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Textile-reinforced cementitious composites have great potential to offer novel design opportunities for thin-section structures thanks to their superior material capabilities. In this work, new cementitious composites with novel reinforcement configurations are developed, which have superior mechanical properties. The cementitious composites contain inclined through-the-thickness reinforcements, and their enhanced performance on thin-section material hardening under flexural loading is demonstrated. Furthermore, a new practical FE modeling approach is proposed that involves the combined use of multiple cohesive regions and 1D reinforcement elements that pass through these regions with a bilinear material law. This approach provides a new computationally efficient modelling framework whereby reinforcement pull-out during hardening is readily captured without resorting to computationally demanding interface laws between the reinforcement and the cementititous matrix. The model can model enhanced hardening of new configurations and provides comparable results with the experimental findings. The model can be used in the modelling and design of novel cementitious composites with engineered reinforcement configurations. Overall, this study aims to open up new avenues for the smart material design of cementitious composites with novel structural reinforcements. [ABSTRACT FROM AUTHOR]

We present a novel approach for estimating a scalar-on-function regression model, leveraging a functional partial least squares methodology. Our proposed method involves computing the functional partial least squares components through sparse partial robust M regression, facilitating robust and locally sparse estimations of the regression coefficient function. This strategy delivers a robust decomposition for the functional predictor and regression coefficient functions. After the decomposition, model parameters are estimated using a weighted loss function, incorporating robustness through iterative reweighting of the partial least squares components. The robust decomposition feature of our proposed method enables the robust estimation of model parameters in the scalar-on-function regression model, ensuring reliable predictions in the presence of outliers and leverage points. Moreover, it accurately identifies zero and nonzero sub-regions where the slope function is estimated, even in the presence of outliers and leverage points. We assess our proposed method’s estimation and predictive performance through a series of Monte Carlo experiments and an empirical dataset—that is, data collected in relation to oriented strand board. Compared to existing methods our proposed method performs favorably. Notably, our robust procedure exhibits superior performance in the presence of outliers while maintaining competitiveness in their absence. Our method has been implemented in the robsfplsr package in. [ABSTRACT FROM AUTHOR]

Melatonin (N‐acetyl‐5‐methoxytryptamine, MLT) is suggested as a preventive agent and potential therapeutic option for breast cancer via its antioxidant as well as anticancer effects by modulating estrogen dependent and independent pathways. However, its rapid metabolic inactivation led scientists to discover novel MLT analogues. Therefore, a series of new indole‐based hydrazide/hydrazone derivatives were synthesized and characterized as MLT analogues in the present study. The initial aim is to investigate the cytotoxicity of novel 1‐ethyl indole hydrazone derivatives against two human breast cancer cells (MCF‐7 and MDA‐MB‐231) as well as a non‐tumorigenic human breast epithelial cell (MCF‐10A). Selective cytotoxic compounds for cancer cells are further investigated for their effects on selected targets; agonist/antagonist activity on estrogen receptor (ER) and inhibitory effects on aromatase and CYP1B1. Their potential antioxidant activity was also investigated by both cell based and cell free in vitro assays. Possible binding of the compounds to the selected targets is also explored by molecular modelling studies. Nonsubstituted compound E1 inhibited human aromatase and the CYP1B1 enzyme with IC50 values of 0.89 μM and 0.5 μM, respectively. Compounds EI 4 and EI 11 exhibited ER antagonist activity with IC50 values of 2.88 μM and 5.29 μM, respectively. Additionally, both EI 4 and EI 11 inhibited CYP1B1 enzyme within 60–100 nanomolar range. In conclusion among 19 tested derivatives EI 1, EI 4 and EI 11 affected either one or more targets besides their selective cytotoxic effect for MCF‐7 cells suggesting that they can be promising candidates in prevention/treatment of ER‐positive breast cancer. Further studies are needed to elucidate their metabolism, in vivo effects, and safety. [ABSTRACT FROM AUTHOR]

The automatic dependent surveillance broadcast (ADS-B) system is one of the key components of the next generation air transportation system (NextGen). ADS-B messages are transmitted in unencrypted plain text. This, however, causes significant security vulnerabilities, leaving the system open to various types of wireless attacks. In particular, the attacks can be intensified by simple hardware, like a software-defined radio (SDR). In order to provide high security against such attacks, radio frequency fingerprinting (RFF) approaches offer reasonable solutions. In this study, an RFF method is proposed for aircraft identification based on ADS-B transmissions. Initially, 3480 ADS-B samples were collected by an SDR from eight aircrafts. The power spectral density (PSD) features were then extracted from the filtered and normalized samples. Furthermore, the support vector machine (SVM) with three kernels (linear, polynomial, and radial basis function) was used to identify the aircraft. Moreover, the classification accuracy was demonstrated via varying channel signal-to-noise ratio (SNR) levels (10–30 dB). With a minimum accuracy of 92% achieved at lower SNR levels (10 dB), the proposed method based on SVM with a polynomial kernel offers an acceptable performance. The promising performance achieved with even a small dataset also suggests that the proposed method is implementable in real-world applications. [ABSTRACT FROM AUTHOR]

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The genus Glaucium Mill., one of the important Papaveraceae family plants, is rich in isoquinoline alkaloids and distributed worldwide. Isolation and identification of bioactive alkaloids from Glaucium grandiflorum Boiss. & Huet. subsp. refractum (Nabelek) Mory var. torquatum (Cullen) Mory and G. corniculatum (L.) Rudolph var. corniculatum (Aslan 2012), and investigation of their antioxidant and anticholinesterase activities. The aerial parts of each plant were dried, powdered, and percolated with methanol, then each extract was fractionated between 50% aqueous acetic acid and petroleum. Their aqueous acidic layer was adjusted to pH 7–8 with NH4OH and extracted with chloroform, the extract was subjected to CC separation and isolation. Structures of the isolated alkaloids were elucidated by 1D and 2D-NMR and mass spectral analyses. The alkaloid extracts and their pure alkaloids were tested for anti-cholinesterase (AChE and BuChE) and antioxidant (ABTS, CUPRAC, β-carotene linoleic acid tests) activities in vitro. Methanol extracts of Glaucium grandiflorum subsp. refractum var. torquatum and G. corniculatum var. corniculatum afforded a novel compound glauciumoline and seven known isoquinoline alkaloids three of which have an aporphine-type and the other five have a protopine-type skeleton. Among them, trans-protopinium (7) and cis-protopinium (8) were isolated from a Glaucium species for the first time. Tertiary amine extracts (TAEs) of both plants showed very strong acetylcholinesterase inhibitory activity. The TAE of the plants also showed strong antioxidant activity while the isolated alkaloids showed no meaningful activity in the anticholinesterase and antioxidant tests. Glaucium species are considered promising therapeutic agents in the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Since some of the classical distributions fail to model data in statistics, necessity of having new distributions arises. Accordingly, studies about expanding well-known distribution families are increasing nowadays. In this paper, bivariate Ali-Mikhail-Haq copula family is reduced to univariate and under which conditions obtained distributions become a distribution function is investigated. Characteristics of these reduced distributions are reviewed, and parameter estimation is done with the help of maximum likelihood estimation method. The new distributions obtained by reducing bivariate or multivariate distributions to univariate are seen as more flexible than basic distributions. This flexibility leads us to think that use of this distribution for modelling different data sets and using them in various fields may be favourable. Therefore, our motivation for this article was to propose a method for reducing bivariate copulas to univariate, which has not been used in literature before. So that, wide range of use will be provided for modelling various data with this new method. The superiorities of the distributions used to model real data sets in the literature before and the newly proposed distributions are compared and evaluated in application. [ABSTRACT FROM AUTHOR]

