Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
1.
Am J Kidney Dis ; 83(2): 173-182.e1, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37726050

RESUMO

RATIONALE & OBJECTIVE: Kidney transplant patients with failing allografts have a physical and psychological symptom burden as well as high morbidity and mortality. Palliative care is underutilized in this vulnerable population. We described kidney transplant clinicians' perceptions of palliative care to delineate their perceived barriers to and facilitators of providing palliative care to this population. STUDY DESIGN: National explanatory sequential mixed methods study including an online survey and semistructured interviews. SETTING & PARTICIPANTS: Kidney transplant clinicians in the United States surveyed and interviewed from October 2021 to March 2022. ANALYTICAL APPROACH: Descriptive summary of survey responses, thematic analysis of qualitative interviews, and mixed methods integration of data. RESULTS: A total of 149 clinicians completed the survey, and 19 completed the subsequent interviews. Over 90% of respondents agreed that palliative care can be helpful for patients with a failing kidney allograft. However, 46% of respondents disagreed that all patients with failing allografts benefit from palliative care, and two-thirds thought that patients would not want serious illness conversations. More than 90% of clinicians expressed concern that transplant patients and caregivers would feel scared or anxious if offered palliative care. The interviews identified three main themes: (1) transplant clinicians' unique sense of personal and professional responsibility was a barrier to palliative care engagement, (2) clinicians' uncertainty regarding the timing of palliative care collaboration would lead to delayed referral, and (3) clinicians felt challenged by factors related to patients' cultural backgrounds and identities, such as language differences. Many comments reflected an unfamiliarity with the broad scope of palliative care beyond end-of-life care. LIMITATIONS: Potential selection bias. CONCLUSIONS: Our study suggests that multiple barriers related to patients, clinicians, health systems, and health policies may pose challenges to the delivery of palliative care for patients with failing kidney transplants. This study illustrates the urgent need for ongoing efforts to optimize palliative care delivery models dedicated to kidney transplant patients, their families, and the clinicians who serve them. PLAIN-LANGUAGE SUMMARY: Kidney transplant patients experience physical and psychological suffering in the context of their illnesses that may be amenable to palliative care. However, palliative care is often underutilized in this population. In this mixed-methods study, we surveyed 149 clinicians across the United States, and 19 of them completed semistructured interviews. Our study results demonstrate that several patient, clinician, system, and policy factors need to be addressed to improve palliative care delivery to this vulnerable population.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Transplante de Rim , Assistência Terminal , Humanos , Estados Unidos , Cuidados Paliativos/métodos , Assistência Terminal/métodos , Aloenxertos
2.
J Clin Periodontol ; 51(7): 905-914, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38710583

RESUMO

AIM: To assess the potential benefits of minimally invasive non-surgical therapy (MINST) in teeth with intrabony defects and to explore factors associated with the outcomes. MATERIALS AND METHODS: A multi-centre trial was conducted in 100 intrabony defects in periodontitis patients in private practice. Steps 1 and 2 periodontal therapy including MINST were provided. Clinical and radiographic data were analysed at baseline and 12 months after treatment, with the primary aim being change in radiographic defect depth at 12 months. RESULTS: Eighty-four patients completed the 12-month follow up. The mean total radiographic defect depth reduced by 1.42 mm and the defect angle increased by 3° (both p < .05). Statistically significant improvements in probing pocket depth (PPD) and clinical attachment level (CAL) were seen at 12 months compared to baseline (p < .001). Fifty-six defects (66.7%) achieved pocket closure (PPD ≤ 4 mm) and 49 defects (58.3%) achieved the composite outcome (PPD ≤ 4 mm and CAL gain ≥3 mm). Deeper and narrower angled defects were positively correlated with radiographic and clinical improvements, respectively. CONCLUSIONS: Improvements in clinical and radiographic outcomes were seen after MINST. This study highlights the generalizability and wide applicability of this approach, further supporting its effectiveness in the treatment of intrabony defects. CLINICAL TRIAL REGISTRATION: NCT03741374. https://clinicaltrials.gov/study/NCT03741374?cond=minimally%20invasive%20non%20surgical%20therapy&locStr=UK&country=United%20Kingdom&distance=50&rank=2.


