Movement efficiency in survivors of childhood acute lymphoblastic leukemia: a report from the St. Jude lifetime cohort study.

PURPOSE: Movement efficiency, a measure of neuromuscular biomechanics, may be modified by physical activity. We aimed to assess the risk of and risk factors for low movement efficiency in survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: Participants underwent an assessment of activity energy expenditure (AEE) with actigraphy, and the gold standard doubly labeled water, where the differences between elimination rates of oxygen and hydrogen from body water are evaluated over a week. Movement efficiency was assessed using the raw residuals of a linear regression between AEEs from accelerometers and doubly labeled water. Elastic-net logistic regressions were used to identify demographic, treatment, and functional variables associated with movement efficiency. RESULTS: The study cohort included 256 non-cancer controls and 302 ALL survivors (48% female), categorized as efficient (N = 24), normal (N = 245), or inefficient (N = 33) based on their movement efficiency. There was no difference in the odds for poor movement efficiency between survivors (n = 33, 10.9%) compared to controls (n = 23, 9.0%, odds ratio [OR]: 1.19, 95% confidence interval [CI]: 0.67, 2.10; p = 0.55). In survivors, neuropathy was associated with a higher risk of being inefficient compared to efficient (OR 4.30, 95% CI 1.03-17.96), while obesity (≥ 30 kg/m2) had a protective association (OR 0.18, 95% CI 0.04-0.87). CONCLUSIONS: Neuropathy was associated with a higher risk of poor movement efficiency in survivors of childhood ALL. IMPLICATIONS FOR CANCER SURVIVORS: These results further highlight impairments associated with treatment-induced neuropathy in survivors of childhood ALL.

Evolving therapies, neurocognitive outcomes, and functional independence in adult survivors of childhood glioma.

BACKGROUND: Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown. METHODS: Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n = 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [with or without surgery], cranial radiation [with or without chemotherapy and/or surgery]), and neurocognitive impairment. Latent class analysis with 5 indicators (employment, independent living, assistance with routine and/or personal care needs, driver's license, marital or partner status) identified classes of functional independence. Path analysis tested associations among treatment exposures, neurocognitive impairment, chronic health conditions, and functional independence. Statistical tests were 2-sided. RESULTS: Cranial radiation exposure decreased over time (51%, 1970s; 46%, 1980s; 27%, 1990s]. However, compared with siblings, survivors with any treatment exposure were at elevated risk for neurocognitive impairment, including surgery only (eg, memory: relative risk = 2.22; task efficiency: relative risk = 1.88; both P < .001). Three classes of functional independence were identified: independent (58%), moderately independent (20%), and nonindependent (22%). Cranial radiation was associated with nonindependence through impaired task efficiency (ß = 0.06), sensorimotor (ß = 0.06), and endocrine (ß = 0.10) chronic health conditions and through the associations between these conditions and task efficiency (each ß = 0.04). Sensorimotor and endocrine chronic health conditions were associated with nonindependence through memory. CONCLUSION: Most long-term glioma survivors achieve adult independence. However, functional nonindependence is associated with treatment-related neurocognitive impairment and chronic health conditions.

Lifestyle and subsequent meningioma in childhood cancer survivors: A report from the St. Jude Lifetime Cohort study.

BACKGROUND: Lifestyle is associated with meningioma risk in the general population. AIMS: We assessed longitudinal associations between lifestyle-associated factors and subsequent meningiomas in childhood cancer survivors. METHODS AND RESULTS: Childhood cancer survivors age ≥18 years in the St. Jude Lifetime Cohort Study were evaluated for body composition, self-reported physical activity, cardiopulmonary fitness, muscle strength, smoking, and alcohol consumption at baseline. Time to first meningioma analyses were performed, adjusted for sex, age at diagnosis and baseline assessment, treatment decade, and childhood cancer treatment exposures. The study included 4,072 survivors (47% female; [mean (SD)] 9 (6) years at diagnosis; 30 (8.5) years at the start of follow-up, with 7.0 (3.3) years of follow-up). 30% of the participants were survivors of acute lymphoblastic leukemia and 29% of the participants had received cranial radiation. During follow-up, 90 participants developed ≥1 meningioma, of whom 73% were survivors of acute lymphoblastic leukemia, with cranial radiation being the strongest risk factor (relative risk [RR] 29.7, 95% confidence interval [CI] 10.6-83.2). Muscle strength assessed by knee extension was associated with a lower risk of developing a meningioma in the adjusted analyses (RR 0.5, 95% CI 0.2-1.0, p = 0.04 for quartiles 3-4 vs. 1). No other lifestyle-associated variable was associated with subsequent meningioma. CONCLUSION: Independent of cranial radiation, muscle strength was associated with a lower risk of developing a subsequent meningioma in childhood cancer survivors.

