Disparity in 90Sr and 137Cs uptake in Alpine plants: phylogenetic effect and Ca and K availability

Background and aims

Uptake of ⁹⁰Sr and ¹³⁷Cs in plants varies widely between soil types and between plant species. It is now recognized that the radionuclide uptake in plants is more influenced by site-specific and plant-specific parameters rather than the bulk radionuclide concentration in soil. We hypothesized that the stress which Alpine plants experience because of the short growing season may enhance the phylogenetic effect on the ¹³⁷Cs and ⁹⁰Sr transfer factors as well as the dependency of the uptake by plant to the concentrations of exchangeable Ca and K of soils.

Methods

We carried out a field study on the ⁹⁰Sr and ¹³⁷Cs uptake by 11 species of Alpine plants growing on 6 undisturbed and geochemically different soils in the Alpine valley of Piora, Switzerland.

Results

Results show that a strong correlation exists between the log TF and the log of exchangeable Ca or K of the soils.

Conclusions

Cs uptake by Phleum rhaeticum (Poales) and Alchemilla xanthochlora (Rosales) is more sensitive to the amount of exchangeable K in the soil than the corresponding uptake by other orders. Moreover, the ⁹⁰Sr results indicate a phylogenetic effect between Non-Eudicot and Eudicots: the order Poales (Phleum rhaeticum) concentrating much less ⁹⁰Sr than Eudicots do.     

A Strontium-Modified Titanium Surface Produced by a New Method and Its Biocompatibility In Vitro

Objective

To present a new and effective method of producing titanium surfaces modified with strontium and to investigate the surface characteristics and in vitro biocompatibility of titanium (Ti) surfaces modified with strontium (Sr) for bone implant applications.

Materials and Methods

Sr-modified Ti surfaces were produced by sequential treatments with NaOH, strontium acetate, heat and water. The surface characteristics and the concentration of the Sr ions released from the samples were examined. Cell adhesion, morphology and growth were investigated using osteoblasts isolated from the calvaria of neonatal Sprague-Dawley rats. Expression of osteogenesis-related genes and proteins was examined to assess the effect of the Sr-modified Ti surfaces on osteoblasts.

Results

The modified titanium surface had a mesh structure with significantly greater porosity, and approximately5.37±0.35at.% of Sr was incorporated into the surface. The hydrophilicity was enhanced by the incorporation of Sr ions and water treatment. The average amounts of Sr released from the Sr-modified plates subjected to water treatment were slight higher than the plates without water treatment. Sr promoted cellular adhesion, spreading and growth compared with untreated Ti surfaces. The Sr-modified Ti plates also promoted expression of osteogenesis-related genes,and expression of OPN and COL-І by osteoblasts. Ti plates heat treated at 700°C showed increased bioactivity in comparison with those treated at 600°C. Water treatment upregulated the expression of osteogenesis-related genes.

Conclusions

These results show that Sr-modification of Ti surfaces may improve bioactivity in vitro. Water treatment has enhanced the response of osteoblasts. The Sr-modified Ti heat-treated at 700°C exhibited better bioactivity compared with that heated at 600°C.     

Adsorption of Radionuclides (134Cs, 85Sr, 226Ra, 241Am) by Extracted Biomasses of Cyanobacteria (Nostoc Carneum, N. Insulare, Oscillatoria Geminata and Spirulina Laxis-Sima) and Phaeophyceae (Laminaria Digitata and L. Japonica; Waste Products from Alginate Production) at Different pH

