Determination of cannabinoids in human cerumen samples by use of UPLC-MS/MS as a potential biomarker for drug use.

A quantitative analytical procedure was developed and validated by the use of Ultra- Performance Liquid Chromatography tandem Mass Spectrometry (UPLC-MS/MS) for the determination of Cannabidiol (CBD), Cannabinol (CBN), Δ9-Tetrahydrocannabinol (Δ9-THC), Cannabichromene (CBC), Cannabigerol (CBG) and 11-Nor- 9- Carboxy- Tetrahydrocannabinol (THC-COOH) in an unconventional biological matrix, cerumen. All the investigated calibration curves were characterized by high correlation values (R2 ≥ 0.9965). The LODs and LOQs ranged from 0.004 to 0.009 µg g-1 and 0.012-0.029 µg g-1, respectively. Intra-assay and inter-assay precision were found to be 0.6-2.5%, and 0.8-2.2%, respectively. All recovery values of cannabinoids, with the use of the optimum cotton swab, at low (0.008 µg g-1 of cerumen), medium (0.037 µg g-1of cerumen) and high (0.16 µg g-1 of cerumen) control levels, were estimated to be above 86%. The method developed here permitted the analysis of real cerumen samples obtained from fourteen cannabis users. In twelve out of fourteen cases, Δ9-THC was found to be positive, while in six cases, three major cannabinoids, CBN, CBG and Δ9-THC were quantified at concentrations 0.02-0.21 µg g-1, 0.01-0.24 µg g-1 and 0.01-4.86 µg g-1, respectively. Subject #8 has the highest amount of the detected substances in both left and right ear, with Δ9-THC at a concentration of 1.85 and 4.86 µg g-1, CBG 0.06 and 0.24 µg g-1, CBN 0.10 and 0.21 µg g-1, respectively. In addition, a detection window for the substances Δ9-Tetrahydrocannabinol, Cannabinol and Cannabigerol, in cerumen, was defined with success. In this case, Δ9-THC reached a maximum detection frame of up to fifteen days after smoking 0.5 g of marijuana cigarette. ANOVA-one-way analysis also indicated that the average earwax production of non-cannabis users differs significantly from the one of cannabis users (p = 0.048, <0.05). On the other hand, no significant difference was noticed between male and female users as the p value exceeded 0.05. In addition, no significant effect was observed on earwax production in regard to age, frequency and the last time of use (p > 0.05). These last three factors proved to have a significant impact on cannabinoids concentrations, since p values were less than 0.05.

Unusual polarimetric properties for interstellar comet 2I/Borisov.

So far, only two interstellar objects have been observed within our Solar System. While the first one, 1I/'Oumuamua, had asteroidal characteristics, the second one, 2I/Borisov, showed clear evidence of cometary activity. We performed polarimetric observations of comet 2I/Borisov using the European Southern Observatory Very Large Telescope to derive the physical characteristics of its coma dust particles. Here we show that the polarization of 2I/Borisov is higher than what is typically measured for Solar System comets. This feature distinguishes 2I/Borisov from dynamically evolved objects such as Jupiter-family and all short- and long-period comets in our Solar System. The only object with similar polarimetric properties as 2I/Borisov is comet C/1995 O1 (Hale-Bopp), an object that is believed to have approached the Sun only once before its apparition in 1997. Unlike Hale-Bopp and many other comets, though, comet 2I/Borisov shows a polarimetrically homogeneous coma, suggesting that it is an even more pristine object.

Where to from here? A quality improvement project investigating burns treatment and rehabilitation practices in India.

OBJECTIVE: To describe the capacity of the Indian healthcare system in providing appropriate and effective burns treatment and rehabilitation services. RESULTS: Health professionals involved in burns treatment or rehabilitation at seven hospitals from four states in India were invited to participate in consultative meetings. Existing treatment and rehabilitation strategies, barriers and enablers to patient flow across the continuum of care and details on inpatient and outpatient rehabilitation were discussed during the meetings. Seventeen health professionals from various clinical backgrounds were involved in the consultation process. Key themes highlighted (a) a lack of awareness on burn first aid at the community level, (b) a lack of human resource to treat burn injuries in hospital settings, (c) a gap in burn care training for medical staff, (d) poor hospital infrastructure and (e) a variation in treatment practices and rehabilitation services available between hospitals. A number of opportunities exist to improve burns treatment and rehabilitation in India. Improvements would most effectively be achieved through promoting multidisciplinary care across a number of facilities and service providers. Further research is required to develop context-specific burn care models, determining how these can be integrated into the Indian healthcare system.

