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1.
Palliat Care Soc Pract ; 17: 26323524231179977, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37533732

RESUMO

Background: Healthcare professionals trained in palliative care (PC) improve satisfaction and decrease healthcare overutilization for patients with serious illness and their families. A continuing education (CE) series on primary PC aligned to the National Clinical Practice Guidelines for Quality PC was developed by local, interdisciplinary experts for a target audience of rural, primary care healthcare professionals. The modules were accessed on an online learning management system platform. Objective: The study objectives were to assess differences in participants' knowledge, competence, performance, and ability to improve patient care as well as commitment to change practice after taking each of the CE modules. Design and Methods: To achieve these objectives, a descriptive design was used with a convenience sample of healthcare professionals who registered for the CE series and completed at least one module. Participants completed demographic questions and an evaluation survey after completing each module. Results: So far, 158 healthcare professionals have registered for the series with the majority being nurses and social workers. Although the professionals reported having extensive healthcare experience, they did not report having the same level of PC experience. The professionals represent nine different states. All the CE modules increased teamwork skills for most participants. The CE modules on cultural aspects and self-care had the biggest influence on participants' ability to improve patient outcomes. Cultural aspects, care of the actively dying, and advance care planning had the greatest impact on participants' knowledge, competence, and performance. Conclusion: The primary PC education series improved self-reported skills in teamwork, practice habits, and meeting goals of healthcare professionals from a variety of disciplines and settings. These enhanced primary PC skills will improve the incorporation of PC into a variety of practice settings, by multiple disciplines to enhance access to PC outside of, and potentially referrals to, specialty PC programs.Palliative care (PC) is an emerging field of healthcare aimed at positively affecting patients living with serious illness and their families. An important factor that influences a health professional's successful delivery of PC may be their knowledge, experiences, and confidence. PC training provided to healthcare professionals improves patients' and healthcare professionals' satisfaction and reduces healthcare expenditures through cost savings and cost avoidance.1,2.

2.
N Z Med J ; 135(1557): 49-63, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35772112

RESUMO

AIM: To provide an up-to-date review of thunderstorm asthma (TA), identifying causative factors, and to discuss implications for management of TA in New Zealand. METHODS: A literature search was carried out to identify articles that investigate the characteristics and causative factors of TA. Nine electronic databases were searched, yielding 372 articles, reduced to 30 articles after screening for duplication and relevance. RESULTS: TA is globally rare, with 29 reported events since 1983, but is expected to increase in frequency as Earth warms. Triggers include both pollen (particularly ryegrass pollen) and fungal spores. Individual risk factors include outdoor exposure, sensitivity to triggering allergens and history of seasonal allergic rhinitis. History of asthma is not a strong risk factor but is associated with severity of outcome. Limited data on demographic characteristics suggests that individuals aged between 20 and 60 and (in Australasia) of Asian/Indian ethnicity are at higher risk. A single TA event has been reported in New Zealand to date, but much of New Zealand may be at risk of future events given that ryegrass pastures are widely distributed, and summer thunderstorms can occur anywhere. CONCLUSIONS: We recommend developing rapidly deployable public messaging to support the health emergency management response to future TA events, together with the instigation of routine aeroallergen monitoring.


Assuntos
Asma , Rinite Alérgica Sazonal , Adulto , Alérgenos/efeitos adversos , Asma/epidemiologia , Asma/etiologia , Asma/terapia , Humanos , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Pólen/efeitos adversos , Adulto Jovem
4.
Animals (Basel) ; 11(11)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34827873

RESUMO

Responding to emergencies requires many different individuals and organisations to work well together under extraordinary circumstances. Unfortunately, the management of animal welfare in emergencies remains largely disconnected from emergency management overall. This is due predominately to professional silos and a failure to understand the importance of human-animal-environment (h-a-e) interdependencies. One Welfare (OW) is a concept with these interrelationships at its core. This paper argues that by adopting an OW framework it will be possible to achieve a transdisciplinary approach to emergency management in which all stakeholders acknowledge the importance of the h-a-e interdependencies and work to implement a framework to support this. Acknowledging that such a transformational change will not be easy, this paper proposes several strategies to overcome the challenges and optimise the outcomes for animal welfare emergency management (AWEM). These include legislation and policy changes including h-a-e interface interactions as business as usual, improving knowledge through interprofessional education and training, incorporating One Welfare champions, and recognising the role of animals as vital conduits into communities.

