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1.  Cytotoxicity of Liposomal Paclitaxel in Breast Cancer Cell Line MCF-7 
Regarding that the breast cancer is the most prevalent disease among women, paclitaxel, an anti-cancer drug, could be used in treatment of this disease. As paclitaxel has adverse effects, it was used of nanoliposome drug delivery technology in order to reduce adverse effects and improve drug efficacy. Certain ratios of phosphatidylcholine, cholesterol and paclitaxel were synthesized to prepare nanoliposomal paclitaxel. Using Zeta sizer device, the mean diameter of nanoliposomal paclitaxel was obtained 421.4 nm and its encapsulation efficiency was 91.3 %. By dialysis, drug release in nanoliposome paclitaxel formulation within 28 h was studied which was 5.53 %. This study showed that cytotoxicity effect of nanoliposomal paclitaxel is more than that of the standard form.
doi:10.1007/s12291-013-0296-1
PMCID: PMC3783912  PMID: 24426237
Breast cancer; Nano drug delivery; Paclitaxel; Nanoliposome
2.  Drug Delivery of Hydroxyurea to Breast Cancer Using Liposomes 
It is clear that cancer is one of the most mortal diseases in the world and the most prevalent among women is breast cancer. As hydroxyurea (HU)—a drug which is used in chemotherapy—has many adverse effects in long-term despite of its therapeutic properties, we made use of nano drug delivery technology in order to reduce adverse effects and increase therapeutic index. Thus, liposomation is a novel way in drug delivery systems. In this study a mixture of phosphatidylcholine and cholesterol was mixed and HU was added to the resultant mixture. The mean diameter of the nanoliposomal HU measured with the Zeta Sizer device (equal to 402.5 nm) and its encapsulation efficiency was 70.8 %. Besides, using dialysis, the pattern of drug release from nanoliposomes has been studied and the results showed that the drug release of nanoliposomal drug within 28 h was equal to 25.85 %. This study showed that the cytotoxicity effect of nanoliposomal drug is more than that of the standard drug.
doi:10.1007/s12291-012-0291-y
PMCID: PMC3689336  PMID: 24426227
Breast cancer; Nano drug delivery; Hydroxyurea; Liposomal
3.  Dental Erosion in Patients with Gastroesophageal Reflux Disease (GERD) in a Sample of Patients Referred to the Motahari Clinic, Shiraz, Iran 
Journal of Dentistry  2014;15(1):33-38.
Statement of Problem: Systematic reviews of the literature show that the dental erosion is associated with the gastroesophageal reflux disease (GERD).The prevalence of the problem may not be exclusively similar in different countries.
Purpose: The purpose of this study was to investigate the association of gastro-esophageal reflux disease (GERD) with dental erosion in a sample of Iranian population regarding the standing difference in the Iranian oral hygiene and diet.
Materials and Method: 140 patients with the average age of 30 to 50 years old comprised the study group. The participants were already eligible for the endoscopic examination, diagnosed by their gastroenterologist. All patients completed a detailed questionnaire regarding the medical and dental situations. After completing the questionnaire and before endoscopy, dental examination was performed by two blinded dentists.The endoscopy was then performed by a gastroenterologist and the patients were divided into three groups of healthy, suspected to GERD, and positive GERD. Data were collected and analyzed by Chi- Square test. The cross tabulation test was performed to compare the qualitative variants and discover the correlations. The statistical significance was adopted as: p < 0.05.
Results: The prevalence of dental erosion in GERD patients (22.6%) was found to be higher than the suspected (5.3%) and the healthy (7%) individuals.
Conclusion: This study declared the GERD patients are at higher risk of developing dental erosion compared to the healthy individuals in a sample of Iranian population.
PMCID: PMC3986576  PMID: 24738088
Dental erosion; Gastroesophageal reflux disease; Risk factor
4.  Treatment of brucellosis: a systematic review of studies in recent twenty years 
Background: The treatment of human brucellosis is controversial. The purpose of this study was to search published clinical trial papers to provide a simple and effective treatment in brucellosis.
