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Objective: Social functioning is an important factor in the evaluation of postoperative health-related quality of life (HRQoL) for pituitary adenoma patients. In a prospective cohort study multidimensional HRQoL of non-functioning (NFA) and functioning (FA) pituitary adenoma patients were evaluated following endoscopic endonasal surgery using the endoscopic endonasal sinus and skull base surgery questionnaire (EES-Q)., Methods: Prospectively, 101 patients were included. The EES-Q was completed preoperatively and postoperatively (2 weeks, 3 months, 1 year). Sinonasal complaints were completed daily during the first week postoperatively. Preoperative and postoperative scores were compared. A generalized estimating equation (uni- and multivariate) analysis was performed to identify significant HRQoL changes related to selected covariates., Results: Two weeks postoperatively, physical ( p  < .05) and social ( p  < .05) HRQoL are worse and psychological ( p  < .05) HRQoL improved compared with preoperatively. Three months postoperatively, psychological HRQoL ( p  = .01) trended back to baseline and no differences in physical or social HRQoL were reported. One year postoperatively, psychological ( p  = .02) and social ( p  = .04) HRQoL improved while physical HRQoL remained stable. FA patients report a worse HRQoL preoperatively (social, p  < .05) and 3 months postoperatively (social, p  < .02 and psychological, p  < .02). Sinonasal complaints peak in the first days postoperatively and gradually return to presurgical levels 3 months postoperatively., Conclusions: The EES-Q provides meaningful information on multidimensional HRQoL to improve patient-centred health care. Social functioning remains the most difficult area in which to achieve improvements. Despite the relatively modest sample size, there is some indication that the FA group continues to show a downward trend (and thus improvement) even after 3 months, when most other parameters reach stability., Level of Evidence: Level II-B., Competing Interests: The authors have no financial or other conflicts to report., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objectives: Endoscopic imaging techniques and endoscopic endonasal surgery (EES) expertise have evolved rapidly. Only few studies have assessed the effect of three-dimensional (3D) endoscopy on endoscopic sinus surgery (ESS). The present study aimed to objectively and subjectively assess the additional value of 3D high-definition (HD) endoscopy in ESS., Design: A randomized crossover study of endoscopic surgery performance, using five ESS tasks of varying complexity, performed on Thiel embalmed human specimens., Setting: Simulated surgical environment., Participants: Thirty participants, inexperienced in ESS., Main Outcome Measures: Performance was assessed using video imaging, surgical navigation and questionnaires. Main outcome measures were as follows: efficiency (defined by time to task completion), distance covered inside the nose, average velocity towards target, accuracy (measured by error rate), and subjective assessment of endoscope characteristics., Results: During ESS tasks, both efficiency and accuracy did not differ significantly between 2D HD and 3D HD endoscopy. Subjectively, imaging characteristics of the 3D HD endoscope were rated significantly better., Conclusions: ESS performance of inexperienced participants was not significantly improved by the use of 3D HD endoscopy during ESS tasks, although imaging characteristics of the 3D HD endoscope were rated significantly better. Surgical field characteristics and surgical techniques are likely to influence any additional value of 3D HD endoscopy., (© 2019 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Objectives: The patients' perspective on health has become increasingly important when assessing treatment outcomes. Recently, the Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire (EES-Q) was developed to determine the impact of endoscopic endonasal surgery on health-related quality of life (HRQoL). The aim of this study was to evaluate the test-retest reliability, construct validity and responsiveness of the EES-Q., Design: Prospective cohort study., Setting: University Medical Center Groningen, tertiary referral hospital, the Netherlands., Participants: One hundred patients who underwent endoscopic endonasal surgery because of sinus or anterior skull base pathology., Main Outcome Measures: Test-retest reliability, construct validity and responsiveness., Results: The EES-Q domains exhibited good test-retest reliability (ICC > 0.90). Construct validity was corroborated by significant positive and negative correlations between the EES-Q and the Sino-Nasal Outcome Test-22 (SNOT-22) and postoperative health status (P < 0.01) respectively. The correlation between the social EES-Q domain and the ability to move and perform usual activities (EuroQol-5D-3L [EQ-5D-3L]) was significant positive (P < 0.01). In patients with paranasal sinus pathology, the EES-Q was responsive to clinical change (Cohen's d = 0.6)., Conclusion: The EES-Q is a reliable and acceptable responsive disease-specific HRQoL instrument. The expected construct validity of the EES-Q is supported by the results in this study. Inconveniences in social functioning had the greatest negative impact on postoperative health status rating. This reflects the importance of a multidimensional HRQoL assessment after EES. The results indicate that the EES-Q is a promising disease-specific tool for the HRQoL assessment after endoscopic endonasal sinus or anterior skull base surgery., (© 2019 John Wiley & Sons Ltd.)

