Time trends in prevalence of p16 positivity and combined HPV/p16 positivity in a large cohort of Danish vulvar cancer patients.

Vulvar cancer is rare, but causes substantial morbidity in affected patients. A subset of vulvar cancers is caused by high-risk human papillomavirus (hrHPV), which primarily exerts its oncogenic effect through upregulation of tumor suppressor protein p16. Tumors positive for both hrHPV and p16 (double positive) are assumed to be HPV-driven, but only few large studies have investigated the combined prevalence of hrHPV and p16 positivity in vulvar cancer over time.

Platysma and the cervical superficial musculoaponeurotic system - Comparative analysis of facial crease and platysmal band development.

Objective: The superficial musculoaponeurotic system connects the mimic muscles to the skin, allowing mimic expressions with regional morphological architectural differences. The aim of this study was to perform an architectural analysis of the cervical platysma-skin interaction, determine the morphological implications in platysmal band development and compare the findings to the facial SMAS architectural types.

Method: Full-thickness blocks of skin, SMAS and platysma from seven hemifaces (three male and two female) and full-thickness blocks of skin, SMAS and mimic muscles of the periorbital, perioral, forehead and midfacial regions from six hemifaces (three male and three female) of donor bodies were collected postmortem.

Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark - the SHADE.

Background: Women living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark.

Methods: From the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011-2014.

Facial fold and crease development: A new morphological approach and classification.

Facial folds and creases are established descriptive anatomical terms for structures of which the morphological characteristics and origins are not clearly defined. The aim of this study was to perform a morphological investigation of the nasolabial fold (NLF), mandibular fold (MF), deep transverse forehead (DTFC), infraorbital fold (IOF) and upper eyelid fold (UEF), correlating their phenotypes to differences in the superficial musculoaponeurotic system (SMAS), noting morphological differences and similarities. Full-graft tissue blocks of skin, subcutaneous tissue, and mimic muscles collected postmortem were studied histologically.

Clinical and analytical performance of the BD Onclarity™ HPV assay for detection of CIN2+ lesions on SurePath samples.

Background: The novel BD Onclarity HPV assay (Onclarity) on the BD Viper™ LT system (BD Diagnostics, Sparks, MD), detects E6/E7 DNA from 13 high-risk HPV genotypes and HPV66. We compared the analytical and clinical performance of the Onclarity Assay to that of Hybrid Capture 2 and LINEAR ARRAY using adjudicated histological outcomes from Danish women referred for colposcopy.

Methods: 276 women from Copenhagen, Denmark were referred for colposcopy with abnormal cytology and/or a positive HPV test.

Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish population-based study from 2011 to 2014.

Background: Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14.

Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population-based study.

The aim was to explore the overall survival (OS) for palatine tonsillar squamous cell carcinoma (TSCC), subdivided, according to certainty of tonsillar tumour origin, into specified tonsillar squamous cell carcinomas (STSCCs) and nonspecified tonsillar squamous cell carcinomas (NSTSCCs), and base of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology Databank, 2000-2010. Patients were treated according to national guidelines (radiotherapy +/- concomitant cisplatin).

Presence of alcoholic steatohepatitis, but no selective histological feature, indicates an increased risk of cirrhosis and premature death.

Objective: The prognostic impact of early stages of histologically confirmed alcoholic liver disease is uncertain. Our aim was to determine the risk of cirrhosis and premature death, and identify prognostic markers, in patients with biopsy-proven alcoholic steatohepatitis - and to compare prognosis in patients with alcoholic pure fatty liver and the general population.

Material And Methods: Patients with biopsy-proven alcoholic fatty liver disease diagnosed during 1976-1987 were identified.

Increasing incidence of base of tongue cancers from 2000 to 2010 due to HPV: the largest demographic study of 210 Danish patients.

Background: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence.

Methods: We performed HPV DNA PCR and p16 immunohistochemistry analysis for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing.

Results: The overall crude incidence of BSCCs increased significantly (5.

A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000-2010: the largest registry-based study to date.

The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000-2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin).

Impact of technology on cytology outcome in cervical cancer screening of young and older women.

Little is known about age-dependent variation in outcomes of cervical cytology with modern technologies. This population-based study evaluated age-dependent changes after routine implementation of ThinPrep and SurePath technology in two independent laboratories, and controlled for time trends in a third laboratory using manually read conventional cytology continually. Data were collected from the Danish National Health Care Registers.

Assessing HER2 amplification by IHC, FISH, and real-time polymerase chain reaction analysis (real-time PCR) following LCM in formalin-fixed paraffin embedded tissue from 40 women with ovarian cancer.

