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BACKGROUND: Due to the high resource consumption of introducing a new drug, drug repurposing plays an essential role in drug discovery. To do this, researchers examine the current drug-target interaction (DTI) to predict new interactions for the approved drugs. Matrix factorization methods have much attention and utilization in DTIs. However, they suffer from some drawbacks. METHODS: We explain why matrix factorization is not the best for DTI prediction. Then, we propose a deep learning model (DRaW) to predict DTIs without having input data leakage. We compare our model with several matrix factorization methods and a deep model on three COVID-19 datasets. In addition, to ensure the validation of DRaW, we evaluate it on benchmark datasets. Furthermore, as an external validation, we conduct a docking study on the COVID-19 recommended drugs. RESULTS: In all cases, the results confirm that DRaW outperforms matrix factorization and deep models. The docking results approve the top-ranked recommended drugs for COVID-19. CONCLUSIONS: In this paper, we show that it may not be the best choice to use matrix factorization in the DTI prediction. Matrix factorization methods suffer from some intrinsic issues, e.g., sparsity in the domain of bioinformatics applications and fixed-unchanged size of the matrix-related paradigm. Therefore, we propose an alternative method (DRaW) that uses feature vectors rather than matrix factorization and demonstrates better performance than other famous methods on three COVID-19 and four benchmark datasets.
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COVID-19 , Aprendizado Profundo , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Interações Medicamentosas , Descoberta de Drogas/métodosRESUMO
BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Compostos de Anilina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Spontaneous dipole orientation is studied for a set of simulated porous ASW ice films on a substrate held at temperatures ranging from 10 K to 140 K. It is found that the water dipoles in the films obtained at the lower temperatures are oriented such that a negative electric field with a magnitude of 108-109 V m-1 is obtained. The magnitude of the field increases approximately linearly with height above the substrate, akin to experimental observations, although the magnitude of our field increases faster. A strong temperature dependence of the surface potential resulting from the spontelectric field is found, where the surface potential decreases when the substrate temperature increases. The surface potential finally becomes close to zero for temperatures around and above 110 K.
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Avian infectious bronchitis virus (IBV) and avian pathogenic Escherichia coli (APEC) are two important respiratory pathogens in the chicken. The co-infection can lead to chronic complications and considerable economic losses in the poultry industry worldwide. In the present study, we compared differential transcriptional profiles in the trachea tissue of three infected groups (IBV, APEC, and co-infection) with the control group to investigate transcriptome profile changes at the early stage of the infection. After the challenge of SPF chickens with IBV IS-1494 like (GI-23) and APEC, serotype O78: K80, or co-infection, the trachea tissue was used for RNA extraction, and changes in the transcriptome were investigated by Illumina RNA-seq technique. Up-regulated and down-regulated differentially expressed genes (DEGs) in the transcriptome of each group's trachea were identified. Gene ontology category, KEGG pathway, and gene interaction networks (STRING analysis) were analyzed to identify relationships among differentially expressed genes. In general, the numbers of up-regulated genes were higher than of down-regulated genes. In the co-infection group, a more severe immune response and macrophage infiltration occurred; an important cluster of pathway signaling in this group's up-regulated genes was an apoptotic cluster, cytokine-mediated signaling cluster, and the PAMPs recognizing cluster. This is the first study to provide a general overview of transcriptome changes in the trachea at the early stage of infection with these pathogens. Keywords: avian infectious bronchitis virus; avian pathogenic E. coli; transcriptome; RNA-Seq.
