The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale.

BACKGROUND: Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset. METHOD: Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA. RESULTS: Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) 0.01), but not between European countries (∆*CFI < 0.01). CONCLUSIONS: Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

Characterization of microsatellite loci in the Hawaiian endemic shrub Schiedea adamantis (Caryophyllaceae) and amplification in related species and genera.

Schiedea adamantis is a rare, perennial shrub endemic to the Hawaiian island of Oahu where it consists of a single population. Using a nonradioactive protocol, 12 microsatellite primers were developed that consisted of di-, tri-, penta- and hexanucleotide repeats. Using multiplexed reactions, all but two primers exhibited polymorphism with an average of 3.67 alleles per primer. Most primers also amplified in 28 additional Schiedea species, revealing wide applicability across the genus; eight and nine primers also amplified in Honckenya peploides and Silene lanceolata, respectively, related genera in the Caryophyllaceae. This is the first known report of microsatellite primers developed in Schiedea.

A cost minimization model for the treatment of minor bleeding episodes in patients with haemophilia A and high-titre inhibitors.

Treatment of acute bleeding episodes in patients with haemophilia A and inhibitory antibodies to factor VIII (FVIII) most often involves the use of bypassing haemostatic agents, such as activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa (rFVIIa). We constructed a cost minimization model to compare the costs of initial treatment with aPCC vs. rFVIIa in the home treatment of minor bleeding episodes. We developed a clinical scenario describing such a case and presented it to a panel of US haemophilia specialists. For each product class, we asked panellists to provide dosing regimens required to achieve complete resolution of a minor haemarthrosis in a child with high-titre inhibitors, and for the probabilities of success at two time points (8-12 and 24 h). Consensus among the panellists was refined by a second round of the process, and the median values resulting were used as inputs to a decision analysis model. Sensitivity analyses were conducted to determine threshold values for key variables. The base case model found that initial treatment with aPCC would result in a mean cost per episode of 21 000 dollars, compared with 33 400 dollars for initial treatment with rFVIIa. Sensitivity analyses over a range of clinically plausible values for cost, dosing, and efficacy did not change the selection of aPCC as the dominant strategy.

The economic impact of factor VIII inhibitors in patients with haemophilia.

The impact on the cost of care for haemophilia patients with inhibitors is not well defined. To quantify the effect on health care expenditures associated with inhibitors to factor VIII (FVIII) or FIX, we conducted a retrospective cohort study examining product use and outcomes in adult and paediatric haemophilia patients with and without inhibitors. Twelve patients with inhibitors to FVIII or FIX (cases) identified in the haemophilia surveillance system (HSS) at two centres were matched on age, severity of haemophilia, and treatment centre to haemophilia patients without inhibitors. Patients with HIV or significant liver disease were excluded from the study. All eligible non-inhibitor control patients were selected for inclusion in the study, resulting in a total of 28 controls. We then tracked product usage and hospitalizations from programme entry until 1998 or loss to follow-up, producing a total database of 184 person-years of experience. A descriptive matched analysis was conducted to examine annual differences in the cost of product used and hospitalizations. We found that the median cost for factor products among haemophilia patients with inhibitors was $55,853/year, $2,760 less than comparable haemophilia patients without inhibitors. The median number of hospitalizations per year was 1.0 for both inhibitor and non-inhibitor patients and the median number of days hospitalized was virtually the same. Although these findings do not appear to support the belief that there is a substantial increase in the cost of care for haemophilia patients with inhibitors, it does document that a few outlier patients can drive the cost of treatment for this disease. As the largest component of the cost of care is that of factor concentrate, it becomes imperative in the current health care environment to better define the true costs and benefits of treatments designed to eradicate or manage inhibitors. A careful cost accounting of immune tolerance induction (ITI) and other therapeutic strategies, taking into account successes and failures and duration and intensity of therapy, should help to better define the costs and benefits of such approaches. Methods to identify high cost inhibitor patients should be developed so that these strategies may be targeted to appropriate candidates.

Working memory and apolipoprotein E: what's the connection?

