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The kinesin-3 motor KIF13B functions in endocytosis, vesicle transport and regulation of ciliary length and signaling. Direct binding of the membrane-associated guanylate kinase (MAGUK) DLG1 to the MAGUK-binding stalk domain of KIF13B relieves motor autoinhibition and promotes microtubule plus-end-directed cargo transport. Here, we characterize angiomotin (AMOT) isoform 2 (p80, referred to as Ap80) as a novel KIF13B interactor that promotes binding of another MAGUK, the polarity protein and Crumbs complex component PALS1, to KIF13B. Live-cell imaging analysis indicated that Ap80 is concentrated at and recruits PALS1 to the base of the primary cilium, but is not a cargo of KIF13B itself. Consistent with a ciliary function for Ap80, its depletion led to elongated primary cilia and reduced agonist-induced ciliary accumulation of SMO, a key component of the Hedgehog signaling pathway, whereas Ap80 overexpression caused ciliary shortening. Our results suggest that Ap80 activates KIF13B cargo binding at the base of the primary cilium to regulate ciliary length, composition and signaling.
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Angiomotinas , Proteínas de Membrana , Cílios/metabolismo , Guanilato Quinases , Proteínas Hedgehog/metabolismo , Proteínas de Membrana/metabolismo , Isoformas de ProteínasRESUMO
INTRODUCTION AND HYPOTHESIS: This study was aimed at evaluating the impact of a mobile app-guided pelvic floor muscle training (PFMT) program on urinary symptoms and quality of life in women suffering from urinary incontinence. METHODS: The study included women with stress urinary incontinence (SUI), who underwent a structured interview and completed validated questionnaires, including the Questionnaire for Urinary Incontinence Diagnosis (QUID), the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), and the Incontinence Quality of Life Questionnaire (I-QOL). These women were randomly assigned to one of two groups: the app group, which received a visual depiction on the expected contraction pattern through a mobile app to support their PFMT exercises, and the control (paper) group. Both groups were instructed to perform PFMT exercises twice daily for 30 days. Data were collected at baseline and at 30, 60, 90, and 120 days after completing the exercises. RESULTS: A total of 154 women participated, with 76 in the app group and 78 in the paper group. The mean ages were 61 (± 6.1) and 60.6 (± 6.8) in the app and paper groups respectively (p = 0.644). Both groups showed significant improvements in QUID SUI scores (p < 0.001), overactive bladder (OAB; p < 0.001), ICIQ-SF scores (p < 0.001), and quality-of-life scores (p < 0.001). When comparing the two groups, the app group exhibited a more substantial reduction in OAB (p = 0.017) as assessed by QUID and total (p = 0.042), psychosocial (p = 0.032) and social embarrassment (p = 0.006) I-QOL scores. CONCLUSIONS: The study findings suggest that PFMT guided by a mobile app with visual guidance leads to greater improvements in storage symptoms and quality of life than the home-based PFMT guidance.
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Aplicativos Móveis , Incontinência Urinária por Estresse , Incontinência Urinária , Feminino , Humanos , Qualidade de Vida , Diafragma da Pelve , Resultado do Tratamento , Incontinência Urinária/terapia , Incontinência Urinária por Estresse/terapia , Terapia por ExercícioRESUMO
OBJECTIVE: This study aimed to analyse the nutritional factors and pressure injury (PI) risk in hospitalised patients post-stroke. METHOD: The research employed a descriptive observational method in which patients ≥18 years of age were followed for six days. Nutritional evaluation was based on anthropometric and dietary factors. The nutritional risk was assessed via anthropometric measurements, Braden nutrition subscale and daily dietary intake. PI risk was evaluated through the Braden Scale. The Wilcoxon test, paired t-test, and Kruskal-Wallis test were applied and corrected with Bonferroni correction or analysis of variance, followed by the post hoc Tukey test. RESULTS: During their hospital stays, the participating 59 patients had an increase in sensory perception (p=0.02) and nutrition (p=0.005) scores. It was observed that patients at high risk of PI did not meet daily nutritional recommendations for calories, proteins, carbohydrates, lipids and micronutrients (zinc, selenium and copper) compared with patients at low-to-moderate risk. Weight (p<0.001), body mass index (p<0.001), calf (p=0.01) and arm (p=0.04) circumferences, and subscapular (p=0.003) and triceps (p<0.001) skinfolds decreased during the six days of hospitalisation. CONCLUSION: From the findings of this study, it was concluded that nutritional factors, such as unmet recommended daily nutritional requirements of macronutrients and micronutrients, and nutritional status are associated with a higher risk of developing a PI.