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Coinfecção/veterinária , Infecções por Coronavirus/veterinária , Infecções por Escherichia coli/veterinária , Doenças das Aves Domésticas , Traqueia , Transcriptoma , Animais , Galinhas , Coinfecção/genética , Infecções por Coronavirus/genética , Escherichia coli , Infecções por Escherichia coli/genética , Perfilação da Expressão Gênica , Vírus da Bronquite Infecciosa , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/virologiaRESUMO
AIM: This study aimed to assess the microleakage of a self-adhesive composite compared to conventional composites in class V cavities. MATERIALS AND METHODS: In this in vitro experimental study, standard class V cavities were prepared in the buccal surface of 204 extracted teeth and randomly divided into six groups for restoration with (A) Vertiseflow (Kerr) self-adhesive composite, (B) acid etching (Kerr) + Vertiseflow, (C) acid etching + Optibond FL (Kerr) + Vertiseflow, (D) Er,Cr:YSGG laser + Vertiseflow, (E) acid etching + Optibond FL + Premise Flowable (Kerr), and (F) acid etching + Optibond FL + Z250 (3M). The teeth in each group were then randomly divided into two subgroups of with and without thermocycling (10,000 cycles between 5°C and 55°C). The microleakage was then determined at the enamel and dentin margins under a stereomicroscope using the dye penetration method. Data were analyzed using the Kruskal-Wallis test (α = 0.05). RESULTS: No significant difference was noted in occlusal margin microleakage of no thermocycling groups, but acid etching + Vertiseflow showed the highest microleakage. At the gingival margin, the difference between acid etching + bonding agent + Z250 and laser + Vertiseflow was significant (p = 0.004). In thermocycling groups, the difference in the microleakage at the occlusal margin of Vertiseflow with that of acid etching + bonding agent + Premise (p = 0.002), acid etching + bonding agent + Vertiseflow (p = 0.009), and acid etching + bonding agent + Z250 (p = 0.037) groups was significant. The difference in the microleakage at the dentin margin was also significant among the groups (p < 0.05). The highest and the lowest microleakages were noted in laser + Vertiseflow and acid etching + bonding agent + Vertiseflow groups, respectively. CONCLUSION: Surface preparation with etching and adhesive application results in lower microleakage in class V cavities. But laser irradiation and the use of self-adhesive composite increase the microleakage. CLINICAL SIGNIFICANCE: It seems that self-adhesive composites cannot provide acceptable marginal integrity without any surface treatment.
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Infiltração Dentária , Cimentos de Resina , Resinas Compostas , Cimentos Dentários , Restauração Dentária Permanente , HumanosRESUMO
OBJECTIVE: Cannabis sativa L has remained the most widely used recreational and abused drug worldwide. This study determined adipose tissue histological changes and the anxiety-like behavior in elevated plus-maze tests in rats treated with C. sativa. METHODS: C. sativa L. was provided from Islamic Azad University Herbarium. To reach cannabis powder, a rotary evaporator was used. Forty-five male Wistar rats were randomly divided into three equal groups of experimental receiving 2 mg/kg of cannabis extract dissolved in 70 % ethanol in 0.6 mL volume subcutaneously daily for three weeks, the sham group subcutaneously injected with equal volume of 70 % ethanol and the control receiving just distilled water, identically. To assess the anxiety level, elevated plus maze was used. Histopathological changes in adipose tissue was evaluated after 7, 14, and 21 days post-intervention. RESULTS: After cannabis administration, inflammation, degeneration and necrosis in adipose tissue occured. Regarding the anxiety level for the percentage of time spent in open arm (OAT), the percentage of time spent in closed arm (CAT), the percentage of time spent in central parts, and head dipping over the side of the maze) after one week, no significant difference was noticed between the groups; but 2 and 3 weeks of cannabis use, the anxiety level significantly increased. CONCLUSION: Histological findings denoted to inflammation, degeneration and necrosis in adipose tissue after cannabis use. Behavioral assessment of anxiety level revealed that one week after cannabis, no changes were seen in anxiety, but 2 and 3 weeks after cannabis use, the anxiety level increased significantly (Fig. 5, Ref. 38).
