Sensitivity Ratio Research Articles

Computed Tomography Optic Nerve Sheath Diameter-to-Eyeball Transverse Diameter Ratio as a Novel Noninvasive Parameter for Prognostication in Traumatic Brain Injury.

Background Traumatic brain injury (TBI) remains a foremost cause of death and disability globally, with elevated intracranial pressure (ICP) being a crucial factor in patient outcomes. While invasive monitoring is the gold standard for assessing ICP, it carries risks and is not always feasible. This study proposes a novel noninvasive parameter using computed tomography (CT) imaging. Aims and objectives The study aims to determine the efficacy of the optic nerve sheath diameter (ONSD)-to-eyeball transverse diameter (ETD) ratio from CT scans in predicting TBI patients' prognosis. The primary objective is to study the ONSD/ETD ratio's efficacy in assessing TBI's severity. The secondary objective is to correlate the ONSD/ETD ratio with the Glasgow Coma Scale (GCS) and Rotterdam computed tomography scoring (RCTS) and assess its clinical benefit. Materials and methods This combined retrospective and prospective analytical study included 308 consecutive patients who underwent CT imaging for TBI at a tertiary care center with a dedicated trauma and neurosurgical unit. We evaluated bilateral ONSD and ETD using axial CT scans. The ONSD/ETD ratio correlated with the GCS, RCTS, and clinical outcomes. Results The cut-off values for elevated ICP were ONSD of >5.17 mm, ETD of <22.2 mm, and ONSD/ETD ratio of >0.21. Variables between GCS (<12 and >12) and the ONSD/ETD ratio (<0.21 and >0.21) were statistically significant (chi-square {χ2} = 18.52, p = 0.000). The ONSD shows a strong positive correlation with RCTS (r = 0.82, p = 0.01), ETD shows a moderate negative correlation with RCTS (r = -0.50), and the ONSD/ETD ratio shows a strong negative correlation with GCS (r = -0.783, p = 0.01). The area under the curve for the ONSD/ETD ratio (0.920) was higher than that for ONSD (0.932) and ETD (0.490). The ONSD/ETD ratio's sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 95.6%, 72.0%, and 100%, respectively, demonstrating that it is an excellent predictor of raised ICP. Conclusion The CT-ONSD/ETD ratio correlates with the severity of TBI as assessed by GCS and RCTS. It could serve as a noninvasive parameter for monitoring ICP and guiding the need for sequential CT in TBI patients, potentially aiding in prognostication and clinical management.

EGFR Inhibitor CL-387785 Suppresses the Progression of Lung Adenocarcinoma.

This study aimed to explore the influence of the irreversible EGFR inhibitor CL-387785 on invasion, metastasis, and radiation sensitization of non-small cell lung cancer cells. The proliferation inhibitory rate at different time points was detected by MTT assay. The apoptosis of H1975 cells treated with CL-387785 was detected using flow cytometry. The invasion and migration of H1975 cells treated with CL-387785 were determined by Transwell assay and wound healing assay. The survival fraction (SF) of H1975 cells cultured with CL- 387785 under X-ray (0, 2, 4, 6, 8, and 10 Gy) was detected by cloning formation experiment, and the sensitization ratio (SER) was calculated by clicking the multi-target model to fit the cell survival curve. CL-387785 restrained H1975 cell proliferation in a concentration- and time-dependent manner. CL-387785 promoted H1975 cell apoptosis and reduced cell migration distance and the number of transmembrane cells. The SF treated by different concentrations of CL-387785 (10, 25, 50, and 100 nM) was all below 0 nM. The radiation SER of CL-387785 (10, 25, 50 and 100 nM) were 1.17, 1.39, 2.88, and 3.64, respectively. The invasion and metastasis of H1975 cells were restrained by irreversible EGFR inhibitor CL-387785. CL-387785 also exhibited the effect of radiotherapy sensitization.

T1/T2 ratio: A quantitative sensitive marker of brain tissue integrity in multiple sclerosis.

