RESUMO
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.
Assuntos
Dermatologia , Penfigoide Bolhoso , Venereologia , Corticosteroides/uso terapêutico , Idoso , Vesícula/tratamento farmacológico , Humanos , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/tratamento farmacológico , Qualidade de VidaRESUMO
OBJECTIVE: Joint injury-induced perturbations to the endocannabinoid system (ECS), a regulator of both inflammation and nociception, remain largely uncharacterized. We employed a mouse model of ACL rupture to assess alterations to nociception, inflammation, and the ECS while using in vitro models to determine whether CB2 agonism can mitigate inflammatory signaling in macrophages and fibroblast-like synoviocytes (FLS). DESIGN: Mice underwent noninvasive ACL rupture (ACLR) via tibial compression-based loading. Nociception was measured longitudinally using mechanical allodynia and knee hyperalgesia testing. Synovitis was assessed using histological scoring and histomorphometry. Gene and protein markers of inflammation were characterized in whole joints and synovium. Immunohistochemistry assessed injury-induced alterations to CB1+, CB2+, and F4/80+ cells in synovium. To assess whether CB2 agonism can inhibit pro-inflammatory macrophage polarization, murine bone marrow-derived macrophages (mBMDM) were stimulated with IL-1ß or conditioned medium from IL-1ß-treated FLS and treated with vehicle (DMSO), the CB2 agonist HU308, or cannabidiol (CBD). Macrophage polarization was assessed as the ratio of M1-associated (IL1b, MMP1b, and IL6) to M2-associated (IL10, IL4, and CD206) gene expression. Human FLS (hFLS) isolated from synovial tissue of OA patients were treated with vehicle (DMSO) or HU308 following TNF-α or IL-1ß stimulation to assess inhibition of catabolic/inflammatory gene expression. RESULTS: ACLR induces synovitis, progressively-worsening PTOA severity, and an immediate and sustained increase in both mechanical allodynia and knee hyperalgesia, which persist beyond the resolution of molecular inflammation. Enrichment of CB2, but not CB1, was observed in ACLR synovium at 3d, 14d, and 28d, and CB2 was found to be associated with F4/80 (+) cells, which are increased in number in ACLR synovium at all time points. The CB2 agonist HU308 strongly inhibited mBMDM M1-type polarization following stimulation with either IL-1ß or conditioned medium from IL-1ß-treated mFLS, which was characterized by reductions in Il1b, Mmp1b, and Il6 and increases in Cd206 gene expression. Cannabidiol similarly inhibited IL-1ß-induced mBMDM M1 polarization via a reduction in Il1b and an increase in Cd206 and Il4 gene expression. Lastly, in OA hFLS, HU308 treatment inhibited IL-1ß-induced CCL2, MMP1, MMP3, and IL6 expression and further inhibited TNF-α-induced CCL2, MMP1, and GMCSF expression, demonstrating human OA-relevant anti-inflammatory effects by targeting CB2. CONCLUSIONS: Joint injury perturbs the intra-articular ECS, characterized by an increase in synovial F4/80(+) cells, which express CB2, but not CB1. Targeting CB2 in murine macrophages and human FLS induced potent anti-inflammatory and anti-catabolic effects, which indicates that the CB2 receptor plays a key role in regulating inflammatory signaling in the two primary effector cells in the synovium. The intraarticular ECS is therefore a potential therapeutic target for blocking pathological inflammation in future disease-modifying PTOA treatments.
Assuntos
Lesões do Ligamento Cruzado Anterior , Fibroblastos/metabolismo , Macrófagos/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Regulação para Cima , Animais , Canabidiol/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Canabinoides/farmacologia , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Interleucina-1beta/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Membrana SinovialRESUMO
BACKGROUND: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States. OBJECTIVES: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. RESULTS: The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.
