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Ohne Zusammenfassung     

Sensitive HPV detection in oropharyngeal cancers

Background  

Human papillomaviruses (HPV) are the aetiological agents of certain benign and malignant tumours of skin and mucosae; the most important of which is cervical cancer. Also, the incidence of ano-genital warts, HPV-anal cancer and oropharyngeal cancers are rising. To help ascertain a useful PCR detection protocol for oropharyngeal cancers, we directly compared three commonly used primer sets in detection of HPV from different clinical samples.     

Chronic ethanol exposure leads to divergent control of dopaminergic synapses in distinct target regions

Neuroadaptations following chronic exposure to alcohol are hypothesized to play important roles in alcohol-induced alterations in behavior, in particular increased alcohol drinking and anxiety like behavior. Dopaminergic signaling plays a key role in reward-related behavior, with evidence suggesting it undergoes modification following exposure to drugs of abuse. A large literature indicates an involvement of dopaminergic signaling in response to alcohol. Using a chronic inhalation model of ethanol exposure in mice, we have begun to investigate the effects of alcohol intake on dopaminergic signaling by examining protein levels of tyrosine hydroxylase and the dopamine transporter, as well as monoamine metabolites in three different target fields of three different dopaminergic nuclei. We have focused on the dorsal lateral bed nucleus of the stria terminalis because of the reported involvement of dorsal lateral bed nucleus of the stria terminalis dopamine in ethanol intake, and the nucleus accumbens and dorsal striatum because of their dense dopaminergic innervation. After either a chronic intermittent exposure or continuous exposure regimen, mice were killed, and tissue punches collected from the dorsal lateral bed nucleus of the stria terminalis, nucleus accumbens, and striatum for Western analysis. Strikingly, we found divergent regulation of tyrosine hydroxylase and dopamine transporter protein levels across these three regions that was dependent upon the means of exposure. These data thus suggest that distinct populations of catecholamine neurons may be differentially regulated by ethanol, and that ethanol and withdrawal interact to produce differential adaptations in these systems.     

Algorithms for digital image processing in diabetic retinopathy

This work examined recent literature on digital image processing in the field of diabetic retinopathy. Algorithms were categorized into 5 steps (preprocessing; localization and segmentation of the optic disk; segmentation of the retinal vasculature; localization of the macula and fovea; localization and segmentation of retinopathy). The variety of outcome measures, use of a gold standard or ground truth, data sample sizes and the use of image databases is discussed. It is intended that our classification of algorithms into a small number of categories, definition of terms and discussion of evolving techniques will provide guidance to algorithm designers for diabetic retinopathy.     

Surveillance of anal carcinoma after radiochemotherapy

Background

Surveillance after radiochemotherapy of anal carcinoma (ACa) with curative intent is recommended in guidelines, but data regarding the effectiveness of follow-up are lacking. We aimed to assess the performance of an ACa surveillance program in a real-life setting.

Methods

We retrospectively summarized clinical history, physical findings, and follow-up investigations (endoanal ultrasound, endoscopy, CT scan) obtained during 42 months (±27 months) from 80 patients after radiochemotherapy of ACa.

Results

In 7/80 cases (8.8%) an incomplete response to therapy was identified at or before the 6?month time point after the end of treatment; 4 of the 7 cases were identified during scheduled follow-up. In 6 cases (7.5%), recurrent disease was found after the 6?month time point. Recurrence was systemic in 5 cases and local/inguinal in 1 case. In 3 of the 6 cases (50%), recurrence was identified during scheduled follow-up. In one asymptomatic patient, a single liver metastasis was detected during scheduled follow-up and the patient remains free of disease 19 months after surgery. Surveillance resulted in a high rate of false-positive findings (70 findings in 604 investigations), of which only 14 could be confirmed.

Conclusion

Scheduled follow-up after treatment of ACa detected recurrent disease at systemic sites, enabling potentially curative treatment in a single case. Effectiveness of abdominal imaging during follow-up after ACa treatment should be tested in a prospective trial.

     

Technical validation of the Di3D stereophotogrammetry surface imaging system

The purpose of this work was to assess the technical performance of a three-dimensional surface imaging system for geometric accuracy and maximum field of view. The system was designed for stereophotogrammetry capture of digital images from three-dimensional surfaces of the head, face, and neck. A mannequin head was prepared for imaging by adding texture in the form of red paint, and facial landmarks as black ink dots. The mannequin was imaged at the manufacturer's recommended settings for human studies. Colour-coded surface difference images among repeated exposures were computed. We compared measurements of physical linear distance with digital measurements. The three-dimensional stereophotogrammetry system had a mean error in the three-dimensional surfaces of 0.057mm, a repeatability error (variance) of 0.0016mm, a mean error of 0.6mm in linear measurements compared with manual measurements, and a field of view of 170 degrees horizontally and 102 degrees vertically.     

Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models

Alcohol use disorder (AUD) is associated with substantial morbidity, mortality, and societal cost, and pharmacological treatment options are limited. The endogenous cannabinoid (eCB) signaling system is critically involved in reward processing, and alcohol intake is positively correlated with release of the eCB ligand 2-arachidonoylglycerol (2-AG) within the reward neurocircuitry. Here we show that genetic and pharmacological inhibition of diacylglycerol lipase (DAGL), the rate-limiting enzyme in the synthesis of 2-AG, reduces alcohol consumption in a variety of preclinical mouse models, ranging from a voluntary free-access model to aversion-resistant drinking and dependence-like drinking induced via chronic intermittent ethanol vapor exposure. DAGL inhibition during either chronic alcohol consumption or protracted withdrawal did not elicit anxiogenic and depression-like behavioral effects. Last, DAGL inhibition also prevented ethanol-induced suppression of GABAergic transmission onto midbrain dopamine neurons, providing mechanistic insight into how DAGL inhibition could affect alcohol reward. These data suggest that reducing 2-AG signaling via inhibition of DAGL could represent an effective approach to reducing alcohol consumption across the spectrum of AUD severity.