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Background: Environmental risk factors are significant contributors to cancer mortality, which are neglected., Purpose: This study aimed to estimate the population attributable fraction of cancer mortality due to the environmental risk factors., Methods: Golestan cohort study is a population-base cohort on 50045 participants between 40-75 with about 18 years of follow up. We detected 2,196 cancer mortality and applied a multiple Cox model to compute the hazard ratio of environmental risk factor on all cancer and cancer-specific mortality. The population attributable fraction was calculated, accordingly., Results: Biomass fuels for cooking, as an indoor air pollution, increased the risk of colorectal, esophageal, gastric cancer, and all-cancer mortality by 84%, 66%, 37%, and 17% respectively. Using gas for cooking, particularly in rural areas, could save 6% [Population Attributable Fraction: 6.36(95%CI: 1.82, 10.70)] of esophageal cancer, 3% [Population Attributable Fraction: 3.43 (0, 7.33)] of gastric cancer, and 6% [Population Attributable Fraction: 6.25 (1.76, 13.63)] of colorectal cancer mortality. Using a healthy tap water source could save 5% [Population Attributable Fraction:5.50(0, 10.93)] of esophageal cancer mortality, particularly in rural areas. There was no significant association between indoor air pollution for heating purposes and animal contact with cancer mortality., Conclusion: Considering the results of this study, eliminating solid fuel for most daily usage, among the population with specific cancer types, is required to successfully reduce cancer related mortality. Adopting appropriate strategies and interventions by policymakers such as educating the population, allocating resources for improving the healthy environment of the community, and cancer screening policies among susceptible populations could reduce cancer related mortalities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rezaei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A new Zn II coordination polymer (CP) based on 2,3-pyrazine dicarboxylic acid (H 2 pzdc) and 4,4'-bipyridine (bpy) (ZCP) was synthesized using a facile slow evaporation method. Single-crystal X-ray diffraction revealed that ZCP is a two-dimensional porous CP, [Zn 2 (pzdc) 2 (bpy)(H 2 O) 2 ] n , with van der Waals forces as the dominant interaction within its layers forming a 6 3 network. Employing energetic ultrasound irradiation, nanoscale ZCP (nZCP) was successfully synthesized and Eu 3+ ions were incorporated within its host lattice (Eu@nZCP). The resulting platform exhibits superior fluorescence characteristics and demonstrates notable optical durability. Therefore, it was used as a dual detection fluorescent sensing platform for the detection of mercury and L-cysteine (L-Cys) in aqueous media through a turn-off/on strategy. In the turn-off process, the fluorescence emission of Eu@nZCP progressively quenches by the addition of Hg II via a photo-induced electron transfer (PET) mechanism. The fluorescence of Eu@nZCP is quenched to establish a low fluorescence background through the incorporation of Hg II . This devised turn-on fluorescent system is suitable for the recognition of L-Cys (based on the strong affinity of L-Cys to the Hg II ion) through a quencher detachment mechanism. This method attained a relatively wide linear range, spanning from 0.001 to 25 µM, with the low detection limit of 5 nM for the sensing of Hg II . Also, the corresponding limit of detection (LOD) for L-Cys is 8 nM in a relatively wide linear range, spanning from 0.001 to 40 µM.

Background: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal opportunistic viral demyelinating infectious disease of the central nervous system (CNS). There are various clinical presenting symptoms for the disease., Case Presentation: This paper presents a clinical case of PML in a patient with B-Chronic lymphocytic leukemia (B-CLL), previously treated with Chlorambucil, later complicated later with COVID-19 and mucormycosis., Conclusion: PML can develop in the setting of cellular immune dysfunction. Late diagnosis of this disease based on nonspecific symptoms is common, therefore when we face a neurological complication in a CLL or immunocompromised patient, we should consider PML infection. A remarkable feature of this case is the possible triggering effect of COVID-19 vaccination for emergence of PML as the disease can be asymptomatic or sub-clinical before diagnosis., (© 2024. The Author(s).)

Objective: The aim of this work is to demonstrate the performance of the ECG noise extraction tool (ECGNExT) which provides estimates of ECG noise that are not significantly different from the inherent noise in an ECG generated by motion artifacts and other sources. In addition, this paper elaborates on use of ECGNExT in an algorithm evaluation context comparing two QRS detection algorithms., Methods: 140 simultaneous pairs of clean ECGs and ECGs corrupted with motion-induced noise from 29 participants under five different and separate motion conditions were collected and analyzed. Estimates of the noise component of the ECGs recorded with noise were obtained using ECGNExT and were then added to the clean ECGs yielding estimated ECGs with noise. Root mean squared error (RMSE) between the recorded and estimated ECGs with noise was calculated for temporal comparison, and band powers of the signals were calculated for spectral comparison., Results: A t-test revealed that the mean RMSE < 150-microvolts with p-value < 0.001 and, and equivalence tests showed that the band powers of the two ECGs were statistically equivalent with ., Conclusion: ECGNExT can reliably estimate the underlying ECG noise while preserving temporal and spectral features., Significance: We previously proposed ECGNExT as a component of ECG analysis algorithm testing during noise conditions and reported its performance based on simulated ECG data. This work provides additional support of the performance and functionality of the ECGNExT algorithm from a study with pairs of simultaneously recorded ECGs with and without noise from human subjects.

Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Influenza is one of the most important agents of pandemic outbreak causing substantial morbidity and mortality. Vaccination strategies of influenza must be adapted annually due to constant antigenic changes in various strains. Therefore, the present study was conducted to evaluate protective immunity of the conserved influenza proteins., Methods: For this purpose, three tandem repeats of M2e (3M2e) and NP were separately expressed in E. coli and were purified using column chromatography. Female Balb/c mice were injected intradermally with a combination of the purified 3M2e and NP alone or formulated with Alum (AlOH 3 ) adjuvant in three doses. The mice were challenged by intranasal administration of H1N1 (A/PR/8/34) 2 weeks after the last vaccination., Results: The results demonstrated that recombinant NP and M2e proteins are immunogenic and could efficiently elicit immune responses in mice compared to non-immunized mice. The combination of 3M2e and NP supplemented with Alum stimulated both NP and M2e-specific antibodies, which were higher than those stimulated by each single antigen plus Alum. In addition, the secretion of IFN-γ and IL-4 as well as the induction of lymphocyte proliferation in mice received the mixture of these proteins with Alum was considerably higher than other groups. Moreover, the highest survival rate (86%) with the least body weight change was observed in the mice immunized with 3M2e and NP supplemented with Alum followed by the mice received NP supplemented with Alum (71%)., Conclusion: Accordingly, this regimen can be considered as an attractive candidate for global vaccination against influenza., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Lymphangioma is a benign malformation of lymphatic vessels usually found in the head and neck areas or axilla. They may involve visceral organs with a lower percentage. Splenic lymphangioma is a rare tumor. This disease is often seen in children but may be diagnosed incidentally in adults. Most patients are asymptomatic, but in large and multifocal lesions, the patient may have some nonspecific symptoms such as abdominal pain, abdominal distention, nausea, vomiting, and loss of appetite. Physical examination may show no specific findings or detect palpable masses. The preoperative diagnosis of splenic lymphangioma is challenging. Histopathological evaluation and sometimes immunohistochemistry tests can result in a definitive diagnosis. In this study, we present an 18-year-old man, with Burkitt's lymphoma who underwent laparotomy and total splenectomy as a result of cystic lesions discovered accidentally during imaging with the final diagnosis of splenic lymphangioma after histopathological evaluation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Neda Soleimani et al.)

