RESUMO
OBJECTIVES: An increased prevalence of periodontitis and perturbation of the oral microbiome has been identified in patients with rheumatoid arthritis (RA). The periodontal pathogen Porphyromonas gingivalis may cause local citrullination of proteins, potentially triggering anti-citrullinated protein antibody production. However, it is not known if oral dysbiosis precedes the onset of clinical arthritis. This study comprehensively characterised the oral microbiome in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals without clinical synovitis (CCP+at risk). METHODS: Subgingival plaque was collected from periodontally healthy and diseased sites in 48 CCP+at risk, 26 early RA and 32 asymptomatic healthy control (HC) individuals. DNA libraries were sequenced on the Illumina HiSeq 3000 platform. Taxonomic profile and functional capability of the subgingival microbiome were compared between groups. RESULTS: At periodontally healthy sites, CCP+at risk individuals had significantly lower microbial richness compared with HC and early RA groups (p=0.004 and 0.021). Microbial community alterations were found at phylum, genus and species levels. A large proportion of the community differed significantly in membership (523 species; 35.6%) and structure (575 species; 39.1%) comparing CCP+at risk and HC groups. Certain core species, including P. gingivalis, had higher relative abundance in the CCP+at risk group. Seventeen clusters of orthologous gene functional units were significantly over-represented in the CCP+at risk group compared with HC (adjusted p value <0.05). CONCLUSION: Anti-CCP positive at-risk individuals have dysbiotic subgingival microbiomes and increased abundance of P. gingivalis compared with controls. This supports the hypothesis that the oral microbiome and specifically P. gingivalis are important in RA initiation.
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Artrite Reumatoide/microbiologia , Disbiose/imunologia , Microbiota/imunologia , Periodontite/microbiologia , Porphyromonas gingivalis/imunologia , Adulto , Anticorpos Antiproteína Citrulinada/sangue , Anticorpos Antiproteína Citrulinada/imunologia , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Disbiose/microbiologia , Feminino , Gengiva/imunologia , Gengiva/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/imunologia , Fatores de RiscoRESUMO
We investigated the meiotic role of Srs2, a multi-functional DNA helicase/translocase that destabilises Rad51-DNA filaments and is thought to regulate strand invasion and prevent hyper-recombination during the mitotic cell cycle. We find that Srs2 activity is required for normal meiotic progression and spore viability. A significant fraction of srs2 mutant cells progress through both meiotic divisions without separating the bulk of their chromatin, although in such cells sister centromeres often separate. Undivided nuclei contain aggregates of Rad51 colocalised with the ssDNA-binding protein RPA, suggesting the presence of persistent single-strand DNA. Rad51 aggregate formation requires Spo11-induced DSBs, Rad51 strand-invasion activity and progression past the pachytene stage of meiosis, but not the DSB end-resection or the bias towards interhomologue strand invasion characteristic of normal meiosis. srs2 mutants also display altered meiotic recombination intermediate metabolism, revealed by defects in the formation of stable joint molecules. We suggest that Srs2, by limiting Rad51 accumulation on DNA, prevents the formation of aberrant recombination intermediates that otherwise would persist and interfere with normal chromosome segregation and nuclear division.
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DNA Helicases/genética , Meiose , Rad51 Recombinase/metabolismo , Recombinação Genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , DNA Helicases/metabolismo , MAP Quinase Quinase 1/metabolismo , Viabilidade Microbiana/genética , Mutação , Agregados Proteicos , Ligação Proteica , Proteínas de Saccharomyces cerevisiae/metabolismo , Esporos FúngicosRESUMO
INTRODUCTION: The majority of women who smoke cigarettes report that concern about weight gain is a barrier to quitting. We developed an intervention incorporating distress tolerance, appetite awareness, and mindful eating skills to target concerns about post-cessation weight gain and emotional eating (DT-W). In the current study, we conducted a pilot randomized controlled trial of DT-W versus a smoking health education (HE) intervention. METHODS: Participants (N = 69 adult female, weight-concerned smokers) were recruited in cohorts of 4-11. Cohorts were randomized to DT-W or HE. DT-W and HE were matched on format (single individual session followed by eight group sessions), inclusion of cognitive behavioral therapy for smoking cessation (CBT) content, and pharmacotherapy (nicotine patches). Follow-up assessments occurred at 1-, 3-, and 6-months post-treatment. RESULTS: The recruitment goal was met; 61 of the 69 participants attended at least one group session. There were no significant differences between DT-W and HE in the number of group sessions attended (DT-W adjusted M = 5.09, HE adjusted M = 5.03, p = .92), ratings of treatment effectiveness or usefulness of skills, or retention at 6-month follow-up (79% in DT-W vs. 78% in HE) (ps > .05), but comprehension ratings were lower in DT-W than in HE (p = .02). CONCLUSIONS: Overall, these results suggest that the study procedures and interventions were feasible and acceptable, but changes to the DT-W intervention content to improve comprehension should be considered prior to conducting a fully powered trial. IMPLICATIONS: A distress tolerance-based treatment targeting fear of weight gain after smoking cessation and post-cessation emotional eating was feasible and acceptable relative to a smoking HE comparison condition, but changes should be considered before conducting a larger trial. Continued innovation in treatment development for weight-concerned smokers is needed.