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Úlcera por Pressão , Humanos , Recém-Nascido , Índice de Massa Corporal , Ingestão de Energia , Micronutrientes , Estado Nutricional , Úlcera por Pressão/etiologia , Fatores de RiscoRESUMO
We present the case of a 26-year-old male patient with no history of interest who consulted the emergency department due to occlusive symptoms. Urgent CT showed the presence of a transverse colonic volvulus in the context of a heterotopic liver, located in the left hypochondrium. There were no clinical or radiological signs of perforation or ischemia, so urgent endoscopic decompression was performed with subsequent elective surgery with a favorable resolution of the condition. Transverse colonic volvulus is rare (<1%) and wandering liver is an exceptional predisposing factor, with less than a hundred published cases. In these patients, endoscopic decompression carries a risk of perforation with high recurrence rates, and surgical treatment should be considered. However, in this case, in the absence of severity criteria, decompressive colonoscopy was considered an urgent treatment and subsequent elective surgery with favorable results.
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OBJECTIVE: Vulvodynia (VVD) is a frequent and harrowing condition for which diagnosis and management remain insufficient. Our study aimed to describe and compare vulvovaginal signs and symptoms of Brazilian women with VVD and controls and describe previous medical assessment, past treatments, and vulvar pain relief among women with VVD. METHODS: This cross-sectional descriptive study included Brazilian women with (n = 151) and without VVD (n = 106). All women were assessed for vaginal infection, vulvar pain intensity by means of a cotton swab test based on a numerical rate scale, and answered the Female Sexual Function Index questionnaire and a structured instrument about current vulvar symptoms. Previous treatments were assessed in the VVD group, and vulvar pain relief achieved with previous treatments was qualified through a 4-point Likert scale. RESULTS: Volunteers were mainly White, with mean age of 30 years. Vulvovaginal signs and symptoms were significantly more frequent in women with VVD (p < .05), and vulvar pain duration was 5.8 (±4) years. More than 50% consulted with three or more physicians, and 49% remained without a conclusive diagnosis. Previous diagnosis and treatment of vulvovaginal infection were often reported by women with VVD. Most of the tried prescriptions were self-reported as providing only low vulvar pain relief. CONCLUSIONS: Prolonged duration of vulvar pain, multiple visits to health care professionals, and poor relief of pain are common aspects in the clinical history of women with VVD. In addition to pain, vulvar fissure, edema, erythema, vaginal discharge, and foul odor are common and should be considered to avoid misdiagnosis. Appropriate treatments to VVD are still poorly reported.
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Vulvodinia , Adulto , Feminino , Humanos , Brasil , Estudos Transversais , Dor , Manejo da Dor , Vulvodinia/diagnóstico , Vulvodinia/terapiaRESUMO
BACKGROUND: Remote care and telehealth have the potential to expand healthcare access, and the COVID-19 pandemic has called for alternative solutions to conventional face-to-face follow-up and monitoring. However, guidance is needed on the integration of telehealth into clinical care of people with rheumatic and musculoskeletal diseases (RMD). OBJECTIVE: To develop EULAR points to consider (PtC) for the development, prioritisation and implementation of telehealth for people with RMD. METHODS: A multidisciplinary EULAR task force (TF) of 30 members from 14 European countries was established, and the EULAR standardised operating procedures for development of PtC were followed. A systematic literature review was conducted to support the TF in formulating the PtC. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtC were formulated. The use of telehealth should be tailored to patient's needs and preferences. The healthcare team should have adequate equipment and training and have telecommunication skills. Telehealth can be used in screening for RMD as preassessment in the referral process, for disease monitoring and regulation of medication dosages and in some non-pharmacological interventions. People with RMD should be offered training in using telehealth, and barriers should be resolved whenever possible.The level of agreement to each statement ranged from 8.5 to 9.8/10. CONCLUSION: The PtC have identified areas where telehealth could improve quality of care and increase healthcare access. Knowing about drivers and barriers of telehealth is a prerequisite to successfully establish remote care approaches in rheumatologic clinical practice.