Background: Despite the many signs of progress in pharmacotherapies, metabolic syndrome (MetS) is one of the main public-health burdens worldwide. Our study aimed to compare the effect of breastfeeding (BF) in women with and without gestational diabetes mellitus (GDM) on MetS incidence., Methods: Of females who participated in the Tehran Lipid and glucose study, women who met our inclusion criteria were selected. The Cox proportional hazards regression model, with adjustment of potential confounders, was done to evaluate the relationship between duration of BF and incident of MetS in women with a GDM history compared to non-GDM., Results: Out of 1176 women, there were 1001 non-GDM and 175 GDM. The median follow-up was 16.3 (11.9, 19.3) years. Results of the adjusted model illustrated that the total BF duration was negatively associated with MetS incidence risk (hazard ratio (HR) 0.98, 95% CI 0.98-0.99) in total participants indicating that per one-month increase of BF duration, the hazard of MetS reduced by 2%. The HR of MetS in Comparison between GDM and non-GDM women demonstrated significantly more reduced MetS incidence with a longer duration of exclusive BF (HR 0.93, 95% CI 0.88-0.98)., Conclusions: Our findings illustrated the protective effect of BF, especially exclusive BF, on MetS incidence risk. BF is more effective in reducing the risk of MetS among women with a history of GDM than among women without such a history., (© 2023. The Author(s).)

Recent advances in the artificial pancreas system provide an emerging treatment option for type 1 diabetes. The performance of the blood glucose regulation directly relies on the accuracy of the glucose-insulin modeling. Sorenson model involves the behavior of different organs and offers precise representation. However, the high complexity of such a model makes the controller design procedure a hard task. Therefore, the high-order nonlinear Sorensen model as a popular high-fidelity physiological model is opted in this paper to analyze the glucose-insulin interactions in great detail, and a new robust nonlinear approach to regulate the blood glucose concentration (BGC) in Type-I diabetic patients is proposed. Inspiring the backstepping technique, for designing an acceptable controller, the model is divided into three main subsystems such that in each subsystem, the virtual control input laws are obtained using both Lyapunov stability and input-to-state theorems. Since the measurement of the parameters in the glucose-insulin system is not accurate, parametric uncertainties are defined in the investigated model. Furthermore, owing to the fact that the only measurable state variable is blood glucose, the estimation of inaccessible state variables is an important issue that is properly considered by the unscented Kalman filter (UKF) estimator. The suggested approach is compared to H ∞ , robust H ∞ , and linear parameter-varying control approaches. The comparison results on 500 simulated patients imply a remarkable superiority of the proposed controller approach to the compared methods in terms of the BGC tracking and the algorithm robustness in the presence of food intake disturbance patterns., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. All rights reserved.)

In Acidithiobacillus ferrooxidans, proteins such as CcO are present in the electron transport pathway. They cause ferrous iron oxidation to ferric leading to the electron release. CcO has two copper atoms (CuA, CuB). CuA plays an important role in electron transfer. According to previous studies, the conversion of histidine to methionine in a similar protein increased the redox potential and was directly related to the number of electrons received. Also, the binding of methionine 233 to CuA and CuB in the wild protein structure is the reason for the selection of the H230 M mutation in the CuA site. Then, wild-type and H230 M mutant were simulated in the presence of a bilayer membrane POPC using the gromacs version 5.1.4. The changes performed in the H230 M mutant were evaluated by MD simulations analyzes. CcO and CoxA proteins are the last two proteins in the chain and were docked by the PatchDock server. By H230 M mutation, the connection between CuA and M230 weakens. The M230 moves further away from CuA, resulting become more flexible. Therefore, the Methionine gets closer to E149 of the CoxA leading to the higher stability of the CcO/CoxA complex. The results of RMSF analysis at the mutation point showed a significant increase. This indicates more flexibility in the active site. And leads to an increase in E 0 in the mutation point, an increase in the rate of electron reception, and an improved bioleaching process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Although predicting the effects of variants near intron-exon boundaries is relatively straightforward, predicting the functional Exon Splicing Enhancers (ESEs) and the possible effects of variants within ESEs remains a challenge. Considering the essential role of CYP2D6/CYP2C19 genes in drug metabolism, we attempted to identify variants that are most likely to disrupt splicing through their effect on these ESEs. ESEs were predicted in these two genes using ESEfinder 3.0, incorporating a series of filters (increased threshold and evolutionary conservation). Finally, reported mutations were evaluated for their potential to disrupt splicing by affecting these ESEs. Initially, 169 and 243 ESEs were predicted for CYP2C19/CYP2D6, respectively. However, applying the filters, the number of predicted ESEs was reduced to 26 and 19 in CYP2C19/CYP2D6, respectively. Comparing prioritized predicted ESEs with known sequence variants in CYP2C19/CYP2D6 genes highlights 18 variations within conserved ESEs for each gene. We found good agreement in cases where such predictions could be compared to experimental evidence. In total, we prioritized a subset of mutational changes in CYP2C19/CYP2D6 genes that may affect the function of these genes and lead to altered drug responses. Clinical studies and functional analysis for investigating detailed functional consequences of the mentioned mutations and their phenotypic outcomes is mostly recommended., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The aim of this study was the enrichment of high-performance microbial communities in biofilters for removal of ammonium and nitrite from aquaculture water. Ammonium oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) were enriched from different environmental water samples. The microbial communities with higher ammonium and nitrite removal activity were selected and adapted to different temperatures [9 °C, 15 °C, room temperature (25 °C), and 30 °C]. The expression of genes involved in nitrification including ammonia monooxygenase (AMO) and nitrite oxidoreductase (NXR) were measured in temperature-adapted AOB and NOB microbiomes. The microbial species present in the selected microbiomes were identified via 16s rRNA sequencing. The microbial communities containing Nitrosomonas oligotropha and Nitrobacter winogradskyi showed the highest ammonium and nitrite removal activity at all temperatures used for adaptation. Furthermore, the microbial communities do not contain any pathogenic bacteria. They also exhibited the highest expression of AMO and NXR genes. Using the enriched microbial communities, we achieved a 288% and 181% improvement in ammonium and nitrite removal over the commonly used communities in biofilters at 9 °C, respectively. These results suggest that the selected microbiomes allowed for a significant improvement of water quality in a recirculating aquaculture system (RAS)., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The genetic disease cystic fibrosis (CF) results when mutations in the gene for the anion channel CFTR reduce CFTR's activity below a critical level. CFTR activity = N·PO·γ (number of channels x open probability x channel conductance). Small molecules are now available that partially restore CFTR function with dramatic improvements in health of CF subjects. Continued evaluation of these and other compounds in development will be aided by accurate assessments of CFTR function. However, measuring CFTR activity in vivo is challenging and estimates vary widely. The most accurate known measure of CFTR activity in vivo is the 'β/M' ratio of sweat rates, which is produced by stimulation with a β-adrenergic agonist cocktail referenced to the same individual's methacholine-stimulated sweat rate. The most meaningful metric of CFTR activity is to express it as a percent of normal function, so it is critical to establish β/M carefully in a population of healthy control subjects. Here, we analyze β/M from a sample of 50 healthy adults in which sweat rates to cholinergic and β-adrenergic agonists were measured repeatedly (3 times) in multiple, (~50) identified sweat glands from each individual (giving ~20,000 measurements). The results show an approximately 7-fold range, 26-187% of the WT average set to 100%. These provide a benchmark against which other measures of CFTR activity can be compared. Factors contributing to β/M variation in healthy controls are discussed., Competing Interests: The authors have declared that no competing interests exist.

