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author:("bari, S.")
2.  Analysis of Deoxynivalenol and Deoxynivalenol-3-glucoside in Hard Red Spring Wheat Inoculated with Fusarium Graminearum 
Toxins  2013;5(12):2522-2532.
Deoxynivalenol (DON) is a mycotoxin affecting wheat quality. The formation of the “masked” mycotoxin deoxinyvalenol-3-glucoside (D3G) results from a defense mechanism the plant uses for detoxification. Both mycotoxins are important from a food safety point of view. The aim of this work was to analyze DON and D3G content in inoculated near-isogenic wheat lines grown at two locations in Minnesota, USA during three different years. Regression analysis showed positive correlation between DON content measured with LC and GC among wheat lines, locality and year. The relationship between DON and D3G showed a linear increase until a certain point, after which the DON content and the D3G increased. Wheat lines having higher susceptibility to Fusarium showed the opposite trend. ANOVA demonstrated that the line and location have a greater effect on variation of DON and D3G than do their interaction among years. The most important factor affecting DON and D3G was the growing location. In conclusion, the year, environmental conditions and location have an effect on the D3G/DON ratio in response to Fusarium infection.
PMCID: PMC3873699  PMID: 24351715
fusarium; wheat; deoxinyvalenol; deoxynivalenol-3-glucoside
3.  Occurrence of Deoxynivalenol and Deoxynivalenol-3-glucoside in Hard Red Spring Wheat Grown in the USA 
Toxins  2013;5(12):2656-2670.
Deoxynivalenol (DON) is a mycotoxin found in wheat that is infected with Fusarium fungus. DON may also be converted to a type of “masked mycotoxin”, named deoxynivalenol-3-glucoside (D3G), as a result of detoxification of the plant. In this study, DON and D3G were measured using gas chromatographic (GC) and liquid chromatography-mass spectrometry (LC-MS) in wheat samples collected during 2011 and 2012 in the USA. Results indicate that the growing region had a significant effect on the DON and D3G (p < 0.0001). There was a positive correlation between both methods (GC and LC-MS) used for determination of DON content. DON showed a significant and positive correlation with D3G during 2011. Overall, DON production had an effect on D3G content and kernel damage, and was dependent on environmental conditions during Fusarium infection.
PMCID: PMC3873704  PMID: 24351720
deoxynivalenol; deoxynivalenol-3-glucoside; wheat; USA
4.  Formulation of nicotine mucoadhesive tablet for smoking cessation and evaluation of its pharmaceuticals properties 
Nicotine replacement therapy (NRT) with gradual decreasing of nicotine is one of the smoking cessation methods. Muccoadhesive formulations are among the novel drug delivery systems that are available in the form of tablets and films, and can be used for NRT. Muccoadhesive nicotine tablets when placed in the upper gum will attach to the buccal mucosa and release nicotine content in a controlled manner. This will meet the immediate and long-term need of the individual to the nicotine, such that the person can decrease his/her dependency on smoking.[1]
Materials and Methods:
In this study, the tablets were prepared using different conventional bioadhesive polymers such as Hydroxypropyl Methycellulose (HPMC) 50cps, sodium carboxy methyl cellulose (NaCMC), and carbapol 934 (CP934) in singular or mixture form. Magnesium hydroxide were used as the pH increasing agent; magnesium stearate as the lubricant; and lactose as the excipiente. Nicotine hydrogen bitartrate, more stable than the liquid, was used in different formulations. Pharmaceutics characteristics such as adhesion degree and drug release rate were evaluated.
Increasing of HPMC 50cps in the formulations decrease speed release of nicotine. The carbapol in formulations beget slow releasing of nicotine. With increasing the percent of lactose, the rate of release in formulations was increased. Formulations, which have HPMC 50cps has best adhesiveness and the formulations contains carbapol had not suitable adhesiveness. Formulations contains NaCMC were very fast release and had not suitable adhesiveness.
The formulation contains mixture of HPMC50cps and CP934 was the best because of suitable adhesiveness and minimum swing in release.