The aim of this study is to determine whether cerebral white matter (WM) microstructural damage, defined by decreased fractional anisotropy (FA) and increased axial (AD) and radial (RD) diffusivities, could be detected as accurately by measuring the T1/T2 ratio, in relapsing-remitting multiple sclerosis (RRMS) patients compared to healthy control (HC) subjects. Twenty-eight RRMS patients and 24 HC subjects were included in this study. Region-based analysis based on the ICBM-81 diffusion tensor imaging (DTI) atlas WM labels was performed to compare T1/T2 ratio to DTI values in normal-appearing WM (NAWM) regions of interest. Lesions segmentation was also performed and compared to the HC global WM. A significant 19.65% decrease of T1/T2 ratio values was observed in NAWM regions of RRMS patients compared to HC. A significant 6.30% decrease of FA, as well as significant 4.76% and 10.27% increases of AD and RD, respectively, were observed in RRMS compared to the HC group in various NAWM regions. Compared to the global WM HC mask, lesions have significantly decreased T1/T2 ratio and FA and increased AD and RD (p < . 001). Results showed significant differences between RRMS and HC in both DTI and T1/T2 ratio measurements. T1/T2 ratio even demonstrated extensive WM abnormalities when compared to DTI, thereby highlighting the ratio's sensitivity to subtle differences in cerebral WM structural integrity using only conventional MRI sequences.

Synergistic Effect of Phloretin Combined With Radiotherapy on Lung Cancer

The purpose of this study was to investigate the synergistic anti-tumor effects of phloretin and radiotherapy (RT) in a Lewis lung cancer (LLC) xenograft model, and the mechanisms involved.Lewis cells were treated with 0, 25, 50, 100, 150 or 200 μg/ml phloretin, the proliferative rate of Lewis cells treated with phloretin for 12, 24 and 32 h was detected by MTT assay; Clone formation experiments were used to demonstrate the synergistic effect of phloretin and radiotherapy; Mice engrafted with the LLC cells were given intraperitoneal injections of saline, phloretin with or without RT. Tumor models were established by laterally transplanting LLC cells in the right thigh of C57BL/J mice. They were randomly divided into four groups, 12 in each group, namely saline group, phloretin group, radiotherapy group, phloretin combined with radiotherapy group. 10 Gy radiotherapy was performed during the administration; some mice were detected by PET-CT, tumor tissues were subjected to immunohistochemistry, flow apoptosis was detected, and some mice were observed for survival.Different concentrations of phloretin inhibited the proliferation of Lewis cells in a time and dose dependent manner (P < 0.05). The radiotherapy sensitization ratio (SER) of 0.5μg phloretin was 1.645 in the LLC cells. The combination of phloretin and RT increased survival compared to free Phloretin and RT (P < 0.05), and prolonged tumor growth delay (TGD). Furthermore, the RT + phloretin combination therapy significantly reduced 18F-FDG uptake, increased apoptosis and decreased the proliferation index (Ki67) in tumor cells compared to either monotherapy.Phloretin combined with radiotherapy has a synergistic anti-tumor effect, possibly by promoting apoptosis, as well as inhibiting proliferation rate and glucose transport.

Transition Detection for Automatic Segmentation of Wrist-Worn Acceleration Data: A Comparison of New and Existing Methods

Introduction: Data from wrist-worn accelerometers often has an inherent natural segmentation that reflects transitioning from one activity to another. The aim of this study was to develop an activity transition detection method to realize this natural segmentation. Methods: Data was gathered from 16 participants who wore triaxial wrist accelerometers in a lab-based protocol and 47 participants in a free-living protocol. Change point detection was used to create a method for detecting activity transitions. The agreement between observed and predicted transitions was assessed by the Matthews Correlation Coefficient (MCC), Root Mean Squared Error (RMSE), and two additional metrics created for this task; the Ratio of Minimum Mean Distance (RMMD) and the Ratio of Sensitivity (RoS). The effects of varying combinations of acceleration axes were also investigated to determine the most effective set of axes. A novel post-processing technique was developed to mitigate a major limitation identified in current transition detection methods. Results: The developed transition detection method achieved a MCC of 0.763, a RMSE of 3.17, a RoS of 2.40, and a RMMD of 3.21, outperforming existing techniques. The post-processing technique developed improved the performance of all methods when identifying transitions. It was found that using solely the y-axis (vertical acceleration) allowed for optimal performance. Conclusion: Change point detection is a valid method for identifying transitions in activity using wrist-worn accelerometer data. The new post processing technique developed improves the performance of transition detection methods.