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COVID-19 , Doenças Musculoesqueléticas , Telemedicina , Acessibilidade aos Serviços de Saúde , Humanos , Doenças Musculoesqueléticas/terapia , PandemiasRESUMO
BACKGROUND: An important but often insufficient aspect of care in people with inflammatory arthritis (IA) is empowering patients to acquire a good understanding of their disease and building their ability to deal effectively with the practical, physical and psychological impacts of it. Self-management skills can be helpful in this regard. OBJECTIVES: To develop recommendations for the implementation of self-management strategies in IA. METHODS: A multidisciplinary taskforce of 18 members from 11 European countries was convened. A systematic review and other supportive information (survey of healthcare professionals (HCPs) and patient organisations) were used to formulate the recommendations. RESULTS: Three overarching principles and nine recommendations were formulated. These focused on empowering patients to become active partners of the team and to take a more proactive role. The importance of patient education and key self-management interventions such as problem solving, goal setting and cognitive behavioural therapy were highlighted. Role of patient organisations and HCPs in promoting and signposting patients to available resources has been highlighted through the promotion of physical activity, lifestyle advice, support with mental health aspects and ability to remain at work. Digital healthcare is essential in supporting and optimising self-management and the HCPs need to be aware of available resources to signpost patients. CONCLUSION: These recommendations support the inclusion of self-management advice and resources in the routine management of people with IA and aim to empower and support patients and encourage a more holistic, patient-centred approach to care which could result in improved patient experience of care and outcomes.
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Artrite Reumatoide/terapia , Autogestão , Espondiloartropatias/terapia , Artrite Psoriásica/terapia , Terapia Cognitivo-Comportamental , Comorbidade , Europa (Continente) , Exercício Físico , Humanos , Educação de Pacientes como Assunto , Participação do Paciente , Reumatologia , Comportamento de Redução do Risco , Autoeficácia , Sociedades MédicasRESUMO
BACKGROUND: Non-adherence to treatment could preclude reaching an optimal outcome. Thirty to 80% of patients with rheumatic and musculoskeletal diseases (RMDs) do not adhere to the agreed treatment. OBJECTIVES: The objective was to establish points to consider (PtCs) for the prevention, screening, assessment and management of non-adherence to (non-)pharmacological treatments in people with RMDs. METHODS: An EULAR task force (TF) was established, and the EULAR standardised operating procedures for the development of PtCs were followed. The TF included healthcare providers (HCPs), comprising rheumatologists, nurses, pharmacists, psychologists, physiotherapists, occupational therapists and patient-representatives from 12 European countries. A review of systematic reviews was conducted in advance to support the TF in formulating the PtCs. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtCs were formulated. The PtCs reflect the phases of action on non-adherence. HCPs should assess and discuss adherence with patients on a regular basis and support patients to treatment adherence. As adherence is an agreed behaviour, the treatment has to be tailored to the patients' needs. The level of agreement ranged from 9.5 to 9.9 out of 10. CONCLUSIONS: These PtCs can help HCPs to support people with RMDs to be more adherent to the agreed treatment plan. The basic scheme being prevent non-adherence by bonding with the patient and building trust, overcoming structural barriers, assessing in a blame-free environment and tailoring the solution to the problem.