5.
Chemosphere ; 278: 130303, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33819884

RESUMO

Freshly erupted volcanic ash contains a range of soluble elements, some of which can generate harmful effects in living cells and are considered potentially toxic elements (PTEs). This work investigates the leaching dynamics of ash-associated PTEs in order to optimize a method for volcanic ash respiratory hazard assessment. Using three pristine (unaffected by precipitation) ash samples, we quantify the release of PTEs (Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, Zn) and major cations typical of ash leachates (Mg, Na, Ca, K) in multiple simulated lung fluid (SLF) preparations and under varying experimental parameters (contact time and solid to liquid ratio). Data are compared to a standard water leach (WL) to ascertain whether the WL can be used as a simple proxy for SLF leaching. The main findings are: PTE concentrations reach steady-state dissolution by 24 h, and a relatively short contact time (10 min) approximates maximum dissolution; PTE dissolution is comparatively stable at low solid to liquid ratios (1:100 to 1:1000); inclusion of commonly used macromolecules has element-specific effects, and addition of a lung surfactant has little impact on extraction efficiency. These observations indicate that a WL can be used to approximate lung bioaccessible PTEs in an eruption response situation. This is a useful step towards standardizing in vitro methods to determine the soluble-element hazard from inhaled ash.


Assuntos
Metais Pesados , Erupções Vulcânicas , Cinza de Carvão , Íons , Pulmão/química , Metais Pesados/análise
6.
Am J Kidney Dis ; 77(5): 748-756.e1, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33465417

RESUMO

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, patients receiving maintenance dialysis are a highly vulnerable population due to their comorbidities and circumstances that limit physical distancing during treatment. This study sought to characterize the risk factors for and outcomes following COVID-19 in this population. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Maintenance dialysis patients in clinics of a midsize national dialysis provider that had at least 1 patient who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from February to June 2020. PREDICTORS: Demographics, dialysis characteristics, residence in a congregated setting, comorbid conditions, measurements of frailty, and use of selected medications. OUTCOMES: COVID-19, defined as having a positive SARS-CoV-2 test result, and all-cause mortality among those with COVID-19. ANALYTICAL APPROACH: Logistic regression analyses conducted to identify clinical characteristics associated with COVID-19 and risk factors associated with mortality among patients following COVID-19. RESULTS: 438 of 7948 (5.5%) maintenance dialysis patients developed COVID-19. Male sex, Black race, in-center dialysis (vs home dialysis), treatment at an urban clinic, residence in a congregate setting, and greater comorbidity were associated with contracting COVID-19. Odds of COVID-19 were 17-fold higher for those residing in a congregated setting (odds ratio [OR], 17.10 [95% CI, 13.51-21.54]). Of the 438 maintenance dialysis patients with COVID-19, 109 (24.9%) died. Older age, heart disease, and markers of frailty were associated with mortality. LIMITATIONS: No distinction was detected between symptomatic and asymptomatic SARS-CoV-2 positivity, with asymptomatic screening limited by testing capacity during this initial COVID-19 surge period. CONCLUSIONS: COVID-19 is common among patients receiving maintenance dialysis, particularly those residing in congregate settings. Among maintenance dialysis patients with COVID-19, mortality is high, exceeding 20%.


