Communication patterns in families affected by parental cancer from the healthy parents' perspective-process evaluation of the complex intervention Family-SCOUT.

PURPOSE: Within families affected by parental cancer, open communication impacts the well-being of parents and their children; however, limited research exists on communication patterns in these families. This sub-study addresses this through the Family-SCOUT study, a multicenter, prospective, interventional, and non-randomized investigation with intervention (IG) and control group (CG). The purpose of this sub-study was to identify and compare the differences in communication patterns between the IG and CG as part of the process evaluation. The research question was addressed in both groups: What communication patterns do healthy parents perceive within their families? METHODS: Using a qualitative approach, the study involved interviewing healthy parents as surrogates for their families. The interviews were audio-recorded, transcribed, and coded using a template analysis. The resulting data were analyzed at the group level. RESULTS: Twenty-three interviews were conducted in the IG and 27 interviews in the CG. The analysis of themes centered on communication patterns as seen in the family structure. Both groups exhibited instances of open communication about fears and wishes as well as the use of child-friendly language when discussing cancer. Notable differences were observed: challenges in open communication with children were sorely reported in CG interviews, and "the illness is discussed when necessary" was sorely described in IG interviews. CONCLUSION: This study underscores the need to address and encourage open communication within families with parental cancer.

Effectiveness of a comprehensive support program for families with parental cancer (Family-SCOUT): results of a multicenter non-randomized controlled trial.

BACKGROUND: Cancer patients with minor children but also their families suffer from significant psychological distress and comorbidity. Protective factors predicting successful coping are well known. Corresponding systematic interventions are rare and limited by access barriers. We developed a comprehensive family-centered intervention for cancer patients with at least one dependent minor. PATIENTS AND METHODS: Family-SCOUT represents a multicentric, prospective, interventional, and controlled study for families with parental cancer and their minor children. In the intervention group (IG), all family members were addressed using a care and case management approach for nine months. Families in the control group (CG) received standard of care. Participating parents were asked to complete the Hospital-Anxiety-Depression-Scale (HADS) questionnaire at enrolment (T0) and after 9 months (T2). The primary outcome was a clinically relevant reduction of distress in at least one parent per family, measured as minimal important difference (MID) of ≥1.6 in the HADS total score. The percentage of families achieving MID is compared between the IG and CG by exact Fisher's test, followed by multivariate confounder analyses. RESULTS: T0-questionnaire of at least one parent was available for 424 of 472 participating families, T2-questionnaire after 9 months was available for 331 families (IG n = 175, CG n = 156). At baseline, both parents showed high levels of distress (HADS total: sick parents IG: 18.7 ± 8.1; CG: 16.0 ± 7.2; healthy partners: IG: 19.1 ± 7.9; CG: 15.2 ± 7.7). The intervention was associated with a significant reduction in parental distress in the IG (MID 70.4% in at least one parent) compared with the CG (MID 55.8%; P = 0.008). Adjustment for group differences from specific confounders retained significance (P = 0.047). Bias from other confounders cannot be excluded. CONCLUSIONS: Parental cancer leads to a high psychosocial burden in affected families. Significant distress reduction can be achieved through an optimized and structured care approach directed at the family level such as family-SCOUT.

Olfactory Bulb Signal Abnormality in Patients with COVID-19 Who Present with Neurologic Symptoms.

BACKGROUND AND PURPOSE: Unique among the acute neurologic manifestations of Severe Acute Respiratory Syndrome coronavirus 2, the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, is chemosensory dysfunction (anosmia or dysgeusia), which can be seen in patients who are otherwise oligosymptomatic or even asymptomatic. The purpose of this study was to determine if there is imaging evidence of olfactory apparatus pathology in patients with COVID-19 and neurologic symptoms. MATERIALS AND METHODS: A retrospective case-control study compared the olfactory bulb and olfactory tract signal intensity on thin-section T2WI and postcontrast 3D T2 FLAIR images in patients with COVID-19 and neurologic symptoms, and age-matched controls imaged for olfactory dysfunction. RESULTS: There was a significant difference in normalized olfactory bulb T2 FLAIR signal intensity between the patients with COVID-19 and the controls with anosmia (P = .003). Four of 12 patients with COVID-19 demonstrated intraneural T2 signal hyperintensity on postcontrast 3D T2 FLAIR compared with none of the 12 patients among the controls with anosmia (P = .028). CONCLUSIONS: Olfactory bulb 3D T2 FLAIR signal intensity was greater in the patients with COVID-19 and neurologic symptoms compared with an age-matched control group with olfactory dysfunction, and this was qualitatively apparent in 4 of 12 patients with COVID-19. Analysis of these preliminary finding suggests that olfactory apparatus vulnerability to COVID-19 might be supported on conventional neuroimaging and may serve as a noninvasive biomarker of infection.