Acidithiobacillus ferrooxidans (Af) is an acidophilic bacterium that grows in rigid surroundings and gets its own energy from the oxidation of Fe 2+ to Fe 3+ . These bacteria are involved in the bioleaching process. Cyc 1 is a periplasmic protein with a crucial role in electron transportation in the respiratory chain. His53 of the Cyc 1 protein, involved in electron transfer to CoxB, was selected for mutation and bioinformatics studies. His53 was substituted by Ile using PyMol software. Molecular dynamics simulations were performed for wild and mutant types of Cyc 1 protein. The conformational changes of mutated protein were studied by analyzing RMSD, RMSF, SASA, Rg, H Bond, and DSSP. The results of the RMSF analysis indicated an increase in the flexibility of the ligand in the mutant. Finally, active site instability leads to an increase in the value of E 0 at the mutation point and improving electron transfer. On the other, His53 in Cyc 1 is interconnected to Glu126 in CoxB through the water molecule (W76) and hydrogen bonding. In the H53I mutation, there was a decrease in the distance between H2O 2030, 2033, and isoleucine 53, and subsequently, the distance to the water molecule 76 between the two proteins was reduced and strengthens the hydrogen bond between Cyc 1 and CoxB, finally improves electron transfer and the bioleaching process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Human T cell leukemia virus-1 (HTLV-1) infection may lead to one or both diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukemia lymphoma (ATLL). The complete interactions of the virus with host cells in both diseases is yet to be determined. This study aims to construct an interaction network for distinct signaling pathways in these diseases based on finding differentially expressed genes (DEGs) between HAM/TSP and ATLL., Results: We identified 57 hub genes with higher criteria scores in the primary protein-protein interaction network (PPIN). The ontology-based enrichment analysis revealed following important terms: positive regulation of transcription from RNA polymerase II promoter, positive regulation of transcription from RNA polymerase II promoter involved in meiotic cell cycle and positive regulation of transcription from RNA polymerase II promoter by histone modification. The upregulated genes TNF, PIK3R1, HGF, NFKBIA, CTNNB1, ESR1, SMAD2, PPARG and downregulated genes VEGFA, TLR2, STAT3, TLR4, TP53, CHUK, SERPINE1, CREB1 and BRCA1 were commonly observed in all the three enriched terms in HAM/TSP vs. ATLL. The constructed interaction network was then visualized inside a mirrored map of signaling pathways for ATLL and HAM/TSP, so that the functions of hub genes were specified in both diseases.

Introduction: Burning mouth syndrome (BMS) is one of the challenging clinical problems not only in its diagnosis and treatment but also its concurring mental impact. This study is aimed at determining the association between psychological factors, including emotional stress, depression, anxiety, and sleep pattern among BMS patients., Methods: In this cross-sectional study, 19 patients with idiopathic BMS were enrolled along with a control group equivalent in age and sex, but without BMS. Questionnaires used were the Visual Analog Scale (VAS), the Pittsburgh Sleep Quality Index (PSQI), and the Depression, Anxiety, and Stress Scale (DASS-21). Demographic information was also recorded and analyzed., Results: There was a significant correlation among the two groups of BMS and non-BMS patients regarding stress, depression, and sleep disorder. The average severity of the burning score was 8.31 among the patients. Furthermore, a significant correlation was observed among mental disorders and educational level and sex, but not with age. There was also no significant correlation among the severity of the burning score with sex, education, and mental disorder., Conclusion: BMS is significantly associated with psychological symptoms. This condition requires proper treatment and support because it can represent psychological or mental issues and/or have a significant effect on daily life., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Fahimeh Rezazadeh et al.)

Fontan operation as the current standard of care for the palliation of single ventricle defects results in significant late complications. Using a mechanical circulatory device for the right circulation to serve the function of the missing subpulmonary ventricle could potentially stabilize the failing Fontan circulation. This study aims to elucidate the hydraulic operating regions that should be targeted for designing cavopulmonary blood pumps. By integrating numerical analysis and available clinical information, the interaction of the cavopulmonary support via the IVC and full assist configurations with a wide range of simulated adult failing scenarios was investigated; with IVC and full assist corresponding to the inferior venous return or the entire venous return, respectively, being routed through the device. We identified the desired hydraulic operating regions for a cavopulmonary assist device by clustering all head pressures and corresponding pump flows that result in hemodynamic improvement for each simulated failing Fontan physiology. Results show that IVC support can produce beneficial hemodynamics in only a small fraction of failing Fontan scenarios. Cavopulmonary assist device could increase cardiac index by 35% and decrease the inferior vena cava pressure by 45% depending on the patient's pre-support hemodynamic state and surgical configuration of the cavopulmonary assist device (IVC or full support). The desired flow-pressure operating regions we identified can serve as the performance criteria for designing cavopulmonary assist devices as well as evaluating off-label use of commercially available left-side blood pumps for failing Fontan cavopulmonary support.

Efficient antibacterial and antifungal properties of silver nanoparticles (AgNPs) sparked its commercial application in several industrial and household products. Drastic increase of AgNPs production raised concerns over aquatic organisms' exposure. The toxic dose, mechanism of toxicity, physiological damages, gene expression alteration, hematological and blood parameter distortion by AgNP needs to be investigated to explore inevitable risk in aquatic animals. In this study, rainbow trout (Oncorhynchus mykiss) (122.4 ± 1.4 g, 23.8 ± 0.7 cm) were exposed to colloidal AgNPs (28.3 ± 12.6 um) to determine the lethal concentration (LC50)(8.9 mg/l). Sub-lethal concentrations (10 %LC50, 25 %LC50, plus LC50 value) impact on hematologic, histological and molecular responses were evaluated. Results showed sever damage to blood cells morphology, and hematologic parameters change including RBC, WBC, Hct and Hb in all AgNP-treated groups. Histological damage in gill and liver of exposed fish were observed. Significant up-regulating of HSP70 and P53 genes were detected in response to AgNPs, whereas, it was found that in comparison to HSP70 gene, P53 induction occurred in lower AgNPs concentrations and lower exposure time. These results indicate adversely effects of AgNPs exposure to aquatic environments., Competing Interests: Declaration of Competing Interest The authors whose names are listed below declare No Conflict of Interest and also certify that they have NO affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: Vaccination is the most effective preventive strategy for influenza disease. As the virus undergoes high antigenic drift, it requires a constant reformulation to obtain high protection., Results: Immunogenicity of a purified chimeric protein containing conserved regions of influenza A/H1N1 viruses including the Hemagglutinin stalk domain, Nucleoprotein, and Matrix protein produced in a prokaryotic system was assessed in vitro and in vivo, alone or in combination with adjuvants by evaluating antibody responses, cytokine production, lymphocyte proliferative assay, and mortality rate after challenge. The animals that received the chimeric protein had specific antibody responses, elicited memory CD4 cells, cytokines of Th1 and Th2 cells and showed 75% protection against influenza virus lethal challenge. The animals injected with the chimeric protein supplemented with Alum showed improved immune responses, but they had 67% protection. In other words, although Alum adjuvant enriched the chimera specific immune responses potently, it could not enhance its protectivity., Conclusion: Regarding the immunogenicity and protectivity of the chimeric protein construct against influenza, findings of the study suggested that the chimeric protein could be considered as a promising influenza vaccine candidate.