Development and Evaluation of Real-Time Reverse Transcription Polymerase Chain Reaction Test for Quantitative and Qualitative Recognition of H5 Subtype of Avian Influenza Viruses.

Avian influenza viruses (AIV) affect a wide range of birds and mammals, cause severe economic damage to the poultry industry, and pose a serious threat to humans. Highly pathogenic avian influenza viruses (HPAI) H5N1 were first identified in Southeast Asia in 1996 and spread to four continents over the following years. The viruses have caused high mortality in chickens and various bird species and deadly infections in humans. Multiple conventional methods have been so far introduced for the detection and identification of avian influenza viruses. Traditional virus isolation methods are gold standard protocol in AI detection; nonetheless, virus isolation in embryonating chicken eggs (ECE) is not a rapid method for the detection of influenza viruses since it is time-consuming and labor-intensive. Furthermore, the isolation of highly pathogenic viruses, such as H5, needs BSL3 laboratories. Real-Time Reverse Transcription-Polymerase Chain Reaction (RRT-PCR) is a sensitive and specific method for the detection of influenza viruses. The application of these nucleic acid-based techniques has increased our ability to identify and perform influenza virus care programs, especially in surveillance programs. The current study aimed to detect H5 subtype of avian influenza (AI) virus using fast, specific, and sensitive TaqMan RRT-PCR. Notably, single step RRT-PCR was used to prevent possible laboratory contamination. The specificity of this test was evaluated using nucleic acid extracted from several poultry pathogenic microorganisms and negative clinical specimens from AI-uninfected birds. The sensitivity analysis of the RRT-PCR assay was performed using in vitro-transcribed RNA copy and 10-fold serial dilution of standard AI virus with specific titer. The results indicated the high sensitivity of this method and the lowest detectable dilution of this method based on RNA copies and 1:10 serial dilutions of the standard virus was 10 1.9 EID50 /100.

The impact of 18F-FDOPA-PET/MRI image fusion in detecting liver metastasis in patients with neuroendocrine tumors of the gastrointestinal tract.

BACKGROUND: This study assesses the value of image fusion using 18F-fluoro-L-DOPA (18F-DOPA) positron emission tomography (PET) and magnetic resonance imaging (MRI) for examining patients with neuroendocrine tumors (NETs) and a suspicion of metastasis of the liver. METHODS: Eleven patients (five women and six men aged between 20 and 81, with a mean age of 54.6 years) were included in the study. All patients underwent whole-body 18F-DOPA PET examinations and contrast-enhanced MRI with diffusion-weighted sequences (DWS). Image fusion was performed using a semiautomatic voxel-based algorithm. Images obtained using PET and MRI were assessed separately. Side-by-side evaluations of fused PET/MRI images were also performed. RESULTS: In total, 55 liver lesions (52 liver metastases and 3 benign lesions) were detected in the 11 patients. Sensitivity detection for liver lesions was higher when using PET/CT than when using contrast-enhanced MRI without DWSs and lower than using MRI with DWSs. The sensitivity of PET/MRI image fusion in the detection of liver metastasis was significantly higher than that of MRI with DWSs (P < 0.05). CONCLUSION: Images of the liver obtained using PET and MRI in patients with NETs exhibited characteristic features. These findings suggest that an appropriate combination of available imaging modalities can optimize patient evaluations.

Overlapping brain Community detection using Bayesian tensor decomposition.

