Cancers, Vol. 10, Pages 165: CRISPR-Mediated Reactivation of DKK3 Expression Attenuates TGF-β Signaling in Prostate Cancer

Cancers, Vol. 10, Pages 165: CRISPR-Mediated Reactivation of DKK3 Expression Attenuates TGF-β Signaling in Prostate Cancer

Cancers doi: 10.3390/cancers10060165

Authors: Hoda Kardooni Estela Gonzalez-Gualda Emmanouil Stylianakis Sina Saffaran Jonathan Waxman Robert M. Kypta

The DKK3 gene encodes a secreted protein, Dkk-3, that inhibits prostate tumor growth and metastasis. DKK3 is downregulated by promoter methylation in many types of cancer, including prostate cancer. Gene silencing studies have shown that Dkk-3 maintains normal prostate epithelial cell homeostasis by limiting TGF-β/Smad signaling. While ectopic expression of Dkk-3 leads to prostate cancer cell apoptosis, it is unclear if Dkk-3 has a physiological role in cancer cells. Here, we show that treatment of PC3 prostate cancer cells with the DNA methyltransferase (DNMT) inhibitor decitabine demethylates the DKK3 promoter, induces DKK3 expression, and inhibits TGF-β/Smad-dependent transcriptional activity. Direct induction of DKK3 expression using CRISPR-dCas9-VPR also inhibited TGF-β/Smad-dependent transcription and attenuated PC3 cell migration and proliferation. These effects were not observed in C4-2B cells, which do not respond to TGF-β. TGF-β signals can regulate gene expression directly via SMAD proteins and indirectly by increasing DNMT expression, leading to promoter methylation. Analysis of genes downregulated by promoter methylation and predicted to be regulated by TGF-β found that DKK3 induction increased expression of PTGS2, which encodes cyclooxygenase-2. Together, these observations provide support for using CRISPR-mediated induction of DKK3 as a potential therapeutic approach for prostate cancer and highlight complexities in Dkk-3 regulation of TGF-β signaling.

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Stanley and me [Humanities]

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Why are women still earning less than men in medicine? [News]

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Community paramedicine is growing in impact and potential [Commentary]

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What constitutes a public health response to the opioid overdose epidemic? [Letters]

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Evaluation of a community paramedicine health promotion and lifestyle risk assessment program for older adults who live in social housing: a cluster randomized trial [Research]

BACKGROUND:

Low-income older adults who live in subsidized housing have higher mortality and morbidity. We aimed to determine if a community paramedicine program — in which paramedics provide health care services outside of the traditional emergency response — reduced the number of ambulance calls to subsidized housing for older adults.

METHODS:

We conducted an open-label pragmatic cluster-randomized controlled trial (RCT) with parallel intervention and control groups in subsidized apartment buildings for older adults. We selected 6 buildings using predefined criteria, which we then randomly assigned to intervention (Community Paramedicine at Clinic [CP@clinic] for 1 yr) or control (usual health care) using computer-generated paired randomization. CP@clinic is a paramedic-led, community-based health promotion program to prevent diabetes, cardiovascular disease and falls for residents 55 years of age and older. The primary outcome was building-level mean monthly ambulance calls. Secondary outcomes were individual-level changes in blood pressure, health behaviours and risk of diabetes assessed using the Canadian Diabetes Risk Questionnaire. We analyzed the data using generalized estimating equations and hierarchical linear modelling.

RESULTS:

The 3 intervention and 3 control buildings had 455 and 637 residents, respectively. Mean monthly ambulance calls in the intervention buildings (3.11 [standard deviation (SD) 1.30] calls per 100 units/mo) was significantly lower (–0.88, 95% confidence interval [CI] –0.45 to –1.30) than in control buildings (3.99 [SD 1.17] calls per 100 units/mo), when adjusted for baseline calls and building pairs. Survey participation was 28.4% (n = 129) and 20.3% (n = 129) in the intervention and control buildings, respectively. Residents living in the intervention buildings showed significant improvement compared with those living in control buildings in quality-adjusted life years (QALYs) (mean difference 0.09, 95% CI 0.01 to 0.17) and ability to perform usual activities (odds ratio 2.6, 95% CI 1.2 to 5.8). Those who received the intervention had a significant decrease in systolic (mean change 5.0, 95% CI 1.0 to 9.0) and diastolic (mean change 4.8, 95% CI 1.9 to 7.6) blood pressure.