We report a nine-year-old male having malignant peripheral nerve sheath tumor (MPNST) of the frontal bone, represented with a twelve-month history of ptosis and proptosis in his right eye and enlarged rapidly in the last three months. Except for slight numbness at his one-third of the right forehead, he had no neurological deficit. The patient's both eyes were having normal eye movements, and he had no visual acuity or field loss. After surgery, we observed the patient with no recurrence for 4 years. [ABSTRACT FROM AUTHOR]

Introduction: Mycosis fungoides (MF) is the most common cutaneous lymphoma, accounting for 50% of all cutaneous lymphomas. Programmed death-1 (PD-1; CD279) is a marker of follicular helper T cells and is expressed by the neoplastic T cells of some types of malignant lymphoma, including MF. About 30% of primary cutaneous T-cell lymphomas are CD30 positive and have a broad spectrum from lymphomatoid papulosis to primary cutaneous anaplastic large cell lymphoma. CD30 expression in MF is important for diagnostic purposes, prognostic value, and a therapeutic perspective. In this study, PD-1 and CD30 expression in early MF lesions has been examined, and its relationship between prognosis and survival has been questioned. The byproducts could be unorthodox treatment options. Methods: We prospectively applied immunohistochemically CD30 and PD-1 antibodies to the biopsies at our institution. We statistically evaluated the relationship between the expression rates of CD30 and PD-1 in atypical lymphocytes, with recurrence and survival. Results: This research with 119 patients was able to show a statistically significant relationship between CD30 and recurrence with PD-1 and poor survival. Conclusions: When evaluated together with treatment options, CD30 and PD-1 are markers that may guide the clinical follow-up of aggressive MF cases. [ABSTRACT FROM AUTHOR]

In this study, we examined executive function (EF) abilities, behavioral and emotional (BE) issues, and overall quality of life (QoL) of adolescents with obesity and compared them with a control group and also aimed to investigate whether the presence of insulin resistance (IR) is associated with these problems. This cross-sectional study included a sample of 50 adolescents aged 11–18 years with obesity and age- and gender-matched 50 normal weight adolescents who had attended and were treated at the pediatric outpatient clinic. Sociodemographic data were collected through personal interviews with the adolescents and their parents. Measurements of the height and weight, fasting blood glucose, and insulin levels of all adolescents were assessed. In addition, the participants and their parents completed the Kiddo-KINDL, the Strengths and Difficulties Questionnaire, and the Behavior Rating Inventory Scale from Executive Function. Of the 50 adolescents with obesity, 27 (54.0 %) were girls, and 23 (46.0 %) were boys, with a mean age of 14.06 ± 1.83 years. Adolescents with obesity have more EF deficiencies, BE difficulties, more problems in peer relationships and lower QoL scores than those without obesity. The QoL was worse in girls, adolescents with obesity, and those with IR. Adolescents with obesity and those with and without IR did not differ about EF deficiencies and BE problems. Addressing these EF deficits and BE problems in interventions for adolescents who have difficulty adapting to lifestyle changes, an essential part of obesity treatment in clinical practice, may contribute to treatment success. [ABSTRACT FROM AUTHOR]

Immunodeficient mice reconstituted with a human immune system (HIS mice) give rise to human T cells, which make them an attractive system to study human immune responses to tumors. However, such HIS mice typically exhibit sub-optimal responses to immune challenges as well as fail to develop antigen-specific B or T cell memory. Here we report HIS mice mediate spontaneous regression of human B cell lymphoma Raji. Tumor regression was dependent on CD4+ and CD8+ T cell responses and resulted in T cell memory. The T cell memory elicited was mainly Raji-specific, however some level of cross-protection was also elicited to a related B cell lymphoma cell line Ramos. Single-cell RNAseq analysis indicated activation of CD8+ T cells in regressing Raji tumors as well as clonal expansion of specific T cell receptors (TCRs). Cloning of TCRs from Raji-infiltrating T cells into a Jurkat reporter cell line showed reactivity specific for Raji tumor cells. Overall, we report a platform for studying in vivo human T cell tumor immunity by highlighting spontaneous Raji tumor regression, clonal TCR expansion, and T cell memory in HIS mice. Raji tumor spontaneously regresses via human T cell-mediated tumor control in human immune system-reconstituted mice. [ABSTRACT FROM AUTHOR]

Melatonin (MLT) is a hormone that is secreted from pineal gland and regulates the circadian rhythm. It is reported to have anticancer effects in hormone dependent breast cancer via endocrine modulation, namely by antagonising the estrogen receptor (ER) or by inhibiting aromatase enzyme. However, its use is restricted because of its short half-life and poor bioavailability. Therefore, indole derived MLT analogues were synthesized previously, and they were shown to have potential antioxidant and anticancer effects. The present research is aimed to investigate the potential of MLT and its two newly synthesized analogues (M6 and M20) on steroidogenesis pathway by using an OECD validated in vitro method, H295R steroidogenesis assay (TG-456 test guideline). The compounds were incubated with H295R, human adenocarcinoma cells, for 48 hours and the hormone levels (testosterone; T and estradiol; E2) were detected by LC-MS/MS. The partial validation of the method was performed by using reference compounds forskolin, prochloraz, letrozole and ketoconazole. MLT decreased both E2 and T levels and its effect on E2 levels were dose dependent. On the other hand, M6 and M20 showed biphasic effects on both hormone levels. None of the compounds decreased H295R cell viability. These results demonstrate that depending on the use and the dose of these melatonin analogues, their potential effects on hormone production can result either in a therapeutical effect (such as anticancer agent) or a non-targeted endocrine related adverse effect when used as a pharmaceutical. [ABSTRACT FROM AUTHOR]

