What explains the negative consequences of adverse childhood experiences on adult health? Insights from cognitive and neuroscience research.
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Biomedical subjects
Publications and source records attributed to M J Weiss.
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OBJECTIVES: To investigate the effect of employment on perceived quality of life (QOL), social integration, and home and leisure activities for individuals with traumatic brain injuries (TBIs). DESIGN: A number of demographic and injury-related variables (age at injury, time since injury, severity of injury, education, gender, preinjury household income, and marital status) were analyzed for their association first with employment and then with the QOL, social integration, and home and leisure activities. Any of these variables showing significant associations were then included along with level of employment in three final multivariate analyses of variance (MANOVAs), again predicting QOL, social integration, and home and leisure activities. SETTING: Urban, suburban, and rural New York state. PARTICIPANTS: 337 adults with TBI who resided in New York state and were between the ages of 18 and 65 years. MAIN OUTCOME MEASURES: The Craig Handicap Assessment Capacity Technique, the Bigelow Quality of Life Questionnaire, the Flanagan Scale of Needs (adapted), and a global QOL measure. RESULTS: Employment showed a strong and consistent relationship with perceived QOL, social integration within the community, and home and leisure activities. Part-time employment may have been superior to full-time employment for individuals with TBI: part-time workers had fewer unmet needs, were more socially integrated, and were more engaged in home activities than full-time workers. Loss of consciousness, as a measure of severity, was unexpectedly predictive of diminished sense of QOL for individuals with less severe injuries. CONCLUSIONS: Being employed contributes to one"s sense of well-being, social integration, and pursuit of leisure and home activities. Select advantages of working part-time for individuals with TBI were identified.
OBJECTIVE: To examine individuals with "hidden" traumatic brain injury (TBI), defined in this study as those who sustained a blow to the head, with altered mental status, and experienced a substantial number of the cognitive, behavioral, and emotional sequelae typically associated with brain injury but did not make the causal connection between the injury and its consequences. DESIGN: Comparison of four groups of individuals matched for age, gender, years of education, and duration of loss of consciousness. SETTING: This study of hidden TBI followed the identification of 143 individuals who, within a larger study of people with TBI who live in the community, identified themselves as "nondisabled" (they were to be part of the comparison sample) but who had experienced a blow to the head that left them at minimum dazed and confused. PARTICIPANTS: 21 of these 143 individuals also reported large numbers of symptoms (eg, headaches, memory problems) associated with TBI. This group (Hidden TBI-High Symptoms group) was compared to three other matched samples: one with known TBI (Known Mild TBI group) and one with no disability (No Disability group) (both of which were drawn from the larger study), and one group of individuals who identified themselves as having no disability but who had experienced a blow to the head that resulted in a few symptoms (Head Trauma-Low Symptoms group). MAIN OUTCOME MEASURES: All study participants were administered an interview that incorporated several existing instruments documenting levels of reported symptoms, emotional well-being/distress, and vocational/social handicaps. RESULTS: The Hidden TBI-High Symptoms group was found to be similar to the Known Mild TBI group in terms of the number and types of symptoms experienced, whereas the Head Trauma-Low Symptoms group was similar in this respect to the No Disability group. The two former groups also evidenced high levels of emotional distress, whereas the two latter groups did not. However, on measures of handicap, the Hidden TBI-High Symptoms and Head Trauma-Low Symptoms groups were similar to the No Disability group and dissimilar from the Known Mild TBI group in that the last group experienced vocational handicap, in particular, whereas the other groups did not. CONCLUSIONS: We conclude that hidden TBI occurs at a nontrivial level (7% of our nondisabled sample). Also, individuals with hidden TBI (with persistent symptoms), unlike those with known mild TBI, are likely to experience emotional distress but not vocational handicap following injury.
The hematopoietic transcription factor GATA-1 is essential for development of the erythroid and megakaryocytic lineages. Using the conserved zinc finger DNA-binding domain of GATA-1 in the yeast two-hybrid system, we have identified a novel, multitype zinc finger protein, Friend of GATA-1 (FOG), which binds GATA-1 but not a functionally inactive mutant lacking the amino (N) finger. FOG is coexpressed with GATA-1 during embryonic development and in erythroid and megakaryocytic cells. Furthermore, FOG and GATA-1 synergistically activate transcription from a hematopoietic-specific regulatory region and cooperate during both erythroid and megakaryocytic cell differentiation. These findings indicate that FOG acts as a cofactor for GATA-1 and provide a paradigm for the regulation of cell type-specific gene expression by GATA transcription factors.
