Tumor T1 Relaxation Time for Assessing Response to Bevacizumab Anti-Angiogenic Therapy in a Mouse Ovarian Cancer Model

Purpose

To assess whether T₁ relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy. Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks. T₁ maps of tumors were generated before, two days, and 2 weeks after initiating therapy. Tumor weight was assessed by MR and at necropsy. Histology for microvessel density, proliferation, and apoptosis was performed.

Results

Bevacizumab treatment resulted in tumor growth inhibition (p<0.04, n=6), confirming therapeutic efficacy. Tumor T₁ relaxation times increased in bevacizumab treated mice 2 days and 2 weeks after initiating therapy (p<.05, n=6). Microvessel density decreased 59% and cell proliferation (Ki67+) decreased 50% in the bevacizumab treatment group (p<.001, n=6), but not apoptosis.

Conclusions

Findings suggest that increased tumor T₁ relaxation time is associated with response to bevacizumab therapy in ovarian cancer model and might serve as an early indicator of response.     

Symptom Clusters in People Living with HIV Attending Five Palliative Care Facilities in Two Sub-Saharan African Countries: A Hierarchical Cluster Analysis

BackgroundSymptom research across conditions has historically focused on single symptoms, and the burden of multiple symptoms and their interactions has been relatively neglected especially in people living with HIV. Symptom cluster studies are required to set priorities in treatment planning, and to lessen the total symptom burden. This study aimed to identify and compare symptom clusters among people living with HIV attending five palliative care facilities in two sub-Saharan African countries.MethodsData from cross-sectional self-report of seven-day symptom prevalence on the 32-item Memorial Symptom Assessment Scale-Short Form were used. A hierarchical cluster analysis was conducted using Ward’s method applying squared Euclidean Distance as the similarity measure to determine the clusters. Contingency tables, X² tests and ANOVA were used to compare the clusters by patient specific characteristics and distress scores.ResultsAmong the sample (N=217) the mean age was 36.5 (SD 9.0), 73.2% were female, and 49.1% were on antiretroviral therapy (ART). The cluster analysis produced five symptom clusters identified as: 1) dermatological; 2) generalised anxiety and elimination; 3) social and image; 4) persistently present; and 5) a gastrointestinal-related symptom cluster. The patients in the first three symptom clusters reported the highest physical and psychological distress scores. Patient characteristics varied significantly across the five clusters by functional status (worst functional physical status in cluster one, p<0.001); being on ART (highest proportions for clusters two and three, p=0.012); global distress (F=26.8, p<0.001), physical distress (F=36.3, p<0.001) and psychological distress subscale (F=21.8, p<0.001) (all subscales worst for cluster one, best for cluster four).ConclusionsThe greatest burden is associated with cluster one, and should be prioritised in clinical management. Further symptom cluster research in people living with HIV with longitudinally collected symptom data to test cluster stability and identify common symptom trajectories is recommended.     

Calprotectin and Platelet Aggregation in Patients with Stable Coronary Artery Disease

