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1.
Pacing Clin Electrophysiol ; 47(4): 483-489, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38407409

RESUMO

BACKGROUND: Atrioventricular block (AVB) secondary to transient causes can recover with its correction. However, studies assessing predictors of recovery and long-term recurrence are lacking. METHODS: Patients with advanced or complete AVB who had a reversible cause admitted in a single expert center were retrospectively studied. Patients with AVB secondary to acute coronary syndromes were excluded from analysis. RESULTS: In a population of 162 patients, the main factors associated with recovery of rhythm without a permanent pacemaker (PPM) implantation were the presence of chronic kidney disease (CKD) on dialysis (OR 7.6; CI 95% 1.2-47.5 (p = .03)); greater serum potassium levels (OR 2.3; CI 95% 1.28-4.0 (p < .01)), higher dosage of bradycardic drugs (OR 2.2; CI 95% 1.13-4.4 (p = .02)), the association between different bradycardic drugs (OR 9.0; CI 95% 2.02-40.3 (p < .01)) and between drug therapy and hyperkaliemia (OR 5.2; CI 95% 1.8-15.1 (p < .01)). There was an overall high burden of conductions abnormalities which did not correlate with recovery of rhythm (OR 0.5; CI 95% 0.19-1.5 (p = .23)). In 29 patients (17.9%) there was a correction of the AVB. During a maximum follow-up of 130 months, 24 patients (82.8%) had a recurrence which warranted a PPM. In the overall cohort only five patients (3%) had sustained recovery of rhythm. CONCLUSIONS: Recovery of AVB was mainly observed with higher doses of drug therapy, higher serum potassium levels or a combination of factors and regardless of baseline conduction abnormalities. The high rate of recurrence during follow-up warrants a close follow-up or PPM implantation at index admission.


Assuntos
Bloqueio Atrioventricular , Marca-Passo Artificial , Humanos , Estudos Retrospectivos , Fatores de Risco , Causalidade , Doença do Sistema de Condução Cardíaco/complicações , Potássio , Marca-Passo Artificial/efeitos adversos
2.
J Eur Acad Dermatol Venereol ; 38(4): 645-656, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38084889

RESUMO

INTRODUCTION: Several classifications of psychodermatology disorders have been proposed, with most of them based on two to four main disorder category groups. However, there is, to date, no classification that has resulted from a consensus established by psychodermatology experts. The DSM-5-TR (Diagnostic and statistical manual of mental disorders (5th ed.), Text Revision) and the ICD-11 (International classification of diseases (11th revision)) also do not provide a systematized approach of psychodermatology disorders. Taking into consideration that classifications are a key pillar for a comprehensive approach to the pathologies of each branch of medicine, the proposal of a classification in psychodermatology appeared as a central need for the recognition of psychodermatological disorders, in an attempt to improve their recognition and, in that sense, to find a common language for the development of this subspecialty that crosses dermatology and psychiatry. METHODS: Previously published classifications in psychodermatology were critically reviewed and discussed by expert opinion from an international multidisciplinary panel of 16 experts in psychodermatology and a new classification system is proposed, considering classical concepts in general dermatology and psychopathology. RESULTS: Two main categories of disorders are presented (a main group related to primary mental health disorders and another main group related to primary skin disorders), which are subsequently subdivided into subgroups considering pathophysiological and phenomenological similarities, including key aspects of dermatological examination, namely the presence of visible skin lesions (primary and secondary skin lesions) and psychopathological correlates. CONCLUSION: This new classification aims to unify previous classifications, systematize the disorders that belong to psychodermatology and highlight their tenuous boundaries, to improve their management. It has been built and approved by the Psychodermatology Task Force of the European Academy of Dermatology and Venereology (EADV), the European Society for Dermatology and Psychiatry (ESDaP) and the Association for Psychoneurocutaneous Medicine of North America (APMNA).


Assuntos
Dermatologia , Transtornos Mentais , Dermatopatias , Humanos , Dermatologia/métodos , Dermatopatias/complicações , Transtornos Mentais/psicologia , Pele , Psicopatologia
3.
Knee Surg Sports Traumatol Arthrosc ; 32(3): 713-724, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38385776

RESUMO

PURPOSE: Patellofemoral instability (PFI) is a common condition that can be caused from multiple factors, including lower limb rotational malalignments. Determining precise criteria for performing corrective torsional osteotomy can be a daunting task due to the lack of consensus on normal and excessive values and the limited evidence-based data in the postoperative results. The purpose was to assess the clinical, functional and imaging outcomes following derotational distal femoral osteotomy (DDFO) in patients with PFI and/or anterior knee pain (AKP) associated with lower limb rotational malalignments. METHODS: Searches were conducted on PubMed, EMBASE and Web of Science databases up to October 2023. Studies reporting outcomes after DDFO in patients with PFI and/or AKP were eligible for the systematic review. The primary outcome was imaging metrics, especially femoral anteversion. Secondary outcomes included the patient-reported outcome measures (PROMs) (clinical and functional). Quantitative synthesis involved the use of weighted averages to calculate pre- to postoperative mean differences (MD) and compare them against the minimal clinically important difference (MCID). RESULTS: Ten studies (309 knees) were included with a mean follow-up of 36.1 ± 11.7 months. Imaging outcomes consistently indicated the correction of femoral anteversion (MD = -19.4 degrees, 95% confidence interval: -20.1 to -18.7) following DDFO. PROMs showed significant improvements in most studies, exceeding the MCID. Patient satisfaction with the DDFO was high (93.3%). CONCLUSIONS: The DDFO was an effective treatment option for correcting excessive femoral anteversion in patients with PFI associated with clinically relevant functional and clinical improvement and a high satisfaction rate. LEVEL OF EVIDENCE: Level IV, systematic review of level II-IV studies.