Assuntos
Perda do Osso Alveolar , Humanos , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Perda do Osso Alveolar/terapia , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/cirurgia , Adulto , Resultado do Tratamento , Idoso , Periodontite/terapia , Periodontite/cirurgia
3.
Medicina (Kaunas) ; 60(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38541146

RESUMO

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in the host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD) are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D, in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiological mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.


Assuntos
Periodontite , Insuficiência Renal Crônica , Deficiência de Vitamina D , Humanos , Deficiência de Vitamina D/complicações , Vitamina D/metabolismo , Insuficiência Renal Crônica/complicações , Doença Crônica , Periodontite/complicações
4.
J Periodontal Res ; 58(2): 213-224, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36537578

RESUMO

Vitamin D plays an essential role in calcium and bone metabolism, immune regulation and possesses profound anti-inflammatory effects. Evidence suggests that low serum vitamin D is associated with increased severity of periodontitis, a chronic inflammatory condition characterised by destruction of the supporting tissues surrounding the tooth, which has several shared risk factors with other chronic non-communicable diseases. The biological functions of vitamin D are mediated by its strong anti-microbial, anti-inflammatory, and host modulatory properties. Experimental periodontitis models involving targeted deletion of 1α-hydroxylase, the enzyme responsible for the conversion of inactive substrate to active 1,25(OH)2 D3 (calcitriol), showed augmented alveolar bone loss and gingival inflammation. Vitamin D receptor (VDR) gene polymorphisms have also been associated with increased severity of periodontitis. Thus, the involvement of vitamin D in the pathogenesis of periodontitis is biological plausible. Clinical studies have consistently demonstrated an inverse relationship between serum 25OHD3 and periodontal disease inflammation. However, due to the paucity of well-designed longitudinal studies, there is less support for the impact of vitamin D status on periodontal disease progression and tooth loss. The evidence emphasises the importance of maintaining vitamin D sufficiency in supporting periodontal health. This review aims to first examine the biological mechanisms by which vitamin D might influence the pathogenesis of periodontal disease and second, discuss the clinical evidence which implicate the role of vitamin D in periodontal disease.


Assuntos
Doenças Periodontais , Periodontite , Humanos , Vitamina D , Vitaminas , Inflamação
5.
Eur J Dent Educ ; 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38147462

RESUMO

INTRODUCTION: Learning in a clinical domain in dentistry is complex and learners may face uncertain clinical scenarios. A simulation curriculum can be designed to have simple clinical scenarios and learning activities which progress in complexity and employ competence assessments of simulated clinical practice before students can undertake authentic practice on patients. This paper presents how scaffolding of competence can be used for designing learning with simulators (haptics and phantom head) demonstrated in a specific domain in restorative dentistry. METHODS: A collaborative workshop as a research approach was undertaken to inform the iterative analysis, development, and discussion on scaffolding the learning design with respect to competence assessments of learning cavity preparation with simulation-based learning technologies. A workshop was conducted, which was collaborative and involved design negotiations between researchers, technologists, and teachers/practitioners in developing the simulation curriculum. RESULTS: A competence assessment with feedback in a specific domain in preparing interproximal caries was used as a context to describe how the learning activities and outcomes were designed to meet assessment of competence with varied levels of simple to complex learning activities and structured sessions. CONCLUSION: Simulation curriculum can be designed and implemented by scaffolding the level of competence that can be learned using simulation between haptics and phantom-head. This brings impetus to the need in meeting the relevant competence criteria in context to a specific affordance of the simulation-based learning technologies to provide optimal patient-centred holistic care.