Background: The patients' perspective of health outcomes has become important input for assessing treatment effects. However, existing endoscopic endonasal surgery (EES) instruments are not fully aligned with the concept of health-related quality of life (HRQoL). A prospective cohort study was therefore conducted to develop a suitable quality-of-life tool to assess nasal morbidity after EES: the Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire (EES-Q)., Methods: The study included 300 patients: 207 with sinus pathology and 93 with anterior skull base pathology. The EES-Q was administered prior to surgery and postoperatively (2 weeks, 3 months, and 1 year). Psychometric instrument properties were tested and relevant health domains were formulated. Seventy-two items were generated by the conventional psychometric approach. An exploratory factor analysis was used to test construct validity. The optimal number of factors to retain was determined by using the eigenvalues-greater-than-1 rule and scree plot. Orthogonal varimax rotation was used to enhance interpretability. Internal consistency was assessed using the Cronbach α., Results: The factor analysis yielded a 3-factor solution, representing physical, psychological, and social functioning. The final version of the instrument consisted of 30 items with a high internal consistency (>0.80) for all 3 HRQoL domains., Conclusions: The EES-Q is a comprehensive, multidimensional, disease-specific instrument. A distinguishing characteristic is that, apart from the physical and psychological domains, the EES-Q also encompasses a social domain. Understanding different HRQoL aspects in patients undergoing EES may help caregivers restore, improve, or preserve the patient's health through individualized care, which depends on identifying their specific needs., (© 2017 ARS-AAOA, LLC.)

We hypothesize that three-dimensional imaging using cone beam computed tomography (CBCT) is suitable for calculating nasoseptal flap (NSF) dimensions. To evaluate our hypothesis, we compared CBCT NSF dimensions with anatomical dissections. The NSF reach and vascularity were studied. In an anatomical study (n = 10), CBCT NSF length and surface were calculated and compared with anatomical dissections. The NSF position was evaluated by placing the NSF from the anterior sphenoid sinus wall and from the sella along the skull base towards the frontal sinus. To visualize the NSF vascularity in CBCT, the external carotic arteries were perfused with colored Iomeron. Correlations between CBCT NSFs and anatomical dissections were strongly positive (r > 0.70). The CBCT NSF surface was 19.8 cm(2) [16.6-22.3] and the left and right CBCT NSF lengths were 78.3 mm [73.2-89.5] and 77.7 mm [72.2-88.4] respectively. Covering of the anterior skull base was possible by positioning the NSF anterior to the sphenoid sinus. If the NSF was positioned from the sella along the skull base towards the frontal sinus, the NSF reached partially into the anterior ethmoidal sinuses. CBCT is a valuable technique for calculating NSF dimensions. CBCT to demonstrate septum vascularity in cadavers proved to be less suitable. The NSF reach for covering the anterior skull base depends on positioning. This study encourages preoperative planning of a customized NSF, in an attempt to spare septal mucosa. In the concept of minimal invasive surgery, accompanied by providing customized care, this can benefit the patients' postoperative complaints.

