Genetic alterations associated with 18F-fluorodeoxyglucose positron emission tomography/computed tomography in head and neck squamous cell carcinoma

BackgroundWe investigated the relationship between genetic alterations and ¹⁸F-FDG PET/CT findings in head and neck squamous cell carcinoma (HNSC).MethodsUsing mRNA-sequences of HNSC samples (480 patients) from the Cancer Genome Atlas (TCGA) portal, gene coexpression networks were constructed via a weighted correlation network analysis (WGCNA) algorithm, and their association with the tumor-to-blood signal ratio on ¹⁸F-FDG PET/CT data (21 patients) was explored. An elastic-net regression model was developed to estimate the PET tumor-to-blood ratio from the gene networks and to derive an FDG signature score (FDG_SS). The FDG_SS was evaluated with regard to clinical variables and general mutational profiles, as well as alterations to oncogenic signaling pathways.FindingsThe FDG_SS values differed across clinical stages (p = 0.027), HPV-status (p< 0.001), and molecular subtypes of HNSC (p< 0.001). Multivariate Cox regression demonstrated that FDG_SS was an independent predictor for overall (p = 0.019) and progression-free survival (p = 0.024). FDG_SS positively correlated with total mutation rate (p = 0.016), aneuploidy (p < 0.001), and somatic copy number alteration scores (p < 0.001). CDKN2A in the cell cycle pathway (q = 0.014) and the TP53 gene in the TP53 pathway (q = 0.005) showed significant differences between high and low FDG_SS patients.ConclusionFDG_SS based on the gene coexpression network was associated with the mutational landscape of HNSC. ¹⁸F-FDG PET/CT is therefore a valuable tool for the in vivo imaging of these cancers, being able to visualize the glucose metabolism of the tumor and allow inferences to be made on the underlying genetic alterations in the tumor.     

Normoxic polymer gel dosimetry using less toxic monomer of N-isopropyl acrylamide and X-ray computed tomography for radiation therapy applications

Background

Polymer gel dosimetry has been used extensively in radiation therapy for its capability in depicting a three dimensional view of absorbed dose distribution. However, more studies are required to find less toxic and more efficient polymers for application in radiotherapy dosimetry.

Aim

The purpose of this work was to evaluate the N-isopropyl acrylamide (NIPAM) gel dosimetric characteristics and optimize the protocol for X-ray computed tomography (CT) imaging of gel dosimeters for radiation therapy application.

Material and methods

A polymer gel dosimeter based on NIPAM monomer was prepared and irradiated with ⁶⁰Co photons. The CT number changes following irradiation were extracted from CT images obtained with different sets of imaging parameters.

Results

The results showed the dose sensitivity of ΔN_CT (H) = 0.282 ± 0.018 (H Gy⁻¹) for NIPAM gel dosimeter. The optimized set of imaging exposure parameters was 120 kV_p and 200 mA with the 10 mm slice thickness. Results of the depth dose measurement with gel dosimeter showed a great discrepancy with the actual depth dose data.

Conclusion

According to the current study, NIPAM-based gel dosimetry with X-ray CT imaging needs more technical development and formulation refinement to be used for radiation therapy application.     

Deep learning for predicting subtype classification and survival of lung adenocarcinoma on computed tomography

ObjectivesThe subtype classification of lung adenocarcinoma is important for treatment decision. This study aimed to investigate the deep learning and radiomics networks for predicting histologic subtype classification and survival of lung adenocarcinoma diagnosed through computed tomography (CT) images.MethodsA dataset of 1222 patients with lung adenocarcinoma were retrospectively enrolled from three medical institutions. The anonymised preoperative CT images and pathological labels of atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, invasive adenocarcinoma (IAC) with five predominant components were obtained. These pathological labels were divided into 2-category classification (IAC; non-IAC), 3-category and 8-category. We modeled the classification task of histological subtypes based on modified ResNet-34 deep learning network, radiomics strategies and deep radiomics combined algorithm. Then we established the prognostic models in lung adenocarcinoma patients with survival outcomes. The accuracy (ACC), area under ROC curves (AUCs) and C-index were primarily performed to evaluate the algorithms.ResultsThis study included a training set (n = 802) and two validation cohorts (internal, n = 196; external, n = 224). The ACC of deep radiomics algorithm in internal validation achieved 0.8776, 0.8061 in the 2-category, 3-category classification, respectively. Even in 8 classifications, the AUC ranged from 0.739 to 0.940 in internal set. Further, we constructed a prognosis model that C-index was 0.892(95% CI: 0.846–0.937) in internal validation set.ConclusionsThe automated deep radiomics based triage system has achieved the great performance in the subtype classification and survival predictability in patients with CT-detected lung adenocarcinoma nodules, providing the clinical guide for treatment strategies.     