Methods: Many studies on brucellosis treatment in a twenty- year span from 1993 to 2012 were searched in PubMed, Web of Science (ISI), Scopus, Google Scholar, Magiran, Iranmedex and SID. The studies that were searched and classified in groups according to combination therapy and monotherapy and their results in treatment outcome were compared. Regimens with lower treatment failure or relapse were considered as more suitable for brucellosis treatment.
Results: The comparison of combined doxycycline and rifampicin (DR) with a doxycycline plus streptomycin (DS) favors the latter regimen. The combined doxycycline/cotrimoxazole (DCTM) showed similar effect with DR. The treatment with the combined regimen including quinolones was similar to DR but with higher relapse rates. Higher relapse rate was searched in monotherapy (13% vs. 4.8%) and in short-term (less than 4 weeks) treatment regimen (22% vs. 4.8%), respectively. Although in children, clinical trials were limited but showed cotrimoxazole plus rifampin for six weeks was the best treatment regimen.
Conclusion: In uncomplicated brucellosis in adult patients, doxycycline-aminoglycoside combination is the first choice with doxycycline- rifampin and doxycycline-cotrimoxazole should be the alternative regimens. The other oral regimens including quinolones may be considered as alternatives. Cotrimoxazole plus rifampin for six weeks may be the regimen of choice for the treatment of patients younger than 8 years old. Gentamicin for 5 days plus cotrimoxazole for six weeks may be a suitable alternative regimen.
PMCID: PMC3755828  PMID: 24009951
Brucellosis; Treatment; Streptomycin; Doxycycline; Relapse
5.  Influenza A virus among the hospitalized young children with acute respiratory infection. Is influenza A co infected with respiratory syncytial virus?  
Background: Both influenza A virus (IAV) and respiratory syncytial virus (RSV) cause acute respiratory infection (ARI) in infants and young children. This study was conducted to determine Influenza A virus and its co infection with RSV among the hospitalized children with ARI.
Methods: A total of 153 throat samples of the hospitalized young children aged between below one year and 5 years with the clinical signs of ARI were collected from the different hospitals in Khuzestan from June 2009 to April 2010. The samples were tested for Influenza A viruses by real time PCR. Positive IAV samples were tested for influenza A sub type H1N1 and for RSV by the nested PCR.
Results: In this study, from the total 153 samples, 35 samples (22.9%) including 15 (42.8%) females and 20 (57.2%) males were positive for influenza A viruses. From the 35 positive samples for IAV, 14 were positive for swine H1N1 subtype. All the positive samples for influenza showed negative for RSV infection which revealed no coinfection with RSV. The prevalence of influenza A among age/sex groups was not significant.
Conclusion: Influenza A is a prevalent viral agent isolated from young children with ARI. Influenza A subtype H1N1 was accounted for the 40 percent all laboratory-proven diagnoses of influenza in 2009. No evidence of coinfection of influenza A and RSV has been observed in the present study.
PMCID: PMC3755862  PMID: 24009929
Respiratory syncytial virus; Influenza A virus; swine H1N1; Acute respiratory infection; Co-infection.
6.  Melioidosis: It is not Far from here 
Tanaffos  2011;10(4):64-68.
In the modern world, with developed traveling facilities, tourism is an important factor in emerging new infectious diseases in non-endemic areas.
Therefore, the epidemiology of infections is a considerable issue for physicians and should be taken into account.
We report a case of melioidosis in a 69-year-old Iranian man during his trip to Southeast Asia.
On admission, he was febrile with tachycardia and tachypnea and had diabetes mellitus and hypertension since eleven years ago.
Bronchoscopy and bronchoalveolar lavage (BAL) were performed. Blood and BAL cultures revealed heavy growth of Burkholderia pseudomallei.
According to the aforementioned culture results, the patient was treated with meropenem and TMP-SMX, while other antibiotics were discontinued.
After 3 weeks, the patient was discharged with stable status and normal pulmonary function; and eradication therapy with TMP-SMX continued for about 3 months. The control lung CT scan after one month demonstrated significant improvement
PMCID: PMC4153165  PMID: 25191391
Meloiodosis; Infection; Burkholderia pseudomallei
7.  Temporomandibular Disorders: Knowledge, Attitude and Practice among Dentists in Tehran, Iran 
Background and aims
Temporomandibular disorders (TMD) account for the most common orofacial pains rising from musculoskeletal origin. The aim of this study was to investigate the level of knowledge, attitudes and practice of dental practitioners regarding TMD in Tehran, Iran.