6.
Ear Hear ; 43(3): 993-1002, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35319518

RESUMO

OBJECTIVES: This study examined the performance of a group of adult cochlear implant (CI) candidates (CIC) on visual tasks of verbal learning and memory. Preoperative verbal learning and memory abilities of the CIC group were compared with a group of older normal-hearing (ONH) control participants. Relations between preoperative verbal learning and memory measures and speech recognition outcomes after 6 mo of CI use were also investigated for a subgroup of the CICs. DESIGN: A group of 80 older adult participants completed a visually presented multitrial free recall task. Measures of word recall, repetition learning, and the use of self-generated organizational strategies were collected from a group of 49 CICs, before cochlear implantation, and a group of 31 ONH controls. Speech recognition outcomes were also collected from a subgroup of 32 of the CIC participants who returned for testing 6 mo after CI activation. RESULTS: CICs demonstrated poorer verbal learning performance compared with the group of ONH control participants. Among the preoperative verbal learning and memory measures, repetition learning slope and measures of self-generated organizational clustering strategies were the strongest predictors of post-CI speech recognition outcomes. CONCLUSIONS: Older adult CI candidates present with verbal learning and memory deficits compared with older adults without hearing loss, even on visual tasks that are independent from the direct effects of audibility. Preoperative verbal learning and memory processes reflecting repetition learning and self-generated organizational strategies in free recall were associated with speech recognition outcomes 6 months after implantation. The pattern of results suggests that visual measures of verbal learning may be a useful predictor of outcomes in postlingual adult CICs.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Percepção da Fala , Idoso , Surdez/reabilitação , Humanos , Fala , Aprendizagem Verbal/fisiologia
7.
Environ Res ; 212(Pt E): 113580, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35671797

RESUMO

Wastewater-based epidemiology is an effective tool for monitoring infectious disease spread or illicit drug use within communities. At the Ohio State University, we conducted a SARS-CoV-2 wastewater surveillance program in the 2020-2021 academic year and compared results with the university-required weekly COVID-19 saliva testing to monitor COVID-19 infection prevalence in the on-campus residential communities. The objectives of the study were to rapidly track trends in the wastewater SARS-CoV-2 gene concentrations, analyze the relationship between case numbers and wastewater signals when adjusted using human fecal viral indicator concentrations (PMMoV, crAssphage) in wastewater, and investigate the relationship of the SARS-CoV-2 gene concentrations with wastewater parameters. SARS-CoV-2 nucleocapsid and envelope (N1, N2, and E) gene concentrations, determined with reverse transcription droplet digital PCR, were used to track SARS-CoV-2 viral loads in dormitory wastewater once a week at 6 sampling sites across the campus during the fall semester in 2020. During the following spring semester, research was focused on SARS-CoV2 N2 gene concentrations at 5 sites sampled twice a week. Spearman correlations both with and without adjusting using human fecal viral indicators showed a significant correlation (p < 0.05) between human COVID-19 positive case counts and wastewater SARS-CoV-2 gene concentrations. Spearman correlations showed significant relationships between N1 gene concentrations and both TSS and turbidity, and between E gene concentrations and both pH and turbidity. These results suggest that wastewater signal increases with the census of infected individuals, in which the majority are asymptomatic, with a statistically significant (p-value <0.05) temporal correlation. The study design can be utilized as a platform for rapid trend tracking of SARS-CoV-2 variants and other diseases circulating in various communities.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , RNA Viral/genética , SARS-CoV-2/genética , Universidades , Águas Residuárias , Vigilância Epidemiológica Baseada em Águas Residuárias
8.
Am J Kidney Dis ; 77(5): 786-795, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33500128

RESUMO

Patients with chronic kidney disease (CKD) experience a high pain and symptom burden. Concurrently, opioid prescription and use in patients with CKD continues to increase, leading to concern for opioid-related risks. Nephrologists increasingly face challenging clinical situations requiring further evaluation and treatment of pain, for which opioid use may be indicated. However, nephrologists are not commonly trained in pain management and may find it difficult to compile the necessary information and tools to effectively assess and treat potentially multidimensional pain. In these situations, they may benefit from using an evidence-based stepwise approach proposed in this article. We address current approaches to opioid use for pain management in CKD and offer a stepwise approach to individualized opioid assessment, focusing on kidney-specific concerns. This includes thorough evaluation of the pain experience, opioid use history, and treatment goals. We subsequently discuss considerations when initiating opioid therapy, strategies to reduce opioid-related risks, and recommended best practices for opioid stewardship in CKD. Using this sequential approach to opioid management, nephrologists can thereby gain a broad overview of key patient considerations, the foundation for understanding implications of opioid use, and a patient-tailored plan for opioid therapy.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Neuralgia/tratamento farmacológico , Dor Nociceptiva/tratamento farmacológico , Insuficiência Renal Crônica/terapia , Dor Crônica/complicações , Medicina Baseada em Evidências , Humanos , Transtornos Relacionados ao Uso de Opioides , Manejo da Dor , Cuidados Paliativos , Guias de Prática Clínica como Assunto , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco
9.
J Periodontal Res ; 56(1): 147-153, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33010184