INTERPRETATION:

A paramedic-led, community-based health promotion program (CP@clinic) significantly lowered the number of ambulance calls, improved QALYs and ability to perform usual activities, and lowered systolic blood pressure among older adults living in subsidized housing. Trial registration: Clinicaltrials.gov, no. NCT02152891

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Coming soon: CMAJ policy on data sharing [Editorial]

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Quadrivalent human papillomavirus vaccination in girls and the risk of autoimmune disorders: the Ontario Grade 8 HPV Vaccine Cohort Study [Research]

BACKGROUND:

Despite demonstrated effectiveness in real-world settings, concerns persist regarding the safety of the quadrivalent human papillomavirus (HPV4) vaccine. We sought to assess the risk of autoimmune disorders following HPV4 vaccination among grade 8 girls eligible for Ontario's school-based HPV vaccination program.

METHODS:

We undertook a population-based retrospective cohort study using Ontario's administrative health and vaccination databases from 2007 to 2013. The self-controlled case series method was used to compare the rate of a composite end point of autoimmune disorders diagnosed during days 7–60 post-vaccination ("exposed" follow-up) to that at any other time ("unexposed"). The analysis was repeated to assess the effect of a history of immune-mediated diseases and time since vaccination. We also conducted an exploratory analysis of individual autoimmune disorders. Rate ratios and 95% confidence intervals (CIs) were estimated using conditional Poisson regression, adjusted for age, seasonality, concomitant vaccinations and infections.

RESULTS:

The study cohort consisted of 290 939 girls aged 12–17 years who were eligible for vaccination between 2007 and 2013. There was no significant risk for developing an autoimmune disorder following HPV4 vaccination (n = 681; rate ratio 1.12, 95% CI 0.85–1.47), and the association was unchanged by a history of immune-mediated disorders and time since vaccination. Exploratory analyses of individual autoimmune disorders found no significant risks, including for Bell palsy (n = 65; rate ratio 1.73, 95% CI 0.77–3.89), optic neuritis (n = 67; rate ratio 1.57, 95% CI 0.74–3.33) and Graves disease (n = 47; rate ratio 1.55, 95% CI 0.92–2.63).

INTERPRETATION:

We did not observe an increased risk of autoimmune disorders following HPV4 vaccination among teenaged girls. These findings should reassure parents and health care providers.

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Whom should we really call a "doctor"? [Letters]

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Herpes zoster ophthalmicus [Practice]

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"Medutainment" -- Are doctors using patients to gain social media celebrity? [News]

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Japanese encephalitis [Practice]

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Family medicine faces shortage of doctors willing to teach [News]

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Cancers, Vol. 10, Pages 164: Development of an Experimental Model for Analyzing Drug Resistance in Colorectal Cancer

Cancers, Vol. 10, Pages 164: Development of an Experimental Model for Analyzing Drug Resistance in Colorectal Cancer

Cancers doi: 10.3390/cancers10060164

Authors: Mohamed Elbadawy Tatsuya Usui Hideyuki Yamawaki Kazuaki Sasaki

Colorectal cancer (CRC) is one of the most common cancers, for which combination treatment of chemotherapy is employed. However, most patients develop drug resistance during the course of treatment. To clarify the mechanisms of drug resistance, various research models have been developed. Recently, we established a human CRC patients-derived three-dimensional (3D) culture system using an air-liquid interface organoid method. It contained numerous cancer stem cells and showed resistance to 5-fluorouracil and Irinotecan. In this review, we introduce conventional and our established models for studying drug resistance in CRC.