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Terapia Cognitivo-Comportamental/métodos , Fumantes/psicologia , Abandono do Hábito de Fumar/psicologia , Fumar/terapia , Estresse Psicológico/terapia , Aumento de Peso , Peso Corporal , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Pessoa de Meia-Idade , Motivação , Projetos Piloto , Fumar/epidemiologia , Fumar/psicologia , Abandono do Hábito de Fumar/métodos , Estados Unidos/epidemiologiaRESUMO
Interosseous tendon inflammation (ITI) has been described in rheumatoid arthritis (RA). Whether ITI occurs in at-risk individuals before the onset of clinical synovitis is unknown. OBJECTIVES: To investigate, by MRI, ITI in anti-cyclic citrullinated peptide (CCP)-positive at-risk individuals (CCP +at risk) and to describe the anatomy, prevalence and clinical associations across the RA continuum. METHODS: Hand MRI was performed in 93 CCP + at risk, 47 early RA (ERA), 28 established 'late' RA (LRA) and 20 healthy controls (HC) and scored for ITI, flexor tenosynovitis (TSV) and RA MRI scoring at the metacarpophalangeal joints (MCPJs). Cadaveric and histological studies were performed to explore the anatomical basis for MRI ITI. RESULTS: The proportion of subjects with ITI and the number of inflamed interosseous tendons (ITs) increased along the disease continuum (p<0.001): 19% of CCP +at risk, 49% of ERA and 57% of LRA had ≥1 IT inflamed . ITI was not found in any HC. ITI was more frequently identified in tender MCPJs compared with nontender MCPJs (28% vs 12%, respectively). No IT tenosynovial sheath was identified in cadavers on dissection or histological studies suggesting MRI findings represent peritendonitis. Dye studies indicated no communication between the IT and the joint. CONCLUSIONS: ITI occurs in CCP + at-risk individuals and can precede the onset of clinical synovitis. The ITs may be important nonsynovial extracapsular targets in the development and progression of RA.
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Anticorpos Antiproteína Citrulinada/sangue , Articulação Metacarpofalângica/diagnóstico por imagem , Tendinopatia/diagnóstico por imagem , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/imunologia , Cadáver , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Articulação Metacarpofalângica/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Sinovite/diagnóstico por imagem , Sinovite/imunologia , Sinovite/patologia , Tendinopatia/imunologia , Tendinopatia/patologia , Tenossinovite/diagnóstico por imagem , Tenossinovite/imunologia , Tenossinovite/patologiaRESUMO
OBJECTIVES: Around 1% of the population test positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies. This biomarker predicts the progression to rheumatoid arthritis (RA) but over a variable time frame. To increase its clinical relevance, this study sought to determine (1) if the proportion of anti-CCP-positive individuals could be enriched by case selection of people attending primary care with new non-specific musculoskeletal (MSK) symptoms but without clinical synovitis (CS) and (2) whether these individuals progress rapidly to inflammatory arthritis (IA), in particular RA. METHODS: In this prospective cohort study, individuals aged ≥18â years with new non-specific MSK symptoms, without CS, were recruited from primary care in the UK. Anti-CCP-positive individuals were invited for follow-up in the rheumatology department, Leeds. Those who tested negative were sent questionnaires 12â months later. RESULTS: 2028 individuals were recruited. Of these, 2.8% (57/2028) were anti-CCP positive, of whom 47% (27/57) developed IA - 24 RA, 1 undifferentiated IA (UIA), 2 polymyositis; 92.6% (25/27) within 12â months, median 1.8â months (IQR 1.0-4.3, range 0.3-16.1). Of the anti-CCP-negative individuals, 1.3% (20/1559) developed IA (1 UIA, 13 RA, 6 psoriatic arthritis); 75% (15/20) within 12â months. The relative risk for developing RA within 12â months in the anti-CCP-positive group was 66.8 (95% CI 32.2 to 138.4, p<0.001); for IA, it was 45.5 (95% CI 25.4 to 81.6, p<0.001). CONCLUSIONS: Selecting individuals with new non-specific MSK symptoms without CS enriched the prevalence of anti-CCP positivity to 2.8%. Those who tested positive had a high risk of rapidly developing RA. The cost-effectiveness of this approach will need to be determined. TRIAL REGISTRATION NUMBER: NCT02012764.