Body mass index modulates the relationship of sugar-sweetened beverage intake with serum urate concentrations and gout

IntroductionBoth sugar-sweetened beverage (SSB) intake and body mass index (BMI) are associated with elevated serum urate concentrations and gout risk. The aim of this study was to determine whether the associations of SSB intake with serum urate and gout are moderated by BMI.MethodThe effects of chronic SSB intake on serum urate and gout status were analysed in a large cross-sectional population study. The effects of an acute fructose load on serum urate and fractional excretion of uric acid (FEUA) were examined over 180 minutes in a short-term intervention study. In all analyses, the responses were compared in those with BMI <25 mg/kg² (low BMI) and ≥25 mg/kg² (high BMI).ResultsIn the serum urate analysis (n = 12,870), chronic SSB intake was associated with increased serum urate in the high BMI group, but not in the low BMI group (P_difference = 3.6 × 10⁻³). In the gout analysis (n = 2578), chronic high SSB intake was associated with gout in the high BMI group, but not in the low BMI group (P_difference = 0.012). In the acute fructose loading study (n = 76), serum urate was increased in the high BMI group at baseline and throughout the observation period (P_{BMI group} <0.0001), but there were similar acute serum urate increases in both BMI groups in response to the fructose load (P_interaction = 0.99). The baseline FEUA was similar between the two BMI groups. However, following the fructose load, FEUA responses in the BMI groups differed (P_interaction <0.0001), with increased FEUA at 120 minutes and 180 minutes in the low BMI group and reduced FEUA at 60 minutes in the high BMI group.ConclusionsThese data suggest that BMI influences serum urate and gout risk in response to chronic SSB intake, and renal tubular uric acid handling in response to an acute fructose load. In addition to many other health benefits, avoidance of SSBs may be particularly important in those with overweight/obesity to prevent hyperuricaemia and reduce gout risk.

Trials registration

Australian Clinical Trials Registry ACTRN12610001036000. Registered 24 November 2010.     

Early cartilage abnormalities at the hip are associated with obesity and body composition measures – a 3.0T MRI community-based study

IntroductionAlthough obesity is a risk factor for hip osteoarthritis (OA), the role of body composition, if any, is unclear. This study examines whether the body mass index (BMI) and body composition are associated with hip cartilage changes using magnetic resonance imaging (MRI) in community-based adults.Methods141 community-based participants with no clinical hip disease, including OA, had BMI and body composition (fat mass and fat free mass) measured at baseline (1990 to 1994), and BMI measured and 3.0 T MRI performed at follow-up (2009–2010). Femoral head cartilage volume was measured and femoral head cartilage defects were scored in the different hip regions.ResultsFor females, baseline BMI (β = −26 mm³, 95% Confidence interval (CI) -47 to −6 mm³, p = 0.01) and fat mass (β = −11 mm³, 95% CI −21 to −1 mm³, p = 0.03) were negatively associated with femoral head cartilage volume. Also, while increased baseline fat mass was associated with an increased risk of cartilage defects in the central superolateral region of the femoral head (Odds Ratio (OR) = 1.08, 95% CI 1.00–1.15, p = 0.04), increased baseline fat free mass was associated with a reduced risk of cartilage defects in this region (OR = 0.82, 95% CI 0.67–0.99; p = 0.04). For males, baseline fat free mass was associated with increased femoral head cartilage volume (β = 40 mm³, 95% CI 6 to 74 mm³, p = 0.02).ConclusionsIncreased fat mass was associated with adverse hip cartilage changes for females, while increased fat free mass was associated with beneficial cartilage changes for both genders. Further work is required to determine whether modifying body composition alters the development of hip OA.     

