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PubMed2006

[Nefopam by continuous intravenous injection and adverse drug reactions: which causality assessment?].

We report the case of a 77-year-old man, with nefopam postoperative analgesia, who developed subacute neurological symptoms, whereas he had profound hypoprotidemia and acute renal failure. Chronological, semiological and bibliographical criteria are in favour of causality assessment. The plasma nefopam concentration (135 ng/ml) during the neurological symptoms is another argument.

Acute Kidney Injury↗

PubMed2006

Judgments of causal efficacy under constant and changing interevent contingencies.

How do people judge constant and varying interevent contingencies? In two experiments, 150 college students rated the efficacy of a potential cause (an experimental fertilizer) of an effect (a plant's blooming). The prevailing probabilistic interevent relation could remain constant for the entirety of the problem or it could change without warning at the midway point: by contingency reversal, by shifting from noncontingency to contingency, or by shifting from contingency to noncontingency. Participants' trial-by-trial ratings sensitively tracked the prevailing positive, negative, and noncontingent interevent relations, even those that entailed an unsignaled change in contingency. Changes in specific cells of the 2 x 2 contingency table differentially affected participants' response to the altered interevent relations. All of this evidence was well described by an associative account of contingency and causal judgments.

Adaptation, Psychological↗

PubMed2005

Causal models of attention-deficit/hyperactivity disorder: from common simple deficits to multiple developmental pathways.

Until recently, causal models of attention-deficit/hyperactivity disorder (ADHD) have tended to focus on the role of common, simple, core deficits. One such model highlights the role of executive dysfunction due to deficient inhibitory control resulting from disturbances in the frontodorsal striatal circuit and associated mesocortical dopaminergic branches. An alternative model presents ADHD as resulting from impaired signaling of delayed rewards arising from disturbances in motivational processes, involving frontoventral striatal reward circuits and mesolimbic branches terminating in the ventral striatum, particularly the nucleus accumbens. In the present article, these models are elaborated in two ways. First, they are each placed within their developmental context by consideration of the role of person x environment correlation and interaction and individual adaptation to developmental constraint. Second, their relationship to one another is reviewed in the light of recent data suggesting that delay aversion and executive functions might each make distinctive contributions to the development of the disorder. This provides an impetus for theoretical models built around the idea of multiple neurodevelopmental pathways. The possibility of neuropathologic heterogeneity in ADHD is likely to have important implications for the clinical management of the condition, potentially impacting on both diagnostic strategies and treatment options.

Animals↗

PubMed2006

Perimenopause and depression: strength of association, causal mechanisms and treatment recommendations.

Perimenopause represents a significant transition in a woman's life. The evidence to support an association between perimenopause and depression is mixed, yet recent prospective studies have provided stronger evidence to support such an association. Interpretation of study data are complicated by methodological issues, such as a lack of standard definition for perimenopause or depression, reducing comparability. A variety of causal factors, including psychological, genetic and physiological, have been implicated in depression during perimenopause, which lends weight to a multifactorial model. Physicians should consider initiating dialogue about menopause and symptom relief at age 40 and screening perimenopausal women for depressive symptoms. Selective serotonin reuptake inhibitors are a first line of treatment for depression, but hormone therapy could be considered for women experiencing menopausal symptoms unless there are contraindications. Future research should focus on establishing temporality and studying these potential relationships among women of different ethnicities.

Depressive Disorder↗

PubMed2005

Experienced disgust causes a negative interpretation bias: a causal role for disgust in anxious psychopathology.