PMCID: PMC3908699  PMID: 24524034
Mucoadhesive tablet; nicotine; smoking cessation
5.  Malignant Mesenchymal Renal Tumor: A Rare Case of Primary Renal Fibrosarcoma 
Malignant mesenchymal neoplasms of kidney constitute a rare group of tumors. Primary fibrosarcoma of kidney is an extremely rare subtype of primary malignant mesenchymal renal neoplasms. An elderly female presented with a gradually increasing abdominal lump and mild abdominal discomfort. On cross-sectional imaging, the lesion showed features suggestive of an atypical renal mass not conforming to either ball or bean type growth pattern. The mass was surgically removed and on histopathological and immunohistological investigations diagnosed to be primary renal fibrosarcoma.
PMCID: PMC3883277  PMID: 24404411
Atypical renal mass; malignant mesenchymal renal tumor; primary renal fibrosarcoma
6.  Ampleur et impact des évènements indésirables graves liés aux soins: étude d'incidence dans un hôpital du Centre-Est tunisien 
La prévention des événements indésirables représente une priorité de santé du fait de leur fréquence et de leur gravité potentielle. Ce travail a été mené afin d'avoir un diagnostic de la situation épidémiologique relative aux événements indésirables survenant dans notre hôpital.
Une étude prospective a été menée auprès de tous les patients qui ont été hospitalisés au CHU Farhat Hached - Sousse (Tunisie) sur une période d'un mois dans quatorze services de l'hôpital. La détection d'évènement indésirable grave (EIG) était basée sur les critères adoptés dans différentes études. Les tests T et Chi 2 ont été utilisés pour identifier les facteurs contribuant à l'apparition d'évènements indésirables.
Au total, 162 EIG ont été identifiés pendant la période. 45% de ces évènements étaient des infections nosocomiales. Ces EIG ont eu comme conséquences un décès chez 9,2% des patients, la mise en jeu du pronostic vital de 26% des patients et la prolongation de la durée de séjour chez 61,7% d'entre eux. L'admission dans des circonstances particulières et l'exposition à des soins invasifs étaient identifiés comme des facteurs de risque potentiels EIG.
Le renforcement de la stratégie de gestion des risques sanitaires en ciblant préférentiellement le risque infectieux constitue une étape fondamentale dans l'amélioration de la sécurité des patients au sein de notre établissement de santé.
PMCID: PMC3976656
Evènements indésirables graves; infections associées aux soins; soins invasifs; gestion des risques; sécurité des patients; Serious Adverse Events; healthcare associated infections; invasive care; Risk Management; Patients safety
7.  Evaluation of PCR-RFLP in the Pre-S Region as Molecular Method for Hepatitis B Virus Genotyping 
Hepatitis Monthly  2013;13(10):e11781.
Hepatitis B virus (HBV) infection is a public health problem in developing countries. HBV genotypes play major role in the evolution of infection since they were involved in different clinical presentations and response to treatment.
This study was conducted to evaluate the efficiency of restriction fragment length polymorphism (RFLP) analysis for HBV genotyping.
Patients and Methods
We investigated 98 samples collected from patients chronically infected with HBV. HBV genotypes were determined by analysis of patterns obtained after amplification in Pre-S region and digestion of the amplicon by two endonucleases AvaII and DpnII. Obtained results were confirmed by partial sequencing in the same region.
Two different HBV genotypes were detected in this study, Genotype D (in 95. 9%) and Genotype A (in 4.1%). Seventy-four samples (75.5%) were successfully genotyped with RFLP analysis and all classified as genotype D. The remaining 24 samples (24.5%) which were un-genotyped by RFLP analysis, were classified by partial sequencing of the pre-S region as HBV genotype D (20 samples, 20.4%) and genotype A (4 samples, 4.1%). Atypical profiles were significantly associated with advanced liver disease (P = 0.001) as well as older age (P < 0.05).
Several previous studies used PCR-RFLP to genotype HBV; however, we showed the high risk to obtain atypical profiles, especially in advanced stages of chronic infection, with as results difficulties to genotype the virus. These profiles resulted from the accumulation of mutations during natural course of infection resulting in a modification in restriction sites for enzymes. So, we recommended completing the investigation by partial sequencing to confirm obtained results.
PMCID: PMC3842526  PMID: 24348634
Hepatitis B Virus; Genotype; Restriction Fragment Length Polymorphism; Direct Sequencing
8.  Medical waste management training for healthcare managers - a necessity? 
This is an interventional study, since a training has been given, performed in order to investigate whether training has significant impact on knowledge levels of healthcare managers (head-nurses, assistant head nurses, hospital managers and deputy managers) regarding bio-medical waste management.