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Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up†

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Soft tissue and visceral sarcomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up†

Soft tissue sarcomas (STSs) gather over 80 histological entities, with even more molecular subsets, characterised by a low to very low incidence in all populations. The majority of sarcomas arise from the soft tissue (close to 75%), with ∼15% gastrointestinal stromal tumours (GISTs) and 10% bone sarcomas. These ESMO–EURACAN (European Society for Medical Oncology–European Reference Network for rare adult solid cancers) Clinical Practice Guidelines cover STSs, while GISTs are covered by dedicated ESMO–EURACAN Clinical Practice Guidelines [1]. Kaposi's sarcoma is not considered in the present document. Extraskeletal Ewing and Ewing-like sarcoma is covered by ESMO Clinical Practice Guidelines on bone sarcomas [2]. In general, the same principles for these tumours in children apply to adults. This is also the case for embryonal and alveolar rhabdomyosarcomas, which are exceedingly rare in adults. On the other hand, pleomorphic rhabdomyosarcoma is viewed as a high-grade, adult-type STS. Extraskeletal osteosarcoma is also a high-grade STS, whose clinical resemblance with osteosarcoma of bone is doubtful (prospective collection of data is encouraged to generate evidence on the therapeutic implications of such a diagnosis). Adult STS pathological subtypes occurring in adolescents should be managed the same way as in adult patients, though the same histotype might display clinical peculiarities when occurring at different ages.

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Measuring Exercise Levels in Drosophila melanogaster Using the Rotating Exercise Quantification System (REQS)

The Rotating Exercise Quantification System (REQS) can induce exercise in Drosophila melanogaster through rotation while simultaneously measuring the amount of activity performed by the animals. Here, we present a point-by-point protocol detailing how to measure activity levels of animals experiencing rotational exercise treatments using the REQS.

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Making Conjugation-induced Fluorescent PEGylated Virus-like Particles by Dibromomaleimide-disulfide Chemistry

Here, we present a procedure to fluorescently functionalize the disulfides on Qβ VLP with dibromomaleimide. We describe Qβ expression and purification, the synthesis of dibromomaleimide-functionalized molecules, and the conjugation reaction between dibromomaleimide and Qβ. The resulting yellow fluorescent conjugated particle can be used as a fluorescence probe inside cells.

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Probing the Structure and Dynamics of Interfacial Water with Scanning Tunneling Microscopy and Spectroscopy

Here, we present a protocol to investigate the structure and dynamics of interfacial water at the atomic scale, in terms of submolecular resolution imaging, molecular manipulation, and single-bond vibrational spectroscopy.

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Sexuality after Male-to-Female Gender Affirmation Surgery

Male-to-Female (MtF) gender affirmation surgery (GAS) comprises the creation of a functional and aesthetic perineogenital complex. This study aimed to evaluate the effect of GAS on sexuality. We retrospectively surveyed all 254 MtF transsexual patients who had undergone GAS with penile inversion vaginoplasty at the Department of Urology, University Hospital Essen, Germany, between 2004 and 2010. In total, we received 119 completed questionnaires after a median of 5.05 years since surgery. Of the study participants, 33.7% reported a heterosexual, 37.6% a lesbian, and 22.8% a bisexual orientation related to the self-perceived gender. Of those who had sexual intercourse, 55.8% rated their orgasms to be more intensive than before, with 20.8% who felt no difference. Most patients were satisfied with the sensitivity of the neoclitoris (73.9%) and with the depth of the neovaginal canal (67.1%). The self-estimated pleasure of sexual activity correlated significantly with neoclitoral sensitivity but not with neovaginal depth. There was a significant correlation between the ease with which patients were able to become sexually aroused and their ability to achieve orgasms. In conclusion, orgasms after surgery were experienced more intensely than before in the majority of women in our cohort and neoclitoral sensitivity seems to contribute to enjoyment of sexual activity to a greater extent than neovaginal depth.