Assuntos
Dermatologia , Guias como Assunto , Pênfigo , Venereologia , Academias e Institutos , Europa (Continente) , Humanos , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológicoRESUMO
BACKGROUND: Childhood obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric condition, with varied symptom presentations that have been differentially associated with clinical characteristics and treatment response. One OCD symptom cluster of particular interest is religious symptoms, including fears of offending religious figures/objects; patients affected by these symptoms have been characterized as having greater overall OCD severity and poorer treatment response. However, the extant literature primarily examines this symptom subtype within adults, leaving a gap in our understanding of this subtype in youth. METHOD: Consequently, this study examined whether presence of religious symptoms in OCD-affected children and adolescents (Nâ¯=â¯215) was associated with greater clinical impairments across OCD symptoms and severity, insight, other psychiatric comorbidity, family variables, or worse treatment response. RESULTS: Results found that youth with religious OCD symptoms presented with higher OCD symptom severity and exhibited more symptoms in the aggressive, sexual, somatic, and checking symptom cluster, as well as the symmetry, ordering, counting, and repeating cluster. Religious OCD symptoms were also significantly associated with poorer insight and higher family expressiveness. No differences in treatment response were observed in youths with versus without religious OCD symptoms. CONCLUSION: Ultimately, youths with religious OCD symptoms only differed from their OCD-affected counterparts without religious symptoms on a minority of clinical variables; this suggests they may be more comparable to youths without religious OCD symptoms than would be expected based on the adult OCD literature and highlights the importance of examining these symptoms within a pediatric OCD sample.
Assuntos
Relações Familiares/psicologia , Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/terapia , Religião e Psicologia , Adolescente , Agressão/psicologia , Criança , Comorbidade , Medo/psicologia , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Religião , Síndrome , Resultado do TratamentoRESUMO
The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m2 as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5-2 mg kg-1 day-1 ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 µg/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 µg/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m2 SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.
Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Citarabina/farmacocinética , Doenças do Cão/tratamento farmacológico , Encefalomielite/veterinária , Imunossupressores/farmacocinética , Meningoencefalite/veterinária , Prednisona/farmacocinética , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/sangue , Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/administração & dosagem , Citarabina/sangue , Citarabina/uso terapêutico , Cães , Combinação de Medicamentos , Encefalomielite/tratamento farmacológico , Feminino , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Injeções Subcutâneas , Masculino , Meningoencefalite/tratamento farmacológico , Prednisona/administração & dosagem , Prednisona/sangue , Prednisona/uso terapêuticoRESUMO
Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]. The patient developed BP with increasing serum titres of anti-BP180 IgG autoantibodies and increasing disease severity during pembrolizumab therapy. High doses of corticosteroids and methotrexate were needed to control the BP. Following the termination of pembrolizumab therapy, imaging showed complete regression of all metastatic sites. This result may indicate a crucial role for T-cell suppressive activity in controlling and preventing BP.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Melanoma/tratamento farmacológico , Penfigoide Bolhoso/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Feminino , Humanos , Melanoma/secundário , Pessoa de Meia-Idade , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/imunologia , Neoplasias Cutâneas/secundárioRESUMO
Prior research has identified OCD subtypes or "clusters" of symptoms that differentially relate to clinical features of the disorder. Given the high comorbidity between OCD and anxiety, OCD symptom clusters may more broadly associate with fear and/or distress internalizing constructs. This study examines fear and distress dimensions, including physical concerns (fear), separation anxiety (fear), perfectionism (distress), and anxious coping (distress), as predictors of previously empirically-derived OCD symptom clusters in a sample of 215 youth diagnosed with primary OCD (ages 7-17, mean age = 12.25). Self-reported separation fears predicted membership in Cluster 1 (aggressive, sexual, religious, somatic obsessions, and checking compulsions) while somatic/autonomic fears predicted membership in Cluster 2 (symmetry obsessions and ordering, counting, repeating compulsions). Results highlight the diversity of pediatric OCD symptoms and their differential association with fear, suggesting the need to carefully assess both OCD and global fear constructs that might be directly targeted in treatment.