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Tecido Adiposo/efeitos dos fármacos , Ansiedade , Comportamento Animal/efeitos dos fármacos , Cannabis/química , Extratos Vegetais/farmacologia , Animais , Emoções , Masculino , Aprendizagem em Labirinto , Ratos , Ratos WistarRESUMO
INTRODUCTION: This study aimed to evaluate knowledge, attitudes, practice associated with Human Papillomavirus (HPV) Vaccine for Young Children among lecturers and health staffs of Shahid Beheshti University of Medical Sciences (SBMU). METHOD: This was a cross-sectional study with 220 adults from five different specialties, randomly selected. Data was collected using 45-item questionnaire on knowledge (12- item), attitude (18-item) and practice (15-item) (KAP) about HPV. The demographic questionnaire included information on age, gender, level of education, occupation, and marital status. Content validity was calculated by content validity ratio (CVR) and content validity index (CVI). Reliability was evaluated using test-retest and by Cronbach's Alpha coefficient, internal consistency was calculated values >0.81 which considered as satisfactory. RESULTS: The mean age of the studied population was 37.70± 8.07 (23-67) years. Of the 220 participants, 80 (36.4%) were males and 140 (63.6%) were females. In evaluating KAP in the men and women, the mean and standard deviation of knowledge were estimated at good level and one-way ANOVA analysis showed significant differences between women and men (p=0.019). There was no significant difference in men and women related to attitude (p=0.92) and practice (p=0.38). CONCLUSION: The KAP about HPV among participants was significantly higher at good levels compared to average levels. Women's knowledge was significantly higher than men. Attitude and practice could have been higher because there was consensus to the usage of vaccine among the specialists to prevent HPV.
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Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Papillomavirus , Adulto , Idoso , Estudos Transversais , Feminino , Política de Saúde , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
The role of environment in shaping material properties is of great significance, but less is known about how non-trivial topology of the environment couples to material states, which can be of non-trivial topology themselves. In this paper, we demonstrate the role of the topology of the environment on the formation of complex nematic fields and defect structures, specifically in the system of nematic colloidal knots. The topological environments around knotted colloidal particles are suggested to exist as spherical surface-patterned nematic cavities imposing radial, uniform or hyperbolic nematic profiles. We show that topologically different nematic environments significantly affect and create differences in the colloidal field structure created within the environment, such as the location, profile and number of topological defects. Specifically, we demonstrate that topological environments in combination with knotted colloidal particles of non-trivial topology lead to the formation of diverse nematic knotted and linked fields. These fields are different adaptations of the knotted shape of the colloidal particles, creating knots and links of topological defects as well as escaped-core defect-like solitonic structures. These are observed in chiral nematic media but here are stabilised in achiral nematic media as a result of the distinct shape of the knotted colloidal particle, with a double helix segment and nematic environmental patterns. More generally, this paper is a contribution towards understanding the role of environment, especially its topology, on the response and defect formation in elastic fields, such as in nematic liquid crystal colloids.
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Theoretical kinetic studies are performed on the multichannel thermal decomposition of acetaldehyde. The geometries of the stationary points on the potential energy surface of the reaction are optimized at the MP2(full)/6-311++G(2d,2p) level of theory. More accurate energies are obtained by single point energy calculations at the CCSD(T,full)/augh-cc-pVTZ+2df, CBS-Q and G4 levels of theory. Here, by application of steady-state approximation to the thermally activated species CH3CHO* and CH2CHOH* and performance of statistical mechanical manipulations, expressions for the rate constants for different product channels are derived. Special attempts are made to compute accurate energy-specific rate coefficients for different channels by using semiclassical transition state theory. It is found that the isomerization of CH3CHO to the enol-form CH2CHOH plays a significant role in the unimolecular reaction of CH3CHO. The possible products of the reaction are formed via unimolecular decomposition of CH3CHO and CH2CHOH. The computed rate coefficients reveal that the dominant channel at low temperatures and high pressures is the formation of CH2CHOH due to the low barrier height for CH3CHO â CH2CHOH isomerization process. However, at high temperatures, the product channel CH3 + CHO becomes dominant.