New Insights into the Microvascular Mechanisms of Drag Reducing Polymers: Effect on the Cell-Free Layer

Drag-reducing polymers (DRPs) significantly increase blood flow, tissue perfusion, and tissue oxygenation in various animal models. In rectangular channel microfluidic systems, DRPs were found to significantly reduce the near-wall cell-free layer (CFL) as well as modify traffic of red blood cells (RBC) into microchannel branches. In the current study we further investigated the mechanism by which DRP enhances microvascular perfusion. We studied the effect of various concentrations of DRP on RBC distribution in more relevant round microchannels and the effect of DRP on CFL in the rat cremaster muscle in vivo. In round microchannels hematocrit was measured in parent and daughter branch at baseline and after addition of DRP. At DRP concentrations of 5 and 10 ppm, the plasma skimming effect in the daughter branch was eliminated, as parent and daughter branch hematocrit were equivalent, compared to a significantly lowered hematocrit in the daughter branch without DRPs. In anesthetized rats (N=11) CFL was measured in the cremaster muscle tissue in arterioles with a diameter of 32.6 ± 1.7 µm. In the control group (saline, N=6) there was a significant increase in CFL in time compared to corresponding baseline. Addition of DRP at 1 ppm (N=5) reduced CFL significantly compared to corresponding baseline and the control group. After DRP administration the CFL reduced to about 85% of baseline at 5, 15, 25 and 35 minutes after DRP infusion was complete. These in vivo and in vitro findings demonstrate that DRPs induce a reduction in CFL width and plasma skimming in the microvasculature. This may lead to an increase of RBC flux into the capillary bed, and thus explain previous observations of a DRP mediated enhancement of capillary perfusion.     

Drug-Related Problems in Patients with Benign Prostatic Hyperplasia: A Cross Sectional Retrospective Study

Benign Prostatic Hyperplasia (BPH) patients are at risk of acquiring drug-related problems (DRPs), as it is present in the majority of aging men. To date, DRPs among BPH patients have not been well studied. We conducted this retrospective study in a tertiary hospital in Malaysia from January 2009 to June 2012 with the aim of identifying the factors associated with DRPs among BPH patients. The Pharmaceutical Care Network Europe Classification Version (PCNE) 5.01 was used as a tool to classify DRPs. We enrolled 203 patients from 259 hospital admissions. A total of 390 DRPs were found and there was an average of 1.5±1.3 problems per hospitalization. 76.1% of hospital admissions included at least one DRP. The most common DRP categories encountered were drug choice problems (45.9%), drug interactions (24.9%), and dosing problems (13.3%). Factors such as advanced age (p = 0.005), a hospital stay of more than 6 days (p = 0.001), polydrug treatments (p<0.001), multiple comorbidities (p<0.001), and comorbid cardiovascular disease (p = 0.011), diabetes mellitus(p = 0.001), hypertension (p<0.001) and renal impairment (p = 0.011) were significantly associated with the occurrence of DRPs. These data indicated that the prevalence of DRPs is high among BPH patients. The identification of different subtypes of DRPs and the factors associated with DRPs may facilitate risk reduction for BPH patients.     

