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The tissue mercury concentrations in six species of fish collected at the 17 Areas of Concern identified by the International Joint Commission on the Canadian side of the Great Lakes were analyzed using an Environment Canada database. A linear increase in mercury concentration with fish length was found, but slopes differed among locations. The temporal pattern over the period 1971–1997 differed across species in fish collected in Lake St. Clair; in at least two species there was evidence of increased mercury concentration during the 1990s that had been suggested in an earlier analysis. Areas of Concern differed significantly in observed tissue concentrations. Differences observed did not consistently parallel expectations associated with the historical presence of chlor-alkali plants in the vicinities of some locations. An attempt to correlate the fish tissue mercury concentration with the frequency of occurrence of infantile cerebral palsy at Areas of Concern was unsuccessful. [Copyright &y& Elsevier]

Geographical variation of organochlorine (OC) concentrations in ringed seal (Phoca hispida) in the Canadian Arctic was studied using univariate and multivariate statistical techniques. The dataset consistedof 80 individual OC components (58 PCB congeners plus DDT- and chlordane (CHL)-related compounds, toxaphene, hexachlorocyclohexanes (HCH), chlorobenzenes (CBz), and dieldrin) determined in 221 ringed seal blubber samples from 13 locations throughout the Canadian Arctic from the period 1983 to 1989. Mean concentrations of the major OC groups in ringed seal blubber (SigmaPCBs, SigmaDDT, SigmaCHL and toxaphene), adjusted for the age and sex of the seals, showed few significant geographical differences. Principal components analysis was used to examine geographical trends. Significant differences in mean factor scores for three of four principal components were found between sampling locations. Locations in the western and high Arctic could be distinguished from those in Hudson Bay by highest scores along principal component two which was associated principally with CBz. PCB congeners with six or more chlorine substitutions declined with increasing north latitude, whereas more volatile OCs (CBz, HCH, less chlorinated PCBs)increased in the proportion of total OCs with latitude. Proportions of less chlorinated PCBs also decreased with increasing longitude, whereas slopes of regressions for more highly chlorinated PCBs increased significantly. The results were generally consistent with the 'coldcondensation' hypothesis of increasing proportions of more volatile OCs with increasing latitude and distance from sources. [ABSTRACT FROM AUTHOR]

Pain, fatigue, and depression are a common cluster of symptoms among cancer patients that impair quality of life and daily activities. We aimed to evaluate the burden of cancer rehabilitation and return-to-work (RTW) rates. Tumor characteristics, lifestyle and household details, treatment data, the use of in-house social services and post-treatment inpatient rehabilitation, and RTW were assessed for 424 women, diagnosed with cervical, uterine, or vaginal/vulvar cancer, receiving curative radio(chemo)therapy. Progression-free RTW rate at 3 months was 32.3%, and increased to 58.1% and 63.2% at 12 and 18 months, respectively. Patients with advanced FIGO stages and intensified treatments significantly suffered more from acute pain and fatigue. A higher Charlson-Comorbidity-Index reliably predicted patients associated with a higher risk of acute fatigue during RT. Aside from the presence of children, no other household or lifestyle factor was correlated with increased fatigue rates. Women aged ≤ 45 years had a significantly higher risk of developing depression requiring treatment during follow-up. Post-treatment inpatient cancer rehabilitation, including exercise and nutrition counseling, significantly relieved fatigue symptoms. The burdens for recovery from cancer therapy remain multi-factorial. Special focus needs to be placed on identifying high-risk groups experiencing fatigue or pain. Specialized post-treatment inpatient cancer rehabilitation can improve RTW rates.

