Sea trout adapt their migratory behaviour in response to high salmon lice concentrations.

Sea trout face growth-mortality trade-offs when entering the sea to feed. Salmon lice epizootics resulting from aquaculture have shifted these trade-offs, as salmon lice might both increase mortality and reduce growth of sea trout. We studied mortality and behavioural adaptations of wild sea trout in a large-scale experiment with acoustic telemetry in an aquaculture intensive area that was fallowed (emptied of fish) synchronically biannually, creating large variations in salmon lice concentrations. We tagged 310 wild sea trout during 3 years, and gave half of the individuals a prophylaxis against further salmon lice infestation. There was no difference in survival among years or between treatments. In years of high infestation pressure, however, sea trout remained closer to the river outlet, used freshwater (FW) habitats for longer periods and returned earlier to the river than in the low infestation year. This indicates that sea trout adapt their migratory behaviour by actively choosing FW refuges from salmon lice to escape from immediate mortality risk. Nevertheless, simulations show that these adaptations can lead to lost growth opportunities. Reduced growth can increase long-term mortality of sea trout due to prolonged exposure to size-dependent predation risk, lead to lower fecundity and, ultimately, reduce the likelihood of sea migration.

Acute hepatic porphyria and cancer risk: a nationwide cohort study.

BACKGROUND: Acute hepatic porphyria (AHP) is considered to be a risk factor for primary liver cancer (PLC), but varying risk estimates have been published. OBJECTIVES: Our aim was to investigate the risk of PLC and other cancers in persons with AHP using a nationwide cohort design. Given that greater numbers of women than men tend to have manifest and more severe AHP, a further aim was to investigate sex differences in this risk. METHODS: The study sample consisted of all Norwegian residents aged 18 years or older during the period 2000-2011. Persons with AHP (n = 251) were identified through the Norwegian Porphyria Centre, and patients with a cancer diagnosis were identified by linkage to the Cancer Registry of Norway. RESULTS: For persons with AHP, the annual incidence rate of PLC was 0.35%. PLC risk was substantially higher for individuals with an AHP diagnosis compared to the reference population [adjusted hazard ratio (aHR) 108, 95% confidence interval (CI) 56-207]. In a meta-analysis of published studies on PLC and AHP, including ours, women had a higher risk than men. In addition, our results suggested that persons with AHP may have increased risks of kidney (aHR 7.4, 95% CI 2.4-23.1) and endometrial cancers (aHR 6.2, 95% CI 2.0-19.3). CONCLUSIONS: Our findings confirmed a substantially higher risk of PLC associated with AHP compared to the general population. In a meta-analysis, the risk was shown to be greater for women than men. The novel findings of a moderate to substantial association between AHP and kidney and endometrial cancers should be investigated further.

Less thrombolysis in posterior circulation infarction-a necessary evil?

OBJECTIVES: Patients with posterior circulation infarction (PCI) have more subtle symptoms than anterior circulation infarction (ACI) and could come too late for acute intervention. This study aimed to describe the clinical presentation, management, and outcome of PCI in the NORSTROKE registry. METHODS: All patients with PCI admitted to the Department of Neurology at Haukeland University Hospital and registered in the NORSTROKE database 2006-2013 were included (n=686). Patients with ACI (n=1758) were used for comparison. RESULTS: Patients with PCI were younger (68.2 vs 71.8, P<.001), had longer median time from symptom onset to admission (3.8 hours vs 2.2 hours, P<.001), and were less likely to arrive at hospital within 4.5 hours from symptom onset (56.2% vs 72.5%, P<.001, ictus known). Patients with PCI scored lower on baseline National Institute of Health Stroke Scale (NIHSS) total score (3.2 vs 6.3, P<.001), and lower or equally on all items of NIHSS, except for ataxia in two limbs. Patients with PCI were less likely to receive i.v. thrombolytic treatment (9.9% vs 21.5%, OR 0.66, CI 0.47-0.94). On day 7, patients with PCI scored lower on NIHSS (2.8 vs 4.9, P<.001), modified Rankin Scale (2.0 vs 2.3, P<.001), and higher on Barthel Index (84.5 vs 76.0, P<.001). CONCLUSIONS: Our study is, to our knowledge, the largest series reporting comprehensively on PCI verified by diffusion-weighted imaging. PCI patients are younger than ACI and have better outcome. PCI and ACI are equally investigated in the acute setting, but thrombolysis rates remain 50% lower in PCI.

