Protonation of non-Watson-Crick base pairs and encapsidation of turnip yellow mosaic virus RNA

The 5' UTR of turnip yellow mosaic virus RNA contains two conserved hairpins with internal loops consisting of C.C and C.A mismatches. In this article, evidence is presented indicating that the 5' proximal hairpin functions as an encapsidation initiation signal. Extensive mutagenesis studies on this hairpin and sequencing of virus progeny showed a clear preference for C.C and C.A mismatches within the internal loop. The importance of these mismatches lies in their pH-dependent protonation and stable base pair formation. Encapsidation efficiency was found to be severely affected for several mutants lacking the protonatable mismatches in the internal loop of the 5' proximal hairpin. Furthermore, gel mobility-shift assays were performed with various RNA hairpins and empty capsids with a hole. Protonatable hairpins containing C.C and/or C.A pairs were found to bind specifically to the interior of the protein shell under acidic conditions (pH 4.5) in the presence of spermidine. Based on these results we propose that this binding of protonated cytosines to the coat protein of turnip yellow mosaic virus may represent a new motif in RNA-protein interactions.     

Identity development, coping, and adjustment in emerging adults with a chronic illness: the sample case of type 1 diabetes

PURPOSE: The present study focused on identity development in emerging adults (aged 18-30 years) with type 1 diabetes. The three study aims were to examine the following: (1) whether identity development was affected by having diabetes, as compared with development in a nondiabetic sample; (2) how identity development was related to depressive symptoms, coping with diabetes, and diabetes-related problems in the diabetic sample; and (3) whether the pathways from identity development to problems with diabetes and depressive symptoms were mediated through coping strategies in the diabetic sample. METHODS: A total of 194 emerging adults with type 1 diabetes and 344 nondiabetic emerging adults participated. RESULTS: First, using analyses of variance, some mean identity differences between the diabetic and comparison samples were found, with emerging adults with diabetes scoring lower on proactive identity exploration. Using cluster analysis, we found that the same identity types or statuses emerged in both the diabetic and nondiabetic samples. Second, in emerging adults with diabetes, these identity statuses were differentially related to diabetes-related problems, depressive symptoms, and illness coping, with the identity statuses representing a strong sense of identity being accompanied by less diabetes-related problems and depressive symptoms and more adequate coping strategies. Third, using structural equation modeling, the pathways from a strong sense of identity to diabetes-related problems and depressive symptoms were mediated through adaptive and maladaptive coping. CONCLUSIONS: Clinicians should be sensitive to the normative task of identity development in emerging adults with diabetes because identity development can function as a resource in coping with and adjusting to diabetes.     

Arterial thrombosis in four patients treated with thalidomide

Thalidomide has been associated with venous thrombotic events, as reported in the post-marketing surveillance reports by Celgene Corporation; as well as case reports in the literature. Seven arterial thrombotic events have been reported in patients receiving thalidomide with 3 cases occurring in patients with other predisposing conditions. We report 4 additional cases of arterial thromboses in 1 lymphoma and 3 myeloma patients treated with thalidomide. The mechanism for these events is unclear; however, it is significant that 2 patients were receiving concomitant anticoagulation with aspirin and warfarin.     

Validation of a nomogram for predicting disease-specific survival after an R0 resection for gastric carcinoma

BACKGROUND: A statistical model for predicting disease-specific survival in patients with gastric carcinoma, based on a single U.S. institution experience, was tested for validity in a sample of patients treated at different institutions. METHODS: The authors analysed 459 patients from the Dutch Gastric Cancer trial that compared limited (D1) with extended (D2) lymph node dissection. The discrimination ability of the nomogram with respect to 5 and 9-year disease-specific survival probabilities was superior to that of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: There was considerable heterogeneity of risk within many of the AJCC stages. Calibration plots suggested that predicted probabilities from the nomogram corresponded closely to actual disease-specific survival. The gastric carcinoma nomogram performed well when applied to patients treated in a large number of institutions. CONCLUSIONS: The nomogram provided predictions that discriminated better than the AJCC staging system, regardless of the extent of lymph node dissection. Patient counseling and adjuvant therapy decision-making should benefit from use of the nomogram.     

Pentobarbital fails to reduce cerebral oxygen consumption early after non-hemorrhagic closed head injury in rats

It is unknown whether barbiturates suppress cerebral oxygen metabolism after cerebral trauma as they do in normal individuals. We evaluated the influence of pentobarbital on cerebral oxygen handling of normal rats and rats subjected to non-hemorrhagic closed head injury (CHI). Oxygen delivery was assessed by measuring cerebral perfusion and oxygen extraction, enabling the calculation of cerebral metabolic rate of oxygen (CMRO2). Mitochondrial function was assessed by studying changes in the oxidized cytochrome oxidase concentration. CHI caused changes in both systemic and cerebral hemodynamics. Cerebral blood flow was reduced to 66% of its control value, but the cerebral metabolic rate of oxygen remained unchanged. Pentobarbital administration induced a significant lowering of the cerebral oxygen consumption in normal rats associated with a secondary decrease in cerebral perfusion. In rats subjected to CHI, pentobarbital was unable to lower the cerebral metabolic demand and did not cause a further decrease in perfusion. Pentobarbital was unable to significantly modulate mitochondrial function in traumatized rats, whereas it exerted this effect in all control animals. We therefore conclude that, in rats subjected to CHI, pentobarbital is unable to perform its beneficial effects on the cerebral metabolism.     