This paper reports the results of an experiment investigating the effect of induced disgust on interpretational bias using the homophone spelling task. Four groups of participants experienced a disgust, anxiety, happy or neutral mood induction and then completed the homophone spelling task which requires the participant to interpret ambiguous words presented through headphones. Both the disgust and anxiety groups interpreted significantly more threat/neutral homophones as threat than both the happy and neutral groups; the disgust group also interpreted significantly fewer positive/neutral homophones as positive than the happy group. These findings are consistent with the view that induced disgust causes a negative interpretational bias which is similar to that reported for anxiety. The results could not be interpreted in terms of the disgust induction concurrently raising levels of self-reported anxiety, but could be interpreted in terms of disgust maintaining existing levels of anxiety. The effect of disgust was to facilitate negative interpretations rather than emotional interpretations regardless of valence. These findings provide the basis for a causal role for disgust in anxious psychopathology. Because the effect is a non-specific emotion-congruent one, elevated disgust levels will result in a predisposition to interpret information in a threatening way across a broad range of anxious- and threat-relevant domains.

Adolescent↗

PubMed2006

C-reactive protein in atherosclerosis: A causal factor?

Atherosclerosis is considered a to be multifactorial disease driven by inflammatory reactions. The process of inflammation also contributes to the pathogenesis of acute atherothrombotic events. C-reactive protein (CRP) is an acute phase protein and its concentration in serum reflects the inflammatory condition of the patient. Levels of CRP are consistently associated with cardiovascular disease (CVD) and predict myocardial infarctions and stroke. Since CRP is present in the atherosclerotic lesion, it may actively contribute to the progression and/or instability of the atherosclerotic plaque. The role of CRP in inflammation and its causality in atherosclerosis are the subject of many investigations but are not yet fully elucidated. This review focuses on recently identified mechanisms by which CRP may modulate and evolve the process of atherosclerosis. We discuss the function of CRP and review the most recent evidence for an independent role of CRP in the development of atherosclerosis. Many studies suggest such a role, but a number of the described effects may be the result of contamination of the CRP preparations.

Apoptosis↗

PubMed2006

A causal relationship discovery-based approach to identifying active components of herbal medicine.

Herbal medicine is widely applied for clinical use in East Asia and other countries. However, unclear correlation between its complex chemical composition and bioactivity prevents its application in the West. In the present study, a stepwise causal adjacent relationship discovery algorithm has been developed to study correlation between composition and bioactivity of herbal medicine and identify active components from the complex mixture. This approach was successfully applied in discovering active constituents from mixed extracts of Radix Salviae miltiorrhizae and Cortex Moutan. Moreover, advantage of the present approach compared with bioassay-guided isolation was demonstrated by its application on a typical herbal drug. The current work offers a new way to virtually screen active components of herbal medicine, and it might be helpful to accelerate the process of new drug discovery from natural products.

Algorithms↗

PubMedDate not supplied

Parental rearing style, premorbid personality, mental health, and quality of life in chronic regional pain: A causal analysis.

The aim of the current study was to establish the causal model among parental bonding, personality characteristics, mental health, quality of life, and chronic regional pain (CRP). Thirty CRP patients and 56 mental illness patients were compared using the Visual Analogue Scale (VAS), Chinese Health Questionnaire (CHQ), Eysenck Personality Questionnaire (EPQ), World Health Organization Quality of Life-Brief-Tawain Version (WHOQOL-BREF-TW), and Parental Bonding Instrument (PBI). There were significant differences in mental health, personality characteristics, and quality of life between the CRP and mental illness groups. Structural equation modeling showed that parental bonding could directly affect personality characteristics, and, hence, directly impact disease and quality of life. CRP is different from mental illness in many dimensions. In this study, CRP appeared to be caused by actual physical dysfunction rather than mental dysfunction.

Case-Control Studies↗

PubMed2005

The causal status of pain catastrophizing: an experimental test with healthy participants.

In the current study we report findings on the effects of experimentally induced catastrophizing about pain on expected pain, experienced pain and escape/avoidance behavior during a cold pressor task in a sample of healthy participants. It was hypothesized that increasing the level of catastrophizing would result in a higher level of expected pain, a higher level of experienced pain, and a shorter duration of ice-water immersion. Also, it was hypothesized that these relations might be stronger for participants who already catastrophized about pain prior to the experiment. The results demonstrated that despite the successful attempt to induce catastrophizing, this neither significantly affected expected pain, experienced pain, and duration of ice-water immersion, nor were these relations moderated by the pre-experimental level of catastrophizing. Although the level of catastrophizing was successfully manipulated, more similar experiments are necessary in order to give a more definite answer on the possible causal status of pain catastrophizing.