Assuntos
COVID-19 , Fragilidade , Cardiopatias/epidemiologia , Controle de Infecções/métodos , Falência Renal Crônica , Diálise Renal , Fatores Etários , Idoso , COVID-19/mortalidade , COVID-19/terapia , Comorbidade , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/etiologia , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Mortalidade , Casas de Saúde/estatística & dados numéricos , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Estados Unidos/epidemiologia
8.
Prehosp Disaster Med ; 35(5): 574-578, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32669138

RESUMO

Volcanoes cause a wide range of hazardous phenomena. Close to volcanic vents, hazards can be highly dangerous and destructive and include pyroclastic flows and surges, ballistic projectiles, lava flows, lahars, thick ashfalls, and gas and aerosol emissions. Direct health impacts include trauma, burns, and exacerbation of respiratory diseases. Far-reaching volcanic hazards include volcanic ashfalls, gas and aerosol dispersion, and lahars. Within Oceania, the island arc countries of Papua New Guinea (PNG), the Solomon Islands, Vanuatu, Tonga, and New Zealand are the most at-risk from volcanic activity. Since 1500ad, approximately 10,000 lives have been lost due to volcanic activity across Oceania, with 39 lives lost since 2000. While volcano monitoring and surveillance save lives, residual risks remain from small, sudden, unheralded eruptions, such as the December 9, 2019 eruption of Whakaari/White Island volcano, New Zealand which has a death toll of 21 at the time of writing. Widespread volcanic ashfalls can affect the habitability of downwind communities by contaminating water supplies, damaging crops and buildings, and degrading indoor and outdoor air quality, as well as disrupting transport and communication networks and access to health services. While the fatality rate due to volcanic eruptions may be low, far greater numbers of people may be affected by volcanic activity with approximately 100,000 people in PNG and Vanuatu displaced since 2000. It is challenging to manage health impacts for displaced people, particularly in low-income countries where events such as eruptions occur against a background of low, variable vaccination rates, high prevalence of infectious diseases, poor sanitation infrastructure, and poor nutritional status. As a case study, the 2017-2018 eruption of Ambae volcano, Vanuatu caused no casualties but triggered two separate mandatory off-island evacuations of the entire population of approximately 11,700 people. On the neighboring island of Santo, a health disaster response was coordinated by local government and provided acute care when evacuees arrived. Involving primary care clinicians in this setting enhanced local capacity for health care provision and allowed for an improved understanding of the impact of displacement on evacuee communities.


Assuntos
Planejamento em Desastres , Erupções Vulcânicas , Ferimentos e Lesões/etiologia , Humanos , Oceania/epidemiologia , Ferimentos e Lesões/epidemiologia
9.
Oral Dis ; 25(5): 1325-1334, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30920100

RESUMO

OBJECTIVES: To determine expression and localization of membrane-associated mucins within human keratinized and non-keratinized oral epithelia, and to explore transcriptional changes associated with primary Sjögren's syndrome. SUBJECTS AND METHODS: Mucin transcripts and glycoproteins were determined by RT-PCR and immunohistochemistry, respectively, in oral keratinized (hard palate) and non-keratinized (buccal) epithelia obtained from three cadavers. Mucin transcripts assessed by quantitative PCR were compared between cells harvested by brushing buccal and palatal epithelia of 25 female primary Sjögren's syndrome patients vs 25 healthy age-matched female control subjects. RESULTS: In hard palate, MUC4 is absent and MUC1 localized to deeper cell layers. Both mucins are within the apical layers of buccal epithelium. MUC15 is localized throughout all palatal cell layers and in all but the basal layer of buccal epithelia. MUC16, MUC20, and MUC21 glycoproteins are localized within all but the basal cell layer of both tissue types. In buccal cells of primary Sjögren's patients, MUC21 transcripts are down-regulated 3.4-fold and MUC20 2.6-fold. Dysregulation of select epithelial mucins may therefore contribute to xerostomia. CONCLUSIONS: Differential expression of multiple mucins and down-regulation in Sjögren's syndrome support further study of oral epithelial mucin physiology and pathophysiology, including their functions in hydration and lubrication of the oral mucosal pellicle.