Fontan patients often develop circulatory failure and are in desperate need of a therapeutic solution. A blood pump surgically placed in the cavopulmonary pathway can substitute the function of the absent sub-pulmonary ventricle by generating a mild pressure boost. However, there is currently no commercially available device designed for the cavopulmonary application; and the risks and benefits of implanting a ventricular assist device (VAD), originally designed for the left ventricular application, on the right circulation of failing Fontan patients is not yet clear. Moreover, further research is needed to compare the hemodynamics between the two clinically-considered surgical configurations for cavopulmonary assist, with Full and inferior vena cava (IVC) support corresponding to the entire venous return or only the inferior venous return, respectively, being routed through the VAD. In this study, we used a numerical model of the failing Fontan physiology to evaluate the Fontan hemodynamic response to a left VAD during the IVC and Full support scenarios. We observed that during Full support, the VAD improved the cardiac output while maintaining blood pressures within safe ranges, and lowered the IVC pressure to <15 mmHg; however, we found a potential risk of lung damage at higher pump speeds due to the excessive pulmonary pressure elevation. IVC support, on the other hand, did not benefit the hemodynamics in the patient cases simulated, resulting in the superior vena cava pressure increasing to an unsafe level of >20 mmHg. The findings in this study may be helpful to surgeons for recognizing the risks of a cavopulmonary VAD and developing coherent clinical strategies for the implementation of cavopulmonary support.

Effects of sub-lethal concentrations (0 (control), 0.009, 0.014, and 0.023 ppm) of the organophosphate insecticide "malathion" to rainbow trout (Oncorhynchus mykiss) after the determination of LC 50 -96 h value (0.093 ppm) were evaluated. Changes in biomarkers of neurotoxicity (acetylcholinesterase (AChE) activity), genotoxicity (DNA damage), and hematological parameters (red (RBC) and white (WBC) blood cell count, hemoglobin (Hb), hematocrit (Hct), mean cell hemoglobin (MCH), mean cell volume (MCV), and mean cell hemoglobin concentration (MCHC)) were assessed for a 15-day exposure. A significant time- and dose-dependent reduction in AChE activities of gill, muscle, brain, and liver tissues was found. However, the AChE activity was less affected by malathion concentration than by exposure time. DNA damage of erythrocytes at different malathion concentrations increased by increasing the experimental time up to the fourth day. A decrease in the count of WBC, RBC, and Hct and an increase in the number of MCH and MCV were observed by increasing malathion exposure dose and time (p < 0.05). An increase in the malathion concentration and exposure time significantly resulted in a decrease in Hb and an increase in MCHC. A significant improvement in AChE activity; DNA damage; and RBC, Hb, Hct, MCV, and MCH indices was detected during a 30-day recovery period, but the WBC count changed insignificantly. The recovery pattern based on 100% water exchange with clean water could be a successful strategy to improve the biomarker responses of rainbow trout habituating in contaminated aquatic environments., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus., Methods: The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed., Results: Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P < 0.0001). At the highest non-toxic concentrations, the PEGylated and unPEGylated ZnO-NPs led to inhibition rates of 94.6 and 52.2%, respectively, which were calculated based on the viral loads. There was a substantial decrease in fluorescence emission intensity in viral-infected cell treated with PEGylated ZnO-NPs compared to the positive control., Conclusions: Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.

Background: Multiple sclerosis (MS) is a neurological disease for which to date there is no cure and the existing disease-modifying drugs just slow down the disease progression., Purpose: In this clinical trial we evaluated the efficacy of Achillea millefolium (A. millefolium) aqueous extract in MS patients., Methods: A triple-blind randomized placebo-controlled parallel group trial was conducted on 75 MS patients. The patients were randomized into three groups including placebo and two groups receiving A. millefolium with two different doses, i.e. 250  mg/day and 500  mg/day, for 1 year. The primary outcome was the annualized relapse rate. Also, number and volume of lesions were obtained from magnetic resonance imaging (MRI) scans. Furthermore, we performed a comprehensive neurological and cognitive tests as follows: changes in the expanded disability status scale (EDSS), the multiple sclerosis functional composite (MSFC), fatigue severity scale (FSS), Ashworth spasticity assessment, Beck depression test, State-trait anxiety inventory (STAI), mini-mental status examination (MMSE), Wisconsin card sorting test (WCST), tower of London test (TOL), word-pair learning, paced auditory serial addition task (PASAT) and standard laboratory tests., Results: This study showed one year administration of A. millefolium (both doses) decreased the annual relapse rate in MS patients. The mean volume change of lesions significantly decreased in the 500 mg A. millefolium group. The add-on therapy also increased time to first relapse and the MSFC z-score; it decreased the EDSS score and improved performance in word-pair learning, PASAT, and WCST., Conclusion: We found beneficial effects of A. millefolium aqueous extract as an add-on therapy in MS patients., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: International data on caries epidemiology confirm that dental caries remains a significant disease of childhood in both developing and developed countries. Based on preventive dentistry, topical fluoride may be a useful measure to arrest caries lesions. Fluoride used in various forms have been proven to be effective in dental caries prevention., Aim: This study aims to compare the effect of fluoridated varnish and silver diamine fluoride (SDF) solution on primary teeth enamel resistance to demineralization., Methods: Forty-five caries-free deciduous canine teeth extracted due to orthodontic reasons, devoid of any defects were selected. Teeth were mounted on acrylic blocks as their buccal surface was exposed and baseline surface microhardness (SMH) determination was accomplished. Enamel samples were randomly distributed into three groups with 15 specimens each. One group was used as control (distilled and deionized water) (C); in the other groups, either a fluoridated varnish (V) or an SDF solution was applied to the enamel blocks. The blocks of each group were submitted to pH-cycling solutions and treatment regimen. After pH-cycling process, SMH determination was done again for all samples., Results: According to the present findings, the percentage of decrease in SMH of control group is numerically greater than other groups and also SDF group shows the most resistance against mineral loss. However, based on one-way ANOVA test, this difference is not statistically significant (P = 0.217)., Conclusion: SDF solution and fluoride varnish display similar effectiveness in preventing the demineralization of deciduous anterior teeth, and no significant difference was observed., Competing Interests: There are no conflicts of interest

The in situ evaluation of the genotoxic impact of the Karaj River was performed using the comet and micronucleus (MN) assays in erythrocytes, liver, gill and kidney of indigenous brown trout, Salmo trutta fario from three different stations, including Varangerud, Asara and Purkan. The results showed that DNA damage significantly increased in sampled fish erythrocytes, liver and gill from low levels in the upstream river (Varangerud) via intermediate levels in downstream (Purkan) to high levels in the middle of the river (Asara), correlating with the river increasing pollution gradient. Gill was the most sensitive tissue followed by blood and liver. Kidney did not respond to the genotoxic gradient of the river. MN test (as a complementary assay) of liver cells of fish was a sensitive biomarker of genotoxic exposure. MN test in blood, gill and kidney did not reflect the genotoxic condition of the river., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Bone marrow-derived mesenchymal stem cells (MSCs) have the potential ability to differentiate into bone, muscle, fat, and cartilage lineage cells. Furthermore, MSCs are known to migrate into tumor-associated stroma of cancer. This tumor microenvironment consists of a dynamic network of growth factors, immune cells, fibroblasts, extracellular matrix, and MSCs. MSCs as nonhematopoietic stem cells affect tumor, epithelial cells by alteration proliferative capacity, morphology, and aggregation pattern of tumor cells., Materials and Methods: This research aimed to further elucidate the MSCs effects in the progress of proliferation, cell cycle, and apoptosis in breast cancer by gene expression analysis in human breast cancer cell lines exposed to MSCs conditioned media (CM). Expression pattern of two genes, including survivin (Birc5) as anti-apoptotic gene and serine threonine kinase 15 as proliferative gene, were studied., Results: Anti-apoptotic and proliferative genes were up-regulated in co-cultured breast tumor cells with MSCs-CM that correlate with tumor progression and poor prognosis., Conclusion: Our results and other findings indicate the interaction of breast tumor cells with MSCs through paracrine factors. Also, the applications of MSCs as therapeutic tools are facing controversial concerns., Competing Interests: There are no conflicts of interest.