BackgroundRecent studies suggest that the inflammation-associated protein calprotectin may be implicated in the pathogenesis of coronary artery disease (CAD). However, the impact of calprotectin levels on platelet aggregation in CAD patients has never been investigated.ObjectivesWe investigated the association between calprotectin levels and platelet aggregation in stable, high-risk CAD patients receiving aspirin as mono antiplatelet therapy. Furthermore, we aimed to investigate independent clinical and laboratory determinants of calprotectin levels.MethodsWe performed a cross-sectional study including 581 stable, high-risk CAD patients. All patients received 75 mg aspirin daily as mono antiplatelet therapy. Platelet aggregation was assessed by 1) impedance aggregometry (Multiplate Analyzer) using arachidonic acid (AA) and collagen as agonists and by 2) the VerifyNow Aspirin Assay. Low-grade inflammation was evaluated by calprotectin, high-sensitive C-reactive-protein (hs-CRP) and interleukin-6. Platelet activation was assessed by soluble P-selectin, and cyclooxygenase-1 inhibition was evaluated by serum thromboxane B₂, both measured by ELISA.ResultsCalprotectin levels correlated positively with platelet aggregation according to Multiplate Analyzer (r=0.12, p=0.01). Additionally, calprotectin was positively associated with leukocytes (r=0.33, p<0.0001), hs-CRP (r=0.31, p<0.0001), interleukin-6 (r=0.28, p<0.0001), soluble P-selectin (r=0.10, p=0.02) and serum thromboxane B₂ (r=0.10, p=0.02). Type 2 diabetes mellitus was an independent predictor of increased calprotectin levels (p=0.004), and trends were seen for body mass index (p=0.06) and smoking (p=0.07). Compliance with aspirin was confirmed by low serum thromboxane B₂ levels in all patients (median [25%;75%]: 1.07 [0.52;1.87] ng/mL).ConclusionCalprotectin levels correlated positively, though weakly, with platelet aggregation and activation as well as serum thromboxane B₂ in high-risk, stable CAD patients treated with aspirin.     

Environmental Factors Related to Pulmonary Tuberculosis in HIV-Infected Patients in the Combined Antiretroviral Therapy (cART) Era

The aim of our study was to evaluate the seasonal variations and whether short-term exposure to environmental risk factors, such as climate and air pollution, is associated with PTB-related hospital admissions in human immunodeficiency virus (HIV)-infected patients in Spain during the era of combined antiretroviral therapy (cART). A retrospective study was carried out using data from the Minimum Basic Data Set (MBDS) and the State Meteorological Agency (AEMET) of Spain. The primary outcome variable was hospital admissions with PTB diagnosis. The environmental risk factors evaluated were season, temperature, humidity, NO₂, SO₂, O₃, PM₁₀, and CO. Overall, HIV-infected patients had a lower frequency of PTB-related hospital admissions in summer (22.8%) and autumn (22.4%), but higher values in winter (26.6%) and spring (28.2%). Using a Bayesian temporal model, PTB-related hospital admissions were less frequent in summer-autumn and more abundant in winter-spring during the first years of follow-up. During the later years of follow-up, the seasonal trends continued resulting in the lowest values in autumn and the highest in spring. When considering short-term exposure to environmental risk factors, lower temperatures at 1 week (odds ratio (OR) = 1.03; p = 0.008), 1.5 weeks (OR = 1.03; p<0.001), 2 weeks (OR = 1.04; p<0.001), and 3 weeks (OR = 1.03; p<0.001) prior to PTB admission. In addition, higher concentration of NO₂ at the time of admission were significantly associated with higher likelihoods of PTB-related hospital admission in HIV-infected patients when 1.5 weeks (OR = 1.1; p = 0.044) and 2 weeks (OR = 1.21; p<0.001) were used as controls. Finally, higher concentration of SO₂ at 1.5 weeks prior to PTB admission was significantly associated with a higher likelihood of PTB-related hospital admissions (OR = 0.92; p = 0.029). In conclusion, our data suggest an apparent seasonal variation in hospital admissions of HIV-infected patients with a PTB diagnosis (summer/autumn vs. winter/spring), as well as a link to short-term exposure to environmental risk factors, such as temperature and ambient NO₂ and SO₂.     

Twelve Weeks of Sprint Interval Training Improves Indices of Cardiometabolic Health Similar to Traditional Endurance Training despite a Five-Fold Lower Exercise Volume and Time Commitment