Sensorineural Hearing Loss after Combined Intensity Modulated Radiation Therapy and Cisplatin-Based Chemotherapy for Nasopharyngeal Carcinoma

PURPOSE: The incidence of sensorineural hearing loss (SNHL) after treatment with combination of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy in nasopharyngeal carcinoma (NPC) patients was evaluated, and relationships of SNHL with host factors, treatment-related factors, and radiation dosimetric parameters were investigated. METHODS: Fifty-one NPC patients treated with IMRT from 2004 to 2009 were analyzed. All patients received neoadjuvant, concurrent, or adjuvant use of cisplatin. Pure tone audiometry was performed during the follow-up period with a median time of 60 months, ranging from 28 to 84 months. Correlation of SNHL at low frequencies (pure tone average, 0.5-2 kHz) with a series of factors was analyzed. RESULTS: Among 102 ears, 12.7% had low-frequency SNHL and 42.2% had high-frequency (4 kHz) SNHL. The incidence of low-frequency SNHL was greater in patients with age > 40, with T-stage 4, or who received cumulative cisplatin dose (CCD) > 200 mg/m² (P = .034, .011, and .003, respectively) and in ears with secretory otitis media (SOM) (P = .002). Several dosimetric parameters were found to be correlated with SNHL. Univariate analysis showed that the minimum radiation dose to 0.1 ml highest dose volume (D0.1 ml) of the cochlea was the best radiation-related predictive parameter. Multivariate analysis indicated that CCD, SOM, and D0.1 ml of cochlea (P = .035, .012, and .022, respectively) were the factors associated with SNHL. CONCLUSION: For NPC patients treated with IMRT and chemotherapy, the incidence of treatment-related SNHL was associated with CCD, D0.1 ml of cochlea, and SOM.     

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

Melanocortin 4 receptor (MC4R) has a major role in energy homeostasis. The rs17782313 polymorphism, mapped 188 kb downstream from MC4R, has been associated with satiety, higher body mass index (BMI) and total calorie intake in adults. To assess the association of rs17782313 with gastric functions, satiation, or satiety, we studied 178 predominantly Caucasian overweight and obese people: 120 females, 58 males; mean BMI 33.4 ± 5.3 kg/m² (SD); age 37.7 ± 11.2 years. Quantitative traits assessed were gastric emptying (GE) of solids and liquids; fasting and postprandial gastric volume; satiation by maximum tolerated volume and 4 symptoms by 100-mm visual analog scales (VAS); and satiety by ad libitum buffet meal. Associations of genotype and quantitative traits were assessed by analysis of covariance (using gender and BMI as covariates), based on a dominant [TC (n = 72) − CC (n = 12) vs. TT (n = 94)] genetic model. rs17782313(C) was associated with postprandial satiation symptoms (median Δ total VAS 26.5 mm, p = 0.036), reduced proportion of solid GE at 2 h (median Δ 6.7 %, p = 0.008) and 4 h (median Δ 3.2 %, p = 0.006), and longer t_½ (median Δ 6 min, p = 0.034). Associations of rs17782313 with obesity may be explained by reduced satiation and GE. The role of MC4R mechanisms in satiation and gastric function deserves further study.     

Visceral fat obesity is highly associated with primary gout in a metabolically obese but normal weighted population: a case control study

IntroductionGout is a chronic inflammatory disease the development of which is associated with obesity-induced metabolic abnormalities. However, a substantial number of non-obese patients (body mass index [BMI] <25 kg/m²) also develop gout in Korea. It was suggested that accumulation of visceral fat rather than subcutaneous fat is associated with metabolic abnormalities and hyperuricemia in patients with gout; therefore, we hypothesized that visceral fat accumulation was increased in non-obese gout patients.MethodsOne hundred and three male patients with primary gout and 204 age-matched healthy controls who attended a health check-up examination were recruited after the review of medical charts. The visceral fat area (VFA) was measured using the bioelectrical impedance analysis (BIA) method, and a VFA >100 cm² was defined as visceral fat obesity (VFO). The frequency of VFO was compared in patients and control groups. The frequencies of metabolic syndrome and related parameters were also investigated.ResultsBMI, waist circumference, total fat mass, serum triglycerides, and serum glucose levels were significantly greater in patients compared with controls. VFA and the prevalence of VFO was increased in gout patients compared with controls. There were positive correlations between VFA and serum triglyceride levels and serum glucose levels. Multivariate regression analysis revealed that VFO is an independent risk factor for gout (odds ratio 2.488, 95% confidence interval 1.041–4.435). In non-obese subgroup analyses (gout patients, n = 38; healthy controls, n = 150), VFA (98.7 ± 19.3 vs. 91.0 ± 16.7, P = 0.016) and the frequency of VFO (47.4 vs. 27.3%, P = 0.017) remained significantly higher in gout patients. There was no difference in either BMI or total fat mass between patients and controls in the non-obese subgroup. The prevalence of metabolic syndrome in patients with gout was 31.7% (33/104), compared with 13.2% (5/38) in the non-obese subgroup according to modified ATP III criteria.ConclusionVFO, measured using BIA, is observed more frequently in patients with primary gout compared with healthy controls, even in non-obese individuals. Therefore, VFO might more properly represent metabolic derangements in patients with gout than general obesity.     