The extracted biomasses of four cyanobacteria (Nostoc carneum, Nostoc insulare, Oscillatoria geminata, and Spirulina laxissima) grown in axenic mass cultures, and of four samples of Laminaria obtained from different locations (L. digitata I and II, France; L. japonica I and II, China; all waste products from alginate production) were tested for their ability to adsorb four radionuclides (¹³⁴Cs, ⁸⁵Sr, ²²⁶Ra, and ²⁴¹Am) under different pH regimes. In addition, two of the cyanobacterial biomasses (N. carneum. and O. geminata) and the four Laminaria biomasses were phosphorylated before being tested as radionuclide adsorbers. The non-phosphorylated cyanobacterial biomasses showed very low adsorption of ¹³⁴Cs but substantially higher removal of ⁸⁵Sr and ²²⁶Ra, which increased with increasing pH. ²⁴¹Am was almost completely removed from the solution at low pH, but less at higher pH. After phosphorylation, removal of ¹³⁴Cs, ⁸⁵Sr and ²²⁶Ra by the cyanobacterial biomasses was improved, particularly at lower pH, but there was almost no adsorption of ²⁴¹Am. The non-phosphorylated Laminaria biomasses showed good removal of ¹³⁴Cs and very good adsorption of ⁸⁵Sr and ²²⁶Ra. Removal of ²⁴¹Am was high at low pH but decreased with increasing pH. After phosphorylation, adsorption of ¹³⁴Cs by Laminaria samples was slightly improved; removal of ⁸⁵Sr and ²²⁶Ra was increased at low pH with a tendency towards decrease in adsorption with increasing pH; but almost no ²⁴¹Am was adsorbed. The origin of the cyanobacterial and Laminaria materials appeared to have little effect on the adsorption of the radionuclides.     

The Formulation of Bacteriophage in a Semi Solid Preparation for Control of Propionibacterium acnes Growth

Aims

To isolate and characterise phage which could lyse P. acnes and to formulate the phage into a delivery form for potential application in topical treatment of acne infection.

Methods and Results

Using standard phage isolation techniques, ten phage capable of lysing P. acnes were isolated from human skin microflora. Their genomes showed high homology to previously reported P. acnes phage. These phage were formulated into cetomacrogol cream aqueous at a concentration of 2.5x10⁸ PFU per gram, and shown to lyse underlying P. acnes cells grown as lawn cultures. These phage formulations remained active for at least 90 days when stored at four degrees Celsius in a light protected container.

Conclusions

P. acnes phage formulated into cetomacrogol cream aqueous will lyse surrounding and underlying P. acnes bacteria, and are effective for at least 90 days if stored appropriately.

Significance and Impact of the Study

There are few reports of phage formulation into semi solid preparations for application as phage therapy. The formulation method described here could potentially be applied topically to treat human acne infections. The potential exists for this model to be extended to other phage applied to treat other bacterial skin infections.     

Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine

Background

Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA). Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model.

Methods

Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl.), infected with C. sinensis (Cs), ingested N-nitrosodimethylamine (NDMA), and both Cs infected and NDMA introduced (Cs+NDMA). The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR) and western blotting.

Principal Findings

CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8^th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA). The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model.

Conclusions/Significance

The present findings suggest that oncogenes, PSMD10 and CDK4, and tumor suppressors, p53 and RB, are involved in the carcinogenesis process of C. sinensis induced CCA in hamsters.     

Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients

Objectives

Experience with therapeutic plasma exchange (TPE) for acute relapses in clinically isolated syndrome (CIS) or multiple sclerosis (MS) patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.

Participants

Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18–69 years).

Outcome Measures

Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS) scoring.

Results

A clinical response to TPE was observed in 65 out of 90 patients (72.2%), with marked improvement in 18 (20.0%) and moderate improvement in 47 out of 90 patients (52.2%). The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001). Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001), no disease modifying drugs (p = 0.017), gadolinium-positive (Gd⁺) MRI lesions (p = 0.001) and EDSS ≤ 5.0 before TPE (p = 0.014). In the multiple logistic regression analysis only the detection of Gd⁺ MRI lesions was significantly altered (p = 0.004).

Conclusion

Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd⁺ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.     

Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models

Objective

Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that ⁸⁹Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR), is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT) with ⁹⁰Y-TSP-A01 in pancreatic cancer mouse models.

Methods

TfR expression in pancreatic cancer cell lines (AsPC-1, BxPC-3, MIAPaCa-2) was evaluated by immunofluorescence staining. ¹¹¹In-labeled anti-TfR antibodies (TSP-A01, TSP-A02) were evaluated in vitro by cell binding assay with the three cell lines and by competitive inhibition assay with MIAPaCa-2. In vivo biodistribution was evaluated in mice bearing BxPC-3 and MIAPaCa-2 xenografts. Tumor volumes of BxPC-3 and MIAPaCa-2 were sequentially measured after ⁹⁰Y-TSP-A01 injection and histological analysis of tumors was conducted.