AimsWe investigated whether sprint interval training (SIT) was a time-efficient exercise strategy to improve insulin sensitivity and other indices of cardiometabolic health to the same extent as traditional moderate-intensity continuous training (MICT). SIT involved 1 minute of intense exercise within a 10-minute time commitment, whereas MICT involved 50 minutes of continuous exercise per session.MethodsSedentary men (27±8y; BMI = 26±6kg/m²) performed three weekly sessions of SIT (n = 9) or MICT (n = 10) for 12 weeks or served as non-training controls (n = 6). SIT involved 3x20-second ‘all-out’ cycle sprints (~500W) interspersed with 2 minutes of cycling at 50W, whereas MICT involved 45 minutes of continuous cycling at ~70% maximal heart rate (~110W). Both protocols involved a 2-minute warm-up and 3-minute cool-down at 50W.ResultsPeak oxygen uptake increased after training by 19% in both groups (SIT: 32±7 to 38±8; MICT: 34±6 to 40±8ml/kg/min; p<0.001 for both). Insulin sensitivity index (CS_I), determined by intravenous glucose tolerance tests performed before and 72 hours after training, increased similarly after SIT (4.9±2.5 to 7.5±4.7, p = 0.002) and MICT (5.0±3.3 to 6.7±5.0 x 10⁻⁴ min^-1 [μU/mL]^-1, p = 0.013) (p<0.05). Skeletal muscle mitochondrial content also increased similarly after SIT and MICT, as primarily reflected by the maximal activity of citrate synthase (CS; P<0.001). The corresponding changes in the control group were small for VO₂peak (p = 0.99), CS_I (p = 0.63) and CS (p = 0.97).ConclusionsTwelve weeks of brief intense interval exercise improved indices of cardiometabolic health to the same extent as traditional endurance training in sedentary men, despite a five-fold lower exercise volume and time commitment.     

Exfoliated oral mucosa cells as bioindicators of short- and long-term systemic titanium contamination

BackgroundHumans are exposed to exogenous sources of titanium-containing particles that can enter the body mainly by inhalation, ingestion, or dermal absorption. Given the widespread use of biomaterials in medicine, the surface of a titanium (Ti) biomedical device is a potential endogenous source of Ti ions and/or Ti-containing particles, such as TiO₂ micro-(MPs) and nano-particles (NPs), resulting from biotribocorrosion processes. Ti ions or Ti-containing particles may deposit in epithelial cells of the oral mucosa, and the latter may therefore serve as bioindicators of short and long-term systemic Ti contamination. The aim of the present study was to histologically and quantitatively evaluate the presence of Ti traces in cells exfoliated from the oral mucosa as possible bioindicators of systemic contamination with this metal at short and long-term experimental time pointsMethodsThirty Wistar rats were intraperitoneally injected with a suspension of titanium dioxide (TiO₂) (0.16 g/100 g body weight of TiO₂ in 5 ml of NaCl 0.9%) using 5 nm NPs (Group: TiO₂-NP5; n = 10), 45 µm MPs (Group: TiO₂-MP45; n = 10), or vehicle alone (Control group; n = 10). At one and six months post-injection, right-cheek mucosa cells were obtained by exfoliative cytology using a cytobrush; they were spray fixed and stained using Safranin or the Papanicolaou technique. The smears were cytologically evaluated (light microscopy) to determine the presence of particulate material, which was also analyzed microchemically (SEM-EDS). Left-cheek mucosa cells were similarly obtained and re-suspended in 5 ml of PBS (pH: 7.2–7.4); the samples corresponding to each group were pooled together and analyzed spectrometrically (ICP-MS) to determine Ti concentration in each of the studied groups. Blood samples were obtained for histological determination of the presence of particulate material on Safranin-stained blood smears and determination of plasma concentration of Ti by ICP-MSResultsDifferent size and shape metal-like particles were observed inside and outside epithelial cells in TiO₂-NP5 and TiO₂-MP45 cytological smears at both one and six months post-injection. EDS analysis showed the presence of Ti in the particles. ICP-MS revealed higher Ti concentrations in both TiO₂ injected groups compared to the control group. In addition, Ti concentration did not vary with time or particle size. Monocytes containing particles were observed in blood smears of TiO₂-exposed animals one- and six-months post-injection. Plasma levels of Ti were significantly higher in TiO₂-NP5- and TiO₂-MP45- exposed animals than in controls (p < 0.05), and Ti concentration was significantly higher at one month than at six months in both TiO₂-exposed groups (p < 0.05).ConclusionsCells exfoliated from the oral mucosa could be used as bioindicators of short- and long-term systemic contamination with Ti. Exfoliative cytology could be used as a simple, non-invasive, and inexpensive diagnostic method for monitoring biotribocorrosion of Ti implants and patient clinical follow-up.     