Feasibility and accuracy of tissue characterization with dual source computed tomography

PurposeTo evaluate the feasibility and accuracy of a model for tissue characterization with dual source computed tomography (DSCT).Methods and MaterialsA model for tissue characterization in CT was used with a parameterization of linear attenuation coefficients. Sixteen chemical substances with effective atomic numbers between 5.21 and 13.08 and electron densities between 2.20 and 4.12 x10²³ electrons/cm³ were scanned at energies of 80 and 140 kV on a DSCT. From the reconstructed dual energy data sets, effective atomic numbers and electron densities of the substances were calculated.ResultsOur presented model using DSCT approximated the effective atomic numbers and effective electron densities of 16 substances very well. The measured effective atomic numbers deviated 3.4 ± 6.8% (R² = 0.994) from theoretical effective atomic numbers. In addition, measured effective electron densities deviated ?0.6 ± 2.2% (R² = 0.999) from theoretical effective electron densities.ConclusionEffective atomic numbers and effective electron densities can be determined with a high accuracy with DSCT. Therefore the model can be of potential benefit for clinical applications of quantitative tissue characterization with DSCT.     

Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup’ik people

n-3 Polyunsaturated fatty acids (n-3 PUFAs) have anti-obesity effects that may modulate risk of obesity, in part, through interactions with genetic factors. Genome-wide association studies (GWAS) have identified genetic variants associated with body mass index (BMI); however, the extent to which these variants influence adiposity through interactions with n-3 PUFAs remains unknown. We evaluated 10 highly replicated obesity GWAS single nucleotide polymorphisms (SNPs) for individual and cumulative associations with adiposity phenotypes in a cross-sectional sample of Yup’ik people (n = 1,073) and evaluated whether genetic associations with obesity were modulated by n-3 PUFA intake. A genetic risk score (GRS) was calculated by adding the BMI-increasing alleles across all 10 SNPs. Dietary intake of n-3 PUFAs was estimated using nitrogen stable isotope ratio (δ¹⁵N) of red blood cells, and genotype–phenotype analyses were tested in linear models accounting for familial correlations. GRS was positively associated with BMI (p = 0.012), PBF (p = 0.022), ThC (p = 0.025), and waist circumference (p = 0.038). The variance in adiposity phenotypes explained by the GRS included BMI (0.7 %), PBF (0.3 %), ThC (0.7 %), and WC (0.5 %). GRS interactions with n-3 PUFAs modified the association with adiposity and accounted for more than twice the phenotypic variation (~1–2 %), relative to GRS associations alone. Obesity GWAS SNPs contribute to adiposity in this study population of Yup’ik people and interactions with n-3 PUFA intake potentiated the risk of fat accumulation among individuals with high obesity GRS. These data suggest the anti-obesity effects of n-3 PUFAs among Yup’ik people may, in part, be dependent upon an individual’s genetic predisposition to obesity.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-013-0340-z) contains supplementary material, which is available to authorized users.     