Assuntos
Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Mucinas/metabolismo , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/patologia , Adulto , Idoso , Estudos de Casos e Controles , Película Dentária , Epitélio , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/genética , Síndrome de Sjogren/genética
10.
J Investig Med High Impact Case Rep ; 7: 2324709618820660, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30791716

RESUMO

Coffin-Lowry syndrome is expressed as different phenotypes in males and females. In males, it is characterized by facial abnormalities, marked developmental disability, and skeletal changes. Approximately 80% of cases are associated with kyphoscoliosis, which can be quite severe, as seen in our patient, causing paraplegia and restrictive lung disease. In this article, we present the third oldest documented male case of Coffin-Lowry syndrome with severe kyphoscoliosis, paraplegia, and restrictive lung disease.


Assuntos
Síndrome de Coffin-Lowry/complicações , Pneumopatias/complicações , Paraplegia/complicações , Escoliose/complicações , Anormalidades Múltiplas/genética , Adulto , Síndrome de Coffin-Lowry/genética , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/genética , Masculino , Paraplegia/genética , Fenótipo , Radiografia Torácica , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Escoliose/diagnóstico por imagem , Escoliose/genética , Tomografia Computadorizada por Raios X
11.
Health Promot Pract ; 19(1_suppl): 63S-69S, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30176771

RESUMO

In the Holyoke Food & Fitness Policy Council (HFFPC) case study, the challenges of providing equitable multistakeholder organizing are examined. The importance of housing the work in the community, power sharing, and having community representation in the leadership is made clear. The HFFPC partnership began with vigor, encountered challenges of trust, transparency, aligned goals and values; it dissolved, and reformed. Because it began with shared values of strong communities and healthy people, the partnership continues to evolve, build local leadership, change narratives, and articulate the need for racial equity in their food system, while shifting local systems and policies that frame who has access to healthy food and safe spaces to exercise in a low-income Latino community.


Assuntos
Participação da Comunidade , Relações Comunidade-Instituição , Promoção da Saúde/métodos , Relações Interprofissionais , Dieta Saudável , Exercício Físico , Alimentos , Disparidades nos Níveis de Saúde , Hispânico ou Latino , Humanos , Liderança , Massachusetts , Estudos de Casos Organizacionais , Desenvolvimento de Programas
12.
Clin Immunol ; 192: 58-67, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29679709

RESUMO

Primary Sjögren's syndrome (pSS) is an autoimmune disease in which the underlying cause has yet to be elucidated. The main objective of this study was to determine the T cell receptor (TCR) repertoires of individual infiltrating T helper (Th)-1 and 17 cells of pSS patients using single-cell analysis. Single-cell analysis of ex-vivo infiltrating T cells demonstrated that pSS patients had higher frequencies of activated Th17 cells. Single-cell TCR sequencing revealed that TCRß variable (TRBV)3-1/joint (J)1-2 (CLFLSMSACVW) and TRBV20-1/J1-1 (SVGSTAIPP*T) were expressed by activated Th1 and Th17 cells in both cohorts. Uniquely, TCRα variable (TRAV)8-2/J5 (VVSDTVLETAGE) was expressed by Th1 cells present only in patients and complementarity-determining region (CDR)3α-specific motif (LSTD*E) present in both Th1/Th17 cells. The study demonstrates that both activated Th1 and Th17 cells of pSS patients showed restricted clonal diversities of which two CDR3 motifs were present in controls and patients, with another two motifs unique to pSS.


