Skin lesions,malaise, and heart failure in a renal transplant recipient

A male Caucasian patient developed nodular erythematous skin lesions, malaise, and clinical signs of progressive heart failure 4 months after renal transplantation. Bronchoscopy with bronchoalveolar lavage performed for a small infiltrate seen on a computed tomography scan revealed Trypanosoma, which had at this point not been suspected as a cause. Parasitemia was present, and reactivation rather than transmission of Chagas' disease was established by performing polymerase chain reaction and serology in the donor and recipient. Treatment with benznidazole and allopurinol successfully reduced parasitemia, but the clinical course was fatal owing to progression of severe myocarditis. The patient had never lived in an endemic area, but had an extensive travel history in South America. The last visit was more than 5 years before transplantation. In non‐endemic countries (United States, Europe), reactivation after transplantation has only been very rarely reported. Given the rising numbers of transplantations in patients with a migration background and extensive travel histories, specific screening procedures have to be considered.     

Satisfaction of Basic Psychological Needs,Self-Determined Exercise Motivation,and Psychological Well-Being in Mothers Exercising in Group-Based Versus Individual-Based Contexts

We compared mothers who exercised predominantly in group settings, those who exercised predominantly in individual settings, and those who exercised equally in group and individual contexts among the following: (a) satisfaction of basic psychological needs (autonomy, competence, and relatedness); (b) self-determined exercise motivation; and (c) psychological well-being. With clear implications for mothers’ exercise interventions we found that exercising either predominantly in group contexts or in mixed group and individual settings was associated with mothers having significantly higher satisfaction of basic psychological needs and self-determined exercise motivation than those exercising predominantly alone.     

“I felt like the angel of death”: role conflicts and moral distress among allied professionals employed by the US cardiovascular implantable electronic device industry

Purpose  

This study aimed to identify themes associated with role conflicts and moral distress experienced by cardiovascular implantable electronic device (CIED) industry-employed allied professionals (IEAPs) in the clinical setting.     

Subsistence agriculture and child growth in Papua New Guinea

Spatial statistical analyses of child anthropometric data were undertaken to assess the influence of systems of subsistence agriculture, in terms of staple foods and cash crops cultivated, on patterns of child growth in Papua New Guinea. These agricultural data explained between a quarter and half of the geographical variation in anthropometric growth indicators. Accounting for differences in altitude, relief and rainfall patterns, though explaining additional geographical variation, did not improve the predictions. Child growth was better in agriculture systems with cassava and sweet potato as staple crops, but worse in systems where banana, sago and taro were staple crops. Both the cultivation of all major cash crops, and sales of fish and food crops improved child growth. More intensive agricultural systems were associated with larger children indicating that the nutritional status of children benefited from intensification as well as from the introduction of cash crops into traditional subsistence systems.     

Lack of in vitro constitutive activity for four previously reported TSH receptor mutations identified in patients with nonautoimmune hyperthyroidism and hot thyroid carcinomas

Objective Constitutively activating mutations (CAMs) of the TSHR are the major cause for nonautoimmune hyperthyroidism. Re‐examination of constitutive activity previously determined in CHO cell lines recently demonstrated the caveats for the in vitro determination of constitutive TSHR activity, which leads to false positive conclusions regarding the molecular origin of hyperthyroidism or hot thyroid carcinomas. Design Mutations L677V and T620I identified in hot thyroid carcinomas were previously characterized in CHO and in 3T3‐Vill cell lines, respectively, stably expressing the mutant without determination of TSHR expression. F666L identified in a patient with hot thyroid nodules, I691F in a family with nonautoimmune hyperthyroidism and F631I identified in a hot thyroid carcinoma were not characterized for their in vitro function. Therefore, we decided to (re)evaluate the in vitro function of these five TSHR variants by determination of cell surface expression, and intracellular cAMP and inositol phosphate levels and performed additionally linear regression analyses to determine basal activity independently from the mutant’s cell surface expression in COS‐7 and HEK_GT cells. Results and Conclusions Only one (F631I) of the five investigated TSHR variants displayed constitutive activity for G_αs signalling and showed correlation with the clinical phenotype. The previous false classification of T620I and L677V as CAMs is most likely related to the fact that both mutations were characterized in cell lines stably expressing the mutated receptor construct without assessing the respective receptor number per cell. Other molecular aetiologies for the nonautoimmune hyperthyroidism and/or hot thyroid carcinomas in these three patients and one family should be elucidated.     

Phospho-CRKL monitoring for the assessment of BCR-ABL activity in imatinib-resistant chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia patients treated with nilotinib

Actual BCR-ABL kinase inhibition in vivo as determined by phospho-CRKL (pCRKL) monitoring has been recognized as a prognostic parameter in patients with chronic myelogenous leukemia treated with imatinib. We report a biomarker sub-study of the international phase I clinical trial of nilotinib (AMN107) using the established pCRKL assay in imatinib-resistant chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia. A minimum dose (200 mg) required for effective BCR-ABL inhibition in imatinib resistant/intolerant leukemia was determined. The pre-clinical activity profile of nilotinib against mutant BCR-ABL was largely confirmed. Substantial differences between peripheral blood baseline pCRKL/CRKL ratios were observed when comparing chronic myeloid leukemia with Ph+ acute lymphoblastic leukemia. Finally, rapid BCR-ABL-reactivation shortly after starting nilotinib treatment was seen in acute lymphoblastic leukemia patients with progressive disease carrying the P-loop mutations Y253H, E255K, or mutation T315I. Monitoring the actual BCR-ABL inhibition in nilotinib treated patients using pCRKL as a surrogate is a means to establish effective dosing and to characterize resistance mechanisms against nilotinib.     

Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease

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