Nursing Home Staffs' Empathy for a Missing Therapy Dog,their Attitudes to Animal-Assisted Therapy Programs and Suitable Dog Breeds

ABSTRACT

The study was conducted at the Returned Soldiers League (RSL) War Veterans Home at Pinjarra Hills (Brisbane, Queensland, Australia) where a spayed female Whippet, Heidi, was placed as a therapy dog. Of the 80 staff members, 47 (58.75%) returned completed questionnaires on attitudes towards Animal-Assisted Therapy (AAT) programs and the disappearance of Heidi two days after placement. The Pet Attitude Scale (Templer et al. 1981) was used in conjunction with the staff attitude questionnaire.

Respondents with high Pet Attitude scores were more upset (χ²₍₂₎=8.41, p<0.05) and liked dogs more (χ²₍₂₎=7.03, p<0.05) than staff with medium or low scores. The staff with high scores were also more pleased when Heidi returned (χ²₍₁₎=15.97, p<0.05). Respondents who wanted a program were those who liked dogs the most (χ²₍₁₎=7.02, p<0.05) and did not think having an AAT program would increase their workload (χ²₍₁₎=3.77, p<0.05). Staff who thought a dog should live at the nursing home were pleased (χ²₍₁₎=5.2, p<0.05) when Heidi returned.

Gentle/placid dogs were more frequently chosen (78.7%) than active dogs as suitable for AAT and the preferred size was medium (57.5%) with a short coat (78.7%).     

Effect of neurogenic acupoint cupping on high sensitive C-reactive protein and pain perception in female chronic pelvic pain: A randomized controlled trial

Objectives:To determine the effect of neurogenic acupoint dry cupping therapy on high sensitive C-reactive protein (hs-CRP) level, pain perception & intensity, and life impact of pelvic pain in women with chronic pelvic pain (CPP), with regard to the biological and neurophysiological impacts of dry cupping on acupoint.Methods:Thirty women with CPP were randomly divided into two equal groups; the study group received dry cupping on neurogenic acupoints plus lifestyle modifications for 8 weeks (n=15), while the control group received only lifestyle modifications for 8 weeks (n=15). Women were assessed pre- and post-rehabilitation program with the hs-CRP blood test, the short-form McGill Pain Questionnaire (SF-MPQ), and the pelvic pain impact questionnaire (PPIQ).Results:Comparing both groups post-treatment revealed that there were significant reductions in levels of hs-CRP, and scores of SF-MPQ & PPIQ (p<0.05) in the study group compared with the control group. Also, there were significant positive correlations between hs-CRP and both SF-MPQ “Visual Analogue Scale (VAS), Present Pain Intensity (PPI) index & Pain Rating Index (PRI)” and PPIQ (p<0.05).Conclusion:Neurogenic acupoint cupping therapy had significantly improving effects on the degree of inflammation, pain perception & intensity, and life impact of pelvic pain in women with CPP.     

Spontaneous Breathing Pattern as Respiratory Functional Outcome in Children with Spinal Muscular Atrophy (SMA)

IntroductionSMA is characterised by progressive motor and respiratory muscle weakness. We aimed to verify if in SMA children 1)each form is characterized by specific ventilatory and thoraco-abdominal pattern(VTAp) during quiet breathing(QB); 2)VTAp is affected by salbutamol therapy, currently suggested as standard treatment, or by the natural history(NH) of SMA; 3)the severity of global motor impairment linearly correlates with VTAp.ResultsIn SMA1, a normal ventilation is obtained in supine position by rapid and shallow breathing with paradoxical ribcage motion. In SMA2, ventilation is within a normal range in seated position due to an increased respiratory rate(p<0.05) with reduced tidal volume(p<0.05) secondary to a poor contribution of pulmonary ribcage(%ΔV_RC,P, p<0.001). Salbutamol therapy had no effect on VTAp during QB(p>0.05) while tachypnea occurred in type I NH. A linear correlation(p<0.001) was found between motor function scales and VTAp.ConclusionA negative or reduced %ΔV_RC,P, indicative of ribcage muscle weakness, is a distinctive feature of SMA1 and SMA2 since infancy. Its quantitative assessment represents a non-invasive, non-volitional index that can be obtained in all children, even uncollaborative, and provides useful information on the action of ribcage muscles that are known to be affected by the disease.Low values of motor function scales indicate impairment of motor but also of respiratory function.     

Is voice therapy an effective treatment for dysphonia? A randomised controlled trial

ObjectivesTo assess the overall efficacy of voice therapy for dysphonia.Design Single blind randomised controlled trial.Setting Outpatient clinic in a teaching hospital.Participants204 outpatients aged 17-87 with a primary symptom of persistent hoarseness for at least two months.Interventions After baseline assessments, patients were randomised to six weeks of either voice therapy or no treatment. Assessments were repeated at six weeks on the 145 (71%) patients who continued to this stage and at 12-14 weeks on the 133 (65%) patients who completed the study. The assessments at the three time points for the 70 patients who completed treatment and the 63 patients in the group given no treatment were compared.ResultsVoice therapy improved voice quality as assessed by rating by patients (P=0.001) and rating by observer (P<0.001). The treatment effects for these two outcomes were 4.1 (95% confidence interval 1.7 to 6.6) points and 0.82 (0.50 to 1.13) points. Amplitude perturbation showed improvement at six weeks (P=0.005) but not on completion of the study. Patients with dysphonia had appreciable psychological distress and lower quality of life than controls, but voice therapy had no significant impact on either of these variables.ConclusionVoice therapy is effective in improving voice quality as assessed by self rated and observer rated methods.

What is already known on this topic

Many patients with dysphonia are treated by voice therapyThe effectiveness of voice therapy in a diverse group of patients is unknown

What this study adds

Voice therapy is an effective treatment for dysphonia in terms of report by patients and perceptual ratings by an expertPsychological distress and reduction in general health status are common in patients with dysphonia but are not significantly affected by a course of voice therapy     

Nuclear Overhauser Enhancement Imaging of Glioblastoma at 7 Tesla: Region Specific Correlation with Apparent Diffusion Coefficient and Histology

Objective

To explore the correlation between Nuclear Overhauser Enhancement (NOE)-mediated signals and tumor cellularity in glioblastoma utilizing the apparent diffusion coefficient (ADC) and cell density from histologic specimens. NOE is one type of chemical exchange saturation transfer (CEST) that originates from mobile macromolecules such as proteins and might be associated with tumor cellularity via altered protein synthesis in proliferating cells.

Patients and Methods

For 15 patients with newly diagnosed glioblastoma, NOE-mediated CEST-contrast was acquired at 7 Tesla (asymmetric magnetization transfer ratio (MTR_asym) at 3.3ppm, B1 = 0.7 μT). Contrast enhanced T1 (CE-T1), T2 and diffusion-weighted MRI (DWI) were acquired at 3 Tesla and coregistered. The T2 edema and the CE-T1 tumor were segmented. ADC and MTR_asym values within both regions of interest were correlated voxelwise yielding the correlation coefficient r_Spearman (r_Sp). In three patients who underwent stereotactic biopsy, cell density of 12 specimens per patient was correlated with corresponding MTR_asym and ADC values of the biopsy site.

Results

Eight of 15 patients showed a weak or moderate positive correlation of MTR_asym and ADC within the T2 edema (0.16≤r_Sp≤0.53, p<0.05). Seven correlations were statistically insignificant (p>0.05, n = 4) or yielded r_Sp≈0 (p<0.05, n = 3). No trend towards a correlation between MTR_asym and ADC was found in CE-T1 tumor (-0.31<r_Sp<0.28, p<0.05, n = 9; p>0.05, n = 6). The biopsy-analysis within CE-T1 tumor revealed a strong positive correlation between tumor cellularity and MTR_asym values in two of the three patients (r_Sp ^patient3 = 0.69 and r_Sp ^patient15 = 0.87, p<0.05), while the correlation of ADC and cellularity was heterogeneous (r_Sp ^patient3 = 0.545 (p = 0.067), r_Sp ^patient4 = -0.021 (p = 0.948), r_Sp ^patient15 = -0.755 (p = 0.005)).

Discussion

NOE-imaging is a new contrast promising insight into pathophysiologic processes in glioblastoma regarding cell density and protein content, setting itself apart from DWI. Future studies might be based on the assumption that NOE-mediated CEST visualizes cellularity more accurately than ADC, especially in the CE-T1 tumor region.     

Moral Hypocrisy on the Basis of Construal Level: To Be a Utilitarian Personal Decision Maker or to Be a Moral Advisor?

BackgroundPeople encounter various moral issues that involve making decisions for others by giving advice.ObjectiveThis study investigated the characteristics of providing suggestions for oneself versus providing suggestions for others in ethical decision-making and the differences between them based on Construal Level Theory (CLT).MethodsA total of 768 undergraduate students from three universities in China were randomly assigned to eight groups on the basis of a grid of two Construal Levels (self or others) by two different numbers of people saved (5 people or 15 people) by two problem situations (trolley problem vs. footbridge problem). The investigation examined participants’ decisions to opt to take action or refrain from action that would have the consequence of saving more people.ResultsThe main effects of Construal Level (F_{1, 752} = 6.46, p = .011), saving number (F_{1, 752} = 35.81, p < .001), and problem situation type (F_{1, 752} = 330.55, p < .001) were all significant. The interaction of the problem situation and saving number (F_{1, 752} = 1.01, p = .31), and social distance and saving number (F_{1, 752} = 0.85, p = .36), and interaction of the three independent factors (F_{1, 752} = 0.47, p = .49) were not significant. However, the interaction of social distance and problem situation (F_{1, 752} = 9.46, p = .002) was significant. Results indicated the participants utilized a component of utilitarian reasoning in the decision-making, and their behaviors appeared more utilitarian at low Construal Levels (CLs) compared to high.ConclusionCLs, saving numbers, and problem situation significantly affected moral decision-making and exhibited significant interaction. Making decisions for oneself (low-construal) rather than giving advice to others (high-construal) was one important factor that determined whether the people were utilitarian or not. Utilitarian considerations are more relevant in impersonal dilemmas.     

Animal-Assisted Therapy and Depression in Adult College Students

Abstract

This study investigated the effects of animal-assisted therapy (A-AT) on self-reported depression in a college population. Forty-four participants were selected on the basis of scores on the Beck Depression Inventory (BDI). They then were assigned to one of three groups: A-AT in conjunction with psychotherapy (directive group), A-AT only (nondirective group), and control. Standardized regressed BDI posttest scores were used as dependent variables in one-way analysis of variance with treatment as the independent variable. Results revealed significant differences among groups, F(2,41)=3.69, p<.05. Duncan's Multiple Ranges Test indicated that standardized regressed BDI post-test scores differed significantly between nondirective (M=5.67) and control groups (M=10.18).     