Materials and methods
A questionnaire, containing 29 questions on etiology, signs and symptoms, diagnosis and treatment of TMD, was given to 200 randomly selected general dental practitioners and specialists as well as 11 TMD ex-perts.
Results
An overall response rate of 97% was achieved among participants (mean age: 39 ± 8.2 years old; mean years in practice: 11.5 ± 7.4). The mean score of knowledge of TMD was found to be 10.85± 2.54 (of a total of 23). TMD specialists were significantly more knowledgeable than general dental practitioners (p<0.05). With respect to attitude, there was a significant difference among various age groups, and by increasing age and years in practice, the attitude towards TMD had weakened. However, no significant difference was recorded between general dental practitioners’ attitude and that of TMD experts towards TMD. There was a positive correlation between subjects’ knowledge and attitude (P= 0.007, r=0.138).
Conclusion
According to the results, the level of knowledge and attitude of general dental practitioners of Tehran regarding TMD is not desirable. The majority are not willing to admit and treat TMD patients.
doi:10.5681/joddd.2010.023
PMCID: PMC3429978  PMID: 22991606
Attitude, dentist; knowledge; practice; temporomandibular disorders
8.  PET Regional Cerebral Blood Flow Change During Working and Declarative Memory: Relationship With Task Performance 
Neuropsychology  1997;11(2):222-231.
Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus–response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography 15O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases.
PMCID: PMC4332579  PMID: 9110329
9.  Effect of Schizophrenia on Frontotemporal Activity During Word Encoding and Recognition: A PET Cerebral Blood Flow Study 
The American journal of psychiatry  2001;158(7):1114-1125.
Objective
Neuropsychological studies have shown that deficits in verbal episodic memory in schizophrenia occur primarily during encoding and retrieval stages of information processing. The current study used positron emission tomography to examine the effect of schizophrenia on change in cerebral blood flow (CBF) during these memory stages.
Method
CBF was measured in 23 healthy comparison subjects and 23 patients with schizophrenia during four conditions: resting baseline, motor baseline, word encoding, and word recognition. The motor baseline was used as a reference that was subtracted from encoding and recognition conditions by using statistical parametric mapping.
Results
Patients’ performance was similar to that of healthy comparison subjects. During word encoding, patients showed reduced activation of left prefrontal and superior temporal regions. Reduced left prefrontal activation in patients was also seen during word recognition, and additional differences were found in the left anterior cingulate, left mesial temporal lobe, and right thalamus. Although patients’ performance was similar to that of healthy comparison subjects, left inferior prefrontal activation was associated with better performance only in the comparison subjects.
Conclusions
Left frontotemporal activation during episodic encoding and retrieval, which is associated with better recognition in healthy people, is disrupted in schizophrenia despite relatively intact recognition performance and right prefrontal function. This may reflect impaired strategic use of semantic information to organize encoding and facilitate retrieval.
PMCID: PMC4332582  PMID: 11431234
10.  A Function of SmeDEF, the Major Quinolone Resistance Determinant of Stenotrophomonas maltophilia, Is the Colonization of Plant Roots 
Applied and Environmental Microbiology  2014;80(15):4559-4565.
Quinolones are synthetic antibiotics, and the main cause of resistance to these antimicrobials is mutation of the genes encoding their targets. However, in contrast to the case for other organisms, such mutations have not been found in quinolone-resistant Stenotrophomonas maltophilia isolates, in which overproduction of the SmeDEF efflux pump is a major cause of quinolone resistance. SmeDEF is chromosomally encoded and highly conserved in all studied S. maltophilia strains; it is an ancient element that evolved over millions of years in this species. It thus seems unlikely that its main function would be resistance to quinolones, a family of synthetic antibiotics not present in natural environments until the last few decades. Expression of SmeDEF is tightly controlled by the transcriptional repressor SmeT. Our work shows that plant-produced flavonoids can bind to SmeT, releasing it from smeDEF and smeT operators. Antibiotics extruded by SmeDEF do not impede the binding of SmeT to DNA. The fact that plant-produced flavonoids specifically induce smeDEF expression indicates that they are bona fide effectors regulating expression of this resistance determinant. Expression of efflux pumps is usually downregulated unless their activity is needed. Since smeDEF expression is triggered by plant-produced flavonoids, we reasoned that this efflux pump may have a role in the colonization of plants by S. maltophilia. Our results showed that, indeed, deletion of smeE impairs S. maltophilia colonization of plant roots. Altogether, our results indicate that quinolone resistance is a recent function of SmeDEF and that colonization of plant roots is likely one original function of this efflux pump.