Ferula gummosa Boiss. is an industrial and pharmaceutical plant that has been highly recognized for its valuable oleo-gum-resin, namely galbanum. Despite the fabulous value of galbanum, very little information on the genetic and biochemical mechanisms of its production existed. In the present study, the oleo-gum-resin and four organs (root, flower, stem, and leaf) of F. gummosa were assessed in terms of metabolic compositions and the expression of genes involved in their biosynthetic pathways. Results showed that the most accumulation of resin and essential oils were occurred in the roots (13.99 mg/g) and flowers (6.01 mg/g), respectively. While the most dominant compound of the resin was β-amyrin from triterpenes, the most abundant compounds of the essential oils were α-pinene and β-pinene from monoterpenes and α-eudesmol and germacrene-D from sesquiterpenes. Transcriptome analysis was performed by RNA sequencing (RNA-seq) for the plant roots and flowers. Differential gene expression analysis showed that 1172 unigenes were differential between two organs that 934 (79.6%) of them were up-regulated in the flowers and 238 (20.4%) unigenes were up-regulated in the roots (FDR ≤0.001). The most important up-regulated unigenes in the roots were involved in the biosynthesis of the major components of galbanum, including myrcene, germacrene-D, α-terpineol, and β-amyrin. The results obtained by RNA-Seq were confirmed by qPCR. These analyses showed that different organs of F. gummosa are involved in the production of oleo-gum-resin, but the roots are more active than other organs in terms of the biosynthesis of triterpenes and some mono- and sesquiterpenes. This study provides rich molecular and biochemical resources for further studies on molecular genetics and functional genomics of oleo-gum-resin production in F. gummosa.

In recent years, analyzing genome-wide expression profiles to find genetic markers has received much attention as a challenging field of research aiming at unveiling biological mechanisms behind complex disorders. The identification of reliable and reproducible markers has lately been achieved by integrating genome-scale functional relationships and transcriptome datasets, and a number of algorithms have been developed to support this strategy. In this paper, we present a promising and easily applicable tool to accomplish this goal, namely CytoGTA, which is a Cytoscape plug-in that relies on an optimistic game theoretic approach (GTA) for identifying subnetwork markers. Given transcriptomic data of two phenotype classes and interactome data, this plug-in offers discriminative markers for the two classes. The high performance of CytoGTA would not have been achieved if the strategy of GTA was not implemented in Cytoscape. This plug-in provides a simple-to-use platform, convenient for biological researchers to interactively work with and visualize the structure of subnetwork markers. CytoGTA is one of the few available Cytoscape plug-ins for marker identification, which shows superior performance to existing methods.

NMR-based metabolomics was applied to explore metabolic impacts of diazinon on sea water adaptation of Persian sturgeon fingerlings, Acipenser persicus. Fingerlings were exposed to sub-lethal concentrations of diazinon in freshwater (FW) for 96 h (short-term trial) and 12 days (long-term trial) and then exposed in brackish water (BW) (12 mg L -1 salinity) for 24 h. After 96 h and 12 days exposure in FW, identified metabolites (amino acids, osmolytes, energy metabolites) showed different change-patterns compared to control group (P < 0.05) as follow: (A) short-term trial: higher plasma levels of glucose, lactate (in all diazinon-exposed fish), acetate and acetoacetate (in 0.9 mg L -1 diazinon treatment); lower levels of creatine (in all diazinon-exposed fish), trimethylamine-N-oxide, choline, taurine, betaine, N,N-dimethylglycine and almost all amino acids in fish exposed to high concentrations of diazinon (0.54 and 0.9 mg L -1 diazinon). (B) Long-term trial: higher plasma levels of lipid oxidation metabolites and almost all amino acids in fish exposed to 0.54 and 0.9 mg L -1 diazinon; lower levels of creatine, trimethylamine-N-oxide, N,N-dimethylglycine, betaine, choline (in all diazinon-exposed fish), glucose (in 0.54 and 0.9 mg L -1 diazinon treatments) and taurine (in 0.9 mg L -1 diazinon treatment). When fish were exposed in BW for 24 h, the plasma levels of osmolytes decreased significantly in almost all experimental groups of short-term and long-term trial (P < 0.05). In short-term trial, the plasma levels of glucose in all groups and lactate in 0.18 and 0.54 mg L -1 diazinon treatments increased after salinity challenge (P < 0.05). However, a significant decrease was observed in lactate levels in 0.9 mg L -1 diazinon treatment (P < 0.05). Also, the plasma levels of amino acids decreased mostly in fish of control group than exposed fish (P < 0.05). The plasma glycerol concentration showed a significant decrease only in fish of 0.54 mg L -1 diazinon treatment (P < 0.05). In long term trial, the energetic metabolites (acetate, acetoacetate, glycerol) showed significant increases mostly in fish exposed to high concentrations of diazinon (P < 0.05). Phosphocreatine was detected only in groups exposed to 0.54 and 0.9 mg L -1 diazinon. Some amino acids decreased in control and diazinon-exposed groups while glycine (in control and 0.18 mg L -1 diazinon treatment), glutamine and alanine (in 0.9 mg L -1 diazinon treatment) elevated significantly after 24 h acclimation in BW (P < 0.05). Our results may help to understand the effects of pesticides on fish osmoregulation from a metabolic approach., (Copyright © 2017. Published by Elsevier Ltd.)

Background: There is increasing recognition of the concordance between marine biogeographic and phylogeographic boundaries. However, it is still unclear how population-level divergence translates into species-level divergence, and what are the principal factors that first initiate that divergence, and then maintain reproductive isolation. This study examines the likely forces driving population and lineage divergences in the broadly-distributed Indo-Pacific spiny lobster Panulirus homarus, which has peripheral divergent lineages in the west and east. The study focuses particularly on the West Indian Ocean, which is emerging as a region of unexpected diversity. Mitochondrial control region (mtCR) and COI sequences as well as genotypes of 9 microsatellite loci were examined in 410 individuals from 17 locations grouped into 7 regions from South Africa in the west, and eastward across to Taiwan and the Marquesas Islands. Phylogenetic and population-level analyses were used to test the significance and timing of divergences and describe the genetic relationships among populations., Results: Analyses of the mtCR revealed high levels of divergence among the seven regions (Ф ST  = 0.594, P < 0.001). Microsatellite analyses also revealed significant divergence among regions, but at a much lower level (F ST  = 0.066, P < 0.001). The results reveal different patterns of mtCR v. nDNA divergence between the two distinct peripheral lineages: a subspecies in South Africa and Madagascar, and a phylogeographically diverged population in the Marquesas. The results also expose a number of other more fine-scale population divergences, particularly in the Indian Ocean., Conclusions: The divergence of peripheral lineages in the west and east of the species' range appear to have been initiated and maintained by very different processes. The pattern of mitochondrial and nuclear divergence of the western lineage, implicates processes of parapatric isolation, secondary contact and introgression, and suggests possible maintenance through adaptation and behavioural reproductive isolation. In contrast, the eastern lineage appears to have diverged through a rare colonisation event, maintained through long-term isolation, and matches expectations of the core-periphery hypothesis. The process of active peripheral speciation may be a common force in the Indo-Pacific that helps drive some of the regions' recognized biogeographic boundaries.

