Tumor-associated immune cells have been discussed as an essential factor for the prediction of the outcome of tumor patients. Lymphocyte-specific genes are associated with a favorable prognosis in colorectal cancer but with poor survival in renal cell carcinoma (RCC). Flow cytometric analyses combined with immunohistochemistry were performed to study the phenotypic profiles of tumor infiltrating lymphocytes (TIL) and the frequency of T cells and macrophages in RCC lesions. Data were correlated with clinicopathological parameters and survival of patients. Comparing oncocytoma and clear cell (cc)RCC, T cell numbers as well as activation-associated T cell markers were higher in ccRCC, whereas the frequency of NK cells was higher in oncocytoma. An intratumoral increase of T cell numbers was found with higher tumor grades (G1:G2:G3/4 D 1:3:4). Tumor-associated macrophages slightly increased with dedifferentiation, although the macrophage-to-T cell ratio was highest in G1 tumor lesions. A high expression of CD57 was found in T cells of early tumor grades, whereas T cells in dedifferentiated RCC lesions expressed higher levels of CD69 and CTLA4. TIL composition did not differ between older (>70 y) and younger (<58 y) patients. Enhanced patients' survival was associated with a higher percentage of tumor infiltrating NK cells and Th1 markers, e.g. HLA-DRC and CXCR3C T cells, whereas a high number of T cells, especially with high CD69 expression correlated with a worse prognosis of patients. Our results suggest that immunomonitoring of RCC patients might represent a useful tool for the prediction of the outcome of RCC patients.

RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswitch by in vitro selection and next-generation sequencing-guided cellular screening. The riboswitch recognizes the small molecule drug ciprofloxacin with a KD in the low nanomolar range and adopts a pseudoknot fold stabilized by ligand binding. It efficiently interferes with gene expression both in lower and higher eukaryotes. By controlling an auxotrophy marker and a resistance gene, respectively, we demonstrate efficient, scalable and programmable control of cellular survival in yeast. The applied strategy for the development of the ciprofloxacin riboswitch is easily transferrable to any small molecule target of choice and will thus broaden the spectrum of RNA regulators considerably.

Although tonsil surgery is one of the most frequent otorhinolaryngological procedures, not many population-based regional or country-wide studies are published on the incidence of postoperative bleeding and its risk factors. 2,216 patients underwent tonsil surgery in 2012 in Thuringia, a federal state in Germany. Most frequent indications were recurrent tonsillitis (44 % of all cases), tonsillar abscess (27 %), and tonsillar hyperplasia (20 %). 29 % of the patients were <10 years of age. Most frequent methods of surgery were tonsillectomy (73 %) and tonsillotomy (19 %). 215 patients (10 %) had 221 events of a postoperative hemorrhage. Re-surgery for hemostasis was necessary in 137 patients (6 %). The interval to re-surgery was 4.4 ± 4.6 days. The re-surgery rate was 8, 0.2, and 15 % after tonsillectomy, tonsillotomy, and radical tonsillectomy, respectively. In cases of recurrent tonsillitis, male gender (p < 0.001), age >24.78 years (median; (p = 0.018), and waiving of perioperative antibiotics (p = 0.029) were independent factors associated with hemorrhage. In cases of tonsillar hyperplasia tonsillectomy instead of tonsillotomy, the only significant risk factor was postoperative hemorrhage (p = 0.005). The overall incidence of tonsillar surgery was 87.6/100,000. The highest incidence was seen for patients 3-4 years of age with 862.7/100,000. In children <10 years, the incidence was always higher for boys than for girls. Throughout all age groups, a reverse gender relation was only seen, if surgery was indicated for recurrent tonsillitis. We recommend establishing national guidelines for indication of tonsil surgery, especially of tonsillectomy, including recommendations for perioperative care to decrease variations in tonsil surgery rates and minimize postoperative complications.

Olfactory training consisting of daily suprathreshold odor exposure over 12 weeks seems to improve olfactory function. It is unknown if a longer period of training might be more effective. A prospective non-randomized clinical study was performed including 39 patients with olfactory loss after an upper respiratory tract infection (URTI) of less than 24 months duration. Patients exposed themselves with suprathreshold concentrations of four odors (rose, eucalyptus, lemon, cloves) applied in ''Sniffin' Sticks'' felt-tip pens over 32 weeks. Olfactory function was performed before (T1), after 16 weeks (T2), and 32 weeks of training (T3) using the 'the Sniffin' Sticks test kit calculating the TDI score (Threshold, Discrimination, Identification). The mean TDI score showed a non-significant trend of improvement at T2, and was significantly increased at T3 (p = 0.021). Overall, 31 patients (79%) showed an increased TDI score at T3. The increase of TDI from T1 to T3 was 4.6 ± 5.1. Age, gender, duration and initial severity of olfactory loss had no influence on the improvement (all p > 0.05). Only patients with a D score lower than the median value of 8 showed a significantly higher increase of the D score at T3 (p = 0.004). The present study confirmed that olfactory training improves olfactory function in patients with olfactory loss after URTI. A longer duration of training over 32 weeks seems to increase the effectiveness in comparison to a 12-week period. This was tested in a completed German multicenter trial to be published soon containing a control group to include the effect of a spontaneous recovery after URTI.