doi:10.1128/AEM.01058-14
PMCID: PMC4148791  PMID: 24837376
12.  In Vitro Evaluation of the Efficacy of Liposomal and Pegylated Liposomal Hydroxyurea 
Breast cancer is one of the most frequent cancer types within women population. Hydroxyurea (HU) is a chemotherapy compound for treatment of patients with cancer diagnosis, including breast cancer associated with several adverse effects. In this study, we applied nanotechnology to decreased drug side effects along with improvement of therapeutic index. Liposomation is widely used in modern pharmacological developments in order to enhance the effects of the drugs. To achieve this, in this study a mixture of phosphatidylcholine and cholesterol was made up and HU was added to the resultant mixture, was then pegylated using Polyethylene Glycol 2000 to increase resistance, applicability and solubility. The mean diameters of nanoliposomal and pegylated nanoliposomal HU were measured by Zeta sizer device and obtained about 402.5 and 338.2 nm. The efficiency of non-pegylated and pegylated liposomal HU was 70.8 and 64.2, respectively. Releasing HU in both formulations was estimated about 25.8 and 21.7 %. Also, this study investigated the cytotoxicity effect of nanoliposomal and pegylated nanoliposomal HU using MTT assay. Results of this investigation showed that the cytotoxic properties of pegylated HU was 3.6 % more than those non-pegylated form, while was 38.93 % more than ordinary from of HU. This study showed that the stability, releasing pattern and cytotoxicity of the pegylated nanoliposomal HU is better than that of nanoliposomal HU.
doi:10.1007/s12291-013-0315-2
PMCID: PMC3903928  PMID: 24478555
Breast cancer; Hydroxyurea; Liposome; Pegylated liposome
13.  The Effect of Wheat Germ Extract on Premenstrual Syndrome Symptoms 
Pre-menstrual syndrome is one of the most common disorders in women and impairs work and social relationships. Several treatment modalities have been proposed including herbal medicines. Considering the properties of wheat germ, this study aimed to determine the effects of wheat germ extract on the symptoms of premenstrual syndrome. This triple blind clinical trial was conducted on 84 women working in hospitals affiliated to Hamadan University of Medical Sciences. Subjects completed daily symptom record form for two consecutive months. After definitive diagnosis of premenstrual syndrome, they were randomly divided into two groups of 50 people. Then, for two consecutive months, 400 mg capsules of wheat germ extract or placebo were used three times a day, from day 16 until day 5 of the next menstrual cycle. Wheat germ significantly reduced physical symptoms (63.56%), psychological symptoms (66.30%), and the general score (64.99%). Although the severity of symptoms decreased in both groups, this reduction was more significant in the wheat germ extract group (p < 0.001). On the other hand, physical symptoms decreased only in the wheat germ extract (p < 0.001) and there was no statistically significant difference in the placebo group. No complications were observed in any of the groups. It seems that using wheat germ extract reduces general, psychological and physical symptoms.