In this study attempts were made to investigate the effect of extremely low frequency magnetic field (ELF-MF) on expression of glucose oxidase gene from Aspergillus niger Z-25 in Pichia pastoris GS115 at optimal environmental conditions. GOX encoding gene from A. niger was expressed in P. pastoris GS115 employing methanol inducible AOX1 promoter. From resistant transformants to high zeocin concentrations, maximum GOX expressing transformant was isolated and used throughout the study. Optimal environmental conditions for achieving maximum glucose oxidase (GOX) production was determined by varying temperature (20-30°C) and final methanol concentration from 0.25-1% (v/v). Maximum GOX production was obtained at 20°C and 0.25% (v/v) final methanol concentration. Exposure carried out at extremely low frequencies ranging from 1 to 5Hz and the field strength of 30-100mT unceasingly. Biomass, GOX, protease productions and cell viability were examined in exposed and non-exposed groups every 12h up to 96h. Among different exposure conditions, the frequency of 2.8Hz significantly increased GOX production and cell viability, decreased non-specific protease activity and improved biomass production regardless of changes in field intensity. Overall, supported by results, P. pastoris exposure to ELF-MF in certain circumstances could effectively further increase maximum production of GOX as achieved by optimized preliminary environmental parameters., (Copyright © 2017 Elsevier Inc. All rights reserved.)

To replenish the depleting populations of sturgeon fishes especially Persian sturgeon, Acipenser persicus in the Caspian Sea, millions of Persian sturgeon fingerlings are farmed through artificial propagation and released into the Iranian river estuaries annually. Fish osmoregulation is a vital physiological process that can be affected during the release. Many Iranian river estuaries are under the influence of pesticides originating from farming activities that may affect osmoregulation. In this study, Persian sturgeon fingerlings were exposed to sublethal concentrations (0, 0.18, 0.54, 0.9mgL(-)(1)) of diazinon for 96h (short-term trial) and 12 days (long-term trial) in fresh water (FW) and then fish were exposed in brackish water (BW) for 24h. After 96h and 12 days of exposure in FW, the lower levels of plasma triidothyronine (T3), thyroxine (T4), Na(+), Cl(-), K(+), gill Na(+)/K(+)- ATPase activity and number of chloride cells were observed in exposed fish (0.54 and 0.9mgL(-)(1) diazinon) compared to control group and 0.18mgL(-)(1) diazinon treatment. Also, higher levels of plasma cortisol (except 0.18mgL(-)(1) diazinon treatment in long-term trial) were observed in diazinon exposed fish compared to control group. However, gill Na(+)/K(+)-ATPase activity and the number of chloride cells were higher in fingerlings exposed to diazinon compared than control. When fish were exposed in BW for 24h, the following changes occurred: (a) in short-term trial: increases in cortisol and Cl(-) levels (0.54mgL(-)(1) diazinon ), Na(+) (0.9mgL(-)(1) diazinon ) and gill Na(+)/K(+)-ATPase activity (0.18mgL(-)(1) diazinon ). In control group, cortisol, T4, Na(+), gill Na(+)/K(+)-ATPase activity and the number of chloride cells increased significantly. (b) In long-term trial: increases in K(+) levels in fish exposed to 0.9mgL(-)(1) diazinon, Na+ in all diazinon concentrations and decreases in chloride cells number in fish exposed to 0.18mgL(-)(1) diazinon. In control group, significant increases were observed in cortisol, T3, Na(+) and chloride cells number. Finally, gill showed many histopathological damages during exposure in FW and BW. Our results suggest that the contamination of river estuaries with diazinon may alter the osmoregulation ability of released Persian sturgeon fingerlings, which could lead to a failure in their restocking program in the Caspian Sea., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Beta-adrenergically-stimulated sweat rates determined by evaporimetry or by sweat bubble imaging are useful for measuring CFTR function because they provide a near-linear readout across almost the full range of CFTR function. They differentiate cystic fibrosis (CF) subjects from CF carriers and carriers from controls. However, evaporimetry, unlike bubble imaging, appears to be unable to detect improved levels of CFTR function in G551D subjects taking the CFTR modulator ivacaftor. Here, we quantify the sensitivity of evaporimetry and bubble imaging methods for assessing low levels of CFTR-dependent sweat rates. To establish sensitivity, we did dose-ranging studies using intradermally injected [cAMP]i-elevating cocktails. We reduced isoproterenol/aminophylline levels while maintaining a high level of atropine to block muscarinic elevation of [Ca2+]i. We stimulated the same sets of glands for both assays and recorded responses for 20 min. In response to a 3-log dilution of the stimulating cocktail (0.1%), bubble responses were detected in 12/12 tests (100%), with 49% ± 3% of glands secreting to produce an aggregate volume of 598 nl across the 12, 20-min tests. This was ~5% of the response to full cocktail. Evaporimetry detected responses in 3/12 (25%) tests with an aggregate secretion volume of 175 nl. After stimulation with a still more dilute cocktail (0.03%), bubble imaging detected 15 ± 13% of glands secreting at a rate ~0.9% of the response to full cocktail, while zero responding was seen with evaporimetry. The bubble imaging method detected secretion down to aggregate rates of <0.2 nl/(cm2·min), or ~1/30th of the average basal transepithelial water loss (TEWL) in the test subject of 4 g/m2·hr or 6.7 nl/(cm2·min). The increased sensitivity of bubble imaging may be required to detect small but physiologically important increases in secretion rates produced by CFTR modulators., Competing Interests: The authors have declared that no competing interests exist.

Aim: Breast cancer is the most common cancer among women worldwide. Science has already proved that some breast cancer genes are inherited from parents. It is generally believed that the probability of cancer diagnosis in carriers of those genes is considerably higher than the normal population. It is in the same direction that modern medicine has introduced prophylactic mastectomy - one of the key preventive methods which is the focus of the present research. Nevertheless, whether women that have been diagnosed with breast cancer would take this approach depends on their local culture and their set of beliefs. In this regard, the present research was meant to evaluate the acceptability rate of prophylactic mastectomy among women in Iran after they are informed of the positive genetic test results., Methods: Six hundred and five healthy women, who had no history of breast cancer, were selected by nonprobability sampling method. A predesigned questionnaire was filled out by the interviewer., Results: Results showed that about 15% of respondents were willing to pick the prophylactic mastectomy in case they are identified as carriers of breast cancer genes. Twenty-two percent of participants with positive family history was agreed with prophylactic mastectomy while in the negative family history group it was about 14%., Conclusion: Preventive mastectomy has a higher rate of acceptability among women who have had a family history of breast cancer. Therefore, it may be concluded that raising public awareness about the advantages of prophylactic mastectomy could help better address breast cancer in Iran.

