Treatment of major depressive disorder (MDD) or dysthymic disorder (DD) in spinal cord injury (SCI) patients: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Although various treatments exist for depression in patients with spinal cord injury (SCI), the comparative effects and relationships between these treatments have not been clearly presented. This study aims to present comprehensive evidence for the treatment of major depressive disorder or dysthymic disorder in patients with SCI by comparing the therapeutic and adverse effects of pharmacological and non-pharmacological treatments through a systematic review and network meta-analysis. METHODS AND ANALYSIS: We will search for studies in five databases (Medline, Central, Embase, PsycINFO and CHINAL) as well as clinical trial registries (US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www. CLINICALTRIALS: gov), WHO International Clinical Trials Registry Platform (www.who.int/trialsearch)) and grey literature (Google Scholar). The references of the included studies, previous systematic reviews and meta-analyses will be reviewed. Study selection, data extraction and quality and risk of bias assessments will be independently performed by two authors (JMH and WSC), and disagreements will be resolved by discussion with JHK. Moreover, a Bayesian network meta-analysis will be performed using R software. ETHICS AND DISSEMINATION: Our systematic review and network meta-analysis will be performed based on existing studies; thus, we did not seek ethical approval. Our results will be published in a peer-reviewed journal and presented at both domestic and international conferences.

Is it worth applying self-irrigation after third molar extraction? A randomised controlled trial.

In this study, we aimed to examine the effectiveness of self-irrigation following the extraction of mandibular third molars. A randomised controlled clinical trial was conducted with 155 patients who had undergone extraction of a mandibular third molar. The irrigation group was instructed to self-irrigate the extraction socket with tap water using a syringe three times a day, starting seven days after the tooth extraction. The incidence of complications and mouth opening, halitosis, plaque/gingival index, and oral health-related quality of life (OHRQoL) were measured. The irrigation group showed a lower incidence of complications than the non-irrigation group. The halitosis, plaque, and gingival scores were lower by mean (SD) 19.66 (5.19), 0.58 (0.06), and 0.62 (0.08), respectively, in the irrigation group than in the non-irrigation group (p = 0.0001). A greater amount of food packing was associated with higher halitosis, plaque, and gingival scores and poorer OHRQoL (p < 0.05). Further, more frequent irrigation was associated with lower halitosis, plaque, and gingival scores and better OHRQoL (p ≤ 0.016). Self-irrigation of the extraction socket using a syringe containing tap water is a very effective method for keeping the extraction socket clean. This technique reduced halitosis, improved plaque and gingival indices, and increased OHRQoL.

Optimal application of compressive palatal stents following mesiodens removal in pediatric patients: A Randomized Controlled Trial / Aplicación óptima de stents palatinos de compresión después de la extracción del mesiodens en pacientes pediátricos: un ensayo controlado aleatorio

Background: There is no scientific evidence supporting the choice of a palatal stent in patients who underwentremoval of an impacted supernumerary tooth. We aimed to investigate the effects of palatal stents in patients whounderwent supernumerary tooth removal through a palatal approach and to suggest the optimal stent thicknessand material.Material and Methods: We recruited 144 patients who underwent extraction of a supernumerary tooth between themaxillary anterior teeth. Subjects were assigned to a control group (CG) or one of four compressive palatal stentgroups (CPSGs) classified by the thickness and material of the thermoplastic acrylic stent used. Palatal gingivalswelling and objective indices (healing, oral hygiene, gingival, and plaque) were evaluated before surgery and onpostoperative days (PODs) 3, 7, and 14; pain/discomfort and the Child Oral Health Impact Profile (COHIP) wereassessed as subjective indices of the effects of the stent.Results: The CPSGs showed faster healing than did the CG on PODs 7 (P<0.001) and 14 (P=0.043); swelling wasmeasured by 1.64±0.88 mm and 4.52±0.39 mm, respectively. Although swelling was least in the 4-mm hard group(0.92±0.33 mm), the difference compared with that in the 2-mm hard group (1.01±0.18 mm) was not significant(P=0.077). The CPSGs showed better COHIP (P<0.001-0.036) and pain scores (P<0.001) than did the CG onPODs 1-3. Conclusions: Compressive palatal stents reduce discomfort by decreasing pain and alleviating swelling. Althougha stent is effective regardless of its thickness and material, 2-mm hard stents maximized such positive effects withminimal discomfort.(AU)

Complications associated with specific characteristics of supernumerary teeth.