MRI Features of Histologically Diagnosed Supratentorial Primitive Neuroectodermal Tumors and Pineoblastomas in Correlation with Molecular Diagnoses and Outcomes: A Report from the Children's Oncology Group ACNS0332 Trial.

BACKGROUND AND PURPOSE: Supratentorial primitive neuroectodermal tumors and pineoblastomas have traditionally been grouped together for treatment purposes. Molecular profiling of these tumors has revealed a number of distinct entities and has led to the term "CNS-primitive neuroectodermal tumors" being removed from the 2016 World Health Organization classification. The purpose of this study was to describe the MR imaging findings of histologically diagnosed primitive neuroectodermal tumors and pineoblastomas and correlate them with molecular diagnoses and outcomes. MATERIALS AND METHODS: Histologically diagnosed primitive neuroectodermal tumors and pineoblastomas were enrolled in this Children's Oncology Group Phase III trial, and molecular classification was retrospectively completed using DNA methylation profiling. MR imaging features were systematically studied and correlated with molecular diagnoses and survival. RESULTS: Of the 85 patients enrolled, 56 met the inclusion criteria, in whom 28 tumors were in pineal and 28 in nonpineal locations. Methylation profiling revealed a variety of diagnoses, including pineoblastomas (n = 27), high-grade gliomas (n = 17), embryonal tumors (n = 7), atypical teratoid/rhabdoid tumors (n = 3), and ependymomas (n = 2). Thus, 39% overall and 71% of nonpineal tumor diagnoses were discrepant with histopathology. Tumor location, size, margins, and edema were predictors of embryonal-versus-nonembryonal tumors. Larger size and ill-defined margins correlated with poor event-free survival, while metastatic disease by MR imaging did not. CONCLUSIONS: In nonpineal locations, only a minority of histologically diagnosed primitive neuroectodermal tumors are embryonal tumors; therefore, high-grade glioma or ependymoma should be high on the radiographic differential. An understanding of molecularly defined tumor entities and their relative frequencies and locations will help the radiologist make more accurate predictions of the tumor types.

Comparative Prey Spectra Analyses on the Endangered Aquatic Carnivorous Waterwheel Plant (Aldrovanda vesiculosa, Droseraceae) at Several Naturalized Microsites in the Czech Republic and Germany.

The critically endangered carnivorous waterwheel plant (Aldrovanda vesiculosa, Droseraceae) possesses underwater snap traps for capturing small aquatic animals, but knowledge on the exact prey species is limited. Such information would be essential for continuing ecological research, drawing conclusions regarding trapping efficiency and trap evolution, and eventually, for conservation. Therefore, we performed comparative trap size measurements and snapshot prey analyses at seven Czech and one German naturalized microsites on plants originating from at least two different populations. One Czech site was sampled twice during 2017. We recorded seven main prey taxonomic groups, that is, Cladocera, Copepoda, Ostracoda, Ephemeroptera, Nematocera, Hydrachnidia, and Pulmonata. In total, we recorded 43 different prey taxa in 445 prey-filled traps, containing in sum 461 prey items. With one exception, prey spectra did not correlate with site conditions (e.g. water depth) or trap size. Our data indicate that A. vesiculosa shows no prey specificity but catches opportunistically, independent of prey species, prey mobility mode (swimming or substrate-bound), and speed of movement. Even in cases where the prey size exceeded trap size, successful capture was accomplished by clamping the animal between the traps' lobes. As we found a wide prey range that was attracted, it appears unlikely that the capture is enhanced by specialized chemical- or mimicry-based attraction mechanisms. However, for animals seeking shelter, a place to rest, or a substrate to graze on, A. vesiculosa may indirectly attract prey organisms in the vicinity, whereas other prey capture events (like that of comparably large notonectids) may also be purely coincidental.

