Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies.

BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues experimentally. OBJECTIVES: To experimentally address the controversies concerning the correct way to record MAPs or calculate ARIs. METHODS: Left ventricular local electrograms were recorded in isolated pig hearts with an exploring electrode grid, with a KCl reference electrode on the left ventricular myocardium, the aortic root, or the left atrium. Local activation was determined from calculated Laplacian electrograms. RESULTS: With the KCl electrode on the aortic root, local electrograms represented local activation. However, with the KCl electrode on the myocardium remote from the exploring electrode, a combined electrogram emerged consisting of local activation recorded from the grid and remote activation recorded from the reference electrode. The remote, inverted monophasic component did not show propagation and did not correlate with the Laplacian complex. When the KCl electrode was placed on the atrium during AV block, remote atrial monophasic components were completely dissociated from local, ventricular deflections. At left ventricular sites with a positive T wave, the Laplacian signal showed that the end of the T wave was caused by remote repolarization. During cooling-induced regional action potential prolongation, the T wave became negative, whereby the positive flank of the T wave remained correlated with repolarization (recorded with a MAP at the same site). CONCLUSIONS: MAPs are recorded from the depolarizing electrode. In both negative and positive T waves, the moment of maximum dV/dt corresponds to local repolarization.     

A comparison in cosmetic outcome between per-operative interstitial breast implants and delayed interstitial breast implants after external beam radiotherapy.

BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome.     

Combined TCRG and TCRA TREC analysis reveals increased peripheral T-lymphocyte but constant intra-thymic proliferative history upon ageing

T-cell receptor (TCR) repertoire diversity, thymic output, clonal size and peripheral T-lymphocyte numbers largely depend on intra-thymic and post-thymic T-lymphocyte proliferation. However, quantitative insight into thymocyte and T-lymphocyte proliferation is still lacking. We developed a new TCRG-based TCR excision circle (TREC) assay, the Vγ-Jγ TREC assay, which we used together with an adjusted δREC-ψJα TREC assay to quantify the proliferative history of human thymocyte and T-lymphocyte subpopulations from children and adults. This revealed that thymocytes undergo ～6–8 intra-thymic cell divisions from the double negative (DN) 3 developmental stage onwards, which appeared independent of age. Thus thymocyte proliferation after the DN3 developmental stages is stable and therefore not contributing to the reduced thymic output upon ageing. Cord blood naive T lymphocytes had already undergone ～2–3 post-thymic cell divisions, which increased to ～6–7 cell divisions in naive T lymphocytes of middle-aged adults, indicating the importance of homeostatic naive T-lymphocyte proliferation from a young age onwards in the maintenance of peripheral T-lymphocyte numbers. In conclusion, our data provide quantitative insight into the proliferative history of thymocyte and T-lymphocyte subpopulations and alterations herein upon ageing. This novel TREC assay approach could prove valuable in immune status monitoring in a variety of conditions.     

Neuroimaging in children, adolescents and young adults with psychological trauma

Childhood psychological trauma is a strong predictor of psychopathology. Preclinical research points to the influence of this type of trauma on brain development. However, the effects of psychological trauma on the developing human brain are less known and a challenging question is whether the effects can be reversed or even prevented. The aim of this review is to give an overview of neuroimaging studies in traumatized juveniles and young adults up till 2012. Neuroimaging studies in children and adolescents with traumatic experiences were found to be scarce. Most studies were performed by a small number of research groups in the United States and examined structural abnormalities. The reduction in hippocampal volume reported in adults with PTSD could not be confirmed in juveniles. The most consistent finding in children and adolescents, who experienced psychological trauma are structural abnormalities of the corpus callosum. We could not identify any studies investigating treatment effects. Neuroimaging studies in traumatized children and adolescents clearly lag behind studies in traumatized adults as well as studies on ADHD and autism.     

Disgusted by Sexual Abuse: Exploring the Association Between Disgust Sensitivity and Posttraumatic Stress Symptoms Among Mothers of Sexually Abused Children

Nonoffending mothers of sexually abused children often exhibit high levels of posttraumatic stress (PTS) symptoms. Emerging evidence suggests that trait‐like individual differences in sensitivity to disgust play a role in the development of PTS symptoms. One such individual difference, disgust sensitivity, has not been examined as far as we are aware among victims of secondary traumatic stress. The current study examined associations between disgust sensitivity and PTS symptoms among mothers of sexually abused children (N = 72). Mothers completed the Impact of Event Scale‐Revised and the Three Domain Disgust Scale (Tybur, Lieberman, & Griskevicius, 2009). More than one third of mothers scored above a suggested cutoff (mean score = 1.5) for high levels of PTS symptoms. Hierarchical linear regression analysis results indicated that sexual disgust sensitivity (β = .39, p = .002) was associated with PTS symptoms (R² = .18). An interaction analysis showed that sexual disgust sensitivity was associated with maternal PTS symptoms only when the perpetrator was not biologically related to the child (β = ?.32, p = .047; R² = .28). Our findings suggested that sexual disgust sensitivity may be a risk factor for developing PTS symptoms among mothers of sexually abused children.     

Risk of invasion and axillary lymph node metastasis in ductal carcinoma in situ diagnosed by core-needle biopsy

BACKGROUND: The aim of the study was to assess the risk of invasion and axillary lymph node metastasis in patients with ductal carcinoma in situ (DCIS) diagnosed by preoperative core-needle biopsy. The data were used to select criteria for patients in whom sentinel node (SN) biopsy might be indicated. METHODS: One hundred and seventy-one women with 172 DCIS lesions diagnosed by core-needle biopsy were analysed. Axillary staging was performed by SN biopsy, axillary node sampling, or level 1-2 axillary lymph node dissection. RESULTS: Invasive breast cancer was found in the surgical specimens from 45 tumours (26.2 per cent). Risk factors for invasion were a palpable lesion (odds ratio (OR) 2.95 (95 per cent confidence interval 1.20 to 7.26); P = 0.019), presence of a mass on mammography (OR 3.06 (1.43 to 6.56); P = 0.004), and intermediate (OR 5.81 (1.18 to 28.57); P = 0.030) or poorly differentiated (OR 5.46 (1.17 to 25.64); P = 0.031) tumour grade. Lymph node metastases were found in ten women with DCIS and invasion on final pathology. Factors associated with metastases were age 55 years or less (P = 0.030), invasion of 1.0 cm or more (P < 0.001) and the presence of vascular invasion (P = 0.001). CONCLUSION: SN biopsy should be considered in women with an initial diagnosis of DCIS on core-needle biopsy who are at risk for invasion; this includes women with a palpable lump, a mass on mammography, and intermediate or poor tumour grade.