A new series of glycyrrhetinic acid derivatives has been synthesized via the introduction of different heterocyclic rings conjugated with an α,β-unsaturated ketone in its ring A. These new compounds ...were screened for their antiproliferative activity in a panel of nine human cancer cell lines. Compound
was the most active derivative, with an IC
of 1.1 µM on Jurkat cells, which is 96-fold more potent than that of glycyrrhetinic acid, and was 4-fold more selective toward that cancer cell line. Further biological studies performed in Jurkat cells showed that compound
is a potent inducer of apoptosis that activates both the intrinsic and extrinsic pathways.
The knowledge has been insufficient concerning the effects of peak flows, and local bend and flow characteristics on annual morphodynamics of consecutive bends in meandering rivers. Therefore, it was ...determined how flow peak magnitude and duration affect morphodynamics, how the short‐term spatial evolution of a given meander bend associates with the neighboring bends, and how local bend and flow characteristics affect morphodynamics. The annual bank and point bar morphodynamics of eight consecutive bends of a subarctic meandering river were analyzed between 2009 and 2012 on the basis of high‐accuracy multitemporal data, measured by mobile and terrestrial laser scanning and an Acoustic Doppler Current Profiler. According to the results, multiple years of highly accurate data are crucial for a broader picture of meandering channel evolution. The results showed for the first time in detail that none of the years were similar in terms of point bar and bank morphodynamics. The duration of point bar submergence and maximum water stage was more important for evolution of the meandering channel than the local effects of each bend. The detailed topographical data of the present study confirmed that the higher the flow and water stage peak the more deposition occurred on point bars. More importantly, the independence of the short‐term spatial evolution of meander bends from the association with neighboring bends was confirmed. Erosion patterns did not relate particularly to the sinuosity or radius of curvature. A clear relation between velocity and bend curvature, on which some meander migration models rely, was not found.
Key Points
Bank and point bar morphodynamics are analyzed by means of multitemporal data
Morphodynamics differ annually, but are rather consistent in a given year
Changes are most dependent on spring flow peak characteristics
A series of new glycyrrhetinic acid derivatives was synthesized via the opening of its ring A along with the coupling of an amino acid. The antiproliferative activity of the derivatives was evaluated ...against a panel of nine human cancer cell lines. Compound
was the most active compound, with an IC
of 6.1 µM on Jurkat cells, which is 17-fold more potent than that of glycyrrhetinic acid, and was up to 10 times more selective toward that cancer cell line. Further biological investigation in Jurkat cells showed that the antiproliferative activity of compound
was due to cell cycle arrest at the S phase and induction of apoptosis.
Objectives: Clinical stage at the time of diagnosis is the most important determinant of prognosis in head and neck cancer. Previously, longer diagnostic delay has been shown to worsen prognosis in ...cancer of tongue, pharynx and larynx. The aim of this study was to evaluate the relative importance of patient and professional diagnostic delays in the prognosis of these head and neck cancers.
Design: Population‐based retrospective cohort study.
Setting: Oulu University Hospital (tertiary referral centre) district, Northern Finland.
Participants: Population‐based cohort of 221 patients with tongue, pharyngeal or laryngeal cancer diagnosed in 1986–1996.
Main outcome measures: Patient and professional diagnostic delays, overall survival.
Results: Delays were significantly longer in laryngeal cancer. Moreover, longer diagnostic delays worsened survival markedly only in laryngeal cancer. Cut‐off points at which the delays showed significant adverse impact in prognosis of laryngeal cancer were ≥3 months in patient delay and ≥6 months in professional delay. If mirror laryngoscopy was not performed at the initial visit, professional delay in laryngeal cancer turned out to be significantly longer.
Conclusions: Diagnostic delays are longer and have a more significant impact on survival in laryngeal cancer than in lingual or pharyngeal cancer. Thus, patients with symptoms suggestive of laryngeal process should always be examined properly at the initial visit in order to shorten the professional diagnostic delay in laryngeal cancer.
Knowledge of underwater morphology is an essential component of many hydrological and environmental applications such as flood modelling and lotic habitat mapping. Remote sensing allows modelling of ...bathymetry at spatial scales that are impossible to achieve with traditional methods. However, the use of passive remote sensing for modelling water depth in fluvial environments remains a challenge. Different methods of computing bathymetry models based on remotely sensed imagery combined with ground measurements for calibration were investigated in order to produce a digital bathymetry model of a reach of the river Tana in Lapland. An empirical deep water correction model was evaluated together with theoretical hydraulically assisted bathymetry (HAB) models. The empirical model produced good results, correlating to known depths at 0.98 (R 2 = 0.96) with a mean error of ±12.0 cm. It was demonstrated that usable levels of accuracy can be achieved with data that had previously been considered unsuitable for bathymetry modelling. Some issues related to channel substrate were addressed. The models based on hydraulic theory were tested for the first time outside the area they were developed in. Both models were found to be rather sensitive to certain assumptions, such as the channel friction parameter. The HAB models are able to produce relative depth estimates that can under certain conditions approach actual depths at accuracies similar to the empirical model. Extensive accuracy assessment was performed in order to evaluate the vertical as well as the spatial accuracy of the three models.
