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Ghanbar Mahmoodi Chalbatani,1,* Hassan Dana,1,2,* Elahe Gharagouzloo,1 Santiago Grijalvo,3,4 Ramon Eritja,3,4 Craig D Logsdon,5,6 Fereidoon Memari,1 Seyed Rouhollah Miri,1 Mahdi Rezvani Rad,7 Vahid Marmari21Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran; 2Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran; 3Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona 08034, Spain; 4Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER BBN), Madrid, Spain; 5Department of Cancer Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA; 6Department of GI Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA; 7Department of Biology, Zabol University, Zabol, Iran*These authors contributed equally to this workAbstract: Cancer is one of the most complex diseases that has resulted in multiple genetic disorders and cellular abnormalities. Globally, cancer is the most common health concern disease that is affecting human beings. Great efforts have been made over the past decades in biology with the aim of searching novel and more efficient tools in therapy. Thus, small interfering RNAs (siRNAs) have been considered one of the most noteworthy developments which are able to regulate gene expression following a process known as RNA interference (RNAi). RNAi is a post-transcriptional mechanism that involves the inhibition of gene expression through promoting cleavage on a specific area of a target messenger RNA (mRNA). This technology has shown promising therapeutic results for a good number of diseases, especially in cancer. However, siRNA therapeutics have to face important drawbacks in therapy including stability and successful siRNA delivery in vivo. In this regard, the development of effective siRNA delivery systems has helped addressing these issues by opening novel therapeutic windows which have allowed to build up important advances in Nanomedicine. In this review, we discuss the progress of siRNA therapy as well as its medical application via nanoparticle-mediated delivery for cancer treatment.Keywords: delivery strategies, lipoplexes, nanovectors, polymeric nanoparticles, siRNA

There continues to be an ongoing need for fair and equitable organ allocation. The Model for End-Stage Liver Disease (MELD) score has evolved as a calculated framework to evaluate and allocate patients for liver transplantation objectively. The original MELD score has undergone multiple modifications as it is continuously scrutinized for its accuracy in objectively representing the clinical context of patients with liver disease. Several refinements and iterations of the score have been developed, including the widely accepted MELD-Na score. In addition, the most recent updated iteration, MELD 3.0, has been created. The MELD 3.0 calculator incorporates new variables such as patient sex and serum albumin levels and assigns new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is anticipated that the use of MELD 3.0 scores will reduce overall waitlist mortality and enhance access for female liver transplant candidates. However, despite the emergence of the MELD score as one of the most objective measures for fair organ allocation, various countries and healthcare systems employ alternative methods for stratification and organ allocation. This review article will highlight the origins of the MELD score, its iterations, the current MELD 3.0, and future directions for managing liver transplantation organ allocation. LAY SUMMARY: Organ donation is crucial for the management of patients unwell with liver disease, but organs must be allocated fairly and equitably. One method used for this is the Model for End-Stage Liver Disease (MELD) score, which helps objectively decide which patient is a candidate for liver transplant. Over time, the MELD score has been refined to better reflect patients' needs. For example, the latest version, MELD 3.0, now considers factors like nutrition and gender. This should ensure that more patients, especially females, are candidates and receive appropriate access to liver transplantation. However, not every country uses the MELD score. Some countries have created their own scoring systems based on local research. This review will explain where the MELD score came from, how it has changed, the current characteristics of the MELD 3.0 score, and what the future might hold for organ allocation in liver transplants., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The application of stem cells in regenerative medicine depends on their biological properties. This scoping review aimed to compare the features of periodontal ligament stem cells (PDLSSCs) with stem cells derived from other sources., Design: An electronic search in PubMed/Medline, Embase, Scopus, Google Scholar and Science Direct was conducted to identify in vitro and in vivo studies limited to English language., Results: Overall, 65 articles were included. Most comparisons were made between bone marrow stem cells (BMSCs) and PDLSCs. BMSCs were found to have lower proliferation and higher osteogenesis potential in vitro and in vivo than PDLSCs; on the contrary, dental follicle stem cells and umbilical cord mesenchymal stem cells (UCMSCs) had a higher proliferative ability and lower osteogenesis than PDLSCs. Moreover, UCMSCs exhibited a higher apoptotic rate, hTERT expression, and relative telomerase length. The immunomodulatory function of adipose-derived stem cells and BMSCs was comparable to PDLSCs. Gingival mesenchymal stem cells showed less sensitivity to long-term culture. Both pure and mixed gingival cells had lower osteogenic ability compared to PDLSCs. Comparison of dental pulp stem cells (DPSCs) with PDLSCs regarding proliferation rate, osteo/adipogenesis, and immunomodulatory properties was contradictory; however, in vivo bone formation of DPSCs seemed to be lower than PDLSCs., Conclusion: In light of the performed comparative studies, PDLSCs showed comparable results to stem cells derived from other sources; however, further in vivo studies are needed to determine the actual pros and cons of stem cells in comparison to each other., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: A cesarean scar defect (CSD) is incomplete healing of the myometrium at the site of a prior cesarean section (CS), complicating more than half of all cesarean sections. While transvaginal ultrasound (TVU) is the most common modality for diagnosing this defect, hysteroscopy remains the gold standard. We aimed to develop an efficient diagnostic tool for CSD among women with abnormal uterine bleeding (AUB) by integrating TVU findings and participants' demographic features., Methods: A single-center cross-sectional study was conducted on 100 premenopausal and non-pregnant women with a history of CS complaining of AUB without a known systemic or structural etiology. Each participant underwent a hysteroscopy followed by a TVU the next day. The defect dimensions in TVU, patients' age, and the number of previous CSs were integrated into a binary logistic regression model to evaluate their predictive ability for a hysteroscopy-confirmed CSD., Results: Hysteroscopy identified 74 (74%) participants with CSD. The variables age, the number of CSs, defect length, and defect width significantly contributed to the logistic regression model to diagnose CSD with odds ratios of 9.7, 0.7, 2.6, and 1.7, respectively. The developed model exhibited accuracy, sensitivity, and specificity of 88.00%, 91.89%, and 76.92%, respectively. The area under the receiver operating curve was 0.955 (P-value < 0.001)., Conclusion: Among non-pregnant women suspected of CSD due to AUB, looking at age, the number of previous CSs, and TVU-based defect width and length can efficiently rule CSD out., (© 2023. The Author(s).)