Adult↗

PubMed2005

ET-18-O-CH3-induced apoptosis is causally linked to COX-2 upregulation in H-ras transformed human breast epithelial cells.

Abnormally elevated expression of cyclooxygenase-2 (COX-2) has been frequently observed in transformed or malignant cells, and certain non-steroidal anti-inflammatory drugs with COX-2 inhibitory activity exert anti-neoplastic or chemopreventive effects. Contrary to this notion, we have found that a novel alkylphospholipid type antitumor agent ET-18-O-CH3 (1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine) induces COX-2 expression in H-ras transformed human breast epithelial cells (MCF10A-ras) while it causes apoptosis at the same concentration range. The addition of a selective COX-2 inhibitor SC-58635 and COX-2 gene knock down with the siRNA blocked ET-18-O-CH3-induced apoptosis, suggesting that COX-2 induction by this drug is causally linked to its apoptosis inducing activity. ET-18-O-CH3 enhanced the transcriptional activities of cyclic AMP response element which is a key regulator of COX-2 expression. 15-Deoxy-Delta(12,14) prostaglandin J2 is, an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), has been known to possess proapoptotic potential in diverse cell types. ET-18-O-CH3 treatment resulted in elevated release of 15d-PGJ2 and DNA binding and transcriptional activity of PPARgamma. Based on these findings, it is likely that ET-18-O-CH3 induces COX-2 expression and production of 15d-PGJ2 which may mediate the ET-18-O-CH3-induced apoptosis in MCF10A-ras cells.

Antineoplastic Agents↗

PubMed2004

Causal attributions for fatigue among late middle-aged and older adults with HIV infection.

Fatigue, a symptom with many possible causes, is highly prevalent among persons with HIV/AIDS. The causal attributions HIV+ individuals make for their fatigue are important because they largely guide the coping responses they use to manage it. In a study to better understand the symptom appraisal process among 100 HIV+ older adults (50+), 49 participants discussed in depth their experience with fatigue. Many participants felt confused, at least initially, about the source of their fatigue, although most offered their HIV disease as a possible cause. However, many who did so also believed it was caused in part by other, generally less threatening causes, such as age, overexertion, or excess weight. HIV medications and other symptoms or comorbidities were also frequently cited as causes of fatigue. Health care professionals and HIV+ peers often helped to shape or reinforce participants' attributions for their fatigue.

Age Factors↗

PubMed2006

Causality of stem cell based neurogenesis and depression--to be or not to be, is that the question?

Mood disorders compose a considerable portion of the worldwide prevailing diseases with high suicide rates and urgent demand for novel therapeutic interventions as efficacious treatment is still lacking. Depression is thought to feature distinct morphological correlatives in the brain and has recently been linked to adult neurogenesis (NG) in the hippocampal formation. Numerous findings give rise to the hypothesis that depression and declining NG in the hippocampus may be causally connected. This implies that depressive symptoms could originate from impairments in NG and, vice versa, that improved NG could mediate antidepressant action and alleviate symptoms. Thus, great hopes rest on the question whether the observed increase in NG following antidepression treatment may have the potential to become a novel drug target and specific mechanism in the development of the next generation of antidepressants that specifically involves targeting of neuropoetic factors in addition to their "traditional" effects as modulators of synaptic transmission. Along the still hypothetical association of depression and NG, however, several controversies and unresolved questions exist with respect to the presently available data and interpretation. This article highlights and summarizes some of the most pressing issues and identifies the crucial ones that await urgent clarification and resolving. Without their reliable answering, the fascinating notion of a neurogenic basis for depression will remain to be greatly speculative.