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1. This experiment was conducted to evaluate the effects of replacing dietary cottonseed meal (CSM) or fermented cottonseed meal (FCSM) for soya bean meal (SBM) on growth performance, carcass characteristics, gastrointestinal microbial populations, and intestinal morphology of broiler chickens. 2. CSM was fermented with Bacillus subtilis, Aspergillus niger and A. oryzae for 7 d. A total of 300 one-d-old male Ross 308 broiler chickens were used in a 42-d experiment in which the birds were randomly allotted to one of 5 dietary treatments (containing 0%, 10% and 20% CSM or FCSM) in a completely randomised design. Birds were reared on litter floor and had free access to feed and water during the experiment. 3. Results indicated that the fermentation process significantly reduced crude fibre and free gossypol, while it increased crude protein content and lactic acid bacteria (LAB) count in CSM. 4. The use of FCSM instead of CSM significantly improved growth performance of broilers. The abdominal fat yield in treatments containing FCSM was significantly lower than in the other treatments. The increase in the population of LAB in the crop and decrease in the population of coliforms in the ileum of birds fed on diets containing FCSM were more significant than in other birds. Villi in the duodenum and jejunum of the birds fed on diets containing FCSM were significantly higher than for the other experimental groups. 5. The positive effects of diets containing FCSM on growth performance and intestinal health of broiler chickens showed that this processed source of protein can serve as an appropriate alternative for SBM in diets for broiler chickens.
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Ração Animal/análise , Galinhas/fisiologia , Óleo de Sementes de Algodão/metabolismo , Dieta/veterinária , Microbioma Gastrointestinal , Intestino Delgado/anatomia & histologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Aspergillus niger/química , Aspergillus oryzae/química , Bacillus subtilis/química , Galinhas/anatomia & histologia , Galinhas/crescimento & desenvolvimento , Galinhas/microbiologia , Óleo de Sementes de Algodão/administração & dosagem , Fermentação , Masculino , Distribuição AleatóriaRESUMO
BACKGROUND: Data on non-small-cell lung cancer (NSCLC) patients with non-classic epidermal growth factor receptor (EGFR) mutations are scarce, especially in non-Asian populations. The purpose of this study was to evaluate prevalence, clinical characteristics and outcome on EGFR-TKI treatment according to type of EGFR mutation in a Dutch cohort of NSCLC patients. METHODS: We retrospectively evaluated a cohort of 240 EGFR-mutated NSCLC patients. Data on demographics, clinical and tumour-related features, EGFR-TKI treatment and clinical outcome were collected and compared between patients with classic EGFR mutations, EGFR exon 20 insertions and other uncommon EGFR mutations. RESULTS: Classic EGFR mutations were detected in 186 patients (77.5%) and non-classic EGFR mutations in 54 patients (22.5%); 23 patients with an exon 20 insertion (9.6%) and 31 patients with an uncommon EGFR mutation (12.9%). Median progression-free survival (PFS) and overall survival (OS) on EGFR-TKI treatment were 2.9 and 9.7 months, respectively, for patients with an EGFR exon 20 insertion, and 6.4 and 20.2 months, respectively, for patients with an uncommon EGFR mutation. Patients with a double uncommon EGFR mutation that included G719X/L861Q/S768I had longer PFS and OS on EGFR-TKI treatment compared with patients with a single G719X/L861Q/S768I EGFR mutation (both P=0.02). CONCLUSIONS: In our Dutch cohort, prevalence and genotype distribution of non-classic EGFR mutations were in accordance with previously reported data. The PFS and OS on EGFR-TKI treatment in patients with an uncommon EGFR mutation were shorter compared with patients with classic EGFR mutations, but varied among different uncommon EGFR mutations.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países BaixosRESUMO