Background: There is extensive evidence that patients with cancer and cancer survivors have a strong need for expert support in relation to the psychological and social consequences of the disease. The requirements set out in the German Cancer Society's cancer center certification system include the routine provision of psycho-oncologic care (POC) and social service counseling for every patient. The current study investigated which organizational and structural characteristics in hospitals account for variations in psychosocial care provision in these centers., Methods: Data routinely collected during the certification process regarding the percentages of psychosocial care provision and characteristics of center sites and hospitals were matched with data with regard to size of the municipality, teaching hospital status, and institutional ownership. Linear multilevel regression analyses were performed to identify the characteristics of hospitals and center sites that were related to psychosocial care provision., Results: Substantial differences were found for different types of cancer (eg, a greater provision of psychosocial care in centers specializing in breast rather than prostate cancer). There was more POC provision in longer-certified centers and less in rural areas and university hospitals. Much of the variation between hospitals remains unexplained., Conclusions: Although the implementation of mandatory psychosocial services generally provides patients with access to POC and social service counseling, the wide differences in the provision of counseling indicate that additional measures are needed to avoid inequalities resulting from the center at which a patient receives cancer treatment. Cancer 2016;122:3538-3545. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: Molybdenum cofactor deficiency (MoCD) is characterised by early, rapidly progressive postnatal encephalopathy and intractable seizures, leading to severe disability and early death. Previous treatment attempts have been unsuccessful. After a pioneering single treatment we now report the outcome of the complete first cohort of patients receiving substitution treatment with cyclic pyranopterin monophosphate (cPMP), a biosynthetic precursor of the cofactor., Methods: In this observational prospective cohort study, newborn babies with clinical and biochemical evidence of MoCD were admitted to a compassionate-use programme at the request of their treating physicians. Intravenous cPMP (80-320 μg/kg per day) was started in neonates diagnosed with MoCD (type A and type B) following a standardised protocol. We prospectively monitored safety and efficacy in all patients exposed to cPMP., Findings: Between June 6, 2008, and Jan 9, 2013, intravenous cPMP was started in 16 neonates diagnosed with MoCD (11 type A and five type B) and continued in eight type A patients for up to 5 years. We observed no drug-related serious adverse events after more than 6000 doses. The disease biomarkers urinary S-sulphocysteine, xanthine, and urate returned to almost normal concentrations in all type A patients within 2 days, and remained normal for up to 5 years on continued cPMP substitution. Eight patients with type A disease rapidly improved under treatment and convulsions were either completely suppressed or substantially reduced. Three patients treated early remain seizure free and show near-normal long-term development. We detected no biochemical or clinical response in patients with type B disease., Interpretation: cPMP substitution is the first effective therapy for patients with MoCD type A and has a favourable safety profile. Restoration of molybdenum cofactor-dependent enzyme activities results in a greatly improved neurodevelopmental outcome when started sufficiently early. The possibility of MoCD type A needs to be urgently explored in every encephalopathic neonate to avoid any delay in appropriate cPMP substitution, and to maximise treatment benefit., Funding: German Ministry of Education and Research; Orphatec/Colbourne Pharmaceuticals., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Social workers are an integral part of care provided in cancer centers that are certified according to the requirements of the German Cancer Society. This article reports on the tasks of social workers in German cancer care and on the proportion of patients that receives social service counseling (SSC) in breast, lung, colorectal, skin, gynecological, prostate, pancreas, neurological, and head and neck cancer centers based on data from 367,297 patients treated between 2009 and 2012. The highest proportions of patients (median >75%) are provided with SSC in breast and colorectal cancer centers, whereas the median is below 30% in skin cancer centers. Variation between centers and center types is high.

In accident patient care, there is a substantial overlap between the scope of duties of hospital social services and tasks fulfilled by the German statutory accident insurances' visiting staff that regularly takes care of accident patients. Therefore, a project on the integration of hospital social services into the organizational structures of the German statutory accident insurance was initiated which aimed at optimising communication and realising synergy effects. A formative evaluation of the project was conducted that provided process- and outcome-related data for a comprehensive evaluation of the strengths and potentials of the project. Report forms containing patient-related information were completed by hospital social services. Forms were evaluated in terms of their utility for case management by accident insurance administrators using a checklist. Project implementation and procedures were documented and evaluated using semi-structured interviews with social services staff and accident insurance employees. Through the model, a comprehensive care for accident patients could be reached. In one third of all cases reviewed, rehabilitation management could be improved by including hospital social services. Moreover, in one third of all cases, care-related activities initiated by accident insurance funds could be reduced by involving local hospital social services. The report form used by hospital social services was evaluated as a useful tool in the context of patient care and rehabilitation management. The model was evaluated by interview participants as a highly targeted approach in accident patients' care management. Implications of the study for improving health care are discussed.

We report a 10-month-old boy with inflammatory and necrotic gingival lesions, fever, irritability, and pseudoparalysis of the legs. Laboratory examinations revealed moderate anemia and skeletal X-rays showed osteopenia, scorbutic rosary at the costochondral junctions, and "corner sign" on the proximal metaphyses of the femora. The boy had been fed only with diluted cow's milk. He had never taken solid food, vitamin C, or iron complement. Seventy-two hours after starting oral vitamin C supplementation, there was significant improvement in the patient's gingival lesions and general health. The clinical presentation and laboratory and imaging findings, together with the dramatic response to ascorbic acid intake, allowed us to confirm the diagnosis of infantile scurvy. Scurvy, a dietary disease due to the deficient intake of vitamin C, is uncommon in the pediatric population. In an infant who has never received vitamin C, the combination of gingival lesions, pseudoparalysis, and irritability strongly suggests a diagnosis of scurvy. The clinical picture, together with the laboratory data, radiological studies, and therapeutic response to vitamin C administration, confirmed the diagnosis.

The myc oncogenes are frequently activated in human tumors, but there is no comprehensive insight into the target genes and downstream cellular pathways of these transcription factors. We applied serial analysis of gene expression (SAGE) to identify targets of N-myc in neuroblastomas. Analysis of 42,000 mRNA transcript tags in SAGE libraries of N-myc- transfected and control neuroblastoma cells revealed 114 up-regulated genes. The majority of these genes have a role in ribosome assembly and activity. Northern blot analysis confirmed up-regulation of all tested transcripts. Induction was complete within 4 h after N-myc expression. The large majority of the ribosomal proteins were induced, as well as genes controlling rRNA maturation. Cellular rRNA content was 45% induced. SAGE libraries and northern blot analysis confirmed up-regulation of many of these genes in N-myc-amplified neuroblastomas. As N-myc can functionally replace c-myc, we analyzed whether N-myc targets were induced by c-myc as well. Approximately 40% of these N-myc targets were up-regulated in a c-myc-transfected melanoma cell line. These data suggest that myc genes function as major regulators of the protein synthesis machinery.