Brain Region-Specific Degeneration with Disease Progression in Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2 Disease).

BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene. Our hypothesis was that regional analysis of cortical brain degeneration may identify brain regions that are affected earliest and most severely by the disease. MATERIALS AND METHODS: Fifty-two high-resolution 3T MR imaging datasets were prospectively acquired on 38 subjects with CLN2. A retrospective cohort of 52 disease-free children served as a control population. The FreeSurfer software suite was used for calculation of cortical thickness. RESULTS: An increased rate of global cortical thinning in CLN2 versus control subjects was the primary finding in this study. Three distinct patterns were observed across brain regions. In the first, subjects with CLN2 exhibited differing rates of cortical thinning versus age. This was true in 22 and 26 of 34 regions in the left and right hemispheres, respectively, and was also clearly discernable when considering brain lobes as a whole and Brodmann regions. The second pattern exhibited a difference in thickness from healthy controls but with no discernable change with age (9 left hemispheres, 5 right hemispheres). In the third pattern, there was no difference in either the rate of cortical thinning or the mean cortical thickness between groups (3 left hemispheres, 3 right hemispheres). CONCLUSIONS: This study demonstrates that CLN2 causes differential rates of degeneration across the brain. Anatomic and functional regions that degenerate sooner and more severely than others compared with those in healthy controls may offer targets for directed therapies. The information gained may also provide neurobiologic insights regarding the mechanisms underlying disease progression.

Environmental impact assessment of radionuclide and metal contamination at the former U sites Taboshar and Digmai, Tajikistan.

Uranium (U) ore mining and processing were initiated in the former Soviet Republics of Tajikistan after the Second World War as part of the USSR nuclear weapon programme. The U mine in Taboshar was opened in 1936, and mining took place from 1945 to 1965, while the Digmai tailings dump was exploited during 1963-1993. The mining, milling and extraction activities have resulted in large amounts of waste rock deposits and U tailing materials placed in the vicinity of inhabited areas. To assess the environmental impact of radionuclides and trace metals in the Taboshar and Digmai mining and tailing sites in Tajikistan, field expeditions were performed in 2006 and 2008. In addition to in situ gamma and radon dose rate measurements, sampling of water, fish, sediments, soils and vegetation including in situ fractionation of water were performed. The U concentrations in water from Taboshar Pit Lake (2.0 mg U/L) were higher than in waters collected in the Digmai area. The Pit Lake and the stream water from the tailing mountain were also characterised by elevated concentrations of As, Mo, Mn and Fe, exceeding the WHO recommended values for drinking water. Uranium, As, Mo and Ni were present as low molecular mass species in the waters, and are therefore considered mobile and potentially bioavailable. The (238)U concentrations in sediments and soils varied between the sites; with peak concentrations (6 kBq/kg dw) in sediments from the Pit Lake, while the soil concentrations were significantly lower (296-590 Bq/kg dw). In contrast, high levels of the radium isotopes ((226)Ra and (228)Ra) were found in the Digmai soil (17-32 kBq/kg dw). Based on sequential extraction results, both U and Pb were found to be quite mobile at the Pit Lake site, showing that these elements were associated with the pH sensitive and redox sensitive amorphous fractions. In tailings, U was found to be quite mobile, but here Pb was rather inert. The transfer of radionuclides and metals from sediments to waters was in general low. In the Pit Lake, U was quite mobile (Kd = 90 L/kg), followed by Ni (1.5 × 10(3) L/kg) and As (6 × 10(3) L/kg), Cu and Cd (1.5 × 10(4) L/kg), while Pb (3 × 10(5) L/kg) was rather inert. The transfer from soil to plant, TFs (kg/kg dw), was in general low, while the bioconcentration factor for water living Poaceae and for fish from water was relatively high (Pb 1.8 × 10(5) and Cd 1 × 10(4)). These legacy sites, containing enhanced levels of natural radioactive material (TENORM) as well as heavy metals, may represent a hazard having a potential radiological and chemical impact on man and the environment, and measures should be taken to reduce the environmental risk to man and biota.