The incidence of and mortality from squamous cell carcinoma (SCC) of the tongue have increased during the recent decades in the Western world. Much effort has been made to predict tumour behaviour, ...but we still lack specific prognostic indicators. The aim of our study was to evaluate the relative importance of the known demographic, clinical and histological factors in a homogeneous population-based group of patients with SCC of the mobile tongue. The demographic and clinical factors were reviewed retrospectively from primary and tertiary care patient files. Histological prognostic factors were determined from pre-treatment biopsies. The TNM stage was found to be the most important prognostic factor. In particular, local spread outside the tongue rather than spread to regional lymph nodes was related to poor prognosis. Several demographic and histopathological factors were closely related to TNM stage. When the cases were divided into stage I-II carcinomas and stage III-IV carcinomas, it appeared that the patient's older age (> 65 years), a high malignancy score and an absence of overexpressed p53 protein were associated with a poorer prognosis in stage I-II carcinomas. Such cases may require more aggressive treatment. Among patients with stage III-IV carcinomas, heavy use of alcohol was significantly associated with a poor disease-specific survival time.
Objectives
To assess health‐related quality of life (QoL) and clinical factors predicting it after tonsillectomy among adult patients with recurrent pharyngitis.
Design
Prospective cohort design.
...Setting
Tertiary referral centre.
Participants
Adults (n = 153) who underwent tonsillectomy for recurrent pharyngitis.
Main outcome measures
QoL 6 months after tonsillectomy measured by the Glasgow Benefit Inventory (GBI). Factors predicting high postoperative QoL were sought using multiple linear regression analysis.
Results
Of the 142 patients (93% of all eligible) responding to the GBI questionnaire, 94 (66%) were female; median age was 26 years (range 14–65). GBI Total Scores varied markedly (range −19 to +69), but on average showed improvement (median +27, interquartile range 18–36), most evidently in the GBI Physical Health Score (median +83), after tonsillectomy. Among routinely recorded clinical characteristics, the number of prior pharyngitis episodes, frequent throat pain, untreated dental caries and chronically infected tonsils made up the optimal subset of factors for predicting the GBI Total Score. However, in a random sample of patients (n = 56) for whom preoperative diary‐based data were also available, somewhat better predictive ability was achieved based on just two diary items: number of days with throat pain and with fever during the preceding few months (correlation coefficient, r, between observed and fitted scores improved from 0.39 to 0.55). Yet, the precision of even these predictions was still quite low.
Conclusions
Adult patients with recurrent pharyngitis were on average satisfied after tonsillectomy, regardless of the aetiology of the episodes. Clinical factors rather modestly predicted which patients benefited most from the operation.
Background
The Cochrane database of systematic reviews is an evidence‐based medicine (EBM) database that provides the highest quality evidence of the effect of various treatments. Quality of life ...(QoL) is an important aspect when treatment effect is considered.
Objective
To assess how often patient‐reported outcome measures (PROM), and specifically the quality of life aspect, were evaluated in the randomised controlled trial projects (RCTs) included in the Cochrane database of systematic reviews of the most common ear, throat and nose operations. Also, to explore the same in ongoing trials registered in ClinicalTrials.gov.
Methods
Structured literature search.
Search strategy and evaluation method
The Cochrane database of systematic reviews that evaluated the effects of ventilation tube insertion, adenoidectomy, tonsillectomy and endoscopic sinus surgery was assessed. The RCTs on which the reviews' conclusions were based were explored, and the outcome variables were recorded. A similar search was carried out in the ClinicalTrials.gov trial register.
Results
In the Cochrane database, we identified seven systematic reviews with 30 RCT projects. Fourteen (49%) collected some sort of PROM and of those, three (10%) used a validated QoL instrument. After the year 2000, the respective figures were 12 of 15 (80%) and 3 of 15 (20%). In ClinicalTrials.gov, we found 500 ongoing studies on the most common ENT operations, nine being RCTs relevant to this review. Five (55%) and three (30%) of the ongoing RCTs in ClinicalTrial.gov assess PROM and QoL topics in ENT surgery, respectively.
Conclusions
Since the introduction of QoL instruments in the 1990s, their use has gradually increased, but validated QoL instruments have been used in only one of 10 RCTs included in EBM databases. Ongoing RCTs consider QoL only slightly more often.
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