OBJECTIVES: The purpose of this study was to identify the characteristics of supernumerary teeth, analyze the associated complications, and to present new clinical knowledge on surgical interventions for supernumerary teeth. STUDY DESIGN: This retrospective cohort study was based on the medical records and radiographic records of patients who underwent surgical extraction of supernumerary teeth. The relationships among the patient's age, gender, anatomic features of supernumerary teeth, and presence and type of complications (i.e., spacing, rotation, delayed eruption of the adjacent tooth, cyst formation.) were investigated. The groups were compared by using the Mann-Whitney U test, the Kolmogorov-Smirnov test, and multiple logistic regression analysis (P < .05). RESULTS: The study population consisted of 705 participants who underwent extraction for 1036 supernumerary teeth. The mean age of the participants was 11.5 years, and 73.5% of the participants were males. The complication rate was 55.6%. Variables associated with an increased risk of complications were the patient's age, dentition, tuberculate shape, and horizontal direction of eruption (P < .05). CONCLUSIONS: An increase in the patient's age or abnormalities in the shape and direction of eruption of supernumerary teeth was associated with complications. These parameters should be considered while formulating the treatment plan.

[Effects of Active Mandibular Exercise for Mouth Opening Limitation Patients after Maxillomandibular Fixation Release: A Non-Randomized Controlled Trial].

PURPOSE: The aim of this study was to evaluate the effects of active mandibular exercise (AME) in patients with limited mouth opening after maxillomandibular fixation (MMF) release. METHODS: The study used a quasi-experimental, nonequivalent control group and a pre test-post test design. Sixty-two patients with Maxillomandibular Fixation Release were assigned to the experimental (n=31) or control group (n=31). The AME was performed in the experimental group for 4 weeks. The exercise AME consisted of maximal mouth opening, lateral excursion and protrusive movement. These movements were repeated ten times a day. After the final exercise of the day, the number of tongue blades used for mouth opening was noted. The effect of AME was evaluated after MMF release at different time intervals: a) immediately, b) after 1 week, c) after 2 weeks, d) after 4 weeks, and e) after 12 weeks. The exercise was assessed using the following criteria: a) mandibular movements, b) pain scores associated with maximal mouth opening, c) discomfort scores associated with range of movement, and d) daily life activities that involve opening the mouth. RESULTS: The experimental group showed significant improvement regarding the range of mandibular movements (maximal mouth opening (F=23.60, p<.001), lateral excursion to the right side (F=5.25, p=.002), lateral excursion to the left side (F=5.97, p=.001), protrusive movement (F=5.51, p=.001)), pain score (F=39.59, p<.001), discomfort score (F=9.38, p<.001). Daily life activities that involve opening the mouth were more favorable compared to those in the control group. CONCLUSION: The AME in patients after MMF release is helpful for increasing mandibular movement range, decreasing pain and discomfort, and improving day life activities that involve opening the mouth. Therefore, AME is highly recommended as an effective nursing intervention.

Frontier orbitals of photosubstitutionally active ruthenium complexes: an experimental study of the spectator ligands' electronic properties influence on photoreactivity.