Assuntos
Artrite Reumatoide/diagnóstico , Autoanticorpos/sangue , Peptídeos Cíclicos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVES: To determine whether ultrasound can identify anti-cyclic citrullinated peptide (anti-CCP) antibody-positive patients without clinical synovitis (CS) who progress to inflammatory arthritis (IA). METHODS: In a prospective study, anti-CCP-positive patients without CS underwent ultrasound imaging of 32 joints (wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints (MTPs)) and were monitored for the development of IA. Associations between baseline ultrasound findings (grey scale (GS), power Doppler (PD) and erosions) and (1) progression to IA and (2) development of CS within an individual joint were measured. RESULTS: Consecutive anti-CCP-positive patients (n=136; mean age 51â years, 100 women) were followed up for median of 18.3â months (range 0.1-79.6). At baseline 96% had GS, 30% had PD and 21% had one or more erosions. IA developed in 57 patients (42%) after median of 8.6â months (range 0.1-52.4). Ultrasound abnormalities (GS ≥2, PD ≥1 or erosion ≥1) were found in 86% at baseline compared with 67% of non-progressors (χ2=6.3, p=0.012). Progression to IA was significantly higher in those with ultrasound findings in any joint (excluding MTPs for GS) (GS ≥2: 55% vs 24%, HR (95% CI) 2.3 (1.0 to 4.9), p=0.038; PD ≥2: 75% vs 32%, 3.7 (2.0 to 6.9), p<0.001 and erosion ≥1: 71% vs 34%, 2.9 (1.7 to 5.1), p<0.001). Furthermore, progression occurred earlier with PD ≥2 (median 7.1 vs 52.4â months) and erosion ≥1 (15.4 vs 46.5). At the individual joint level, the trend for progression to CS was more significant for GS and PD (GS ≥2: 26% vs 3%, 9.4 (5.1 to 17.5), p<0.001; PD ≥2: 55% vs 4%, 31.3 (15.6 to 62.9), p<0.001). CONCLUSION: Ultrasound features of joint inflammation may be detected in anti-CCP-positive patients without CS. Ultrasound findings predict progression (and rate of progression) to IA, with the risk of progression highest in those with PD signal. TRIAL REGISTRATION NUMBER: NCT02012764; Results.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Autoanticorpos/sangue , Progressão da Doença , Peptídeos Cíclicos/imunologia , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Feminino , Humanos , Articulações/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Ultrassonografia/métodosRESUMO
OBJECTIVE: To compare neonatal intensive care unit (NICU) admission rates and length of stay (LOS) of late preterm infants (LPIs) born before and after opening a specialized care nursery (SCN) at our academic, pediatric tertiary care center with â¼4,500 total deliveries annually. STUDY DESIGN: Retrospective chart review of inborn LPIs (35(0/7)-36(6/7) weeks) who were asymptomatic or minimally symptomatic at birth and delivered 7 months before the opening of the SCN (pre-SCN) or 7 months subsequently (post-SCN). Infants were excluded for major congenital anomalies or other conditions requiring immediate NICU admission. The pre-SCN options for care were standard couplet care or NICU. The post-SCN options for care were standard couplet care, SCN, or NICU. RESULTS: Pre-SCN (n = 109), 73 (67%) infants received standard couplet care, while 36 (33%) infants were ever admitted/transferred to the NICU. Post-SCN (n = 112), 59 (53%) infants received standard couplet care, while 20 (18%) were ever admitted/transferred to the NICU. A total of 33 (29%) infants were admitted/transferred to the SCN and avoided a NICU stay. Median LOS for all infants was 3 days. CONCLUSION: The frequency of LPIs admitted/transferred to the NICU decreased by â¼50% after the opening of the SCN. LOS did not differ by birth cohort, but did differ significantly by location of care (standard couplet care < SCN < NICU).