Whole-lesion histogram analysis metrics of the apparent diffusion coefficient as a marker of breast lesions characterization at 1.5 T.

INTRODUCTION: To retrospectively assess the role of whole-lesion apparent diffusion coefficient (ADC) in the characterization of breast tumors by comparing different histogram metrics. METHODS: 49 patients with 53 breast lesions underwent magnetic resonance imaging (MRI). ADC histogram parameters, including the mean, mode, 10th/50th/90th percentile, skewness, kurtosis, and entropy ADCs, were derived for the whole-lesion volume in each patient. Mann-Whitney U-test, area under the receiver-operating characteristic curve (AUC) were used for statistical analysis. RESULTS: The mean, mode and 10th/50th/90th percentile ADC values were significantly lower in malignant lesions compared with benign ones (all P < 0.0001), while skewness was significantly higher in malignant lesions P = 0.02. However, no significant difference was found between entropy and kurtosis values in malignant lesions compared with benign ones (P = 0.06 and P = 1.00, respectively). Univariate logistic regression showed that 10th and 50th percentile ADC yielded the highest AUC (0.985; 95% confidence interval [CI]: 0.902, 1.000 and 0.982; 95% confidence interval [CI]: 0.896, 1.000 respectively), whereas kurtosis value yielded the lowest AUC (0.500; 95% CI: 0.355, 0.645), indicating that 10th and 50th percentile ADC values may be more accurate for lesion discrimination. CONCLUSION: Whole-lesion ADC histogram analysis could be a helpful index in the characterization and differentiation between benign and malignant breast lesions with the 10th and 50th percentile ADC be the most accurate discriminators.

Biomechanics of the human intervertebral disc: A review of testing techniques and results.

Many experimental testing techniques have been adopted in order to provide an understanding of the biomechanics of the human intervertebral disc (IVD). The aim of this review article is to amalgamate results from these studies to provide readers with an overview of the studies conducted and their contribution to our current understanding of the biomechanics and function of the IVD. The overview is presented in a way that should prove useful to experimentalists and computational modellers. Mechanical properties of whole IVDs can be assessed conveniently by testing 'motion segments' comprising two vertebrae and the intervening IVD and ligaments. Neural arches should be removed if load-sharing between them and the disc is of no interest, and specimens containing more than two vertebrae are required to study 'adjacent level' effects. Mechanisms of injury (including endplate fracture and disc herniation) have been studied by applying complex loading at physiologically-relevant loading rates, whereas mechanical evaluations of surgical prostheses require slower application of standardised loading protocols. Results can be strongly influenced by the testing environment, preconditioning, loading rate, specimen age and degeneration, and spinal level. Component tissues of the disc (anulus fibrosus, nucleus pulposus, and cartilage endplates) have been studied to determine their material properties, but only the anulus has been thoroughly evaluated. Animal discs can be used as a model of human discs where uniform non-degenerate specimens are required, although differences in scale, age, and anatomy can lead to problems in interpretation.

Adherence to Mediterranean diet and 10-year incidence (2002-2012) of diabetes: correlations with inflammatory and oxidative stress biomarkers in the ATTICA cohort study.

BACKGROUND: The purpose of this work was to investigate the links between oxidative stress, inflammation and coagulation and their effect on Mediterranean diet-diabetes relationship. METHODS: In 2001-2002, a random sample of 1514 men (18-87 years old) and 1528 women (18-89 years old) was selected to participate in the ATTICA study, where Athens is the major metropolis. A validated questionnaire was used to assess lifestyle and dietary factors. Adherence to Mediterranean diet was recorded using MedDietScore. Among others, oxidative stress and inflammatory biomarkers were recorded. During 2011-2012, the 10-year follow-up was performed. Diabetes incidence was defined according to the American Diabetes Association criteria. RESULTS: A total of 191 incident cases of diabetes were documented, yielding an incidence of 12.9% (13.4% in men and 12.4% in women). Medium and high adherence was found to decrease diabetes risk by 49% (95% CI: 0.30, 0.88) and 62% (95% CI: 0.16, 0.88), respectively, compared with low adherence. A logarithmic trend between Mediterranean diet and diabetes incidence was also revealed (p for trend = 0.042). Individuals with abnormal waist circumference (>94 for men, >80 for women) were benefited the most. Wholegrain cereals, fruits and legumes had the greatest predictive ability. The anti-diabetic effect of Mediterranean diet correlated with measurements of tumour necrosis factor-α, homocysteine and total antioxidant capacity. CONCLUSIONS: The reported results support the role of Mediterranean diet as a promising dietary tool for the primary prevention of diabetes, by attenuating inflammation and fostering total antioxidant capacity. This dietary pattern may have therapeutic potential for many cardiometabolic disorders associated with inflammation and/or oxidative stress.