STUDY QUESTION: Is polycystic ovary morphology (PCOM) associated with metabolic syndrome (MS), insulin resistance (IR) and dyslipidemia? SUMMARY ANSWER: No associations between PCOM and metabolic disorders were found. WHAT IS KNOWN ALREADY: Polycystic ovary morphology has a prevalence of 21-63% in healthy women of reproductive age. Results of studies focusing on metabolic abnormalities among females with PCOM, are insufficient and controversial. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional population-based study from five provinces in Iran. A standard questionnaire was filled out during face-to-face interviews and clinical examinations were done. All study subjects were invited to undergo blood sampling and ultrasonographic assessment. PARTICIPANTS/MATERIALS, SETTING, METHODS: From a total of 1772 women, 809 participants met the inclusion criteria of this study, i.e. non-pregnant, reproductive-age, ovulatory, normo-androgenic, without hyperprolactinemia/thyroid dysfunction. Participants were divided into two groups; 126 women with PCOM on ultrasound assessment, as the case and 683 women with normal ovarian morphology, as the control groups. The association of PCOM with MS, IR and dyslipidemia were analyzed using logistic regression models, adjusted for confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE: Mean systolic blood pressure (SBP), high density lipoprotein (HDL) and androstenedione (A4) serum levels of women with PCOM were significantly higher than in the normal group (P = 0.04, 0.05 and 0.008, respectively). Comparison between groups revealed dyslipidemia to be higher among controls. However the results of logistic regression models, after adjustment for possible confounding variables showed that there were no significant association between prevalence of MS, IR and dyslipidemia with PCOM. LIMITATIONS, REASONS FOR CAUTION: Due to the study being cross-sectional, blood samples were collected only once thus we did not measure serum concentrations of progesterone in the luteal phase, which determines subclinical anovulation. Moreover, due to budget limitations, enzyme immunoassay was used for androgenic measurements while mass spectrometry-based assays have been known as the gold standard method. However we defined our groups very strictly to overcome these limitations. WIDER IMPLICATIONS OF THE FINDINGS: It seems that biochemical and metabolic characteristics of women with PCOM do not differ significantly to those of normal women. To clarify the association between PCOM and metabolic characteristics, longitudinal studies investigating long-term metabolic disorders among women with PCOM are highly recommended. STUDY FUNDING/COMPETING INTEREST: No external funding was used for this study. No conflicts of interest are declared.
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Doenças Metabólicas/epidemiologia , Síndrome do Ovário Policístico/complicações , Adulto , Estudos Transversais , Dislipidemias/complicações , Dislipidemias/epidemiologia , Feminino , Humanos , Resistência à Insulina , Irã (Geográfico)/epidemiologia , Modelos Logísticos , Doenças Metabólicas/complicações , Doenças Metabólicas/patologia , Síndrome do Ovário Policístico/patologia , PrevalênciaRESUMO
PURPOSE: There is much controversy regarding the use of oral contraceptive pills (OCPs) on cardiometabolic parameters, which is why this longitudinal population-based study was conducted to assess the impact of OCP use and its duration on cardiometabolic factors. METHODS: Of 5532 reproductive-aged participants of the Tehran lipid and glucose study, 3160 women who met our inclusion criteria were subdivided according to the duration of OCPs consumption into four sub-groups: (1) Non-users; (2) <11 month users; (3) 12-35 month users, and (4) ≥36 month users, and their cardiometabolic parameters were compared. RESULTS: No statistical significant differences were observed between the cardiometabolic parameters of these sub-groups, after further adjustment for confounding factors including age, parity, and education, except for mean low-density lipoprotein-cholesterol which was significantly higher in women who used OCPs for >36 months in comparison to non-OCP users. The odds ratio of hypercholesterolemia was significantly higher in women who used OCPs for >36 months in comparison to non-OCP users; being 1.5 times higher than non-users (95 % CI 1.01-2.2). CONCLUSION: Results showed that if used for less than 3 years, OCPs have no cardiometabolic effects.