In the rubber industry, fillers are used to improve certain properties of rubber composites and to make rubber compound recipes cheaper. In this study, the usability of boron industrial waste clay with no monetary value in place of silica filler with commercial value in the rubber industry was investigated and a more economical compound recipe was tried to be obtained. For this purpose, firstly, boron industrial waste clay was characterized by X-ray fluorescence spectrometer, X-ray diffractometer and scanning electron microscope, and thermogravimetric analysis-differential thermal analysis. Then, the boron samples were used instead of commercial silica, which is the filler widely used in the production of conveyor belts, and both laboratory scale and industrial scale production of boron industrial waste filled rubber composites (BIWFRC) were carried out. The rheological and physico-mechanical properties (tensile strength, elongation at break, abrasion, hardness) of BIWFRC were compared with the properties of silica filled rubber composites (SFRC). Furthermore, the effect of thermal oxidative aging on both the tensile strength and elongation at break of SFRC and BIWFRC was also investigated. According to the results, it has been observed that the filler material obtained from boron wastes can be used in rubber products. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the effects of various obstetric and perinatal factors on the severity of retinopathy of prematurity (ROP). Methods: Infants born at ≤ 32 weeks of gestation, with less than 1500 g gestational weight and having at least stage 1 ROP, were reviewed. Group1A included treatment-requiring ROP (TR-ROP), and group 2A included the remaining patients not requiring treatment. Group 1B included stage 3 ROP cases, and group 2B included the remaining stage 2 or 1 ROP cases. Group 1C included cases with zone III disease, and group 2C the remaining. The control group (group C) was composed of premature infants without ROP. The multiple comparisons were made among groups 1A, 2A, and C; 1B, 2B, and C; 1C, 2C, and C. Results: A total of 311 infants were included. Group 1A included 34 cases, group 1B 60, group 1C 51, and group C 98. Antenatal steroid administration, gestational diabetes mellitus (GDM), gestational weight (GW), gestational age (GA), sepsis, continuous positive airway pressure (CPAP) time, and invasive mechanical ventilation (MV) time were associated with TR-ROP, stage 3 ROP, and zone I, and II disease (p < 0.05). Pregestational diabetes mellitus (DM) was only associated with stage 3 ROP (p = 0.031). Gestational hypertension was only associated with zone I and II disease (p = 0.034). The use of low-molecular-weight heparin may be protective against stage 3 disease (p = 0.031). Conclusion: Antenatal steroid administration, GDM, GW, GA, sepsis, CPAP time, and invasive MV time were risk factors for TR-ROP and stage 3 ROP, while pregestational DM was only associated with stage 3 ROP. [ABSTRACT FROM AUTHOR]

Pedagogical beliefs are a critical factor in terms of integrating technology into teaching, but very few technology acceptance models (TAMs) have considered them. Hence, this study aims to extend the TAM by incorporating pre-service teachers' conception of teaching and learning. The revised model examined the influence of pre-service mathematics teachers' constructivist and traditional pedagogical beliefs on their technology acceptance through perceived ease of use, perceived usefulness, attitude toward technology, and behavioral intention to use. Survey data were collected from 714 pre-service mathematics teachers in Turkey and analyzed through path analysis. The results showed that pre-service mathematics teachers' pedagogical beliefs were more constructivist-oriented than traditional-oriented, and constructivist beliefs had a significant influence on the components of the TAM. On the other hand, pre-service teachers' traditional-oriented beliefs did not influence their perceived usefulness of and attitudes toward technology but had positive effects on perceived ease of use. Implications for pre-service mathematics teacher education were discussed. [ABSTRACT FROM AUTHOR]

The incidence of obesity and related diseases has increased dramatically in the last decade. Some endocrine disruptors have been shown to interact with metabolic processes via various cellular mechanisms, and disrupt homeostasis in adipose tissue, resulting in weight gain and obesity. These chemicals are called "obesogens". Today, with the increased use of industrial chemicals, individuals are exposed to a mixture of chemicals at very low doses. Most of these industrial chemicals have been investigated for their possible endocrine-disrupting and obesogenic effects. Besides these chemicals, pharmaceuticals can also have similar adverse effects; however, limited studies have been performed to investigate such effects of drugs. Furthermore, there are few studies investigating the relationship between prenatal exposure to pharmaceuticals and childhood obesity. Therefore, to clarify the endocrine-disrupting and obesogenic effects of the pharmaceuticals, which are prescribed during pregnancy, mechanistic studies should be performed, and necessary precautions should be taken. In this paper, we reviewed the mechanisms of obesogens, briefly overview several well-known obesogenic industrial chemicals, and focused more on potential obesogenic pharmaceuticals. [ABSTRACT FROM AUTHOR]