Synergistic effect and reduced toxicity by intratumoral injection of cytarabine-loaded hyaluronic acid hydrogel conjugates combined with radiotherapy on lung cancer.

The aim of this study was to explore the synergistic anti-tumor effects of cytarabine hyaluronic acid-tyramine (Ara-HA-Tyr) hydrogel conjugates and radiotherapy (RT) in the Lewis lung cancer (LLC) xenograft model, and the mechanisms involved. The radiotherapy sensitization ratio (SER) of 0.5μg cytarabine (Ara-C) was 1.619 in the LLC cells. Ara-HA-Tyr was prepared by encapsulating Ara-C into hyaluronic acid-tyramine (HA-Tyr) conjugates. The hydrogels were formed through the oxidative coupling of tyramines by hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). Mice engrafted with the LLC cells were given intra-tumoral injections of saline, Ara-C or Ara-HA-Tyr, with or without RT. The combination of Ara-HA-Tyr and RT increased survival compared to free Ara-C and RT (p < 0.05), and prolonged tumor growth delay (TGD). Furthermore, the RT + Ara-HA-Tyr combination therapy significantly reduced 18F-FDG uptake, induced cell cycle arrest at G2/M-phase, increased apoptosis and histone H2AX phosphorylation (γ-H2AX), and decreased the proliferation index (Ki67) in tumor cells compared to either monotherapy. Taken together, Ara-C encapsulated with HA-Tyr effectively sensitized tumor xenografts to RT and showed significantly less systemic toxicity. Graphical abstract In this work, Ara-C encapsulated with hyaluronic acid-tyramine conjugates (HA-Tyr) was prepared and used to investigate its synergistic anti-tumor efficacy by combination with radiotherapy in the Lewis lung cancer xenograft model. The synergistic mechanism may be related to tumor cell cycle redistribution, apoptosis and expression of histone H2AX phosphorylation.

Breast cancer subtype and screening sensitivity in the Quebec Mammography Screening Program.

ObjectiveIn mammography screening, interval cancers present a problem. The metric ‘screening sensitivity’ monitors both how well a programme detects cancers and avoids interval cancers. To our knowledge, the effect of breast cancer surrogate molecular subtypes on screening sensitivity has never been evaluated. We aimed to measure the 2-year screening sensitivity according to breast cancer subtypes.MethodsWe studied 734 women with an invasive breast cancer diagnosed between 2003 and 2007 after participating in one regional division of Quebec’s Mammography Screening Program. They represented 83% of all participating women with an invasive BC diagnosis in that region for that period. Tumours were categorized into ‘luminal A-like’, ‘luminal B-like’, ‘triple-negative’ and ‘HER2-positive’ subtypes. We used logistic regression and marginal standardization to estimate screening sensitivity, sensitivity ratios (SR) and sensitivity differences. We also assessed the mediating effect of grade.ResultsAdjusted 2-year screening sensitivity was 75.4% in luminal A-like, 66.1% in luminal B-like, 52.9% in triple-negative and 45.3% in HER2-positive, translating into sensitivity ratios of 0.88 (95% confidence interval [CI] = 0.78–0.98) for luminal B-like, 0.70 (CI = 0.56–0.88) for triple-negative and 0.60 (CI = 0.39–0.93) for HER2-positive, when compared with luminal A-like. Grade entirely mediated the subtype-sensitivity association for triple negative and mediated it partly for HER2-positive. Screening round (prevalent vs. incident) did not modify results.ConclusionThere was substantial variation in screening sensitivity according to breast cancer subtypes. Aggressive phenotypes showed the lowest sensitivity, an effect that was mediated by grade. Tailoring screening according to women’s subtype risk factors might eventually lead to more efficient programs.