PMCID: PMC4277629  PMID: 25561922
Premenstrual syndrome; Wheat germ extract; Menstrual disorders; Herbal medicine
14.  Assessment of vulnerable atherosclerotic and fibrotic plaques in coronary arteries using 68Ga-DOTATATE PET/CT 
Activated macrophages which express somatostatin receptor-2 (SSTR-2) play a vital role in rupture of the vulnerable atherosclerotic plaques, which result in death. 68Ga-DOTATATE binds to somatostatin receptors 2, and therefore, can serve as potential radiotracer to detect atherosclerotic plaques. The purpose of this study was to generate preliminary data with this agent in vulnerable or fibrotic atherosclerotic plaques in the coronary arteries. We evaluated a total of 44 patients with neuroendocrine tumors (NET) who underwent 68Ga-DOTATATE PET/CT. In each subject, 7 segments in the coronary arteries were assessed, maximum SUV values and target-to-background ratios (TBRs) were calculated. The lesions detected by CT (a total of 308) were divided into 3 groups based on the Hounsfield unites (HU), and of which, 131 with HU less than 70 were classified as being normal (Control Group), 129 with HU 71-188 as fibrotic plaques (Group 2), and. 48 lesions with HU more than 188 as atherosclerotic plaques (Group 3). The mean TBR value in the normal group was 1.345 ± 0.58 while the mean TBR value in the fibrotic plaque group was 1.752 ± 1.50 (p 0.0043) and in atherosclerotic plaques group was (2.043 ± 1.76, p<0.0001). There was a significant correlation (p=0.0026) between 68Ga-DOTATATE uptake and the progression to formation of atherosclerotic plaques, based on HU. In patients with neuroendocrine tumors, 68Ga-DOTATATE PET/CT showed significantly increased uptake in the fibrotic and vulnerable atherosclerotic plaques compared to normal coronary arteries suggesting a potential role of this tracer for molecular assessment of coronary artery disease in this population.
PMCID: PMC4299775  PMID: 25625028
Atherosclerotic plaques; 68Ga-DOTATATE; somatostatin receptor; cardiovascular risk factors; macrophage
15.  Grant Writing 101 
Writing a grant is a hefty undertaking. Start by surrounding yourself with a successful mentor and accompanying team with a good track record. Get organized, select clear goals and objectives to your project. Once the foundation for the grant is set, begin by generating a robust hypothesis. Once your hypothesis is clearly defined, you should contact the project officer of the specific grant for which you are applying; they can help identify if the proposal meets an area of need. The basic components of a grant include the following: the face page, which highlights the key contributors; followed by table of contents; abstract; biographical sketches, which are minicurriculum vitae; budget; research plan, which is composed mostly of background, significance, and specific aims; and lastly, references cited. Be sure to follow specific formatting. Use resources including the internet to find an appropriate grant. Finally, given the confines of a busy surgical practice and the significant amount of work necessary to complete a grant, it is essential that the work begins early and well in advance of the proposed deadline.
doi:10.1055/s-0033-1356722
PMCID: PMC3835460  PMID: 24436682
grant hypothesis; mentorship; face page; biographical sketches; budget; research plan; specific aims; letters of support
16.  Faculty Development in Surgery 
doi:10.1055/s-0033-1356717
PMCID: PMC3835585  PMID: 24436677
17.  SIAM (Suicide intervention assisted by messages): the development of a post-acute crisis text messaging outreach for suicide prevention 
BMC Psychiatry  2014;14(1):294.
Background
Suicidal behaviour and deliberate self-harm are common among adults. Research indicates that maintaining contact either via letter or postcard with at-risk adults following discharge from care services can reduce reattempt risk. Feasibility trials demonstrated that intervention through text message was also effective in preventing suicide repetition amongst suicide attempters. The aim of the current study is to investigate the effect of text message intervention versus traditional treatment on reducing the risk of suicide attempt repetition among adults after self-harm.
Methods/design
The study will be a 2-year multicentric randomized controlled trial conducted by the Brest University Hospital, France. Participants will be adults discharged after self–harm, from emergency services or after a short hospitalization. Participants will be recruited over a 12-month period. The intervention is comprised of an SMS that will be sent at h48, D7, D15 and monthly. The text message enquires about the patients’ well-being and includes information regarding individual sources of help and evidence-based self help strategies. Participants will be assessed at the baseline, month 6 and 13. As primary endpoint, we will assess the number of patients who reattempt suicide in each group at 6 months. As secondary endpoints, we will assess the number of patients who reattempt suicide at 13 month, the number of suicide attempts in the intervention and control groups at 6 and 13 month, the number of death by suicide in the intervention and control groups at month 6 and 13. In both groups, suicidal ideations, will be assessed at the baseline, month 6 and 13. Medical costs and satisfaction will be assessed at month 13.