RESUMO

OBJECTIVES: The overall aim was to propose a plausible model of the dentogingival junction (DGJ) to deepen our understanding of the extrinsic influences responsible for the development of the junctional epithelial phenotype. The specific objective was to test the hypothesis that epithelial migration and proliferation would be inhibited by periodontal ligament (PDL) fibroblasts in an in vitro model of the DGJ consisting of 3D organotypic cultures. BACKGROUND: Previously, we showed that 3D organotypic cultures containing human gingival fibroblasts (HGF) supported the development of a multi-layered epithelium, while constructs containing human periodontal ligament fibroblasts (HPDLF) resulted in epithelial atrophy (Lu EMC, Hobbs C, Dyer CJ, Ghuman M, Hughes FJ. J Perio Res., 2020). However, changes in epithelial phenotype have not been studied within an in vitro model of the DGJ. METHODS: The in vitro model of the DGJ comprised of a donor HGF construct (H400 epithelium overlying HGF-collagen matrix) supported by a dimensionally larger recipient collagen bed enriched with HPDLF. Samples were harvested, fixed and processed for immunohistochemistry. The changes in epithelial migration and proliferation following contact with HPDLF were assessed by measuring the horizontal extension of the epithelial outgrowth on the recipient collagen matrix. RESULTS: Within our in vitro model of the DGJ, epithelial migration and proliferation were inhibited following contact with the recipient HPDLF. By contrast, the control set-up showed a relative increase in epithelial growth, where the epithelium came into contact with the recipient HGF. Overall, there were limited changes in the molecular expression of keratin markers. CONCLUSION: This study has proposed a plausible in vitro model of the DGJ to illustrate the role of different fibroblasts in the regulation of dentogingival epithelia. Furthermore, it suggests that the anatomical positional stability of the JE and its apparent resistance to apical migration could be associated with its interaction with the PDL.


Assuntos
Gengiva , Ligamento Periodontal , Proliferação de Células , Células Cultivadas , Colágeno , Fibroblastos , Humanos
10.
J Periodontal Res ; 55(6): 859-867, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32885443

RESUMO

OBJECTIVES: To investigate the underlying molecular mechanisms by which gingival and periodontal ligament (PDL) fibroblasts regulate epithelial phenotype. BACKGROUND: Fibroblast populations regulate the epithelial phenotype through epithelial-mesenchymal interactions (EMI). Previous studies have proposed that maintenance of the junctional epithelium (JE) is dependent on the differential effects from gingival and PDL tissues. However, these cell populations are undefined and the signalling mechanisms which may regulate JE are unknown. METHODS: Immunohistochemical analyses were performed on formalin-fixed paraffin-embedded sections of dentogingival tissues to identify phenotypic differences in fibroblast populations. The effect of distinct fibroblasts on epithelial phenotype was studied via 3D organotypic cultures, consisting of an H400 epithelium supported by human gingival fibroblasts (HGF) or human periodontal ligament fibroblasts (HPDLF), embedded in collagen gel. To investigate the involvement of Wnt signalling in EMI, the Wnt antagonist rhDKK1 was added to HGF constructs. The gene expression of Wnt antagonists and agonists was tested via RNA extraction and qPCR. Specific gene silencing using RNA interference was performed on HPDLF/HGF constructs. RESULTS: Gingival fibroblasts were characterized by Sca1 expression, and PDL fibroblasts, characterized by Periostin and Asporin expression. Through the construction of 3D organotypic cultures, we showed that HGF supported epithelial multilayering, whilst HPDLF failed to support epithelial cell growth. Furthermore, HGF constructs treated with rhDKK1 resulted in a profound reduction in epithelial thickness. We identified SFRP4 to be highly specifically expressed in HPDLF, at both the mRNA and protein levels. A knockdown of SFRP4 in HPDLF constructs led to an increase in epithelial growth. CONCLUSION: The study demonstrates the presence of phenotypically distinct fibroblast populations within dentogingival tissues and that these specific populations have different influences on the epithelium. Our data suggest that a downregulation of Wnt signalling within PDL may be important in maintaining the integrity and anatomical position of the JE.