Uranium activity ratio in water and fish from pit lakes in Kurday, Kazakhstan and Taboshar, Tajikistan.

Kurday in Kazhakstan and Taboshar in Tajikistan were U mining sites operated during the 1950s and 1960s as part of the USSR nuclear weapon program. Today, they represent sources of potential U contamination of the environment. Within both mining sites, open pits from which U ore was extracted have been filled with water due to ground water inflow and precipitation. These artificial pit lakes contain fish consumed occasionally by the local people, and wild and domestic animals are using the water for drinking purposes. To assess the potential impact from U in these pit lakes, field work was performed in 2006 in Kurday and 2006 and 2008 in Taboshar. Results show that the U concentration in the lake waters were relatively high, about 1 mg/L in Kurday Pit Lake and about 3 mg/L in Taboshar Pit Lake. The influence of U-bearing materials on the lakes and downstream waters were investigated by measuring the U concentration and the (234)U/(238)U activity ratios. In both Kurday and Taboshar, the ratios increased distinctively from about 1 at the pit lakes to >1.5 far downstream the lakes. The concentrations of (238)U in gill, liver, muscle and bones in fish from the pit lakes were much higher than in the reference fish. Peak concentration of U was seen in bones (13 mg/kg w.w.), kidney (9.1 mg/kg w.w.) and gills (8.9 mg/kg w.w.) from Cyprinus auratus caught in the Taboshar Pit Lake. Bioconcentration factors (BCF) calculated for organs from fish caught in the Taboshar Pit Lake, with the same tendency seen in the Kurday Pit Lake, showed that U accumulates most in bone (BCF = 4.8 L/kg w.w.), gills (BCF = 3.6 L/kg w.w.), kidney (BCF = 3.6 L/kg w.w.), and liver (BCF = 2.5 L/kg w.w.), while least was accumulated in the muscle (BCF = 0.12 L/kg w.w.).

Po-210 and Pb-210 in water and fish from Taboshar uranium mining Pit Lake, Tajikistan.

Polonium-210 in water and (210)Pb and (210)Po in different fish organs from 3 different fish species in Taboshar Pit Lake (n = 13), located in the uranium mining area in Tajikistan, and in Kairakkum Reservoir (reference lake, n = 3), have been determined as part of a Joint project between Norway, Kazakhstan, Kyrgyzstan and Tajikistan. The average activity concentration of (210)Pb and (210)Po in liver, muscle and bone of Carassius auratus was higher than the concentration in similar tissues of C. carpio and Sander lucioperca from the reference site. The accumulation of (210)Po was higher than for (210)Pb, and the accumulation of (210)Po was highest in the liver of C. auratus (3673 ± 434 Bq kg(-1) ww). Although the average activity concentration of (210)Pb in liver and bones of C. auratus from Pit Lake were fairly similar, a huge variation in the liver activity concentrations (25-327 Bq kg(-1) ww) was found. The results confirm direct uptake of unsupported (210)Po into the liver, and that the distributions of (210)Po and (210)Pb in fish organs were different. The BCF (L/kg) for (210)Po in bone, liver and muscle clearly demonstrates high accumulation of (210)Po in C. auratus, especially in the liver. The average BCFs of liver, bone and muscle were >1.4 × 10(5), >2.5 × 10(4) and >1.4 × 10(4), respectively. All fish in the Pit Lake were found to be in the same trophic level, however, a linear correlation between log (210)Po in liver and δ(15)N could indicate biomagnification of (210)Po in liver of C. auratus. In regards to the recommended Annual Limit of Intake (ALI) for (210)Po, the concentration of (210)Po in muscle tissues of C. auratus is alarming, as there is a high probability for the local population at risk to exceed the recommended ALI through consumption of fish from Taboshar Pit Lake.