Short communication: Is consumption of a cheese rich in angiotensin-converting enzyme-inhibiting peptides, such as the Norwegian cheese Gamalost, associated with reduced blood pressure?

Epidemiological and clinical studies have shown that angiotensin-converting enzyme (ACE)-inhibiting peptides derived from dairy products may decrease blood pressure. These peptides have been identified in many cheeses, and Gamalost, a traditional Norwegian cheese, is particularly rich in these peptides. The aim of this cross-sectional study was to examine whether frequency of Gamalost intake was associated with blood pressure in a Norwegian population sample. Blood pressure and other clinical measurements, including the factors of metabolic syndrome, were obtained from 168 participants (56% female, mean age = 51 yr) who completed a questionnaire about dietary habits and other health-related factors. Mean Gamalost intake was 2 servings per week. The prevalence of hypertension was 23.8% in the population, with mean systolic and diastolic blood pressures of 128 and 78 mmHg, respectively. Intake of Gamalost was inversely associated with systolic blood pressure. Each increase in frequency unit of Gamalost intake corresponded to a reduction in systolic blood pressure of 0.72 mmHg, after controlling for sex, age, education, waist circumference, physical activity, smoking status, and dairy food intake. Results from this study indicate that consumption of Gamalost (or other foods rich in ACE-inhibiting peptides) may reduce blood pressure.

Predictors for PaO2 and hypoxemic respiratory failure in COPD-A three-year follow-up.

BACKGROUND: Knowledge about predictors for developing hypoxemia in the course of chronic obstructive pulmonary disease (COPD) progression is limited. The objective of the present study was to investigate predictors for overall PaO2, for a potential change in PaO2 over time, and for first occurrence of hypoxemia. METHODS: 419 patients aged 40-76 years with COPD GOLD stages II-IV underwent clinical and pulmonary function measurements, including repeated arterial blood gases over three years. Airway obstruction, lung hyperinflation, markers of systemic inflammation and cardiovascular health, exacerbation frequency, smoking habits, and body composition were tested as possible predictors of PaO2 and first episode of hypoxemia. RESULTS: In multivariate adjusted longitudinal analyses, forced expiratory volume in 1 second, total lung capacity and functional residual capacity (all in% predicted), resting heart rate and fat mass index were all associated with overall PaO2 (all P < 0.005). We found no change in PaO2 over time (ρ = 0.33), nor did we find evidence that any of the tested variables predicted change in PaO2 over time. In multivariate adjusted survival analyses, functional residual capacity and resting heart rate were predictors of episodic hypoxemia (both ρ < 0.005). CONCLUSIONS: This longitudinal study identified pulmonary, cardiac and metabolic risk factors for overall PaO2 and episodic hypoxemia, but detected no change in PaO2 over time.

Playing online videogames-more than just entertainment? A qualitative study of virtual social participation in persons with spinal cord injury.

Introduction: Spinal cord injury (SCI) affects many aspects of life, physically, emotionally and socially. Engaging in online videogames holds the potential to facilitate increased social interactions for individuals with SCI. The aim of this study is to increase our understanding of the experiences people with SCI have with using online videogames as an arena for social participation. Methods: A focus group interview was conducted with seven participants with SCI, aged 15-35, all experienced in using online videogames as a method of socializing. The data was analyzed using thematic analysis. Results: The participants highlighted that playing online videogames way of maintaining social connections and expanding their social network. However, they faced challenges due to limited knowledge and negative attitudes from others regarding use of videogames as a social arena. Three main themes were developed from the findings: "Disabling social barriers", "Attitudes towards gaming" and "Gaming-connecting people". Conclusion: Healthcare professionals should consider videogames as a leisure activity and facilitate their use, recognizing their potential for social interaction and well-being. Prioritizing activities that promote social interaction is crucial for good health.