The study was conducted on 240 volunteers during June – August 2010 in 12 hospitals serving in Istanbul (private, public, university, training-research hospitals and other healthcare institutions). A survey form prepared by the project guidance team was applied to the participants through the internet before and after the training courses. The training program was composed of 40 hours of theory and 16 hours of practice sessions taught by persons known to have expertise in their fields. Methods used in the analysis of the data chi-square and t-tests in dependent groups.
67.5% (162) of participants were female. 42.5% (102) are working in private, and 21.7% in state-owned hospitals. 50.4% are head-nurses, and 18.3% are hospital managers.
A statistically significant difference was found among those who had received medical waste management training (preliminary test and final test) and others who had not (p<0.01). It was observed that information levels of all healthcare managers who had received training on waste management had risen at the completion of that training session.
On the subject of waste management, to have trained healthcare employees who are responsible for the safe disposal of wastes in hospitals is both a necessity for the safety of patients and important for its contribution to the economy of the country.
PMCID: PMC3776293  PMID: 24499642
Healthcare managers; Medical waste training; Medical waste management
9.  Acute Toxicity of Opuntia Ficus Indica and Pistacia Lentiscus Seed Oils in Mice 
Opuntia ficus indica and Pistacia lentiscus L. seeds are used in traditional medicine. The objective of this study was to investigate the toxicity of the fixed oil of Opuntia ficus indica and Pistacia lentiscus L. seeds in mice through determination of LD50 values, and also the physicochemical characteristics of the fixed oil of these oils. The acute toxicity of their fixed oil were also investigated in mice using the method of Kabba and Berhens. The fixed oil of Pistacia lentiscus and Opuntia ficus indica seeds were extracted and analyzed for its chemical and physical properties such as acid value, free fatty acid percentage (% FFA), iodine index, and saponification value as well as refractive index and density. LD50 values obtained by single doses, orally and intraperitoneally administered in mice, were respectively 43 ± 0,8 ;[40.7– 45.4 ] ml/kg body wt. p.o. and 2.72 ± 0,1 ;[2.52–2.92] ml/kg body wt. i.p. for Opuntia ficus indica ; and 37 ± 1 ;[34.4 − 39.8 ] ml/kg body wt. p.o. and 2.52 ± 0,2 ;[2.22 − 2.81 ] ml/kg body wt. i.p. for Pistacia lentiscus respectively. The yields of seed oil were respectively calculated as 20.25% and 10.41%. The acid and free fatty acid values indicated that the oil has a low acidity
PMCID: PMC3746649  PMID: 23983398
Opuntia ficus indica L.; Pistacia lentiscus L.; seed oil; acute toxicity
10.  Maternal and Neonatal Urinary Iodine Status and its Effect on Neonatal TSH Levels in a Mildly Iodine-Deficient Area 
Objective: Iodine deficiency and excess are the most important factors that affect screening and recall rates of congenital hypothyroidism. The purpose of this study was to investigate the urinary iodine status in newborns and their mothers and its effects on neonatal thyroid-stimulating hormone (TSH) levels in a mildly iodine-deficient area.
Methods: A total of 116 newborns and their mothers were included in the study. Urinary iodine levels were measured from healthy mothers and their babies on the 5th day following birth. Neonatal TSH levels were screened, and TSH and free thyroxine (fT4) levels were measured on the15th day in the recall cases. T4 treatment was started in infants with high TSH and low fT4 levels. These measurements were repeated on the 30th day in these newborns.
Results: Ninety-nine percent of the mothers included in the study were using iodized salt. The median urinary iodine level in the newborns was 279 µg/L, while it was 84 µg/L in their mothers. The rate of iodine deficiency among the mothers was 56.8%, and the rate of iodine excess was 8.6%. This rate was 10.3% for iodine deficiency and 61.2% for iodine excess in the newborns. The recall rate at the screening was 9.5% (n=11). The urinary iodine levels were above 200 µg/L in three newborns who had transient hyperthyrotropinemia.