Assessment of disease severity in late infantile neuronal ceroid lipofuscinosis using multiparametric MR imaging.

BACKGROUND AND PURPOSE: LINCL is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene that encodes for tripeptidyl peptidase 1, a lysosomal enzyme necessary for the degradation of products of cellular metabolism. With the goal of developing quantitative noninvasive imaging biomarkers sensitive to disease progression, we evaluated a 5-component MR imaging metric and tested its correlation with a clinically derived disease-severity score. MATERIALS AND METHODS: MR imaging parameters were measured across the brain, including quantitative measures of the ADC, FA, nuclear spin-spin relaxation times (T2), volume percentage of CSF (%CSF), and NAA/Cr ratios. Thirty MR imaging datasets were prospectively acquired from 23 subjects with LINCL (2.5-8.4 years of age; 8 male/15 female). Whole-brain histograms were created, and the mode and mean values of the histograms were used to characterize disease severity. RESULTS: Correlation of single MR imaging parameters against the clinical disease-severity scale yielded linear regressions with R2 ranging from 0.25 to 0.70. Combinations of the 5 biomarkers were evaluated by using PCA. The best combination included ADC, %CSF, and NAA/Cr (R2=0.76, P<.001). CONCLUSIONS: The multiparametric disease-severity score obtained from the combination of ADC, %CSF, and NAA/Cr whole-brain MR imaging techniques provided a robust measure of disease severity, which may be useful in clinical therapeutic trials of LINCL in which an objective assessment of therapeutic response is desired.

Differential diagnosis of normal pressure hydrocephalus by MRI mean diffusivity histogram analysis.

BACKGROUND AND PURPOSE: Accurate diagnosis of normal pressure hydrocephalus is challenging because the clinical symptoms and radiographic appearance of NPH often overlap those of other conditions, including age-related neurodegenerative disorders such as Alzheimer and Parkinson diseases. We hypothesized that radiologic differences between NPH and AD/PD can be characterized by a robust and objective MR imaging DTI technique that does not require intersubject image registration or operator-defined regions of interest, thus avoiding many pitfalls common in DTI methods. MATERIALS AND METHODS: We collected 3T DTI data from 15 patients with probable NPH and 25 controls with AD, PD, or dementia with Lewy bodies. We developed a parametric model for the shape of intracranial mean diffusivity histograms that separates brain and ventricular components from a third component composed mostly of partial volume voxels. To accurately fit the shape of the third component, we constructed a parametric function named the generalized Voss-Dyke function. We then examined the use of the fitting parameters for the differential diagnosis of NPH from AD, PD, and DLB. RESULTS: Using parameters for the MD histogram shape, we distinguished clinically probable NPH from the 3 other disorders with 86% sensitivity and 96% specificity. The technique yielded 86% sensitivity and 88% specificity when differentiating NPH from AD only. CONCLUSIONS: An adequate parametric model for the shape of intracranial MD histograms can distinguish NPH from AD, PD, or DLB with high sensitivity and specificity.

Acute and sub-lethal effects in juvenile Atlantic salmon exposed to low µg/L concentrations of Ag nanoparticles.