Discussion
This paper describes the design and deployment of a trial SIAM; an easily reproducible intervention that aims to reduce suicide risk in adults after self-harm. It utilizes several characteristics of interventions that have shown a significant reduction in the number of suicide reattempts. We propose to assess its efficacy in reducing suicide reattempt in the suicide attempter (SA) population.
Trial registration
The study was registered on Clinical Trials Registry (clinicaltrials.gov): NCT02106949, registrerd on 06 June 2014.
doi:10.1186/s12888-014-0294-8
PMCID: PMC4245803  PMID: 25404215
Prevention and control; Recurrence; Suicide, attempted; Telephone; Tertiary prevention; Text messaging
18.  A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma 
Purpose
This phase I study investigated the maximum-tolerated dose (MTD), safety, pharmacodynamics, immunological correlatives, and anti-tumor activity of CP-870,893, an agonist CD40 antibody, when administered in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDA).
Experimental Design
Twenty-two patients with chemotherapy-naïve advanced PDA were treated with 1000 mg/m2 gemcitabine once weekly for 3 weeks with infusion of CP-870,893 at 0.1 mg/kg or 0.2 mg/kg on day 3 of each 28 day cycle.
Results
CP-870,893 was well-tolerated; one dose-limiting toxicity (grade 4 cerebrovascular accident) occurred at the 0.2 mg/kg dose level, which was estimated as MTD. The most common adverse event was cytokine release syndrome (grade 1 to 2). CP-870,893 infusion triggered immune activation marked by an increase in inflammatory cytokines, an increase in B cell expression of co-stimulatory molecules, and a transient depletion of B cells. Four patients achieved a partial response (PR). [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) demonstrated >25% decrease in FDG uptake within primary pancreatic lesions in 6 of 8 patients; however, responses observed in metastatic lesions were heterogeneous with some lesions responding with complete loss of FDG uptake while other lesions in the same patient failed to respond. Improved overall survival correlated with a decrease in FDG uptake in hepatic lesions (R = −0.929; p = 0.007).
Conclusions
CP-870,893 in combination with gemcitabine was well-tolerated and associated with anti-tumor activity in patients with PDA. Changes in FDG uptake detected on PET/CT imaging provide insight into therapeutic benefit. Phase II studies are warranted.
doi:10.1158/1078-0432.CCR-13-1320
PMCID: PMC3834036  PMID: 23983255
Pancreatic cancer; immunotherapy; CD40; CP-870,893; PET imaging; heterogeneity
19.  Commercially available probiotic drinks containing Lactobacillus casei DN-114001 reduce antibiotic-associated diarrhea 
World Journal of Gastroenterology : WJG  2014;20(42):15837-15844.
AIM: To investigate the effect of Lactobacillus-containing commercially available probiotic formulations in Germany during antibiotic treatment with an analysis of cost-efficiency.
METHODS: In an observational study, we analyzed the frequency of bowel movements from 258 patients with infections in a primary care hospital in western Germany; 107 of the patients were offered a probiotic drink containing at least 10 billion cultures of Lactobacillus casei DN 114001 b.i.d. The economic analysis was based on the costs of patient isolation vs preventive intake of probiotics. In a second pilot study, two commercially available probiotic drinks with different Lactobacillus casei strains were directly compared in 60 patients in a randomized controlled fashion.
RESULTS: In the first study, the incidence of antibiotic-associated diarrhea (AAD) was significantly reduced in the intervention group (6.5% vs 28.4%), and the duration of AAD in days was significantly shorter (1.7 ± 1.1 vs 3.1 ± 2.1). Higher age and creatinine and lower albumin were identified as risk factors for AAD. Ampicillin was the antibiotic with the highest rate of AAD (50%) and with the greatest AAD reduction in the probiotic group (4.2%, relative risk reduction 92%). The economic analysis showed a cost advantage of nearly 60000 €/year in a department of this size. The second study confirmed the preventive effect of the drink with Lactobacillus casei DN114001; however, there were no advantages found for the other tested probiotic drink containing Lactobacillus casei Shirota.
