Different studies have shown that HPV16‐positive OPSCC can be subdivided based on integration status (integrated, episomal and mixed forms). Because we showed that integration neither affects the levels of viral genes, nor those of virally disrupted human genes, a genome‐wide screen was performed to identify human genes which expression is influenced by viral integration and have clinical relevance. Thirty‐three fresh‐frozen HPV‐16 positive OPSCC samples with known integration status were analyzed by mRNA expression profiling. Among the genes of interest, Aldo‐keto‐reductases 1C1 and 1C3 (AKR1C1, AKR1C3) were upregulated in tumors with viral integration. Additionally, 141 OPSCC, including 48 HPV‐positive cases, were used to validate protein expression by immunohistochemistry. Results were correlated with clinical and histopathological data. Non‐hierarchical clustering resulted in two main groups differing in mRNA expression patterns, which interestingly corresponded with viral integration status. In OPSCC with integrated viral DNA, often metabolic pathways were deregulated with frequent upregulation of AKR1C1 and AKR1C3 transcripts. Survival analysis of 141 additionally immunostained OPSCC showed unfavorable survival rates for tumors with upregulation of AKR1C1 or AKR1C3 (both p <0.0001), both in HPV‐positive (p ≤0.001) and ‐negative (p ≤0.017) tumors. OPSCC with integrated HPV16 show upregulation of AKR1C1 and AKR1C3 expression, which strongly correlates with poor survival rates. Also in HPV‐negative tumors, upregulation of these proteins correlates with unfavorable outcome. Deregulated AKR1C expression has also been observed in other tumors, making these genes promising candidates to indicate prognosis. In addition, the availability of inhibitors of these gene products may be utilized for drug treatment.

Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.

Objective Investigation of the gustatory function in a large cohort of cochlear implanted patients using lateralized taste‐strip tests. Patients and Methods One hundred and seven unilaterally or bilaterally profoundly hearing impaired or deaf patients who received cochlear implants (n = 113) were included in this study. Data on gustometry, subjective gustatory dysfunction, and the detailed surgical procedure were acquired retrospectively. Gustatory function, assessed using lateralized taste‐strip tests, was performed the day before, 3 days after cochlear implantation, and on the day of the initial CI adjustment (39 days ±7.3 SD). Results Averaged taste‐strip scores of the cohort declined significantly from preoperatively 12.3 [11.8; 12.7] (mean [95% confidence intervals]) to 10.5 [9.7; 11.2] on the implanted side about 6 weeks after surgery. Patients with intraoperatively exposed and rerouted, or a severed, chorda tympani nerve (CTN) showed significantly reduced unilateral postoperative scores (10.1 [8.8; 11.4] and 9.3 [8.1; 10.5], respectively), when compared to not exposing or to leaving a bony layer over the CTN. Total taste‐strip test scores showed a significant decline 6 weeks postoperatively in CI‐patients expressing a subjective gustatory dysfunction (from 23.6 [21.4; 25.8] to 17.5 [14.2; 20.8]), as opposed to patients with a documented subjectively normal taste. Conclusion We consider postoperative gustatory dysfunction as a relevant side effect post cochlear implantation, at least within the first month. Taste‐strip based gustometry is a suitable diagnostic tool to assess taste function in CI patients and is recommended to be performed routinely. Level of Evidence 3, retrospective, nonrandomized follow‐up study.

The nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC) is a heterodimeric enzyme with an α and β subunit. NO binds to heme of the β-subunit of sGC, activates the enzyme in the reduced heme iron state in vascular smooth muscle cells (VSMCs), and generates cGMP-inducing vasodilatation and suppression of VSMC proliferation. In the complex tumor milieu with higher levels of reactive oxygen species (ROS), sGC heme iron may become oxidized and insensitive to NO. To change sGC from an NO-insensitive to NO-sensitive state or NO-independent manner, protein expression of sGC in VSMC is required. Whether sGCαβ exists at the protein level in arterial VSMCs of oropharyngeal squamous cell carcinoma (OPSCC) is unknown. In addition, whether differences in the genetic profile between human papillomavirus (HPV)-positive and HPV-negative OPSCC contributes to the regulation of sGCαβ is unclear. Therefore, we compared the effects of HPV-positive and HPV-negative OPSCC on the expression of sGCαβ in arterial VSMCs from tumor-free and tumor-containing regions of human tissue sections using quantitative immunohistochemistry. In comparison to the tumor-free region, we found a decrease in expression of both α- and β-subunits in the arterial VSMC layer of the tumor-containing areas. The OPSCC-induced significant downregulation of the α- and β-subunits of sGC in arterial VSMC was HPV-independent. We conclude that the response of sGC to NO in tumor arterial VSMCs may be impaired by oxidation of the heme of the β-subunit, and thus, α- and β-subunits of sGC could be targeted to degradation under oxidative stress in OPSCC in an HPV-independent manner. The degradation of sGCαβ in VSMCs may result in increased proliferation of VSMCs, promoting tumor arteriogenesis in OPSCC. This can be interrupted by preserving the active heterodimer sGCαβ in arterial VSMCs.

Consation of feed-dependent white muscle disease in suckling lambs in Turkey 50 pregnant ewes kept on a farm in Anatolia (Turkey) were divided into two groups of 25 animals each. They were fed local feeding-stuffs. The untreated group served as the control while the second group received 1 mg Na2Se03 per day over a period of 5 weeks before lambing and 3 weeks after lambing.Except for retarded growth and diminished resistance against infections, which are both typical signs of Se-deficiency, no clinical white muscle disease (WMD) was diagnosed in lambs of the control group although the Se-supply of 0.04-0.06 mg/kg of the diet was insufficient. Se-levels and Se-GSH-Px-activities in blood, liver, kidney and skeletal muscle remained low as described by other authors as characteristic for the development of WMD. The Se-supplemented ration contained 0.71 mg Se/kg during pregnancy and 0.66 mg/kg during the lactation period. Se-concentrations and Se-GSH-Pxactivities in the blood of the ewes as well as those in the milk (0.1 mg Se/l) and Se-contents and GSH-Px-activities in liver, kidneys and skeletal muscle in the lambs were normal.So far as the farms studied can be considered as typical for conditions in Central-Anatolia, the results indicate that sheep and lambs in this region are exposed to a possible insufficient supply of selenium, exacerbated by S-deficiency. This leads to high rearing losses in suckling lambs; even though clinical WMD could not be diagnosed, there was diminished rearing performance.