Objectives: Factors associated with disease activity of axial spondyloarthritis (axSpA) and switching of biologic disease-modifying anti-rheumatic drugs have not been clearly defined. We aimed to evaluate clinical characteristics of patients with axSpA, factors related to remission in treat to target era and predictive factors for biologic disease-modifying anti-rheumatic drug switching. Method: A multicenter, observational cross-sectional study was performed between February 2019 and August 2019. We included all consecutive patients ≥ 18 years with axSpA. Demographic and clinical variables were prospectively recorded. Clinical tools included Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). Results: There were 969 patients with a mean age of 43.4 ± 10.8 years. There were 143 patients (14.8%) with remission and 223 (23.1%) patients with low disease activity. Male sex (p = 0.021), positive family history (p = 0.036), and human leukocyte antigen-B27 (p = 0.011) were predictors of remission by ASDAS-CRP. There were 654 patients (67.5%) who did not switch to another drug. The highest BASMI and MASES scores were calculated in patients with very high disease activity (p < 0.05). In patients with drug switching, the disease duration was significantly higher (p < 0.001) and the age at diagnosis was significantly lower (p = 0.016). There were significantly more patients with uveitis and higher scores of MASES and BASMI in patients who switch to another biologic disease-modifying anti-rheumatic drugs (p = 0.003, p = 0.009, and p = 0.004, respectively). Conclusions: In patients with axSpA, male sex, younger age, and HLA-B27 positivity are associated with remission, while longer disease duration and accompanied uveitis appear to be related with drug switching. Clinical trial registration number and date: NCT04139954/25.10.2019. Key Points • Achievement of remission and/or low disease activity rates in patients with axSpA were assessed in a big registry from a real-life data. • Predictive factors for switching to another bDMARD were evaluated in axSpA patients. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have major functions in the development and progression of colorectal cancer (CRC) as tumor suppressors or oncogenes. The aim of the current research was to assess the role of miR-485-3p and miR-4728-5p in the pathogenesis of CRC. In this study, fresh tumor and adjacent non-tumor tissue samples were obtained from a total of 59 CRC patients, 37 from colon and 22 from rectum. The expression profiles of miR-485-3p and miR-4728-5p were determined using qRT-PCR. miRNA-related transcription factor (TF) regulatory networks were constructed using the TransmiR v2.0, TF-regulated target genes were determined using the Human.mirFFL.DB and TRRUST v2.0, functional annotation and pathway enrichment analyses were performed using DIANA-mirPath v3.0 and -Tarbase v7.0. The results demonstrated that the expression levels of both miR-485-3p and miR-4728-5p were very significantly downregulated in CRC tissues (fold changes = 0.42 ± 0.70 and 0.59 ± 1.06, respectively; both p = 0.000). On the other hand, lower expression levels of miR-485-3p were detected in the both rectum and colon. Moreover, the decrease in the expression levels of miR-4728-5p was correlated with increasing age. However, these differences were not statistically significant according to the FDR-related p‑values (0.126 and 0.168, respectively). By bioinformatics analyses, miR-485-3p and miR-4728-5p-related TFs were identified. Some of these TFs, namely, AR, CREB1, CEBPB, FOXA1, GTF2I, MAZ, NCOR2, NFIC, NRF1, SIN3A, SREBF1, SREBF2, p53 and YY1, appeared to be associated with CRC and were, therefore, selected to construct miRNA‒TF-gene networks of potential targets for the early diagnosis and treatment of CRC. Pathway enrichment analysis indicated Hippo signaling pathway as heavily regulated by miR-485-3p. It seems that the decrease in expression levels of miR-485-3p and miR-4728-5p might be associated with development of colorectal cancer. [ABSTRACT FROM AUTHOR]

This paper uses bibliometric analysis to evaluate the literature on immigration, crime, and violence to find out how these concepts are studied across disciplines. The paper gave specific attention to the field of Criminology to demonstrate the variation of the use of these concepts in the literature and how much it differs from other disciplines. To meet these expectations, we examined how journals are categorized based on covering how immigration and crime interact in social science disciplines. Moreover, the analysis maps how research articles interact in different journals and what types of topics receive the most attention among researchers by looking at cross-citation data and keyword selection. The findings show that, overall, the number of publications used at least one of the studied items (immigration, crime, and violence) as a keyword increased tremendously in the last two decades. The most studied concept amongst all disciplines is violence, followed by gender and crime with the combination of migration, immigration, immigrants. The topic has been mostly studied from the 'receiving country' perspective and funding leads to an increase in publications. The findings suggest Criminology is the top field producing most of the studies in the field followed by public healthrelated research. These findings suggest that migration, when it is connected to crime and violence, is considered an individual- and social-level challenge requiring the attention of experts in understanding criminal and deviant behavior as well as experts from public health. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis is a chronic inflammatory disease with different disease activity grades. Several registries have been designed to determine the appropriate regimens of disease-modifying antirheumatic drugs to obtain sustained clinical remission. We examined epidemiological and clinical characteristics of rheumatoid arthritis patients using a clinical registry database (BioSTaR) and analyzed the differences in patients with sustained and switched therapies. Methods: A multicenter, observational cross-sectional study for rheumatoid arthritis was performed between February 2019 and September 2020 using the BioStaR-RA registry. Demographic and clinical characteristics were prospectively recorded into a specifically designed electronic database. The patients were divided into three groups due to the heterogeneity of the study cohort. Patients were grouped as Group I (Initial; within the first 6 months of treatment with biological/targeted synthetic drugs), Group ST (Sustained Treatment; any first drug lasting for at least 6 months without any change), and Group S (Switch; any switching to another drug). Comparative analysis was performed between sustained treatment (Group ST) and drug switching (Group S) groups. Results: The study included a total of 565 patients. The mean age was 53.7 ± 12.8 years, and the majority were female (80.4%). There were 104, 267, and 194 patients in Groups I, ST, and S, respectively. Erosive arthritis and hematological extra-articular involvement were more frequently detected in Group S than Group ST (p = 0.009 and p = 0.001). The patients in Group S had significantly higher disease activity scores (DAS28-CRP, CDAI, and SDAI) (p = 0.025, p = 0.010, and p = 0.003). There were significantly more patients with moderate disease activity in Group S (p < 0.05). Conclusions: The groups with sustained treatment and switching included patients with different disease activity status, although higher disease activity was determined in switchers. Overall, moderate disease activity and remission were the most common disease activity levels. Lower disease activity scores, lower hematologic manifestations, better functional status, and lesser radiographic damage are associated with sustained treatment. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the histopathological and analgesic effects of intrathecal administration of dexmedetomidine, preservative-free racemic ketamine, and magnesium sulfate in Sprague Dawley rats. This study included 40 male Sprague Dawley rats weighing between 240 and 260 g. After the intrathecal catheterization, the rats were randomly divided into four groups. Following the baseline measurements, no drugs were administered in the control group (group C). Simultaneously, 0.02 ml (1 μgr/kg) of dexmedetomidine was administered in group D, 0.02 ml (1 mg/kg) preservative-free racemic ketamine in group K and 0.02 ml (0.05 mg/kg) magnesium sulfate in group M via intrathecal route. Concomitantly, the hot-plate test was used to measure the analgesic effect of drugs. For histopathological evaluation, the rats were sacrificed to obtain the medulla spinalis. Results: The hot-plate test revealed that the mean response time was 6.3 ± 1.2 s in baseline measurements without medication. However, prolongation in the mean response times of the drug-administered groups to the hot-plate test was also observed. Upon histopathological examination, myelin degeneration was detected in all study groups. No inflammation was observed in rats in group D, whereas inflammation was noted in only two rats in group K. Concerning the presence of red neurons, the only group that differed from the control group belonged to group K. Conclusions: Dexmedetomidine, preservative-free racemic ketamine, and magnesium sulfate have an analgesic effect when administered intrathecally in rats. Of these drugs, preservative-free racemic ketamine stands out as the most histopathologically safe drug. [ABSTRACT FROM AUTHOR]