Silver nanoparticles (Ag-NP) are components in numerous commercial products and are discharged into the environment in quantities that are largely unknown. In the present study, juvenile Atlantic salmon were exposed to 1, 20, and 100 µg/L (48 h, static renewal) of a commercially available Ag-NP colloidal suspension in natural (soft) lake water. A solution of AgNO(3) containing 20 µg/L Ag(I) ions was also included to discriminate the effect of NPs from that of ionic silver. Furthermore, the commercial Ag-NP suspension was compared to an in-house synthesised colloidal NP suspension prepared from AgNO(3) and NaBH(4) in citrate buffer. The size distribution of Ag in all exposure solutions was characterised by 0.22 µm filtration and 10 kDa hollow fibre cross-flow ultrafiltration in combination with ICP-MS. All exposures were characterised by a relatively high proportion of Ag-NP in the colloidal size fraction 3-220 nm. For assessment of biological effects, acute toxicity, gill histopathology, blood plasma parameters (Na, Cl, glucose, haemoglobin), and gene expression of a selection of gill biomarkers were measured. Results showed that the gills accumulated Ag in all exposure groups apart from the fish exposed to 1 µg/L Ag-NP. Accumulated Ag caused concentration-dependent response increases in general stress markers such as plasma glucose and gill gene expression of heat shock protein 70. Furthermore, induction of the metallothionein A gene indicated that Ag had been internalized in the gills, whereas a concentration-dependant inhibition of Na/K ATPase expression indicated impaired osmoregulation at as low as 20 µg/L concentrations of Ag-NP. The commercial Ag-NP suspension caused acute gill lamellae necrosis at high concentrations (100 µg/L), potentially giving rise to the substantial (73%) fish mortality at this concentration. The two different Ag-NP preparations gave comparable results for several endpoints measured, but differed in MT-A induction and mortality, thus emphasising the variation in effects that may arise from different Ag-NP preparations.

Using quantitative CT perfusion for evaluation of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH leading to permanent neurologic deficits, infarction, and death. Our aim was to prospectively evaluate the diagnostic accuracy of CTP and to determine a quantitative threshold for DCI in aneurysmal SAH. MATERIALS AND METHODS: Patients with SAH were prospectively enrolled in a protocol approved by the institutional review board. CTP was performed during the typical time period for DCI, between days 6 and 8 following SAH. Quantitative CBF, CBV, and MTT values were obtained by using standard region-of-interest placement sampling of gray matter. The reference standard for DCI is controversial and consisted of clinical and imaging criteria in this study. In a subanalysis of vasospasm, DSA was used as the reference standard. ROC curves determined the diagnostic accuracy by using AUC. Optimal threshold values were calculated by using the patient population utility method. RESULTS: Ninety-seven patients were included; 41% (40/97) had DCI. Overall diagnostic accuracy was 93% for CBF, 88% for MTT, and 72% for CBV. Optimal threshold values were 35 mL/100 g/min (90% sensitivity, 68% specificity) for CBF and 5.5 seconds (73% sensitivity, 79% specificity) for MTT. In the subanalysis (n = 57), 63% (36/57) had vasospasm. Overall diagnostic accuracy was 94% for CBF, 85% for MTT, and 72% for CBV. Optimal threshold values were 36.5 mL/100 g/min (95% sensitivity, 70% specificity) for CBF and 5.4 seconds (78% sensitivity, 70% specificity) for MTT. CONCLUSIONS: CBF and MTT have the highest overall diagnostic accuracy. Threshold values of 35 mL/100 g/min for CBF and 5.5-second MTT are suggested for DCI on the basis of the patient population utility method. Absolute threshold values may not be generalizable due to differences in scanner equipment and postprocessing methods.

Arterial spin labeling and altered cerebral blood flow patterns in the minimally conscious state.

OBJECTIVE: To use arterial spin labeling (ASL) to compare cerebral blood flow (CBF) patterns in minimally conscious state (MCS) patients with those in normal controls in an observational study design. METHODS: Subjects meeting MCS criteria and normal controls were identified. A pseudocontinuous ASL sequence was performed with subjects and controls in the resting awake state. Multiple CBF values for 10 predetermined regions of interest were sampled and average CBF was calculated and compared between controls and subjects. RESULTS: Ten normal controls were identified, with ages ranging from 26 to 54 years. Four subjects met the MCS criteria and received an ASL study, with one patient receiving a second study at a later date. Subjects ranged in age from 19 to 58 years and had traumatic brain injury, stroke, or hypoxic-ischemic encephalopathy. Regional CBF for controls ranged from 21.6 to 57.2 mL/100 g/min, with a pattern of relatively increased blood flow posteriorly including the posterior cingulate, parietal, and occipital cortices. CBF patterns for MCS subjects showed greater variability (from 7.7 to 33.1 mL/100 g/min), demonstrating globally decreased CBF in gray matter compared with that in normal controls, especially in the medial prefrontal and midfrontal regions. In the one subject studied longitudinally, global CBF values increased over time, which correlated with clinical improvement. CONCLUSIONS: We identified globally decreased CBF and a selective reduction of CBF within the medial prefrontal and midfrontal cortical regions as well as gray matter in MCS patients. ASL may serve as an adjunctive method to assess functional reserve in patients recovering from severe brain injuries.