Animals↗

PubMed2004

Characterization of the metabolite produced by Mycosphaerella pinodes, the causal agent of mycosphaerella blight on field peas (Pisum sativum L.).

The metabolite produced by Mycosphaerella pinodes, the causal agent of mycosphaerella blight on field peas, was detected by thin layer chromatography (TLC) and was analyzed for its chemical and pathogenic characteristics. One blue dot was detected using 254nm UV light on TLC plate, and a spray of rho-anisaldehyde (110 degrees C, 30 min) also produced a blue dot. The solvent systems used for TLC analysis were ethyl acetate/water/acetone (5/2/5), chloroform/methanol/glacial acetic acid (19/10/2), toluene/ethyl acetate/90% formic acid (6/3/1), diethylether/methanol/water/90% formic acid (95/4/1/1), and bezene/methanol/acetic acid (24/2/1), with R(f) values (min-max) of 0.09-0.18, 0.88-0.95, 0.06-0.15, 0.39-0.47 and 0.05-0.12, respectively. The recovered metabolite from the TLC plate displayed UV absorption peaks at 212, 244, 250, 256 and 261 nm. The proposed formula of the main component of the metabolite was C16H12N3O6. The TLC-purified metabolite induced symptom of discoloration on detached pea leaves.

Ascomycota↗

PubMed2026

Transmitochondrial pigs reveal causal effects of mitochondrial DNA on backfat thickness via nuclear epigenetic reprogramming.

Mitochondrial DNA (mtDNA) polymorphisms have been associated with production traits in farm animals, including backfat thickness in pigs, yet direct in vivo evidence establishing a causal link between specific mtDNA haplotypes and fat deposition remains limited. In this study, we generated transmitochondrial pigs (mitopigs) by combining the Dapulian nuclear genome with Wuzhishan mtDNA via somatic cell nuclear transfer, introducing 23 mtDNA mutations relative to controls. Mitopigs exhibited significantly increased backfat thickness at 5 months, a difference that persisted in their offspring, without significant differences in body weight, body size, or litter size. Fibroblasts derived from mitopigs exhibited reduced mtDNA copy numbers, decreased expression of mitochondrial biogenesis genes (PPARA, PPARGC1A, RRM2B, and LRPPRC), impaired mitochondrial respiration, elevated reactive oxygen species (ROS), and upregulated adipogenic transcription factors (CEBPA, CEBPB, and PPARG). Consistent with these fibroblast findings, backfat tissue of mitopigs showed corresponding upregulation of adipogenic transcription factors and downregulation of mitochondrial biogenesis genes. Integrated transcriptomic and whole-genome bisulfite sequencing (WGBS) analyses revealed nuclear transcriptional reprogramming that was closely associated with differential DNA methylation, predominantly affecting mitochondrial function and lipid metabolism pathways. Mitopig fibroblasts also showed a pro-inflammatory response to lipopolysaccharide stimulation, with elevated expression of IL-12, NOS2, RELA, and TNF-α. Our findings provide direct in vivo evidence that mtDNA variants regulate adiposity in pigs through mitochondrial dysfunction, oxidative stress, and nuclear epigenetic modulation, highlighting the potential for incorporating mtDNA haplotype information into pig breeding programs as a complementary strategy to nuclear genomic selection.

Adipogenesis↗

PubMed2006

A nine-year genetic survey of the causal agent of Dutch elm disease, Ophiostoma novo-ulmi in Winnipeg, Canada.