Two advances in murine embryonic stem (ES) cell technology and their applications for the study of hematopoietic stem cells (HSCs) are discussed in this article. First, ES cells induced to differentiate in vitro form hematopoietic lineages in a fashion that recapitulates the ontogeny of blood formation in the embryo. This system offers a unique opportunity to isolate, examine, and manipulate the most primitive hematopoietic progenitors. Second, targeted gene ablation (knockout) studies in ES cells have identified several genes that are required for normal hematopoiesis and may function in the formation, maintenance, and differentiation of HSCs. Insights into murine hematopoiesis gained through the study of ES cells generally should be applicable to other vertebrates, including humans.
PURPOSE: To assist clinicians in the diagnosis and management of ocular siderosis. METHODS: The diagnosis and management of three cases of ocular siderosis secondary to a retained iron-containing intraocular foreign body are described. RESULTS: Noteworthy features included: 1) the characteristic features of a tonic or Adies pupil (one case) and 2) the failure of high-resolution computed tomography scanning and plain film radiography to detect the intraocular foreign body (two of three cases). In contrast, ultrasonography demonstrated the intraocular foreign bodies in all cases and accurately localized them to the inferior retinal quadrants. A third noteworthy finding was that a preoperative electroretinogram reduction in amplitudes of as much as 40% compared with that of the uninvolved eye was compatible with excellent vision, and that the electroretinogram returned to normal after the intraocular foreign body was removed. CONCLUSIONS: Ocular siderosis should be considered in the differential diagnosis of a tonic or Adies pupil. To detect an occult intraocular foreign body, clinicians should not rely exclusively on computed tomography scanning or plain film radiography, but should also use B-mode echography with careful study of the inferior quadrants. In ocular siderosis a preoperative electroretinogram reduction in amplitudes of as much as 40% may be reversible after intraocular foreign body removal.
The zinc finger transcription factor GATA-1 is essential for erythropoiesis. In its absence, committed erythroid precursors arrest at the proerythroblast stage of development and undergo apoptosis. To study the function of GATA-1 in an erythroid cell environment, we generated an erythroid cell line from in vitro-differentiated GATA-1- murine embryonic stem (ES) cells. These cells, termed G1E for GATA-1- erythroid, proliferate as immature erythroblasts yet complete differentiation upon restoration of GATA-1 function. We used rescue of terminal erythroid maturation in G1E cells as a stringent cellular assay system in which to evaluate the functional relevance of domains of GATA-1 previously characterized in nonhematopoietic cells. At least two major differences were established between domains required in G1E cells and those required in nonhematopoietic cells. First, an obligatory transactivation domain defined in conventional nonhematopoietic cell transfection assays is dispensable for terminal erythroid maturation. Second, the amino (N) zinc finger, which is nonessential for binding to the vast majority of GATA DNA motifs, is strictly required for GATA-1-mediated erythroid differentiation. Our data lead us to propose a model in which a nuclear cofactor(s) interacting with the N-finger facilitates transcriptional action by GATA-1 in erythroid cells. More generally, our experimental approach highlights critical differences in the action of cell-specific transcription proteins in different cellular environments and the power of cell lines derived from genetically modified ES cells to elucidate gene function.
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BACKGROUND: The aim of this morphological investigation was to obtain more information about the structural and cellular mechanisms of interalveolar pore formation in postnatal lung development. Assuming that alveolar pore formation is related to the general thinning of interalveolar walls observed in the postnatal period, we have focused our attention on the topographical relationship between epithelial cells and connective tissue in the septum. Thereby we tried to formulate a uniform concept of pore formation. METHODS: After fixation with glutaraldehyde and osmiumtetroxide, tissue blocks of rat lungs aged 44 days were embedded in Epon. Serial sections were obtained in order to analyse precisely pores and supposed sites of pore formation (type II cells and thin spots in transsections of interalveolar walls). RESULTS: We made the following observations: there are pores with or without type II cells in the neighbourhood, and "pre-pores" with either fully transseptal granular pneumocytes, or thin spots in the interalveolar wall consisting of one or two layers of type I cell epithelium or of type II and type I cells without intervening connective tissue. CONCLUSIONS: From these findings we deduce that there is a general principle of interalveolar pore formation which consists in the formation of transseptal interepithelial cell contacts (i.e., between cells of type II and type I or type I and type I), promoted by the thinning of interalveolar walls in the stage of microvascular maturation. Within the zone of contact the cells thin out and give way to form an interalveolar opening.
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The case of a 13-year-old boy with autism, severe mental retardation, and a seizure disorder who was able to demonstrate valid facilitated communication was described. In three independent trials, short stories were presented to him, followed by validation test procedures with an uninformed facilitator providing physical support to the subject's arm. In Trials 1 and 3, several specific answers were provided that clearly indicated that the young man, not the uninformed facilitator, was the source of the information. Moreover, some responses seemed to imply that the subject was employing simple inferential and abstract reasoning. This case study adds to the small, but growing number of demonstrations that facilitated communication can sometimes be a valid method for at least some individuals with developmental disabilities.