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Cuidado do Lactente/métodos , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Berçários Hospitalares , Especialização , Centros Médicos Acadêmicos , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Idade Gestacional , Hospitalização , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Gravidez , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto JovemAssuntos
Artrite Reumatoide/imunologia , Aterosclerose/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Peptídeos Cíclicos/imunologia , Rigidez Vascular/imunologia , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Aterosclerose/epidemiologia , Aterosclerose/imunologia , Autoanticorpos/análise , Autoanticorpos/imunologia , Doenças Cardiovasculares/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/metabolismo , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Papel (figurativo) , Rigidez Vascular/fisiologiaRESUMO
Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential.
Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Processamento de Proteína Pós-Traducional , Animais , Antígenos/química , Antioxidantes/química , Artrite Reumatoide/metabolismo , Linfócitos B/citologia , Biomarcadores/metabolismo , Citrulina/química , Humanos , Inflamação/metabolismo , Oxigênio/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
To investigate whether posttraumatic stress disorder (PTSD) from past trauma, alexithymia and suppression would impact on the experience of Posttraumatic Stress symptoms (PTSS) and psychological well-being following romantic relationship dissolution. One hundred and eighty-nine participants completed questionnaires measuring PTSD, alexithymia, suppression, PTSS and psychological well-being. The results showed that following relationship dissolution, higher levels of intrusion and avoidance (PTSS) and lower levels of psychological well-being were associated with PTSD from past trauma. Difficulty describing feelings was associated negatively with intrusion; difficulty identifying feelings was associated positively with psychological well-being. Suppression was associated negatively with avoidance. To conclude, PTSD from past traumas was related to PTSS symptoms and poor psychological well-being. Alexithymia and suppression were also related to the above outcomes but in a symptom-specific manner.
Assuntos
Adaptação Psicológica , Sintomas Afetivos/epidemiologia , Divórcio/psicologia , Acontecimentos que Mudam a Vida , Repressão Psicológica , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adolescente , Adulto , Sintomas Afetivos/psicologia , Aprendizagem da Esquiva , Fatores de Confusão Epidemiológicos , Demografia/estatística & dados numéricos , Divórcio/estatística & dados numéricos , Emoções/fisiologia , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Psicometria/estatística & dados numéricos , Análise de Regressão , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
Visual objects in the peripersonal space (PPS) are perceived faster than farther ones appearing in the extrapersonal space (EPS). This shows preferential processing for visual stimuli near our body. Such an advantage should favour visual perceptual learning occurring near, as compared with far from observers, but opposite evidence has been recently provided from online testing protocols, showing larger perceptual learning in the far space. Here, we ran two laboratory-based experiments investigating whether visual training in PPS and EPS has different effects. We used the horizontal Ponzo Illusion to create a lateralized depth perspective while participants completed a visual search task in which they reported whether or not a specific target object orientation (e.g., a triangle pointing upwards) was present among distractors. This task was completed before and after a training phase in either the (illusory) near or far space for 1 h. In Experiment 1, the near space was in the left hemispace, whereas in Experiment 2, it was in the right. Results showed that, in both experiments, participants were more accurate after training in the far space, whereas training in the near space led to either improvement in the far space (Experiment 1), or no change (Experiment 2). Moreover, we found a larger visual perceptual learning when stimuli were presented in the left compared with the right hemispace. Differently from visual processing, visual perceptual learning is more effective in the far space. We propose that depth is a key dimension that can be used to improve human visual learning.
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Natural gas has become a leading source of alternative energy with the advent of techniques to economically extract gas reserves from deep shale formations. Here, we present an assessment of private well water quality in aquifers overlying the Barnett Shale formation of North Texas. We evaluated samples from 100 private drinking water wells using analytical chemistry techniques. Analyses revealed that arsenic, selenium, strontium and total dissolved solids (TDS) exceeded the Environmental Protection Agency's Drinking Water Maximum Contaminant Limit (MCL) in some samples from private water wells located within 3 km of active natural gas wells. Lower levels of arsenic, selenium, strontium, and barium were detected at reference sites outside the Barnett Shale region as well as sites within the Barnett Shale region located more than 3 km from active natural gas wells. Methanol and ethanol were also detected in 29% of samples. Samples exceeding MCL levels were randomly distributed within areas of active natural gas extraction, and the spatial patterns in our data suggest that elevated constituent levels could be due to a variety of factors including mobilization of natural constituents, hydrogeochemical changes from lowering of the water table, or industrial accidents such as faulty gas well casings.
