Keywords: DRD4 exon III VNTR polymorphism; −521 C/T promoter polymorphism; attachment disorganization; dopamineIn non-clinical low-risk populations 15% of infants show disorganized attachment behavior 1,2 with their caregivers in the Strange Situation, 3 a mildly stressful laboratory procedure testing infants' ability to cope with separation anxiety. Disorganization of early attachment has been primarily ascribed to inadequate parenting, 2,4,5 and has been associated with childhood behavior problems 6,7 and adolescent psychopathological tendencies. 5We have recently reported an association between the DRD4 exon III 48 basepair repeat polymorphism and disorganization of infants' attachment behavior towards their mother in a low-social-risk group of 1-year-old infants: 8 the risk for disorganized attachment among infants carrying the 7-repeat allele was fourfold. Here we report further evidence for the involvement of the dopamine D4 receptor gene in attachment disorganization. The same group of infants was genotyped for the functional −521 C/T single nucleotide polymorphism (SNP) in the upstream regulatory region of the DRD4 gene 9 in order to test the association with attachment disorganization both alone and in interaction with the DRD4 exon III 7-repeat allele. While the −521 C/T genotype itself had no effect on attachment status ( 2 = 0.41, df = 2, P = 0.82), there was an interaction between the structural 48-bp repeat polymorphism and the −521 C/T promoter polymorphism: the association between disorganized attachment and the 7-repeat allele was enhanced in the presence of the −521 T allele ( 2 = 6.61 and 6.67, df = 1, P Ͻ 0.025 for CT and TT genotypes, respectively). In the presence of both risk alleles the odds ratio for disorganized attachment increased tenfold. This result supports our previous postulation that the DRD4 gene plays a role in the development of attachment behavior in low-risk, non-clinical populations. Molecular Psychiatry (2002) 7, 27-31. DOI: 10.1038/ sj/mp/4000986The role of dopamine receptor and transporter genes in both normal traits and psychopathology has been intensively studied in the past decade.10,11 One of the most frequently targeted candidate genes is the highly polymorphic dopamine D4 receptor (DRD4) gene. 12,13A 48-bp VNTR polymorphism has been identified in exon III with the 4-repeat allele being the most common, followed by the 7-repeat form 14 which is 2-3 times less potent in dopamine-mediated coupling to adenylyl cyclase than the 4-repeat form.15 Evidence linking the 7-repeat allele of the DRD4 gene with infant temperament traits of negative emotionality [16][17][18] and maladaptive behavioral problems, especially attention deficit hyperactivity disorder (ADHD) in children, is being accumulated. 19-21Recently, we found that the 7-repeat DRD4 allele was 2.5 times more frequent among one-year-old infants who showed disorganized attachment behavior, ie were unable to cope with the stress elicited by the two brief separations from the caregiver in the Strange Situation exper...
Background Refractory cardiogenic shock is still a major clinical challenge with high mortality rates, although several devices can be used to conquer this event. These devices have different advantages and disadvantages originating from their insertion or cannulation method, therefore many complications can occur during their use. The aim of our study was to develop and create prototypes of a novel minimal invasively insertable, transapical cannula for surgical ventricular assist devices, which uniquely incorporates the inflow and outflow routes for the blood of the patient in itself, therefore it enables the use for only one cannula for patients in cardiogenic shock. Methods To define the available space for the planned cannula in the left ventricle and ascending aorta, we analyzed computed tomography scans of 24 heart failure patients, who were indicated to left ventricular assist device therapy. Parallel to these measurements, hydrodynamical calculations were performed to determine the sizes of the cannulas, which were necessary to provide effective cardiac output. Results After the designing steps, we produced prototypes of double-lumened, tube-in-tube apically insertable devices for three different patient groups, which included a separated venous and an arterial part using 3D modelling and printing technology. All the created cannulas are able to provide 5 l/min circulatory support. Conclusion As a result of our research we created a sizing method based on the specific analysis of computed tomography pictures of end stage heart failure patients and a cannula concept, which can provide effective antegrade flow for patients in cardiogenic shock. We believe the improved version of our tool could have a significant therapeutic role in the future after further development based on animal and in vivo tests.
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