Comparison of inoculation methods for selecting common bean genotypes with physiological resistance to white mold

Although different methods of inoculation have been proposed to assess the reaction of common bean to white mold (WM) caused by Sclerotinia sclerotiorum, a thorough comparison among them is lacking. In this study, six approaches were tested to identify the most reproducible and efficient method for discriminating six common bean genotypes of carioca market class based on their resistance to white mold. These included: modified straw test (ST), cotton pad (CP), infected flower on intact plant (IFIP) or on detached leaf (IFDL), and mycelium disc on intact plant (MDIP) or on detached leaf (MDDL). All experiments were conducted in a greenhouse or laboratory in a completely randomized design with four replicates. Several statistics including coefficient of variation (CV), standard deviation, intraclass correlation coefficient (ICC), p value for Bartlett’s test for homoscedasticity and sensitivity ratio (SR) were used as criteria for discrimination. The Spearman’s correlation coefficient was used to test the association between the methods. Results showed ST as the most suitable for selecting WM-resistant genotypes, followed by the IFIP method.

Detecting Insulin Sensitivity Changes for Individuals with Type 1 Diabetes

Background: A method to calculate changes in insulin needs was developed in the OpenAPS (Open Source Artificial Pancreas System) community. Individuals have natural fluctuations in insulin needs, but excessive periods of sensitivity or resistance may indicate ongoing physiological trends and therefore impact T1D management. Methods: Autosens analyzes each CGM data point for 24 hours, comparing observed change to expected impact from insulin. Autosens calculates the deviation for the median of the last 8 and 24 hours of CGM data points and determines the sensitivity ratio (SR) required to neutralize the median deviation. Autosens was run retrospectively to obtain an hourly SR value (first calculated SR every hour) for (N=1)*16 individuals using OpenAPS; with M=5393 data points, and range=922 to 20,473. A SR of &amp;gt;1.0 indicates resistance; &amp;lt;1.0 indicates sensitivity. Histograms were created to visualize SR for each participant. Mean SR ± SD was calculated and those falling beyond ± 10% of 1.0 were classified as being resistant and sensitive respectively. Results: Mean SR for 12 individuals fell within ±10% of 1.0. 1 individual tended toward sensitivity [0.79 ± 16]. 3 individuals tended toward resistance [1.2 ± 0.28; 1.33 ± 0.30; 1.41 ± 0.37]. Conclusion: Such idiographic visualization of SR can be useful for detecting overall patterns of sensitivity/resistance potentially unaccounted for by the user’s pump settings. Disclosure D.M. Lewis: Consultant; Self; Tandem Diabetes Care, Inc.. S. Leibrand: None. T.J. Street: None. S.S. Phatak: None.

Sequence‑dependent effect of sorafenib in combination with natural phenolic compounds on hepatic cancer cells and the possible mechanism of action.

Sorafenib (Nexavar, BAY43-9006 or Sora) is the first molecular targeted agent that has exhibited significant therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond well to Sora and novel therapeutic strategies to optimize the efficacy of Sora are urgently required. Plant-based drugs have received increasing attention owing to their excellent chemotherapeutic and chemopreventive activities; they are also well tolerated, non-toxic, easily available and inexpensive. It is well known that certain biologically active natural products act synergistically with synthetic drugs used in clinical applications. The present study aimed to investigate whether a combination therapy with natural phenolic compounds (NPCs), including curcumin (Cur), quercetin (Que), kaempherol (Kmf) and resveratrol (Rsv), would allow a dose reduction of Sora without concomitant loss of its effectiveness. Furthermore, the possible molecular mechanisms of this synergy were assessed. The hepatic cancer cell lines Hep3b and HepG2 were treated with Sora alone or in combination with NPCs in concomitant, sequential, and inverted sequential regimens. Cell proliferation, cell cycle, apoptosis and expression of proteins associated with the cell cycle and apoptosis were investigated. NPCs markedly potentiated the therapeutic efficacy of Sora in a sequence-, type-, NPC dose- and cell line-dependent manner. Concomitant treatment with Sora and Cur [sensitization ratio (SR)=28], Kmf (SR=18) or Que (SR=8) was associated with the highest SRs in Hep3b cells. Rsv markedly potentiated the effect of Sora (SR=17) on Hep3b cells when administered in a reverse sequential manner. By contrast, Rsv and Que did not improve the efficacy of Sora against HepG2 cells, while concomitant treatment with Cur (SR=10) or Kmf (SR=4.01) potentiated the cytotoxicity of Sora. Concomitant treatment with Sora and Cur or Kmf caused S-phase and G2/M phase arrest of liver cancer cells and markedly induced apoptosis compared with mono-treatment with Sora, Cur or Kmf. Concomitant treatment with Sora and Cur reduced the protein levels of cyclins A, B2 and D1, phosphorylated retinoblastoma and B-cell lymphoma (Bcl) extra-large protein. By contrast, Sora and Cur co-treatment increased the protein levels of Bcl-2-associated X protein, cleaved caspase-3 and cleaved caspase-9 in a dose-dependent manner. In conclusion, concomitant treatment with Sora and Cur or Kmf appears to be a potent and promising therapeutic approach that may control hepatic cancer by triggering cell cycle arrest and apoptosis. Additional studies are required to examine the potential of combined treatment with Sora and NPCs in human hepatic cancer and other solid tumor types in vivo.