Results

MIAPaCa-2 cells showed the highest TfR expression, followed by AsPC-1 and BxPC-3 cells. ¹¹¹In-TSP-A01 and ¹¹¹In-TSP-A02 bound specifically to the three cell lines according to TfR expression. The dissociation constants for TSP-A01, DOTA-TSP-A01, TSP-A02, and DOTA-TSP-A02 were 0.22, 0.28, 0.17, and 0.22 nM, respectively. ¹¹¹In-TSP-A01 was highly accumulated in tumors, especially in MIAPaCa-2, but this was not true of ¹¹¹In-TSP-A02. The absorbed dose for ⁹⁰Y-TSP-A01 was estimated to be 8.3 Gy/MBq to BxPC-3 and 12.4 Gy/MBq to MIAPaCa-2. MIAPaCa-2 tumors treated with 3.7 MBq of ⁹⁰Y-TSP-A01 had almost completely disappeared around 3 weeks after injection and regrowth was not observed. Growth of BxPC-3 tumors was inhibited by 3.7 MBq of ⁹⁰Y-TSP-A01, but the tumor size was not reduced.

Conclusion

⁹⁰Y-TSP-A01 treatment achieved an almost complete response in MIAPaCa-2 tumors, whereas it merely inhibited the growth of BxPC-3 tumors. ⁹⁰Y-TSP-A01 is a promising RIT agent for pancreatic cancer, although further investigation is necessary to improve the efficacy for the radioresistant types like BxPC-3.     

Age at Menarche,Level of Education,Parity and the Risk of Hysterectomy: A Systematic Review and Meta-Analyses of Population-Based Observational Studies

Background

Although rates have declined, hysterectomy is still a frequent gynaecological procedure. To date, there has been no systematic quantification of the relationships between early/mid-life exposures and hysterectomy. We performed a systematic review and meta-analyses to quantify the associations between age at menarche, education level, parity and hysterectomy.

Methods

Eligible studies were identified by searches in PubMed and Embase through March 2015. Study-specific estimates were summarised using random effects meta-analysis. Heterogeneity was explored using sub-group analysis and meta-regression.

Results

Thirty-two study populations were identified for inclusion in at least one meta-analysis. Each year older at menarche was associated with lower risk of hysterectomy—summary hazard ratio 0.86 (95% confidence interval: 0.78, 0.95; I² = 0%); summary odds ratio 0.88 (95% confidence interval: 0.82, 0.94; I² = 61%). Low education levels conferred a higher risk of hysterectomy in the lowest versus highest level meta-analysis (summary hazard ratio 1.87 (95% confidence interval: 1.25, 2.80; I² = 86%), summary odds ratio 1.51 (95% confidence interval: 1.35, 1.69; I² = 90%)) and dose-response meta-analysis (summary odds ratio 1.17 (95% confidence interval: 1.12, 1.23; I² = 85%) per each level lower of education). Sub-group analysis showed that the birth cohort category of study participants, the reference category used for level of education, the year the included article was published, quality of the study (as assessed by the authors) and control for the key variables accounted for the high heterogeneity between studies in the education level meta-analyses. In the meta-analyses of studies of parity and hysterectomy the results were not statistically significant.

Conclusions

The present meta-analyses suggest that the early life factors of age at menarche and lower education level are associated with hysterectomy, although this evidence should be interpreted with some caution due to variance across the included studies.     

Fractal Analysis and Hurst Parameter for Intrapartum Fetal Heart Rate Variability Analysis: A Versatile Alternative to Frequency Bands and LF/HF Ratio

Background

The fetal heart rate (FHR) is commonly monitored during labor to detect early fetal acidosis. FHR variability is traditionally investigated using Fourier transform, often with adult predefined frequency band powers and the corresponding LF/HF ratio. However, fetal conditions differ from adults and modify spectrum repartition along frequencies.

Aims

This study questions the arbitrariness definition and relevance of the frequency band splitting procedure, and thus of the calculation of the underlying LF/HF ratio, as efficient tools for characterizing intrapartum FHR variability.

Study Design

The last 30 minutes before delivery of the intrapartum FHR were analyzed.

Subjects

Case-control study. A total of 45 singletons divided into two groups based on umbilical cord arterial pH: the Index group with pH ≤ 7.05 (n = 15) and Control group with pH > 7.05 (n = 30).