Exploring the path of Mediterranean diet on 10-year incidence of cardiovascular disease: the ATTICA study (2002-2012).

BACKGROUND AND AIMS: A Mediterranean diet has been associated with lower all-cause and cardiovascular disease (CVD) morbidity and mortality, but the clinical and behavioral pathway has not been well understood and appreciated. The aim of this work was to explore the path between adherence to a Mediterranean-type diet, lifestyle behaviors, clinical status, and a 10-year incidence of CVD. METHODS AND RESULTS: The ATTICA study was carried out in the Athens area during 2001-2002 and included 3042 participants free of CVD at baseline (49.8% men, aged 18-89). Adherence to a Mediterranean diet was assessed using the MedDietScore (range 0-55). During 2011-2012, 2583 out of the 3042 participants were found during the 10-year follow-up (15% lost to follow-up). Adherence to a Mediterranean diet decreased CVD risk (relative Risk (RR) per 1/55 unit = 0.96, 95% confidence interval (CI): 0.93, 1.00), independently of various sociodemographic, lifestyle, and clinical factors. Subgroup analyses revealed that participants with an unhealthy lifestyle (i.e., smokers, and obese and sedentary persons) remained protected from CVD through a greater adherence to a Mediterranean diet (RR for smokers = 0.92, 95%CI: 0.88, 0.97; RR for obese participants = 0.90, 95%CI: 0.82, 0.979; and RR for sedentary participants = 0.95, 95%CI: 0.90, 0.99). Path analysis revealed that adherence to a Mediterranean diet not only decreases the levels of C-reactive protein and interleukin-6 but also has an independent protective role against CVD risk per se (total effect of the MedDietScore on CVD = -0.003, 95%CI: -0.005 to 0.000). CONCLUSION: Adherence to a Mediterranean diet confers a considerable reduction on CVD risk, independent of various factors. Therefore, even subjects with unhealthy lifestyle behaviors may benefit from adherence to this diet, suggesting another dimension to prevention strategies.

Radiation doses in a newly founded Interventional Cardiology department.

Coronary angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA) radiation doses were investigated in a recently founded Interventional Cardiology (IC) department. The study includes 336 procedures (177 CAs and 159 PTCAs) carried out with a Philips digital flat detector monoplane system. Patient dose was measured in terms of kerma-area product (KAP) and cumulative dose. Using appropriate conversion factors, peak skin dose (PSD) and effective dose (E) were estimated. Median values of KAP (Gy cm(2)), PSD (mGy) and E (mSv) were: 34 478 and 6.1, respectively for CA and 80 885 and 14.4 for PTCA, within European and international reference levels. Only 1.5 % of patients received radiation dose over the 2 Gy threshold (PTCA procedures) for deterministic effects and none reported any skin effect. Radiation doses were within international standards and comparable with other radiological examinations. The percentage of the high-risk patients for radiation skin effects is extremely low.

Evaluation of radiation dose during pacemaker implantations.

The purpose was to evaluate patient radiation doses and compare with other interventional procedures. One hundred and twenty-eight procedures were carried out with a recently installed mobile undercouch C-arm machine with a 23-cm diameter image intensifier. The radiation dose is provided by the X-ray machine, in terms of cumulative dose (CD). Kerma-Area product (KAP) was then estimated from CD and the X-ray field size. Other patient parameters recorded were patient weight, age, kilovolt, milliampere and fluoroscopy time (T). Median (range) CD, KAP and T were 15.2 mGy (3.2-110 mGy), 6.3 Gy cm(2) (1.3-45.7 Gy cm(2)) and 5.2 (1.5-27.4 min) min, respectively. Median E was 1.1 mSv (conversion factor: 0.18 mSv per Gy cm(2)), which corresponds to approximately one lumbar spine X-ray radiography. The effective dose is much lower than a coronary angiography (8 mSv) or an electrophysiology study (6 mSv). Radiation dose is low compared with other interventional cardiology procedures.