Classification of Different Dried Vine Fruit Varieties in China by HS-SPME-GC-MS Combined with Chemometrics

The volatile profiles of six dried vine fruit varieties produced in Xinjiang province were detected by HS-SPME–GC-MS. In total, 80 compounds were identified; among them, rose oxide, linalool oxide A, linalool oxide B, 3,7-dimethyl-1,5-octadien-3,7-diol, 2-heptenol, and 3-octen-2-one are reported for the first time in dried vine fruits. Chemometrics was used to classify the different dried vine fruit varieties. Principal component analysis (PCA) overviewed the data structure of the six dried vine fruit varieties and two subsets—muscat and non-muscat varieties obtained. Partial least squares discriminant analysis (PLS-DA) was conducted to classify different varieties based on their volatile compounds and generated a perfect classification model with an accuracy of 100% for the external test set. Additionally, to find out potential markers, two variable selection methods were combined with the PLS-DA model and compared—variable importance in projection (VIP) and sensitivity ratio (SR). The SR method was more efficient at identifying the potential volatile markers. The potential markers can successfully classify different dried vine fruit varieties.

Ratio dependence in small number discrimination is affected by the experimental procedure.

Adults, infants and some non-human animals share an approximate number system (ANS) to estimate numerical quantities, and are supposed to share a second, ‘object-tracking,’ system (OTS) that supports the precise representation of a small number of items (up to 3 or 4). In relative numerosity judgments, accuracy depends on the ratio of the two numerosities (Weber’s Law) for numerosities >4 (the typical ANS range), while for numerosities ≤4 (OTS range) there is usually no ratio effect. However, recent studies have found evidence for ratio effects for small numerosities, challenging the idea that the OTS might be involved for small number discrimination. Here we tested the hypothesis that the lack of ratio effect in the numbers 1–4 is largely dependent on the type of stimulus presentation. We investigated relative numerosity judgments in college students using three different procedures: a simultaneous presentation of intermingled and separate groups of dots in separate experiments, and a further experiment with sequential presentation. As predicted, in the large number range, ratio dependence was observed in all tasks. By contrast, in the small number range, ratio insensitivity was found in one task (sequential presentation). In a fourth experiment, we showed that the presence of intermingled distractors elicited a ratio effect, while easily distinguishable distractors did not. As the different ratio sensitivity for small and large numbers has been often interpreted in terms of the activation of the OTS and ANS, our results suggest that numbers 1–4 may be represented by both numerical systems and that the experimental context, such as the presence/absence of task-irrelevant items in the visual field, would determine which system is activated.