Belgium experience with metal-on-metal surface arthroplasty

Hybrid metal-on-metal surface arthroplasty of the hip has recently been introduced, with a vast number of implants used in European countries including Belgium. This article presents results in 252 hips with a mean follow-up of 2.8 years. Using a tight press-fit with minimal cement mantle as the technique of femoral fixation, there have been only three failures. The main complications have been avascular necrosis of the femoral head and femoral neck fracture. In most cases, patients returned to a high functional level with no restrictions in their physical activity and were highly satisfied. Future refinements in surgical technique and instruments will make this procedure more accessible and reproducible for the surgeon.     

Selection of treatment for patients with carotid artery disease: medication, carotid endarterectomy, or carotid artery stenting

Patients presenting with atherosclerosis of the extracranial carotid arteries may be offered carotid endarterectomy (CEA), carotid artery stenting (CAS), or medical therapy to reduce their risk of stroke. In many cases, the choice between treatment modalities remains controversial. An algorithm based on patients' neurologic symptoms, comorbidities, limiting factors for CAS and CEA, and personal preferences was developed to determine the optimal treatment in each case. This algorithm was then employed to determine therapy in 308 consecutive patients presenting to a single institution during one calendar year. Ninety-five (30.8%) patients presented with an asymptomatic carotid stenosis of more than 80% and 213 (69.2%) with a symptomatic stenosis of more than 50%. According to our algorithm, 59 (62.1%) of the 95 asymptomatic patients received CAS, 20 (21.1%) received CEA, and 16 (16.8%) received medical therapy. All symptomatic patients underwent intervention; 153 (71.8%) were treated with CAS and 60 (28.2%) with CEA. Combined 30-day stroke and death rates after CAS were 1.7% in asymptomatic patients and 2.6% in symptomatic patients. After CEA, these rates were 0% and 3.3%, respectively. Careful selection of treatment modality according to predetermined criteria can result in improved outcomes.     

Comparison of changes in physical self-concept, global self-esteem, depression and anxiety following two different psychomotor therapy programs in nonpsychotic psychiatric inpatients

BACKGROUND: The first objective of this study was to compare the changes in physical self-concept, global self-esteem, depression and anxiety after participation in one of two 16-week psychomotor therapy programs for nonpsychotic psychiatric inpatients. The second objective was to study the relationship between changes in these variables. METHODS: One hundred and ninety-nine inpatients were randomly assigned to either a personalized psychomotor fitness program, consisting of aerobic exercise and weight training, or a general program of psychomotor therapy, consisting of different forms of physical exercises and relaxation training. Physical self-concept was evaluated using the Dutch version of the Physical Self-Perception Profile at baseline, after 8 weeks, and after completion of the 16-week interventions. At the same time points, additional variables of global self-esteem, depression and anxiety were assessed by means of the Rosenberg Self-Esteem Inventory, the Beck Depression Inventory and the Trait Anxiety Inventory, respectively. RESULTS: After 16 weeks, both groups showed significant improvements in all outcome measures (p values ranged from 0.01 to < 0.0001), with no between-group differences. In both groups, the improvement in physical self-concept was correlated with increased global self-esteem and decreased depression and anxiety levels (p < 0.01). CONCLUSIONS: The results suggest that both psychomotor therapy programs are equally effective in enhancing physical self-concept. The relationship between improvements in physical self-concept and enhancements in global self-esteem, depression and anxiety supports the potential role of the physical self-concept in the recovery process of depressed and anxious psychiatric inpatients.     

Magnetic resonance angiography of the circle of Willis in migraine patients

We analysed records of 244 consecutive adult outpatients who presented at our neurological polyclinic between 1996 and 2001 with migraine and who underwent a MRA of the circle of Willis. In 80 cases, a definitive migraine diagnosis according to the International Headache Society criteria (1988) could be retrieved from the patient records. Of these, 63 patients had migraine without aura and 17 patients had migraine with aura. Two MRA procedures were abrupted because of claustrophobia and another two MRA studies were unreliable because of movement artefacts. In only one patient of the remaining 240, an aneurysm was suspected with MRA. However, a conventional angiography did not confirm any cerebrovascular abnormality. All other exams were considered normal. This retrospective study argues against a systematic screening of migraine patients with MRA.