Validation of the multiple sclerosis international quality of life (MusiQoL) questionnaire in Norwegian patients.

OBJECTIVES: To assess the validity and reliability of the multidimensional, self-administered Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire, previously validated in a large international sample, in Norwegian patients. PATIENTS AND METHODS: Patients with different types and severities of multiple sclerosis (MS) were recruited from a single MS centre in Norway. All patients completed the MusiQoL and Short Form-36 (SF-36) QoL questionnaires at baseline and a mean of 21 (SD 7) days later. A neurologist collected sociodemographic, MS history and outcome data. Construct validity, internal consistency, reproducibility and external consistency were tested. RESULTS: One hundred and four patients were evaluated. Construct validity was confirmed in terms of satisfactory item internal consistency correlations in eight of nine MusiQoL dimensions (Spearman's correlation: 0.34-0.79) and scaling success of item discriminant validity (75.0-100%). All dimensions of the MusiQoL questionnaire exhibited satisfactory internal consistency (Cronbach's alpha: 0.44-0.87) and reproducibility (intraclass correlation coefficients: 0.36-0.86). External validity testing showed that the global MusiQoL score correlated significantly with all but one individual SF-36 dimension score (Spearman's correlation: 0.29-0.56). CONCLUSIONS: These results demonstrate that the Norwegian-language version of the MusiQoL questionnaire is a valid and reliable instrument for assessing health-related QoL in Norwegian patients with MS.

Histopathologic Changes, Ultrastructure, and Molecular Characterization of an Adenovirus in a Sun Conure (Aratinga solstitialis).

In this case report, we describe the pathologic changes and the ultrastructural and molecular characteristics of an adenovirus in a sun conure (Aratinga solstitialis) that presented with a history of sudden death. On histologic examination, there was multifocal hepatic and splenic necrosis. Within some hepatocytes and unidentified cells in the spleen, renal interstitial fibroblasts, and ovarian stroma were intranuclear amphophilic inclusion bodies. Electron microscopy of affected tissue showed intranuclear icosahedral viral particles with an inner capsid (29.2-33.8 nm in diameter) and an outer capsid (70.2-71.7 nm in diameter). Next-generation sequencing and BLAST analysis of complementary DNA synthesized from RNA extracted from formalin-fixed tissues showed an adenovirus, designated sun conure adenovirus (SCAdv). A DNA in situ hybridization (ISH) probe, constructed from the SCAdv and similar sequences from GenBank, was also positive in the intranuclear inclusion bodies, whereas standard ISH for psittacine adenovirus 1 was negative. These results show that ancillary diagnostic testing, such as next-generation sequencing, even using formalin-fixed, paraffin-embedded tissues, along with ISH, can be useful in identifying additional, unknown viruses that show similar pathology to commonly known viruses but do not show up as positive on routine diagnostic tests.

Reporte de caso- Cambios histopatológicos, ultraestructura y caracterización molecular de un adenovirus en una cotorra solar (Aratinga solstitialis). En este reporte de caso, se describen los cambios patológicos y las características ultraestructurales y moleculares de un adenovirus en una cotorra solar (Aratinga solstitialis) que se presentó con un historial de muerte súbita. En el examen histológico, hubo necrosis hepática y esplénica multifocal. Dentro de algunos hepatocitos y células no identificadas en el bazo, los fibroblastos intersticiales renales y en el estroma ovárico se encontraron cuerpos de inclusión anfofílicos intranucleares. La microscopía electrónica del tejido afectado mostró partículas víricas intranucleares icosaédricas con una cápside interna (de 29.2 a 33.8 nm de diámetro) y una cápside externa (de 70.2 a 71.7 nm de diámetro). Mediante el análisis de secuenciación de segunda generación y por la Herramienta de Búsqueda de Alineaciones Local Básica (con siglas en inglés BLAST) del ADN complementario sintetizado a partir de ARN extraído de tejidos fijados con formalina mostraron un adenovirus, denominado adenovirus de cotorra solar (SCAdv). Se construyó una sonda de ADN para hibridación in situ (ISH), a partir de la secuencia del virus SCAdv y de secuencias similares de GenBank, que generó reacción positiva en los cuerpos de inclusión intranucleares, mientras que la hibridación in situ estándar para el adenovirus I de psitácidos fue negativa. Estos resultados muestran que las pruebas de diagnóstico complementarias, como la secuenciación de segunda generación, utilizando tejidos fijados con formalina e incluidos en parafina junto con la hibridación in situ pueden ser útiles para identificar virus adicionales desconocidos que muestran una patología similar a los virus comúnmente conocidos, pero que no se detectan con las pruebas diagnósticas de rutina.