Background: The only beneficial treatment option for the management of inferior vena cava (IVC) tumor thrombus is complete tumor removal. The aim of this study was to report our experience in surgical and clinical outcomes in patients with tumor thrombosis in IVC., Methods: A retrospective chart review of patients who underwent surgical resection of IVC tumor at our institution over the past 10 years was performed. The patients were identified using a prospectively maintained database., Results: We identified 51 patients, the mean age was 53.4 ± 16.8 years, and 25.4% were female. They were divided into three groups based on tumor thrombosis level. Twenty patients (39.2%) required sternotomy, and cardiopulmonary bypass (CPB) was used in 19 (37.2%) patients, and 2 (3.9%) cases underwent coronary artery bypass graft. The perioperative complications were severe bleeding (3 patients), pulmonary embolism (2 patients), and duodenal perforation (1 patient). Three (5.8%) in-hospital deaths occurred, and all were due to severe abdominal bleeding. After a mean follow-up time of 46.5 ± 42.0 months, 29 (56.9%) patients were alive. The mean survival time was 75.2 ± 8.4 months. In multivariate analysis, higher age ( p  = 0.033) and male gender ( p  = 0.033) proved to be independent prognostic factors., Conclusions: Tumor thrombus extending to the IVC is a rare and challenging event. Although using CPB may be safe and result in long-term survival with acceptable function, excessive bleeding during surgery may limit the use of this method.

Digital realization of neuron models, especially implementation on a field programmable gate array (FPGA), is one of the key objectives of neuromorphic research, because the effective hardware realization of the biological neural networks plays a crucial role in implementing the behaviors of the brain for future applications. In this paper, a hybrid FitzHugh Nagumo-Morris Lecar (FNML) neuron model with electromagnetic flux coupling is considered, and two multiplierless piecewise linear (PWL) models, which have similar behaviors to the biological neuron, are presented. A comparison between digital implementation results of the original FNML and PWL models illustrates that, the PWL1 model provides a 65% speed-up with an overall saving (in FPGA resources) of 66.2%, and the PWL2 model yields a 71% speed-up with an overall saving of 78.2%.

Despite the plethora of literature regarding isolation and characterization of periodontal ligament stem cells (PDLSCs), due to the existence of controversies in the results, in this comprehensive review, we aimed to summarize and compare the effect of isolation methods on PDLSC properties, including clonogenicity, viability/proliferation, markers expression, cell morphology, differentiation, and regeneration. Moreover, the outcomes of included studies, considering various parameters, such as teeth developmental stages, donor age, periodontal ligament health status, and part of the teeth root from which PDLSCs were derived, have been systematically discussed. It has been shown that from included studies, PDLSCs can be isolated from teeth at any developmental stages, health status condition, and donor age. Furthermore, a non-enzymatic digestion method, named as an explant or outgrowth technique, is a suitable protocol for PDLSCs isolation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: It has been shown that mechanical forces can induce or promote osteogenic differentiation as well as remodeling of the new created bone tissues. To apply this characteristic in bone tissue engineering, it is important to know which mechanical stimuli through which signaling pathway has a more significant impact on osteogenesis., Methods: In this systematic study, an electronic search was conducted using PubMed and Google Scholar databases. This study has been prepared and organized according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Included studies were first categorized according to the in vivo and in vitro studies., Results: Six types of mechanical stresses were used in these articles and the most commonly used mechanical force and cell source were tension and bone marrow-derived mesenchymal stem cells (BMMSCs), respectively. These forces were able to trigger twelve signaling pathways in which Wnt pathway was so prominent., Conclusion: 1) Although specific signaling pathways are induced through specific mechanical forces, Wnt signaling pathways are predominantly activated by almost all types of force/stimulation, 2) All signaling pathways regulate expression of RUNX2, which is known as a master regulator of osteogenesis, 3) In Tension force, the mode of force administration, i.e, continuous or noncontinuous tension is more important than the percentage of elongation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Scientists encounter many obstacles in traditional cancer therapies, including the side effects on the healthy cells, drug resistance, tumor relapse, the short half-life of employed drugs in the blood circulation, and the improper delivery of drugs toward the tumor site. The unique traits of stem cells (SCs) such as self-renewal, differentiation, tumor tropism, the release of bioactive molecules, and immunosuppression have opened a new window for utilizing SCs as a novel tool in cancer treatment. In this regard, engineered SCs can secrete anti-cancer proteins or express enzymes used in suicide gene therapy which locally induce apoptosis in neoplastic cells via the bystander effect. These cells also stand as proper candidates to serve as careers for drug-loaded nanoparticles or to play suitable hosts for oncolytic viruses. Moreover, they harbor great potential to be employed in immunotherapy and combination therapy. However, tactful strategies should be devised to allow easier transplantation and protection of SCs from in vivo immune responses. In spite of the great hope concerning SCs application in cancer therapy, there are shortcomings and challenges to be addressed. This review tends to elaborate on recent advances on the various applications of SCs in cancer therapy and existing challenges in this regard., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This study aimed to analyze the effect of fabrication factors on both biological and physico-chemical features of 3-dimensional (3D) printed composite scaffolds., Method: Electronic search was done according to the PRISMA guideline in PubMed and Scopus databases limited to English articles published until May 2021. Studies in which composite scaffolds were fabricated through computer-aided design and computer-aided manufacturing (CADCAM)- based methods were included. Articles regarding the features of the scaffolds fabricated through indirect techniques were excluded., Results: Full text of 121 studies were reviewed, and 69 met the inclusion criteria. According to analyzed studies, PCL and HA were the most commonly used polymer and ceramic, respectively. Besides, the solvent-based technique was the most commonly used composition technique, which enabled preparing blends with high concentrations of ceramic materials. The most common fabrication method used in the included studies was Fused Deposition Modeling (FDM). The addition of bio-ceramics enhanced the mechanical features and the biological behaviors of the printed scaffolds in a ratio-dependent manner. However, studies that analyzed the effect of ceramic weight ratio showed that scaffolds with the highest ceramic content did not necessarily possess the optimal biological and non-biological features., Conclusion: The biological and physico-chemical behaviors of the scaffold can be affected by pre-printing factors, including utilized materials, composition techniques, and fabrication methods. Fabricating scaffolds with high mineral content as of the natural bone may not provide the optimal condition for bone formation. Therefore, it is recommended that future studies compare the efficiency of different kinds of biomaterials rather than different weight ratios of one type., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Advances in Cancer immunotherapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death protein 1 (PD1), and programmed cell death ligand 1 (PD-L1) are three co-inhibitory receptors that are expressed in the tumor microenvironment. Immune checkpoint inhibitors (ICI) that target these biomarkers unleash the properties of effector T cells that are licensed to kill cancer cells. Immune checkpoint blockade has dramatically changed the treatment landscape of many cancers. In this Review, we describe the current data regarding clinical trials of ICIs in six important cancers, including hepatocellular carcinoma (HCC), renal cell cancer (RCC), hodgkin lymphoma (HL), non-hodgkin lymphoma (NHL), non-small cell lung cancer (NSCLC), and head and neck cancer carcinoma (HNSCC)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ring resonators are well-known optical biosensors thanks to their relatively high Q-factor and sensitivity, in addition to their potential to be fabricated in large arrays with a small footprint. Here, we investigated the characteristics of a polymer ring resonator with a partially tapered waveguide for Biomedical Sensing. The goal is to develop a more sensitive biosensor with an improved figure of merit. The concept is more significant field interaction with the sample under test in tapered segments. Waveguide width is hereby gradually reduced to half. Sensitivity improves from 84.6 to 101.74 [nm/RIU] in a relatively small Q-factor reduction from 4.60 × 10 3 for a strip waveguide to 4.36 × 10 3 for a π/4 partially tapered one. After the study, the number of tapered parts from zero to fifteen, the obtained figure of merit improves from 497 for a strip ring to 565 for a π/4 tapered ring close to six tapered ones. Considering the fabrication process, the three-tapered one is suggested. The all-polymer material device provides advantages of a low-cost, disposable biosensor with roll-to-roll fabrication compatibility. This design can also be applied on silicon on isolator, or polymer on silicon-based devices, thereby taking advantage of a higher Q-factor and greater sensitivity.