The 2A/2B cleavage of aphtho- and cardiovirus 2A polyproteins is mediated by their 2A proteins 'cleaving' at their own C termini. We have analysed this activity using artificial reporter polyprotein systems comprising green fluorescent protein (GFP) linked via foot-and-mouth disease virus (FMDV) 2A to beta-glucuronidase (GUS) -- forming a single, long, open reading frame. Analysis of the distribution of radiolabel showed a high proportion of the in vitro translation products (approximately 90%) were in the form of the 'cleavage' products GUS and [GFP2A]. Alternative models have been proposed to account for the 'cleavage' activity: proteolysis by a host-cell proteinase, autoproteolysis or a translational effect. To investigate the mechanism of this cleavage event constructs encoding site-directed mutant and naturally occurring '2A-like' sequences were used to program in vitro translation systems and the gel profiles analysed. Analysis of site-directed mutant 2A sequences showed that 'cleavage' occurred in constructs in which all the candidate nucleophilic residues were substituted -- with the exception of aspartate-12. This residue is not, however, conserved amongst all functional '2A-like' sequences. '2A-like' sequences were identified within insect virus polyproteins, the NS34 protein of type C rotaviruses, repeated sequences in Trypanosoma spp. and a eubacterial alpha-glucosiduronasesequence(Thermatoga maritima aguA). All of the 2A-like sequences analysed were active (to various extents), other than the eubacterial alpha-glucosiduronase 2A-like sequence. This method of control of protein biogenesis may well not, therefore, be confined to members of the PICORNAVIRIDAE: Taken together, these data provide additional evidence that neither FMDV 2A nor '2A-like' sequences are autoproteolytic elements.

The simian retrovirus-1 (SRV-1) gag-pro frameshift signal was identified in previous work, and the overall structure of the pseudoknot involved was confirmed (ten Dam E, Brierley I, Inglis S, Pleij C, 1994, Nucleic Acids Res 22:2304-2310). Here we report on the importance of specific elements within the pseudoknot. Some mutations in stem S1 that maintain base pairing have reduced frameshift efficiencies. This indicates that base pairing in itself is not sufficient. In contrast, frameshifting correlates qualitatively with the calculated stability of mutations in S2. The stems thus play different roles in the frameshift event. The nature of the base in L1 has little influence on frameshift efficiency. It is however required to bridge S2; deleting it lowers frameshifting from 23 to 9%. In L2, frameshift efficiency was not affected in a mutant that changed 10 to 12 bases. This makes it unlikely that the primary sequence of L2 plays a role in -1 frameshifting, in contrast to readthrough in Moloney murine leukemia virus (Wills N, Gesteland R, Atkins J, 1994, EMBO J 13:4137-4144). Deletions of 2 and 3 bases gave more frameshifting than the wild type, probably reflecting the increased stability of the pseudoknot due to a shorter loop L2. Deleting even more bases reduces frameshifting compared to wild-type levels. At this point, stress will build up in L2, and this will reduce overall pseudoknot stability.

The pro and pol genes of simian retrovirus-1 (SRV-1) are expressed as parts of a fusion protein generated by -1 ribosomal frameshifting. To investigate the requirements for frameshifting at the gag-pro overlap, we have inserted a stretch of 58 nucleotides containing the proposed frameshift signal into a plasmid that allows monitoring of translation in all three reading frames. In vitro translation of mRNAs derived from this plasmid indicated that the 58 nucleotides from the SRV-1 gag-pro overlap were sufficient to induce an efficient -1 shift in a heterologous context. Mutational analysis demonstrated that the slip site is formed at the heptanucleotide G GGA AAC. The frameshift efficiency of the wild type sequence in rabbit reticulocyte lysate was 23%. A second component of the frameshift signal is formed by a pseudoknot seven bases downstream of the slip site. The presence of this pseudoknot was confirmed by mutational analysis, employing complementary and compensatory base changes, and by probing the structure of short RNA transcripts containing the frameshift signal. Adding increasing amounts of an SRV-1 pseudoknot containing RNA transcript to a translation reaction programmed with an SRV-1 frameshift reporter mRNA had no effect on the frameshift efficiency, arguing against the role of a specific pseudoknot-recognising factor in the frameshifting process.

Ribosomal frameshifting on retroviral RNAs has been proposed to be mediated by slippage of two adjacent tRNAs into the -1 direction at a specific heptanucleotide sequence. Here we report a computer-aided analysis of the structure around the established or putative frameshift sites in a number of retroviral, coronaviral, toroviral, and luteoviral RNAs and two dsRNA yeast viruses. In almost all cases a stable hairpin was predicted four to nine nucleotides downstream of the shifty heptanucleotide. More than half of the resulting hairpin loops give rise to potential pseudoknotting with sequences downstream of this hairpin. Especially in the case of the shifty heptanucleotides U UUA AAC and G GGA AAC, stable downstream pseudoknots are present. Indications were also found for the presence of pseudoknots downstream of amber stop condons at readthrough sites in some retroviral RNAs.