CONCLUSION: In contrast to a drink containing Lactobacillus casei Shirota, a commercially available probiotic drink containing Lactobacillus casei DN 114001 cost-efficiently reduces the prevalence of AAD during antibiotic treatment.
doi:10.3748/wjg.v20.i42.15837
PMCID: PMC4229551  PMID: 25400470
Antibiotics-associated diarrhea; Probiotics; Lactobacillus casei
20.  Multifocal kaposiform hemangioendothelioma of soft tissue with bilateral pulmonary involvement in an adolescent 
Korean Journal of Pediatrics  2014;57(11):500-504.
Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor of intermediate malignancy with resemblance to Kaposi sarcoma. It occurs predominantly in pediatric age groups as a cutaneous lesion with focal infiltration into the adjacent soft tissue and bone. Although visceral involvement is very uncommon, several cases with bone, retroperitoneal, or mediastinal involvement have been described. KHE has been reported to occasionally occur in unusual sites such as the thymus, tonsils, larynx, paranasal sinuses, deltoid muscle, spleen, uterine cervix, thoracic spine, and even the breast. Multifocal KHE is an extremely rare entity with few reports available in the literature, none of which describes pulmonary involvement. Herein, we report a unique case of multifocal KHE in a 13-year-old boy presenting with a huge soft tissue mass in the upper extremity complicated by bilateral pulmonary nodules that developed into large, necrotic tumor masses.
doi:10.3345/kjp.2014.57.11.500
PMCID: PMC4279012  PMID: 25550706
Kaposiform hemangioendothelioma; Bone; Pulmonary neoplasm; Multifocal; Adolescent
21.  Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial 
Journal of Clinical Oncology  2013;31(30):3823-3830.
Purpose
In this prospective National Cancer Institute–funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non–small-cell lung cancer (NSCLC).
Patients and Methods
Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models.
Results
Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak.
Conclusion
Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.
doi:10.1200/JCO.2012.47.5947
PMCID: PMC3795891  PMID: 24043740
22.  Study of Toxicity Effect of Pegylated Nanoliposomal Artemisinin on Breast Cancer Cell Line 
Nano carriers have greatly revolutionized the treatment of most diseases recently. One of these nano carriers, liposomes, has got particular significance. On the other hand, Artemisinin which is used as an effective anticancer drug has some side effects. To reduce such side effects, liposomes can be employed. In order to prepare pegylated nanoliposomal artemisinin, particular proportions of phosphatidylcholine, polyethylene glycol 2000 and artemisinin were combined. As a result, the mean diameter of nano liposomes is 455 nm. Besides, the encapsulation efficiency and the drug release from pegylated nanoliposomes for pegylated nanoliposomal artemisinin are respectively 91.62 ± 3.5 and 5.17 %. The results also show that IC50 of the produced formulation is less than that of the standard drug. This study reveals that the amount of artemisinin cytotoxicity compared to standard drug is increased by pegylated nanoliposomal formulation.
doi:10.1007/s12291-013-0306-3
PMCID: PMC3783905  PMID: 24426245
Artemisinin; Nanoliposome; Breast cancer; Pegylation
23.  Effects of In Vitro Zinc Sulphate Additive to The Semen Extender on Water Buffalo (Bubalusbubalis) Spermatozoa before and after Freezing  
Background
The objective of the study was to investigate the effects of in vitro zinc sulphate additive to semen extender on sperm parameters (progressive motility, viability, membrane integrity and DNA stability) after cryopreservation.
Materials and Methods
In this Prospective longitudinal laboratory study, semen samples of 5 buffalo bulls of 3-5 years old were collected at 5 different occasions from Iran, Urmia during summer and autumn 2011, 25 samples were used in each treatment. Sperm progressive motility, viability and abnormal morphology were measured before and at 0.5 (T0), 1(T1) and 2(T2) hours after diluting semen(1:10 v/v) in Tris-citric acid based extender (without egg yolk and glycerol) at 37˚C containing none (control group), 0.072, 0.144, 0.288, 0.576 and 1.152 mg/L zinc sulphate to investigate dose and time effects. Next, a Tris-citric acid-egg yolk-glycerol extender (20% egg yolk and 7% glycerol) containing the same amount of zinc sulphate was prepared, diluted semen (1:10 v/v) was cooled and kept into a refrigerated chamber (4˚C) for 4 hours to equilibrate. Sperm progressive motility, viability, abnormal morphology, membrane integrity and DNA damage were estimated.The equilibrated semen was loaded in 0.5 ml French straws and frozen in liquid nitrogen. Later, the frozen semen was thawed and the same parameters as well as total antioxidant capacity (TAC) of the frozen-thawed semen were determined.
