Quantitative Alterations in Cutaneous Langerhans Cells During the Evolution of Malignant Melanoma of the Skin

Melanomas are associated with a T-cell predominant infiltrate that may cause their regression. Langerhans cells (LC) are essential for initiation and maintenance of specific T-cell- mediated responses in the skin. Therefore, a change in this antigen-presenting LC population may alter the host response. To determine whether the LC population varies during the evolution of primary cutaneous melanoma 32 melanocytic lesions, nevi, and cutaneous melanomas were studied by quantitative immunohistology. The monoclonal antibody, Leu-6, and the avidin biotin complex immunoperoxidase method were used to identify LC. Compared with histologically normal melanoma-adjacent skin, epidermal LC were depleted above “deeply invasive” melanomas but were relatively unchanged above nevi, “early invasive” melanomas, and cutaneous metastatic melanoma nodules. Dermal LC were significantly increased around in situ and “early invasive” melanomas but not around “deeply invasive” melanomas or cutaneous metastatic nodules. Dermal LC are thus associated with early transformed melanocytes and may present neoantigens to T lymphocytes in situ or after LC maturation in the draining lymph node. Melanoma-associated LC decline in number as melanoma progresses

Long-term work outcomes and the efficacy of multidisciplinary rehabilitation programs on labor force participation in cancer patients - a protocol for a longitudinal prospective cohort study

Background. Many cancer survivors experience late effects of cancer treatment and therefore struggle to return to work. Norway provides rehabilitation programs to increase labor force participation for cancer survivors after treatment. However, the extent to which such programs affect labor force participation has not been appropriately assessed. This study aims to investigate i) labor force participation, sick leave and disability rates among cancer survivors up to 10 years after being diagnosed with cancer and identify comorbidities contributing to long-term sick leave or disability pensioning; ii) how type of cancer, treatment modalities, employment sectors and financial- and sociodemographic factors may influence labor force participation; ii) how participation in rehabilitation programs among cancer survivor affect the long-term labor force participation, the number of rehospitalizations and incidence of comorbidities. Design and methods. Information from four medical, welfare and occupational registries in Norway will be linked to information from 163,279 cancer cases (15.68 years old) registered in the Norwegian Cancer Registry from 2004 to 2016. The registries provide detailed information on disease characteristics, comorbidities, medical and surgical treatments, occupation, national insurance benefits and demographics over a 10-year period following a diagnosis of cancer. Expected impact of the study for Public Health. The study will provide important information on how treatment, rehabilitation and sociodemographic factors influence labor force participation among cancer survivors. Greater understanding of work-related risk factors and the influence of rehabilitation on work-participation may encourage informed decisions among cancer patients, healthcare and work professionals and service planners.publishedVersio

Unexplained chronic liver disease in Ethiopia: a cross-sectional study

BACKGROUND: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. METHODS: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. RESULTS: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25-40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. CONCLUSION: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation

Exploring causal pathways of child behavior and maternal mental health in families with a child with congenital heart disease: a longitudinal study

BACKGROUND: A congenital heart defect (CHD) can increase the risk of mental health problems in affected children and their parents. The extent to which risk factors for these problems are shared in families or are specific to the individual family member is unclear. METHOD: Prospective data from the Norwegian Mother and Child Cohort Study (MoBa; n=93009) were linked with a nationwide CHD registry, and 408 children with CHD were identified. Mothers' reports on child internalizing problems and their own distress were assessed by questionnaires at child ages 6, 18 and 36 months. A structural model was applied to distinguish between familial (shared) factors and individual-specific factors for mental health problems. RESULTS: CHD was a substantial risk factor for problems in children and their mothers at all time points. CHD contributed on average 31% and 39% to the variance in children's and mothers' problems respectively. Both shared familial and individual-specific factors unique to CHD families contributed to risk for mental health problems. Whereas individual-specific risk factors contributed to the stability of problems in mothers, the effect of these factors lasted only a short time in children. Mutual influences over time were found between the mother's and the child's mental health at 18 and 36 months. CONCLUSIONS: The burden of CHD in a child is shared between family members but is also specific to the individual. This study points to a need for both an individual and a family-based approach to provide psychological support to children with CHD and their parent

The Benthic Chamber experiment in Storfjorden (Norway) 2005 - effects of CO2 on microbes, nanobenthos and meiofauna

Årsliste 2007Carbon capture and storage (CCS) either sub-seabed or in the ocean is considered among the options for reducing future emissions of CO2 to the atmosphere. Such storage does, however, introduce the possibility of CO2 leakage and interaction with marine fauna. It is therefore important to obtain knowledge on possible effects of CO2 that is introduced to the sea floor. Results from experiments on environmental effects of enhanced concentrations of CO2 at the sediment/water interface are presented. The key part of the project was the Japanese Benthic Chamber system (BC) developed to perform experiments with CO2 in sedimentary environments in situ. The BC is equipped with chambers which enclose sections of the sea floor. Two similar experiments were carried out at 400 m depth in Storfjorden, Norway in September, 2005. The pCO2 exposures in the water above the sediment in the chambers were programmed to maintain levels of approximately 5,000 µatm (pH=7.0) and 20,000 µatm (pH=6.3) respectively in two experimental chambers. The pCO2 in the third control chamber was 500 µatm (pH=7.8). This report gives a description of the experiment and the results from measured physical and chemical parameters (pH, NO3, NH4, SiO2 and oxygen) in the water overlying the sediment in the experimental chambers and biological responses (meiobenthos, nanobenthos, bacteria, Archaea, bacterial DNA and ATP, methane production, sulphate reduction) in the chamber sediments. The results from the different research groups and methods clearly show effects of elevated CO2 concentrations on biological processes such as reduced bacterial density and increased nanobenthos densities. Methane formation and sulphate reduction was favoured by the condition in the 5,000 µatm chamberRIT

In Utero Exposure to Maternal Tobacco Smoke and Subsequent Obesity, Hypertension, and Gestational Diabetes Among Women in The MoBa Cohort

Background: Environmental factors influencing the developmental origins of health and disease need to be identified and investigated. In utero exposure to tobacco smoke has been associated with obesity and a small increase in blood pressure in children; however, whether there is a corresponding increased risk of conditions such as diabetes and hypertension during adulthood remains unclear

Maternal microchimerism in cord blood and risk of childhood-onset type 1 diabetes

Background Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common and persistent. MMc has been detected with increased frequency in the circulation and pancreas of type 1 diabetes (T1D) patients. We investigated for the first time whether MMc levels at birth predict future T1D risk. We also tested whether cord blood MMc predicted MMc in samples taken at T1D diagnosis. Methods Participants in the Norwegian Mother and Child Cohort study were human leukocyte antigen (HLA) class II typed to determine non‐inherited, non‐shared maternal alleles (NIMA). Droplet digital (dd) polymerase chain reaction (PCR) assays specific for common HLA class II NIMA (HLADQB1*03:01, *04:02, and *06:02/03) were developed and validated. MMc was estimated as maternal DNA quantity in the fetal circulation, by NIMA specific ddPCR, measured in cord blood DNA from 71 children who later developed T1D and 126 controls within the cohort. Results We found detectable quantities of MMc in 34/71 future T1D cases (48%) and 53/126 controls (42%) (adjusted odds ratio [aOR] 1.27, 95% confidence interval (CI) 0.68‐2.36), and no significant difference in ranks of MMc quantities between cases and controls (Mann‐Whitney P = .46). There was a possible association in the NIMA HLA‐DQB1*03:01 subgroup with later T1D (aOR 3.89, 95%CI 1.05‐14.4). MMc in cord blood was not significantly associated with MMc at T1D diagnosis. Conclusions Our findings did not support the hypothesis that the degree of MMc in cord blood predict T1D risk. The potential subgroup association with T1D risk should be replicated in a larger cohort

Znf202 Affects High Density Lipoprotein Cholesterol Levels and Promotes Hepatosteatosis in Hyperlipidemic Mice

Background: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. Methodology and Principal Findings: We generated mouse Znf202 expression vectors, the functionality of which was established in several in vitro systems. Next, effects of adenoviral znf202 overexpression in vivo were determined in normo- as well as hyperlipidemic mouse models. Znf202 overexpression in mouse hepatoma cells mhAT3F2 resulted in downregulation of members of the Apoe/c1/c2 and Apoa1/c3/a4 gene cluster. The repressive activity of Znf202 was firmly confirmed in an apoE reporter assay and Znf202 responsive elements within the ApoE promoter were identified. Adenoviral Znf202 transfer to Ldlr-/- mice resulted in downregulation of apoe, apoc1, apoa1, and apoc3 within 24 h after gene transfer. Interestingly, key genes in bile flux (abcg5/8 and bsep) and in bile acid synthesis (cyp7a1) were also downregulated. At 5 days post-infection, the expression of the aforementioned genes was normalized, but mice had developed severe hepatosteatosis accompanied by hypercholesterolemia and hypoalphalipoproteinemia. A much milder phenotype was observed in wildtype mice after 5 days of hepatic Znf202 overexpression. Interestingly and similar to Ldl-/- mice, HDL-cholesterol levels in wildtype mice were lowered after hepatic Znf202 overexpression. Conclusion/Significance: Znf202 overexpression in vivo reveals an important role of this transcriptional regulator in liver lipid homeostasis, while firmly establishing the proposed key role in the control of HDL levels