Effects of combined gamma-irradiation and metal (Al+Cd) exposures in Atlantic salmon (Salmo salar L.).

These experiments were designed to investigate transcriptional effects in Atlantic salmon (Salmo salar) after exposure in vivo to ionizing gamma radiation combined with subtoxic levels of aluminum (Al) and cadmium (Cd). Juvenile fish (35 g) in freshwater with or without Al and Cd (255 microg Al/L + 6 microg Cd/L) were exposed to a 75 mGy dose of gamma-irradiation, and induced responses were compared to those of controls. The transcriptional levels of eight genes encoding proteins known to respond to stress in fish were quantified in liver of fish exposed for 5 h to gamma radiation, to Al and Cd or to the combination of Al, Cd and gamma radiation. The studied genes were caspase 3B, caspase 6A, caspase 7, p53 (apoptosis), glutathione reductase (GR), phospholipid hydroperoxide glutathione peroxidase (GSH-Px), (oxidative stress), metallothionein (MT-A) (metal stress) and ubiquitin (Ubi) (protein degradation). The results showed that gamma-irradiation alone induced significant upregulation of caspase 6A, GR, GSH-Px, MT-A and Ubi compared to the control group, while 5 h exposure to Al+Cd alone did not induce any of the studied genes compared to the control. No significant upregulation of the series of investigated genes could be observed in fish exposed to gamma-irradiation in combination with Al+Cl. In conclusion, the results suggest that the presence of Al+Cd in the water counteracted the gamma-irradiation effect by modifying the transcription of genes encoding proteins involved in the defense mechanisms against free radicals in the cells.

Environmentally relevant mixed exposures to radiation and heavy metals induce measurable stress responses in Atlantic salmon.

These experiments were designed to identify stress effects in 3 key organs in Atlantic Salmon (Salmo salar, L.) after exposure in vivo to very low doses of radiation, and subtoxic levels of aluminum (Al) and cadmium (Cd) alone or in combination. Six fish per group were sacrificed after exposure and the anterior kidney, fin, and gill were dissected and sentfor assay of bystander signal production as a stress response end point. Radiation doses as low as 4 mGy delivered over 5 h, alone or in combination with Cd and/or Al, caused bystander signals to be produced in tissues harvested from in vivo exposed salmon. The effects vary among different organs and are not consistently additive or synergistic for a given treatment although gill cells do show high degrees of synergism between radiation and metal exposure. Data for individual fish did not suggest any systemic sensitivity to the stressors. Interestingly, the data for Cd suggest that lower toxicity is found when the metal is used in combination with radiation exposure. Expression of two proteins associated with survival responses (Bcl-2) or death responses (cmyc) after radiation was measured in the tissue cultures and showed a highly significant correlation with response outcome. The results, although complex, indicate that these stress signal responses may aid in the mechanistic investigation of mixed contaminant effects in fish exposed to metals and radiation.

Accurate localization of brain activity in presurgical FMRI by structure adaptive smoothing.

An important problem of the analysis of functional magnetic resonance imaging (fMRI) experiments is to achieve some noise reduction of the data without blurring the shape of the activation areas. As a novel solution to this problem, recently the propagation-separation (PS) approach has been proposed. PS is a structure adaptive smoothing method that adapts to different shapes of activation areas. In this paper, we demonstrate how this method results in a more accurate localization of brain activity. First, it is shown in numerical simulations that PS is superior over Gaussian smoothing with respect to the accurate description of the shape of activation clusters and results in less false detections. Second, in a study of 37 presurgical planning cases we found that PS and Gaussian smoothing often yield different results, and we present examples showing aspects of the superiority of PS as applied to presurgical planning.

Neurological deterioration in late infantile neuronal ceroid lipofuscinosis.