We compare HER2 receptor amplification analysis by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and real-time polymerase chain reaction (real-time PCR) DNA copy-number assay following laser capture microdissection (LCM) in formalin-fixed paraffin embedded tissue from 40 women with verified ovarian cancer. We speculate that LCM should result in a more accurate assessment of HER2 amplification in our real-time PCR assay compared with IHC and FISH. HER2 overexpression measured by IHC, FISH, or real-time PCR was found in 5.

The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor.

The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane proximal domain of the human PRLR and find that the tryptophans of the motif adopt a T-stack conformation in the unbound state.

beta-Sheet aggregation of kisspeptin-10 is stimulated by heparin but inhibited by amphiphiles.

The murine 10-residue neurohormone kisspeptin (YNWNSFGLRY) is an important regulator of reproductive behavior and gonadotrophin secretion. It is known to form a random coil in solution, but undergoes a structural change in the presence of membranes although the nature of this change is not fully determined. The peptide's conformational versatility raises the question whether it is also able to form ordered aggregates under physiological conditions, which might be relevant as a storage mechanism.

Divorcing folding from function: how acylation affects the membrane-perturbing properties of an antimicrobial peptide.

Many small cationic peptides, which are unstructured in aqueous solution, have antimicrobial properties. These properties are assumed to be linked to their ability to permeabilize bacterial membranes, accompanied by the transition to an alpha-helical folding state. Here we show that there is no direct link between folding of the antimicrobial peptide Novicidin (Nc) and its membrane permeabilization.

Quantitative use of paramagnetic relaxation enhancements for determining orientations and insertion depths of peptides in micelles.

We describe the background and implementation of a method to determine, at atomic resolution, the insertion depths and orientations of peptides embedded in micelles. A nonperturbing paramagnetic agent--Gd(DTPA-BMA)--was used to induce paramagnetic relaxation enhancements (PREs) of peptide atoms inside the micelle. By calibrating these PREs it was possible to translate them into distance restraints that could be used for structure calculation.

Final results of a long-term, clinical follow-up in fatty liver patients.

Objective: There is increasing focus on non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to conduct a long-term clinical follow-up of patients with biopsy-confirmed fatty liver without inflammation or significant fibrosis (pure fatty liver), to analyse for potential risk factors at the time of index liver biopsy important for survival and the development of cirrhosis and to describe the causes of death.

Material And Methods: Patients were linked through their personal identification number to the Danish National Registry of Patients and the Register of Causes of Death.

Effect of glycosylation on the extracellular domain of the Ag43 bacterial autotransporter: enhanced stability and reduced cellular aggregation.

Autotransporters constitute the biggest group of secreted proteins in Gram-negative bacteria and contain a membrane-bound beta-domain and a passenger domain secreted to the extracellular environment via an unusually long N-terminal sequence. Several passenger domains are known to be glycosylated by cytosolic glycosyl transferases, promoting bacterial attachment to mammalian cells. In the present study we describe the effect of glycosylation on the extracellular passenger domain of the Escherichia coli autotransporter Ag43alpha, which induces frizzy colony morphology and cell settling.

Authority from grief, presence and place in the making of roadside memorials.

Those who make memorials for the victims of motor vehicle crashes assume an authority to do so that stems from three main elements of experience: the overwhelming empowerment of grief; the belief that the presence of the deceased can be felt and recognized; and the understanding that the place where life was lost is a special place for memorialization. The strength of grief, the power of presence and the importance of place allows ordinary people to assume and, therefore, challenge the authority of the church and the government as official purveyors and regulators of mourning ritual.

Histological characteristics and prognosis in patients with fatty liver.

Objective: The clinical-pathological spectrum of fatty liver ranges from simple steatosis to end-stage fibrotic liver disease. However, no histological characteristics have been identified that can predict progression from pure steatosis to fibrotic liver disease in non-alcoholic fatty liver disease. The objective of this study was to investigate whether histological characteristics in patients with fatty liver without inflammation could predict mortality or development of cirrhosis.

Long term prognosis of fatty liver: risk of chronic liver disease and death.

Background And Aims: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease and the risk of death in a cohort diagnosed with pure fatty liver without inflammation.

Three fatal cases of PMA and PMMA poisoning in Denmark.

Paramethoxyamphetamine (PMA) and paramethoxymetamphetamine (PMMA) are methoxylated phenylethylamine derivatives with effects similar to methylenedioxymetamphetamine (MDMA) and sold as such. However, PMA and PMMA are more potent than MDMA, but have a slower onset of action, which encourages users to take more. Three fatal cases involving PMA and PMMA in Denmark in year 2000 are investigated including history, pathological, and toxicological findings.