Electrospun polyhydroxybutyrate (PHB) fibers were dip-coated by polymethyl methacrylate-co-methacrylic acid, poly(MMA-co-MAA), which was synthesized in different molar ratios of the monomers via free-radical polymerization. Fabricated platfrom was employed for immobilization of the dengue antibody and subsequent detection of dengue enveloped virus in enzyme-linked immunosorbent assay (ELISA). There is a major advantage for combination of electrospun fibers and copolymers. Fiber structre of electrospun PHB provides large specific surface area available for biomolecular interaction. In addition, polymer coated parts of the platform inherited the premanent presence of surface carboxyl (-COOH) groups from MAA segments of the copolymer which can be effectively used for covalent and physical protein immobilization. By tuning the concentration of MAA monomers in polymerization reaction the concentration of surface -COOH groups can be carefully controlled. Therefore two different techniques have been used for immobilization of the dengue antibody aimed for dengue detection: physical attachment of dengue antibodies to the surface and covalent immobilization of antibodies through carbodiimide chemistry. In that perspective, several different characterization techniques were employed to investigate the new polymeric fiber platform such as scanning electron microscopy (SEM), atomic force microscopy (AFM), water contact angle (WCA) measurement and UV-vis titration. Regardless of the immobilization techniques, substantially higher signal intensity was recorded from developed platform in comparison to the conventional ELISA assay., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: Polycystic ovary syndrome is a common endocrine disorder affecting women both physically and psychologically and can lead to a poor quality of life compared to their normal counterparts. The aim of the present study was to assess the impact of various clinical features of polycystic ovary syndrome on the health-related quality of life of Iranian women diagnosed with this syndrome., Materials and Methods: A total of 796 women diagnosed with polycystic ovary syndrome, aged 15-49 years, completed the questionnaires, interviews, and medical assessments required for this study. A reliable and validated Persian version of the health-related quality of life questionnaire for polycystic ovary syndrome patients was used. Linear regression models were used to assess the association between the symptoms of polycystic ovary syndrome and health-related quality of life., Results: The mean age of participants was 28.02 years. 35.4% of the subjects were classified as overweight or obese. Hirsutism, was reported to have the strongest impact on the patients' health-related quality of life, followed in descending order by body mass index, irregular menses and infertility. The relative level of hirsutism was directly proportional to decrease in health-related quality of life score (p<0.001)., Conclusions: The results of the study found that hirsutism had the strongest impact on the health-related quality of life measures in Iranian women diagnosed with polycystic ovary syndrome. Health care officials need to evaluate in depth the effect of each clinical feature of polycystic ovary syndrome separately and design management strategies, keeping in mind the psychological and physical manifestations.

Background: The Swedish Dementia Registry (SveDem) was developed with the aim to improve the quality of diagnostic work-up, treatment and care of patients with dementia disorders in Sweden., Methods: SveDem is an internet based quality registry where several indicators can be followed over time. It includes information about the diagnostic work-up, medical treatment and community support (www.svedem.se). The patients are diagnosed and followed-up yearly in specialist units, primary care centres or in nursing homes., Results: The database was initiated in May 2007 and covers almost all of Sweden. There were 28 722 patients registered with a mean age of 79.3 years during 2007-2012. Each participating unit obtains continuous online statistics from its own registrations and they can be compared with regional and national data. A report from SveDem is published yearly to inform medical and care professionals as well as political and administrative decision-makers about the current quality of diagnostics, treatment and care of patients with dementia disorders in Sweden., Conclusion: SveDem provides knowledge about current dementia care in Sweden and serves as a framework for ensuring the quality of diagnostics, treatment and care across the country. It also reflects changes in quality dementia care over time. Data from SveDem can be used to further develop the national guidelines for dementia and to generate new research hypotheses.

Panulirus homarus is an economically important spiny lobster that is widespread through the Indo-West Pacific Region, but has an uncertain taxonomic status, with three or four geographic subspecies having been described. This study used mitochondrial (16S, COI and control region) and nuclear (18S, ITS-1) DNA sequences to examine specimens of all putative subspecies and forms from throughout their range, in order to determine their genetic validity, and understand the evolutionary history of this species. Despite the range of diversity present in the loci examined, the results were consistent across genes. P. h. rubellus from the SW Indian Ocean comprised the most divergent lineage that was reciprocally monophyletic with respect to all other P. homarus (approx. 9% divergence in COI), and has likely evolved reproductive barriers. The putative P. h. "Brown" subspecies from the Marquesas Is in the central Pacific also comprised a somewhat divergent monophyletic lineage (approx. 3% in COI), but may simply be an allopatric population. The widespread P. h. homarus was not diverged at all from the described P. h. megasculpta from the NW Indian Ocean. The degree of evolutionary divergence of populations at the extremes distribution of the species is somewhat surprising, given the long pelagic larval stage, but suggests that allopatric speciation has been an important driver in the evolution of the genus.

The objective of this study was to investigate the toxicity effects of acute and sublethal of Roundup® as a glyphosate-based herbicide on acetylcholinesterase (AChE) activity and several hematological and biochemical parameters of Cyprinus carpio. The LC₅₀-96 h of Roundup® to C. carpio was found to be 22.19 ppm. Common carp was subjected to Roundup® at 0 (control), 3.5, 7 and 14 ppm for 16 days, and the AChE activity is verified in tissues of gill, muscle, brain and liver. After 5 days, a significant decrease was observed in the AChE activity of muscle, brain and liver tissues. Besides, a time- and dose-dependent increase in mean cell hemoglobin (MCH) and mean cell volume (MCV) was observed. In contrast, a significant decrease was found in the quantities of hemoglobin (Hb), hematocrit (HCT) and, red (RBC) and white (WBC) blood cell count. Also, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in Roundup® treated groups were significantly higher than the controlled group at experimental periods. However, the level of alkaline phosphatase (ALP) had a significant reduction behavior during the sampling days. It seems that the changes in hematological and biochemical parameters as well as AChE activity could be used as efficient biomarkers in order to determine Roundup® toxicity in aquatic environment., (© 2013 Elsevier Inc. All rights reserved.)

The present study is the first report on optimization of recovery conditions of fishes exposed to pesticides using response surface methodology-central composite rotatable design (RSM-CCRD). The sub-lethal toxicity bioassay of Roundup® (2 ppm ~10 percent LC₅₀, 96 h) in common carp (1, 4, 9, 16, 25, 35 and 40 day) was investigated. After exposure for 16 days to Roundup®, some the fishes were introduced to herbicide-free water. The effects of four recovery parameters including time (5-25 d), temperature (18-26 °C), water exchange rate (WER, 10-30), and salinity (0-8 ppt) on the levels of biomarkers of genotoxicity (DNA damage), neurotoxicity (acetylcholinesterase activity (AChE)), and the serum alanine (ALT) and aspartate (AST) aminotransferase in plasma were studied. The polynomial equations were significantly fitted for all response variables with high R² values (>0.95), which revealed no indication of lack of fit. The optimum conditions for the maximum AChE activity (37.14 nmol/min/mg protein) and the minimum levels of DNA damage (8.00 percent tail DNA), ALT (27.0 IU/L) and AST (91.0 IU/L) were time of 20 d, temperature of 20 °C, WER of 25 and water salinity of 6 ppt. Thus, a promising improvement for the recovery trend of fishes exposed to Roundup® stress was obtained under the optimized conditions using RSM-CCRD., (© 2013 Elsevier Inc. All rights reserved.)