First-trimester combined screening for trisomy 21 at 7-14 weeks' gestation.

OBJECTIVE: To establish an algorithm for first-trimester combined screening for trisomy 21 with biochemical testing from 7 to 14 weeks' gestation and ultrasound testing at 11-13 weeks. METHODS: This was a multicenter study of 886 pregnancies with trisomy 21 and 222 475 unaffected pregnancies with measurements of free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 7-14 weeks' gestation. Multiple regression modeling of log-transformed marker values was used to produce log multiples of the median (MoM) values for PAPP-A and free ß-hCG. The models included terms for the center attended and the machine used for biochemical analysis, gestational age, maternal racial origin, maternal weight, smoking status and method of conception. Bivariate Gaussian distributions were fitted to log MoM PAPP-A and log MoM free ß-hCG in trisomy 21 and in unaffected pregnancies. In each case the patient-specific risk for trisomy 21 was estimated by multiplying the individual maternal age-related risk with the likelihood ratio (LR) for fetal nuchal translucency (NT) according to the mixture model and the combined LR for maternal serum free ß-hCG and PAPP-A. Estimates of detection rates for trisomy 21 and false-positive rates were calculated for combined screening with measurements of NT at 12 weeks together with measurements of free ß-hCG and PAPP-A from 8 to 13 weeks. RESULTS: In trisomy 21 pregnancies the mean log MoM free ß-hCG increased linearly with gestation between 7 and 14 weeks, whereas the relation between log MoM PAPP-A and gestation was fitted by a quadratic equation such that the maximum separation between trisomy 21 and unaffected pregnancies occurs at 9-10 weeks. At a false-positive rate of 3% the detection rate of combined screening at 12 weeks was 86% and this increased to 90% by biochemical testing at 9 weeks and ultrasound scanning at 12 weeks. The detection rate increased to 92% by measuring PAPP-A at 9 weeks and free ß-hCG at the time of the scan at 12 weeks. CONCLUSION: The performance of first-trimester biochemical screening for trisomy 21 is best at 9-10 weeks rather than at 7-8 or 11-14 weeks.

Paclitaxel plus gallium nitrate and filgrastim in patients with refractory malignancies: a phase I trial.

To determine the maximally tolerated dose of paclitaxel with and without filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a 120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m2/24 hours, 40 patients were entered onto a trial lasting from September 1994 to September 1996. Eligibility included a diagnosis of an advanced malignancy not amenable to curative therapy and up to one previous chemotherapy regimen for metastatic disease. Gallium was administered at a fixed dose of 300 mg/m2/day as a continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m2 was given concurrently with the last 24 hours of the gallium as a 24-hour intravenous infusion. Cycles were repeated every 21 days. Once the maximum tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 microg/kg/day days 7-16) was added and paclitaxel dose escalation continued. The MTD for paclitaxel without G-CSF was 110 mg/m2 and 225 mg/m2 with G-CSF, with neutropenia being the dose-limiting toxicity. A partial response was noted in a patient who had thymoma and a complete response was achieved in a patient who had colon cancer. The recommended phase II dosage is gallium nitrate at 300 mg/m2/day over 120 hours, with paclitaxel at 110 mg/m2 over 24 hours without G-CSF or 225 mg/m2 over 24 hours with G-CSF and 0.5 mg calcitriol on days 1 through 7. Further trials of this modified regimen for outpatient administration are in progress.

Sequence variation in the src gene product affects metastasis formation: the central, but not exclusive, role of the tumor immune response.

Sequence variation in the src gene product could, in principle, influence metastasis formation through either of 2 effects: an alteration in tumor antigenicity or a non-immune-mediated change in one or more src-associated functions. Our present results establish that both mechanisms underlie the difference in relative levels of metastasis formation induced by the v-src vs. the c-src(527) oncogene. A point that emerges from this analysis is the segregation, within a chicken line genotypically uniform at the major histocompatibility (B) complex (MHC), of a phenotype defined by strong resistance to secondary v-src-induced tumor challenge. The pattern of segregation is consonant with the possibility that a gene unlinked to the MHC governs immune response levels to v-src-encoded tumor antigen.

Endogenous c-src as a determinant of the tumorigenicity of src oncogenes.