BACKGROUND: Late infantile neuronal ceroid lipofuscinosis (LINCL) is associated with progressive degeneration of the brain and retina starting in early childhood. METHODS: Thirty-two individual neurologic, ophthalmologic, and CNS imaging (MRI and MRS) assessments of 18 children with LINCL were analyzed. Disease severity was followed by two rating scales, one previously established but modified to solely assess the brain and exclude the retinal disease (modified Hamburg LINCL scale), and a newly developed scale, with expanded evaluation of the CNS impairment (Weill Cornell LINCL scale). RESULTS: For the 18 children, the Weill Cornell scale yielded a closer correlation with both age and time since initial clinical manifestation of the disease than did the modified Hamburg scale. There were no significant differences as a function of age or time since initial manifestation of the disease in the rating scales among the most frequent CLN2 mutations (G3556C, 56% of all alleles or C3670T, 22% of all alleles). Measurements of cortical MRS N-acetyl-aspartate content, MRI ventricular, gray matter and white matter volume, and cortical apparent diffusion coefficient correlated to a variable degree with the age of the children and the time since initial clinical manifestation of the disease. All imaging measurements correlated better with the Weill Cornell CNS scale compared to the modified Hamburg LINCL scale. CONCLUSION: The data suggest that the Weill Cornell late infantile neuronal ceroid lipofuscinosis (LINCL) scale, together with several of the MRI measurements, may be useful in the assessment of severity and progression of LINCL and for the evaluation of novel therapeutic strategies.

Assessing disease severity in late infantile neuronal ceroid lipofuscinosis using quantitative MR diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (LINCL), a form of Batten disease, is a fatal neurodegenerative genetic disorder, diagnosed via DNA testing, that affects approximately 200 children in the United States at any one time. This study was conducted to evaluate whether quantitative data derived by diffusion-weighted MR imaging (DWI) techniques can supplement clinical disability scale information to provide a quantitative estimate of neurodegeneration, as well as disease progression and severity. MATERIALS AND METHODS: This study prospectively analyzed 32 DWI examinations from 18 patients having confirmed LINCL at various stages of disease. A whole-brain apparent diffusion coefficient (ADC) histogram was fitted with a dual Gaussian function combined with a function designed to model voxels containing a partial volume fraction of brain parenchyma versus CSF. Previously published whole-brain ADC values of age-matched control subjects were compared with those of the LINCL patients. Correlations were tested between the peak ADC of the fitted histogram and patient age, disease severity, and a CNS disability scale adapted for LINCL. RESULTS: ADC values assigned to brain parenchyma were higher than published ADC values for age-matched control subjects. ADC values between patients and control subjects began to differ at 5 years of age based on 95% confidence intervals. ADC values had a nearly equal correlation with patient age (R2=0.71) and disease duration (R2=0.68), whereas the correlation with the central nervous system disability scale (R2=0.27) was much weaker. CONCLUSION: This study indicates that brain ADC values acquired using DWI may be used as an independent measure of disease severity and duration in LINCL.

Multiple stressor effects of radiation and metals in salmon (Salmo salar).

These experiments were designed to look at the cellular effects in key organs in Atlantic salmon (Salmo salar) after exposure in vivo to radiation and subtoxic levels of aluminum (Al) and cadmium (Cd), alone or in combination. Salmon (25g) were exposed to a single 0.5Gy dose of gamma-irradiation in water containing Cd, Al or Cd+Al. Three fish per group were sacrificed after 1h and the liver, pronephros, fin and gill of each was dissected. Small explants of each tissue were set up. After 2 days, the culture medium was harvested and filtered then placed on a reporter cell line for determination of stress signal activity (bystander effects). Radiation in combination with Cd and/or Al, caused bystander effects in tissues harvested from in vivo exposed salmon. The effects vary between different organs and are not consistently additive or synergistic for a given treatment. Tissue type appears to be critical. Liver cultures produce a toxic factor which is lethal to reporter cells, and therefore no liver data could be obtained. It is hoped that this stress signal response will prove to be a useful indicator of environmental stress in species inhabiting aquatic ecosystems.