Outcome Measures

Frequency band-based LF/HF ratio and Hurst parameter.

Results

This study shows that the intrapartum FHR is characterized by fractal temporal dynamics and promotes the Hurst parameter as a potential marker of fetal acidosis. This parameter preserves the intuition of a power frequency balance, while avoiding the frequency band splitting procedure and thus the arbitrary choice of a frequency separating bands. The study also shows that extending the frequency range covered by the adult-based bands to higher and lower frequencies permits the Hurst parameter to achieve better performance for identifying fetal acidosis.

Conclusions

The Hurst parameter provides a robust and versatile tool for quantifying FHR variability, yields better acidosis detection performance compared to the LF/HF ratio, and avoids arbitrariness in spectral band splitting and definitions.     

Role of Caffeine Intake on Erectile Dysfunction in US Men: Results from NHANES 2001-2004

Objectives

Caffeine is consumed by more than 85% of adults and little is known about its role on erectile dysfunction (ED) in population-based studies. We investigated the association of caffeine intake and caffeinated beverages with ED, and whether these associations vary among comorbidities for ED.

Material and Method

Data were analyzed for 3724 men (≥20 years old) who participated in the National Health and Nutrition Examination Survey (NHANES). ED was assessed by a single question during a self-paced, computer-assisted self-interview. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable logistic regression analyses using appropriate sampling weights were conducted.

Results

We found that men in the 3^rd (85-170 mg/day) and 4^th (171-303 mg/day) quintiles of caffeine intake were less likely to report ED compared to men in the lowest 1^st quintile (0-7 mg/day) [OR: 0.58; 95% CI, 0.37–0.89; and OR: 0.61; 95% CI, 0.38–0.97, respectively], but no evidence for a trend. Similarly, among overweight/obese and hypertensive men, there was an inverse association between higher quintiles of caffeine intake and ED compared to men in the lowest 1^st quintile, P≤0.05 for each quintile. However, only among men without diabetes we found a similar inverse association (P_trend = 0.01).

Conclusion

Caffeine intake reduced the odds of prevalent ED, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive, but not among diabetic men. Yet, these associations are warranted to be investigated in prospective studies.     

Short and Long-Term Effects of Telaprevir on Kidney Function in Patients with Hepatitis C Virus Infection: A Retrospective Cohort Study

Background

Recent reports suggest that telaprevir, a protease inhibitor used to treat hepatitis C infection, is associated with decline in kidney function during therapy, particularly in patients with baseline renal impairment.

Methods

Patients treated with telaprevir in a single healthcare network were retrospectively reviewed. Kidney function was determined at baseline, during therapy, and twelve weeks and twelve months after telaprevir discontinuation. Significant creatinine rise during therapy was defined as an increase in serum creatinine ≥ 0.3mg/dL from baseline during treatment with telaprevir.

Results

Between July 2011 to January 2013,seventy-eight patients began treatment. The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects. The average rise in serum creatinine during therapy was 0.22mg/dL (standard deviation 0.22mg/dL). Thirty-one percent experienced a significant creatinine rise during therapy. Decline in estimated glomerular filtration rate (eGFR) was lower in those with baseline eGFR < 90 mL/min/1.73m² compared to the group with baseline eGFR ≥ 90 mL/min/1.73m² (12 vs. 18 mL/min/1.73m², P = 0.047). Serum creatinine fully normalized by twelve weeks after cessation of telaprevir in 83% of patients, however experiencing a significant creatinine rise during telaprevir use was associated with a 6.6mL/min/1.73m² decrease in estimated glomerular filtration rate at twelve months in an adjusted model.

Conclusions

Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m² as previously reported.     

Efficacy of Ciprofloxacin for Treatment of Cholera Associated with Diminished Susceptibility to Ciprofloxacin to Vibrio cholerae O1

Objective

We identified a poor clinical response to treatment of cholera with a single 1 g dose of ciprofloxacin, a standard treatment for cholera.

Methods

To determine reasons for the poor response and better therapeutic approaches we examined the minimal inhibitor concentration (MIC, n = 275) and disc-diffusion zone sizes (n = 205) for ciprofloxacin and nalidixic acid of V. cholerae O1 strains isolated in Bangladesh from 1994 to 2012, and reexamined data from 161patients infected with Vibrio cholerae O1 recruited in four clinical trials who received single- or multiple-dose ciprofloxacin for treatment of cholera and compared their clinical response to the V. cholerae O1 susceptibility.