UNLABELLED: This study investigates whether systematic analyses of methodological issues contribute to improve and renew the diagnostic role of quantitate esophageal scintigraphy. METHODS: Forty-seven patients with normal (n = 26) and pathologic (n = 21) esophageal function were studied with scintigraphy and manometry, using the latter findings as the gold standard. Scintigraphic data were analyzed by receiver operator characteristic (ROC) methods to: establish the optimal decision threshold for six different quantitative parameters, evaluate their inherent discrimination capacity and compare liquid compared with solid bolus data. RESULTS: Quantitative parameters have shown remarkable differences in their potential to discriminate between normal and pathologic findings (percentage of emptying at definite time points > mean time > transit time > mean transit time > Tmax). Sensitivity of 95% at a specificity of 96% was the optimum obtained. At comparable specificity levels, solid bolus studies generally demonstrated higher sensitivity than liquid bolus studies. CONCLUSION: The diagnostic performance of optimized esophageal scintigraphy is close to that of manometry. Our findings do not only renew the role of esophageal scintigraphy as an accurate screening test for esophageal motility disorders but also invalidate recent reservations about the diagnostic potential of this method.
Six patients with unilateral epiretinal membrane of the macula perceived the spontaneous Pulfrich psychophysical stereo-illusion, suggesting a relative conduction delay on the side of the membrane. In three of these patients, visual-evoked potential studies were also obtained and confirmed an absolute conduction delay in the anterior pathway on the side of the epiretinal membrane in two patients and an absence of the P 100 wave on the side of the epiretinal membrane in the third patient. It is important to recognize that the Pulfrich psychophysical stereo-illusion can be spontaneously perceived in macula disease, and therefore, the test may not always distinguish optic nerve from macula disease.
The transcription factor GATA-1 recognizes a consensus motif present in regulatory regions of numerous erythroid-expressed genes. Mouse embryonic stem cells lacking GATA-1 cannot form mature red blood cells in vivo. In vitro differentiation of GATA-1- embryonic stem cells gives rise to a population of committed erythroid precursors that exhibit developmental arrest and death. We show here that the demise of GATA-1- erythroid cells is accompanied by several features characteristics of apoptosis. This process occurs despite normal expression of all known GATA target genes examined, including the erythropoietin receptor, and independent of detectable accumulation of the tumor suppressor protein p53. Thus, in addition to its established role in regulating genes that define the erythroid phenotype, GATA-1 also supports the viability of red cell precursors by suppressing apoptosis. These results illustrate the multifunctional nature of GATA-1 and suggest a mechanism by which other hematopoietic transcription factors may ensure the development of specific lineages.
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Mouse embryonic stem (ES) cells lacking the transcription factor GATA-1 do not produce mature red blood cells either in vivo or in vitro. To define the consequences of GATA-1 loss more precisely, we used an in vitro ES cell differentiation assay that permits enumeration of primitive (EryP) and definitive (EryD) erythroid precursors and recovery of pure erythroid colonies. In contrast to normal ES cells, GATA-1- ES cells fail to generate EryP precursors. EryD precursors, however, are normal in number but undergo developmental arrest and death at the proerythroblast stage. Contrary to initial expectations, arrested GATA-1(-)-definitive proerythroblasts express GATA target genes at normal levels. Transcripts of the related factor GATA-2 are remarkably elevated in GATA-1- proerythroblasts. These findings imply substantial interchangeability of GATA factors in vivo and suggest that GATA-1 normally serves to repress GATA-2 during erythropoiesis. The approach used here is a paradigm for the phenotypic analysis of targeted mutations affecting hematopoietic development.
A better understanding of scintigraphic findings may lead to a wider acceptance of esophageal transit studies. The purpose of this study, therefore, was to correlate standard manometric parameters with the quantitative and qualitative characteristics of liquid and semi-solid bolus transport. Twenty-nine patients were simultaneously investigated with esophageal scintigraphy and manometry. Single-swallow and sum-image data of six consecutive swallows were analyzed. No significant relationship between transit time and the velocity of the peristaltic wave could be identified, which suggests that factors other than peristaltic velocity (e.g., pharyngeal pump) essentially modulate esophageal transit. There was also no linear correlation between esophageal emptying and peristaltic amplitudes. Emptying was normal in patients with amplitudes greater than 30 mmHg and reduced in those with amplitudes less than 30 mmHg. This suggests that a threshold pressure greater than 30 mmHg is necessary to propel a test bolus adequately. Patterns in condensed images have been shown to specifically reflect the events in corresponding manometric recordings. Normal and different pathologic types of peristalsis presented analogous findings in both modalities. Thus, an analysis of the relationship between bolus transport and contraction parameters in simultaneous studies increases understanding of quantitative and qualitative scintigraphic results.
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