Two robust findings in the Alzheimer's literature are that patients with Alzheimer's disease (AD) show executive function and primacy deficits. The present study examined whether we would find similar deficits when comparing two groups of middle-aged individuals who differed with respect to genetic risk for AD, based on their apolipoprotein E (APOE) genotype. All individuals were screened as normal on a battery of standardized cognitive measures. They were tested on the "Operation span task", which engages the central executive component of working memory [J. Exp. Psychol.: Gen. 128 (1999) 309, J. Exp. Psychol.: Gen. 126 (1997) 211, J. Mem. Language 39 (1998) 418] by dividing attention between processing math operations and remembering words. Individuals were grouped according to APOE genotype ( epsilon 4 carrier versus epsilon 4 non-carrier), matched on age and education, and their Total span and Primacy scores were compared. Despite having no overt symptoms of dementia or deficits on a series of standardized psychometric tests, the epsilon 4 carriers showed divided-attention and primacy deficits on the Operation span task, when compared to the epsilon 4 non-carriers. As a point of comparison, Primacy scores were extracted from the first trial of the "Buschke selective reminding task" [J. Verbal Learn. Verbal Behav. 12 (1973) 543] for these same individuals, and no group differences were found. The Buschke task is a list-learning task that does not require divided attention. These findings suggested that the epsilon 4 carriers were less able to divide their attention, when compared to the epsilon 4 non-carriers. The findings provide the first direct evidence for a relationship between APOE genotype and cognitive performance on measures of divided attention and primacy with non-demented individuals who showed no cognitive impairments on standardized measures.

Evaluation of eight in vitro assays for assessing the cytotoxicity of cigarette smoke condensate.

The accurate assessment of cytotoxicity is important for evaluating the potential of a test agent to induce pathologies that result from cell killing and to determine appropriate doses for other endpoints, such as genetic toxicology studies. The objective of this work was to determine the most sensitive assays for assessing cytotoxicity in Chinese hamster ovary (CHO) cells following short-term (1 h) and long-term (24 h) exposure to cigarette smoke condensate (CSC). Eight in vitro cytotoxicity assays with different endpoints were used to evaluate the cytotoxicity of Kentucky reference 1R4F (K1R4F) CSC in CHO cells. The assays used for this study were neutral red uptake, LDH release, kenacid blue binding, MTT formation, XTT formation, acid phosphatase activity, sulforhodamine B binding and resazurin binding. Four of the more widely used cytotoxicity assays (neutral red, MTT, kenacid blue and LDH) were also evaluated at 3-, 6-, 12- and 18-h time points. At the 1-h exposure time, LDH was the most sensitive with toxicity observed beginning at 100 microg/ml. None of the other assays demonstrated a concentration-dependent increase in toxicity after 1-h exposures even at the maximum concentration of 150 microg/ml of CSC. Following 24 h of exposure, neutral red and kenacid blue were the most sensitive. The results of our study indicate the assay that measured membrane integrity was the most sensitive for short exposure times, whereas the neutral red and kenacid blue assays that measured total cell number were more sensitive for longer exposure times.

Porcine factor VIII: pharmacoeconomics of inhibitor therapy.

The treatment of acquired haemophilia is characteristically exceedingly expensive and thus a cost-benefit analysis of the several available treatment strategies is urgently needed. To address this issue, decision-analysis techniques were used to construct a cost-minimization model to compare the cost of treatment with porcine factor VIII (pFVIII), human FVIII (hFVIII) or an activated prothrombin complex concentrate (APCC). This model was based upon the results of a comprehensive literature search of all relevant clinical studies and case series. To supplement these data, a panel of haemophilia specialists was presented with a clinical scenario describing an acquired haemophilia patient with an acute haemorrhage in whom the human and porcine inhibitor titres were initially unknown. Based on this scenario and on their own clinical experience, the expert panel assessed the applicability of the model as initially constructed, assigned probabilities of success to each treatment and recommended appropriate initial dosing and follow-up regimens. This information was incorporated into the model and a simulation was conducted from which the costs of care were calculated. Sensitivity analyses were then conducted on all parameters. The results of the model show that treatment initiated with pFVIII would be more cost effective compared with treatment sequences initiated with an APCC or hFVIII, respectively. The model indicates that initial treatment with pFVIII in this scenario may be the preferred strategy clinically, as well as on economic grounds.

Quantification of changes in c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells following chemical treatment.