A COMPARATIVE STUDY OF THE OVINE HAEMOGRAM: CELL-DYN 3500 VERSUS MANUAL METHODS

Manual hematology techniques traditionally applied in farm animal medicine are time consuming and labor-intensive, especially when large numbers of samples have to be processed. As a result, several automated hematology instruments have been developed for use in these species. An automated hematology analyzer (Abbott Cell-Dyne 3500 system) was used in performing a complete blood cell count and differential counts of white blood cells in sheep blood samples. The system was compared with basic manual hematologic techniques. A linear regression was used to assess correlation between the two methods. Correlation coefficients (R2) were good for the hematocrit, the total white blood cell count, the neutrophils, the lymphocytes and the platelet count, while a poor correlation existed in monocytes, eosinophils and basophils. The automated and the manual technique were also compared in terms of sensitivity using the Sensitivity Ratio (SR). The automated analyzer was slightly more sensitive than the manual technique for all parameters tested except for monocytes, eosinophils and basophils were the difference was greater and the automated analyzer was 1.5, 2.5 and 2 times more reliable, respectively. The method bias was also calculated. It seems that the overall performance of the automated analyzer justifies its utilization in sheep blood analysis, although as for any analyzer used in any species, a stained blood film evaluation remains an indispensable technique to confirm the results being reported by the automated analyzer and provide additional information for the ovine haemogram.

Comparison of five electrocardiographic methods for differentiation of wide QRS-complex tachycardias

To compare the sensitivity (SN), specificity (SP), and diagnostic accuracy (ACC) for ventricular tachycardia (VT) diagnosis of five electrocardiographic methods for wide QRS-complex tachycardia (WCT) differentiation, specifically the Brugada, Bayesian, Griffith, and aVR algorithms, and the lead II R-wave-peak-time (RWPT) criterion. We retrospectively analysed 260 WCTs from 204 patients with proven diagnoses. The SN, SP, ACC, and likelihood ratios (LRs) were determined for the five methods. Of the 260 tracings, there were 159 VTs and 101 supraventricular tachycardias. All five methods were found to have a similar ACC although the RWPT had a lower ACC than the Brugada algorithm (68.8 vs. 77.5%, P = 0.04). The RWPT had lower (60%) SN than the Brugada (89.0%), Griffith (94.2%), and Bayesian (89%) algorithms (P < 0.001). The Griffith algorithm showed lower (39.8%) SP than the RWPT (82.7%), Brugada (59.2%), and Bayesian (52.0%) algorithms (P< 0.05). The positive LRs for a VT diagnosis for the RWPT criterion and the Brugada, Bayesian, aVR, and Griffith algorithms were 3.46, 2.18, 1.86, 1.67, and 1.56, respectively. The present study is the first independent 'head-to-head' comparison of several WCT differentiation methods. We found that all five algorithms/criteria had rather moderate ACC, and that the newer methods were not more accurate than the classic Brugada algorithm. However, the algorithms/criteria differed significantly in terms of SN, SP, and LR, suggesting that the value of a diagnosis may differ depending on the method used.

Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location

We investigated variations in sensitivity of an immunochemical (I-FOBT) and a guaiac (G-FOBT) faecal occult blood test according to type and location of lesions in an average-risk 50- to 74-year-old population. Screening for colorectal cancer by both non-rehydrated Haemoccult II G-FOBT and Magstream I-FOBT was proposed to a sample of 20 322 subjects. Of the 1615 subjects with at least one positive test, colonoscopy results were available for 1277. A total of 43 invasive cancers and 270 high-risk adenomas were detected. The gain in sensitivity associated with the I-FOBT was calculated using the ratio of sensitivities (RSN) according to type and location of lesions, and amount of bleeding. The gain in sensitivity by using I-FOBT increased from invasive cancers (RSN=1.48 (1.16–4.59)) to high-risk adenomas (RSN=3.32 (2.70–4.07)), and was inversely related to the amount of bleeding. Among cancers, the gain in sensitivity was confined to rectal cancer (RSN=2.09 (1.36–3.20)) and concerned good prognosis cancers, because they involve less bleeding. Among high-risk adenomas, the gain in sensitivity was similar whatever the location. This study suggests that the gain in sensitivity by using an I-FOBT instead of a G-FOBT greatly depends on the location of lesions and the amount of bleeding. Concerning cancer, the gain seems to be confined to rectal cancer.