Background: Considering the complications associated with autogenous bone grafting, the use of freezedried bone allograft (FDBA) granules may be considered as an alternative treatment plan., Objectives: The aim of this study was to evaluate the effect of metformin on both the proliferation and osteogenic capability of dental pulp stem cells (DPSCs) cultured on FDBA granules., Material and Methods: First, a pilot study was conducted only on DPSCs to confirm cellular viability and the osteoinducing effect of 100 μmol/L metformin. Next, the cells were loaded on FDBA granules and treated with and without metformin. Finally, the following analyses were performed: scanning electron microscopy (SEM) (cell attachment); the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (proliferation); and alkaline phosphatase (ALP) activity analysis (osteogenic differentiation)., Results: The SEM images revealed that metformin enhanced the adhesion of DPSCs on FDBA granules. In addition, metformin was shown to increase cell proliferation/viability from day 1 to day 7. Compared to the control, a significant difference was observed after 7 days of treatment. Metformin enhanced the osteogenic capability of FDBA in both standard and osteoinducing conditions. An increase in ALP activity was significant after 7 days of treatment. The positive effect of metformin on differentiation was significant in osteoinducing conditions., Conclusions: Metformin can be applied as an additional osteoinductive factor in bone regeneration treatment. Moreover, scaffolds with controlled release of metformin can be considered a proper osteoinductive bone substitute that may lessen the complications related to applying allograft scaffolds alone.

The frequency and intensity of natural disasters such as hurricanes, wildfires, and floods are predicted to change as greenhouse gas concentrations increase. These disasters may represent sources of information for individuals as they update their beliefs related to climate change. Using a dataset that includes climate beliefs of respondents, we examine the effect of natural disasters on climate change beliefs and find that hurricanes significantly increase the probability that survey respondents from a given county believe that climate change is occurring and that it is human caused. We find that past experience with certain types of natural disasters (e.g., hurricanes) impacts beliefs regarding whether climate change is occurring and if it is human caused. The research contributes to the literature evaluating climate change attitudes by using spatially disaggregate information on climate change beliefs and exposure to a set of natural disasters over time. Characterizing beliefs and attitudes toward climate change and related policies is important since these beliefs are a determinant of individual adaptation and support for policies related to reducing carbon emissions., (© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021.)