Lung tumors frequently exhibit altered expression of oncogenes and/or tumor suppressor genes. Although some of these alterations are believed to arise from chemical exposure, the ability of specific chemicals to cause distinct changes in gene expression is not well characterized. We previously reported the development of a quantitative reverse transcriptase/polymerase chain reaction (RT/PCR) method for measuring c-myc mRNA levels, and reported that c-myc proto-oncogene expression is significantly increased in small-cell lung carcinoma cells. In the present study, quantitative RT/PCR was used to assess the effect of model toxins cycloheximide (CHX), a protein synthesis inhibitor, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a DNA alkylating agent, on c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells. Expression of c-myc was evaluated at 1-100 microM CHX and MNNG and was compared to the cytotoxic response as measured by the neutral red assay. Cycloheximide elicited a dose-dependent increase in c-myc mRNA levels in NHBE and A549 cells, but did not alter expression of the housekeeping gene beta-actin. A maximum increase for c-myc expression (200% of control) was observed 5 h after treatment with noncytotoxic concentrations. In contrast, MNNG elicited a dose-dependent decrease in c-myc expression in A549 cells, but no significant change in c-myc was observed in NHBE cells. The results from this study suggest that the quantitative RT/PCR method may be an appropriate technique for monitoring gene expression changes following chemical exposure. Hence, these types of studies may assist in the identification of specific chemicals which may induce the genetic alterations involved in the development of lung cancer as well as provide information relevant to the interactive effects of chemicals within complex mixtures.

Hippocampal complex and retrieval of recent and very remote autobiographical memories: evidence from functional magnetic resonance imaging in neurologically intact people.

It has been argued that the role of the hippocampus in memory is time-limited: during a period of memory consolidation, other brain regions such as the neocortex are said to acquire the ability to support memory retention and retrieval on their own. An alternative view is that retention and retrieval of memory for autobiographical episodes depend on the hippocampal complex, regardless of the age of the memory. We examined the participation of the hippocampal complex in a functional magnetic resonance imaging (fMRI) study in which participants were asked to recollect autobiographical events that occurred either within the last 4 years or more than 20 years ago. We found equivalent levels of hippocampal activation in both conditions in all participants (N = 10). In addition, activation in neocortical regions did not differ as a function of the age of the memory, even though most of the recent memories recalled were less than 2 years old and the remote memories more than 35 years old. The results support the notion that the hippocampal complex participates in retention and recovery of even very old autobiographical memories, and place boundary conditions on theories of memory consolidation.

Cognitive impairment and enduring negative symptoms: a comparative study of geriatric and nongeriatric schizophrenia patients.

Chronically institutionalized geriatric (n = 174; average length of hospitalization = 35.1 years) and nongeriatric (n = 59; average length of hospitalization = 17.3 years) schizophrenia patients were classified with regard to their enduring negative symptoms (ENS) over a year. All patients completed neuropsychological tests that have been previously found to be implicated in geriatric schizophrenia: the Mini-Mental State Examination (MMSE), the Modified Boston Naming Test, Constructional Praxis, and Word List Learning and Delayed Recall. With MMSE scores used as covariates, ENS status and age group effects were examined on the cognitive measures at the second assessment. Results indicated that there was considerable specificity of cognitive impairment in the ENS syndrome even in patients with a chronic course of unremitting illness. Furthermore, when specific cognitive measures were examined and global impairment statistically controlled for, patients with ENS manifested a distinct pattern of impairment, rather than uniformly inferior performance. In particular, patients with ENS performed more poorly on tests putatively sensitive to frontal and parietal lobe functions, replicating earlier results on younger patients with a much better overall functional outcome. These data suggest that ENS defines a distinct subgroup of patients that can be identified even against the backdrop of chronic institutionalization.

Dysfunction in the neural circuitry of emotion regulation--a possible prelude to violence.

Emotion is normally regulated in the human brain by a complex circuit consisting of the orbital frontal cortex, amygdala, anterior cingulate cortex, and several other interconnected regions. There are both genetic and environmental contributions to the structure and function of this circuitry. We posit that impulsive aggression and violence arise as a consequence of faulty emotion regulation. Indeed, the prefrontal cortex receives a major serotonergic projection, which is dysfunctional in individuals who show impulsive violence. Individuals vulnerable to faulty regulation of negative emotion are at risk for violence and aggression. Research on the neural circuitry of emotion regulation suggests new avenues of intervention for such at-risk populations.

Memory performance of geriatric and nongeriatric chronic schizophrenic patients: a cross-sectional study.