Assuntos
Água Potável/análise , Poluentes Químicos da Água/análise , Qualidade da Água , Poços de Água/análise , Cromatografia Gasosa , Indústrias Extrativas e de Processamento , Espectrometria de Massas , Campos de Petróleo e Gás , TexasRESUMO
Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS) signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present study, we examined extracts of twelve species of Caribbean gorgonian corals, for mechanisms that regulate microbial colonization, such as antibacterial activity and QS regulatory activity. Ethanol extracts of gorgonians collected from Puerto Rico and the Florida Keys showed a range of both antibacterial and QS activities using a specific Pseudomonas aeruginosa QS reporter, sensitive to long chain AHLs and a short chain N-acylhomoserine lactones (AHL) biosensor, Chromobacterium violaceium. Overall, the gorgonian corals had higher antimicrobial activity against non-marine strains when compared to marine strains. Pseudopterogorgia americana, Pseusopterogorgia acerosa, and Pseudoplexuara flexuosa had the highest QS inhibitory effect. Interestingly, Pseudoplexuara porosa extracts stimulated QS activity with a striking 17-fold increase in signal. The stimulation of QS by P. porosa or other elements of the holobiont may encourage colonization or recruitment of specific microbial species. Overall, these results suggest the presence of novel stimulatory QS, inhibitory QS and bactericidal compounds in gorgonian corals. A better understanding of these compounds may reveal insight into coral-microbial ecology and whether a therapeutic potential exists.
Assuntos
Antozoários/química , Antozoários/microbiologia , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Animais , Comunicação Celular/efeitos dos fármacos , Florida , Porto RicoRESUMO
OBJECTIVE: In 2005, the Ontario Ministry of Education announced a policy requiring that all elementary students be provided with opportunities to participate in a minimum of 20 minutes of sustained moderate-to-vigorous physical activity (MVPA) each school day during instructional time. To the authors' knowledge, this policy has never been formally evaluated. In a form of natural experiment with Project BEAT, we explored within 16 Toronto District School Board schools the proportion of children who participate in DPA, and the proportion who achieve sustained MVPA within these sessions; these are the objectives of this article. METHODS: Consent was given by 1027 parents/guardians for their children to participate (boys, n=478; girls, n=549). Physical activity (PA) was measured using accelerometry and classroom schedules collected to identify sessions of DPA. The frequency of DPA and number and duration of sustained bouts of MVPA (> or =5 min) were computed and explored relative to PA levels and health outcomes. RESULTS: Fewer than half of the participating children were provided with DPA every day and not a single child engaged in sustained MVPA for > or =20 minutes. On the more positive side, children who engaged in DPA every day were significantly more active than their peers. Those accumulating at least 1 bout of MVPA were more active and likely to meet PA guidelines, and fewer of these children were overweight. CONCLUSION: The majority of schools are not meeting the DPA policy. However, as the frequency and intensity of DPA increases, so do positive health outcomes. This paper provides supporting evidence that when this policy is implemented, the intended health benefits are achievable.