Assuntos
Adaptação Psicológica , Ansiedade de Separação , Ansiedade , Medo/psicologia , Transtorno Obsessivo-Compulsivo , Estresse Psicológico , Adolescente , Comportamento do Adolescente/psicologia , Ansiedade/diagnóstico , Ansiedade/psicologia , Ansiedade de Separação/diagnóstico , Ansiedade de Separação/psicologia , Técnicas de Observação do Comportamento/métodos , Criança , Comportamento Infantil/psicologia , Comportamento Compulsivo/psicologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Comportamento Obsessivo/diagnóstico , Comportamento Obsessivo/psicologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Perfeccionismo , Estresse Psicológico/diagnóstico , Estresse Psicológico/psicologiaRESUMO
Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS). Mutations in smoothened (SMO) encoding a receptor for sonic hedgehog have been reported in sporadic BCCs but not in BCNS. We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in three BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with the type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in increased SMO transactivating activity, and the patient responded to vismodegib therapy. Activating mutations in SMO may cause BCNS. The identification of a gain-of-function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumours, whether sporadic or inherited.
Assuntos
Síndrome do Nevo Basocelular/genética , Mutação/genética , Neoplasias Cutâneas/genética , Receptor Smoothened/genética , Sequência de Bases/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNARESUMO
Background: In dogs undergoing vertebral column stabilization, post-operative computed tomography (CT) evaluates implant placement. The impact on the interpretation of metallic artifact associated with titanium implants in dogs remains to be established. Our objective was to quantify metallic artifact on CT associated with titanium pedicle screws. Methods: The study design included an in vitro model and a retrospective review of 11 dogs with vertebral column stabilization. Twenty four titanium pedicle screws (6 each: 2.0 mm, 2.7 mm, 3.5 mm, and 4.5 mm) were inserted into a 20% ballistic gel, and CT scan of the construct was performed. Three blinded raters used a bone window to measure the maximum width (effective size) of each screw, one rater measured effective size using an ultrawide window and 45 titanium pedicle screws (3×2.0 mm, 5×2.7 mm, 30×3.5 mm, and 7×4.5 mm) in 11 clinical cases. Effective size measurements were compared to actual screw sizes. Results: The effective size was 26.9-43.8%, 9.2-18.5%, and 21.1-30.5% larger than the actual size for the in vitro system (bone window), in vitro system (ultrawide window), and clinical cases, respectively. The mean gross difference for the in vitro measurements varied by implant size (p < 0.001) and was positively correlated with implant size (r = 0.846), but the mean percentage difference was negatively correlated with implant size (p < 0.001). Overestimation was larger for the in vitro model bone window compared to the ultrawide window (p < 0.001) and clinical cases (p = 0.001). Conclusion: Metallic artifact associated with titanium pedicle screws on CT resulted in an overestimation of screw size. This information might aid in the interpretation of implant placement on post-operative imaging.
RESUMO
Reactive angioendotheliomatosis (RAE) is a diagnostically challenging condition characterized by multiple possible clinical presentations, which makes diagnosis challenging. We present a rare case of RAE mimicking cellulitis in a 74-year-old woman with a valvular disease and also end-stage renal disease, for which she was being treated with haemodialysis.
Assuntos
Celulite (Flegmão)/diagnóstico , Hemangioendotelioma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Doenças das Valvas Cardíacas/complicações , Humanos , Falência Renal Crônica/complicaçõesRESUMO
BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is the term given to a complex and heterogeneous group of cornification disorders associated with mutations in at least eight distinct genes. Mutation distribution and prevalence rates are instrumental for the design of diagnostic strategies in ARCI but have not yet been systematically explored in the Israeli population. Previous data suggest that the demographic features specific to Middle Eastern populations, such as a high frequency of consanguineous marriages, may have an effect on the molecular epidemiology of genodermatoses. METHODS: We systematically assessed all families with ARCI presenting at our clinics over a period of 9 years, using a combination of homozygosity mapping, direct sequencing and PCR-restriction fragment length polymorphism assays. RESULTS: In total, 20 families with ARCI were assessed, and causative mutations were identified in 7 genes: TGM1 (30% of patients), ALOX12B (20%), ABCA12 (5%), CYP4F22 (10%), ALOXE3 (10%), LIPN (5%) and NIPAL4 (5%) Two families (10%) had mutations mapped to an ARCI-associated locus on 12p11.2-q13, while no mutation was found for one additional kindred. In the subgroup of families of Arab Muslim origin, mutations were identified most frequently in ALOX12B and TGM1 (31%), whereas the other subgroups displayed a subtype distribution very similar to that previously reported in western populations. CONCLUSIONS: The present data point to the need for population-tailored mutation screening strategies in genetically heterogeneous genodermatoses, based on the relative prevalence of the disease subsets.