Gender-specific genetic associations of polymorphisms in ACE,AKR1C2, FTO and MMP2 with weight gain over a 10-year period

Weight gain, when it leads to overweight or obesity, is nowadays one of the major health problems. ACE, FTO, AKR1C2, TIMP4 and MMP2 genes have been implicated in previous studies on weight regulation. This study investigated the contribution of polymorphisms in these five candidate genes to the risk of weight gain over a 10-year time period. Two groups were selected from participants of the Doetinchem cohort study who were followed over a 10-year period: A stable weight group (±2 kg/10 year; n = 259) and a weight gainers group who increased their body weight by roughly 10 % (>8 kg/10 year; n = 237). Starting BMI was between 20 and 35 kg/m² and baseline age between 20 and 45 years. Selected SNPs and insert/deletion in candidate genes were measured in each group. In men, the allelic distribution of FTO rs9939609 (χ²p = 0.005), ACE rs4340 (χ²p = 0.006) and AKR1C2 rs12249281 (χ²p = 0.019) differed between the weight stable and weight gainers group. Interaction between FTO rs9939609 and ACE rs4340 was observed. In women, the allelic distribution of MMP2 rs1132896 differed between the weight stable and weight gainers group (χ²p = 0.00001). The A-allele of FTO was associated with a 1.99× higher risk of gaining weight in men (OR 1.99, p = 0.020), while in women, the C-allele of MMP2 was associated with a 2.50× higher risk of weight gain (OR 2.50, p = 0.001) over the 10-year period. We found that FTO in men and MMP2 in women are associated with weight gain over a 10-year follow-up period.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0434-2) contains supplementary material, which is available to authorized users.     

Whole-Body Insulin Sensitivity Rather than Body-Mass-Index Determines Fasting and Post-Glucose-Load Growth Hormone Concentrations

Background

Obese, non-acromegalic persons show lower growth hormone (GH) concentrations at fasting and reduced GH nadir during an oral glucose tolerance test (OGTT). However, this finding has never been studied with regard to whole-body insulin-sensitivity as a possible regulator.

Methods

In this retrospective analysis, non-acromegalic (NonACRO, n = 161) and acromegalic (ACRO, n = 35), non-diabetic subjects were subdivided into insulin-sensitive (IS) and –resistant (IR) groups according to the Clamp-like Index (CLIX)-threshold of 5 mg·kg⁻¹·min⁻¹ from the OGTT.

Results

Non-acromegalic IS (CLIX: 8.8±0.4 mg·kg⁻¹·min⁻¹) persons with similar age and sex distribution, but lower (p<0.001) body-mass-index (BMI = 25±0 kg/m², 84% females, 56±1 years) had 59% and 70%, respectively, higher (p<0.03) fasting GH and OGTT GH area under the curve concentrations than IR (CLIX: 3.5±0.1 mg·kg⁻¹·min⁻¹, p<0.001) subjects (BMI = 29±1 kg/m², 73% females, 58±1 years). When comparing on average overweight non-acromegalic IS and IR with similar anthropometry (IS: BMI: 27±0 kg/m², 82% females, 58±2 years; IR: BMI: 27±0 kg/m², 71% females, 60±1 years), but different CLIX (IS: 8.7±0.9 vs. IR: 3.8±0.1 mg·kg⁻¹·min⁻¹, p<0.001), the results remained almost the same. In addition, when adjusted for OGTT-mediated glucose rise, GH fall was less pronounced in IR. In contrast, in acromegalic subjects, no difference was found between IS and IR patients with regard to fasting and post-glucose-load GH concentrations.

Conclusions

Circulating GH concentrations at fasting and during the OGTT are lower in non-acromegalic insulin-resistant subjects. This study seems the first to demonstrate that insulin sensitivity rather than body-mass modulates fasting and post-glucose-load GH concentrations in non-diabetic non–acromegalic subjects.     

Evaluation of 18F-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

PurposeProstate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of ¹⁸F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence.Methods71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01–67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq ¹⁸F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of ¹⁸F-PSMA-1007 were evaluated.Results56 (79%) patients showed at least one pathological finding on ¹⁸F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7–10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001).Conclusion¹⁸F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients.     