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Política de Saúde , Monitorização Ambulatorial/instrumentação , Atividade Motora , Serviços de Saúde Escolar/organização & administração , Aceleração , Criança , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Ontário , Avaliação de Programas e Projetos de SaúdeRESUMO
Women experiencing incarceration (WEI) in the United States are disproportionately impacted by HIV, yet HIV pre-exposure prophylaxis (PrEP) is underutilized by women in the United States. In order to inform an intervention to promote PrEP initiation during incarceration and facilitate linkage to PrEP care following release from incarceration, we conducted individual, semistructured qualitative interviews with WEI (N = 21) and key stakeholders (N = 14). While WEI had little or no previous knowledge about PrEP, they viewed it as something that would benefit women involved in the criminal justice system. Participants stated that HIV-related stigma and underestimation of HIV risk might serve as barriers to PrEP initiation during incarceration. Participants reported that competing priorities, difficulty scheduling an appointment, and lack of motivation could interfere with linkage to PrEP care in the community. Further, cost, substance use, and difficulty remembering to take the medication were cited most commonly as likely barriers to adherence.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Serviços de Saúde Comunitária/organização & administração , Infecções por HIV/prevenção & controle , Adesão à Medicação/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Profilaxia Pré-Exposição/métodos , Prisioneiros/estatística & dados numéricos , Estigma Social , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Motivação , Pesquisa Qualitativa , Assunção de Riscos , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/psicologia , Estados UnidosRESUMO
Synovial sarcoma is a soft tissue cancer associated with a recurrent t(X:18) translocation that generates one of two fusion proteins, SYT-SSX1 or SYT-SSX2. In this study, we demonstrate that SYT-SSX2 is a unique oncogene. Rather than confer enhanced proliferation on its target cells, SYT-SSX2 instead causes a profound alteration of their architecture. This aberrant morphology included elongation of the cell body and formation of neurite-like extensions. We also observed that cells transduced with SYT-SSX2 often repulsed one another. Notably, cell repulsion is a known component of ephrin signaling. Further analysis of SYT-SSX2-infected cells revealed significant increases in the expression and activation of Eph/ephrin pathway components. On blockade of EphB2 signaling SYT-SSX2 infectants demonstrated significant reversion of the aberrant cytoskeletal phenotype. In addition, we discovered, in parallel, that SYT-SSX2 induced stabilization of the microtubule network accompanied by accumulation of detyrosinated Glu tubulin and nocodazole resistance. Glu tubulin regulation was independent of ephrin signaling. The clinical relevance of these studies was confirmed by abundant expression of both EphB2 and Glu tubulin in SYT-SSX2-positive synovial sarcoma tissues. These results indicate that SYT-SSX2 exerts part of its oncogenic effect by altering cytoskeletal architecture in an Eph-dependent manner and cytoskeletal stability through a concurrent and distinct pathway.
Assuntos
Citoesqueleto/metabolismo , Efrinas/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Sarcoma Sinovial/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Efrinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Células NIH 3T3 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor EphB2/metabolismo , Retroviridae/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tirfostinas/farmacologiaRESUMO
Many women who smoke cigarettes report that concern about weight gain is a barrier to quitting. Indeed, most quitters gain weight and some attribute relapses to weight gain concern. Contingency management (CM), which refers to reinforcing a target behavior with financial incentives, has been demonstrated effective for promoting smoking abstinence and weight management independently. We conducted a pilot trial to establish the feasibility of dual CM, in which both smoking cessation and weight maintenance were incentivized, as a smoking cessation intervention for female weight-concerned smokers. Participants (N = 10) received a 12-week intervention during which they earned financial incentives for smoking abstinence, verified by breath carbon monoxide (CO) testing, and for maintaining their weight (larger incentives for gaining less than five pounds, smaller incentives for 5-10 pound gain) while abstaining from smoking. They attended an end of intervention visit at week 13 and a follow-up visit at week 26. Total compensation was up to $550 ($255 for participation independent of smoking and weight, $145 for smoking abstinence incentives, and $150 for weight maintenance incentives). Results indicated that five of the 10 participants (50%) were continuously abstinent for at least 4 weeks and received at least 2 weight maintenance incentives. Three participants (33%) were abstinent at every visit they attended from quit date through week 26; 2 of these 3 had gained more than 10 pounds by week 26. Additional formative research to test alternative incentive schedules and modalities should be conducted before CM-W is evaluated in a larger trial. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Assuntos
Manutenção do Peso Corporal , Fumantes/psicologia , Abandono do Hábito de Fumar/métodos , Adulto , Estudos de Viabilidade , Feminino , Humanos , Motivação , Projetos Piloto , Produtos do Tabaco , Redução de PesoRESUMO
STUDY OBJECTIVE: To assess how the addition of a pediatric and adolescent gynecologist (PAG) in an area where one has not previously been available affects the use of long-acting reversible contraception (LARC) among adolescent and adult women 13-24 years of age. DESIGN: Retrospective chart review. SETTING: Academic practice including 12 general practice obstetric/gynecologists (GP) and 1 PAG, and Title X clinics in 3 neighboring counties in West Virginia. PARTICIPANTS: Patients receiving an intrauterine device (IUD) or implant during 2010-2016. INTERVENTIONS: Subject charts were reviewed for age and date at insertion, provider (GP, PAG, and Title X), device type, parity, discontinuation, and sequential LARC placement. MAIN OUTCOME MEASURES: Frequencies of LARC and relative risks (RR) with 95% confidence intervals were calculated for the 13- to 17-year and 18- to 24-year age groups and compared between provider type. RESULTS: The frequency of LARC increased over time for all providers for participants age 13-24; the PAG had the highest frequency of LARC among participants aged 13-17 years. The RR for IUD provision for the PAG provider among those aged 13-17 years was 3.1 and 32.5 times greater compared to GP and Title X (P < .001). Title X providers were 2.9 (2.27, 3.79) and 2.8 (2.06, 3.81) times more likely to provide implants to patients aged 13-17 years compared to PAG and GP, respectively (P < .001). CONCLUSIONS: A PAG provider can have a positive impact on LARC uptake among adolescents in a community where this specialist has not previously been available. This is most noted among 13- to 17-year-old patients receiving IUDs.
