Dutch youth of parents with a mental illness reflect upon their feelings of guilt and shame

Children of parents with a mental illness (COPMI) have a higher risk of acquiring a mental illness themselves. Feelings of guilt and shame could increase COPMI risks of acquiring mental health disorder symptoms. These feelings of guilt and shame could also impact the quality of the parent-child relationship. Data were drawn from the qualitative part of a mixed method study featuring 18 face-to-face interviews with Dutch COPMI aged 12–21. Interviewees were asked about their experiences with guilt and shame related to their parent with mental illness and the extent they felt that these feelings affected their relationships with their parents. Qualitative thematic analysis (QTA) revealed that most COPMI youth described feelings of guilt and some of them reported feelings of shame. They reported making behavioral adjustments especially using caution in parental communication. In their perception, guilt and shame did not have long-term impacts on their relationships with parents.     

8p21.3 deletions are rare causes of non-syndromic autism spectrum disorder

neurogenetics - A de novo 0.95 Mb 8p21.3 deletion had been identified in an individual with non-syndromic autism spectrum disorder (ASD) through high-resolution copy number variant analysis....     

New simplified molecular design for functional T cell receptor

We have produced a chimeric single-chain T cell receptor (TcR) that combines the specific antibody recognition function and TcR/CD3 signaling properties within the same polypeptide chain. This hybrid molecule consisted of a single-chain antibody combining site that was connected over a short spacer to the transmembrane and cytoplasmic region of CD3ζ. When expressed on TcR^? or TcR⁺ T cell hybridomas it could mediate recognition of relevent target cells and subsequent production of lymphokines; i.e. it could functionally replace the TcR/CD3 complex. Therefore, the single-chain TcR model presented here represents an interesting and useful means for the creation of T cells with new specificities.     

Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma

Background

Vascular endothelial growth factor (VEGF)-targeted therapy has become standard treatment for patients with metastatic renal cell cancer (mRCC). Since these therapies can induce tumor necrosis and minimal tumor shrinkage, Response Evaluation Criteria in Solid Tumors (RECIST) may not be optimal for predicting clinical outcome.

Objective

To systematically determine the optimal early posttherapy imaging changes (EPTIC) to separate responders and nonresponders at the first posttreatment follow-up computed tomography (CT).

Design, setting, and participants

Seventy mRCC patients with 155 target lesions treated with first-line sunitinib, sorafenib, or bevacizumab at academic medical centers underwent contrast-enhanced thoracic and abdominal CT at baseline and first follow-up after therapy initiation (median: 78 d after therapy initiation; range: 31–223 d).

Measurements

Evaluations were performed according to (1) RECIST 1.0; (2) Choi criteria; (3) tumor shrinkage (TS) of ≥10% decrease in sum of the longest unidimensional diameter (SLD); and (4) 15% or 20% decrease in mean CT tumor density. Correlation with time to treatment failure (TTF) and overall survival (OS) were compared and stratified by response to each of the radiologic criteria.

Results and limitations

Eleven patients were considered responders by RECIST 1.0; 49 based on Choi criteria; 31 patients had ≥10% decrease in the SLD; and 36 and 32 patients had ≥15% and ≥20% decrease, respectively, in mean tumor density on CT. Only the threshold of 10% decrease in the SLD was statistically significant in predicting TTF (10.4 vs 5.1 mo; p = 0.02) and OS (32.5 vs 15.8 mo; p = 0.002). Receiver operating characteristic analysis yielded a 10% decrease in SLD as the optimal size change threshold for responders. The retrospective nature of the study and measurements by a single oncoradiologist are inherent limitations.

Conclusions

In the retrospectively analyzed study population of mRCC patients receiving VEGF-targeted agents, a 10% reduction in the SLD on the first follow-up CT was an optimal early predictor of outcome.     

The heart of children with steroid-resistant nephrotic syndrome: is it all podocin?

Mutations in the gene NPHS2 encoding podocin are responsible for a recessive form of steroid-resistant nephrotic syndrome (SRNS). The common phenotype is of massive proteinuria in early childhood that tends to progress to end-stage renal failure. Extrarenal manifestations have not been described. Twenty-two children with SRNS from six unrelated Arab families were found to be homozygous for the R138X mutation in NPHS2. Eighteen patients underwent cardiac evaluation at diagnosis of SRNS while they had normal BP and preserved renal function. Cardiac anomalies were detected in 16 (89%) children: Left ventricular hypertrophy in eight, pulmonary stenosis in six, discrete subaortic stenosis in two, and Ebstein anomaly and ventricular septal defect in one each. The remaining four affected individuals were assessed only once they had end-stage renal failure. They had severe left ventricular hypertrophy and experienced repeated episodes of heart failure. Two control groups were equally evaluated. The first consisted of 37 siblings without nephrotic syndrome, of whom only one carrier had a cardiac defect (P < 0.001). None of the second group, which included 22 children with persistent nephrotic syndrome as a result of other causes, had a cardiac anomaly (P < 0.001). Cardiac disorders in homozygotes for mutations in NPHS2 cannot be attributed to an association by chance or to a state of persistent nephrotic syndrome. Because human podocin mRNA is expressed in fetal heart, it is speculated that it may have a role in normal cardiac development. Cardiac evaluation is recommended at the time of diagnosis of SRNS due to mutations in podocin.     