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Doenças Musculoesqueléticas , Fisioterapeutas , Doenças Reumáticas , Europa (Continente) , Humanos , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/prevenção & controle , Terapeutas Ocupacionais , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Revisões Sistemáticas como AssuntoRESUMO
INTRODUCTION AND HYPOTHESIS: Short questionnaires are important for validating the clinical diagnosis of urinary incontinence (UI). We sought to validate and culturally translate the Questionnaire for Urinary Incontinence Diagnosis (QUID) for the Brazilian Portuguese language. METHODS: A cross-sectional study with 457 women (330 with urinary incontinence and 127 controls) was performed in a Southeastern Brazilian outpatient clinic. Patients answered a pilot-tested, notarized, six-item questionnaire (QUID) for internal consistency as well as a control questionnaire (ICIQ-SF and ICIQ-OAB) for construct validity. In both groups, floor and ceiling effects were calculated. Within UI women, test-retest (n = 41) and responsiveness to conservative treatment (n = 74) were also analyzed. RESULTS: Internal consistency (Cronbach's alpha) from the QUID was adequate between the UI (0.845-0.850) and control (0.724-0.775) groups. Mean QUID scores were statistically different between UI and control groups (p < 0.05). No ceiling or floor effects were observed in incontinent patients. Test-retest reliability after 4 weeks (intraclass correlation coefficient [ICC]: 0.780-0.814) and responsiveness (0.867-0.889) were also adequate within UI women. Construct validity was adequate at all correlations between QUID and ICIQ-SF and ICIQ-OAB (r: 0.19-0.58; p <0.05). Responsiveness was demonstrated by a statistically significant difference in questions/subscale sores after physical therapy. CONCLUSION: The QUID presented adequate cultural translation, reliability, and good responsiveness to treatment in the Brazilian Portuguese language.
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Idioma , Incontinência Urinária , Brasil , Estudos Transversais , Feminino , Humanos , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , Incontinência Urinária/diagnósticoRESUMO
Background and Objectives: Symptomatic irreversible pulpitis in permanent mature teeth is a common indication for nonsurgical root canal treatment (NSRCT), but contemporary studies have reported on vital pulp therapy (VPT) applied in such teeth as a less invasive treatment. This systematic review assessed the outcomes of VPT, including partial and full pulpotomy performed with hydraulic calcium silicate cements (HCSCs) in permanent mature posterior teeth diagnosed with symptomatic irreversible pulpitis. Materials and Methods: The PRISMA guidelines were followed. The search strategy included PubMed®, EMBASE, Cochrane library and grey literature electronic databases. The quality assessment of the identified studies followed the Cochrane Collaboration Risk of Bias, ROBINS-I and Newcastle-Ottawa Scale tools. Results: The search of primary databases identified 142 articles, of which 9 randomized controlled trials and 3 prospective cohort studies were selected for review. The risk-of-bias was assessed as 'high' or 'serious', 'fair', and 'low' for three, seven and two articles, respectively. One to five years after VPT using HCSCs, the success rates mostly ranged from 78 to 90%. Based on two articles, the outcomes of the VPT and NSRCT were comparable at one and five years. Despite the necessity for the intra-operative pulp assessment in VPT procedures, the majority of the studies did not fully report on this step or on the time needed to achieve hemostasis. Small sample sizes, of under 23 teeth, were reported in three studies. Conclusions: The reviewed 12 articles reported favorable outcomes of the VPT performed with HCSCs in permanent mature posterior teeth with symptomatic irreversible pulpitis, with radiographic success in the range of 81 to 90%. Two articles suggested comparable outcomes of the VPT and root canal treatment. Universal case selection and outcome criteria needs to be established for VPT when considered as an alternative to NSRCT. This evidence supports the need for further research comparing longer-term outcomes of both of the treatment modalities.
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Pulpite , Dentição Permanente , Humanos , Estudos Prospectivos , Pulpite/terapia , Pulpotomia , Resultado do TratamentoRESUMO
OBJECTIVES: To assess the educational needs of people with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), test differences across patient subgroups and identify factors independently associated with their educational needs. METHODS: This was a cross-sectional analytic study. Patients with AS and PsA completed the Portuguese version of the Educational Needs Assessment Tool (PortENAT). Data were Rasch-transformed before descriptive and inferential analyses were undertaken. Univariable and multivariable analyses were used to determine differences between patient subgroups and factors independently associated with their educational needs. RESULTS: The study included 121 patients with AS and 132 with PsA. The level of educational needs varied by diagnostic group, but higher needs for both subgroups were reported regarding the "Disease process", "Feelings" and "Managing pain" domains. Overall, patients with AS had a higher level of educational needs than those with PsA. In both diagnostic groups, female gender was independently associated with higher educational needs. In the PsA group, a shorter disease duration was independently associated with higher educational needs in the following domains: "Managing pain", "Movement" and "Feelings". CONCLUSIONS: Educational needs vary by diagnostic group, gender and disease duration. These differences merit consideration in the design of patient education interventions.
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Artrite Psoriásica , Educação de Pacientes como Assunto , Espondilite Anquilosante , Artrite Psoriásica/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Avaliação das Necessidades , Manejo da Dor , Espondilite Anquilosante/psicologiaRESUMO
Background and objectives: The long-term outcome of endodontic microsurgery (EMS) performed on root-filled teeth affected by post-treatment apical periodontitis (AP) has been a matter of debate, re-launched by the introduction of novel root-end filling materials which have been proven to improve the short-term outcome of EMS. The purpose of this systematic review and meta-analysis is to evaluate the clinical and radiographic long-term outcome of endodontic microsurgery in teeth diagnosed with secondary AP through radiographic evaluation. Materials and Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion and exclusion criteria were defined a priori to select the best longitudinal evidence. Only randomized clinical trials (RCT) and prospective clinical studies (PCS), with a follow-up ≥ 2-year, and exhibiting well-established clinical and radiographic outcome criteria, were selected. Results: A total of 573 articles were obtained, from which 10 fulfill inclusion criteria: 6 PCS and 4 RCT. Meta-analysis showed a pooled proportion of success rate of 91.3%, from an overall amount of 453 treated teeth included in RCT; from overall 839 included teeth in PCS, a pooled success rate of 78.4% was observed, with the follow-up time ranging from 2 to 13-years. Survival rate outcomes varied from 79 to 100% for the same follow-up period. Five prognostic factors with influence on the outcome were disclosed: smoking habits, tooth location and type, absence/presence of dentinal defects, interproximal bone level, and root-end filling material. Conclusions: High success rates and predictable results can be expected when EMS is performed by trained endodontists, allowing good prognosis and preservation of teeth affected by secondary AP.
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Endodontia , Microcirurgia , Humanos , Prognóstico , Estudos Prospectivos , Materiais Restauradores do Canal Radicular , Resultado do TratamentoRESUMO
The predicted environmental changes may be detrimental to initial seedling growth, particularly the expected increase in air temperature. We therefore investigated the thermal limits for growth and development of Vriesea friburgensis and Alcantarea imperialis seedlings in the context of oxidative stress. The optimal temperatures for the growth of V. friburgensis and A. imperialis were 25 and 25-30⯰C, respectively. Extreme temperatures (15, 30, or 35⯰C) induced oxidative stress in both species with significant accumulation of hydrogen peroxide (H2O2) and nitric oxide (NO). Under oxidative stress, the amount of chlorophyll decreased in both species, more prominently in V. friburgensis, while carotenoid levels dramatically increased in A. imperialis. Notably, the activities of superoxide dismutase, catalase (CAT), and ascorbate peroxidase increased in A. imperialis at extreme temperatures. Similar results were observed for V. friburgensis; however, the activity of CAT remained unaffected regardless of temperature. Seedlings of A. imperialis survived at a wider range of temperatures than V. friburgensis, which had greater than 40% mortality when growing at 30⯰C. Overall, precise control of cellular H2O2 and NO levels takes place during the establishment of A. imperialis seedlings, allowing the species to cope with relatively high temperatures. The thermal limits of the fundamental niches of the species investigated, determined based on the ability of seedlings to cope with oxidative stress, were distinct from the realized niches of these species. The results suggest that recruitment success is dependent on the ability of seedlings to handle extreme temperature-triggered oxidative stress, which limits the regeneration niche.
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Bromeliaceae/metabolismo , Estresse Oxidativo , Plântula/metabolismo , Temperatura , Aclimatação , Ascorbato Peroxidases/metabolismo , Bromeliaceae/crescimento & desenvolvimento , Carotenoides/metabolismo , Catalase/metabolismo , Clorofila/metabolismo , Peróxido de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Plântula/crescimento & desenvolvimento , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Endoscopic sleeve gastroplasty is a safe and feasible treatment for obesity. This study is focused on our technique modification which suggests a different suturing pattern in order to distribute suture tension more evenly. METHODS: A retrospective study of 148 patients (121 women) who underwent this procedure and were monitored for 12 months was conducted. The average age was 41.53 ± 10 years. The average BMI was 35.11 ± 5.5 kg/m2 with the average initial weight being 98.7 ± 17 kg. A subgroup of the first 72 patients (60 women) were monitored for 18 months. A new running "Z" stitch pattern was used to provide gastric cavity reduction by means of 4 parallel suture rows. The stitch pattern was intended to provide a homogenous distribution of the disruptive force on the suture among all stitch points. RESULTS: %TWL was 17.53 ± 7.57 in 12 months and 18.5 ± 9% in 18 months indicating durability of the procedure. Patients with a BMI < 35 benefited most from an endoscopic gastroplasty. Leptin did not predict a response to endoscopic gastroplasty and decreased in all patients. In just one case there was a mild bleeding (0.67%) at the insertion point of the helix, which was resolved by sclerotherapy. CONCLUSIONS: Endoscopic gastroplasty offers a real choice for obese patients. This single-center experience with a modified suturing pattern provides a successful technique for weight loss.
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Endoscopia/métodos , Gastroplastia/métodos , Obesidade/cirurgia , Técnicas de Sutura , Adulto , Índice de Massa Corporal , Feminino , Humanos , Leptina/sangue , Masculino , Estudos Retrospectivos , Redução de PesoRESUMO
During cytokinesis, the antiparallel array of microtubules forming the central spindle organizes the midbody, a structure that anchors the ingressed cleavage furrow and guides the assembly of abscission machinery. Here, we identified a role for the flavoprotein monooxygenase MICAL3, an actin disassembly factor, in organizing midbody-associated protein complexes. By combining cell biological assays with cross-linking mass spectrometry, we show that MICAL3 is recruited to the central spindle and the midbody through a direct interaction with the centralspindlin component MKLP1. Knock-out of MICAL3 leads to an increased frequency of cytokinetic failure and a delayed abscission. In a mechanism independent of its enzymatic activity, MICAL3 targets the adaptor protein ELKS and Rab8A-positive vesicles to the midbody, and the depletion of ELKS and Rab8A also leads to cytokinesis defects. We propose that MICAL3 acts as a midbody-associated scaffold for vesicle targeting, which promotes maturation of the intercellular bridge and abscission.
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Citocinese/fisiologia , Oxigenases de Função Mista/metabolismo , Fuso Acromático/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Oxigenases de Função Mista/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fuso Acromático/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic neurodevelopmental disorder that affects up to 3% of the general population. Although epigenetic mechanisms play a role in neurodevelopment disorders, epigenetic pathways associated with OCD have rarely been investigated. Oxytocin is a neuropeptide involved in neurobehavioral functions. Oxytocin has been shown to be associated with the regulation of complex socio-cognitive processes such as attachment, social exploration, and social recognition, as well as anxiety and other stress-related behaviors. Oxytocin has also been linked to the pathophysiology of OCD, albeit inconsistently. The aim of this study was to investigate methylation in two targets sequences located in the exon III of the oxytocin receptor gene (OXTR), in OCD patients and healthy controls. We used bisulfite sequencing to quantify DNA methylation in peripheral blood samples collected from 42 OCD patients and 31 healthy controls. RESULTS: We found that the level of methylation of the cytosine-phosphate-guanine sites in two targets sequences analyzed was greater in the OCD patients than in the controls. The higher methylation in the OCD patients correlated with OCD severity. We measured DNA methylation in the peripheral blood, which prevented us from drawing any conclusions about processes in the central nervous system. CONCLUSION: To our knowledge, this is the first study investigating DNA methylation of the OXTR in OCD. Further studies are needed to evaluate the roles that DNA methylation and oxytocin play in OCD.
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Metilação de DNA , Epigênese Genética , Transtorno Obsessivo-Compulsivo/genética , Receptores de Ocitocina/genética , Adulto , Ilhas de CpG , Éxons , Feminino , Humanos , Modelos Lineares , Masculino , Transtorno Obsessivo-Compulsivo/sangue , Escalas de Graduação Psiquiátrica , Receptores de Ocitocina/sangue , Índice de Gravidade de DoençaRESUMO
Cost-effective intervention thresholds (ITs) based on FRAX(®) were determined for Portugal. Assuming a willingness to pay (WTP) of 32,000 per quality-adjusted life years (QALYs), treatment with generic alendronate is cost effective for men and women aged 50 years or more, with 10-year probabilities for major osteoporotic fractures and hip above 8.8 and 2.5 %, respectively. The aim of the present study was to identify the 10-year probabilities of a major and hip osteoporotic fracture using FRAX(®) validated for Portugal, above which pharmacologic interventions become cost effective in the Portuguese context. A previously developed and validated state transition Markov cohort model was populated with epidemiologic, economic and quality-of-life fracture data from Portugal. Cost-effectiveness of FRAX(®)-based ITs was calculated for generic alendronate and proprietary zoledronic acid, denosumab and teriparatide were compared to "no intervention", assuming a WTP of 32,000 (two times national Gross Domestic Product per capita) per QALYs. In the Portuguese epidemiological and economic context, treatment with generic alendronate was cost effective for men and women aged 50 years or more, with 10-year probabilities at or above 8.8 % for major osteoporotic fractures and 2.5 % for hip fractures. Cost-effective threshold 10-year probabilities for major osteoporotic and hip fractures were higher for zoledronic acid (20.4 and 10.1 %), denosumab (34.9 and 10.1 %) and teriparatide (77.8 and 62.6 %), respectively. A tool is provided to perform the calculation of cost-effective ITs for different medications, according to age group and diverse levels of WTP. Cost-effective ITs, for different medications, age groups and WTP, based on 10-year probabilities of major and hip fracture probabilities calculated with FRAX are provided.
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Algoritmos , Conservadores da Densidade Óssea/economia , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Idoso , Alendronato/uso terapêutico , Estudos de Coortes , Análise Custo-Benefício/métodos , Denosumab/uso terapêutico , Feminino , Fraturas do Quadril/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/economia , Ácido Risedrônico/uso terapêuticoRESUMO
An imbalance in stimulated cytokine production is associated with the etiopathogenesis of numerous diseases such as major depressive disorder (MDD) and periodontal disease. Increased cytokine levels have been reported in the gingival crevicular fluid (GCF) of patients with MDD. Thirty-six outpatients with MDD participated in this study. Each outpatient was age-matched (± 3 years) with a healthy control (n=36). The patients were controlled for race and smoking habits. Unstimulated and stimulated interleukin 6 (IL-6), interleukin 1ß (IL-1ß), and interferon-γ (INF-γ) production in whole blood culture (WBC) and IL-6 and IL-1ß levels in the GCF were evaluated. Circulating levels of IL-6 and IL-1ß (unstimulated) as well as GCF IL-1ß were modestly lower in MDD patients, compared to the levels in age-matched controls (Mann-Whitney, p=0.002, 0.0075, ANCOVA, p=0.025, respectively). In the unstimulated group, there was no correlation between the levels of circulating IL-6 and GCF IL-6 (r=0.07, p=0.67), and between the levels of circulating IL-1ß and the IL-1ß level in the CGF (r=-0.08, p=0.63). In the LPS stimulation group, there was no correlation between the levels of circulating levels of IL-6 and GCF IL-6 (r=0. 02, p=0.91) or between the circulating IL-1ß and GCF IL-1ß (r=0.13, p=0.42). We observed modest immunosuppression in MDD patients (evaluated by no stimulation whole blood culture [WBC]), especially in patients with melancholic depression, chronic depression, and severe depression.
Assuntos
Citocinas/imunologia , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/psicologia , Gengiva/imunologia , Periodontite/imunologia , Periodontite/psicologia , Adulto , Estudos de Casos e Controles , Citocinas/sangue , Citocinas/metabolismo , Transtorno Depressivo Maior/sangue , Feminino , Gengiva/metabolismo , Líquido do Sulco Gengival/imunologia , Líquido do Sulco Gengival/metabolismo , Humanos , Interferon gama/sangue , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Índice Periodontal , Periodontite/sangueRESUMO
INTRODUCTION: Strongyloides has been shown to infrequently mimic inflammatory bowel disease (IBD) or to disseminate when a patient with IBD and unrecognized strongyloides is treated with immunosupression. CASE REPORT: A man from Ecuador, living in Spain for years, with a history of type 2 diabetes mellitus and psoriasis treated with topical corticosteroids, was admitted to the hospital with an 8-month history of diarrhoea. Blood tests showed hyperglycemia, hyponatremia, elevated CRP and faecal calprotectin. Colonoscopy suggested IBD. The patient improved with steroids, pending biopsy results, and he was discharged. Biopies were compatible with IBD, but careful examination revealed strongyloides. He was given a prescription of albendazole. He had to be readmitted due to SIADH, which resolved with fluid restriction. Upon discharge albendazole was prescribed again. The patient skipped most of the out-patient-clinic visits. He returned a year later on 10 mg/week methotrexate, asymptomatic, with 20% eosinophilia, and admitting he had never taken the strongyloides treatment for economical reasons. He then received a week of oral albendazol at the hospital. Biopsies and blood cell count were afterwards normal (eosinophils 3.1%) and serology for strongyloides antibodies was negative. DISCUSSION: This case is of interest for four rarely concurring reasons. It´s a worm infection that mimics IBD; the infection was diagnosed by colon biopsy; the infection caused a SIADH; and, most interestingly, even though the patient is on immunosupression, he remains asymptomatic.
Assuntos
Doenças Inflamatórias Intestinais/diagnóstico , Estrongiloidíase/diagnóstico , Adulto , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunossupressores/uso terapêutico , Síndrome de Secreção Inadequada de HAD/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/parasitologia , Masculino , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/parasitologiaRESUMO
OBJECTIVES: To identify and synthesise the best available evidence on the accuracy of the currently available tools for predicting fracture risk. METHODS: We systematically searched PubMed MEDLINE, Embase and Cochrane databases to 2014. Two reviewers independently selected articles, collected data from studies, and carried out a hand search of the references of the included studies. The Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS) checklist was used, and the primary outcome was the area under the curve (AUC) and 95% CIs, obtained from receiver operating characteristic (ROC) analyses. We excluded tools if they had not been externally validated or were designed for specific disease populations. Random effects meta-analyses were performed with the selected tools. RESULTS: Forty-five studies met inclusion criteria, corresponding to 13 different tools. Only three tools had been tested more than once in a population-based setting: FRAX (26 studies in 9 countries), GARVAN (6 studies in 3 countries) and QFracture (3 studies in the UK, 1 also including Irish participants). Twenty studies with these three tools were included in a total of 17 meta-analyses (for hip or major osteoporotic fractures; men or women; with or without bone mineral density). CONCLUSIONS: Most of the 13 tools are feasible in clinical practice. FRAX has the largest number of externally validated and independent studies. The overall accuracy of the different tools is satisfactory (>0.70), with QFracture reaching 0.89 (95% CI 0.88 to 0.89). Significant methodological limitations were observed in many studies, suggesting caution when comparing tools based solely on the AUC.