Assuntos
Análise de Célula Única/métodos , Síndrome de Sjogren/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adulto , Idoso , Motivos de Aminoácidos/genética , Motivos de Aminoácidos/imunologia , Sequência de Aminoácidos , Estudos de Coortes , Feminino , Humanos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Síndrome de Sjogren/genética , Síndrome de Sjogren/metabolismo , Células Th1/metabolismo , Células Th17/metabolismo
13.
Sci Rep ; 7(1): 12512, 2017 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-28970488

RESUMO

The development of Sjögren's syndrome (SjS) is a dynamic and temporal process with a female predilection. Following the initial influx of immune cells, T cell clusters develop, accelerating the pathology in the salivary glands. Proinflammatory cytokines, IFN-γ and IL-17A, produced by T cells contribute synergistically to the disease. In this study, we examined the sexual dimorphism in cellular infiltrates of the salivary glands by using functional single-cell microengraving analysis. Using high-throughput sequencing, we investigated the clonal diversity of the T cell receptors (TCRs) of infiltrating IFN-γ and IL-17A-producing T cells in male and female SjS-susceptible (SjSs) C57BL/6.NOD-Aec1Aec2 mice. There were elevated frequencies of IFN-γ and IL-17A-producing effector T cell populations in female SjSS mice compared to male SjSS mice. MEME analysis shows high frequency and unique, sexually dimorphic motifs in the TCR hypervariable regions in the SjSS mice. Male mice selected for TRAV8/TRAJ52 (CATDLNTGANTGKLTFG) TCR genes in Th1 cells and TRBV16/(TRBD1/2)TRBJ1-7 (CGGKRRLESIFR) in Th1 and Th17 cells. Female SjSS mice selected for TRAV8/TRAJ52 (CATDLNTGANTGKLTFG), TRAV13D-2/TRAJ23 (CVYLEHHFE), and TRBV23/(TRBD2)TRBJ2-2 (CRKLHSCATCALNFL) in Th1 cells. These findings suggest that there is an elevated prevalence of pathogenic effector T cells in the glands with a sexually dimorphic selection bias of TCR repertoires.


Assuntos
Interferon gama/genética , Interleucina-17/genética , Glândulas Salivares/imunologia , Síndrome de Sjogren/genética , Animais , Seleção Clonal Mediada por Antígeno/genética , Seleção Clonal Mediada por Antígeno/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Interferon gama/imunologia , Interleucina-17/imunologia , Masculino , Camundongos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Caracteres Sexuais , Análise de Célula Única , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Células Th1/imunologia , Células Th17/imunologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-27754454

RESUMO

The greater Wellington region, New Zealand, is highly vulnerable to large earthquakes because it is cut by active faults. Bulk water supply pipelines cross the Wellington Fault at several different locations, and there is considerable concern about severe disruption of the provision of reticulated water supplies to households and businesses in the aftermath of a large earthquake. A number of policy initiatives have been launched encouraging householders to install rainwater tanks to increase post-disaster resilience. However, little attention has been paid to potential health hazards associated with consumption of these supplies. To assess health hazards for householders in emergency situations, six 200-litre emergency water tanks were installed at properties across the Wellington region, with five tanks being allowed to fill with roof-collected rainwater and one tank being filled with municipal tapwater as a control. Such tanks are predominantly set aside for water storage and, once filled, feature limited drawdown and recharge. Sampling from these tanks was carried out fortnightly for one year, and samples were analysed for E. coli, pH, conductivity, a range of major and trace elements, and organic compounds, enabling an assessment of the evolution of water chemistry in water storage tanks over time. Key findings were that the overall rate of E. coli detections in the rain-fed tanks was 17.7%, which is low in relation to other studies. We propose that low incidences of may be due to biocidal effects of high zinc concentrations in tanks, originating from unpainted galvanised steel roof cladding. Lead concentrations were high compared to other studies, with 69% of rain-fed tank samples exceeding the World Health Organisation's health-based guideline of 0.01 mg/L. Further work is required to determine risks of short-term consumption of this water in emergency situations.


