kidney capsule. After transfers of donor blastocysts, implantation and live births were obtained in +/+ and W/Wv mice containing a single ovary transplant. Our results demonstrate that uterine mast cells are not required for the production of a decidual cell response, implantation, gestation or the birth of live offspring in mice.

Alterations in hypothalamic content of luteinizing hormone-releasing hormone associated with pineal-mediated testicular regression in the golden hamster.

The adult male golden hamster will undergo testicular regression when exposed to a short photoperiod, blinding, or late afternoon injections of melatonin. The present study was conducted to compare the effects of all three treatments on serum gonadotropin levels and testicular weights, and to evaluate the effects of these treatments on hypothalamic content of both immunoreactive and bioactive luteinizing hormone-releasing hormone (LHRH) levels. Hamsters were blinded (BL), exposed to a short photoperiod (SP), or received daily injections of melatonin (MEL) for 15 wk. Each treatment (BL, SP, MEL) induced a temporally similar decline in serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), and testicular weight. Spontaneous recrudescence occurred earliest in the MEL group, with serum gonadotropins and testicular weight returning to normal by 15 wk. The SP group exhibited recovery of serum gonadotropins but not testicular weight by 15 wk. The BL group demonstrated partial recovery of serum FSH levels by 15 wk, with no recovery in either serum LH or testicular weight. Each treatment group demonstrated increased hypothalamic content of immunoreactive LHRH which was temporally correlated with the decreases of serum gonadotropins. Additionally, the MEL and SP groups demonstrated decreased immunoreactive LHRH levels during spontaneous recrudescence. Extracts of hypothalami from all treatment groups were bioactive on control hamster pituitary cells. These results indicate that there are temporal differences among the three common treatments and that these differences are manifested in serum gonadotropins, testicular weight and hypothalamic LHRH. Hypothalamic LHRH levels determined by radioimmunoassay and bioassay show periods of increase and decrease which coincide with periods of altered serum gonadotropin levels in all groups.

Altered responses to androgen in diabetic male rats.

In male rats, experimentally induced diabetes mellitus has been reported to be associated with reduced serum levels of gonadotropins and testosterone as well as decreased sex accessory organ weights. The purpose of the present study was to determine if the decreased accessory organ weights and gonadotropin levels observed in diabetic animals result from alterations in the ability of target tissues to respond to testosterone. Adult, male, Wistar rats were injected with streptozotocin (STZ) and either maintained as untreated diabetics or treated with daily injections of insulin. Semi-starved animals were included to control for any effects on the reproductive system due to body weight change alone. These three groups, plus intact controls, were maintained for 30 days with one-half of the animals from each group receiving silastic tubing implants of testosterone of various lengths. It was determined that, in uncontrolled diabetic and semi-starved animals, the serum levels of LH, FSH, and testosterone were decreased, as were the weights of seminal vesicles and ventral prostate glands. Insulin treatment restored LH, FSH, and testosterone levels to normal. Sex accessory glands exhibited slight, but significant, recovery in diabetic animals treated with insulin. Implants of testosterone that resulted in physiologic serum levels of testosterone were effective in depressing serum LH and FSH levels as well as in maintaining normal seminal vesicle and ventral prostate weights in control and semi-starved animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the pineal in the alteration of hamster Sertoli cell responsiveness to FSH during testicular regression.

Testicular regression was induced in adult hamsters by optic enucleation, short photoperiod, or melatonin injections. The melatonin injected group, while undergoing testicular regression, showed a quite different time course from the optic enucleated and short photoperiod groups. All three methods resulted in the restoration of Sertoli cell responsiveness to FSH in vitro from the adult level to that of Sertoli cells from immature hamsters 18-20 days of age. the melatonin injected group showed a shift in testis weight which resulted in a half maximal restoration of Sertoli cell responsiveness to FSH compared to the other groups. This restoration of Sertoli cell responsiveness to FSH was blocked by pinealectomy. These data indicate that the pineal has a specific (but not necessarily direct) effect on Sertoli cell function. In addition, the effect of melatonin injections is qualitatively but not quantitatively similar to optic enucleation and short photoperiod both with regard to testicular regression and alteration of Sertoli cell response.