Results

Although all 275 isolates of V. cholerae O1 remained susceptible to ciprofloxacin using standard MIC and disc-diffusion thresholds, the MIC⁹⁰ to ciprofloxacin increased from 0.010 in 1994 to 0.475 μgm/ml in 2012. Isolates became frankly resistant to nalidixic with the MIC⁹⁰ increasing from 21 μgm/ml in 1994 to >256 μgm/ml and 166 of 205 isolates from 1994 to 2005 being frankly resistant using disc-diffusion testing. Isolates resistant to nalidixic acid by disc-diffusion testing had a median ciprofloxacin MIC of 0.190 μgm/ml (10^th-90^th centiles 0.022 to 0.380); nalidixic acid-susceptible isolates had a median ciprofloxacin MIC of 0.002 (0.002 to 0.012).The rate of clinical success with single-dose ciprofloxacin treatment for nalidixic acid-susceptible strains was 94% (61 of 65 patients) and bacteriologic success 97% (63/65) compared to 18% (12/67) and 8% (5/67) respectively with nalidixic acid-resistant strains (P<0.001 for both comparisons). Multiple-dose treatment with ciprofloxacin had 86% and 100% clinical and bacteriologic success rates respectively in patients infected with nalidixic acid-susceptible strains of V. cholerae O1 compared to clinical success 67% and bacteriologic success 60% with nalidixic acid-resistant strains.

Conclusions

Single-dose ciprofloxacin is not effective for treating cholera caused by V. cholerae O1 with diminished susceptibility to ciprofloxacin, and nalidixic acid disc-diffusion testing effectively screens for such isolates.     

Comparison of the accumulation of 137Cs and 90Sr by six spring wheat varieties

The uptake of ¹³⁷Cs and ⁹⁰Sr by six varieties of spring wheat (Triticum aestivum) was compared in field trials on land contaminated by the Chernobyl accident. All the experimental varieties are officially adopted for agricultural use in Belarus and are used in large-scale production. Under identical conditions of nutrition, the productivity of the varieties varied significantly by a factor of 1.3. The extent of ¹³⁷Cs and ⁹⁰Sr accumulation by wheat grain, quantified as the concentration ratio, differed between the varieties by as much as a factor of 1.6, for both radionuclides. There was a significant linear positive correlation between the ⁹⁰Sr activity concentration in grain and straw, and the calcium concentration. The correlation between ¹³⁷Cs and potassium was not significant. The results suggest that certain varieties of spring wheat used in normal agricultural practice accumulate less ¹³⁷Cs and ⁹⁰Sr into grain than others. Some spring wheat varieties accumulated relatively less ¹³⁷Cs, but did not accumulate less ⁹⁰Sr. One variety, Quattro, had a significantly lower uptake of both ⁹⁰Sr (for grain) and ¹³⁷Cs (for both grain and straw) than that of the other varieties tested. The reduction efficiency achieved by the use of these varieties, however, is not as high as that achieved by soil amelioration techniques in the past. Nevertheless, since there are no additional costs or production losses associated with these varieties, their use in the contaminated areas is worth considering as a simple, practical, and effective contribution to reducing the uptake of both ⁹⁰Sr and ¹³⁷Cs and allowing farmers to produce food-grade grain.     

Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized Controlled Phase-II Trial

Objective

To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H²) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP).

Design

Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention.

Setting

Community-based and patient-centered self-care for behavioral intervention in urban settings of China.

Participants

A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H² plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients).

Intervention

KM2H² is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke.

Outcome Measures

Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention.

Results

Relative to the standard care, receiving KM2H² was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively.

Conclusion

The program KM2H² is efficacious to reduce the risk of heart attack and stroke among senior patients who are on anti-hypertensive medication. Findings of this study provide solid data supporting a formal phase-III trial to establish the effectiveness of KM2H² for use in community settings for prevention.