Background: Human amniotic membranes (HAMs), as a biological membrane with healing, osteogenic, and cell therapy potential, has been in the spotlight to enhance the outcomes of treating bone defects. Present study aims to clinically assess the potential of HAM loaded with buccal fat pad-derived stem cells (BFSCs) as an osteogenic coverage for onlay bone grafts to maxillomandibular bone defects., Materials and Methods: Nine patients with jaw bone defects were enrolled in the present study. The patients were allocated to two study groups: Iliac crest bone graft with HAM coverage (n = 5), and Iliac bone grafts covered with HAM loaded with BFSCs (n = 4). Five months following the grafting and prior to implant placement, cone beam computed tomography was performed for radiomorphometric analysis., Results: The mean increase in bone width was found to be significantly greater in the HAM + BFSCs group (4.42 ± 1.03 mm versus 3.07 ± 0.73 mm, p < 0.05). Further, the changes in vertical dimension were greater in the HAM + BFSCs group (4.66 ± 1.06 mm versus 4.14 ± 1.03 mm, p > 0.05)., Conclusion: Combined use of HAM with mesenchymal stem cells may enhance bone regeneration specifically in the horizontal dimension. Moreover, this methodology reduces the amount of harvested autogenous bone and diminish secondary bone resorption., (Copyright © 2019 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: Eradication of Aggregatibacter actinomycetemcomitans ( A. actionmycetemcomitans ), as an opportunistic periodontopathogen, and inhibition of its virulence factor expression require a new adjunctive therapeutic method. In this study, we accessed the expression level of rcpA gene, as a virulence factor associated with A. actinomycetemcomitans biofilm formation, following treatment by antimicrobial photodynamic therapy (aPDT) using indocyanine green (ICG) doped with chitosan nanoparticles (CS-NPs@ICG)., Materials and Methods: CS-NPs@ICG was synthesized and examined using scanning electron microscopy (SEM). A. actinomycetemcomitans ATCC 33384 strain was treated with CS-NPs@ICG, as a photosensitizer, which was excited with a diode laser at the wavelength of 810 nm with the energy density of 31.2 J/cm2. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the changes in rcpA gene expression level., Results: Synthetized CS-NPs@ICG was confirmed via SEM. The results revealed that CS-NPs@ICG-mediated aPDT could significantly decrease rcpA gene expression to 13.2-fold (P<0.05). There was a remarkable difference between aPDT using CS-NPs@ICG and ICG (P<0.05). The diode laser, ICG, and CS-NPs@ICG were unable to significantly downregulate rcpA gene expression (P>0.05)., Conclusion: aPDT with CS-NPs@ICG leads to a decrease of the virulence factor of A. actinomycetemcomitans and can be used as an adjunct to routine treatments for successful periodontal therapy in vivo., Competing Interests: CONFLICT OF INTEREST STATEMENT None declared., (Copyright© Dental Research Center, Tehran University of Medical Sciences.)

Background: Depressive disorders are a major public health problem in developed and developing countries. Recently, several risk factors have been described for depressive disorders in children and adolescents. The aim of the present study was to identify the main risk factors that can affect the incidence of depression in Iranian children and adolescents., Methods: A total of 30,546 children and adolescents (between 6 and 18 years of age) participated in a cross-sectional study to identify the predictors of depressive disorders. Depressive disorders were assessed using the Persian version of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL). In addition, a demographic characteristics questionnaire was completed by parents of the participants. The data was analyzed using the SPSS 22 software via performing the descriptive analysis and the multiple logistic regression analysis methods. P-values less than 0.05 were considered statistically significant., Results: Results showed that a higher age (15-18), being female, and the father's unemployment were associated with an increased odds ratio for depressive disorders. The age of 10-14 (OR = 2.1; 95% CI, 1.57-2.81), the age of 15-18 (OR = 4.44; 95% CI, 3.38-5.83), female gender (OR = 1.44; 95% CI, 1.2-1.73) and the father's unemployment (OR = 1.59; 95% CI, 1.01-2.5) were significant positive predictors, whereas, the mother's job (as a housewife) (OR = 0.66; 95% CI, 0.45-0.96) and a history of psychiatric hospitalization of the father and mother (OR = 0.34; 95% CI, 0.15-0.78 and OR = 0.34; 95% CI, 0.14-0.84) were negative predictors for depressive symptoms., Conclusion: Depressive symptoms are common in children and adolescents and are correlated with age and gender. The assessment of the prevalence of psychiatric disorders, especially the depressive disorders and their comorbidities, may help to prevent mood disorders in children and adolescents., (Copyright © 2019. Published by Elsevier B.V.)

This case report seeks to describe efficient clinical application of adipose-derived stem cells (AdSCs) originated from buccal fat pad (BFP) in combination with conventional guided bone regeneration as protected healing space for reconstruction of large alveolar defects after extraction of multiple impacted teeth. The first case was a 19-year-old woman with several impacted teeth in the maxillary and mandibular regions, which could not be forced to erupt and were recommended for surgical extraction by the orthodontist. After this procedure, a large bone defect was created, and this space was filled by AdSC loaded natural bovine bone mineral (NBBM), which was protected with lateral ramus cortical plates, microscrews, and collagen membrane. After 6 months of post-guided bone regeneration, the patient received 6 and 7 implant placements, respectively, in the maxilla and mandible. At 10 months postoperatively, radiographic evaluation revealed thorough survival of implants. The second case was a 22-year-old man with the same complaint and large bony defects created after his teeth were extracted. After 6 months of post-guided bone regeneration, he received 4 dental implants in his maxilla and 7 implants in the mandible. At 48 months postoperatively, radiographs showed complete survival of implants. This approach represented a considerable amount of 3-dimensional bone formation in both cases, which enabled us to use dental implant therapy for rehabilitation of the whole dentition. The application of AdSCs isolated from BFP in combination with NBBM can be considered an efficient treatment for bone regeneration in large alveolar bone defects.