Assuntos
Araquidonato 12-Lipoxigenase/genética , Eritrodermia Ictiosiforme Congênita/genética , Mutação , Transglutaminases/genética , Povo Asiático/genética , Predisposição Genética para Doença , Humanos , Israel , Repetições de Microssatélites , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNARESUMO
Congenital hypotrichosis associated with juvenile macular dystrophy (HJMD; MIM601553) is an autosomal recessive disorder of unknown etiology, characterized by hair loss heralding progressive macular degeneration and early blindness. We used homozygosity mapping in four consanguineous families to localize the gene defective in HJMD to 16q22.1. This region contains CDH3, encoding P-cadherin, which is expressed in the retinal pigment epithelium and hair follicles. Mutation analysis shows in all families a common homozygous deletion in exon 8 of CDH3. These results establish the molecular etiology of HJMD and implicate for the first time a cadherin molecule in the pathogenesis of a human hair and retinal disorder.
Assuntos
Caderinas/genética , Distrofias Hereditárias da Córnea/genética , Hipotricose/genética , Mutação , Adolescente , Mapeamento Cromossômico , Cromossomos Humanos Par 16 , Distrofias Hereditárias da Córnea/complicações , Marcadores Genéticos , Homozigoto , Humanos , Hipotricose/complicações , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Deleção de SequênciaRESUMO
AIMS: Insulin sensitivity and acute insulin response measure key components of Type 2 diabetes aetiology that contribute independently to risk in the Insulin Resistance Atherosclerosis Study. As insulin sensitivity and acute insulin response are not routinely measured in a clinical setting, we evaluated three fasting biomarker models, homeostasis model assessment of insulin sensitivity (HOMA-%S), ß-cell function (HOMA-%B) and a Diabetes Risk Score, as potential surrogates for risk associated with insulin sensitivity, acute insulin response and the interaction of these two measures, the disposition index. METHODS: Models were calculated from baseline plasma biomarker concentrations for 664 participants who underwent a frequently sampled intravenous glucose tolerance test. To assess relationships among biomarker models and test measures, we calculated improvement in risk estimation gained by combining each fasting measure with each frequently sampled intravenous glucose tolerance test measure using logistic regression. RESULTS: The strongest correlates of acute insulin response, insulin sensitivity and disposition index were HOMA-%B (r(s)(2) = 0.23), HOMA-%S (r(s)(2) = 0.48) and Diabetes Risk Score (r(s)(2) = 0.34), respectively. Individual areas under the curves for prediction of diabetes were 0.549 (HOMA-%B), 0.694 (HOMA-%S), 0.700 (insulin sensitivity), 0.714 (acute insulin response), 0.756 (Diabetes Risk Score) and 0.817 (disposition index). Models combining acute insulin response with Diabetes Risk Score (area under the curve 0.798) or HOMA-%S (area under the curve 0.805) nearly equalled disposition index, outperforming other individual measures (P < 0.05). Insulin sensitivity plus Diabetes Risk Score (area under the curve 0.760) was better than insulin sensitivity (P = 0.03), but not better than Diabetes Risk Score alone. HOMA-%S plus insulin sensitivity (area under the curve 0.704) was not significantly better than either alone. CONCLUSIONS: The Diabetes Risk Score and HOMA-%S were excellent surrogates for insulin sensitivity, capturing the predictive power of insulin sensitivity. Diabetes Risk Score captured some of the additional predictive power of acute insulin response, but the HOMA models did not. No fasting model was as predictive as disposition index, but the Diabetes Risk Score was the best surrogate.