Trial Registration

ISRCTN Register ISRCTN12608966     

向日葵(Helianthus annuus L.)对133Cs、88Sr的吸收和分布

通过盆栽试验研究了向日葵(Helianthus annuus L.)对土壤中不同处理浓度¹³³Cs和⁸⁸Sr的吸收,以及¹³³Cs和⁸⁸Sr在向日葵不同部位的分布。结果表明：随着处理浓度的增加,植物中¹³³Cs或⁸⁸Sr的含量增加。同一处理浓度下,⁸⁸Sr含量约比¹³³Cs含量高一个数量级。¹³³Cs和⁸⁸Sr在植物不同部位分布不同。根部中¹³³Cs含量高于植物的其他部位（茎、叶、花）。不同于¹³³Cs在植物中的分布,⁸⁸Sr除在根中的分布外,主要转运到了叶片。¹³³Cs和⁸⁸Sr在向日葵体内的分布与目前对放射性¹³⁷Cs和⁹⁰Sr的研究结果相似,所以¹³³Cs和⁸⁸Sr可分别预测¹³⁷Cs和⁹⁰Sr的运转。向日葵是治理大面积低放核素污染土壤的较佳植物种类。     

Neutron Activated Samarium-153 Microparticles for Transarterial Radioembolization of Liver Tumour with Post-Procedure Imaging Capabilities

Introduction

Samarium-153 (¹⁵³Sm) styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (⁹⁰Y) microspheres in liver radioembolization therapy. Unlike the pure beta emitter ⁹⁰Y, ¹⁵³Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post-procedure imaging following therapy.

Methods

The microparticles were prepared using commercially available cation exchange resin, Amberlite IR-120 H⁺ (620–830 μm), which were reduced to 20–40 μm via ball mill grinding and sieve separation. The microparticles were labelled with ¹⁵²Sm via ion exchange process with ¹⁵²SmCl₃, prior to neutron activation to produce radioactive ¹⁵³Sm through ¹⁵²Sm(n,γ)¹⁵³Sm reaction. Therapeutic activity of 3 GBq was referred based on the recommended activity used in ⁹⁰Y-microspheres therapy. The samples were irradiated in 1.494 x 10¹² n.cm^-2.s^-1 neutron flux for 6 h to achieve the nominal activity of 3.1 GBq.g^-1. Physicochemical characterisation of the microparticles, gamma spectrometry, and in vitro radiolabelling studies were carried out to study the performance and stability of the microparticles.

Results

Fourier Transform Infrared (FTIR) spectroscopy of the Amberlite IR-120 resins showed unaffected functional groups, following size reduction of the beads. However, as shown by the electron microscope, the microparticles were irregular in shape. The radioactivity achieved after 6 h neutron activation was 3.104 ± 0.029 GBq. The specific activity per microparticle was 53.855 ± 0.503 Bq. Gamma spectrometry and elemental analysis showed no radioactive impurities in the samples. Radiolabelling efficiencies of ¹⁵³Sm-Amberlite in distilled water and blood plasma over 48 h were excellent and higher than 95%.

Conclusion

The laboratory work revealed that the ¹⁵³Sm-Amberlite microparticles demonstrated superior characteristics for potential use in hepatic radioembolization.     

Triage of Atypical Glandular Cell by SOX1 and POU4F3 Methylation: A Taiwanese Gynecologic Oncology Group (TGOG) Study

Introduction

Invasive procedures including loop electrosurgical excision, cervical conization, and endometrial sampling are often recommended when atypical glandular cells (AGC) are detected on Pap smear with unsatisfactory colposcopy. These invasive procedures may result in patient anxiety, increased medical expense, and increasing the risk of preterm delivery in subsequent pregnancies. This study was performed to assess methylation biomarkers in the triage of AGC on Pap smear for invasive procedures.

Methods

We conducted a multicenter study in 13 medical centers in Taiwan from May 2012 to May 2014. A total of 55 samples diagnosed “AGC not otherwise specified” (AGC-NOS) were included. All patients with AGC underwent colposcopy, cervical biopsy, endometrial sampling, and conization if indicated. Multiplex quantitative methylation-specific polymerase chain reaction (QMSPCR) was performed. Sensitivity, specificity, and accuracy were calculated for detecting CIN3⁺ and endometrial complex hyperplasia.

Results

In 55 patients with AGC, the sensitivity for methylated (^m) SOX1^m, PAX1 ^m, ZNF582^m,PTPRR^m, AJAP1^m, HS3ST2^m, and POU4F3^m for detecting CIN3⁺ and endometrial complex hyperplasia lesions was 100, 86, 71, 86, 86, 57, and 100%; specificity was 67, 79, 85, 50, 52, 96, and 52%, respectively. Testing for high risk-HPV had a sensitivity of 57% and specificity of 75% for CIN3+ and endometrial complex hyperplasia lesions.

Conclusion

Methylated (^m) SOX1^m and POU4F3^m could be new methylation biomarkers for detection of CIN3⁺ and endometrial complex hyperplasia in AGC. Women with AGC and positive SOX1^m / POU4F3^m, colposcopy, cervical conization or endometrial sampling should be considered.     

Dietary Inulin Fibers Prevent Proton-Pump Inhibitor (PPI)-Induced Hypocalcemia in Mice

Background

Proton-pump inhibitor-induced hypomagnesemia (PPIH) is the most recognized side effect of proton-pump inhibitors (PPIs). Additionally, PPIH is associated with hypocalcemia and hypokalemia. It is hypothesized that PPIs reduce epithelial proton secretion and thereby increase the pH in the colon, which may explain the reduced absorption of and Mg²⁺ and Ca²⁺. Fermentation of dietary oligofructose-enriched inulin fibers by the microflora leads to acidification of the intestinal lumen and by this enhances mineral uptake. This study aimed, therefore, to improve mineral absorption by application of dietary inulin to counteract PPIH.

Methods

Here, C57BL/J6 mice were supplemented with omeprazole and/or inulin. Subsequently, Mg²⁺ and Ca²⁺ homeostasis was assessed by means of serum, urine and fecal electrolyte measurements. Moreover, the mRNA levels of magnesiotropic and calciotropic genes were examined in the large intestine and kidney by real-time PCR.

Results

Treatment with omeprazole significantly reduced serum Mg²⁺ and Ca²⁺ levels. However, concomitant addition of dietary inulin fibers normalized serum Ca²⁺ but not serum Mg²⁺ concentrations. Inulin abolished enhanced expression of Trpv6 and S100g in the colon by omeprazole. Additionally, intestinal and renal mRNA levels of the Trpm6 gene were reduced after inulin intake.

Conclusions

This study suggests that dietary inulin counteracts reduced intestinal Ca²⁺ absorption upon PPI treatment. In contrast, inulin did not increase intestinal absorption of Mg²⁺ sufficiently to recover serum Mg²⁺. The clinical potential of dietary inulin treatment should be the subject of future studies.     

Predictors of Study Attrition in a Randomized Controlled Trial Evaluating a Perinatal Home-Visiting Program with Mothers with Psychosocial Vulnerabilities

Objective

Randomised controlled trials evaluating perinatal home-visiting programs are frequently confronted with the problem of high attrition rates. The aim of the present study is to identify predictors of study attrition in a trial evaluating a perinatal home-visiting program in France.

Materials and Methods

CAPEDP is a French randomized trial comparing a perinatal home-visiting program using psychologists versus usual care (N = 440). The first assessment was at inclusion into the trial at the 27^th week of pregnancy and the final assessment when the child reached the age of two. Attrition rates were calculated at 3 and 24 months postpartum. Stepwise logistic regression was used to identify predictors of early (between inclusion and 3 months postpartum) and later (between 3 and 24 months postpartum) attrition among social, psychological and parenting factors.

Results

Attrition rates were 17% and 63% at 3 and 24 months respectively. At 24 months, there was significantly more attrition in the control arm (70.6%) compared to the intervention arm (55.2%). Five independent predictors of early attrition were identified: having already had an abortion; having greater attachment insecurity as measured with the Vulnerable Attachment Style Questionnaire (VASQ); having lower global severity of psychiatric symptoms as assessed with the Symptom Check-List (SCL-90) at inclusion, being neither currently employed nor studying; and declaring no tobacco consumption during pregnancy. Being randomized into the control arm, having undergone early parental loss before age 11 and having lower global severity of psychiatric symptoms (SCL-90) at 3 months postpartum were the only variables associated with later attrition.

Conclusion

This study provides key information for identifying mothers who may require specific support to avoid study attrition in trials evaluating a home-visiting program.