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Condylar Degradation from Decreased Occlusal Loading following Masticatory Muscle Atrophy

Objective. The masticatory muscles are the most important contributor to bite force, and the temporomandibular joint (TMJ) receives direct occlusal loading. The present study aimed to investigate condylar remodeling after masseter muscle atrophy in rats. Methods. Sixty 5-week-old female Sprague-Dawley rats were divided into the following 3 groups: the control group, soft diet (SD) group, and botulinum toxin (BTX) group. The cross-sectional area (CSA) of the masseter muscles was investigated as well as atrogin-1/MuRF-1 expression. Changes in the condylar head were evaluated by H-E, toluidine blue staining, and contour measurements. The biomechanical sensitive factors PTHrP Ihh, Col2a1, and ColX of condylar cartilage were detected by immunohistochemical staining and western blotting. Furthermore, micro-CT and tartrate-resistant acid phosphatase (TRAP) staining were performed to determine the osteopenia in subchondral bone. Results. The histological and protein analysis demonstrated muscle hypofunction in the SD and BTX groups. Condylar cartilage contour was diminished due to different treatments; the immunohistochemistry and protein examination showed that the expressions of PTHrP, Ihh, Col2a1, and ColX were suppressed in condylar cartilage. A steady osteoporosis in subchondral bone was found only in the BTX group. Conclusion. The current results suggested that a steady relationship between muscular dysfunction and condylar remodeling exists.

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Bioactive Natural Products 2018

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Efficacy of Adjunctive Bioactive Materials in the Treatment of Periodontal Intrabony Defects: A Systematic Review and Meta-Analysis

Objectives. Lots of bioactive materials have been additionally applied for the treatment of periodontal intrabony defect. However, there is dearth of studies to systematically evaluate the supplementary role of them in periodontal regeneration. The goal of this meta-analysis is to evaluate the adjunctive effects of bioactive materials such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), enamel matrix derivative (EMD), and amnion membrane (AM) on the outcomes of bone grafting treatment for periodontal intrabony defects. Methods. Articles published before December 2017 were searched electronically in three databases (PubMed, Embase, and Cochrane Central), with no date or language limits. Randomized controlled trials (RCTs) on the assessment of effectiveness of the four biomaterials in conjunction with demineralized freeze-dried bone allografts (DFDBA) in the treatment of periodontal intrabony defects were enrolled in this meta-analysis. Data were analyzed with STATA 12. Results. Nine studies were included. PRF and PRP significantly improved pocket depth (PD) reduction and clinical attachment loss (CAL) gain. Only PRF exhibited a positive result in recession reduction (RecRed). Only PRP showed a statistically significant increase in bone fill. AM merely gained more CAL. EMD did not improve any clinical outcome. Conclusion. Our data suggest that PRF/PRP could be taken as a preferred adjunct to facilitate periodontal regeneration of intrabony defects.

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Intestinal Myiasis Caused by Sarcophaga spp. in Cusco, Peru: A Case Report and Review of the Literature

Myiasis is the infestation by dipterous fly larvae in humans and animals. The larvae can infect living or necrotic tissue involving the skin, nasopharynx, genitourinary, and gastrointestinal tracts. The accidental ingestion of eggs causes infection of the intestinal tract. We report a case of intestinal myiasis caused by Sarcophaga spp. larvae in a two-year-old child from Limatambo province in the Cusco region of Peru. Live larvae were identified incidentally in this child's stool sample during the study screening for Strongyloides stercoralis. The child did not have any constitutional or abdominal symptoms. The morphological examination of the specimen under magnification revealed Sarcophaga spp. larvae. We performed a literature review of publications reporting intestinal myiasis caused by Sarcophaga spp. and discussed key aspects of this infestation.

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Salivary Antioxidant Status in Patients with Oral Lichen Planus: Correlation with Clinical Signs and Evolution during Treatment with Chamaemelum nobile

Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease, which manifests as a succession of outbreaks. OLP was associated with salivary oxidative stress. Randomized, double blind, parallel-group study was performed. The sample consisted of 55 clinically and histopathologically diagnosed OLP patients. Twenty-six patients were treated with 2% Chamaemelum nobile gel and 29 with a placebo. Nonstimulated (basal) saliva was collected on the first day of the study and 4 weeks later. Salivary total antioxidant status (TAS) was evaluated by four different methods: two TAC (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) equivalent antioxidant capacity methods (TAC1 and TAC2), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing ability of plasma (FRAP). At baseline (T1), no statistically significant differences were detected in any of the TAS analytes between the two groups of patients. After four weeks of treatment, a statistically significant increase was detected in FRAP in the placebo group (0.323 [0.090–0.467] versus 0.406 [0.197–0.848] mmol/) (). Significant correlations were observed between pain and drainage and TAC1, CUPRAC, and FRAP and between xerostomia and the TAC1, TAC2, CUPRAC, and FRAP. The results of the present study showed that in patients with OLP increases of TAS in saliva are associated with increase in pain and xerostomia and decrease in drainage, suggesting a worsening condition of the patient. The use of Chamaemelum nobile gel would be recommended for disease stabilization.

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Serum Adipocyte Fatty Acid-Binding Protein 4 Levels Are Independently Associated with Radioisotope Glomerular Filtration Rate in Type 2 Diabetic Patients with Early Diabetic Nephropathy

Serum fatty acid-binding protein 4 (FABP4) has been linked to renal dysfunction. This study evaluated the association between serum FABP4 and the radioisotope glomerular filtration rate (rGFR) in type 2 diabetic patients (T2DM) with early diabetic nephropathy. Twenty healthy controls and 172 patients with T2DM were enrolled. Serum FABP4 and renal impairment biomarkers including urinary albumin-to-creatinine ratio (UACR), serum retinal-binding protein 4 (RBP4), urinary cystatin C-to-creatinine ratio (CysC/Cr), and neutrophil gelatinase-associated lipocalin-to-creatinine ratio (NGAL/Cr) were measured. Diethylenetriaminepentaacetic acid (99mTc-DTPA) was used to test rGFR. Serum FABP4 levels were higher in T2DM patients compared with the controls. There was no significant correlation between serum FABP4 and UACR in patients with T2DM. Multivariate stepwise regression analysis showed that, in patients with T2DM, FABP4 was significantly associated with rGFR while CysC/Cr and RBP4 were significantly associated with UACR independently. But UACR had no independent association with rGFR. NGAL/Cr had no significant correlation with either rGFR or UACR. FABP4 might be an early biomarker for diabetic nephropathy if combined with UACR.

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Acute Biochemical, Cardiovascular, and Autonomic Response to Hyperbaric (4 atm) Exposure in Healthy Subjects

The aim of this study was to explore the effect of a hyperbaric environment alone on the cardiovascular system by ensuring elimination of factors that may mask the effect on hyperbaria. The research was performed in a hyperbaric chamber to eliminate the effect of physical activity and the temperature of the aquatic environment. Biochemical analysis and examination with the Task Force Monitor device were performed before and immediately after exposure. TFM was used for noninvasive examination of the cardiovascular system and the functional evaluation of the autonomic nervous system. Natriuretic peptides were measured as biochemical markers which were involved in the regulation of haemodynamic circulation vasoconstriction (urotensin II). L-arginine acted as a precursor of the level of the nitric oxide whereas angiotensin II and angiotensin (1–7) were involved in cardiac remodeling. The study group is comprised of 18 volunteers who were professional divers of similar age and experience. The results shown in our biochemical studies do not exceed reference ranges but a statistically significant increase indicates the hyperbaric environment is not without impact upon the human body. A decrease in HR, an increase in mBP, dBP, and TPR, and increase in parasympathetic heart nerves activity suggest an increase in heart afterload with a decrease in heart activity within almost one hour after hyperbaric exposure. Results confirm that exposure to a hyperbaric environment has significant impact on the cardiovascular system. This is confirmed both by changes in peptides associated with poorer cardiovascular outcomes, where a significant increase in the studied parameters was observed, and by noninvasive examination.

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A Preliminary Study of microRNA-208b after Acute Myocardial Infarction: Impact on 6-Month Survival

Introduction. miRNAs contribute to a variety of essential biological processes including development, proliferation, differentiation, and apoptosis. Circulating microRNAs are very stable and have shown potential as biomarkers of cardiovascular disease. microRNA-208b expression was increased in the blood of patients with acute myocardial infarction (AMI) and has been proposed as a biomarker for early diagnosis. In this pilot study, we investigate the potential of circulating miR-208b as a prognostic biomarker of 6-month survival in AMI patients. Methods. Plasma samples from 21 patients and 8 age- and gender-matched healthy adults were collected, and circulating levels of miR-208b were detected using quantitative real-time PCR. Results. miR-208b levels were higher in healthy control subjects (9.6-fold; ). Within the AMI patients, the levels of miR-208b were significantly lower in the survivor versus nonsurvivor group (fold change = 6.51 and 14.1, resp.; ). The Kaplan-Meier curve revealed that the 6-month survival time was significantly higher among AMI patients with a relative expression of miR-208b lower than 12.38. The hazard ratio (HR) for the relative expression of miR-208b (

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Evaluation of the Effect of Different Types of Abrasive Surface Treatment before and after Zirconia Sintering on Its Structural Composition and Bond Strength with Resin Cement

This study evaluated the effect of air abrasion before and after sintering with different particle type, shape, and size on the surface morphology, monoclinic phase transformation, and bond strength between resin cement and zirconia surface using primer containing silane and MDP. Airborne particle abrasion (APA) was performed on zirconia before and after sintering with different particle shape and size (50 μm Al2O3 and 25 μm silica powder). 120 square shaped presintered zirconia samples (Amann Girrbach) were prepared (3 mm height × 10 mm width × 10 mm length) and polished with grit papers #800, 1000, 1200, 1500, and 2000. Samples were divided into 6 groups according to surface treatment—group A: (control) no surface treatment; group B: APA 50 μm Al2O3 before sintering (BS); group C: APA 50 μm Al2O3 after sintering (AS); group D: APA25 μm silica powder (BS); group E: APA25 μm silica powder (AS) at a pressure of 3.5 bar; and group F: APA 25 μm silica powder (AS) at a pressure of 4 bar. Samples were analyzed using XRD, AFM, and SEM. The samples were submitted to shear bond strength (SBS) test. A dual cure resin cement (RelyX Ultimate) and primer (Scotchbond Universal) were used. Data were analyzed with ANOVA and Tukey test . APA in group B significantly increased the surface roughness when compared to all other groups. A significant monoclinic phase transformation (t-m) value was observed in groups C and F and a reverse transformation occurred in presintered groups. The SBS value of group A was and the highest significant shear bond strength value was for groups B () and C ( MPa) with no significant difference between them. Conclusions. The use of APA 50 μm Al2O3 before sintering and the application of primer containing MDP seem to be valuable methods for durable bonding with zirconia. The use of APA 50 μm Al2O3 after sintering induced the highest (t-m) phase transformation.

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Does Adding Silver Nanoparticles to Leukocyte- and Platelet-Rich Fibrin Improve Its Properties?

Objectives. Leucocyte- and platelet-rich fibrin (L-PRF) membrane can be used in various regenerative treatments. In the case of classical heterologous membrane exposure, microorganisms can be colonized on it and jeopardize the success of treatment. The aim of this study was to compare the antibacterial, mechanical, and histologic characteristics of the L-PRF membrane before and after the addition of silver nanoparticles (SNP). Materials and Method. This study was performed on 10 volunteer men aged 25-35 years. 20 ml whole bloods were collected from each person and L-PRFs were made by routine and SNP modified method. Mechanical, antibacterial, and histological properties were evaluated. Results. The antibacterial efficacy of L-PRF and nanosilver-modified L-PRF was presented as Klebsiella pneumonia had growth on the L-PRF membrane after 12 hours. After 24 hours, Klebsiella pneumonia and Streptococcus viridans had growth on L-PRF and only Klebsiella pneumonia had growth on SNP-L-PRF. The tensile strength and stiffness were significantly higher in the SNP-L-PRF. Precipitation of the SNPs was patchy in the outer layers and quite homogeneous in the inner core. Conclusion. Modification of L-PRF with SNP improves the mechanical properties and antibacterial activity of the L-PRF. It can play an important role in regenerative procedures.

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Relationship between Tongue Temperature Estimated by Infrared Thermography, Tongue Color, and Cold-Heat Pathological Patterns: A Retrospective Chart Review Study

Tongue diagnosis is a technique used to determine cold-heat pathologic patterns (CHPPs). Herein, we reviewed electronic medical records of tongue temperature measured using infrared thermography (IRT), tongue color (luminance, green/red, and blue/yellow balance), cold-heat pattern questionnaires (CHPQ), and body temperature for 134 women with gynecological problems (age, 38.97 ± 11.49 years). The temperatures of seven tongue regions (root, center, tip, and both sides of the center and root) were determined, and the effects of age, regional differences, and their correlations with color parameters were examined. Factor analysis was conducted separately with the 10 cold pattern (CP) and 10 heat pattern (HP) items. Tongue temperature showed an age effect (; -0.198 to -0.210) and regional differences (both sides of the root > center and root > tip). Tongue temperature was positively correlated with luminance (r: 0.236-0.246), indicating that a higher temperature was associated with a brighter color. The factor analysis extracted two factors (cold sensitivity-pain and discharge-complexion factors) from the CP items and three factors (heat sensation-pain, discharge-breath, and cold preference-thirst factors) from the HP items. Tongue temperature was negatively correlated with the discharge-complexion factor of CP and the discharge-breath factor of HP (r: -0.171 to -0.203), indicating that a lower tongue temperature may be a consequence of emission of excessive heat in HP and a lower blood perfusion in CP. Body temperature did not correlate with the CHPQ factor scores. In conclusion, tongue temperatures measured using IRT may be a partial indicator of CHPPs.

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Acupuncture for Diarrhoea-Predominant Irritable Bowel Syndrome: A Network Meta-Analysis

Background. The objective of this study was to compare the efficacy and side effects of acupuncture, sham acupuncture, and drugs in the treatment of diarrhoea-predominant irritable bowel syndrome. Methods. Randomized controlled trials (RCTs) assessing the effects of acupuncture and drugs were comprehensively retrieved from electronic databases (such as PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database, and CBM) up to December 2017. Additional references were obtained from review articles. With document quality evaluations and data extraction, Network Meta-Analysis was performed using a random-effects model under a frequentist framework. Results. A total of 29 studies (n = 9369) were included; 19 were high-quality studies, and 10 were low-quality studies. NMA showed the following: (1) the ranking of treatments in terms of efficacy in diarrhoea-predominant irritable bowel syndrome is acupuncture, sham acupuncture, pinaverium bromide, alosetron = eluxadoline, ramosetron, and rifaximin; (2) the ranking of treatments in terms of severity of side effects in diarrhoea-predominant irritable bowel syndrome is rifaximin, alosetron, ramosetron = pinaverium bromide, sham acupuncture, and acupuncture; and (3) the treatment of diarrhoea-predominant irritable bowel syndrome includes common acupoints such as ST25, ST36, ST37, SP6, GV20, and EX-HN3. Conclusion. Acupuncture may improve diarrhoea-predominant irritable bowel syndrome better than drugs and has the fewest side effects. Sham acupuncture may have curative effect except for placebo effect. In the future, it is necessary to perform highly qualified research to prove this result. Pinaverium bromide also has good curative effects with fewer side effects than other drugs.