Assuntos
Aterosclerose/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Resistência à Insulina , Insulina/sangue , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Sensibilidade e EspecificidadeAssuntos
Anormalidades Craniofaciais , Sindactilia , Humanos , Intestinos/anormalidades , Mutação , Anormalidades da Pele , SíndromeRESUMO
The impact of foliar fertilization with zinc (ZnSO4) and manganese (MnSO4 on 137Cs uptake by spring wheat and potato was studied. The experiments were conducted during 3 years (2014-2016) in a137Cs-contaminated area, Zhytomyr region of Ukraine. The fertilization was carried out on podzolic loamy sand soil, poor in most of the microelements. Both crops were fertilized at four successive stages of growth. Foliar application of fertilizers caused higher yield of wheat grain/straw and potato tubers yield in 2014-2015 years but had no effect in 2016. Thus, the overall effect of fertilization between 2014 and 2016 was less pronounced and generally insignificant. Application of Zn, Mn and EDTA reduced 137Cs uptake by wheat grain and potato tubers, when fertilized at earlier stages of growth and development in years 2014 and 2015 by factor 1.5-2.0, while in 2016 the effect was generally statistically insignificant. It is suggested, that reduction of 137Cs uptake by spring wheat and potato, at least partly, was caused by an effect of radionuclide dilution due to the higher biomass of the plants. A foliar spray of EDTA at earlier stages of plant growth and development may be considered as a potential countermeasure aiming reducing 137Cs uptake from soil to plants, even if such effect appeared to be conditional.
Assuntos
Radioisótopos de Césio , Ácido Edético , Monitoramento de Radiação , Poluentes Radioativos do Solo/análise , Solanum tuberosum/fisiologia , Triticum/fisiologia , Fertilizantes , Manganês , Solo , Ucrânia , ZincoRESUMO
Although exposure-based cognitive behavior therapy (CBT) and pharmacotherapy have demonstrated efficacy for obsessive-compulsive disorder (OCD), the lack of clinicians effectively trained in these treatments significantly limit effective intervention options for affected youth. This is very unfortunate since child onset is reported by 50% of adults with OCD. To ameliorate this serious global issue the 14 nation International Obsessive-Compulsive Disorders Accreditation Task Force (ATF) of The Canadian Institute for Obsessive Compulsive Disorders (CIOCD) has developed knowledge and competency standards recommended for specialized treatments for OCD through the lifespan. Currently available guidelines are considered by experts to be essential but insufficient because there are not enough clinicians with requisite knowledge and competencies to effectively treat OCD. This manuscript presents knowledge and competency standards recommended for specialized cognitive behavior therapy (CBT) for pediatric OCD, derived from comprehensive literature review and expert synthesis. In addition to standards covering the elements of individual CBT-based assessment and treatment, family and school interventions are addressed given the critical role these domains play in the psychosocial development of youths. The ATF standards presented in these phase two papers will be foundational to the upcoming development of certification (individuals) and accreditation (sites) for specialized treatments in OCD through the lifespan.
Assuntos
Terapia Cognitivo-Comportamental , Transtorno Obsessivo-Compulsivo , Adolescente , Adulto , Terapia Comportamental , Canadá , Criança , Transtorno da Personalidade Compulsiva , Humanos , Transtorno Obsessivo-Compulsivo/terapia , Resultado do TratamentoRESUMO
AIMS/HYPOTHESIS: Exercise training improves glucose homeostasis, but large inter-individual differences are reported, suggesting a role of genetic factors. We investigated whether variants either confirmed or newly identified as diabetes susceptibility variants through genome-wide association studies (GWAS) modulate changes in phenotypes derived from an IVGTT in response to an endurance training programme. METHODS: We analysed eight polymorphisms in seven type 2 diabetes genes (CDKAL1 rs7756992; CDKN2A and CDKN2B rs10811661 and rs564398; HHEX rs7923837; IGF2BP2 rs4402960; KCNJ11 rs5215; PPARG rs1801282; and TCF7L2 rs7903146) in a maximum of 481 sedentary, non-diabetic white individuals, who participated in a 20-week endurance training programme. Associations were tested between the variants and changes in IVGTT-derived phenotypes. RESULTS: The only evidence of association with training response was found with PPARG rs1801282 (Pro12Ala). We observed that Ala carriers experienced greater increase in overall glucose tolerance (Deltaglucose disappearance index Ala/Ala 0.22 +/- 0.22, Pro/Ala 0.14 +/- 0.06, Pro/Pro 0.004 +/- 0.03; p = 0.0008), glucose effectiveness (Ala/Ala 0.28 +/- 0.41, Pro/Ala 0.44 +/- 0.14, Pro/Pro 0.09 +/- 0.06; p = 0.004), acute insulin response to glucose (Ala/Ala 64.21 +/- 37.73, Pro/Ala -11.92 +/- 40.30, Pro/Pro -46.30 +/- 14.70; p = 0.03) and disposition index (Ala/Ala 551.8 +/- 448.5, Pro/Ala 534.6 +/- 218.3, Pro/Pro -7.44 +/- 88.18; p = 0.003). CONCLUSIONS/INTERPRETATION: Compared with Pro/Pro individuals, PPARG Ala carriers experienced greater improvements in glucose and insulin metabolism in response to regular endurance training. However, we did not find evidence of association between type 2 diabetes susceptibility variants recently identified through GWAS and glucose homeostasis response to exercise. Our results extend those of previous studies showing that Ala carriers appear to be more responsive to beneficial health effects of lifestyle interventions.