We have compared the tumorigenicity of two src oncogenes, v-src and c-src(527), whose respective protein products pp60v-src and pp60c-src(527) show a different spectrum of amino acid substitutions vis-à-vis the c-src protooncogene-encoded product pp60c-src. Whereas the extent of primary tumor growth induced by c-src(527) was quite similar in the two chicken lines tested, the extent of v-src-induced tumor growth showed a marked line dependence. As examined with a line of chickens that shows immune-mediated regression of v-src-induced tumors, a weaker tumor immunity, as correlated with a greater level of primary tumor growth, resulted from inoculation of c-src(527) DNA than of v-src DNA. These observations indicated that the v-src-specific amino acid substitutions define a major tumor antigenicity. That a separate src-associated antigenicity is also targetable by the tumor immune response followed from the finding that the level of protective immunity against the growth of c-src(527) DNA-induced tumors was augmented under conditions of the prior regression of v-src DNA-induced tumors. As this latter antigenicity may include one or more c-src(527)-encoded peptides that are equivalent to c-src-encoded self peptides, these observations suggest that a host tolerance to pp60c-src can be broken so as to permit a tumor immune response based on recognition of self peptides of pp60c-src(527).

Major histocompatibility (B) complex control of the formation of v-src-induced metastases.

Previous observations have shown that the major histocompatibility (B) complex is a determinant of the growth of v-src-induced primary tumors. In the present study, we have observed with two chicken lines congenic for B complex alleles that the control of v-src-mediated oncogenesis by the B complex extends to metastasis formation. In addition, our results show that the differences in metastasis frequencies between these two lines are correlated with the relative strengths of their respective tumor immune responses.

[Computerized tomography studies of normal morphology and volumetry of parenchymatous epigastric organs in humans]. / Computertomographische Untersuchungen zur normalen Morphologie und Volumetrie parenchymatöser Oberbauchorgane des Menschen.

Variations in the area and dimensions of the liver and spleen in the craniocaudal direction show a similar behaviour despite individual differences in the size and shape of the organs. The liver has its largest areal extent in the upper half of the organ. In the case of the spleen, it is not possible for the largest areal extent to be assigned to a particular region of the organ. The 5-type liver classification of FROMMHOLD and KOISCHWITZ (1982) provided the basis for a study of the frequency distribution of those types among a total of 116 organs. Type 2 (location of the greater part of the liver to the right of the vertebral column) was found to be the most frequent type, whereas type 5 (left lobe of the liver larger than the right one) could not be found. Of the 183 splenic organs included in these studies, 21% showed lobulation and 6%, an accessory spleen. The morphological studies of 334 adrenal glands enabled the most frequent variants of form to be represented summarily. The determination of liver dimensions, which was done on 37 organs, yielded a mean value of 16.6 cm for the craniocaudal extent, 15.5 cm for the dorsoventral extent, and 16.6 cm for the lateromedial extent. From the examinations performed on 38 individuals it was possible to determine a mean value of 11.1 cm for the craniocaudal extent of the spleen, 11.8 cm for the anatomical length of the spleen, 10.4 cm for the width of the spleen, and 4.2 cm for the thickness of the spleen. The mean value of the width of pancreas was 20.5 mm at the head, 19.6 mm at the corpus, and 18 mm at the tail. The mean length of pancreas was of the order of 129 mm. These results were obtained from examinations made on 96 pancreatic organs. Evaluation of a total of 200 computer tomograms yielded mean values of 22 mm for the length. 14 mm for the width, and 5 mm for the leg thickness of the left adrenal gland. The respective mean values obtained for the right adrenal gland were 28 mm, 9 mm, and 4 mm respectively. Determination of the volume of liver on 37 organs yielded a mean value of 1,331 cm3. For the spleen, examinations performed on 38 organs showed the mean volume to be in the order of 169 cm3. For the volume of pancreas, a mean value of 40.4 cm3 was determined.

The detection of alpha-fetoprotein in HBs Ag and HBe Ag carriers.

We detected the alpha-fetoprotein (AFP) in 100 sera of HBsAg and HBeAg carriers, by radioimmunoassay (RIA). High values of AFP in 12 HBsAg carriers (mean value: 168,5 ng/ml) were found. Lower values were found in 3 HBeAg carriers (mean value: 22,5 ng/ml). We will study the prognostic and diagnostic value of this carcinoembryonic antigen in HBsAg and HBeAg carriers, and will consider the possible role of AFP in the development of primary hepatocellular carcinoma. We believe that the increased AFP levels seen during hepatic parenchymal regeneration may depress immunity in some cases, or alter immunosupervision in others, and this facilitates the development of neoplasia in liver.