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Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Colesterol/metabolismo , Anticoncepcionais Orais Combinados/administração & dosagem , Triglicerídeos/metabolismo , Adolescente , Adulto , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
STUDY DESIGN: This is a clinical trial (phase 1). OBJECTIVES: The objective of this study was to asses the safety and feasibility of bone marrow mesenchymal stem cell (MSC) and Schwann cell (SC) co-injection through cerebral spinal fluid (CSF) for the treatment of patients with chronic spinal cord injury. METHODS: Six subjects with complete spinal cord injury due to trauma according to International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) developed by the American Spinal Injury Association were enrolled. They received autologous co-transplantation of MSC and SC through lumbar puncture. Neurological status of the patients was determined by ISNCSCI, as well as by assessment of functional status by Spinal Cord Independent Measure. Before and after cell transplantation, magnetic resonance imaging (MRI) was performed for all the patients. Before the procedure, all the patients underwent electromyography, urodynamic study (UDS) and MRI tractograghy. After transplantation, these assessments were performed in special cases when the patients reported any changes in motor function or any changes in urinary sensation. RESULTS: Over the mean 30 months of follow-up, the radiological findings were unchanged without any evidence of neoplastic tissue overgrowth. American Spinal Injury Association class in one patient was changed from A to B, in addition to the improvement in indexes of UDS, especially bladder compliance, which was congruous with axonal regeneration detected in MRI tractography. No motor score improvement was observed among the patients. CONCLUSION: No adverse findings were detected at a mean of 30 months after autologous transplantation of the combination of MSCs and SCs through CSF. It may suggest the safety of this combination of cells for spinal cord regeneration.
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Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células de Schwann/transplante , Traumatismos da Medula Espinal/líquido cefalorraquidiano , Traumatismos da Medula Espinal/terapia , Regeneração da Medula Espinal , Adulto , Líquido Cefalorraquidiano/citologia , Doença Crônica , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Pessoa de Meia-Idade , Células de Schwann/citologia , Traumatismos da Medula Espinal/diagnóstico , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Resultado do TratamentoRESUMO
Treatment of previously untreated patients (PUPs) with severe haemophilia A is complicated by the formation of inhibitors. Prediction of PUPs with high risk is important to allow altering treatment with the intention to reduce the occurrence of inhibitors. An unselected multicentre cohort of 825 PUPs with severe haemophilia A (FVIII<0.01 IU mL(-1) ) was used. Patients were followed until 50 exposure days (EDs) or inhibitor development. All predictors of the existing prediction model including three new potential predictors were studied using multivariable logistic regression. Model performance was quantified [area under the curve (AUC), calibration plot] and internal validation (bootstrapping) was performed. A nomogram for clinical application was developed. Of the 825 patients, 225 (28%) developed inhibitors. The predictors family history of inhibitors, F8 gene mutation and an interaction variable of dose and number of EDs of intensive treatment were independently associated with inhibitor development. Age and reason for first treatment were not associated with inhibitor development. The AUC was 0.69 (95% CI 0.65-0.72) and calibration was good. An improved prediction model for inhibitor development and a nomogram for clinical use were developed in a cohort of 825 PUPs with severe haemophilia A. Clinical applicability was improved by combining dose and duration of intensive treatment, allowing the assessment of the effects of treatment decisions on inhibitor risk and potentially modify treatment.
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Fator VIII/imunologia , Hemofilia A/diagnóstico , Hemofilia A/imunologia , Isoanticorpos/imunologia , Adolescente , Criança , Pré-Escolar , Fator VIII/genética , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia A/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Razão de Chances , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Accumulated evidence have proposed that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are connected to breast cancer (BC) risk. We have done a case-control study with 258 BC patients and 209 control women to examine the potential association of Hsa-mir-603 rs11014002 C>T polymorphisms with BC susceptibility. The polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Our findings showed that the rs11014002 C>T variant was not associated with an increased risk of BC in codominant (OR=0.67, 95%CI=0.42-1.08, P=0.121, CT vs CC; and OR=0.18, 95%CI=0.02-1.67, P=0.170, TT vs CC), dominant (OR=0.64, 95%CI=0.41-1.01, P=0.062, CT+TT vs CC), and recessive (OR=0.20, 95%CI=0.02-1.81, P=0.178, TT vs CC+CT) inheritance models tested. While, the T allele significantly decreased the risk of BC (OR= 0.63; 95% CI =0.41-0.95; P=0.032) compared to C allele. In conclusion, the findings indicated that Mir603 rs11014002 T allele might contribute to decrease the risk of BC in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are warranted to confirm our findings.
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Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Gradação de Tumores , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , RiscoRESUMO
Soil samples at two depths were collected and analyzed to determine the concentrations of 16 polycyclic aromatic hydrocarbons (PAHs), organic carbon, and soil pH. The Σ16PAHs were 0.13 to 3.92 mg kg(-1) at depth 1 and 0.21 to 50.32 mg kg(-1)at depth 2. The averages of the PAH compounds indicate that the area is contaminated with oil, and this pollution was greater at depth 2. Interpolation maps showed that the southern region, especially at depth 2, has been contaminated more by anthropogenic activity. The diagnostic ratios indicate several sources of pollution of the agricultural soil. A comparison of average PAHs and standard values revealed that higher molecular weight compounds in the topsoil (InP and BghiP) and subsoil (BaA, BkF, BaP, DBA, and BghiP) exceed standard values for farmland. The pH interpolation map for both depths showed that most of the area has alkaline soil from long-term irrigation with untreated urban wastewater.
Assuntos
Agricultura , Monitoramento Ambiental , Indústria de Petróleo e Gás , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes do Solo/análise , Solo/química , Irã (Geográfico)RESUMO
PURPOSE: Non-obstructive azoospermia (NOA) is one the many causes of male infertility (10 %) resulting from testicular failure. Multiple testicular biopsies fail to find mature sperm in at least 50 % of cases Therefore; hunting for sensitive and specific biomarkers of spermatogenesis that could better determine the fertility status in NOA can lead to improved management of male infertility. Therefore, we evaluated sperm production through analyses of germ cell-specific transcripts (DAZ, TSPY1, SPTRX3 and SPTRX1) in semen and testicular biopsies of men with azoospermia. METHODS: We collected semen (N=83) and testis biopsies (N=31) from men with non-obstructive azoospermia. We later extracted RNA and synthesized cDNA using washed semen precipitate and testicular tissues. We also performed semi-nested PCR with designed specific primers. Using H&E method, an expert pathologist performed the histopathological evaluation. Having categorized the patients into three groups based on histopathological results, we calculated the agreement between molecular results of semen and tissues with histopathological findings for each patient using Kappa statistical test. RESULTS: Molecular findings of precipitated semen and testicular tissues were in disagreement with histopathological results in most cases. Molecular analysis of testis biopsies showed significant difference (Kappa coefficient=0.009, P value=0.894) with histopathological results; TSPY1, DAZ, SPTRX3 and SPTRX1 were respectively detected in 94 %, 94 %, 17.6 % and 52.9 % of men diagnosed with germ cell aplasia. CONCLUSIONS: Molecular analysis of semen does not provide sufficient sensitivity and specificity to be used as a screening test at the present time, but it is a useful adjunct to histopathological methods in men with NOA. Spermatid/sperm specific transcripts indicated the possibility to find mature sperm following repeated multiple testicular sperm extraction (TESE) or microdisection TESE (mTESE).
Assuntos
Azoospermia/genética , Infertilidade Masculina/patologia , Espermatogênese/genética , Testículo/patologia , Adulto , Azoospermia/patologia , Biópsia , Proteínas de Ciclo Celular/biossíntese , Proteína 1 Suprimida em Azoospermia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Infertilidade Masculina/genética , Masculino , Proteínas de Membrana/biossíntese , Proteínas de Ligação a RNA/biossíntese , Sêmen/citologia , Espermatozoides/patologia , Testículo/metabolismo , Tiorredoxinas/biossínteseRESUMO
The natural incidence of Tomato mosaic virus (ToMV) in common sow thistle (Sonchus oleraceus) from vegetable fields was assessed to determine the role of this weed species as a virus inoculum source. Twenty sow thistle plants with virus-like foliar symptoms including mosaic and malformations were collected from five vegetable fields in Tehran province, Iran, and analyzed by double antibody sandwich (DAS)-ELISA for the presence of ToMV, Tobacco mosaic virus (TMV), and Cucumber mosaic virus (CMV) using specific polyclonal antibodies (Agdia, Elkhart, IN). Six out of the 20 sow thistle plants tested by ELISA were infected with ToMV. This virus was detected in three of five vegetable fields surveyed, while CMV and TMV were not detected. Mosaic symptoms were associated with the ToMV infection, similar to those caused by TMV in common sow thistle in Iran (2). Viral infection was confirmed by RT-PCR using previously described specific primers to amplify a region in the coat protein gene of ToMV (3). The RT-PCR resulted in the amplification of an expected fragment of ~480 bp from ToMV-infected but not from healthy plants. The nucleotide sequence of the amplified DNA fragment was purified (GeneJET Gel Extraction Kit, Fermentas, Germany), directly sequenced, and deposited in GenBank as Accession No. KF527464. BLAST analysis showed 95 to 97% and 98 to 100% identity at the nucleotide and amino acid levels, respectively, with comparable sequences of other ToMV isolates (GenBank AF062519, FN985165, GQ280794, and JX857634). Mechanical inoculation of sow thistle plants with sap of symptomatic sow thistles reproduced symptoms of field-infected sow thistles. The presence of ToMV in the inoculated plants was confirmed by ELISA and RT-PCR. This suggested that ToMV could be the causal agent of the disease on sow thistle. In our earlier studies, the distribution and genetic diversity of ToMV isolates infecting vegetable crops and weed plants were studied (1); however, to our knowledge, this is the first report of ToMV infecting common sow thistle in Iran. References: (1) V. Aghamohammadi et al. J. Plant Pathol. 95:339, 2013. (2) A. Alishiri et al. Plant Pathol. J. 29:260, 2013. (3) B. Letschert et al. J. Virol. Methods 106:10, 2002.
RESUMO
PURPOSE: To describe the sensory innervation of the triangular fibrocartilage complex (TFCC) to understand the potential for selective denervation as an alternative treatment for recalcitrant pain from stable TFCC IA lesions after failed nonsurgical treatment. METHODS: Eleven fresh cadaveric limbs were dissected with × 3.2 loupe magnification in a proximal to distal manner. The candidate nerves were the dorsal cutaneous branch of the ulnar nerve, volar sensory branch of the ulnar nerve, anterior interosseous nerve, posterior interosseous nerve, medial antebrachial cutaneous nerve, and palmar cutaneous branch of the median nerve. We identified neural continuity to the TFCC histologically with S-100 protein antibody staining. RESULTS: In the 11 specimens, the TFCC was innervated by the dorsal cutaneous branch of the ulnar nerve (100%), medial antebrachial cutaneous nerve (91%), volar branch of the ulnar nerve (73%), anterior interosseous nerve (27%), posterior interosseous nerve (18%), and palmar branch of the median nerve (9%). CONCLUSIONS: These results provide an initial step in planning an operative partial TFCC denervation for recalcitrant TFCC IA injuries that fail nonsurgical treatment and possibly also arthroscopic debridement. CLINICAL RELEVANCE: Based on the results of this anatomic study, it is possible to create an algorithm for performing nerve blocks of the TFCC that would aid in planning a surgical denervation procedure.