Assuntos
Desastres , Chuva , População Urbana , Microbiologia da Água , Água/química , Escherichia coli/isolamento & purificação , Substâncias Perigosas/isolamento & purificação , Nova Zelândia , Compostos Orgânicos/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Abastecimento de Água/normas , Zinco/isolamento & purificação
15.
J Immunol Methods ; 437: 28-36, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27460476

RESUMO

Anti-muscarinic type 3 receptor autoantibodies (anti-M3R) are reported as potential inhibitors of saliva secretion in Sjögren's syndrome (SjS). However, despite extensive efforts to establish an anti-M3R detection method, there is no clinical test available for these autoantibodies. The purpose of this study was to propose inclusion of anti-M3R testing for SjS diagnosis through investigation of their prevalence using a modified In-Cell Western (ICW) assay. A stable cell line expressing human M3R tagged with GFP (M3R-GFP) was established to screen unadsorbed and adsorbed plasma from primary SjS (n=24), rheumatoid arthritis (RA, n=18), systemic lupus erythematosus (SLE, n=18), and healthy controls (HC, n=23). Anti-M3R abundance was determined by screening for the intensity of human IgG interacting with M3R-GFP cells by ICW assay, as detected by an anti-human IgG IRDye800-conjugated secondary antibody and normalized to GFP. Method comparisons and receiver-operating-characteristic (ROC)-curve analyses were performed to evaluate the diagnostic value of our current approaches. Furthermore, clinical parameters of SjS were also analyzed in association with anti-M3R. Anti-M3R was significantly elevated in SjS plasma in comparison with HC, SLE, or RA (P<0.01). SjS anti-M3R intensities were greater than two-standard deviations above the HC mean for both unadsorbed (16/24, 66.67%) and adsorbed (18/24, 75%) plasma samples. Furthermore, anti-M3R was associated with anti-SjS-related-antigen A/Ro positivity (P=0.0353). Linear associations for anti-M3R intensity indicated positive associations with focus score (R(2)=0.7186, P<0.01) and negative associations with saliva flow rate (R(2)=0.3052, P<0.05). Our study strongly supports our rationale to propose inclusion of anti-M3R for further testing as a non-invasive serological marker for SjS diagnosis.


Assuntos
Autoantígenos/imunologia , RNA Citoplasmático Pequeno/imunologia , Receptor Muscarínico M3/imunologia , Ribonucleoproteínas/imunologia , Testes Sorológicos/métodos , Síndrome de Sjogren/diagnóstico , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Autoanticorpos/sangue , Feminino , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Receptor Muscarínico M3/genética , Proteínas Recombinantes de Fusão/genética
16.
Arthritis Res Ther ; 18(1): 95, 2016 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-27142093

RESUMO

BACKGROUND: Sjögren's syndrome (SjS) monocytes have a pro-inflammatory phenotype, which may influence SjS pathogenesis. MicroRNAs (miRNAs) are small endogenously expressed molecules that can inhibit protein expression of their targeted genes and have important functions in regulating cell signaling responses. We profiled miRNAs in SjS monocytes to identify a SjS-specific miRNA profile and determine the potential roles of miRNAs in SjS pathogenesis. METHODS: Total RNA was extracted from healthy control (HC, n = 10), SjS (n = 18), systemic lupus erythematosus (SLE, n = 10), and rheumatoid arthritis (RA, n = 10) peripheral blood CD14(+) monocytes for miRNA microarray analysis. To validate select miRNAs from the microarray analysis, the original cohort and a new cohort of monocyte RNA samples from HC (n = 9), SjS (n = 12), SLE (n = 8), and RA (n = 9) patients were evaluated by quantitative reverse transcription (RT)-PCR. Functional predictions of differentially expressed miRNAs were determined through miRNA target prediction database analyses. Statistical analyses performed included one-way analysis of variance with Bonferroni post tests, linear regression, and receiver operating characteristic curve analyses. RESULTS: MiRNAs were predominantly upregulated in SjS monocytes in comparison with controls. Quantitative RT-PCR confirmations supported co-regulation of miR-34b-3p, miR-4701-5p, miR-609, miR-300, miR-3162-3p, and miR-877-3p in SjS monocytes (13/30, 43.3 %) in comparison with SLE (1/17, 5.8 %) and RA (1/18, 5.6 %). MiRNA-target pathway predictions identified SjS-associated miRNAs appear to preferentially target the canonical TGFß signaling pathway as opposed to pro-inflammatory interleukin-12 and Toll-like receptor/NFkB pathways. CONCLUSIONS: Our results underscore a novel underlying molecular mechanism where SjS-associated miRNAs may collectively suppress TGFß signaling as opposed to pro-inflammatory interleukin-12 and Toll-like receptor/NFκB pathways in SjS pathogenesis.