Saffron (Crocus Sativus L.), Combined with Endurance Exercise,Synergistically Enhances BDNF,Serotonin, and NT-3 in Wistar Rats

Background:Evidence indicates that combined approaches based on exercise and nutrition benefit neural development. We aimed to determine the effect of saffron and endurance training on hippocampus neurogenic factors, neurotrophin-3 gene expression in soleus muscle, and short-term memory in Wistar rats.Methods:The study analyzed four groups of ten rats each: control, exercise, saffron, and saffron plus exercise. The rats in the exercise groups were trained on a rodent motor-driven treadmill. All rats were gavage daily with either saffron extract (40 mg/kg) or water. After eight weeks of intervention all rats were evaluated using the novel object recognition (NOR) test. Blood and tissue samples were collected to measure proteins and neurotrophin-3 gene expression.Results:Rats that received saffron treatment combined with exercise had significantly greater brain-derived neurotrophic factor (BDNF) and serotonin in hippocampus compared to the control and saffron-only-treated rats (p< 0.05). Neurotrophin-3 mRNA in soleus muscle was higher in the saffron plus exercise group than rats in the other three groups (p< 0.05). Hippocampus 5-hydroxyindolacetic acid and short-term memory were significantly greater in all the intervention groups than in the control group (p< 0.05).Conclusion:Saffron, combined with endurance exercise, synergistically increased hippocampus BDNF, serotonin, and muscular neurotrophin-3 mRNA in Wistar rats.Key Words: Endurance Exercise, Memory, Hippocampus, Saffron, Neurotransmitter     

Promoter Hypermethylation-Related Reduced Somatostatin Production Promotes Uncontrolled Cell Proliferation in Colorectal Cancer

BackgroundSomatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and compare the SST expression during normal aging and colorectal carcinogenesis at mRNA and protein levels. Furthermore, we tested the methylation status of SST in biopsy samples, and the cell growth inhibitory effect of the SST analogue octreotide in human colorectal adenocarcinoma cell line.MethodsColonic samples were collected from healthy children (n1 = 6), healthy adults (n2 = 41) and colorectal cancer patients (CRCs) (n₃ = 34) for SST mRNA expression analysis, using HGU133 Plus2.0 microarrays. Results were validated both on original (n₁ = 6; n₂ = 6; n₃ = 6) and independent samples ((n₁ = 6; n₂ = 6; n₃ = 6) by real-time PCR. SST expressing cells were detected by immunohistochemistry on colonic biopsy samples (n₁ = 14; n₂ = 20; n₃ = 23). The effect of octreotide on cell growth was tested on Caco-2 cell line. SST methylation percentage in biopsy samples (n₁ = 5; n₂ = 5; n₃ = 9) was defined using methylation-sensitive restriction enzyme digestion.ResultsIn case of normal aging SST mRNA expression did not alter, but decreased in cancer (p<0.05). The ratio of SST immunoreactive cells was significantly higher in children (0.70%±0.79%) compared to CRC (0%±0%) (p<0.05). Octreotide significantly increased the proportion of apoptotic Caco-2 cells. SST showed significantly higher methylation level in tumor samples (30.2%±11.6%) compared to healthy young individuals (3.5%±1.9%) (p<0.05).ConclusionsIn cancerous colonic mucosa the reduced SST production may contribute to the uncontrolled cell proliferation. Our observation that in colon cancer cells octreotide significantly enhanced cell death and attenuated cell proliferation suggests that SST may act as a regulator of epithelial cell kinetics. The inhibition of SST expression in CRC can be epigenetically regulated by promoter hypermethylation.     

Neighbourhood Characteristics and Long-Term Air Pollution Levels Modify the Association between the Short-Term Nitrogen Dioxide Concentrations and All-Cause Mortality in Paris