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Isolated Knee Arthritis as Early and Only Symptom of Whipple’s Disease

We report a case of isolated Whipple's disease involving the knee of a 64-year-old female patient who presented recurrent monoarthritis whose origin was not clear. Initially, the cause of the gradually invalidating symptoms was related to a meniscal lesion and a diffuse minor grade chondropathy, but pain and functional impairment suggested that more exams were needed. Biopsies were performed during arthroscopy. The histology showed highly inflammatory infiltrates with PAS staining negative for Tropheryma while PCR revealed the infection with Tropheryma whipplei. This, following the recommendation of a rheumatologist and infectious disease specialist, led to biopsies of the gastrointestinal tract and analysis of the cerebrospinal fluid that showed no other organ involvement. This confirms the scientific literature that an isolated monoarthritis without involvement of the gastrointestinal tract caused by this bacterium is rare but can occur as an early manifestation of potentially fatal systemic disease. Moreover, a review of the scientific literature showed the uncertainty about epidemiology of this rare disease, suggesting that more and specific data are required.

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Bibliometric Analysis of Global Scientific Research on lncRNA: A Swiftly Expanding Trend

To investigate trends in long-noncoding (lnc) RNA research systematically, we compared the contribution of publications among different regions, institutions, and authors. Publications on lncRNA were retrieved from Web of Science (WoS) from 1975 to 2017. A total of 3879 papers were identified, and together they were cited 62967 times. The literature on lncRNA had been continuously growing since 2006, and the expansion might continue at a rapid pace until around 2021. China contributed the greatest proportion (63.47%) of lncRNA publications, and the USA ranked second in the number of publications (944 articles), while it had the highest citation frequency (43168 times) and H-index (97). The journal Oncotarget has the greatest number of publications on lncRNA research, with 305 papers. The keywords could be stratified into two clusters: cluster 1 (application) and cluster 2 (characteristics). Correspondingly, the "TNM stage," "epithelial mesenchymal transition (EMT)," "cell apoptosis," and "overall survival" are research hotspots since 2015. Thus, research on lncRNA showed a swiftly expanding trend, with China making the largest contribution. The focus on lncRNA is gradually shifting from "characteristics" to "application."

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Burkholderia pseudomallei Adaptation for Survival in Stressful Conditions

Burkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis, which can be fatal in humans. Melioidosis is prevalent in the tropical regions of Southeast Asia and Northern Australia. Ecological data have shown that this bacterium can survive as a free-living organism in environmental niches, such as soil and water, as well as a parasite living in host organisms, such as ameba, plants, fungi, and animals. This review provides an overview of the survival and adaptation of B. pseudomallei to stressful conditions induced by hostile environmental factors, such as salinity, oxidation, and iron levels. The adaptation of B. pseudomallei in host cells is also reviewed. The adaptive survival mechanisms of this pathogen mainly involve modulation of gene and protein expression, which could cause alterations in the bacteria's cell membrane, metabolism, and virulence. Understanding the adaptations of this organism to environmental factors provides important insights into the survival and pathogenesis of B. pseudomallei, which may lead to the development of novel strategies for the control, prevention, and treatment of melioidosis in the future.

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Mediastinal Ectopic Pancreas with Abundant Endocrine Cells Coexisting with Mediastinal Cyst and Thymic Hyperplasia

Mediastinal ectopic pancreas is a rare condition with only 28 cases reported in the literature. Here we report a 21-year-old female patient who presented with dyspnea and intermittent severe chest pain of 7 years' duration. Computerized tomography scan (CT-scan) of the chest revealed a mediastinal cyst. The cyst was resected and it demonstrated on histopathological examination the presence of pancreatic tissue with increased number of islets of Langerhans, coexistent with mediastinal cyst and thymic hyperplasia. We made a review of all previously reported cases of this entity.

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