Background: It has clearly been demonstrated that Enterococcus faecalis, as a persistent microorganism, is the major agent in the etiopatogeny of endodontic infections. Recently, the limitations of conventional endodontic therapy have given rise to many attempts to introduce antimicrobial photodynamic therapy (aPDT) as an alternative treatment. The aim of this study was to analyze the ex vivo effect of aPDT in combination with 2.0% chlorhexidine (CHX) as a conventional therapy on colony count and expression patterns of genes associated with biofilm formation of E. faecalis., Materials and Methods: A total of 125 extracted human single-rooted teeth were divide into six groups (A-F; n = 20) and were incubated with E. faecalis. Group A- photosensitizer (indocyanine green [ICG]); B- diode laser; C- aPDT; D- 2.0% CHX; E- aPDT with photosensitizer modified by 2.0% CHX; and F- control group (no procedure was performed). Five remaining teeth were used to confirm the presence of E. faecalis biofilm via scanning electron microscope. Counts of colony forming units (CFUs) in each group were evaluated separately and quantitative real-time PCR (qRT-PCR) was then applied to monitor genes expression of fsrC, efa, and gelE involved in E. faecalis biofilm., Results: The results showed that none of the tested groups achieved eradication or inhibition of biofilm. On the other hand, aPDT + 2.0% CHX, 2.0% CHX, and ICG- mediated aPDT groups showed significantly less CFU/mL than ICG and diode laser groups. The group with the lowest CFU/mL count was the aPDT + 2.0% CHX, being statistically different from all other groups that could decrease the expression levels of efa, gelE, and fsrC genes 6.8-, 8.3-, and 12.1-fold, respectively., Conclusion: Based on the results, the synergism effect of ICG-aPDT with 2.0% CHX leads to modulation of the virulence of E. faecalis strains biofilm model by suppressing the expression of the genes associated with biofilm formation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Currently, antibodies are progressively applied in medicine for different purposes, including diagnostic and therapeutic indications. Over twenty monoclonal antibodies utilized for many therapeutic reasons from therapy of cancers, immune disorders, and osteoporosis to localized bony defects. In addition, therapeutic antibodies represented various findings in bone tissue engineering., Objectives: The current study aims to systematically review the available literature on antibody assisted bone regeneration in animal models., Methods: A through electronic search was conducted from January 1992 to June 2017 limited to English language publications on administrations of antibodies for bone regeneration. Data extraction was ere performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement., Results: Twenty studies were selected and analyzed in this systematic review. Among these studies, six articles reported in vitro results in addition to in vivo evaluations. The data is tabulated according to the route of administrations as locally administrated antibody which includes anti-bone morphogenetic protein 2 (anti-BMP2) and systemic administrated antibodies, which include anti-sclerostin and anti- Dickkopf-1 (DKK1). Data are summarized and reported by the following variables: Type of study, types of cells for in vitro investigations, types of animal models and defects characteristics, types of scaffolds used in the defect site, duration of follow-ups; and outcomes of assessments., Conclusions: A novel approach of administration of antibodies demonstrated promising results for bone tissue engineering. However, more investigations, particularly in larger animals, are required for their further possible clinical administration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background and Objective: Today, resistance to multiple classes of antibiotics, and notably to the β-lactam and aminoglycosides in A. baumannii is becoming a great problem and it necessitates to make a new approach to combat with multidrug-resistant (MDR), extensive drug-resistance (XDR) or Pandrug-resistant (PDR) isolates. In this case, a new strategy and ways should be designed and introduced against such infections. Therefore the aim of the present study was the evaluation of antibacterial activity of nanoconjugate gentamicin and amikacin with gold against clinical isolates of A. baumannii that were collected from burn wound infection. There are some patents of gold nanoparticles that are conjugated with antibiotics (WO2017161296A1, US20090181101A1)., Methods: Eighteen A. baumannii were collected from burn wound infections. For confirmation and detection of aminoglycoside-resistant genes, PCR was carried out. Gold nanoparticles and nanoconjugates were prepared according to the protocol. For the evaluation of the nanoconjugate, Dynamic light cattering, Transmission electron microscopy and FTIR Analysis were carried out. Then, the antibacterial activity of nanoconjugates was conducted by using micro broth dilution method., Result: Prevalence of aminoglycoside-resistant genes was aacC1, aphA6, aadA1, aadB genes 55.5%, 22.2%, 38.8% and 22.2% respectively. Synthesis of bare nanoconjugates resulted in nanoparticle in a size of 10 nm. Amikacin bound to Gnps showed excellent antibacterial activity (94.5%) and just one isolate showed intermediate resistance. Also, gentamicin bound to Gnps had a good antimicrobial effect (50%) in contrast to gentamicin alone., Conclusion: Our study showed that a combination of amikacin and gentamicin with Gnps has a significant antibacterial efficiency against clinical isolates of A. baumannii. Gnps can be used as extraordinary molecular carriers for targeting, and delivery of the antibiotic molecules to the specific infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The tissue engineering scaffold acts as an extracellular matrix that interacts to the cells prior to forming new tissues. The chemical and structural characteristics of scaffolds are major concerns in fabricating of ideal three-dimensional structure for tissue engineering applications. The polymer scaffolds used for tissue engineering should possess proper architecture and mechanical properties in addition to supporting cell adhesion, proliferation, and differentiation. Much research has been done on the topic of polymeric scaffold properties such as surface topographic features (roughness and hydrophilicity) and scaffold microstructures (pore size, porosity, pore interconnectivity, and pore and fiber architectures) that influence the cell-scaffold interactions. In this review, efforts were given to evaluate the effect of both chemical and structural characteristics of scaffolds on cell behaviors such as adhesion, proliferation, migration, and differentiation. This review would provide the fundamental information which would be beneficial for scaffold design in future. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 431-459, 2017., (© 2015 Wiley Periodicals, Inc.)