BackgroundWhile a great number of papers have been published on the short-term effects of air pollution on mortality, few have tried to assess whether this association varies according to the neighbourhood socioeconomic level and long-term ambient air concentrations measured at the place of residence. We explored the effect modification of 1) socioeconomic status, 2) long-term NO₂ ambient air concentrations, and 3) both combined, on the association between short-term exposure to NO₂ and all-cause mortality in Paris (France).MethodsA time-stratified case-crossover analysis was performed to evaluate the effect of short-term NO₂ variations on mortality, based on 79,107 deaths having occurred among subjects aged over 35 years, from 2004 to 2009, in the city of Paris. Simple and double interactions were statistically tested in order to analyse effect modification by neighbourhood characteristics on the association between mortality and short-term NO₂ exposure. The data was estimated at the census block scale (n=866).ResultsThe mean of the NO₂ concentrations during the five days prior to deaths were associated with an increased risk of all-cause mortality: overall Excess Risk (ER) was 0.94% (95%CI=[0.08;1.80]. A higher risk was revealed for subjects living in the most deprived census blocks in comparison with higher socioeconomic level areas (ER=3.14% (95%CI=[1.41-4.90], p<0.001). Among these deprived census blocks, excess risk was even higher where long-term average NO₂ concentrations were above 55.8 μg/m³ (the top tercile of distribution): ER=4.84% (95%CI=[1.56;8.24], p for interaction=0.02).ConclusionOur results show that people living in census blocks characterized by low socioeconomic status are more vulnerable to air pollution episodes. There is also an indication that people living in these disadvantaged census blocks might experience even higher risk following short-term air pollution episodes, when they are also chronically exposed to higher NO₂ levels.     

Predictive value of vascular calcification identified in 4D planning CT of lung cancer patients treated with stereotactic body radiation therapy

PurposeThe aim was to identify vascular calcification in 4DCT scan of lung cancer patients and establish the association between overall survival (OS) and vascular calcification, as surrogate for vascular health.MethodsVascular calcification within the thoracic cavity were segmented in 334 lung cancer patients treated with stereotactic body radiation therapy (SBRT). This has been done automatically on 4D planning CT and average reconstruction scans. Correlation between cardiac comorbidity and calcification volumes was evaluated for patients with recorded Adult Co-Morbidity Evaluation (n = 303). Associations between the identified calcifications and OS were further investigated.ResultsThe volume of calcification from the average scan was significantly lower than from each phase (p < 0.001). The highest level of correlations between cardiac comorbidity and volume of the calcifications were found for one phase representing inhale and two phases representing exhale with the least motion blurring due to respiration (p < 0.005). The volume of the calcifications was subsequently averaged over these three phases. The average of calcification volumes over the three phases (denoted by inhale-exhale) showed the highest likelihood in univariate analysis and was chosen as vascular calcification measure. Cox-model suggested that tumor volume (Hazard Ratio [HR] = 1.46, p < 0.01) and inhale-exhale volume (HR = 1.05, p < 0.05) are independent factors predicting OS after adjusting for age, sex, and performance status.ConclusionIt was feasible to use. It 4DCT scan for identifying thoracic calcifications in lung cancer patients treated with SBRT. Calcification volumes from inhale-exhale phases had the highest correlation with overall cardiac comorbidity and the average of the calcification volume obtained from these phases was an independent predictive factor for OS.     

The effects of a diet rich in fish oil on human neutrophils: Identification of leukotriene B5 as a metabolite

Diets that are enriched with fish oil have been shown to alter arachidonic acid metabolism via the cyclooxygenase pathway. Recently it has been shown that one of the major component fatty acids of fish oil, eicosapentaenoate (EPA), is a substrate for the leukotriene B (LTB) pathway when added exogenously to human neutrophils . We fed a diet that contained 8–10 gm/day of EPA to four human subjects for three weeks and compared the arachidonate metabolism of their neutrophils to the same functions while the subjects were on their usual diet. The fish oil-supplementation increased neutrophil EPA content from undetectable levels to 7.4 ± 2.4% (p<0.01, expressed as % of total fatty acid), and decreased arachidonate from 15.4 ± 2.3% to 12.8 ± 2.3% (p<0.05). Leukotriene B₅ was identified as a metabolite during the fish oil-diet by its chromatographic profile and mass spectrum. During the experimental diet LTB₄ decreased from 160 ± 37 ng/10⁷ neutrophils to 120 ± 12 (p<0.05), and LTB₅ increased from 0 to 39 ± 9 ng/10⁷ neutrophils (p<0.005). The diet had no effect on neutrophil aggregation or adherence to nylon fibers.