Assuntos
Ginecologia/estatística & dados numéricos , Dispositivos Intrauterinos/estatística & dados numéricos , Contracepção Reversível de Longo Prazo/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/organização & administração , Estudos Retrospectivos , West Virginia , Adulto JovemRESUMO
The presence of a disease continuum in inflammatory arthritis (IA) is a recognised concept, with distinct stages from at-risk stage (presence of anti citrullinated-peptide autoantibody) to diagnosis of rheumatoid arthritis (RA), including therapy-induced remission. Despite T-cell dysregulation being a key feature of RA, there are few reports of T-cell phenotyping along the IA-continuum. We investigated the disturbances of naïve, regulatory and inflammation related cell (IRC) CD4+ T-cell subsets in 705 individuals across the IA-continuum, developing a simple risk-score (summing presence/absence of a risk-associated with a subset) to predict progression from one stage to the next. In 158 at-risk individuals, the 3 subsets had individual association with progression to IA and the risk-score was highly predictive (p < 0.0001). In evolving IA patients, 219/294 developed RA; the risk-score included naïve and/or Treg and predicted progression (p < 0.0001). In 120 untreated RA patients, the risk-score for predicting treatment-induced remission using naïve T-cells had an odds ratio of 15.4 (p < 0.0001). In RA patients in treatment-induced remission, a score using naïve T-cells predicted disease flare (p < 0.0001). Evaluating the risk of progression using naïve CD4+ T-cells was predictive of progression along the whole IA-continuum. This should allow identification of individuals at high-risk of progression, permitting targeted therapy for improved outcomes.
Assuntos
Artrite Reumatoide/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Progressão da Doença , Feminino , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Linfócitos T Reguladores/patologiaRESUMO
Women who are pregnant report receiving little or no advice about physical activity during pregnancy from their obstetric provider. The purpose of this study was to assess the effectiveness of an evidence-based educational brochure on both immediate and two-week retention of knowledge about exercise during pregnancy. Thirty-two women of childbearing age (age: 25.0 ± 4.0 years, body mass index: 29.5 ± 6.5 kg/m2, 93.7% Caucasian, 83.4% had at least some college) completed a survey before exposure to an evidence-based educational brochure regarding exercise during pregnancy. Post surveys were taken immediately after viewing the educational brochure and again 2-weeks later. After exposure to educational brochures, survey scores on both surveys were significantly higher immediately-post and two-weeks post compared to baseline survey scores (Survey 1 (assessing beliefs) - pre: 79.2 ± 8.9%, post: 92.6 ± 7.4%, 2-weeks post: 92.0 ± 6.5%, p < 0.001; Survey 2 (assessing knowledge) - pre: 65.3 ± 16.4%, post: 81.3 ± 14.9%, 2-weeks post: 78.8 ± 12.4%, p < 0.001). No significant differences detected between immediate post and 2-weeks post for either Survey 1 (p = 0.72) or Survey 2 (p = 0.52); suggesting the information was retained. An evidence-based educational brochure is effective for improving and retaining information 2-weeks later regarding exercise during pregnancy. However, replication studies in more diverse populations are needed to confirm the results of this pilot study. The long-term goal for this line of research is to urge health care providers to consider providing patients with educational information in order to improve knowledge and patient-provider communication on this topic.