Myc family proteins play an important role in cellular processes such as proliferation, differentiation, apoptosis and transformation. A number of interaction partners of Myc have been identified, such as Max, p107, TBP, YY1, Miz-1, AP-2 and Nmi. Both Max and Nmi also bind to MycN. In contrast to the well defined binding of Max to Myc family proteins the interaction of Nmi with Myc or MycN is only poorly characterized. By employing the yeast two-hybrid system we have mapped the regions of MycN and Myc responsible for binding to Nmi. For MycN exclusively a central region mediates binding to Nmi. In contrast, for Myc a C-terminal portion of the protein, and possibly also a central part, is involved in Nmi interaction. Nmi does not interact with Max and has no transactivation capabilities in yeast, suggesting that Nmi alone is not a transcriptional activator in mammalian cells. Immunofluorescence demonstrates that both in 293 embryonic kidney cells and in Kelly neuroblastoma cells all detectable ectopically expressed Nmi is localized in the cytoplasm, in part in a punctate, granular pattern. MycN, which is highly expressed in Kelly cells consequent to amplification, appears to be localized exclusively in the nuclei. This directly demonstrates that in the same cell at least the major proportion of MycN and Nmi is localized in different cellular compartments. This result is confirmed by the finding that endogenous Nmi, which is expressed in Kelly cells only after stimulation with interferon gamma, is detected exclusively in the cytoplasm of these cells. Therefore only a very small amount of MycN and Nmi is likely to be involved in MycN/Nmi interaction in vivo.

Saethre-Chotzen syndrome, a common autosomal dominant craniosynostosis in humans, is characterized by brachydactyly, soft tissue syndactyly and facial dysmorphism including ptosis, facial asymmetry, and prominent ear crura. Previously, we identified a yeast artificial chromosome that encompassed the breakpoint of an apparently balanced t(6;7) (q16.2;p15.3) translocation associated with a mild form of Saethre-Chotzen syndrome. We now describe, at the DNA sequence level, the region on chromosome 7 affected by this translocation event. The rearrangement occurred approximately 5 kb 3' of the human TWIST locus and deleted 518 bp of chromosome 7. The TWIST gene codes for a transcription factor containing a basic helix-loop-helix (b-HLH) motif and has recently been described as a candidate gene for Saethre-Chotzen syndrome, based on the detection of mutations within the coding region. Potential exon sequences flanking the chromosome 7 translocation breakpoint did not hit known genes in database searches. The chromosome rearrangement downstream of TWIST is compatible with the notion that this is a Saethre-Chotzen syndrome gene and implies loss of function of one allele by a positional effect as a possible mechanism of mutation to evoke the syndrome.

Geographical variation of organochlorine (OC) concentrations in ringed seal (Phoca hispida) in the Canadian Arctic was studied using univariate and multivariate statistical techniques. The dataset consisted of 80 individual OC components (58 PCB congeners plus DDT- and chlordane (CHL)-related compounds, toxaphene, hexachlorocyclohexanes (HCH), chlorobenzenes (CBz), and dieldrin) determined in 221 ringed seal blubber samples from 13 locations throughout the Canadian Arctic from the period 1983 to 1989. Mean concentrations of the major OC groups in ringed seal blubber (SigmaPCBs, SigmaDDT, SigmaCHL and toxaphene), adjusted for the age and sex of the seals, showed few significant geographical differences. Principal components analysis was used to examine geographical trends. Significant differences in mean factor scores for three of four principal components were found between sampling locations. Locations in the western and high Arctic could be distinguished from those in Hudson Bay by highest scores along principal component two which was associated principally with CBz. PCB congeners with six or more chlorine substitutions declined with increasing north latitude, whereas more volatile OCs (CBz, HCH, less chlorinated PCBs) increased in the proportion of total OCs with latitude. Proportions of less chlorinated PCBs also decreased with increasing longitude, whereas slopes of regressions for more highly chlorinated PCBs increased significantly. The results were generally consistent with the 'cold condensation' hypothesis of increasing proportions of more volatile OCs with increasing latitude and distance from sources.

While fluorescence polarization is a powerful tool for the measurement of ligand-receptor (e.g. antigen-antibody) interactions, its application in routine clinical chemistry and immunochemistry has been limited because collection of data was error prone, and because analysis of data previously required tedious and imprecise manual graphical methods. We present the series of linear and curvilinear regressions required to calculate parameters (p', Q', pf, Qf, Pb, Qb, Fb max, a and Ko) and their corresponding standard errors. The values of a and Ko are comparable to those obtained by the method of finding the minimal the sum of squares. A menu operated computer program that uses these regressions, simplifies the collection, analysis and presentation of fluorescence polarization data. A simple spread sheet system permits the insertion, deletion or modification of data. The results are presented in graphical and tabular form, either on a monitor, a printer or an X-Y plotter. The system has its own graphical routines.