The synthesis and characterization of [Ru(tpy)(R2bpy)(L)](X)n complexes (tpy = 2,2':6',2''-terpyridine, R2bpy = 4,4'-dimethyl-2,2'-bipyridine (dmbpy), or 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (tfmbpy), X = Cl- or PF6-, and n = 1 or 2) are described. The dmbpy and tfmbpy bidentate ligands allow for investigating the effects of electron-donating and electron-withdrawing ligands, respectively, on the frontier orbital energetics as well as the photoreactivity of these ruthenium polypyridyl complexes for five prototypical monodentate ligands L = Cl-, H2O, CH3CN, 2-(methylthio)ethanol (Hmte), or pyridine. According to spectroscopic and electrochemical studies, the dmbpy analogues displayed a singlet metal-to-ligand charge transfer (1MLCT) transition at higher energy than the tfmbpy analogues. The shift of the 1MLCT to higher energy results from the lowest unoccupied molecular orbital (LUMO) for the dmbpy analogues being tpy-based, whereas for the tfmbpy analogues orbital inversion occurs resulting in a tfmbpy-based LUMO. The energy level of the highest occupied molecular orbital (HOMO) was considerably affected by the nature of the monodentate ligand. Visible light irradiation of the complexes demonstrated that the tfmbpy analogue increased the rate and quantum yields of photosubstitution reactions, compared to the dmbpy analogue, suggesting that the electron-withdrawing substituents allowed better thermal accessibility of the triplet metal-centered (3MC) state from the photochemically generated triplet metal-to-ligand charge transfer (3MLCT) excited state. A correlation between the photolability of the monodentate ligands and the electrochemical reversibility of the metal-based oxidation is also reported.

Neural stem cells derived from epiblast stem cells display distinctive properties.

Pluripotent stem cells can be derived from preimplantation and postimplantation mouse embryos. Embryonic stem cells (ESCs) derived from blastocysts are in a "naive" pluripotent state and meet all of the criteria for pluripotency, including the ability to generate live pups through tetraploid complementation. Epiblast stem cells (EpiSCs) derived from postimplantation epiblasts are in a "primed" pluripotent state. ESCs and EpiSCs show different phenotypes and gene expression patterns, and EpiSCs are thought to be less pluripotent than ESCs. In this study, we addressed whether EpiSCs can be differentiated into specialized cell types in vitro. To do this, we first derived EpiSCs from E5.5-6.5 mouse embryos containing the Oct4-GFP transgene. We found that EpiSCs expressed pluripotency markers and differentiated into all three germ layers in intro and in vivo. Interestingly, EpiSCs also efficiently differentiated into a homogenous population of neural stem cells (NSCs) in vitro. The EpiSC-derived NSCs (EpiSC-NSCs) expressed NSC markers (Nestin, Sox2, and Musashi), self-renewed for more than 20 passages, and differentiated into neuronal and glial neural cell subtypes in vitro. We then transplanted the EpiSC-NSCs into the neonatal mouse brains, and found that they were able to survive and differentiate into robust neurons and glial cells in the mouse brains, demonstrating that primed pluripotent EpiSCs efficiently form functional NSCs. We compared the global gene expression patterns of NSCs differentiated from EpiSC-NSCs, ESCs, and brain tissue and found that the expression patterns of most genes, including pluripotency and NSC specificity, were similarly clustered, but that the developmental process-related genes were distantly clustered. Moreover, the global gene expression pattern of brain-derived NSCs was more similar to that of ESC-derived NSCs than that of EpiSC-derived NSCs. Taken together, these results indicate that although NSCs, regardless of their origins, display very similar in vitro and in vivo differentiation properties, their global gene expression profiles may differ, depending on the pluripotency state, i.e., naive or primed.

Conversion of genomic imprinting by reprogramming and redifferentiation.

Induced pluripotent stem cells (iPSCs), generated from somatic cells by overexpression of transcription factors Oct4, Sox2, Klf4 and c-Myc have the same characteristics as pluripotent embryonic stem cells (ESCs). iPSCs reprogrammed from differentiated cells undergo epigenetic modification during reprogramming, and ultimately acquire a similar epigenetic state to that of ESCs. In this study, these epigenetic changes were observed in reprogramming of uniparental parthenogenetic somatic cells. The parthenogenetic pattern of imprinted genes changes during the generation of parthenogenetic maternal iPSCs (miPSCs), a process referred to as pluripotent reprogramming. We determined whether altered imprinted genes are maintained or revert to the parthenogenetic state when the reprogrammed cells are redifferentiated into specialized cell types. To address this question, we redifferentiated miPSCs into neural stem cells (miPS-NSCs) and compared them with biparental female NSCs (fNSCs) and parthenogenetic NSCs (pNSCs). We found that pluripotent reprogramming of parthenogenetic somatic cells could reset parthenogenetic DNA methylation patterns in imprinted genes, and that alterations in DNA methylation were maintained even after miPSCs were redifferentiated into miPS-NSCs. Notably, maternally methylated imprinted genes (Peg1, Peg3, Igf2r, Snrpn and Ndn), whose differentially methylated regions were fully methylated in pNSCs, were demethylated and their expression levels were found to be close to the levels in normal biparental fNSCs after reprogramming and redifferentiation. Our findings suggest that pluripotent reprogramming of parthenogenetic somatic cells followed by redifferentiation leads to changes in DNA methylation of imprinted genes and the reestablishment of gene expression levels to those of normal biparental cells.

Reestablishment of the inactive X chromosome to the ground state through cell fusion-induced reprogramming.

The restricted gene expression pattern of a differentiated cell can be reversed by fusion of the somatic cell with a more developmentally potent cell type, such as an embryonic stem (ES) cell. During this reprogramming process, somatic cells obtain most of the characteristics of pluripotent cells. Reactivation of an inactive X chromosome (Xi) is an important epigenetic marker confirming the pluripotent reprogramming of somatic cells. Female somatic cells contain one active X chromosome (Xa) and one Xi, and following the fusion of these cells with male ES cells, the Xi becomes activated, resulting in XaXaXaY fusion hybrid cells. To monitor Xi reactivation, transgenic female neural stem cells (fNSCs) carrying a green fluorescent protein (GFP) reporter gene expressed on the Xa (X-GFP), but not on the Xi, were used for reprogramming. XaXi(GFP) NSCs, whose GFP reporter was silenced, were fused with HM1 ES cells (XY) to induce pluripotent reprogramming. The Xi(GFP) of NSCs were found to be activated on day 4 post-fusion, indicating reactivation of the Xi. Hybrid cells showed pluripotent cell-specific characteristics cells including inactivation of the NSC marker Nestin, DNA demethylation of Oct4, DNA methylation of Nestin, and reactivation of the Xi. Following differentiation of the (GFP-positive) hybrid cells through embryoid body formation, the proportion of GFP-negative cells was found to be approximately 26 %, indicating that there was random inactivation of one of the three Xas. Here, we showed that the Xi of somatic cells is reprogrammed to the Xa state and that cellular differentiation occurs randomly, i.e., regardless of the Xa or Xi state, indicating that the memory of the Xi of somatic cells has been erased and reset to the ground state (i.e., inner cell mass-like state), indicating that random X-chromosome inactivation occurs upon differentiation.

Neural stem cells achieve and maintain pluripotency without feeder cells.

BACKGROUND: Differentiated cells can be reprogrammed into pluripotency by transduction of four defined transcription factors. Induced pluripotent stem cells (iPS cells) are expected to be useful for regenerative medicine as well as basic research. Recently, the report showed that mouse embryonic fibroblasts (MEF) cells are not essential for reprogramming. However, in using fibroblasts as donor cells for reprogramming, individual fibroblasts that had failed to reprogram could function as feeder cells. METHODOLOGY/PRINCIPAL FINDING: Here, we show that adult mouse neural stem cells (NSCs), which are not functional feeder cells, can be reprogrammed into iPS cells using defined four factors (Oct4, Sox2, Klf4, and c-Myc) under feeder-free conditions. The iPS cells, generated from NSCs expressing the Oct4-GFP reporter gene, could proliferate for more than two months (passage 20). Generated and maintained without feeder cells, these iPS cells expressed pluripotency markers (Oct4 and Nanog), the promoter regions of Oct4 and Nanog were hypomethylated, could differentiated into to all three germ layers in vitro, and formed a germline chimera. These data indicate that NSCs can achieve and maintain pluripotency under feeder-free conditions. CONCLUSION/SIGNIFICANCE: This study suggested that factors secreted by feeder cells are not essential in the initial/early stages of reprogramming and for pluripotency maintenance. This technology might be useful for a human system, as a feeder-free reprogramming system may help generate iPS cells of a clinical grade for tissue or organ regeneration.