It has been found that specific regions in the brain are dedicated to specific functions. Detection and analysis of the constituent functional networks of the brain is of great importance for understanding the brain functionality and diagnosing some neuropsychiatric illnesses. In this paper, we introduce Non-negative Tensor Factorization (NTF) methods to identify the overlapping communities in brain networks using resting-state functional Magnetic Resonance Imaging (rs-fMRI) data. Instead of taking average over a group of subjects, we use individual subject connectivity matrices to build the tensor data. Decomposed factors indicate the community membership probabilities and inter-subject variability indices modeling the community strengths over subjects. In contrast to the methods based on Non-negative Matrix Factorization (NMF) which are generally applied to the average connectivity matrices, using tensor factorization modeling preserves the information conveyed by the individual subjects. The experiments are carried out on simulated data as well as real Human Connectome Project (HCP) rs-fMRI datasets. To evaluate the effectiveness of the proposed framework, we have computed reproducibility over time and groups of subjects. Test-retest reliability is also examined through computing the intra-class correlation coefficient (ICC) index. The results show that the proposed NTF-based frameworks lead to stable and accurate results.

Development and Evaluation of Real-Time RT-PCR Test for Quantitative and Qualitative Recognition of Current H9N2 Subtype Avian Influenza Viruses in Iran.

Avian influenza H9N2 subtype viruses have had a great impact on Iranian industrial poultry production economy since introduction in the country. To approach Rapid and precise identification of this viruses as control measures in poultry industry, a real time probe base assay was developed to directly detect a specific influenza virus of H9N2 subtype -instead of general detection of Influenza A viruses- which has been endemic over two last decades in the country. An Iranian avian influenza virus strain of A/Iran/chicken/772/1998 H9N2 subtype were selected as reference strain for of primers and probe designing. The high agreement value of 99% indicated that the devolved real time assay for detection of H9 subtype viruses could easily replace the conventional method of virus isolation particularly in investigation of viruses like national surveillance plan. The limit of detection was almost one EID50 which was the least real infectious unit could be detected. So it can be said that this sensitive assay provided a powerful tool to not to miss any significant viral biological activity neither in the host body nor in the environment. A high level of correlation coefficient (R2 = 0.998) also indicated a good correlation between Ct values and viral concentrations. , it can be conclude that the real time RT-PCR could be easily replace virus isolation in detection of H9N2 influenza viruses especially in large monitoring program. The ability in quantifying of the virus concentration extends usage of test in more accurate studies.

Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer.

Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).

Enhanced osteoconductivity of polyethersulphone nanofibres loaded with bioactive glass nanoparticles in in vitro and in vivo models.

OBJECTIVES: There is growing need for new scaffold constructions for synthetic bone graft substitutes to repair large bone lesions. A very promising and important class of new implants for tissue engineering is based on three-dimensional scaffolds and bioceramics. MATERIALS AND METHODS: In this study, after investigation of mechanical properties of polyethersulphone (PES) nanofibres, fabricated by electrospinning methodology and coated with bioactive glass (BG), cells of the MG-63 line were cultured on surfaces of these scaffolds. Their capacity to support MG-63 proliferation was also investigated in vitro by MTT assay. Osteoconductivity on these scaffolds was investigated by the common osteogenic markers alkaline phosphatase (ALP) activity, calcium mineral deposition and bone-related gene activation. Next, a bone reconstruction of rat critical-size defects model was evaluated using radiographic imaging analysis (digital mammography), computed tomography and histological examination. RESULTS: In vitro results indicated that biocompatibility and osteogenic markers of MG-63 cells were significantly enhanced after coating PES with BG. Based on in vivo results, new bone formation in the defect site was enhanced in implanted rats in comparison with a control group. The highest reconstruction was observed in animals implanted with BG-coated nanofibres. CONCLUSIONS: Osteoconductivity of PES nanofibres was markedly enhanced after coating them with BG, and introduction of this construct as new bone-graft substitute for bone loss and defects is indicated.

Cereal, fruit and vegetable fibre intake and the risk of the metabolic syndrome: a prospective study in the Tehran Lipid and Glucose Study.