Can pT0 stage of prostate cancer be predicted before radical prostatectomy?

OBJECTIVES: To report our experience with biopsy-proven pT0 prostate cancer over the last 10 yr. METHODS: We retrospectively analysed a series of 1950 consecutive patients treated with radical prostatectomy (RP) for clinically localized prostate cancer between 1996 and 2005 at our institution. The patients without residual tumour on RP specimen were defined as pT0 patients. The group of pT0 patients was compared with a control group of 295 patients operated consecutively during the same period. RESULTS: Overall, 11 (0.5%) patients were classified as pT0 on pathologic examination of the RP specimen. There was no pT0 tumour in the control group. Among the pT0 patients, five characteristics were particularly frequent: T1c clinical stage (90.9%), prostate-specific antigen (PSA) or=60 g (100%). All these characteristics were present in 8 of the 11 (72.7%) pT0 patients, while they were present in only 12 of the 295 (4.1%) controls. These parameters, when combined together, had a sensitivity of 72%, a specificity of 96%, and an accuracy of 99% for the prediction of pT0 stage. With a mean follow-up of 30 months after RP, no pT0 patient had clinical or biologic evidence of prostate cancer. CONCLUSIONS: In our experience, the rate of pT0 tumours after RP is 0.5%. The combination of clinical stage, preoperative PSA, number of positive biopsy cores, Gleason score, and prostate weight could help to predict pT0 stage after RP.     

Imaging of lung cancer in the era of molecular medicine

Recent discoveries characterizing the molecular basis of lung cancer brought fundamental changes in lung cancer treatment. The authors review the molecular pathogenesis of lung cancer, including genomic abnormalities, targeted therapies, and resistance mechanisms, and discuss lung cancer imaging with novel techniques. Knowledge of the molecular basis of lung cancer is essential for radiologists to properly interpret imaging and assess response to therapy. Quantitative and functional imaging helps assessing the biologic behavior of lung cancer.     

Rhenium-188 and technetium-99m nitridobis(N-ethoxy-N-ethyldithiocarbamate) leucocyte labelling radiopharmaceuticals: [ReN(NOET)2] and [TcN(NOET)2], NOET = Et(EtO)NCS2: Their in vitro localization and chemical behaviour

In this study, we have investigated the preparation of rhenium-188 nitridobis(N-ethoxy-N-ethyldithiocarbamate) [¹⁸⁸ReN(NOET)₂] (NOET = Et(EtO)NCS₂), analogous to the known technetium-99m radiopharmaceutical. The new ¹⁸⁸Re complex was synthesized in good yield with a satisfactory radiochemical purity, using a kit method. The subcellular localization of both radiopharmaceuticals in granulocytes was observed by microautoradiography. The uptake was independent of the radionuclide and predominantly nuclear. Furthermore, HPLC was used to characterize the ^99mTc complex before and after blood cell labelling and revealed that the intact radiopharmaceutical was involved.     

“In-house” pharmacological management for computed tomography coronary angiography: heart rate reduction, timing and safety of different drugs used during patient preparation

We retrospectively evaluated the effect, timing and safety of different pharmacological strategies during 64-slice CT coronary angiography (CT-CA). From the institutional database of CT-CA we enrolled 560 consecutive patients with suspected coronary artery disease. The type of drug preparation (group 1 = no treatment; group 2 = oral metoprolol; group 3 = other; group 4?=?intravenous (IV) atenolol; group 5?=?IV atenolol + nitrates; NR = non-responders), timing, and adverse effects were recorded. Heart rate (HR) during different preparation phases was recorded. Four adverse effects were recorded, none of which was attributable to pharmacological treatment. In all groups, except group 1, the HR on arrival was significantly reduced by the pharmacological treatment (p?<?0.01). Group 4 showed the best (?16?±?8 bpm) HR reduction. There was no significant effect on HR due to nitrates (p?=?0.49), while a slight increase due to contrast material was noted (p?<?0.05). Average time required for preparation was 44?±?25 min. Groups 4 and 5 showed the most effective timing (8?±?9 min and 8?±?8 min, respectively; p?<?0.01). Pharmacological preparation in patients undergoing CT-CA is safe and effective. Best results in terms of HR reduction and fast preparation are obtained with IV administration of beta-blockers.