Assuntos
Glicemia/metabolismo , Exercício Físico/fisiologia , PPAR gama/genética , Substituição de Aminoácidos , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Diabetes Mellitus/psicologia , Família , Frequência do Gene , Genes p16 , Variação Genética , Genótipo , Intolerância à Glucose/sangue , Intolerância à Glucose/genética , Teste de Tolerância a Glucose , Homeostase , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Estilo de Vida , Polimorfismo Genético , Fatores de RiscoRESUMO
AIMS/HYPOTHESIS: The majority of type 2 diabetes genome-wide association studies (GWAS) to date have been performed in European-derived populations and have identified few variants that mediate their effect through insulin resistance. The aim of this study was to evaluate two quantitative, directly assessed measures of insulin resistance, namely insulin sensitivity index (S(I)) and insulin disposition index (DI), in Hispanic-American participants using an agnostic, high-density single nucleotide polymorphism (SNP) scan, and to validate these findings in additional samples. METHODS: A two-stage GWAS was performed in Hispanic-American samples from the Insulin Resistance Atherosclerosis Family Study. In Stage 1, 317,000 SNPs were assessed using 229 DNA samples. SNPs with evidence of association with glucose homeostasis and adiposity traits were then genotyped on the entire set of Hispanic-American samples (n = 1,190). This report focuses on the glucose homeostasis traits: S(I) and DI. RESULTS: Although evidence of association did not reach genome-wide significance (p = 5 x 10(-7)), in the combined analysis SNPs had admixture-adjusted p values of p (ADD) = 0.00010-0.0020 with 8 to 41% differences in genotypic means for S(I) and DI. CONCLUSIONS/INTERPRETATION: Several candidate loci were identified that are nominally associated with S(I) and/or DI in Hispanic-American participants. Replication of these findings in independent cohorts and additional focused analysis of these loci is warranted.
Assuntos
Aterosclerose/genética , Estudo de Associação Genômica Ampla , Hispânico ou Latino/genética , Resistência à Insulina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Mapeamento Cromossômico/métodos , DNA/genética , Diabetes Mellitus Tipo 2/genética , Família , Jejum , Feminino , Genótipo , Glucose/metabolismo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Reprodutibilidade dos Testes , Estados Unidos , População Branca/genéticaRESUMO
BACKGROUND: Individuals with Obsessive-Compulsive Disorder (OCD) may lack insight into the irrational nature of their symptoms. Among adults with OCD, poor insight has been linked to greater symptom severity, increased likelihood of comorbid symptoms, lower adaptive functioning, and worse treatment outcomes. Parallel work regarding insight among children and adolescents, with OCD, is lacking. The aim of this research was to examine links between insight and demographic, cognitive, and clinical factors among youth with OCD. METHODS: Seventy-one youths with OCD (mean age = 11.7; 63% = male) were assessed as part of a larger treatment trial. Insight was measured via clinician interview. RESULTS: Youth with low insight had poorer intellectual functioning and reported decreased perception of control over their environment. Additionally, youth with low insight were more likely to be younger, to report higher levels of depressive symptoms, and to report lower levels of adaptive functioning. CONCLUSION: This set of cognitive, developmental and clinical factors that may predispose youth with OCD to have diminished insight. Data provide initial empirical support for diagnostic differences between youth and adults with regard to requiring intact insight. Implications for treatment are discussed.