BACKGROUND: The present study aimed to determine whether total fibre or specific fibre food sources are associated with the incidence of the metabolic syndrome (MetS) after 3 years of follow-up in the Tehran Lipid and Glucose Study. METHODS: This population-based prospective study, conducted within the framework of the Tehran Lipid and Glucose Study, included 1582 adults, who were aged 19-84 years and free of MetS at baseline. Usual dietary fibre intake was assessed at baseline using a 168-item food frequency questionnaire. Anthropometrics, blood pressure, and fasting blood glucose and lipid profiles were measured at baseline and 3 years later. The MetS was defined according to the definition of the revised Adult treatment Panel III. RESULTS: During the 3-year follow-up, there was 15.2% incidence of MetS. Among sources of dietary fibre, fruit fibre was significantly and inversely associated with the occurrence of MetS, after adjustment for confounding factors, with a 21% lower risk [odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.60-0.97] in the highest tertile of intake compared to the lowest tertile. Subjects in the highest tertile of cereal fibre intake had lower odds of MetS compared to those in the lowest tertile (OR = 0.73, 95% CI = 0.52- 0.97) and this association disappeared after adjustment for confounders. No significant association was found between intakes of vegetables, legumes and nut fibre with the incidence of MetS. CONCLUSIONS: Among specific fibre food sources, fruit fibre had a protective effect against the risk of MetS.

Two-year experience of orthotopic liver transplantation in afzalipoor hospital, kerman, southeastern iran.

BACKGROUND: End-stage liver diseases are common in Iran. The only therapeutic option for these patients is liver transplantation. OBJECTIVE: To present our 2-year experience of liver transplantations in Afzalipoor Hospital, Kerman, southeastern Iran. METHODS: From November 2009 to September 2011, 12 patients underwent orthotopic liver transplantation in our center. Their data including demographics, indications for transplantation, MELD scores, post-operative complications and their management were collected. RESULTS: Patients (7 women and 5 men) aged between 14 and 55 years. Indications for the transplantation included HBV infection (n=5), cryptogenic cirrhosis (n=2), Wilson's disease, alcoholism (n=1), HCV infection (n=1), Budd-Chiari syndrome (n=1), and autoimmune hepatitis (n=1). MELD score of patients ranged from 16 to 30. All patients received tacrolimus, mycophenolate mofetile and corticosteroid, postoperatively. 2 patients died of pulmonary and intra-abdominal infections with resultant to multiple organ failure. Nonfunctioning of transplanted liver and ongoing bleeding resulted in death in another patients. 9 patients are well doing and have excellent liver functions. CONCLUSION: We had relatively successful results in our experience of orthotopic liver transplantation. Vicinity of our center to Shiraz Transplant Center would be an important factor in this success.

Secretory expression and purification of a soluble NADH cytochrome b5 reductase enzyme from Mucor racemosus in Pichia pastoris based on codon usage adaptation.

The genome of Mucor racemosus was analyzed to determine the relative levels of codon usage. The codon bias differed from that of Escherichia coli. The active, soluble isoform of NADH cytochrome b5 reductase containing 228 amino acids was successfully overexpressed and secreted using alpha factor in Pichia pastoris under the control of the alcohol oxidase promoter and finally purified. The culture medium and incubation time were optimized, and the maximum expression level observed was about 23 U/ml using X-33 recombinant yeast grown for 120 h with 0.5% (v/v) methanol in complex media.

Amyloid PET and MRI in Alzheimer's disease and mild cognitive impairment.

The neurodegenerative disorder Alzheimer's disease (AD) is the most common form of dementia. It is characterized by progressive impairment of cognitive functions and behavior. To distinguish clinically AD from other forms of dementia is an ongoing challenge. In addition, although mild cognitive impairment (MCI) is recognized as a risk factor for dementia, it remains a challenge to predict on an individual level who will convert to become demented. Amyloid beta (Abeta) is one of the crucial pathological findings in AD. Recently, amyloid tracers for PET imaging have been developed successfully which may offer the unique possibility for measuring fibrillar Abeta load in the living brain. Therefore, in the near future positron emission tomography (PET) may become an important tool for in vivo amyloid imaging contributing to early (differential) diagnosis as well as evaluation of treatment response in AD. Moreover, Abeta may play a role in prediction the conversion of MCI to AD. In this paper we review the recent development of the molecular imaging technique PET and its different radiopharmaceuticals on the trail for imaging amyloid in AD and the conversion of MCI to AD.

Case report: Gluteal injection site granulomas: false positive finding on FDG-PET in patients with non-small cell lung cancer.