Assuntos
MicroRNAs/imunologia , Monócitos/imunologia , Síndrome de Sjogren/imunologia , Transcriptoma , Fator de Crescimento Transformador beta/imunologia , Perfilação da Expressão Gênica , Humanos , Receptores de Lipopolissacarídeos/imunologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Fator de Crescimento Transformador beta/metabolismo
17.
Genom Data ; 7: 178-84, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26981401

RESUMO

TH17 cells and their associated signature cytokines, IL-17 and IL-22, are highly elevated in primary Sjögren's syndrome (pSjS). The levels of IL-22 present in sera showed significant correlations with many disease parameters, specifically hyposalivation, anti-SSB, anti-SSA/SSB, hypergammaglobulinemia and rheumatoid factor. The present study aims to examine the biological function of IL-22 on human salivary glands. To accomplish the goal, microarray analysis using the HumanHT-12 v4 Expression BeadChip was utilized to determine the biological function of IL-22. Differential expression analyses were conducted using the LIMMA package from the Bioconductor project. MTT assay, flow cytometry and Western blotting were used to identify the function of IL-22 on human salivary gland cells. Results indicate an extensive effect of IL-22 on many major molecular functions including activation of antimicrobial genes and downregulation of immune-associated pathways. Functional studies performed in-vitro using human salivary gland cells treated with IL-22 indicated a direct effect of IL-22 on cell cycling, specifically reducing cellular proliferation at the G2-M phase by activation of STAT3. These results suggest the important role of IL-22 in the salivary gland function. The present study suggests that IL-22 might be involved in regulating inflammation and controlling the cell proliferation in SjS.

18.
J Am Dent Assoc ; 147(4): 295-305, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26762707

RESUMO

BACKGROUND: Salivary dysfunction in Sjögren disease can lead to serious and costly oral health complications. Clinical practice guidelines for caries prevention in Sjögren disease were developed to improve quality and consistency of care. METHODS: A national panel of experts devised clinical questions in a Population, Intervention, Comparison, Outcomes format and included use of fluoride, salivary stimulants, antimicrobial agents, and nonfluoride remineralizing agents. The panel conducted a systematic search of the literature according to pre-established parameters. At least 2 members extracted the data, and the panel rated the strength of the recommendations by using a variation of grading of recommendations, assessment, development, and evaluation. After a Delphi consensus panel was conducted, the experts finalized the recommendations, with a minimum of 75% agreement required. RESULTS: Final recommendations for patients with Sjögren disease with dry mouth were as follows: topical fluoride should be used in all patients (strong); although no study results link improved salivary flow to caries prevention, the oral health community generally accepts that increasing saliva may contribute to decreased caries incidence, so increasing saliva through gustatory, masticatory, or pharmaceutical stimulation may be considered (weak); chlorhexidine administered as varnish, gel, or rinse may be considered (weak); and nonfluoride remineralizing agents may be considered as an adjunct therapy (moderate). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The incidence of caries in patients with Sjögren disease can be reduced with the use of topical fluoride and other preventive strategies.