Assuntos
Diferenciação Celular , Fibroblastos , Gengiva , Proliferação de Células , Células Cultivadas , Inserção Epitelial , Humanos , Ligamento Periodontal
11.
Matern Child Health J ; 23(4): 451-458, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30542985

RESUMO

Objectives Data on the potential effect of dental cleaning and community water fluoridation (CWF) on pregnancy outcomes are scarce. While numerous studies confirm the cost-effectiveness of fluoride in preventing dental caries, the benefit of CWF during pregnancy has not been well established. Methods This cross-sectional study used data from 2009 to 2016 Massachusetts Pregnancy Risk Assessment Monitoring System and restricted to singleton live births (n = 9234, weighted response rate = 64.3%). Our exposures were: (1) dental cleaning alone during pregnancy; (2) CWF alone; and (3) dental cleaning and CWF combined (DC-CWF). Women without dental cleaning during pregnancy and CWF comprised our reference group. The outcome was preterm birth, (birth < 37 weeks gestation). This study used multivariate logistic regression modeling, controlling for maternal sociodemographic characteristics, previous medical risk and behavioral factors, and calculated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). Results During 2009-2016, the prevalence of preterm birth among women with a singleton live birth was 8.5% in Massachusetts. Overall, 58.7% of women had dental cleaning during pregnancy, and 63.6% lived in CWF. After adjusting for potential confounders, the associations between dental cleaning alone and preterm birth (aRR = 0.74 [95% CI 0.55-0.98]), and DC-CWF and preterm birth (aRR = 0.74 [95% CI 0.57-0.95]) were significant, while the association between CWF alone and preterm birth was not significant (aRR = 0.81 [95% CI 0.63-1.05]), compared to women without dental cleaning and CWF. Conclusions for Practice This study shows that the prevalence of preterm birth was lower among women with DC only and DC-CWF.


Assuntos
Assistência Odontológica/estatística & dados numéricos , Fluoretação/estatística & dados numéricos , Adulto , Estudos Transversais , Assistência Odontológica/métodos , Feminino , Fluoretação/métodos , Idade Gestacional , Humanos , Recém-Nascido , Massachusetts/epidemiologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Prevalência , Medição de Risco/métodos
12.
BMC Oral Health ; 19(1): 233, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672124

RESUMO

BACKGROUND: Accurate prediction of the behaviour of oral squamous cell carcinoma (OSCC) is necessary to determine prognosis and provide appropriate treatment. Therefore, it is important to investigate potential prognostic markers to determine their predictive ability. Histological assessment of specific features at the invading front of oral squamous cell carcinomas has shown to provide accurate and reproducible prognostic information. Proliferating cell nuclear antigen (PCNA) is a nuclear marker known to reflect cell turnover and may be used as a marker for tumour aggressiveness. METHODS: Twenty cases of OSCC were histologically assessed to evaluate the correlation between proliferating cell nuclear antigen expression and invasive front grading. Each case was first assessed on a haematoxylin and eosin stained slide and an invading front grading (IFG) score was determined. In order to obtain a PCNA score, immunohistological staining was carried out using the peroxidase-labelled streptavidin-biotin technique with the monoclonal antibody PC10. RESULTS: In all cases, tumour islands had a periphery of intensely stained proliferating cell nuclear antigen-positive epithelial cells. The average IFG score was 8 ± 1.8, and the average PCNA score was 75% ± 11.2. Regression analysis was done using data from the IFG score and PCNA score and taking the latter as the predictor variable. The Pearson correlation coefficient was 0.134, with a p-value of 0.572. CONCLUSION: Since the correlation between PCNA score and IFG score was not significant (p > 0.05), we conclude that there is no association between cell proliferation at the invading tumour front and the histological grading of OSCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Antígeno Nuclear de Célula em Proliferação/análise , Diferenciação Celular/fisiologia , Epitélio/patologia , Humanos , Prognóstico
13.
J Cutan Med Surg ; 21(4): 334-338, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28358590