Background: Traditional attempts to grow bone grafts in vitro have been based on culturing cell-scaffold constructs under static culture conditions. However, limitations associated with this approach have led to the development of various types of technologies and equipments. One of these is a bioreactor acting as an intermediate between static (in vitro) and dynamic (in vivo) conditions, which can mimic physiological and mechanical body conditions., Objective: The aim of this study was to systematically review the available literature on application of different types of bioreactors in bone tissue engineering., Methods: A thorough search in PubMed and Google Scholar databases from January 2011 to December 2016 was performed. All in vitro and in vivo studies about bioreactor applications in bone tissue engineering were included and categorized according to bioreactor types., Conclusion: A comprehensive systematic review of all the studies from the past five years yielded several findings: (1) combined bioreactors seem effective in bone tissue engineering; (2) 1- 2 ml/min is an appropriate flow rate range; (3) a cylinder is an appropriative scaffold shape; and (4) incubation of the scaffold with cells prior to transfer to the bioreactor followed by administration of osteogenic medium in the bioreactor seems an efficient approach to help cells properly attach and differentiate., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted., (Creative Commons Attribution License)

Objective: This study aims to evaluate the spinal sagittal balance and the spinopelvic parameters in patients with degenerative lumbar spinal stenosis and healthy controls in Iranian population., Methods: We performed a case-control study in which 48 patients with lumbar spine stenosis and 54 age- and sex-matched healthy subjects with back pain were eligible for participation. We used INFINITT picture archiving and communication systems (PACS) of the Chamran Hospital for selecting the patients for the study group. The sagittal balance, pelvic incidence, lumbar lordosis, and sacral slope were measured in all the patients and controls using thoracolumbosacral radiographies in the standing position., Results: There was no significant difference between the 2 groups regarding the baseline characteristics. The prevalence of sagittal imbalance was significantly higher in the patients with lumbar spine stenosis in comparison with the controls (31.2% vs. 14.8%; P<0.001). The sacral slope was significantly lower in patients with lumbar canal stenosis than the healthy controls (31.39°±11.2 vs. 43.7°±8.4; P<0.001). The lumbar lordosis was significantly lower in patients with lumbar canal stenosis than the controls (31.27°±12.4 vs. 45.8°±10.7; P < 0.001). The pelvic incidence was not significantly different between the 2 groups (50.16°±11.9 vs. 52°±9.6; P=0.342)., Conclusion: The degenerative lumbar canal stenosis is associated with increased sagittal imbalance and decreased lumbar lordosis and sacral slope in a sample of the Iranian adult population., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: Gingival recession can lead to root exposure and discomfort for patients. There are various techniques for root coverage. The aim of this study was to compare the use of gingival unit graft (palatal graft including the marginal gingiva and papillae) with free gingival graft for treatment of localized gingival recession., Materials and Methods: In this randomized controlled clinical trial, 18 bilateral localized recessions of Miller class I and II were treated in nine systemically healthy patients. Recessions were randomly treated with gingival unit graft in one side and conventional free gingival graft in the other side. Clinical parameters including clinical attachment level, keratinized tissue width, probing depth and vertical recession depth (VRD) were recorded at baseline and at one, three and six months after surgery. The healing index and patient satisfaction were also evaluated. One-way and two-way repeated measures ANOVA and paired t-test were used for statistical analyses., Results: Both techniques caused significant improvement in clinical parameters. Gingival unit graft produced higher satisfaction esthetically (P=0.050, 0.024 and 0.024, respectively at the three time points), higher healing index (P<0.001), higher root coverage percentage at one month after surgery (34.04%, P=0.011) and greater reduction of recession width three months after surgery (P=0.007) but the reduction in VRD at this side was not significantly greater., Conclusions: Gingival unit graft might be an acceptable modality in Miller Class I/II recession defects. This technique may have advantages over free gingival graft such as significantly superior clinical and esthetic results.

Aim: To evaluate adhesion, proliferation and differentiation of human dental pulp stem cells (hDPSCs) on four commercially available scaffold biomaterials., Methods: hDPSCs were isolated from human dental pulp tissues of extracted wisdom teeth and established in stem cell growth medium. hDPSCs at passage 3-5 were seeded on four commercially available scaffold biomaterials, SureOss (Allograft), Cerabone (Xenograft), PLLA (Synthetic), and OSTEON II Collagen (Composite), for 7 and 14 d in osteogenic medium. Cell adhesion and morphology to the scaffolds were evaluated by scanning electron microscopy (SEM). Cell proliferation and differentiation into osteogenic lineage were evaluated using DNA counting and alkaline phosphatase (ALP) activity assay, respectively., Results: All scaffold biomaterials except SureOss (Allograft) supported hDPSC adhesion, proliferation and differentiation. hDPSCs seeded on PLLA (Synthetic) scaffold showed the highest cell proliferation and attachment as indicated with both SEM and DNA counting assay. Evaluating the osteogenic differentiation capability of hDPSCs on different scaffold biomaterials with ALP activity assay showed high level of ALP activity on cells cultured on PLLA (Synthetic) and OSTEON II Collagen (Composite) scaffolds. SEM micrographs also showed that in the presence of Cerabone (Xenograft) and OSTEON II Collagen (Composite) scaffolds, the hDPSCs demonstrated the fibroblastic phenotype with several cytoplasmic extension, while the cells on PLLA scaffold showed the osteoblastic-like morphology, round-like shape., Conclusion: PLLA scaffold supports adhesion, proliferation and osteogenic differentiation of hDPSCs. Hence, it may be useful in combination with hDPSCs for cell-based reconstructive therapy.

To achieve greater transit-time reduction and improvement in reliability of transport services, there is an increasing need to assist transport planners in understanding the value of punctuality; i.e. the potential improvements, not only to service quality and the consumer but also to the actual profitability of the service. In order for this to be achieved, it is important to understand the network-specific aspects that affect both the ability to decrease transit-time, and the associated cost-benefit of doing so. In this paper, we outline a framework for evaluating the effectiveness of proposed changes to average transit-time, so as to determine the optimal choice of average arrival time subject to desired punctuality levels whilst simultaneously minimizing operational costs. We model the service transit-time variability using a truncated probability density function, and simultaneously compare the trade-off between potential gains and increased service costs, for several commonly employed cost-benefit functions of general form. We formulate this problem as a constrained optimization problem to determine the optimal choice of average transit time, so as to increase the level of service punctuality, whilst simultaneously ensuring a minimum level of cost-benefit to the service operator.

Among the many related issues of diabetes management, its complications constitute the main part of the heavy burden of this disease. The aim of this paper is to develop a risk advisor model to predict the chances of diabetes complications according to the changes in risk factors. As the starting point, an inclusive list of (k) diabetes complications and (n) their correlated predisposing factors are derived from the existing endocrinology text books. A type of data meta-analysis has been done to extract and combine the numeric value of the relationships between these two. The whole n (risk factors) - k (complications) model was broken down into k different (n-1) relationships and these (n-1) dependencies were broken into n (1-1) models. Applying regression analysis (seven patterns) and artificial neural networks (ANN), we created models to show the (1-1) correspondence between factors and complications. Then all 1-1 models related to an individual complication were integrated using the naïve Bayes theorem. Finally, a Bayesian belief network was developed to show the influence of all risk factors and complications on each other. We assessed the predictive power of the 1-1 models by R2, F-ratio and adjusted R2 equations; sensitivity, specificity and positive predictive value were calculated to evaluate the final model using real patient data. The results suggest that the best fitted regression models outperform the predictive ability of an ANN model, as well as six other regression patterns for all 1-1 models.

Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a very rare congenital heart anomaly. Most of the cases are asymptomatic during infancy and childhood. We report ARCAPA associated with aberrant right subclavian artery in a 2-month male infant presenting with heart failure. We used computed tomography angiography for confirming the diagnosis and also for post-operative follow-up.

Setting: Waterpipe smoking is an emerging topic in tobacco research that may have unrecognised health hazards., Objective: To determine whether waterpipes are a source of bacterial contamination., Methods: A total of 15 restaurants and waterpipe cafés were randomly selected from the list of locations serving waterpipe tobacco in Kerman city, Iran. Different parts of the waterpipe devices were sampled, including the disposable mouthpiece, the mouthpiece of the hose and the water in the bowl of the waterpipe. The samples were smeared onto bacterial culture media, including eosin methylene blue, blood agar and MacConkey agar growth media, and incubated at 37°C. After 24-48 h, they were examined for colony growth., Results: Of 285 samples from different parts of the waterpipes, 236 (82.8%) showed positive cultures; the rate of contamination ranged from 69% in the fixed mouthpiece to 96% in bowl water. Coagulase-negative staphylococci (32.9%), Streptococcus spp (26.9%), Neisseria spp (13.7%) and Escherichia coli (9.4%) were the most frequent contaminants., Conclusion: Waterpipes are frequently contaminated with microorganisms. This study revealed potential microbial hazards in waterpipes that may contribute to respiratory tract colonisation.

Generating a reliable computer-simulated synthetic population is necessary for knowledge processing and decision-making analysis in agent-based systems in order to measure, interpret and describe each target area and the human activity patterns within it. In this paper, both synthetic reconstruction (SR) and combinatorial optimisation (CO) techniques are discussed for generating a reliable synthetic population for a certain geographic region (in Australia) using aggregated- and disaggregated-level information available for such an area. A CO algorithm using the quadratic function of population estimators is presented in this paper in order to generate a synthetic population while considering a two-fold nested structure for the individuals and households within the target areas. The baseline population in this study is generated from the confidentialised unit record files (CURFs) and 2006 Australian census tables. The dynamics of the created population is then projected over five years using a dynamic micro-simulation model for individual- and household-level demographic transitions. This projection is then compared with the 2011 Australian census. A prediction interval is provided for the population estimates obtained by the bootstrapping method, by which the variability structure of a predictor can be replicated in a bootstrap distribution.

One important use of layered semiconductors such as molybdenum disulfide (MoS2) could be in making novel heterojunction devices leading to functionalities unachievable using conventional semiconductors. Here we demonstrate a metal-semiconductor-metal heterojunction photodetector, made of MoS2 and amorphous silicon (a-Si), with rise and fall times of about 0.3 ms. The transient response does not show persistent (residual) photoconductivity, unlike conventional a-Si devices where it may last 3-5 ms, thus making this heterojunction roughly 10X faster. A photoresponsivity of 210 mA/W is measured at green light, the wavelength used in commercial imaging systems, which is 2-4X larger than that of a-Si and best reported MoS2 devices. The device could find applications in large area electronics, such as biomedical imaging, where a fast response is critical.

The dental follicle (DF) plays an essential role in tooth eruption via regulation of bone resorption and bone formation. Bone morphogenetic protein-6 (BMP6) expression in the DF is coincident with bone growth in the tooth crypt. DF stem cells (DFSCs) have been shown to possess strong osteogenic capability. This study aims to determine the expression of BMP6 in DFSCs and to elucidate the role of BMP6 in the osteogenesis of DFSCs. DFSCs and their non-stem cell counterpart, DF cells (DFCs), were obtained from the DFs of rat pups. We showed that expression of BMP6 was significantly higher in the DFSCs than in the DFCs. DFSCs lost osteogenic capability during in vitro expansion, and DFSCs in late passages had reduced BMP6 expression as compared to early passages of DFSCs when they were subjected to osteogenic induction. Addition of exogenous human recombinant BMP6 (hrBMP6) to the osteogenic medium dramatically enhanced the osteogenesis of the late-passage DFSCs. Knockdown of BMP6 by short interfering RNA in the DFSCs in early passages resulted in a decrease in osteogenesis, which could be restored by addition of hrBMP6. We concluded that DFSCs need to express high levels of BMP6 to maintain their osteogenesis capability. Increased BMP6 expression seen in vivo in the DF may reflect the activation of DFSCs for osteogenic differentiation for bone growth during tooth eruption., (© 2014 S. Karger AG, Basel.)

This study was carried out to evaluate the genetic effect of quantitative trait loci (QTLs) conferring drought tolerance in wheat. A population of 120 F(2) individuals from the cross between the drought-tolerant S-78-11 and drought-sensitive Tajan cultivars were analyzed for their segregation under drought stress conditions. The relative water content under drought stress conditions exhibited continuous variation, indicating the minor gene effects on the trait. Single-marker analysis (SMA) was carried out to detect the main QTL association with drought tolerance. The SMA results revealed that the simple sequence repeat markers GWM182 and GWM292 on chromosome 5D and GWM410 on chromosome 5A exhibited significant association with drought tolerance, accounting for 30, 22, and 21% of the total variation, respectively. The 3 genetic loci, especially GWM182, can be used in marker-assisted selection methods in drought tolerance breeding in wheat.

Background: Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients., Objective: The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concurrent donor bone marrow cell infusion (DBMI)., Methods: Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre- and post-transplant (days 14, 30, and 90) sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA specific panel for antibody specification., Results: Of 40 patients, 9 (22.5%) experienced acute rejection episodes (ARE) (6/20 cases in non-infused versus 3/20 in DBMI patients). The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones (88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively). A total of 10% (4/40) of patients developed donor specific anti-HLA antibodies (DSA) and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls., Conclusion: Our findings reveal an association between pre- and post-transplant anti-HLA antibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts.

Objective: We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients., Patients and Methods: We analyzed the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20 controls)., Results: Patients with acute rejection episodes (ARE)-3/20 DBMI and 6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01). Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P < .0001, respectively)., Conclusions: Higher levels of sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

Organ transplant survival has been improved with CsA, but the PK of CsA may be affected by many drugs and foods. This study was performed to investigate the impact of orange juice on PK of CsA in children who had received a renal transplant. This cross-over placebo-controlled study was performed on 10 pediatric kidney-transplanted patients. All children received orange juice (Thomson novel) or water. After morning dose of CsA, patients were given 250 mL orange juice or water and investigation of the PK was performed in 12 h. Co-administration of orange juice with CsA compared with water did not significantly increase the area under the curve from 0-12 h (AUC(0-12)) of CsA (orange juice 2833 +/- 553, water 3053 +/- 1532, p > 0.05). Also, there were not significant effects on peak concentration (C(max)) or time to C(max) (t(max)). Orange juice can be used with CsA and there was no interaction between the juice and CsA in pediatric renal transplants.

For folate-receptor-targeted anticancer therapy, docetaxel (DTX) nanoparticles (NPs) were produced employing polylactide-co-glycolide-polyethylene glycol-folate (PLGA-PEG-FOL) conjugate. The FOL-conjugated di-block copolymer was synthesized by coupling the PLGA-PEG-NH(2) di-block copolymer with an activated folic acid. It was expected that FOL moieties were exposed on the micellar surface. The conjugates assisted in the formation of DTX NPs with an average size of 200 nm in diameter through an emulsification/solvent diffusion method. The FOL-targeted NPs showed a greater extent of intracellular uptake in FOL-receptor-positive cancer cells (SKOV3) in comparison with the non-targeted NPs, indicating that the FOL-receptor-mediated endocytosis mechanism could have a role in the cellular uptake of NPs. These results suggested that FOL-targeted DTX NPs could be a potentially useful delivery system for FOL-receptor-positive cancer cells.

The aim of our study was to investigate the effect of tangerine juice on the pharmacokinetics of cyclosporine A (CsA), in children who had received a renal transplant. This placebo-controlled study was done on ten kidney transplant recipients with stable cyclosporine trough levels who received either tangerine (Unshio Satsuma) juice or water. Patients were given their morning doses of CsA and then 250 ml water or the juice, and 12 h, investigations of the pharmacokinetics (PK) were performed. The main outcome measures were peak concentration and time to peak and area under the concentration-time curve. Administration of CsA with tangerine juice compared with water did not increase significantly the area under the whole-blood concentration versus time curve from 0-12 h (AUC(0-12)) of CsA, (tangerine juice 2,797 +/- 1,361 (P = 0.5); water 3,053 +/- 1,532). Co-administration of tangerine juice with CsA compared with water had no significant effects on the AUC(0-12), peak concentration (C(max)) or time to C(max) (t(max)) of the CsA in pediatric renal transplantation.

We report the DNA sequence of a 34,038 bp segment of Saccharomyces cerevisiae chromosome XV. Subsequent analysis revealed 20 open reading frames (ORFs) longer than 300 bp and two tRNA genes. Five ORFs correspond to genes previously identified in S. cerevisiae, including RPLA2, PRE6, MSE1, IFM1 and SCM2 (TAT2, TAP2, LTG3). Two putative proteins share considerable homology with other proteins in the current data libraries. ORF O2145 shows 41.2% identity with the glycophospholipid-anchored surface glycoprotein Gas1p of S. cerevisiae and ORF O2197 has 53.2% identity to chromosome segregation protein Dis3p of Schizosaccharomyces pombe.

The SFP2 gene of Saccharomyces cerevisiae has been characterized. The deduced amino acid sequence contained twelve highly hydrophobic domains and showed 50, 47, 44 and 48% homologies to Neurospora crassa sulfate permease II (CYS14), soybean GMAK170 nodulin, human colon mucosa protein (DRA) and a putative open reading frame (ORF) downstream of Escherichia coli prs (phosphoribosyl pyrophosphatate synthetase) gene, respectively, in the aligned regions. Cells lacking SFP2 were viable and displayed no obvious decrease in their growth rate. Southern blot analysis revealed that SFP2 exists as a single copy in haploid genome. Northern blot analysis showed that SFP2 produced a 2.8-kb transcript which was highly expressed under sulfur derepressing condition. SFP2 mRNA was found to turn over with a half-life of approximately 15 min, which may contribute to the regulation of sulfate permease function, and reached its maximal level in about 22 h after depression.