Cardiac Mechanics and Ventricular Twist by Three-Dimensional Strain Analysis in Relation to B-Type Natriuretic Peptide as a Clinical Prognosticator for Heart Failure Patients

BackgroundThree dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored.MethodsWe studied 200 subjects (mean age: 60.2±16 years, 54% female, female n = 107) with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis (Artida, Toshiba Medical Systems, Tokyo, Japan). We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes.ResultsThe global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all p<0.001). Global twist measurements were estimated to be 9.49°, 9.77°, 8.32°, and 4.56°, respectively. We observed significant differences regarding 3D-derived longitudinal, radial, and global 3D strains between the different disease categories (p<0.05), even when age, gender, BMI and heart rate were matched. In addition, 3D-derived longitudinal, circumferential, and 3D strains were all highly correlated with brain natriuretic peptide levels (p<0.001). At a mean 567.7 days follow-up (25^th–75^th IQR: 197–909 days), poorer 3D-derived longitudinal, radial, and global 3D strain measurements remained independently associated with a higher risk of cardiovascular related death or hospitalization due to heart failure, after adjusting for age, gender, and left ventricular ejection fraction (all p<0.05).Conclusions3D-based strain analysis may be a feasible and useful diagnostic tool for discriminating the extent of myocardial dysfunction. Furthermore, it is able to provide a prognostic value beyond traditional echocardiographic parameters in terms of ejection fraction.     

Identifying high‐density areas of oysters using species distribution modeling: Lessons for conservation of the native Ostrea edulis and management of the invasive Magallana (Crassostrea) gigas in Sweden

AimUnderstanding spatial patterns of the distribution of adult native oyster, Ostrea edulis, and the invasive Magallana (Crassostrea) gigas is important for management of these populations. The aim of this study was to use ensemble SDM’s to (a) identify and predict conservation hotspots, (b) assess the current level of protection for O. edulis, and (c) quantify the amount of overlap between the two species where interactions with M. gigas are most likely.LocationSkagerrak, Sweden.MethodsWe used data collected by video at depths from 0.5 to 10 m in 436 sites. Models of occurrence and densities >1 m⁻² were fitted and assessed using ensemble methods (“biomod2” package). Models of high‐density hotspots were used to predict, map, and quantify areal extent of the species in order to assess the degree of overlap with protected areas and the potential for interactions between the two species.ResultsBoth species were widely distributed in the region. Observations of high‐density habitats, mainly occurring at depths of ≈3 and 0.5 m for O. edulis and M. gigas, respectively, were found in 4% and 2% of the sites. Models provided useful predictions for both species (AUC = 0.85–0.99; sensitivity = 0.74–1.0; specificity = 0.72–0.97). High‐density areas occupy roughly 15 km² each with substantial overlap between species. 50% of these are protected only by fisheries regulations, 44% are found in Natura 2000 reserves and 6% of the predicted O. edulis enjoys protection in a national park.Main conclusionsData collection by video in combination with SDM’s provides a realistic approach for large‐scale quantification of spatial patterns of marine population and habitats. O. edulis and M. gigas are common in the area, but a large proportion of the most valuable O. edulis habitats are not found in protected areas. The overlap between species suggests that efforts to manage the invasive M. gigas need to be integrated with management actions to conserve the native O. edulis.     

Prevalence,incidence and characteristics of the metabolic syndrome (MetS) in a cohort of Mexican Mestizo early rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs: the complex relationship between MetS and disease activity