Inferring Atlantic salmon post-smolt migration patterns using genetic assignment.

Understanding migratory patterns is important for predicting and mitigating unwanted consequences of environmental change or anthropogenic challenges on vulnerable species. Wild Atlantic salmon undergo challenging migrations between freshwater and marine environments, and the numbers of salmon returning to their natal rivers to reproduce have declined over several decades. Mortality from sea lice linked to fish farms within their seaward migration routes is proposed as a contributing factor to these declines. Here, we used 31 microsatellite markers to establish a genetic baseline for the main rivers in the Hardangerfjord, western Norway. Mixed stock analysis was used to assign Atlantic salmon post-smolts caught in trawls in 2013-2017 back to regional reporting units. Analyses demonstrated that individuals originating from rivers located in the inner region of the fjord arrived at the outer fjord later than individuals from middle and outer fjord rivers. Therefore, as post-smolts originating from inner rivers also have to migrate longer distances to exit the fjord, these data suggest that inner fjord populations are more likely to be at risk of mortality through aquaculture-produced sea lice, and other natural factors such as predation, than middle or outer fjord populations with earlier exit times and shorter journeys. These results will be used to calibrate models estimating mortality from sea lice on wild salmon for the regulation of the Norwegian aquaculture industry.

Ensemble methods for stochastic networks with special reference to the biological clock of Neurospora crassa.

A major challenge in systems biology is to infer the parameters of regulatory networks that operate in a noisy environment, such as in a single cell. In a stochastic regime it is hard to distinguish noise from the real signal and to infer the noise contribution to the dynamical behavior. When the genetic network displays oscillatory dynamics, it is even harder to infer the parameters that produce the oscillations. To address this issue we introduce a new estimation method built on a combination of stochastic simulations, mass action kinetics and ensemble network simulations in which we match the average periodogram and phase of the model to that of the data. The method is relatively fast (compared to Metropolis-Hastings Monte Carlo Methods), easy to parallelize, applicable to large oscillatory networks and large (~2000 cells) single cell expression data sets, and it quantifies the noise impact on the observed dynamics. Standard errors of estimated rate coefficients are typically two orders of magnitude smaller than the mean from single cell experiments with on the order of ~1000 cells. We also provide a method to assess the goodness of fit of the stochastic network using the Hilbert phase of single cells. An analysis of phase departures from the null model with no communication between cells is consistent with a hypothesis of Stochastic Resonance describing single cell oscillators. Stochastic Resonance provides a physical mechanism whereby intracellular noise plays a positive role in establishing oscillatory behavior, but may require model parameters, such as rate coefficients, that differ substantially from those extracted at the macroscopic level from measurements on populations of millions of communicating, synchronized cells.

Healthcare-associated infection among residents of long-term care facilities: a cohort and nested case-control study.

Knowledge of infection control measures in nursing homes is limited. This study aimed to assess the incidence of, and potential risk factors for, healthcare-associated infection in long-term care facilities in Norway. Incidence of healthcare-associated infection was recorded prospectively in six long-term care facilities located in two major cities in Norway between 1 October 2004 and 31 March 2005. For each resident with an infection we aimed for two controls in a nested case-control study to identify potential risk factors. Incidence of infection was 5.2 per 1000 resident-days. Urinary and lower respiratory tract infections were the most common. Patients confined to their beds [odds ratio (OR=2.7)], who stayed <28 days (OR=1.5), had chronic heart disease (OR=1.3), urinary incontinence (OR=1.5), an indwelling urinary catheter (OR=2.0) or skin ulcers (OR=1.8) were shown to have a greater risk for infection. Age, sex and accommodated in a two- versus single-bed room were not significant factors. Incidence of infection in nursing homes in Norway is within the range reported from other countries. This study identified several important risk factors for healthcare-associated infection. There is a need to prevent infection by implementing infection control programmes including surveillance in long-term care facilities.

Clinical field testing of polyurethane feet for trans-tibial amputees in tropical low-income countries.

In a prospective controlled study, 172 polyurethane feet of different designs were fitted to 155 amputees with trans-tibial prostheses. These were followed in respect of their durability. The amputee compliance was in general good, and 87% were satisfied with their device. After 18 months the failure rate of 20% with the CIREC spring-blade foot was significantly better than the others, but poorer craftsmanship, higher complaint rate and lower compliance rate cast some doubt on the results. The results with the conventional SACH foot constructions with polyurethane as filling and covering materials were so poor after 18 months that their use cannot be recommended in tropical areas of the developing world.

Clinical field testing of vulcanized rubber feet for trans-tibial amputees in tropical low-income countries.

In a prospective, controlled study, 186 prosthetic rubber feet of different designs were fitted to amputees with trans-tibial prostheses. There were 158 amputees available for follow-up. The amputee compliance was good and 89% were satisfied with their device. After 18 months of use one VI-Solid rubber foot from VVAF in Cambodia had failed, as compared to 11% failures with the same foot with a heel cavity, 3% with the EB-1 sandwich construction from POF in Vietnam, all performing significantly better than the 62% encountered with the vulcanized rubber foot from ICRC in Cambodia; the latter representing half of the feet failing in amputees walking bare-footed. Nearly all failures were located at the foot-sole or the keel. The failure rate was 20% for the HI-Cambodia foot after 12 months. After 24 months of use, still only one VI-Solid rubber foot had failed and this foot design was found superior to the others in regard of durability.

Three Different Outcomes in Older Community-dwelling Patients Receiving Intermediate Care in Nursing Home after Acute Hospitalization.

OBJECTIVES: To evaluate the recovery and outcome of older communitydwelling patients admitted to intermediate care (IC) in nursing homes after acute hospitalization, and to compare patients who were able and unable to return directly to their own homes. DESIGN: Prospective, observational, cohort study conducted between June 2011 and 2014. SETTING: A 19- bed IC unit in a nursing home with increased multidisciplinary staffing. PARTICIPANTS: A total of 961 community-dwelling patients, ≥70 years of age, considered to have a rehabilitation potential and no major cognitive impairment or delirium, transferred from internal medicine, cardiac, pulmonary and orthopaedic hospital departments. MEASUREMENTS: Demographic data, clinical information, comprehensive geriatric assessment (CGA), discharge destination and length of stay. Residence status and mortality 1 month, 2 months, 3 months, and 6 months after discharge from the hospital. RESULTS: The trajectory of recovery was divided into 3 groups: 1) Rapid recovery, able to return home after median 14 days in IC (n=785, 82%); 2) Slow recovery, requiring additional transfer to other nursing home after IC, but still able to return home within 2 months (n=106, 11%). 3) Poor recovery, requiring transfer to other nursing home after IC and still in a nursing home or dead at 2 months (n=66, 7%). Significant different clinical characteristics were demonstrated between the patients in the 3 groups. After 6 months, the recovery of patients with rapid or slow recovery was similar, 87% were living at home, compared to only 20% of the patients with poor recovery. In multiple logistic regression analysis, slow or poor recovery was significantly associated with low scores on the Barthel index and orthopaedic admission diagnosis. CONCLUSIONS: Although the majority of patients selected for treatment in the IC unit were able to recover and return home, a group of patients needed extra time, up to 2 months, to recover and another group had a poor chance of recovering and returning home. Different caring pathways for different patient groups may be considered in the PAC setting.

Patient knowledge, practices and challenges to health care system in early diagnosis of mycobacterial adenitis.

OBJECTIVE: To assess diagnostic delay, knowledge and practices related to tuberculosis among patients with mycobacterial adenitis. DESIGN: A cross sectional study involving comparison analysis of high-risk groups. SETTING: Seven hospitals in rural and semi-rural districts of Arusha. SUBJECTS: Four hundred and twenty six clinically diagnosed adenitis patients. INTERVENTIONS: Biopsy specimens were processed for culture, histology, and sera for HIV testing. A questionnaire was used to assess knowledge, practice, and diagnostic time. MAIN OUTCOME MEASURES: Tribal comparisons were made using proportions and means. RESULTS: About 90% (387/423) of patients first visited medical facilities within a mean time of 10.1(SD, 15.7) weeks after becoming aware of their illness, and a diagnosis was made at a mean of 27 (SD, 25) weeks. Non-Iraqw patients, especially the Datoga, practised drinking raw milk (35.2% 43/122), eating raw animal products (18.8% 24/128) and living in houses with poor ventilation (33.6% 44/131), more than Iraqw patients. Of the investigations done, 14.5% (60/415) were culture positive, 11.3% (16/142) were HIV positive, and 73.6% (128/174) had histological features consistent with tuberculosis. The knowledge of TB spread by air droplets was poorer in Iraqw (74.1%, 203/274) than in non-lraqw (61.1%, 77/126) patients. About 35.0% (45/129) of non-lraqw and 27.3% (79/289) of Iraqw patients were not aware that TB could be transmitted from animals to humans. CONCLUSIONS: The health system diagnostic delay is about twice the patient delay. The knowledge and practices related to both human and bovine TB transmission were poor in all patients, especially in the patients from nomadic tribes.

Interferon-alpha2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Norwegian Study Group on Interferon-alpha in Multiple Sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of interferon-alpha2a (IFN-alpha2a) in relapsing-remitting MS (RRMS). BACKGROUND: Several immune-modulating therapy regimens of IFN-alpha have shown varying results in MS. A recent pilot study suggested benefits from IFN-alpha2a. METHODS: Ninety-seven patients were randomized to receive subcutaneous injections of placebo (33 patients) or 4.5 million international units (mIU) (32 patients) or 9.0 mIU (32 patients) of IFN-alpha2a three times weekly for 6 months, with a further 6 months of follow-up. Monthly gadodiamide-enhanced MRI was the primary method of evaluating efficacy. RESULTS: IFN-alpha2a treatment resulted in fewer new MRI lesions during the treatment period (p < 0.003). The probability of no new lesions during treatment was >2.5 times higher with 9.0 mIU IFN-alpha2a than with placebo (p < 0.005). The median number of lesions at the end of treatment was lower with IFN-alpha2a treatment than with placebo (p = 0.0004), but the difference disappeared during follow-up. The total number of lesions (mean) increased by 4.78 with placebo, 0.86 with 4.5 mIU IFN-alpha2a, and 0.28 with 9.0 mIU IFN-alpha2a during treatment (p = 0.030). No treatment effect on exacerbation rate, progression of disability, or quality of life was detected. Nine patients discontinued treatment, five because of adverse events. CONCLUSIONS: IFN-alpha2a treatment significantly reduced disease activity as measured by MRI, but the efficacy disappeared within 6 months after discontinuation of treatment. A long-term study of more patients using disability as a primary outcome measure is needed to evaluate the clinical impact.

Localization of Fc gamma receptors and complement receptors CR1 on human peripheral nerve fibres by immunoelectron microscopy.

The localization of receptors for the Fc part of IgG (Fc gamma R) and for the complement C3b/C4b components (CR1) on human peripheral nerve fibres was investigated by indirect immunoperoxidase staining of frozen nerve sections with monoclonal antibodies. Transmission electron microscopy revealed that Fc gamma R and CR1 are localized to the entire surface membrane and inner membrane (axolemma) of the Schwann cell. Myelin and axons were not stained. The presence of Fc gamma R and CR1 in human Schwann cells adds further evidence for the immunocompetence of these cells.

Immunohistochemical detection of p53 in archival formalin-fixed tissues of lip and intraoral squamous cell carcinomas from Norway.

We investigated the expression of p53 in 82 formalin-fixed, paraffin-embedded archival tissue specimens of lip and intraoral squamous cell carcinomas (SCCs) from the period 1930-1995, by immunohistochemistry using three monoclonal antibodies (MAbs DO-7, DO-1 and 1801). Before incubation, sections were pretreated with 0.1% Protease enzyme at 37 degrees C for 10 min followed by 5 + 5 min microwave oven heating at 700 W and 425 W, respectively. Formalin-fixed tissues of 10 carcinomas of the uterine cervix positive for p53 were used as controls. With one or more of the three MAbs, p53 was expressed in 73% of the 82 SCCs examined. With only protease enzyme pretreatment or microwave oven heating, p53 was expressed in 9/82 and 12/82 of the SCCs, respectively. Of the 82 SCCs, 60%, 45% and 23% expressed p53 with DO-7, DO-1 and 1801, respectively. The kappa coefficient indicated poor agreement between these results for the antibodies, and for lip and intraoral SCCs, except for p53 expression in intraoral SCCs demonstrated by DO-1/1801, which showed fair agreement. The present study suggests that combined protease pretreatment and microwave oven heating of tissue sections improved unmasking of p53 antigenic sites in archival material stored for up to 65 years.

Expression of keratin 13, 14 and 19 in oral squamous cell carcinomas from Sudanese snuff dippers: lack of association with human papillomavirus infection.

In stratified squamous epithelia, altered expression of keratins (Ks) is one possible marker of malignant potential. In the epithelium of the uterine cervix, presence of human papillomaviruses (HPVs) is increasingly regarded as a marker of risk for cervical cancer. However, a similar role in oral cancer and precancer remains controversial. To address these questions, formalin-fixed, paraffin-embedded oral carcinomas from Sudanese snuff dippers (n=14) and oral carcinomas from Sudanese (n=14), Swedish (n=19) and Norwegian (n=41) non-snuff dippers were examined by immunohistochemistry for expression of K types 13, 14 and 19 using monoclonal antibodies. HPV infection was searched for in all the carcinomas by in situ hybridization (ISH) using the cocktail HPV OmniProbe and the ViraType probe. Carcinomas from Sudanese (snuff dippers/non-snuff dippers) were also examined for HPV infection by polymerase chain reaction (PCR) using the general HPV primers GP5+/GP6+. For the oral carcinomas from snuff dippers, moderate to intense expression of K13 (71%; 10/14), K14 (86%; 12/14) and K19 (93%; 13/14) was found. For the oral carcinomas from non-snuff dippers, weak to moderate expression of K13 (64%; 47/74), K14 (43%; 32/74) and K19 (45%; 33/74) was found. HPV DNA was not detected in any of the carcinomas from three countries when examined by ISH. The Sudanese (from snuff dippers/non-snuff dippers) oral carcinomas were also negative for HPV DNA with the PCR. The present study shows that (i) there is a high level of expression of K13, K14 and K19 in oral carcinomas from snuff dippers compared to those from non-snuff dippers, (ii) this high level of expression may arise from dysregulation of keratinocyte proliferation and maturation caused by damaging effects of snuff, (iii) the HPV genome is not found in Sudanese (snuff dippers/non-snuff dippers), Swedish or Norwegian oral carcinomas, and (iv) this may suggest that these viruses do not play a prominent role in the aetiology of oral carcinomas from these countries.

Species differences in central oxytocin receptor gene expression: comparative analysis of promoter sequences.

The distribution of oxytocin binding sites in the brain is highly variable among mammals. Using two species of microtine rodents (voles) with strikingly different patterns of oxytocin binding sites in the brain, we demonstrate that these differences are due to differences in region specific gene expression and not post-translational processing. The distribution of oxytocin receptor mRNA closely resembles the distribution of oxytocin receptor binding sites in both species. Analysis of the 5' flanking region of the oxytocin receptor gene from both species reveals few differences in potential regulatory elements which could explain the differences in gene expression. These data suggest that species differences in oxytocin receptor binding are due to species differences in: i) distant DNA sequences further upstream or downstream which may influence expression; ii) the distribution of regulatory proteins such as transcription factors in the brain or iii) epigenetic factors, such as prenatal and perinatal environment which may affect gene expression in the adult.