Assuntos
Cárie Dentária/prevenção & controle , Síndrome de Sjogren/complicações , Administração Tópica , Anti-Infecciosos/uso terapêutico , Assistência Odontológica/normas , Cárie Dentária/etiologia , Fluoretos/administração & dosagem , Fluoretos/uso terapêutico , Humanos , Salivação/efeitos dos fármacos , Síndrome de Sjogren/terapia , Xerostomia/etiologia , Xerostomia/terapia
19.
Mol Immunol ; 68(2 Pt C): 606-16, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26505653

RESUMO

Sjögren's syndrome (SjS) is an autoimmune condition that primarily affects salivary and lacrimal glands, causing loss of secretion. We have previously shown that microRNA-146a (miR-146a) is over-expressed in the salivary glands and peripheral blood mononuclear cells (PBMC) of SjS-prone mice (C57BL/6.NOD-Aec1Aec2, B6DC) and in PBMC of SjS patients. The purpose of this research was to identify a target molecule of miR-146a and identify subpopulations of cells affected by altered miR-146a in the salivary glands of SjS-prone mice. In silico analyses identified costimulatory molecule CD80 as a potential target of miR-146a. Luciferase assay of the human CD80 3'untranslated region demonstrated miR-146a directly inhibited CD80 protein expression as indicated by reduced luciferase reporter expression and an examination of B6DC salivary glands revealed a reduction in CD80 protein. More interestingly, the specific reduction in CD80 protein was detected from the salivary gland epithelial cell population and in interstitial dendritic cells in the glands as well. The reduction in CD80 protein levels in salivary gland epithelial cells were negatively associated with elevated miR-146a expression. Therefore, this study provides the first indication that salivary gland epithelial cells may be critically involved in SjS progression by altering CD86:CD80 protein ratio in response to miR-146a upregulation.


Assuntos
Antígeno B7-1/biossíntese , Antígeno B7-2/biossíntese , Regulação da Expressão Gênica/imunologia , MicroRNAs/genética , Síndrome de Sjogren/genética , Animais , Antígeno B7-1/genética , Antígeno B7-1/imunologia , Antígeno B7-2/imunologia , Western Blotting , Modelos Animais de Doenças , Citometria de Fluxo , Imunofluorescência , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/imunologia , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Sjogren/imunologia , Transfecção , Regulação para Cima
20.
J Biol Chem ; 290(5): 2993-3008, 2015 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-25512380

RESUMO

Saliva functions in innate immunity of the oral cavity, protecting against demineralization of teeth (i.e. dental caries), a highly prevalent infectious disease associated with Streptococcus mutans, a pathogen also linked to endocarditis and atheromatous plaques. Gel-forming mucins are a major constituent of saliva. Because Muc19 is the dominant salivary gel-forming mucin in mice, we studied Muc19(-/-) mice for changes in innate immune functions of saliva in interactions with S. mutans. When challenged with S. mutans and a cariogenic diet, total smooth and sulcal surface lesions are more than 2- and 1.6-fold higher in Muc19(-/-) mice compared with wild type, whereas the severity of lesions are up to 6- and 10-fold higher, respectively. Furthermore, the oral microbiota of Muc19(-/-) mice display higher levels of indigenous streptococci. Results emphasize the importance of a single salivary constituent in the innate immune functions of saliva. In vitro studies of S. mutans and Muc19 interactions (i.e. adherence, aggregation, and biofilm formation) demonstrate Muc19 poorly aggregates S. mutans. Nonetheless, aggregation is enhanced upon adding Muc19 to saliva from Muc19(-/-) mice, indicating Muc19 assists in bacterial clearance through formation of heterotypic complexes with salivary constituents that bind S. mutans, thus representing a novel innate immune function for salivary gel-forming mucins. In humans, expression of salivary MUC19 is unclear. We find MUC19 transcripts in salivary glands of seven subjects and demonstrate MUC19 glycoproteins in glandular mucous cells and saliva. Similarities and differences between mice and humans in the expression and functions of salivary gel-forming mucins are discussed.


Assuntos
Cárie Dentária/metabolismo , Cárie Dentária/microbiologia , Imunidade Inata/fisiologia , Mucinas/metabolismo , Saliva/metabolismo , Streptococcus mutans/patogenicidade , Adulto , Animais , Cárie Dentária/imunologia , Feminino , Humanos , Imunidade Inata/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Mucinas/genética
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