RESUMO

BACKGROUND: Liquid nitrogen cryotherapy is a commonly used technique to treat a wide variety of dermatologic conditions including actinic keratoses, non-melanoma skin cancers, verrucae, and seborrheic keratoses. The risks associated with liquid nitrogen cryotherapy are important to know and discuss with patients prior to treatment. OBJECTIVE: We report a case of cellulitis secondary to liquid nitrogen cryotherapy for actinic keratosis. We sought to review the literature for an estimate of secondary infection rates following cryotherapy treatment. METHODS: We searched Pubmed using the terms cryotherapy and infection or cellulitis. We then looked at articles classified as clinical trials where cryotherapy was used to treat skin conditions. We then selected clinical trials that listed cellulitis or infection as an adverse event. RESULTS AND CONCLUSION: There were no case reports, case series, or review articles detailing the risk of infection from liquid nitrogen cryotherapy. We found 8 articles classified as clinical trials on Pubmed that did list infection as an adverse event. The risk of infection from these studies varied from approximately 2% to 30%. There was a great degree of heterogeneity in treatment sites, length of treatment, and treatment targets. While it is difficult to determine the true incidence of infection from liquid nitrogen cryotherapy, clinicians should endeavor to inform patients of this potential risk.


Assuntos
Celulite (Flegmão) , Crioterapia/efeitos adversos , Nitrogênio/efeitos adversos , Idoso , Braço/patologia , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/patologia , Crioterapia/métodos , Eritema/etiologia , Feminino , Humanos , Ceratose Actínica/terapia , Nitrogênio/uso terapêutico
14.
Hum Mol Genet ; 22(6): 1249-61, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23223014

RESUMO

Unlike genome-wide association studies, few comprehensive studies of copy number variation's contribution to complex human disease susceptibility have been performed. Copy number variations are abundant in humans and represent one of the least well-studied classes of genetic variants; in addition, known rheumatoid arthritis susceptibility loci explain only a portion of familial clustering. Therefore, we performed a genome-wide study of association between deletion or excess homozygosity and rheumatoid arthritis using high-density 550 K SNP genotype data from a genome-wide association study. We used a genome-wide statistical method that we recently developed to test each contiguous SNP locus between 868 cases and 1194 controls to detect excess homozygosity or deletion variants that influence susceptibility. Our method is designed to detect statistically significant evidence of deletions or homozygosity at individual SNPs for SNP-by-SNP analyses and to combine the information among neighboring SNPs for cluster analyses. In addition to successfully detecting the known deletion variants on major histocompatibility complex, we identified 4.3 and 28 kb clusters on chromosomes 10p and 13q, respectively, which were significant at a Bonferroni-type-corrected 0.05 nominal significant level. Independently, we performed analyses using PennCNV, an algorithm for identifying and cataloging copy numbers for individuals based on a hidden Markov model, and identified cases and controls that had chromosomal segments with copy number <2. Using Fisher's exact test for comparing the numbers of cases and controls with copy number <2 per SNP, we identified 26 significant SNPs (protective; more controls than cases) aggregating on chromosome 14 with P-values <10(-8).


Assuntos
Artrite Reumatoide/genética , Estudo de Associação Genômica Ampla , Deleção de Sequência , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Feminino , Homozigoto , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
15.
Biochemistry ; 53(22): 3523-5, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24866698

RESUMO

Next-generation sequencing results from bead-based aptamer libraries have demonstrated that traditional DNA/RNA alignment software is insufficient. This is particularly true for X-aptamers containing specialty bases (W, X, Y, Z, ...) that are identified by special encoding. Thus, we sought an automated program that uses the inherent design scheme of bead-based X-aptamers to create a hypothetical reference library and Markov modeling techniques to provide improved alignments. Aptaligner provides this feature as well as length error and noise level cutoff features, is parallelized to run on multiple central processing units (cores), and sorts sequences from a single chip into projects and subprojects.


Assuntos
Aptâmeros de Nucleotídeos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Técnica de Seleção de Aptâmeros/métodos , Análise de Sequência de DNA/métodos , Software , Sequenciamento de Nucleotídeos em Larga Escala/tendências , Distribuição Aleatória , Técnica de Seleção de Aptâmeros/tendências , Análise de Sequência de DNA/tendências , Software/tendências
16.
Arthritis Rheum ; 65(9): 2457-68, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23740775