Positron-emission-tomography (PET) with fludeoxyglucose F-18 ([(18)F] fluoro-2-deoxy-D-glucose, FDG) has become an established imaging modality in patients with lung cancer for mediastinal lymph node staging and the detection of extrathoracic metastases. However, tracer accumulations are not limited to malignant tissue but are also found in muscles and benign inflammatory processes. We report on two patients with lung cancer in whom FDG-PET revealed suspicious tracer accumulations in the buttock. Ultrasound (US) revealed a hyperechogenic nodule with poorly defined margins in both patients. On specific inquiry both patients reported on repeated "intramuscular" gluteal injections. Histology after US guided biopsy showed an accumulation of macrophages within fibrous tissue, compatible with injection site granulomas. The reported cases underline that (18)F-FDG may accumulate in benign, ancillary processes that have to be distinguished from distant metastases. Tracer accumulation in the buttocks may be highly suggestive of injection site granulomas, especially if the patient reports on "intramuscular" injections. In this setting, US is a widely available modality to distinguish metastasis from adipose tissue necrosis.

New approaches in nuclear medicine for early diagnosis of Alzheimer's disease.

Dementia, Alzheimer's disease (AD) being the most common cause of it, is a major and growing medical and social problem, particularly in the advanced age, with the highest rate in the population over 75 y. Recent sophisticated therapeutic measures require more sensitive diagnostic tests to recognize early stages of the disease. In this paper, the current neuronuclear imaging literature is reviewed with regard to early and differential diagnosis of dementia. Functional imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET) could provide the clinician with additional information complementary to morphological assessments, thus contributing to achieve a more adequate diagnosis, and also with information regarding prodromal stages of AD.

Expression of somatostatin receptors in inflammatory lesions and diagnostic value of somatostatin receptor scintigraphy in patients with ANCA-associated small vessel vasculitis.

OBJECTIVE: To assess the usefulness of somatostatin receptor (SSTR) scintigraphy for the evaluation of disease activity in the upper and lower respiratory tract in ANCA-associated vasculitis (AASV). METHODS: Thirty-two consecutive patients with AASV were subjected to SSTR scintigraphy as part of their initial diagnostic evaluation and follow-up. The presence of SSTRs in inflammatory lesions was evaluated with immunohistochemistry in selected cases. RESULTS: In AASV, specificity of SSTR scintigraphy for active vs non-active disease was 96% for pulmonary disease and 100% for ear, nose and throat (ENT) involvement, while sensitivity was 86% and 68%, respectively. Absence of previously present tracer accumulation characterized treatment responders, and treatment resistance was reflected by repeated positive scintigraphy. We could demonstrate the expression of SSTRs in lung and mucosal biopsies obtained from patients with active Wegener's granulomatosis and with microscopic polyangiitis. CONCLUSION: SSTR scintigraphy is useful for the assessment of AASV, indicating disease activity, disease extent and treatment efficacy. SSTRs are expressed in both granulomatous as well as non-granulomatous AASV.

Metabolic impairment of brain metabolism in patients with Lewy body dementia.

A reliable assessment of dementia is essential for a differentiated treatment. Recent studies have demonstrated a poor accuracy of clinical criteria for diagnosis of Lewy body dementia. Diffuse Lewy body disease (LBD) is the second most common cause of senile degenerative dementia and is characterized histologically by the occurrence of Lewy bodies in allocortical, neocortical and subcortical structures. Seven male patients (mean age 81 years) with clinically suspected diffuse LBD were investigated with 18F-fluorodeoxyglucose (FDG)-PET using a Siemens ECAT-ART PET-scanner. The 18F-FDG-PET showed a diffuse glucose hypometabolism in the entire cerebral cortex with relative sparing of the primary sensory-motor cortex in all patients. This diffuse metabolic impairment in the entire cortex with relative sparing of central region seems to be a typical pattern for LBD, distinct from Alzheimer's disease.

[New design concept to improve medical application software]. / Neues Design-Konzept zur Verbesserung der medizinischen Anwendersoftware.

Up to now, there has been no software model available that adequately addresses the growing importance of flexibility in using different information tools. Based on Java, Jini technology provides distributed and therefore robust software architecture. In case of an application crash, Jini is able to minimize the damage by adding functions that reverse the effects of the crash. Owing to increasing user mobility, it is necessary to be able to receive location-independent information. The growing use of powerful telecommunications suggests the application of 'wireless application protocol' (WAP) mobile telephones also for medical purposes. This paper presents the application of these new software trends (Jini and wireless application protocol).