A safe rehabilitation exercise for anterior cruciate ligament (ACL) injuries needs to be compatible with the normal knee arthrokinematics to avoid abnormal loading on the joint structures. The objective of this study was to measure the amount of the anterior tibial translation (ATT) of the ACL-deficient knees during selective open and closed kinetic chain exercises. The intact and injured knees of fourteen male subjects with unilateral ACL injury were imaged using uniplanar fluoroscopy, while the subjects performed forward lunge and unloaded/loaded open kinetic knee extension exercises. The ATTs were measured from fluoroscopic images, as the distance between the tibial and femoral reference points, at seven knee flexion angles, from 0° to 90°. No significant differences were found between the ATTs of the ACL-deficient and intact knees at all flexion angles during forward lunge and unloaded open kinetic knee extension (P < 0.05). During loaded open kinetic knee extension, however, the ATTs of the ACL deficient knees were significantly larger than those of the intact knees at 0° (P = 0.002) and 15° (P = 0.012). It was suggested that the forward lunge, as a weight-bearing closed kinetic chain exercise, provides a safer approach for developing muscle strength and functional stability in rehabilitation program of ACL-deficient knees, in comparison with open kinetic knee extension exercise.

Worldwide, lung cancer is the most common form of cancer. Saffron has been used in folk medicine for centuries. We investigated the potential of saffron to induce cytotoxic and apoptotic effects in lung cancer cells (A549). We also examined the caspase-dependent pathways activation of saffron-induced apoptosis against the A549 cells. A549 cells were incubated with different concentrations of saffron extract; then cell morphological changes, cell viability, and apoptosis were determined by the normal invertmicroscope, MTT assay, Annexin V and propidium iodide, and flow cytometric analysis, respectively. Activated caspases were detected by treatment of saffron in lung cancer cells using fluorescein-labeled inhibitors of polycaspases. The proliferation of the A549 cells were decreased after treatment with saffron in a dose- and time-dependent manner. The percentage of apoptotic cells increased with saffron concentrations. Saffron induced morphological changes, decreased percentage of viable cells, and induced apoptosis. Saffron could induce apoptosis in the A549 cells and activate caspase pathways. The levels of caspases involved in saffron-induced apoptosis in the A549 cells indicating caspase-dependent pathway were induced by saffron. The anticancer activity of the aqueous extract of saffron could be attributed partly to its inhibition of the cell proliferation and induction of apoptosis in cancer cells through caspase-dependent pathways activation.

A suite of 5 different biomarker responses were selected and measured in 3 different phases of detoxification process in mudskipper Periophthalmus waltoni from 3 different stations including Soltani Inlet, Shif Island and Ameri Port in Bushehr coastal area of the Persian Gulf. The selected biomarkers were 7-ethoxyresorufin O-deethylase (EROD), glutathione S-transferase (GST), biliary fluorescent aromatic compounds (FACs), DNA damage using the Comet assay and micronucleus (MN). Spatial variations in biomarker responses were observed in different sites. EROD, GST, FACs, DNA damage and MN were significantly elevated in mudskippers in the most oil impacted site (Soltani inlet). Based on the assessments, bile metabolites, EROD and GST induction appear to be sensitive to polycyclic aromatic hydrocarbons (PAHs) and can be considered as complementary biomarkers; therefore P. waltoni has the potential to be used as a bioindicator in these types of ecosystems., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In recent years, recombinant monoclonal antibodies and their derivatives have emerged as important targeted therapy agents. Monoclonal antibodies are extremely difficult to produce. So, the cost of production is very high and many people cannot afford these drugs. In this regard, choosing inexpensive and easy ways to manipulate production systems such as bacterial hosts to reduce the cost of manufacturing these critical components are considered as vital step for developmental issues in recombinant expression systems. We, therefore, attempted to generate a polycistronic construct of anti HER-2 F(ab')2 fragment antibody for insertion in an expression bacterial plasmid. Also some modifications were made in the hinge region to express antibody F(ab')2 fragment in its authentic form preventing from multiple varieties of disulfide bond formation. Finally, synthesized construct was cloned in pET-32 Ek/LIC vector without using restriction enzyme digestion or ligation reactions. The results of this study showed that modified F(ab')2 fragment was simply and successfully inserted in Escherichia coli (E.coli) using the Ligation Independent Cloning technology.

Background: This study aimed to evaluate the accuracy of Euroscore (European System for Cardiac Operative Risk Evaluation) in predicting perioperative mortality after cardiac surgery in Iranian patient population., Methods: Data on 1362 patients undergoing coronary bypass graft surgery (CABG) from 2007 to 2009 were collected. Calibration was assessed by Hosmer-Lemeshow goodness-of-fit. Area under the curve (AUC) was used to assess score validity. Odds ratios were measured to evaluate the predictive value of each risk factor on mortality rate., Results: The overall perioperative in hospital mortality was 3.6% whereas the Euroscore predicted a mortality of 3.96%. Euroscore model fitted well in the validation databases. The mean AUC was 66%. Mean length of intensive care unit (ICU) stay was 2.5 ± 2.5 days. Among risk factors, only left ventricular dysfunction, age and neurologic dysfunction were found to be related to mortality rate., Conclusions: Euroscore did not have acceptable discriminatory ability in perioperative in hospital mortality in Iranian patients. It seems that development of a local mortality risk scores corresponding to our patients epidemiologic characteristics may improve prediction of outcome.

Background: There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF). Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated., Methods: Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression., Results: The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05). Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57%) and 6 (52.17%) after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002), followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009) and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031)., Conclusions: Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect.

Background: To complete long-distance ski races, regular physical exercise is required. This includes not only cross-country skiing but also endurance exercise during the snow-free seasons. The aim of this study was to determine whether the level of physical exercise is associated with future risk of severe osteoarthritis independent of previous diseases and injuries., Methodology/principal Findings: We used a cohort that consisted of 48 574 men and 5 409 women who participated in the 90 km ski race Vasaloppet at least once between 1989 and 1998. Number of performed races and finishing time were used as estimates of exercise level. By matching to the National Patient Register we identified participants with severe osteoarthritis, defined as arthroplasty of knee or hip due to osteoarthritis. With an average follow-up of 10 years, we identified 528 men and 42 women with incident osteoarthritis. The crude rate was 1.1/1000 person-years for men and 0.8/1000 person-years for women. Compared with racing once, participation in ≥ 5 races was associated with a 70% higher rate of osteoarthritis (multivariable-adjusted hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.33 to 2.22). The association was dose-dependent with an adjusted HR of 1.09, 95% CI 1.05 to 1.13 for each completed race. A faster finishing time, in comparison with a slow finishing time, was also associated with an increased rate (adjusted HR 1.51, 95% CI 1.14 to 2.01). Contrasting those with 5 or more ski races and a fast finish time to those who only participated once with a slow finish time, the adjusted HR of osteoarthritis was 2.73, 95% CI 1.78 to 4.18., Conclusions/significance: Participants with multiple and fast races have an increased risk of subsequent arthroplasty of knee and hip due to osteoarthritis, suggesting that intensive exercise may increase the risk.