RESUMO

OBJECTIVE: To identify genetic determinants of granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: We carried out a genome-wide association study (GWAS) of 492 GPA cases and 1,506 healthy controls (white subjects of European descent), followed by replication analysis of the most strongly associated signals in an independent cohort of 528 GPA cases and 1,228 controls. RESULTS: Genome-wide significant associations were identified in 32 single-nucleotide polymorphic (SNP) markers across the HLA region, the majority of which were located in the HLA-DPB1 and HLA-DPA1 genes encoding the class II major histocompatibility complex (MHC) DPß chain 1 and DPα chain 1 proteins, respectively. Peak association signals in these 2 genes, emanating from SNPs rs9277554 (for DPß chain 1) and rs9277341 (DPα chain 1) were strongly replicated in an independent cohort (in the combined analysis of the initial cohort and the replication cohort, P = 1.92 × 10(-50) and 2.18 × 10(-39) , respectively). Imputation of classic HLA alleles and conditional analyses revealed that the SNP association signal was fully accounted for by the classic HLA-DPB1*04 allele. An independent single SNP, rs26595, near SEMA6A (the gene for semaphorin 6A) on chromosome 5, was also associated with GPA, reaching genome-wide significance in a combined analysis of the GWAS and replication cohorts (P = 2.09 × 10(-8) ). CONCLUSION: We identified the SEMA6A and HLA-DP loci as significant contributors to risk for GPA, with the HLA-DPB1*04 allele almost completely accounting for the MHC association. These two associations confirm the critical role of immunogenetic factors in the development of GPA.


Assuntos
Predisposição Genética para Doença , Granulomatose com Poliangiite/genética , Cadeias beta de HLA-DP/genética , Polimorfismo de Nucleotídeo Único , Semaforinas/genética , Adulto , Alelos , Feminino , Frequência do Gene , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Genótipo , Granulomatose com Poliangiite/imunologia , Haplótipos , Humanos , Complexo Principal de Histocompatibilidade , Masculino
17.
Cell Rep ; 43(2): 113670, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38219147

RESUMO

Neuronal protein synthesis is required for long-lasting plasticity and long-term memory consolidation. Dephosphorylation of eukaryotic initiation factor 2α is one of the key translational control events that is required to increase de novo protein synthesis that underlies long-lasting plasticity and memory consolidation. Here, we interrogate the molecular pathways of translational control that are triggered by neuronal stimulation with brain-derived neurotrophic factor (BDNF), which results in eukaryotic initiation factor 2α (eIF2α) dephosphorylation and increases in de novo protein synthesis. Primary rodent neurons exposed to BDNF display elevated translation of GADD34, which facilitates eIF2α dephosphorylation and subsequent de novo protein synthesis. Furthermore, GADD34 requires G-actin generated by cofilin to dephosphorylate eIF2α and enhance protein synthesis. Finally, GADD34 is required for BDNF-induced translation of synaptic plasticity-related proteins. Overall, we provide evidence that neurons repurpose GADD34, an effector of the integrated stress response, as an orchestrator of rapid increases in eIF2-dependent translation in response to plasticity-inducing stimuli.


Assuntos
Fatores de Despolimerização de Actina , Fator Neurotrófico Derivado do Encéfalo , Actinas , Fator de Iniciação 2 em Eucariotos , Neurônios
18.
Case Rep Dent ; 2023: 6614653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181619

RESUMO

Introduction: Extraction sockets associated with buccal dehiscences and gingival recessions pose particular surgical and restorative challenges. In these cases, unassisted healing following flapless tooth extraction results in severe bone and soft tissue deformities and an aesthetic compromise. Root coverage procedures prior to ridge reconstruction may enable predictable alveolar augmentation. Case Presentation. This is the first case report describing the utilisation of modified tunnel procedure to facilitate ridge reconstruction consisting of ovate pontic and xenograft, of tooth #25 in a 38-year-old-male. The 6 months and 1-year reviews showed optimal soft tissue aesthetics, 100% root coverage of the tooth #25, and bone augmentation, which enabled placement of 10.0 mm × 4.0 mm (3i) implant in a prosthetically driven position. The 6-year review continued to show favourable clinical outcomes. Conclusion: Compromised extraction sockets containing buccal dehiscence and associated with gingival recessions may benefit from soft tissue augmentation procedures to enhance the clinical outcome of ridge reconstruction.