Memory functioning has been studied extensively in nongeriatric schizophrenic patients, leading to the suggestion that schizophrenic patients manifest a "subcortical" pattern of memory deficits. Few previous studies examined very poor outcome patients with a chronic course of hospitalization. This study examined the association of age and global cognitive dysfunction with verbal and spatial learning and delayed recall, as well as examining differential impairments in delayed recall as compared to delayed recognition memory. Sixty-six chronic schizophrenic patients were studied, with 30 of these patients over the age of 65. Verbal (California Verbal Learning Test) and spatial (Biber Figure Learning Test) serial learning and delayed memory tests were administered. All aspects of memory functioning were correlated with estimates of global cognitive status. When global cognitive status was controlled, age effects were still found for the majority of the memory measures. Delayed recognition memory was not spared, being performed as poorly as delayed recall. In contrast to previous studies of better-outcome patients with schizophrenia, geriatric patients with chronic schizophrenia performed more poorly than nongeriatric patients. The lack of sparing of delayed recognition memory suggests that previous findings of specific recall memory deficit and a subcortical profile of memory impairments may apply to schizophrenic patients with less severe global cognitive impairments. These data suggest that poor-outcome patients may have a pattern of memory impairments that has some features in common with cortical dementia.

Comparison of the cytotoxic and mutagenic potential of liquid smoke food flavourings, cigarette smoke condensate and wood smoke condensate.

Although products of pyrolysis are often cytotoxic and mutagenic, the relationship between the type of material pyrolysed and the toxicity of the resulting pyrolysis products is poorly understood. The objective of this study was to evaluate and compare the cytotoxicity and mutagenicity of several types of common pyrolysis products. The cytotoxicity and mutagenicity of these products were assessed by using neutral red uptake and Ames mutagenicity assays, respectively. The biological activities of four liquid smoke food flavourings (LSF) were compared with two other pyrolysis-derived materials; cigarette smoke condensate (CSC) and a wood smoke condensate (WSC). Results indicated all of the mixtures exhibited a concentration-dependent cytotoxic response. The CSC and WSC were less cytotoxic than three of the LSFs, but more cytotoxic than one of the brands. The CSC was mutagenic in two Salmonella strains; however, none of the LSFs or WSC was mutagenic using TA98, and only three of the LSFs were positive with TA100. The six pyrolysis-derived materials evaluated in this study showed differing patterns and magnitudes of cytotoxicity and mutagenicity. These results indicate that the cytotoxicity and mutagenicity of complex mixtures derived from pyrolysis products are affected by the type of material pyrolysed and/or the method used to prepare the mixture. The cytotoxic potential of some commercial smoke flavourings is greater than cigarette smoke condensate and several of the food flavourings are mutagenic in one Salmonella strain.

Regional brain function, emotion and disorders of emotion.

Significant progress has been made in our understanding of the neural substrates of emotion and its disorders. Neuroimaging methods have been used to characterize the circuitry underlying disorders of emotion. Particular emphasis has been placed on the prefrontal cortex, anterior cingulate, parietal cortex, and the amygdala as critical components of the circuitry that may be dysfunctional in both depression and anxiety.

Chemical and biological studies of a new cigarette that primarily heats tobacco. Part 2. In vitro toxicology of mainstream smoke condensate.

The genotoxic and cytotoxic potential of mainstream cigarette smoke condensate (CSC) from a new cigarette that primarily heats tobacco (TOB-HT) was compared with that of CSC from a Kentucky reference low "tar" cigarette (1R4F) representative of the current US cigarette market, and Kentucky Reference 1R5F, representative of ultra-low "tar" cigarettes on the US market. TOB-HT was evaluated at concentrations which induced concentration-dependent positive responses with 1R4F and 1R5F in an in vitro toxicology test battery which included sister chromatid exchange, chromosome aberration, and neutral red cytotoxicity assays in CHO cells, and the Ames bacterial mutagenicity assay. CSC from 1R4F and 1R5F was positive in the Ames assay with Salmonella typhimurium strains TA98, TA100, TA1538 and TA1537, and negative with TA1535, while CSC from TOB-HT was negative in all five strains. CSC from 1R4F and 1R5F cigarettes was positive in sister chromatid exchange (SCE), chromosome aberration (CA) and neutral red cytotoxicity assays, while CSC from the TOB-HT cigarette yielded negative results in all the above endpoints. These data indicate that in these assays the genotoxic and cytotoxic potential of CSC from the new cigarette that primarily heats tobacco is significantly less than CSC from Kentucky reference 1R4F and 1R5F cigarettes, which are representative of cigarettes currently sold in the US.

Chemical and biological studies of a new cigarette that primarily heats tobacco. Part 3. In vitro toxicity of whole smoke.