Conclusions: Iodine deficiency was more frequently observed in nursing mothers, and iodine excess was more frequently seen in their newborns. The iodine excess noted in the newborns was attributed to the use of antiseptics containing iodine. The iodine excess leads to increases in recall rates, screening costs, and frequency of transient hyperthyrotropinemia.
Conflict of interest:None declared.
PMCID: PMC3701928  PMID: 23748060
Urinary iodine; maternal; neonatal; screening; hyperthyrotropinemia
11.  Preclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H 
EJNMMI Research  2013;3:35.
[18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared.
Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors.
Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation.
This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient between radiation dosimetry derived by either method was 0.9666.
PMCID: PMC3655042  PMID: 23647774
Dosimetry; Preclinical microPET; Organ harvesting; SV2
12.  Diagnostic Performance of MRI for Assessing Tumor Response in HER2 Negative Breast Cancer Receiving Neoadjuvant Chemotherapy Is Associated with Molecular Biomarker Profile 
Clinical Breast Cancer  2012;12(2):110-118.
This study aimed to evaluate the influence of hormonal receptor and Ki-67 proliferation marker in predicting MRI accuracy of measuring residual tumor size in HER2 negative breast cancer receiving neoadjuvant chemotherapy (NAC).
Fifty-four women were studied. Patients received AC and/or taxane-based regimens. The accuracy of MR determined clinical complete response (CCR) was compared to pathological complete response (pCR). The size of detectable residual tumor on MRI was correlated with pathology-diagnosed tumor size using Pearson’s correlation.
MRI correctly diagnosed 16 of the 17 pCR patients. There were 8 false negative diagnoses, 7 hormonal receptor (HR) positive and one HR negative. The overall sensitivity, specificity, and accuracy of MRI were 78%, 94%, and 83%, respectively. The positive predictive value was 97% and the negative predictive value was 67%. For MRI-pathology tumor size correlation, HR negative cancers showed a higher correlation (R=0.79) than HR positive cancers (R= 0.58). A worse MRI-pathology size discrepancy was found in HR positive cancer than in HR negative cancer (1.6±2.8 cm vs. 0.56±0.9 cm, p=0.05). Tumors with a low Ki-67 proliferation (<40%) showed a larger size discrepancy than those with a high Ki-67 proliferation (≥40%) (1.2±2.0 cm vs. 0.4±0.8 cm p=0.05).
The results showed that the diagnostic performance of MRI for breast cancer undergoing NAC is associated with molecular biomarker profile. Among HER2 negative tumors, the accuracy of MRI was worse in HR positive than negative cancers, and also worse in low proliferative than high proliferative tumors. These findings may help in surgical planning.
PMCID: PMC3342312  PMID: 22444717
13.  Brucellar spondylodiscitis affecting non-contiguous spine levels 
BMJ Case Reports  2011;2011:bcr0120113788.
Brucellosis is a zoonosis that affects several organs. The spine is the most common site of musculoskeletal involvement. However, multiple-level spinal involvement is rare in brucella spondylodiscitis. The authors report a case of a 56-year-old male shepherd who had developed a spondylodiscitis affecting simultaneously the cervical, thoracic and lumbar regions. The diagnosis was established by using MRI after the brucella-agglutination test was found to be positive. A high degree of suspicion in the diagnosis of brucellar spondylodiscitis is essential to reduce the delay for the treatment. Thus, it should be essentially included in the differential diagnosis of longstanding cervical, thoracic or back pain, particularly in regions where brucellosis is endemic. Screening serological tests for brucella should be used more widely in cases with low index of suspicion, especially in endemic areas.
PMCID: PMC3070343  PMID: 22700074
14.  Sub-inhibitory concentration of biogenic selenium nanoparticles lacks post antifungal effect for Aspergillus niger and Candida albicans and stimulates the growth of Aspergillus niger  
The antifungal activity of selenium nanoparticles (Se NPs) prepared by Klebsiella pneumoniae has been reported previously for different fungi. In the present study, freshly prepared Se NPs produced by K. pneumoniae were purified and characterized by transmission electron microscopy and Energy-Dispersive X-ray spectroscopy (EDS) and its post antifungal effects for two fungi were evaluated.
Materials and Methods
The minimum inhibitory concentrations (MICs) of Se NPs, determined by serial dilution were 250 µg/ml for Aspergillus niger and 2,000 µg/ml for Candida albicans. The effect of exposure of A. niger and C. albicans to Se NPs on later growth was evaluated by incubating the fungi for 1 hour at 25 °C in media containing 0, 1, 2 and 4 x MIC of Se NPs and diluting the cultures 100 times with Se free medium. The kinetics of growth of the fungi in control cultures and in non-toxic Se NPs concentration of, 0.01 × MIC, 0.02 × MIC or 0.04 × MIC were measured.
The exposure of A. niger and C. albicans to 2 and 4 x MIC of Se NPs stimulated the growth of both fungi in the absence of toxic concentrations of Se. The strongest stimulation was observed for A. niger.
It is concluded that exposure to high concentration of the Se NPs did not have any post-inhibitory effect on A. niger and C. albicans and that trace amounts of this element promoted growth of both fungi in a dose- dependent-manner. The role of nanoparticles serving as needed trace elements and development of microorganism tolerance to nanoparticles should not be dismissed while considering therapeutic potential.
PMCID: PMC3577562  PMID: 23466957
Selenium nanoparticle; Aspergillus niger; Candida albicans; Antifungal activity
15.  Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy 
In addition to being a risk factor for breast cancer, breast density has been hypothesized to be a surrogate biomarker for predicting response to endocrine-based chemotherapies. The purpose of this study was to evaluate whether a noninvasive bedside scanner based on diffuse optical spectroscopic imaging (DOSI) provides quantitative metrics to measure and track changes in breast tissue composition and density. To access a broad range of densities in a limited patient population, we performed optical measurements on the contralateral normal breast of patients before and during neoadjuvant chemotherapy (NAC). In this work, DOSI parameters, including tissue hemoglobin, water, and lipid concentrations, were obtained and correlated with magnetic resonance imaging (MRI)-measured fibroglandular tissue density. We evaluated how DOSI could be used to assess breast density while gaining new insight into the impact of chemotherapy on breast tissue.
This was a retrospective study of 28 volunteers undergoing NAC treatment for breast cancer. Both 3.0-T MRI and broadband DOSI (650 to 1,000 nm) were obtained from the contralateral normal breast before and during NAC. Longitudinal DOSI measurements were used to calculate breast tissue concentrations of oxygenated and deoxygenated hemoglobin, water, and lipid. These values were compared with MRI-measured fibroglandular density before and during therapy.
Water (r = 0.843; P < 0.001), deoxyhemoglobin (r = 0.785; P = 0.003), and lipid (r = -0.707; P = 0.010) concentration measured with DOSI correlated strongly with MRI-measured density before therapy. Mean DOSI parameters differed significantly between pre- and postmenopausal subjects at baseline (water, P < 0.001; deoxyhemoglobin, P = 0.024; lipid, P = 0.006). During NAC treatment measured at about 90 days, significant reductions were observed in oxyhemoglobin for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) and postmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentration for premenopausal subjects (-11.9%; 95% CI, -17.1 to -6.7) compared with baseline. Lipid increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5), and water increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6). Percentage change in water at the end of therapy compared with baseline correlated strongly with percentage change in MRI-measured density (r = 0.864; P = 0.012).
DOSI functional measurements correlate with MRI fibroglandular density, both before therapy and during NAC. Although from a limited patient dataset, these results suggest that DOSI may provide new functional indices of density based on hemoglobin and water that could be used at the bedside to assess response to therapy and evaluate disease risk.
PMCID: PMC3672664  PMID: 23433249
16.  Management of thoracic trauma in emergency service: Analysis of 1139 cases 
Objective: Thoracic trauma is a common cause of significant morbidity and mortality. This study presents a series of thoracic trauma with the aim to assess epidemiologic features, distribution of pathologies, additional systemic injuries, diagnosis, management and outcome.
Methodology: Between January 2007 and December 2011, all patients with thorax trauma admitted to the emergency service of our hospital were retrospectively reviewed with respect to age, gender, etiological factors, distribution of pathologies, additional systemic injuries, diagnosis, treatment modalities, referral and outcome.
Results: A total of 1139 patients with thorax trauma were included in the study. Of these, 698 (61.3%) were male and 441 (38.7%) were female, and the average age was 54.17±17.39 years. 1090 (95.7%) of the patients had blunt trauma, whereas 49 (4.3%) had penetrating trauma. Etiological factors were falls in 792 (69.5%), motor vehicle accidents in 259 (22.8%), animal related accidents in 39 (3.4%) and penetrating injuries in 49 (4.2%) patients. It was found that 229 (20%) patients had single, 101 (8.9%) had double, 5 (3%) had three or more, 10 (0.9%) had bilateral rib fractures and 19 (1.7%) had sternal fracture. Pneumothorax was diagnosed in 58 (5.1%) patients, whereas hemothorax, hemopneuomothorax and other system injuries were diagnosed in 36 (3.2%), 38(3.3%) and 292 (25.6%) respectively. In our series, thirteen patients (mortality rate 1.1%) died as result of hemorrhagic shock (n=8), respiratory distress (n=3) and severe multiple trauma (n=2).
Conclusion: Although majority of the patients with thorax trauma receive treatment as outpatients; thoracic traumas may be a life threatening condition, and should be identified and treated immediately. Mortality varies based on etiological factors, additional systemic pathologies, capabilities of the hospital especially diagnostic and treatment facilities in emergency services. We believe that a multidisciplinary approach to the patients with severe thorax trauma, and the opportunities of emergency bedside thoracotomy in emergency services will significantly reduce the morbidity and mortality.
PMCID: PMC3809198  PMID: 24353508
Thoracic trauma; Hemothorax; Pneumothorax; Rib fractures; Mortality
17.  Focusing on Risk Communication About Medicines 
Drug Safety  2012;35:971-975.
PMCID: PMC3585946  PMID: 23061774
18.  A “Novel” Protocol for the Analysis of Hydroxycinnamic Acids in Leaf Tissue of Chicory (Cichorium intybus L., Asteraceae) 
The Scientific World Journal  2012;2012:142983.
A “novel” protocol is presented for easy and reliable estimation of soluble hydroxycinnamate levels in Cichorium intybus L. leaf tissue in large-scale experiments. Samples were standardized by punching 6 discs per leaf, and hydroxycinnamates were extracted by submerging the discs in 80% ethanol with 5% acetic acid for at least 48 h in the darkness at 4°C. Residual dry mass of the discs was used for a posteriori correction of compound levels. Chlorophyll was eliminated by chloroform, and the aqueous phases were transferred to microplates, dried, and dissolved in 50% methanol for HPLC analysis and storage. An HPLC program of 8 min was developed for the analysis of the extracts. Comparisons with extractions of liquid nitrogen powders indicated that the novel extraction method was reliable. No degradation of the major hydroxycinnamates—caftaric, chlorogenic, and chicoric acids—was observed, during maceration at ambient temperatures, or after storage for 1 year.
PMCID: PMC3523586  PMID: 23304076
19.  Spatial Shrinkage/Expansion Patterns between Breast Density Measured in Two MRI Scans Evaluated by Non-rigid Registration 
Physics in medicine and biology  2011;56(18):5865-5875.
Breast MRI acquires many images from the breast, and computer-aided algorithms and display tools are often used to assist radiologist’s interpretation. Women with lifetime risk greater than 20% in developing breast cancer are recommended to receive annual screening MRI, but the current breast MRI computer-aided-diagnosis systems do not provide the necessary function for comparison of images acquired at different times. The purpose of this work was to develop registration methods for evaluating the spatial change pattern of fibroglandular tissue between two breast MRI scans of the same woman taken at different times. The registration method is based on rigid alignment followed by non-rigid Demons algorithm. The method was tested in 3 different subjects who had different degree of changes in the fibroglandular tissue, including two patients who showed different spatial shrinkage patterns after receiving neoadjuvant chemotherapy before surgery, and one control case from a normal volunteer. Based on the transformation matrix, the collapse of multiple voxels on the baseline images to one voxel on the follow-up images is used to calculate the shrinkage factor. Conversely, based on the reverse transformation matrix the expansion factor can be calculated. The shrinkage/expansion factor, the deformation magnitude and direction, as well as the Jacobian determinate at each location can be displayed in a 3D rendering view to show the spatial changes between two MRI scans. These different parameters show consistent results, and can be used for quantitative evaluation of the spatial change patterns. The presented registration method can be further developed into a clinical tool for evaluating the therapy-induced changes and for early diagnosis of breast cancer in screening MRI.
PMCID: PMC3498815  PMID: 21852724
20.  The “Dot in Circle” Sign on MRI in Maduramycosis: A Characteristic Finding 
Mycetoma or Maduramycosis is a localized chronic suppurative infection characterized by exuberant granulation tissue, discharging sinuses, and bone involvement later in the course of the disease. Early clinical diagnosis before the appearance of sinuses and grains (aggregates of organism surrounded by granulation tissue, which are discharged from the draining sinuses) is difficult. Delay in diagnosis may lead to amputation of the affected part. Definitive diagnosis is through biopsy and microbiological examination. However, at times diagnosis may still be difficult. The recently described “dot in circle” sign on magnetic resonance imaging (MRI) is easy to recognize and highly specific. We present a case of mycetoma foot with characteristic MRI features.
PMCID: PMC3515922  PMID: 23230548
Dot in circle sign; maduramycosis; MRI; mycetoma
21.  Effects of body mass index on intraocular pressure and ocular pulse amplitude 
To investigate the effects of body mass index (BMI) on intraocular pressure (IOP) and ocular pulse amplitude (OPA).
Totally 140 healthy individuals without any systemic diseases were included in the study. BMI (kg/m2) was calculated for every individual. IOP and OPA were measured with Pascal Dynamic contour tonometer (DCT). Blood pressure was also measured along with the DCT. The patients were divided into three groups according to BMI as: Group1, BMI<25; Group2, 25≤BMI<30; Group3, BMI≥30. Mean values of IOP, OPA, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were used in statistical analysis.
In Group1, the means of IOP, OPA, were 16.8±2.3mmHg, 2.7±0.7mmHg respectively; and SBP, DBP were 120.0±6.1mmHg, and 77.4±5.6mmHg respectively. In group2, the mean IOP, OPA, SBP, and DBP were found to be 16.6±2.1mmHg, 2.4±0.7mmHg, 121.7±5.3mmHg, and 79.5±4.9mmHg respectively. In group3, the mean IOP, OPA, SBP, and DBP were found to be 17.3±1.7mmHg, 2.1±0.7mmHg, 122.4±5.7mmHg, and 79.7±5.2mmHg respectively. There were no statistically significant difference between groups in terms of IOP, SBP and DBP, while OPA values were significantly lower in group3 (P=0.001).
Decreased OPA values in individuals with higher BMI may indicate that subjects with higher BMI have lower choroidal perfusion and lower ocular blood flow.
PMCID: PMC3484700  PMID: 23166873
body mass index; choroidal perfusion; intraocular pressure; ocular pulse amplitude; obesity
22.  Ectonucleotidase CD38 Demarcates Regulatory, Memory-Like CD8+ T Cells with IFN-γ-Mediated Suppressor Activities 
PLoS ONE  2012;7(9):e45234.
Regulatory CD8+ T cells are critical for self-tolerance and restricting excessive immune responses. The variety of immune functions they fulfill, the heterogeneity of their phenotype, and the mechanism of action are still poorly understood. Here we describe that regulatory CD8+ T cells exhibiting immunosuppressive actions in vitro and in vivo are recognized as CD38high T cells and present in naive mice. CD38 is a glycosylated membrane protein with ectonucleotidase properties. CD8+CD38high (CD44+CD122+CD62Lhigh) lymphocytes suppress CD4+ effector T-cell proliferation in an antigen-non specific manner via IFN-γ. While direct cell-to-cell contact is needed for this suppressor activity, it is independent of membrane-bound TGF-β and granzyme B release. IL-15 potentiates the suppressive activity of CD8+CD38high T cells and controls their survival and expansion. In humans CD8+CD38high T cells inhibit CD4+ effector T cell proliferation. In vivo, CD8+CD38high, but not CD8+CD38− T cells mitigate murine experimental autoimmune encephalomyelitis (EAE) by reducing the clinical score and delaying disease occurrence. EAE suppression is enhanced by pre-treatment of CD8+CD38high T cells with IL-15. These findings add evidence that the expression of ectoenzyme receptor family members positively correlates with suppressor functions and identifies CD8+CD38high T cells as potential inhibitors of excessive immune responses.
PMCID: PMC3444472  PMID: 23028866
23.  Brain energization in response to deep brain stimulation of subthalamic nuclei in Parkinson's disease 
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson's disease (PD). Here, we compared resting-state 18F-fluorodeoxyglucose (FDG) positron emission tomography images in the stimulator off (DBS_OFF) and on (DBS_ON) conditions in eight PD patients in an unmedicated state, on average 2 years after bilateral electrode implantation. Global standardized uptake value (SUV) significantly increased by ∼11% in response to STN-DBS. To avoid any bias in the voxel-based analysis comparing DBS_ON and DBS_OFF conditions, individual scan intensity was scaled to a region where FDG-SUV did not differ significantly between conditions. The resulting FDG-SUV ratio (FDG-SUVR) was found to increase in many regions in response to STN-DBS including the target area of surgery, caudate nuclei, primary sensorimotor, and associative cortices. Contrary to previous studies, we could not find any regional decrease in FDG-SUVR. These findings were indirectly supported by comparing the extent of areas with depressed FDG-SUVR in DBS_OFF and DBS_ON relatively to 10 normal controls. Altogether, these novel results support the prediction that the effect of STN-DBS on brain activity in PD is unidirectional and consists in an increase in many subcortical and cortical regions.
PMCID: PMC3137472  PMID: 21468092
FDG uptake; neurosurgery; Parkinson's disease; positron emission tomography; SUV
24.  A Study of Psychological Distress in Two Cohorts of First-Year Medical Students that Underwent Different Admission Selection Processes 
Medical training is often regarded as a stressful period. Studies have previously found that 21.6%–50% of medical students experience significant psychological distress. The present study compared the prevalence and levels of psychological distress between 2 cohorts of first-year medical students that underwent different admission selection processes.
A comparative cross-sectional study was conducted by comparing 2 cohorts of first-year medical students; 1 group (cohort 1) was selected based purely on academic merit (2008/2009 cohort) and the other group (cohort 2) was selected based on academic merit, psychometric assessment, and interview performance (2009/2010 cohort). Their distress levels were measured by the General Health Questionnaire, and scores higher than 3 were considered indicative of significant psychological distress.
The prevalence (P = 0.003) and levels (P = 0.001) of psychological distress were significantly different between the 2 cohorts. Cohort 1 had 1.2–3.3 times higher risk of developing psychological distress compared to cohort 2 (P = 0.007).
Cohort 2 had better psychological health than cohort 1 and was less likely to develop psychological distress. This study provided evidence of a potential benefit of multimodal student selection based on academic merit, psychometric assessment, and interview performance. This selection process might identify medical students who will maintain better psychological health.
PMCID: PMC3629662  PMID: 23610547
medical; psychology; school admission criteria; student
25.  Genetic structure and local adaptation of European wheat yellow rust populations: the role of temperature-specific adaptation 
Evolutionary Applications  2011;5(4):341-352.
Environmental heterogeneity influences coevolution and local adaptation in host–parasite systems. This also concerns applied issues, because the geographic range of parasites may depend on their capacity to adapt to abiotic conditions. We studied temperature-specific adaptation in the wheat yellow/stripe rust pathogen, Puccinia striiformis f.sp. tritici (PST). Using laboratory experiments, PST isolates from northern and southern France were studied for their ability to germinate and to infect bread and durum wheat cultivars over a temperature gradient. Pathogen origin × temperature interactions for infectivity and germination rate suggest local adaptation to high- versus low-temperature regimes in south and north. Competition experiments in southern and northern field sites showed a general competitive advantage of southern over northern isolates. This advantage was particularly pronounced in the southern ‘home’ site, consistent with a model integrating laboratory infectivity and field temperature variation. The stable PST population structure in France likely reflects adaptation to ecological and genetic factors: persistence of southern PST may be due to adaptation to the warmer Mediterranean climate; and persistence of northern PST can be explained by adaptation to commonly used cultivars, for which southern isolates are lacking the relevant virulence genes. Thus, understanding the role of temperature-specific adaptations may help to improve forecast models or breeding programmes.
PMCID: PMC3353355
climate change; genotype × environment interaction; local adaptation; plant pathogen; Puccinia striiformis f.sp. tritici; temperature adaptation; wheat; yellow/stripe rust

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