Analysis of Alkenone Unsaturation Indices with Fast Gas Chromatography/Time-of-Flight Mass Spectrometry

Extensively purified C37 alkenone references and mixtures thereof were analyzed by gas chromatography/flame ionization detection (GC/FID) and fast gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS), to establish the latter as an alternative, fast, and reliable analysis method for alkenone unsaturation indices (U(k')(37)). This index is a tool for past sea surface temperature reconstructions with extensive use in paleoclimate and paleoceanographic research. TOF-MS was chosen because of its unique capability to acquire full-range spectra at high data rates (up to 500 spectra s(-1)) and to produce homogeneous spectra across a gaschromatographic peak, allowing faster separations than conventional GC/MS and the employment of enhanced peak deconvolution algorithms. Analysis time per sample could be reduced to run times of <10 min, i.e., by a factor of approximately 10 compared to conventional GC/FID (90-100 min) methods. However, %@mt;sys@%%@ital@%%@bold@%U%@reset@%%@rsf@%%@sx@%37%@be@%%@ital@%k%@rsf@%'%@sxx@%%@mx@% values from GC/TOF-MS showed deviations from those obtained by GC/FID, resulting from sensitivity differences between the C37:2 and C37:3 alkenone when analyzed by GC/TOF-MS. A solution to this bias is presented by determining compound-specific linear response factor equations to derive sensitivity ratios (SR) that allow conversion of GC/TOF-MS values into calibrated GC/FID data. Using alkenone mixtures of known composition and a variety of samples from natural environments, the applicability of this approach is demonstrated.

Mini‐Mental State Examination: standardization and validation for the elderly Slovenian population

For more than two decades Mini-Mental State Examination (MMSE) has been adapted to the Slovenian language as 'Kratek preizkus spoznavnih sposobnosti' (KPSS). In this study, we evaluated the influences of age and education on the KPSS score, looking for the cut-off point with the optimal ratio of sensitivity (SE) and specificity (SP) to support the use of the KPSS as a screening tool. During the years 2000-03 we examined 258 Slovenian volunteers. Volunteers were divided in two groups based on clinical criteria. A total of 189 were healthy, aged from 45 to 96 years, 69 were demented patients aged from 46 to 91 years, of both sexes, all different levels of education and different degrees of dementia. Median value, SE, SP, positive predictive power and negative predictive power were calculated at cut-off points 23/24, 24/25, 25/26 and 26/27. Younger age and higher education (at least 10 years of education) were each associated with higher KPSS scores. The Slovenian modification of the MMSE demonstrates an optimal cut-off score at 25/26 points for screening dementia in the Slovenian population, due to the best SP (75%)/SE (73%) ratio. The cut-off level 26/27 is recommended for screening highly educated persons.

Cytotoxicity of adriamycin, idarubicin, and vincristine in acute myeloid leukemia: chemosensitization by verapamil in relation to P-glycoprotein expression.

A 4-day colorimetric tetrazolium dye (MTT) assay was used to assess the cytotoxicity of adriamycin (ADM), vincristine (VCR), and idarubicin (IDA) in blasts isolated from 37 patients with newly diagnosed and pretreated acute myeloid leukemia (AML). The effect of verapamil (VRP) as a chemosensitizer was studied in relation to the expression of the membrane efflux pump P-glycoprotein (PGP) as determined by a semiquantitative flow-cytometric proceder. A slight positive correlation was found between the fraction of cells expressing PGP and the ID50 values for ADM and VCR, but not between cellular PGP content and sensitivity to IDA. The overall data showed no significant sensitization effect of VRP. However, in specimens with more than 10% cells expressing PGP, 2 microM VRP sensitized cells to ADM and VCR significantly. The median of sensitization ratios (SRs), i.e., the ratios of cytotoxic drug ID50 in the absence/presence of VRP, were 1.89 and 2.0, respectively. No sensitizing effect of VRP on the cytotoxicity of IDA was observed. Related to the clinical status, the median fraction of PGP-positive blasts was elevated fourfold in pretreated patients (n = 16) in comparison to patients with de novo AML (n = 19). No differences in ID50 values were observed between newly diagnosed and pretreated patients. However, SRs for ADM and VCR were higher in samples of pretreated patients compared with de novo AML. PGP-mediated cellular drug resistance may thus be circumvented in leukemic blasts by application of chemosensitizers or, potentially, alternative anthracyclines.