The causal agent of Dutch elm disease, Ophiostoma ulmi s. lat., has been spreading across North America since the 1920s. The population of the pathogen in Winnipeg, Manitoba, Canada was surveyed in 1993 and 2002 using a combination of RAPD marker analysis, vegetative compatibility tests, and surveys for viral double-stranded RNA (dsRNA). The data presented here show that the population, based on the vegetative compatibility and RAPD analysis, was highly genetically uniform, and has remained so for the nine-year duration of the study. The pathogen population was also monitored for the presence and spread of dsRNA molecules that, depending on identity, can be associated with a diseased phenotype and reduction of virulence in the pathogen. The current study found a very low incidence of dsRNA, and did not find any evidence for spread of these molecules through the population, even though there appeared to be no barriers to the transfer of the dsRNA between Winnipeg isolates. Despite the observation that isolates infected with the Winnipeg dsRNA showed no obvious phenotypic differences, the low incidence of dsRNA in general suggests that infected isolates do not compete as successfully as the uninfected isolates. The highly clonal nature of the pathogen population may be exploited in a control strategy.

Ascomycota↗

PubMed2004

Comparing dynamic causal models.

This article describes the use of Bayes factors for comparing dynamic causal models (DCMs). DCMs are used to make inferences about effective connectivity from functional magnetic resonance imaging (fMRI) data. These inferences, however, are contingent upon assumptions about model structure, that is, the connectivity pattern between the regions included in the model. Given the current lack of detailed knowledge on anatomical connectivity in the human brain, there are often considerable degrees of freedom when defining the connectional structure of DCMs. In addition, many plausible scientific hypotheses may exist about which connections are changed by experimental manipulation, and a formal procedure for directly comparing these competing hypotheses is highly desirable. In this article, we show how Bayes factors can be used to guide choices about model structure, both concerning the intrinsic connectivity pattern and the contextual modulation of individual connections. The combined use of Bayes factors and DCM thus allows one to evaluate competing scientific theories about the architecture of large-scale neural networks and the neuronal interactions that mediate perception and cognition.

Attention↗

PubMed2004

Modelling functional integration: a comparison of structural equation and dynamic causal models.

The brain appears to adhere to two fundamental principles of functional organisation, functional integration and functional specialisation, where the integration within and among specialised areas is mediated by effective connectivity. In this paper, we review two different approaches to modelling effective connectivity from fMRI data, structural equation models (SEMs) and dynamic causal models (DCMs). In common to both approaches are model comparison frameworks in which inferences can be made about effective connectivity per se and about how that connectivity can be changed by perceptual or cognitive set. Underlying the two approaches, however, are two very different generative models. In DCM, a distinction is made between the 'neuronal level' and the 'hemodynamic level'. Experimental inputs cause changes in effective connectivity expressed at the level of neurodynamics, which in turn cause changes in the observed hemodynamics. In SEM, changes in effective connectivity lead directly to changes in the covariance structure of the observed hemodynamics. Because changes in effective connectivity in the brain occur at a neuronal level DCM is the preferred model for fMRI data. This review focuses on the underlying assumptions and limitations of each model and demonstrates their application to data from a study of attention to visual motion.

Algorithms↗

PubMed2005

Cerebral pathways in processing of affective prosody: a dynamic causal modeling study.

This study was conducted to investigate the connectivity architecture of neural structures involved in processing of emotional speech melody (prosody). 24 subjects underwent event-related functional magnetic resonance imaging (fMRI) while rating the emotional valence of either prosody or semantics of binaurally presented adjectives. Conventional analysis of fMRI data revealed activation within the right posterior middle temporal gyrus and bilateral inferior frontal cortex during evaluation of affective prosody and left temporal pole, orbitofrontal, and medial superior frontal cortex during judgment of affective semantics. Dynamic causal modeling (DCM) in combination with Bayes factors was used to compare competing neurophysiological models with different intrinsic connectivity structures and input regions within the network of brain regions underlying comprehension of affective prosody. Comparison on group level revealed superiority of a model in which the right temporal cortex serves as input region as compared to models in which one of the frontal areas is assumed to receive external inputs. Moreover, models with parallel information conductance from the right temporal cortex were superior to models in which the two frontal lobes accomplish serial processing steps. In conclusion, connectivity analysis supports the view that evaluation of affective prosody requires prior analysis of acoustic features within the temporal and that transfer of information from the temporal cortex to the frontal lobes occurs via parallel pathways.

Adult↗