19.
Womens Health Issues ; 33(2): 167-174, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36463011

RESUMO

INTRODUCTION: As an increasing number of people with disabilities become pregnant and give birth, understanding their vulnerabilities for poor mental health and life stress can help to improve their health and well-being. We examined whether people with disabilities are more likely to experience stressful life events 12 months before childbirth, postpartum depressive symptoms (PDS), and lack of postpartum partner and social support, and compared these associations by race/ethnicity. METHODS: Using the Massachusetts Pregnancy Risk Assessment Monitoring System 2016-2020 data (n = 6,483), we used univariate and multivariable logistic regression models to estimate the associations of disability with stressful life events, PDS, and postpartum partner and social support, and calculated risk ratio (RR), adjusted RR, and 95% confidence interval (CI). We also conducted stratified analyses by race/ethnicity. RESULTS: The prevalence of disability was 10.7% overall, and 8.8% among White non-Hispanic people, 14.3% among Black non-Hispanic people, 15.5% among Hispanic people, and 8.3% among Asian non-Hispanic people. Compared with people without disabilities, those with disabilities were more likely to report emotional stress (RR, 1.54; 95% CI, 1.36-1.74), partner-related stress (RR, 2.55; 95% CI, 2.23-2.91), financial stress (RR, 1.55; 95% CI, 1.44-1.68), traumatic stress (RR, 2.27; 95% CI, 1.85-2.79), and PDS (RR, 3.77; 95% CI, 3.13-4.53). People with disabilities were also more likely to lack a partner's emotional support (RR, 2.57; 95% CI, 2.21-2.97), financial support from the newborn's father (RR, 2.89; 95% CI, 2.39-3.51), and social support while feeling tired or frustrated (RR, 2.05; 95% CI, 1.68-2.52). These associations remained statistically significant after adjustment for maternal factors and newborn's birth year. Strong associations of disability with stressful life events (including emotional stress and partner-related stress), PDS, lacking partner's emotional support, and social support existed across racial/ethnic groups. CONCLUSIONS: Pregnant people with disabilities may benefit from additional screening for stressful life events and depression during pregnancy and postpartum. Multidisciplinary efforts that combine mental health screening and treatment, peer support groups, increased health care provider training about caring for people with disabilities during pregnancy, and better access to care for pregnant people with disabilities are needed to improve their health and support their desire to become parents.


Assuntos
Depressão , Pessoas com Deficiência , Gravidez , Feminino , Recém-Nascido , Humanos , Depressão/epidemiologia , Etnicidade , Período Pós-Parto , Apoio Social
20.
Matern Child Health J ; 16(4): 802-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21556697

RESUMO

Women with disabilities are at greater risk for physical abuse than women without disabilities. However, no previous population-based studies have examined physical abuse against women with disabilities around the time of pregnancy, a critical period for mother and child. The objective of this study was to describe the prevalence of physical abuse before and during pregnancy among a representative sample of Massachusetts women with and without disabilities. Data from the 2007-2008 Massachusetts Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed in 2010. Disability prevalence was 4.9% (95% CI = 3.9-6.2) among Massachusetts women giving birth during 2007-2008. The prevalence of physical abuse during the 12-months before pregnancy among women with disabilities was 13.6% (95% CI = 7.2-24.0) compared to 2.8% for women without disabilities (95% CI = 2.1-3.7). Similarly, 8.1% (95% CI = 4.0-15.7) of women with disabilities compared to 2.3% (95% CI = 1.7-3.1) of women without disabilities experienced physical abuse during pregnancy. Multivariate analyses indicated that women with disabilities were more likely to report physical abuse before pregnancy (OR = 4.3, 95% CI = 1.9-9.7), during pregnancy (OR = 2.8, 95% CI = 1.1-7.1), or during either time period (OR = 3.2, 95% CI = 1.4-7.1) than women without disabilities while controlling for maternal age, education, race/Hispanic ethnicity, marital status and household poverty status. No difference was observed by disability status in the likelihood of prenatal-care providers talking to women about physical abuse. These analyses reveal disproportionate prevalence of physical abuse before and during pregnancy among women with disabilities. Screening for physical abuse and timely referral of women in need of assistance are critical to optimize health outcomes for both mother and child.


Assuntos
Pessoas com Deficiência/estatística & dados numéricos , Maus-Tratos Conjugais/estatística & dados numéricos , Adolescente , Adulto , Aconselhamento , Feminino , Humanos , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Vigilância da População , Período Pós-Parto , Gravidez , Cuidado Pré-Natal , Prevalência , Medição de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA