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2.
Biophys J ; 122(7): 1334-1341, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36823986

RESUMO

The polymerase chain reaction (PCR) is a central technique in biotechnology. Its ability to amplify a specific target region of a DNA sequence has led to prominent applications, including virus tests, DNA sequencing, genotyping, and genome cloning. These applications rely on the specificity of the primer hybridization and therefore require effective suppression of hybridization errors. A simple and effective method to achieve that is to add blocker strands, also called clamps, to the PCR mixture. These strands bind to the unwanted target sequence, thereby blocking the primer mishybridization. Because of its simplicity, this method is applicable to a broad nucleic-acid-based biotechnology. However, the precise mechanism by which blocker strands suppress PCR errors remains to be understood, limiting the applicability of this technique. Here, we combine experiments and theoretical modeling to reveal this mechanism. We find that the blocker strands both energetically destabilize the mishybridized complex and sculpt a kinetic barrier to suppress mishybridization. This combination of energetic and kinetic biasing extends the viable range of annealing temperatures, which reduces design constraint of the primer sequence and extends the applicability of PCR.


Assuntos
Ácidos Nucleicos , Primers do DNA/genética , Reação em Cadeia da Polimerase/métodos , Hibridização de Ácido Nucleico , Temperatura
3.
Life Sci ; 316: 121442, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36708988

RESUMO

AIMS: Protein disulfide isomerase (PDI) is an essential enzyme involved in oxidative protein folding. PDI is S-nitrosylated in the brains of Alzheimer's disease patients, and S-nitrosylated PDI is considered one of main causes of Alzheimer's disease. However, the mechanisms underlying PDI S-nitrosylation have not yet been elucidated. Because glutathione (GSH) depletion is a pathological feature of Alzheimer's disease, we investigated the effect of GSH depletion on the S-nitrosylation level of PDI. MAIN METHODS: SH-SY5Y cells, which is a human derived neuroblastoma cells, were used in this study. Glutamate and buthionine sulfoximine (BSO) were used as GSH depletors. S-nitrosylated PDI was detected by biotin-switch assay. KEY FINDINGS: GSH depletion by glutamate, a cystine/glutamate antiporter xCT inhibitor, increased S-nitrosylated PDI at C343 in SH-SY5Y cells, and induced IRE1α phosphorylation. BSO, a γ-glutamylcysteine synthetase inhibitor, also increased S-nitrosylated PDI and phosphorylated IRE1α upon GSH depletion. Because S-nitrosylated PDI at C343 is stable in neuro cells, S-nitrosylated PDI by GSH depletion progresses to neurodegeneration by the induction of endoplasmic reticulum stress via phosphorylated IRE1α signaling from the early to late stage. Furthermore, treatment with neohesperidin, but not N-acetylcysteine (NAC), improved PDI S-nitrosylation level in GSH-depleted SH-SY5Y cells because nitrosylated compound of NAC induces PDI S-nitrosylation. SIGNIFICANCE: The results of our study provide a new insight into the mechanisms of neurodegeneration, and may be useful for the development of drugs for Alzheimer's diseases.


Assuntos
Doença de Alzheimer , Neuroblastoma , Humanos , Isomerases de Dissulfetos de Proteínas/metabolismo , Endorribonucleases , Neuroblastoma/patologia , Proteínas Serina-Treonina Quinases , Glutationa , Glutamatos
4.
Pharmaceuticals (Basel) ; 15(4)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35455480

RESUMO

This paper evaluates a one-year treatment outcome after full or reduced photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) combination therapy for pachychoroid neovasculopathy (PNV). After the initial combination therapy, a total of 29 eyes from 29 patients (16 for full treatment and 13 for reduced treatment), exhibited reduced, central retinal thickness and central choroidal thickness, and the improvements were maintained for 1 year after the initial combination therapy. Twenty-two eyes (75.9%) required no additional treatments for 1 year. The recurrence rate was 31.3% in the full treatment and 15.4% in the reduced treatment, with no significant differences between them. One shot of anti-VEGF and full or reduced PDT combination therapy had similar efficacy in treating PNV. Further prospective, large-scale, and long-term studies are required to determine a better treatment for PNV.

5.
DEN Open ; 2(1): e76, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35310696

RESUMO

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a systemic condition associated with fibroinflammatory lesions and is characterized by elevated serum IgG4 levels and IgG4-positive cell infiltration into the affected tissues. It has been reported that IgG4-RD affects a variety of organs but uncommonly affects the gastrointestinal tract. In particular, there are few cases of lesions in the small intestine, except for sclerosing mesenteritis, which were mostly diagnosed from surgical specimens. Herein, we describe the case of a 70-year-old man who initially presented with abdominal pain, headache, later cognitive decline, and gait disturbance caused by IgG4-RD. Colonoscopy revealed irregular ulcers in the terminal ileum, and computed tomography of the head showed hypertrophic pachymeningitis. Numerous IgG4-positive cells were detected in the ileal and dural biopsies. We diagnosed the patient with IgG4-RD and started steroid pulse therapy. After initiation of treatment, the symptoms quickly improved. The patient was discharged from the hospital after starting oral prednisolone treatment (30 mg). The dosage was gradually reduced to 10 mg. A follow-up colonoscopy revealed scarring of the ileal ulcers. This case may provide valuable information regarding the endoscopic findings of small intestinal lesions in IgG4-RD.

7.
Materials (Basel) ; 15(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35009516

RESUMO

Dental implants with tapered conical connections are often combined with zirconia abutments for esthetics; however, the effect of the titanium base on the implant components remains unclear. This study evaluated the effects of a titanium base on the fracture resistance of zirconia abutments and damage to the tapered conical connection implants. Zirconia (Z) and titanium base zirconia (ZT) abutments were fastened to Nobel Biocare (NB) implants and Straumann (ST) implants and subjected to static load testing according to ISO 14801:2016. The experiments were performed with 3 mm of the platform exposed (P3) and no platform exposed (P0). The fracture loads were statistically greater in the titanium base abutments than the zirconia abutments for the NB and ST specimens in the P0 condition. In the P3 condition of the ST specimens, the deformation volume of the ZT group was significantly greater than the Z group. The titanium base increased the fracture resistance of the zirconia abutments. Additionally, the titanium base caused more deformation in the P3 condition. The implant joint design may also affect the amount of damage to the implants when under a load. The mechanical properties of the abutment should be considered when selecting a clinical design.

8.
J Prosthodont ; 31(1): 59-64, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33829613

RESUMO

PURPOSE: To assess the influence of liquid attached on the tooth surfaces on the accuracy (trueness and precision) of intraoral scanners and the effectiveness of the drying method (using compression air) to exclude the influence of liquid on the scanning results. MATERIALS AND METHODS: A mandibular jaw model was scanned using an industrial computed tomography scanner to obtain a reference model. A scanning platform was designed to simulate three specific tooth surface states (dry, wet, blow-dry). Two kinds of liquids (ultra-pure water and artificial saliva) were used for the test. Two intraoral scanners (Trios 3 and Primescan) were used to scan the mandibular jaw model 10 times under each condition. All scanning data were processed and analyzed using dedicated software (Geomagic Control 2015). Trueness and precision comparison were conducted within the 12 groups of 3D models divided based on different intraoral scanners and liquids used under each condition. The root mean square (RMS) value was used to indicate the difference between the aligned virtual models. The color maps were used to evaluate and observe the deviation distribution patterns. The 3-way ANOVA (condition, intraoral scanner, liquid) followed by the Tukey test were used to assess precision and trueness. The level of significance was set at 0.05. RESULTS: The mean RMS values obtained from wet condition were significantly higher than those of the dry and blow-dry condition (p < 0.001, F = 64.033 for trueness and F = 54.866 for precision), which indicates less accurate trueness and precision for wet condition. For two different types of liquids, the mean RMS value was not significantly different on trueness and precision. The deviations caused by liquid were positive and mainly distributed in the pits and fissures of the occlusal surface of posterior teeth, the interproximal area of the teeth, and the margin of the abutments. CONCLUSIONS: Liquid on the tooth surface could affect intraoral scanning accuracy. Blow-drying with a three-way syringe can reduce scanning errors.


Assuntos
Técnica de Moldagem Odontológica , Dente , Desenho Assistido por Computador , Imageamento Tridimensional , Modelos Dentários
9.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34832922

RESUMO

To evaluate choroidal volume and thickness changes after photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). Chronic CSC eyes with a history of PDT were selected. Average choroidal volume, average choroidal thickness, the maximum and minimum choroidal thickness of the macula irradiated area and peripheral non-irradiated areas before and after one and three months of treatment were examined. A total of 14 patients with chronic CSC and 9 controls without any eye pathology were enrolled. The mean choroidal volume in CSC before and, and after one and three months of treatment were 2.36 (standard deviation: 0.70), 1.90 (0.69), 1.86 (0.66) mm3 for the central area, 1.25 (0.38), 1.14 (0.35), 1.13 (0.34) mm3 for superior nasal area, 1.47 (0.41), 1.28 (0.43), 1.26 (0.43) mm3 for superior temporal area, 1.07 (0.49), 0.95 (0.38), 0.93 (0.35) mm3 for inferior nasal area, 1.17 (0.38), 1.04 (0.32), 1.03 (0.33) mm3 for inferior temporal area. This study revealed the choroidal volume changes in a short period after PDT and a decrease in unirradiated choroidal volume was also shown after the treatment. The algorithm provided on the ARI Network enables to evaluate the choroidal changes quantitatively and qualitatively.

10.
Biochim Biophys Acta Gen Subj ; 1865(11): 129998, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474117

RESUMO

BACKGROUND: Dementia places a significant burden on both patients and caregivers. Since diabetes is a risk factor for dementia, it is imperative to identify the relationship between diabetes and cognitive disorders. Protein disulfide isomerase (PDI) is an enzyme for oxidative protein folding. PDI S-nitrosylation is observed in the brain tissues of Alzheimer's disease patients. The aim of this study is to clarify the relationship between PDI S-nitrosylation and diabetes. METHODS: We used SH-SY5Y cells cultured in high-glucose media. RESULTS: S-nitrosylated PDI level increased at 7 days and remained high till 28 days in SH-SY5Y cells cultured in high-glucose media. Using PDI wild-type- or PDI C343S-expressing SH-SY5Y cells, PDI C343 was identified as the site of glucose-induced S-nitrosylation. IRE1α and PERK were phosphorylated at day 14 in the SH-SY5Y cells cultured in high-glucose media, and the phosphorylated status was maintained to day 28. To determine the effect of S-nitrosylated PDI on endoplasmic reticulum stress signaling, SH-SY5Y cells were treated with S-nitrosocystein (SNOC) for 30 min, following which the medium was replaced with SNOC-free media and the cells were cultured for 24 h. Only phosphorylated IRE1α treated with SNOC was associated with PDI S-nitrosylation. Neohesperidin, a flavonoid in citrus fruits, is a natural antioxidant. The treatment with neohesperidin in the final 7 days of glucose loading reversed PDI S-nitrosylation and improved cell proliferation. CONCLUSION: Glucose loading leads to S-nitrosylation of PDI C343 and induces neurodegeneration via IRE1α phosphorylation. GENERAL SIGNIFICANCE: The results may be useful for designing curative treatment strategies for dementia.


Assuntos
Glucose/metabolismo , Neuroblastoma/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Humanos , Estresse Oxidativo , Células Tumorais Cultivadas
11.
Int J Implant Dent ; 7(1): 59, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34227040

RESUMO

BACKGROUND: Immediate implant placement with simultaneous contour augmentation such as guided bone regeneration (GBR) or connective tissue grafting (CTG) has been widely performed. However, few prospective studies have evaluated both peri-implant bone and soft tissue changes between the preoperative and postoperative periods. The purpose of this study is to quantify the horizontal dimensional changes of the facial bone and soft tissue following immediate implant placement with contour augmentation. MATERIAL AND METHODS: Twenty patients who underwent immediate implant placement in the anterior maxilla received GBR and CTG (test group) or GBR only (control group). Cone-beam computed tomography (CBCT) scans were taken preoperatively and 1 year after the definitive prosthesis connection, and then, they were superimposed. On the CBCT images of the two stages, the horizontal distance from the implant platform to the facial bone surface (BW) and the horizontal soft tissue width (GW) were measured at the implant platform level and 2 mm apical to the implant platform level. The sum of BW and GW (=TW) was used to assess the facial mucosal contour. RESULTS: BW decreased significantly from preoperative to 1 year after prosthesis connection with a mean decrease of 0.47 mm (P =0.021) in the control group and a mean decrease of 0.50 mm (P = 0.019) in the test group at the implant platform level. GW increased significantly with a mean increase of 1.37 mm (P =0.005) in the test group at the implant platform level. TW decreased significantly with a mean decrease of 0.46 mm in the control group (P =0.049) but increased significantly with a mean increase of 0.87 mm in the test group (P =0.005) at the implant platform level. CONCLUSIONS: Immediate implant placement with CTG showed a soft tissue gain of 1.37 mm compensated for bone resorption, thus still preserving the preoperative mucosal contour. CTG should be performed with immediate implant placement in cases where preoperative mucosal contours need to be maintained.


Assuntos
Tomografia Computadorizada de Feixe Cônico Espiral , Tomografia Computadorizada de Feixe Cônico , Humanos , Maxila/diagnóstico por imagem , Estudos Prospectivos , Próteses e Implantes
12.
Materials (Basel) ; 14(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066506

RESUMO

The attainment of a good aesthetic outcome in dental implant treatment requires inter-implant papilla reconstruction, which is very difficult to perform. Maintenance of the inter-implant bone is essential for maintenance of the inter-implant papilla. The aim of this study was to investigate the mechanical influences of the implant-abutment connection type and inter-implant distance on the inter-implant bone by using three-dimensional finite element analysis. Three computer-aided design models of two-piece implants were designed: external connection (EC), internal connection (IC), and conical connection (CC). In each model, two identical implants were placed with inter-implant distances of 3.0, 2.5, and 2.0 mm. The maximum principal stress and microgap were evaluated. The stress values of the inter-implant bone decreased in the following order: IC, EC, and CC. The microgap decreased in the following order: EC, IC, and CC. Regardless of the type of implant-abutment connection, the stress of the inter-implant bone increased as the inter-implant distance decreased. The microgap barely changed as the inter-implant distance decreased. A CC implant is a mechanically advantageous implant-abutment connection type for maintenance of the inter-implant bone. With an inter-implant distance of less than 3.0 mm, use of a CC implant might suppress absorption of the inter-implant bone.

13.
Int J Implant Dent ; 7(1): 28, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33870473

RESUMO

BACKGROUND: In dental implant treatment, the placement position of the implant body is important. The hypothesis is that there are factors that have a greater impact than the factors that have been studied so far. MATERIAL AND METHODS: The deviation between planned and actually placed implants was measured three-dimensionally by modified treatment evaluation method in 110 patients who underwent implant placement with guided surgery for partial edentulism. Ten factors that seemed to affect errors in placement were selected: the type of tooth, type of edentulism, distance from the remaining teeth, the type of implant, implant length, number of implants, method of guidance, the number of teeth supporting the surgical guide, number of anchor pins, and presence or absence of a reinforcement structure. The effect of each factor that corrected each confounding was calculated using multivariate analysis. RESULTS: In this study, 188 implant bodies were set to target, and the errors measurement data of the implant position were as follows: average Angle, 2.5 ± 1.6° (95% CI 2.25-2.69); Base, 0.67 ± 0.37 mm (95% CI 0.62-0.72); and Apex, 0.92 ± 0.47 mm (95% CI 0.86-0.98). As the result of multivariate analysis, larger errors were present in the partially guided group than the fully guided group. The number of teeth supporting the surgical guide significantly influenced the error in placement position. The error caused by the number of anchor pins was significantly different for the Angle. Similarly, the presence of the reinforcement structure influenced the error significantly for the Angle. CONCLUSIONS: It was suggested that the smaller errors could be present by performing guided surgery with full guidance and devising the design of the guide such as the number of teeth supporting the surgical guide, the setting of the anchor pin, and the reinforcement structure.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Cirurgia Assistida por Computador , Desenho Assistido por Computador , Humanos , Imageamento Tridimensional , Análise Multivariada , Estudos Retrospectivos
14.
Transl Psychiatry ; 11(1): 132, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602898

RESUMO

Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia.


Assuntos
Esquizofrenia , Animais , Proteínas de Transporte , Exoma/genética , Humanos , Camundongos , Mutação de Sentido Incorreto , Linhagem , Esquizofrenia/genética , Sequenciamento do Exoma
15.
Ophthalmol Sci ; 1(4): 100081, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36246945

RESUMO

Purpose: To elucidate the prevalence of soft drusen, pseudodrusen, and pachydrusen and their 5-year changes in a Japanese population. Design: Longitudinal population-based cohort study conducted from 2013 through 2017. Participants: Residents 40 years of age or older. Methods: Nonmydriatic color fundus photographs were used to grade drusen subtypes and retinal pigment epithelium (RPE) abnormalities according to the Three Continent Age-Related Macular Degeneration Consortium. The 5-year changes of each drusen were investigated. Main Outcome Measures: The prevalence of each drusen subtype and the 5-year changes of each drusen. Results: Among 1731 participants, 1660 participants had gradable photographs that were assessed. The age-adjusted prevalence of soft drusen, pachydrusen, and pseudodrusen was 4.3% (95% confidence interval [CI], 3.2%-5.8%), 7.7% (95% CI, 6.2%-9.7%), and 2.8% (95% CI, 1.7%-4.2%), respectively. Pachydrusen accounted for 82.0% (n = 50) of the extramacular drusen (n = 61). Pigment abnormalities were seen in 28.3% and 8.3% of eyes with soft drusen and pachydrusen, respectively (P < 0.0001). Longitudinal changes were investigated in 1444 participants with follow-up examinations, which showed an increase in size in 8.3% and 3.7% and regression in 1.7% and 5.5% for eyes with soft drusen and pachydrusen, respectively. No participants demonstrated RPE atrophy after pachydrusen regression. Conclusions: The prevalence of pachydrusen was higher than that of soft drusen and pseudodrusen combined. Pachydrusen may regress over time and typically is not associated with RPE atrophy as detected using color fundus photographs.

16.
Inflammation ; 44(1): 206-216, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32772240

RESUMO

Sjögren's syndrome (SS) is a chronic autoimmune disease targeting salivary and lacrimal glands. C-X-C motif chemokine ligand 10 (CXCL10) expression is upregulated in lip salivary glands (LSGs) of primary SS (pSS) patients, and CXCL10 involved in SS pathogenesis via immune-cell accumulation. Moreover, interferon (IFN)-γ enhances CXCL10 production via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. We investigated the effects of baricitinib, a selective JAK1/2 inhibitor, on both IFN-γ-induced CXCL10 production and immune-cell chemotaxis. We used immunohistochemical staining to determine the expression levels and localization of JAK1 and JAK2 in LSGs of SS patients (n = 12) and healthy controls (n = 3). We then evaluated the effect of baricitinib in an immortalized normal human salivary gland ductal (NS-SV-DC) cell line. Immunohistochemical analysis of LSGs from pSS patients revealed strong JAK1 and JAK2 expression in ductal and acinar cells, respectively. Baricitinib significantly inhibited IFN-γ-induced CXCL10 expression as well as the protein levels in an immortalized human salivary gland ductal-cell clone in a dose-dependent manner. Additionally, western blot analysis showed that baricitinib suppressed the IFN-γ-induced phosphorylation of STAT1 and STAT3, with a stronger effect observed in the case of STAT1. It also inhibited IFN-γ-mediated chemotaxis of Jurkat T cells. These results suggested that baricitinib suppressed IFN-γ-induced CXCL10 expression and attenuated immune-cell chemotaxis by inhibiting JAK/STAT signaling, suggesting its potential as a therapeutic strategy for pSS.


Assuntos
Azetidinas/farmacologia , Quimiocina CXCL10/antagonistas & inibidores , Interferon gama/farmacologia , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Purinas/farmacologia , Pirazóis/farmacologia , Fator de Transcrição STAT1/antagonistas & inibidores , Ductos Salivares/metabolismo , Sulfonamidas/farmacologia , Azetidinas/uso terapêutico , Linhagem Celular Transformada , Quimiocina CXCL10/biossíntese , Feminino , Humanos , Janus Quinase 1/biossíntese , Janus Quinase 2/biossíntese , Células Jurkat , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Fator de Transcrição STAT1/biossíntese , Ductos Salivares/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/metabolismo , Sulfonamidas/uso terapêutico
17.
J Prosthodont Res ; 65(2): 198-201, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32938864

RESUMO

PURPOSE: This study investigated the relationship between peri-implant tissue health and the presence of keratinized mucosa (≥ 2 mm) using multivariate analysis. METHODS: A total of 334 dental implants placed in 111 partially edentulous patients (34 males, 77 females) and restored with fixed prostheses were included in this study. The patients were recalled 12-146 months after completion of the prosthodontic treatment. Clinical parameters included modified plaque index (mPI), modified bleeding index (mBI), probing pocket depth (PPD), and radiographic bone loss (BL). The effects of the following potential explanatory variables on these parameters were analyzed: the presence of keratinized mucosa, age, sex, oral hygiene status, history of periodontitis, cigarette smoking, implant site, and time elapsed since prosthesis delivery. Statistical analysis included multivariate ordinal logistic regression and generalized estimating equations. Significance wa s established when two-sided p-values were less than 0.05. RESULTS: The mPI, mBI, and PPD in the presence or absence of keratinized mucosa did not show statistically significant differences. However, the presence of keratinized mucosa was significantly related to BL (odds ratio 4.33, p < 0.01). CONCLUSIONS: The results of our study suggest that the presence of keratinized mucosa is useful for reducing bone resorption and can help to maintain peri-implant tissue health.


Assuntos
Implantes Dentários , Boca Edêntula , Índice de Placa Dentária , Feminino , Humanos , Masculino , Mucosa Bucal , Mucosa , Análise Multivariada
18.
J Neural Transm (Vienna) ; 127(11): 1517-1526, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32388794

RESUMO

Panic disorder (PD) is a common and debilitating neuropsychiatric disorder characterized by panic attacks coupled with excessive anxiety. Both genetic factors and environmental factors play an important role in PD pathogenesis and response to treatment. However, PD is clinically heterogeneous and genetically complex, and the exact genetic or environmental causes of this disorder remain unclear. Various approaches for detecting disease-causing genes have recently been made available. In particular, genome-wide association studies (GWAS) have attracted attention for the identification of disease-associated loci of multifactorial disorders. This review introduces GWAS of PD, followed by a discussion about the limitations of GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative strategies to address these challenges are then proposed, such as epigenome-wide association studies (EWAS) and rare variant association studies (RVAS) using next-generation sequencing. To date, however, few reports have described these analyses, and the evidence remains insufficient to confidently identify or exclude rare variants or epigenetic changes in PD. Further analyses are therefore required, using sample sizes in the tens of thousands, extensive functional annotations, and highly targeted hypothesis testing.


Assuntos
Estudo de Associação Genômica Ampla , Transtorno de Pânico , Epigênese Genética , Predisposição Genética para Doença , Humanos , Transtorno de Pânico/genética
19.
J Neural Transm (Vienna) ; 127(11): 1501-1515, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32285255

RESUMO

Twin studies of psychiatric disorders such as schizophrenia and autism spectrum disorder have employed epidemiological approaches that determine heritability by comparing the concordance rate between monozygotic twins (MZs) and dizygotic twins. The basis for these studies is that MZs share 100% of their genetic information. Recently, biological studies based on molecular methods are now being increasingly applied to examine the differences between MZs discordance for psychiatric disorders to unravel their possible causes. Although recent advances in next-generation sequencing have increased the accuracy of this line of research, there has been greater emphasis placed on epigenetic changes versus DNA sequence changes as the probable cause of discordant psychiatric disorders in MZs. Since the epigenetic status differs in each tissue type, in addition to the DNA from the peripheral blood, studies using DNA from nerve cells induced from postmortem brains or induced pluripotent stem cells are being carried out. Although it was originally thought that epigenetic changes occurred as a result of environmental factors, and thus were not transmittable, it is now known that such changes might possibly be transmitted between generations. Therefore, the potential possible effects of intestinal flora inside the body are currently being investigated as a cause of discordance in MZs. As a result, twin studies of psychiatric disorders are greatly contributing to the elucidation of genetic and environmental factors in the etiology of psychiatric conditions.


Assuntos
Transtorno do Espectro Autista , Esquizofrenia , Transtorno do Espectro Autista/genética , Epigênese Genética , Humanos , Esquizofrenia/genética , Estudos em Gêmeos como Assunto , Gêmeos Dizigóticos , Gêmeos Monozigóticos/genética
20.
Clin Implant Dent Relat Res ; 22(3): 311-318, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32212303

RESUMO

BACKGROUND: In the treatment of anterior implants, few studies have quantitatively evaluated the effects of connective tissue grafts on labial bone resorption and soft tissue recession. PURPOSE: To evaluate the influence of connective tissue grafting (CTG) on the peri-implant tissue morphology by quantitatively measuring change over time the tissue surrounding the implant in the anterior esthetic zone. MATERIAL AND METHODS: Twenty-six patients who received implants with platform shifting in the anterior esthetic region were included in this follow-up study. Patients were classified as those who received CTG [CTG (+) group] and those who did not [CTG (-) group]. The vertical and horizontal dimensions of the buccal alveolar bone of the implant and its surrounding soft tissues were evaluated using cone-beam computed tomography. RESULTS: At 1 year after connection of the superstructure, labial soft tissue recession was on average 0.64 mm in the CTG (-) group and 0.09 mm in the CTG (+) group, and this difference was significant (P < .001). Furthermore, mean labial bone resorption was 0.65 mm in the CTG (-) group and 0.13 mm in the CTG (+) group, and also this difference was significant (P = .003). CONCLUSIONS: Within the limitations of this study, these findings suggest that CTG may be effective in both reducing labial bone resorption around the implant and reducing the recession of the soft tissue.


Assuntos
Implantes Dentários para Um Único Dente , Implantes Dentários , Tecido Conjuntivo/transplante , Estética , Seguimentos , Humanos , Estudos Prospectivos , Resultado do Tratamento
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