Results
The results showed that zinc sulphate additive at the rate of 0.288 mg/L gave a higher protection of sperm progressive motility (53.7 ± 1.8% vs. 40.5 ± 1.7%), viability (70.8 ± 1.8% vs. 60.1 ± 1.5%), membrane integrity (67.3 ± 1.6% vs. 56.6 ± 1.7%), DNA stability (10.1 ± 0.47% vs. 11.8 ± 0.33% damaged DNA) through the process of dilution, equilibration and freeze-thawing and caused a higher TAC level (81 ± 3.3% vs. 63 ± 3.2 µmol/L) after freez-thawing compared to the control group. Adding 0.576 and 1.152 mg/L zinc sulphate, however, was deleterious to the sperm and significantly reduced the studied sperm parameters.
Conclusion
Adding 0.288 mg/L zinc sulphate to the extender, compared to the control group, gives a better sperm preservation upon freezing processes which in turn, may results in higher semen fertility. But, addition of higher zinc sulphate concentrations (0.576 and 1.152 mg/L) are detrimental to buffalo spermatozoa.
PMCID: PMC4221520  PMID: 25379162
Semen; Zinc; Buffalo
24.  Expression analysis for genes involved in arachidonic acid biosynthesis in Mortierella alpina CBS 754.68 
Brazilian Journal of Microbiology  2014;45(2):439-445.
The time courses for production of fungal biomass, lipid, phenolic and arachidonic acid (ARA) as well as expression of the genes involved in biosynthesis of ARA and lipid were examined in Mortierella alpina CBS 754.68. A significant increase in the arachidonic acid content in lipids that coincided with reduced levels of lipid was obtained. Reduced gene expression occurred presumably due to the steady reduction of carbon and nitrogen resources. However, these energy resources were inefficiently compensated by the breakdown of the accumulated lipids that in turn, induced up-regulated expression of the candidate genes. The results further indicated that the expression of the GLELO encoding gene is a rate-limiting step in the biosynthesis of ARA in the early growth phase.
PMCID: PMC4166267  PMID: 25242926
Mortierella alpina; arachidonic acid; lipid; gene expression; real time PCR
25.  Inflammatory cells’ role in acetic acid-induced colitis 
Background:
Free radicals are the known mechanisms responsible for inducing colitis with two origins: Inflammatory cells and tissues. Only the inflammatory cells can be controlled by corticosteroids. Our aim was to assess the importance of neutrophils as one of the inflammatory cells in inducing colitis and to evaluate the efficacy of corticosteroids in the treatment of inflammatory bowel disease (IBD).
Materials and Methods:
Thirty-six mice were divided into six groups of six mice each. Colitis was induced in three groups by exposing them to acetic acid through enema (group 1), ex vivo (group 3), and enema after immune suppression (group 5). Each group had one control group that was exposed to water injection instead of acetic acid. Tissue samples were evaluated and compared based on macroscopic damages and biochemical and pathological results.
Results:
Considering neutrophilic infiltration, there were significant differences between groups 1, 3, 5, and the control of group 1. Groups 3, 5, and their controls, and group 1 and the control of group 3 had significant differences in terms of goblet depletion. Based on tissue originated H2O2, we found significant differences between group 1 and its control and group 3, and also between groups 5 and the control of group 3. All the three groups were significantly different from their controls based on Ferric Reducing Ability of Plasma (FRAP) and such differences were also seen between group 1 with two other groups.
Conclusion:
Neutrophils may not be the only cause of oxidation process in colitis, and also makes the effectiveness of corticosteroids in the treatment of this disease doubtful.
doi:10.4103/2277-9175.140666
PMCID: PMC4202508  PMID: 25337523
Acetic acid-induced colitis; corticosteroid; inflammatory bowel disease; neutrophil infiltration

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