Mainstream smoke from Kentucky reference low "tar" (1R4F) and ultra-low "tar" (1R5F) cigarettes and a test cigarette (TOB-HT), that primarily heats tobacco, was compared for cytotoxic and genotoxic potential using cellular smoke exposure technology (CSET). CSET includes a computer controlled 30-port AMESA/Battelle-Geneva smoke generator which exposes cultured mammalian Chinese hamster ovary cells (CHO) to whole smoke. Cytotoxicity was assessed using the neutral red assay and genotoxicity was assessed using the sister chromatid exchange (SCE) assay. Compared on a per cigarette basis, mainstream smoke from 1R5F and the TOB-HT cigarette was significantly less cytotoxic and genotoxic than the smoke from the 1R4F cigarette. The cytotoxic and genotoxic activity of smoke from the TOB-HT cigarettes was slightly greater than the smoke from the ultra-low "tar" Kentucky 1R5F reference cigarettes. In conclusion, in these assays mainstream whole smoke of the TOB-HT cigarette had slightly greater cytotoxic and genotoxic potential compared with an ultra-low "tar" 1R5F Kentucky reference cigarette and significantly less activity compared with the whole mainstream smoke from a low "tar" 1R4F Kentucky reference cigarette, representative of the US market average cigarette for FTC yields of "tar", CO and nicotine.

Comparative cytotoxicity studies of smoke condensates from different types of cigarettes and tobaccos.

The neutral red assay, a rapid and accurate method for estimating the cytotoxicity of chemicals, has been used to assess the cytotoxicity of cigarette smoke condensate (CSC), a complex chemical mixture containing over 3000 identified compounds. The first objective was to optimize the neutral red assay for evaluation of CSCs. This study also assessed and compared the cytotoxicity of smoke condensates from three reference cigarettes which differ in 'tar' content; cigarettes of different tobacco type composition; an ultra-low tar cigarette (R1); and an RJR test cigarette which heats but does not burn tobacco. Finally, this study investigated the cytotoxicity of a specific CSC component, nicotine, and its metabolite, cotinine. Exposure times of 24 hours or longer using CHO cells provided optimal conditions for evaluation of CSC cytotoxicity. The cytotoxicity of CSCs from reference cigarettes was similar. CSC from cigarettes comprised of flue-cured tobacco exhibited greater cytotoxicity than CSC from cigarettes comprised of burley tobacco. CSC from the R1 cigarette exhibited similar cytotoxicity compared with 1R4F CSC. The CSC from a cigarette that heated but did not burn tobacco (RJR test cigarette) demonstrated no cytotoxicity in CHO cells. Finally, nicotine and cotinine were not cytotoxic to CHO cells. The neutral red assay has been proved useful for quantifying differences in cytotoxicity of smoke condensates from cigarettes which vary in 'tar' yield and for assessing specific smoke constituents.

Evaluation of the genotoxic and cytotoxic potential of mainstream whole smoke and smoke condensate from a cigarette containing a novel carbon filter.

A novel carbon filter has been developed which primarily reduces the amount of certain vapor phase constituents of tobacco smoke with greater efficiency than the charcoal filters of cigarettes currently in the market. In vitro indicators of genotoxic and cytotoxic potential were used to compare the cigarette smoke condensate (particulate phase) or whole cigarette smoke (vapor phase and particulate phase) from cigarettes containing the novel carbon filter with smoke condensate or whole smoke from commercial or prototype cigarettes not containing the novel carbon filter. Ames bacterial mutagenicity, sister chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells, and neutral red cytotoxicity assays in CHO cells were utilized to assess the genotoxic and cytotoxic potential of the cigarette smoke condensates. SCE and neutral red cytotoxicity assays were utilized to assess the genotoxic and cytotoxic potential of the whole smoke. As expected, the novel carbon filter did not significantly affect the genotoxic or cytotoxic activity of the smoke condensate, although we did observe that the use of low-nitrogen tobacco reduced the mutagenicity of the condensate in Salmonella typhimurium strain TA98. However, the whole smoke from cigarettes containing the novel carbon filter demonstrated significant reductions in genotoxic and cytotoxic potential compared to cigarettes without the novel carbon filter. The toxicity of the smoke was correlated (r = 0.7662 for cytotoxicity and r = 0.7562 for SCE induction) to the aggregate mass of several vapor phase components (acetone, acetaldehyde, acrolein, acrylonitrile, 1,3-butadiene, ammonia, NOx, HCN, benzene, isoprene, and formaldehyde) in the smoke of the cigarettes utilized in this study. In conclusion, this novel carbon filter, which significantly reduced the amount of carbonyls and other volatiles in mainstream cigarette smoke, resulted in significant reductions in the genotoxic and cytotoxic activity of the smoke as measured by these assays.