IntroductionA higher prevalence of metabolic syndrome (MetS) has been described in rheumatoid arthritis (RA), along with an association with disease activity. Objectives were to describe prevalence of MetS at RA diagnosis in a cohort of Mexican Mestizo early RA patients, and to define a causal association between MetS and disease activity.MethodsThe study population was a prospective cohort. At baseline and at fixed 6-months-intervals, patients had medical evaluations, fasting serum glucose, triglycerides, high-density lipoprotein cholesterol and acute reactant-phase determinations. MetS was defined according to international criteria and body mass index (BMI) ≥30 kg/m² was used as a surrogate of the waist circumference. The study was approved by the internal review board. Appropriated statistics and Cox regression analysis were used. All statistical tests were two-sided and evaluated at the 0.05 significance level.ResultsUp to March 2014, data from 160 patients were analyzed. At baseline, they were more frequently middle-aged females and had moderate to high disease activity. Prevalence of MetS varied from 11.3% to 17.5% in patients and was lower to that from matched controls (versus 26.3% to 30%, P ≤0.01).Up to last follow-up, 39 patients (34.5%) developed incidental MetS. In the Cox regression analysis, cumulative disease activity score (DAS) 28 (odds ratio (OR): 1.81, 95% confidence interval (CI): 1.346 to 2.433, P = 0.000) and baseline BMI (OR: 1.13, 96% CI: 1.035 to 1.236, P = 0.007) were the only predictors for incidental MetS.RA patients with incidental MetS accumulated more disease activity and had less frequent remission than their counterparts. Logistic regression analysis showed that incidental MetS (OR: 0.2, 95% CI: 0.01 to 0.99, P = 0.052) and baseline DAS28 (OR: 0.4, 95% CI: 0.2 to 0.9, P = 0.02) were the only predictors for achieving or maintaining sustained (≥6 months) remission.ConclusionsMetS prevalence in a cohort of early RA patients was lower than that from matched controls. Cumulative disease activity and higher BMI were risk factors for incidental Mets; higher baseline disease activity and incidental MetS prevented sustained remission. In addition to disease activity, MetS needs to be controlled to impact disease outcomes.     

Effect of dexamethasone prodrug on inflamed temporomandibular joints in juvenile rats

IntroductionJuvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ.MethodsJoint inflammation was initiated by injecting two doses of complete Freund’s adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague–Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson’s correlations.ResultsCFA caused a significant reduction in CsGoInf (p < 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p < 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. <0.01 % lymphocytes in contralateral controls (p < 0.0001). Both P-DEX TMJ (10.1 ± 1.2 %) and systemic P-DEX (8.9 ± 1.7 %) reduced lymphocytes (p < 0.002). The total area of inflammatory infiltrate was significantly less in the systemic injection group than in the group that received CFA injections alone (2.6 ± 1.5 mm² vs. 8.0 ± 1.3 mm²; p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm²).ConclusionsHigh-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density.     

Heritability and genetic etiology of habitual physical activity: a twin study with objective measures

Twin studies with objective measurements suggest habitual physical activity (HPA) are modestly to highly heritable, depending on age. We aimed to confirm or refute this finding and identify relevant genetic variants using a candidate gene approach. HPA was measured for 14 days with a validated triaxial accelerometer (Tracmor) in two populations: (1) 28 monozygotic and 24 dizygotic same-sex twin pairs (aged 22 ± 5 years, BMI 21.8 ± 3.4 kg/m², 21 male, 31 female pairs); (2) 52 and 65 unrelated men and women (aged 21 ± 2 years, BMI 22.0 ± 2.5 kg/m²). Single nucleotide polymorphisms (SNPs) in PPARD, PPARGC1A, NRF1 and MTOR were considered candidates. Association analyses were performed for both groups separately followed by meta-analysis. Structural equation modeling shows significant familiality for HPA, consistent with a role for additive genetic factors (heritability 57 %, 95 % CI 32–74 %, AE model) or common environmental factors (47 %, 95 % CI 23–65 %, CE model). A moderate heritability was observed for the time spent on low- and high-intensity physical activity (P ≤ 0.05), but could not be confirmed for the time spent on moderate-intensity physical activity. For PPARD, each additional effect allele was inversely associated with HPA (P ≤ 0.01; rs2076168 allele C) or tended to be associated with HPA (P ≤ 0.05; rs2267668 allele G). Linkage disequilibrium existed between those two SNPs (alleles A/G and A/C, respectively) and meta-analysis showed that carriers of the AAGC haplotype were less physically active than carriers of the AAAA and AA AC haplotypes combined (P = 0.017). For PPARGC1A, carriers of AA in rs8192678 spent more time on high-intensity physical activity than GG carriers (P = 0.001). No associations were observed with SNPs in NRF1 and MTOR. In conclusion, HPA may be modestly heritable, which is confirmed by an association with variants in PPARD.