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Background: To evaluate the face-specific quality of life after hypoglossal-facial jump nerve suture for patients with long-term facial paralysis. Methods: A single-center retrospective cohort study was performed. Forty-one adults (46% women; median age: 55 years) received a hypoglossal-facial jump nerve suture. Sunnybrook and eFACE grading was performed before surgery and at a median time of 42 months after surgery. The Facial Clinimetric Evaluation (FaCE) survey and the Facial Disability Index (FDI) were used to quantify face-specific quality of life after surgery. Results: Hypoglossal-facial jump nerve suture was successful in all cases without tongue dysfunction. After surgery, the median FaCE Total score was 60 and the median FDI Total score was 76.3. Most Sunnybrook and eFACE grading subscores improved significantly after surgery. Younger age was the only consistent independent predictor for better FaCE outcome. Additional upper eyelid weight loading further improved the FaCE Eye comfort subscore. Sunnybrook grading showed a better correlation to FaCE assessment than the eFACE. Neither Sunnybrook nor eFACE grading correlated to the FDI assessment. Conclusion: The hypoglossal-facial jump nerve suture is a good option for nerve transfer to reanimate the facial muscles to improve facial motor function and face-specific quality of life.

The palatine tonsils, localized in the oropharynx, are easily accessible secondary lymphoid tissue in humans. Inflammation of the palatine tonsils, local and chronic in case of chronic tonsillitis (CT) or acute in the presence of a peritonsillar abscess (PTA), ranks among the most common diseases in otolaryngology. However, the functionality of tonsillar immune cells, notably T-cells, in the context of these immune pathologies is poorly understood. We have examined the functional status of human tonsillar T-cells in CT and compared it to the acute inflammatory setting of a PTA. Patients presenting with CT (n = 10) or unilateral PTA (n = 7) underwent bilateral tonsillectomy and a subgroup of 8 patients underwent additional blood sampling. T-cells were purified via automated magnetic selection and subjected to flow cytometry-based immunophenotyping. In addition, the response to T-cell receptor (TCR) stimulation was assessed at the level of proximal signaling, activation marker expression and proliferation. We observed no difference between the percentage of T helper (CD4(+)) cells from tonsil tissue in CT and PTA, but observed a trend towards a higher percentage of T helper cells in the blood of patients with PTA versus CT, probably reflecting an acute, systemic bacterial infection in the former cohort. Tonsils from CT harbored more PD-1(+) CD4(+) T-cells, pointing to T-cell exhaustion due to chronic infection. This notion was supported by functional studies that showed a tendency to weaker TCR responses of tonsillar T-cells from CT. Intriguingly, tonsillar T-cells recurrently featured a dampened response to T-cell receptor stimulation at the level of receptor proximal signaling steps compared to peripheral T-cells. In sum, our study documents distinct differences in tonsillar T-cell class distribution and function between the various pathological conditions. Our observations are consistent with the concept that tonsillar T-cells react to infections by eliciting specific immunological responses in chronic versus acute settings of inflammation.

Objectives There is a lack of data on patients' and diagnostic factors for prognostication of complete recovery in patients with Bell's palsy. Design and setting Cohort register‐based study of 368 patients with Bell's palsy and uniform diagnostics and standardised treatment in a university hospital from 2007 to 2017 (49% female, median age: 51 years). Main outcome measures Clinical data, facial grading, electrodiagnostics, motor function tests, non‐motor function tests and onset of prednisolone therapy were assessed for their impact on the probability of complete recovery using univariable and multivariable statistics. Results Median onset of treatment was 1.5 days. 46% of patients had a House‐Brackmann scale at baseline of ≥ III. The median recovery time was 2.6 months (95% confidence interval [CI] = 2.1‐3.0). 54.9% achieved a complete recovery. If prednisolone therapy started later than 96 hours after onset, the recovery rate decreased significantly. Beyond less severe palsy, no abnormal electroneurography side difference, no pathological spontaneous activity in electromyography and normal stapedius reflex testing were the most powerful tool for prognostication of recovery after Bell's palsy. Conclusion Beyond severity of the palsy, facial electrodiagnostics and stapedius reflex testing are the most powerful tool for prognostication of recovery time after Bell's palsy. Prednisolone therapy should have started at best within a time window of 96 hours after onset to reach the highest probability of complete recovery.