With the increasing demands of technology integration by the institutions, educators felt the need to develop themselves professionally. In this study, as a way of professional development, we focused on one-on-one technology mentoring for in-service teachers because the experiences of mentors would shed light on professional development programs in the context of both mentors’ progress and mentoring in-service teachers. Mentors for teachers were assigned to facilitate teachers’ ICT usage and ICT integration skills. The mentorship implementation lasted two semesters with 42 mentors’ participation. The determination of the content of the mentoring process was completely based on the needs and interests of the teachers. After the implementation, the perceptions and experiences of the mentors were asked and coded through content analysis. According to the analysis, the responses of the mentors were grouped into five main categories; (a) affordances of the technology mentoring process, (b) the contribution of the project to the teachers, (c) the contribution of the project to the mentors, (d) the challenges experienced by the mentors, and (e) the weaknesses of and the suggestions for the mentoring process. The findings of this study indicated that future ICT coordinators believed that one-on-one technology mentoring in real school settings is an effective way not only for training in-service teachers but also for creating awareness of being an ICT coordinator and developing ICT mentoring skills. [ABSTRACT FROM AUTHOR]

Following the recent developments in information and communication technologies (ICT), educators cannot opt-out using technology in educational settings. Yet, research studies have indicated that teachers' lack of ICT knowledge is considered among the barriers for successful technology integration. Within this framework, this study aimed at documenting the perceptions of in-service teachers about individualized technology-related (ITR) mentoring processes based on the TPACK model. The ITR mentorship provided one-to-one mentoring sessions lasting two semesters at the schools where the teachers worked. The collaboration between the mentor and the mentee (teacher), called ITR mentorship, included not only the support for technological needs of the teachers but also preparing course materials for teaching specific content of the subject. Through mixed methodology, quantitative and qualitative data were collected from participating 31 (17 mathematics and 14 language) teachers. At the end of the study, the change in perceived TPACK levels of teachers was quantitatively examined and qualitatively supported with their views on this process. It was found that technology-related TPACK constructs significantly increased through one-to-one mentoring due to its non-threatening atmosphere, enabling flexible time and content, and addressing the needs of the teachers. In the light of these findings, the ITR mentorship can be suggested for the professional development of teachers and considered for in-service teacher trainings. [ABSTRACT FROM AUTHOR]

The rheumatoid arthritis impact of disease (RAID) score was developed as a patient-derived composite response index for the evaluation of the disease impact on cases with rheumatoid arthritis (RA). The aim of this study was to evaluate the psychometric properties and performance of RAID score in the real-life settings. Cases with RA from our multi-center, nationwide registry called Biologic and targeted Synthetic antirheumatic drugs Registry RA (BioStaR RA) were included in this cross-sectional observational study. Demographic data, disease duration, pain, patient's global assessment (PGA) and physician's global assessment (PhyGA) were recorded. DAS28-ESR, DAS28-CRP, the simplified disease activity index (SDAI) and the clinical disease activity index (CDAI) were assessed as disease activity evaluations. The health assessment questionnaire-disability index (HAQ-DI) and RAID were completed by all the participants. The construct validity was tested by the analysis of correlations between RAID score and scores of PGA, disease activity indexes and HAQ-DI. We also evaluated the discriminatory ability of RAID to distinguish patients with different levels of disease activity and disability and the cut-off values were calculated by ROC analysis. 585 cases with RA were included in this investigation. The RAID score was significantly positively correlated with PGA, all disease activity indexes and HAQ-DI (p < 0.001). The discriminatory ability of RAID score in different disease activity and disability groups was also demonstrated (p < 0.001). To estimate DAS28-ESR (remission/low + moderate + high), RAID score cut-off points were 2.88 (sensitivity 73%, specificity 62%), 3.23 (sensitivity 75%, specificity 60%) and 3.79 (sensitivity 74%, specificity 58%), respectively. Our study indicated that RAID was a reliable tool in daily clinical practice by presenting its correlations with disease activity and disability assessments and by showing its discriminatory ability in these parameters in the real-life experiences. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the effect of subacromial decompression on the results of full thickness rotator cuff repair applied arthroscopically. Examination was also made of the effect of acromion type on the subacromial decompression procedure in patients applied with arthroscopic rotator cuff repair. Methods: The study included a total of 150 patients, comprising 102 (68%) females and 48 (32%) males with a full thickness rotator cuff tear repaired arthroscopically. The patients were separated into three groups of 50. Group A comprised those with acromioplasty and bursectomy applied additional to the repair. In Group B, only bursectomy was performed additional to the repair and in Group C, only rotator cuff repair was applied. Evaluation was made of the post-operative long-term pain and functional results. Results: The mean age of the cases was 65.63±9.22 years (range, 46-86 years). The affected side was right side in 95 (63.3%) cases and left side in 55 (36.7%). No statistically significant difference was determined between the groups according to the post-operative Constant Murley and ASES scores (p>0.05). In the paired comparisons, the post-operative VAS scores of Group C were higher than those of Groups A and B (p=0.018, p=0.029, p<0.05). No statistically significant difference was determined between Group A and Group B in respect of the post-operative VAS scores (p>0.05). Conclusion: In the arthroscopic repair of full thickness rotator cuff tears, neither acromioplasty, coracoacromial ligament loosening nor bursectomy were determined to have any positive effect on the results. Whatever the acromion type, there is no need for an additional subacromial decompression procedure after rotator cuff repair, in respect of pain and functional outcomes. Only acromial spurs should be gently removed paying attention to the coraco-acromial ligament. [ABSTRACT FROM AUTHOR]

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects. [ABSTRACT FROM AUTHOR]

Among teacher beliefs, technology acceptance has a crucial role in effective technology integration into teaching. There is a need to examine the factors affecting future teachers' acceptance of technology in Turkey, where great investments have been made on the dissemination of technology in schools, and great emphasis has been put on the effective use of technology. The purpose of this study was to investigate Turkey's pre-service mathematics teachers' intentions to use technology in their future teaching. Technology Acceptance Model (TAM) was used as a framework and was expanded with different variables, including facilitating conditions, subjective norms, and technology self-efficacy. In this study, the relationships between these variables were examined. Data were collected from 530 pre-service mathematics teachers using a self-reported questionnaire, which explained their intentions to use technology. To test the model, a structural equation modeling approach was used. The results indicated that facilitating conditions, subjective norms, and attitudes toward technology were significant predictors of intention to use technology. Technology self-efficacy significantly determined the perceived ease of use. Perceived ease of use and perceived usefulness of technology significantly influenced pre-service teachers' attitudes toward technology. Not only technical infrastructure but also technical and design support would be provided in schools to increase pre-service teachers' intention to use technology. In addition, teacher educators would provide learning environments where pre-service teachers experience more with current technology. [ABSTRACT FROM AUTHOR]

Cancer is a serious health problem. It still affects millions of people. In vitro cell culture is a method used to study the behavior of cells. The interest in grape seed is due to its high content of antioxidants in the form of proanthocyanidins. Its antioxidant capacity is greater than known antioxidants. Ishikawa cells were cultured in complete DMEM/F-12 medium containing 100 units/mL-100 µg/mL of penicillinstreptomycin and 10% fetal bovine serum in 37 °C and 5% CO2 incubator. After incubation of Ishikawa cells MTT (5 mg/mL) dye was added (20 µL/well) and plates were incubated again for two hours. Cell death mode triggered by grape seed extract on Ishikawa cells was analyzed by using the Annexin-V technique. To test the activation of caspases on Ishikawa cells exposed to grape seed extract Caspase 3/7 technique was used. For analysis of results one way variance analysis for multiple comparisons of GraphPad Prism 6.0 for Windows was used. Grape seed extract showed its toxicity on Ishikawa cells in dose dependent manner in 24 and 48 hours of exposure. Annexin-V technique showed that grape seed extract induced apoptosis on Ishikawa cells. When compared to the control group. Ishikawa cells treated with grape seed extract imply to total apoptosis percentage of 22.90%. Based on this finding it can be concluded that grape seed extract has apoptosis inducing activity on Ishikawa cells in short application time. Thus, grape seed extract worth to be elucidated for its further anticancer effects with deeper mechanistic studies in order to provide an option for designing novel anticancer drug as supplement or alternative to current chemotherapeutics. [ABSTRACT FROM AUTHOR]

Cancer is a serious problem with significant impacts on health systems. Combination therapy is the cornerstone of cancer treatment today. Our research aims to obtain specific data about the agents that can be used in combination with chemotherapeutics in cancer treatment. In our study MTT cytotoxicity assessment, transmission electron microscopic analysis of ultrastructural changes, detection of phosphatidylserine translocation and caspase 3/7 analysis were performed on Ishikawa cancer cell lines. Cytotoxicity test results showed that resveratrol has ant proliferative activity on Ishikawa cells in a dosedependent manner. Transmission electron microscopy findings indicated important ultra-structural changes on Ishikawa cells caused by resveratrol. Apoptotic profiles of Ishikawa cells were investigated via the annexin-V technique. Compared to the control Ishikawa cells in the population of resveratrol treated cells, the percentage of total apoptotic cells were detected to be 27.75%. Activation of caspases is an indicator of apoptosis pathways that are triggered into the cells. The total percentage of activated caspases was detected to be 5.35% when compared to that of control cells. The highlight of our research is the transmission electron microscope examination. With this examination, morphological changes in mitochondria caused by the anticancer effect of resveratrol were determined. [ABSTRACT FROM AUTHOR]

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The purpose of this study was to investigate the human security aspect of the Syrian refugee crisis and to analyse the vulnerability and victimization of Syrian refugees in Turkey. Among the several categories within the human security model (i.e. economic, food, health, environmental, personal, community, and political) as conceptualized by the United Nations Development Programme (UNDP), the study analysed the personal (i.e. individual) security of Syrian refugees in Turkey. A qualitative research design was employed with an applied ethnographic approach which included semi‐structured interviews, observations, document analysis, and field notes. Five main themes were identified regarding the personal security of Syrians: violence, homelessness, prostitution and early marriage, child labour, and deadly journeys. The results of the study indicate that Syrian refugees are exposed to several human insecurity parameters at the individual level, which are largely neglected by the Turkish state. Consequently, Turkey's failure to promote the human security of the Syrian refugees contributes to their forced migration to Western countries, where 'freedom from fear', 'freedom from want', and 'freedom from indignity' are relatively assured. [ABSTRACT FROM AUTHOR]

This work reports the production of activated carbons (AC) from bitter orange peel by using ZnCl2 or H3PO4 as activating agent at two different carbonization temperatures (450 °C and 550 °C). Surface morphology analyses of produced bitter orange activated carbons (BOACs) were done by SEM. The surface areas of the produced BOACs, functional groups on the AC surfaces and compositions, were determined by using BET, FT-IR, and TGA analyses. Furthermore, their application for the removal of methylene blue (MB) was studied. The parameters affecting adsorption, such as pH and temperature, were evaluated. BOAC produced with ZnCl2 at 550 °C, exhibits the highest surface area (1450.6 m2 g−1), whereas BOAC produced with ZnCl2 at 450 °C yielded with the highest adsorption capacity (108.9 m2 g−1). Langmuir isotherm shows a good fit for the BOACs. Adsorption kinetics were studied and follows pseudo-second-kinetic model. The thermodynamic parameter studies indicate that the adsorption process is endothermic and spontaneous. [ABSTRACT FROM AUTHOR]

A fundamental understanding of the evaporation/condensation phenomena is vital to many fields of science and engineering, yet there is many discrepancies in the usage of phase-change models and associated coefficients. First, a brief review of the kinetic theory of phase change is provided, and the mass accommodation coefficient (MAC, α) and its inconsistent definitions are discussed. The discussion focuses on the departure from equilibrium; represented as a macroscopic "drift" velocity. Then, a continuous flow, phase change driven molecular-dynamics setup is used to investigate steady-state condensation at a flat liquid-vapor interface of argon at various phase-change rates and temperatures to elucidate the effect of equilibrium departure. MAC is computed directly from the kinetic theory-based Hertz–Knudsen (H-K) and Schrage (exact and approximate) expressions without the need for a priori physical definitions, ad-hoc particle injection/removal, or particle counting. MAC values determined from the approximate and exact Schrage expressions ( α a p p S c h r a g e and α e x a c t S c h r a g e ) are between 0.8 and 0.9, while MAC values from the H-K expression ( α H − K ) are above unity for all cases tested. α e x a c t S c h r a g e yield value closest to the results from transition state theory [J Chem Phys, 118, 1392–1399 (2003)]. The departure from equilibrium does not affect the value of α e x a c t S c h r a g e but causes α H − K to vary drastically emphasizing the importance of a drift velocity correction. Additionally, equilibrium departure causes a nonuniform distribution in vapor properties. At the condensing interface, a local rise in vapor temperature and a drop in vapor density is observed when compared with the corresponding bulk values. When the deviation from bulk values are taken into account, all values of MAC including α e x a c t S c h r a g e show a small yet noticeable difference that is both temperature and phase-change rate dependent. [ABSTRACT FROM AUTHOR]

The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is used as a new instrument in measuring the function, disability and health of patients with spondyloarthritis (SpA). However, the real-world evidence of ASAS HI is very limited. In the present study, our objective is to evaluate the psychometric properties and performance of ASAS HI in the real-world setting as well as comparing ASAS HI with the current instruments to assess the construct validity and determine the cut-off points in patients with both ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). A total of 991 patients with axSpA who fulfilled either the ASAS classification criteria for axial SpA (axSpA) or the Modified New York Criteria (mNY) for AS were recruited from the Biologic and targeted Synthetic antirheumatic drugs Registry (BioStaR) SpA. The construct validity of ASAS HI against the Bath Ankylosing Spondylitis Disease Activities Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score–C-Reactive Protein (ASDAS-CRP) the Bath Ankylosing Spondylitis Functional index (BASFI) was performed. Using the receiver operating characteristic (ROC) curves analysis, the cut-off points were calculated. Of all the recruited patients, 851 (85.9%) were AS and 140 (14.1%) were nr-axSpA. The difference in the mean ASAS HI scores of the patients with AS and the ones with nr-axSpA were not statistically significant (6.12 ± 4.29 and 6.42 ± 4.86, respectively). The mean ASAS HI score was significantly higher in females and small city residents. The ASAS HI had a strong construct validity against ASDAS-CRP, BASDAI and BASFI. A cut-off point of ≤ 4 was determined to discriminate good and moderate, as well as ≥ 12 to discriminate moderate and poor health status. In conclusion, ASAS HI is a reliable instrument to evaluate health and functioning for both patients with AS and nr-axSpA in clinical practice. [ABSTRACT FROM AUTHOR]

Aim: Adolescence is an important period of development and during this period young people are more susceptible to mental illnesses. Therefore, a comprehensive knowledge of the factors that mediate stress response can help developing our understanding of these diseases. The aim of this study is to examine the activity of hypothalamo–pituitary–adrenal axis and determine factors affecting this activity in adolescents. Material and Methods: The adolescents between the ages of 14 and 17, who participated in the official amateur tennis tournament, were included in the study. The data form, including questions for the assessment of the stress level and sociodemographic variables was filled. Then, salivary cortisol levels were measured before (-5 minutes) and after (+5 minutes) the first match of the official tennis tournament. Results: The mean salivary cortisol levels were 40.8±53.8 ng/ml, before the game and 98.8±150.5 ng/ml, after the game (p=0.008). The salivary cortisol levels were statistically higher, after the game, in males, those who won, and those who felt anxious compared the before. Conclusion: The results of this study showed that salivary cortisol level can be used in the assessment of stress response in adolescents and various factors such as gender, mood, and state of winning are effective on cortisol response. [ABSTRACT FROM AUTHOR]

AIM: This study aims to compare the protective effects of ambrisentan, a selective endothelin typeA receptor antagonist, and bosentan, a dual endothelin typeA/B receptor antagonist, on experimental renal ischemia reperfusion injury. METHOD: The study sample consisted of 21 female rats, which were divided into 3 groups: Control, Ambrisentan and Bosentan. For the ischemia-reperfusion injury model, left-kidney nephrectomy was performed after sacrificing the animals. In the immunohistochemical examination, caspase-3 was examined, and then the apoptotic index was determined. In the biochemical examination, the activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase, and the levels of nitrite (NOx), TNF-a, and IL-1ß were determined. RESULTS: There were statistically significant differences between the groups in terms of total injury score grade in range of 0 3 (p=0.001). The glomerular and tubular apoptotic indices were higher in the control group as compared to those of the ambrisentan and bosentan groups (p=0.001). There were no statistically significant differences in terms of SOD, CAT, GPx, MDA, IL-1ß and TNF-a measurements among the groups (p>0.05). CONCLUSIONS: In the experimentally created renal ischemia reperfusion model, both ambrisentan and bosentan increased the NOx level, decreased the apoptosis, and protected the kidney from renal ischemia reperfusion injury. However, no significant superiority was found between ambrisentan and bosentan in terms of their protective effects (Tab. 3, Fig. 2, Ref. 31). [ABSTRACT FROM AUTHOR]

Clinical observations suggest that responses to cancer immunotherapy are correlated with intra-tumoral T cell receptor (TCR) clonality, tumor mutation burden (TMB) and host HLA genotype, highlighting the importance of host T cell recognition of tumor antigens. However, the dynamic interplay between T cell activation state and changes in TCR repertoire in driving the identification of potential immunodominant antigen(s) remains largely unexplored. Here, we performed single-cell RNA-sequencing on CD8+ tumor-infiltrating T cells (TILs) using the murine colorectal tumor model MC38 to identify unique TCR sequences and validate their tumor reactivity. We found that the majority of clonally expanded TILs are tumor-reactive and their TCR repertoire is unique amongst individual MC38 tumor-bearing mice. Our query identified that multiple expanded TCR clones recognized the retroviral epitope p15E as an immunodominant antigen. In addition, we found that the endogenous retroviral genome encoding for p15E is highly expressed in MC38 tumors, but not in normal tissues, due to epigenetic derepression. Further, we demonstrated that the p15E-specific TILs exhibit an activated phenotype and an increase in frequency upon treatment with anti-41BB and anti-PD-1 combination immunotherapy. Importantly, we showed that although p15E-specific TILs are not required to mount a primary anti-tumor response, they contributed to the development of strong immune memory. Overall our results revealed that endogenous retroviral antigens expressed by tumor cells may represent an important and underappreciated category of tumor antigens that could be readily targeted in the clinic. [ABSTRACT FROM AUTHOR]

Introduction: Many women and men of reproductive age want to regulate their fertility. Among the contraceptive methods, intrauterine devices are especially preferred. However, the most important disadvantage of the intrauterine devices is pelvic infection. In this retrospective study, the aim was to examine the relationship between IUD use and pelvic infection. Methods: Our research was planned as a retrospective study. 76 women diagnosed with pelvic infection in our hospital constitute the case group, and 80 women who applied to the outpatient clinic with different gynecological problems other than infection constitute the control group. The contraceptive method used by the participants was determined from the information obtained. The contraceptive method last used by the participants in the reproductive period was taken as a basis. Results: There was no statistical difference between the two groups in terms of age, parity, gravida, and the number of living children (p>0.05). It was determined that the frequency of pelvic infection was higher in intrauterine devices users compared to the control group. This is also statistically significant (p<0.01). Participants using intrauterine devices and non-intrauterine devices users were compared for signs and symptoms of infection. It was observed that intrauterine devices users who underwent tubo-ovarian abscess had a statistically significantly lower response to medical treatment compared to those who did not use IUDs (p<0.01). Conclusion: Pelvic infections must be ruled out before intrauterine devices application. After intrauterine devices application, women should be educated about the signs and symptoms of pelvic infection and carefully monitored. [ABSTRACT FROM AUTHOR]

With the rapid developments in technology, training of pre-service teachers in terms of technology integration has become a crucial issue for all stakeholders of education. However, it is important to investigate the relationships among pre-service teachers' teaching beliefs, skills, and educational technology integration competencies before training pre-service teachers of all fields. Within the scope of this objective, a model was proposed to investigate the relations among pre-service teachers' epistemological beliefs, conceptions of teaching and learning (COTL), and educational technology integration competencies. As for the participants, 1499 pre-service teachers enrolled at the School of Education at Northwestern region of Turkey participated in the study. An Educational Technology Integration Competencies Scale, Epistemological Beliefs Scale, and COTL Scale, which were developed by the researchers, were utilized to collect the data. At the end of the study, it was found that there were significant relations between pre-service teachers' beliefs (epistemological beliefs and COTL) and their educational technology integration competencies, which is parallel with the findings of the studies in the literature. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the factors affecting the pre-service computer science teachers' attitudes towards computer programming (ATCP). The sample consists of 119 preservice teachers at a public state university. The influences of students' demographic characteristics (gender, grade level, and high school type), their achievement in computer programming courses, perceived learning, and computer programming self-efficacy on their ATCP were tested using multiple linear regression. Descriptive, correlation and regression analyses revealed three findings: (1) students had moderately high ATCP, (2) their ATCP had significant correlations with their achievement in computer programming courses, computer programming self-efficacy, and perceived learning, and (3) three variables (achievement in computer programming courses, computer programming self-efficacy, and perceived learning) were significant predictors of their ATCP. [ABSTRACT FROM AUTHOR]

1. A causal association is reported between prolonged exposures to elevated levels of estrogen and breast cancer. Therefore inhibiting aromatase (CYP19A), which catalyses the conversion of androgens to estrogens, is an important approach in prevention and treatment of estrogen receptor positive (ERþ) breast cancer. 2. Melatonin, a natural indolic hormone, is reported to prevent free radical induced carcinogenesis and block local estrogen synthesis in breast tissue via aromatase inhibition. However several features of melatonin limit its therapeutic use. 3. In the present study aromatase inhibiting potential of 2-methyl indole hydrazones are investigated, and compared with melatonin, by two in vitro models; a cell-free assay using a fluorescence substrate and a cell-based assay where cell proliferation was determined in ERþhuman breast cancer cells (MCF-7 BUS) in the absence of estrogen and the presence of testosterone. Aromatase inhibitory effect is also explored by molecular modelling studies. 4. In biological activity assays monochloro substituted indole hydrazones were found to have stronger aromatase inhibitory activity among all tested derivatives and were more active than melatonin. This finding is further confirmed by molecular modelling. 5. These results may be useful in the design and synthesis of novel melatonin analogues with higher inhibitory potency against aromatase. [ABSTRACT FROM AUTHOR]

Background & aims: The early steps in the pathophysiology of celiac disease (CD) leading to loss of tolerance to gluten are poorly described. Our aim was to use RNA sequencing of duodenal biopsies in patients with active CD, CD in remission, and non-CD controls to gain insight into CD pathophysiology, identify additional genetic signatures linked to CD, and possibly uncover targets for future therapeutic agents. Methods: We performed whole transcriptome shotgun sequencing of intestinal biopsies in subjects with active and remission CD and non-CD controls. We also performed functional pathway analysis of differentially expressed genes to identify statistically significant pathways that are up or down regulated in subjects with active CD compared to remission CD. Results: We identified the upregulation of novel genes including IL12R, ITGAM and IGSF4 involved in the immune response machinery and cell adhesion process in the mucosa of subjects with active CD compared to those in remission. We identified a unique signature of genes, related to innate immunity, perturbed exclusively in CD irrespective of disease status. Finally, we highlight novel pathways of interest that may contribute to the early steps of CD pathogenesis and its comorbidities such as the spliceosome, pathways related to the innate immune response, and pathways related to autoimmunity. Conclusions: Our study confirmed previous findings based on GWAS and immunological studies pertinent to CD pathogenesis and describes novel genes and pathways that with further validation may be found to contribute to the early steps in the pathogenesis of CD, ongoing inflammation, and comorbidities associated with CD. [ABSTRACT FROM AUTHOR]

Context: Internal rigid fixation provides immediate stability of the occipito-cervical (OC) junction for treatment of instability; however, in current practice, the optimal OC junction stabilization method is debatable. Aims: The aim of this study to test the safety and efficacy of a newly designed modified inside-outside occipito-cervical (MIOOC) plate system for the treatment of instability. Settings and Design: This was a feasibility study of MIOCC plate system. Subjects and Methods: Five male and four female patients with OC instability were treated using MIOOC plate system. Stabilization rate, safety, and efficacy were evaluated radiologically and clinically. Results: Mean age of the patients was 35 ± 11 (range: 22–58) years. Etiology of OC instability included trauma, neoplasm, congenital abnormalities, and iatrogenic. The fusion levels ranged from occiput-C3 to occiput-C6. Mean follow-up duration was 22 ± 10 (range: 6–46) months. There were neither complication nor was there any need for plate revision or screw pullout. Mortality occurred in one patient due to primary malignancy at 6 months; otherwise, no morbidity was observed. During the follow-up, no recurrent subluxation or newly developed instability at adjacent levels occurred. All patients showed a satisfactory union at the most recent follow-up examination. Conclusions: These preliminary results suggest that the MIOCC plate system is a useful and safe method for providing immediate internal stability of the OC junction. Using a multi-piece plate design in this plate system provided easy implantation and a better interface between plate and OC bones. Further, clinical studies and long-term results are needed to determine the reliability of the MIOOC plate system. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis of pregnancy (GPPP) is a rare and severe condition that may impair the health of the mother and fetus. Effective treatment is essential, as treatment options for GPPP are limited due to concerns about unfavorable pregnancy outcomes. We report the case of a 22-year-old woman with GPPP that was unresponsive to systemic corticosteroids. We effectively treated the condition with infliximab at 30 weeks' gestation with an immediate clinical response and no detected serious adverse events except for an oral herpes infection in the patient and low birth weight in the neonate. Future studies are necessary to evaluate the safety and efficacy of infliximab treatment in GPPP. [ABSTRACT FROM AUTHOR]