Assuntos
Fêmur , Articulação Patelofemoral , Humanos , Fêmur/cirurgia , Articulação do Joelho/cirurgia , Resultado do Tratamento , Satisfação do Paciente , Osteotomia/métodos , Dor , Articulação Patelofemoral/cirurgia
4.
J Zoo Wildl Med ; 55(2): 369-380, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38875193

RESUMO

The Scottish population of the European wildcat (Felis silvestris), the only remaining native felid species in the United Kingdom, is critically endangered and was declared functionally extinct by the International Union for Conservation of Nature in 2019. This retrospective study investigated the causes of morbidity and mortality reported in the United Kingdom captive wildcat population from 01 January 2000 to 31 December 2021. The aim was to assess the health and welfare of ex situ wildcats and, by making recommendations for management based on study findings, contribute to the sustainability of the population under managed care. Younger wildcats accounted for 85.7% of all morbidity cases (kittens, 7/77; young adults, 59/77), and the gastrointestinal (67.5% [52/77]), musculoskeletal (10.4% [8/77]), and integumentary (5.2% [4/77]) systems were most affected. Mortality was primarily associated with disease of the gastrointestinal (13.5% [12/89]), respiratory (13.5% [12/89]), neurological (5.6% [5/89]), and renal (5.6% [5/89]) systems. One quarter of all the histopathology examinations reported gastritis with associated Helicobacter-like organisms, often combined with pancreatitis or cholangiohepatitis. Neonates represented 25% (22/89) of all deaths, a high percentage compared with that of previous reviews in other nondomestic felids.


Assuntos
Animais Selvagens , Animais , Reino Unido/epidemiologia , Estudos Retrospectivos , Felis , Masculino , Espécies em Perigo de Extinção , Feminino
5.
Am J Med Genet A ; 191(2): 599-604, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36416207

RESUMO

The ZDHHC9 gene encodes the Zinc Finger DHHC-Type Containing 9 protein that functions as a palmitoyltransferase. Variants in this gene have been reported as the cause of Raymond-type X-linked intellectual disability with only 16 families described in the literature. This study reviews molecular and clinical data from previously reported patients and reports the case of a 13-year-old patient with a splicing variant in ZDHHC9 presenting intellectual disability, developmental delay, facial dysmorphisms, and skeletal defects. Although intellectual disability and developmental delay with severe speech delay have been reported in all cases with available clinical data, the remaining clinical signs differ significantly between patients. Missense, nonsense, frameshift, and splicing variants, in addition to large exonic deletions, have been described suggesting a loss of function mechanism. Though variants are distributed in almost all exons, most missense and nonsense variants affect arginine residues located in the cytoplasmic domains of this transmembrane protein, suggesting possible mutational hotspots.


Assuntos
Deficiência Intelectual , Adolescente , Humanos , Éxons/genética , Mutação da Fase de Leitura , Genes Ligados ao Cromossomo X/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Deficiência Intelectual/metabolismo , Mutação , Fenótipo
6.
Acta Derm Venereol ; 103: adv8488, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37606153

RESUMO

There are no previous studies of the psychopathology associated with different aetiologies of chronic pruritus. A systematic review was performed of cohort and case-control studies comparing healthy controls with patients with chronic pruritus related to primary dermatoses, systemic diseases, psychogenic pruritus, idiopathic pruritus, prurigo nodularis and/or lichen simplex chronicus. The review was registered in PROSPERO and performed according to the PRISMA statement, which allowed the inclusion of 26 studies. The quality of eligible studies was assessed using the modified Newcastle-Ottawa Scale. Most of the studies concern primary dermatoses and systemic diseases. Sleep disorders are a common comorbidity interrelated with pruritus, anxiety and depressive symptoms, in primary dermatoses. Sleep disorders are linked with pruritus and depressive symptoms in end-stage renal disease and hepatobiliary disease. Depressive and anxiety symptoms are associated with psychogenic pruritus. Psychogenic pruritus, lichen simplex chronicus and some primary dermatoses are linked with personality characteristics. Further studies are required to explore in depth the psychopathology linked with psychogenic pruritus and prurigo nodularis, as well as psychopathology linked with other primary dermatoses and systemic disorders associated with chronic pruritus, and to better differentiate psychogenic pruritus from psychopathological characteristics linked with other aetiologies of chronic pruritus, in order to improve the management of patients with chronic pruritus.


Assuntos
Transtornos Mentais , Neurodermatite , Prurigo , Humanos , Prurido/diagnóstico , Prurido/epidemiologia , Transtornos Psicofisiológicos , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia
7.
Acta Derm Venereol ; 103: adv6485, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37345973

RESUMO

Perceived stigmatization places a large psychosocial burden on patients with some skin conditions. Little is known about the experience of stigmatization across a wide range of skin diseases. This observational cross-sectional study aimed to quantify perceived stigmatization and identify its predictors among patients with a broad spectrum of skin diseases across 17 European countries. Self-report questionnaires assessing perceived stigmatization and its potential predictors were completed by 5,487 dermatology outpatients and 2,808 skin-healthy controls. Dermatological diagnosis, severity, and comorbidity were clinician-assessed. Patients experienced higher levels of perceived stigmatization than controls (p < 0.001, d = 0.26); patients with psoriasis, atopic dermatitis, alopecia, and bullous disorders were particularly affected. Multivariate regression analyses showed that perceived stigmatization was related to sociodemographic (lower age, male sex, being single), general health-related (higher body mass index, lower overall health), disease-related (higher clinician-assessed disease severity, presence of itch, longer disease duration), and psychological (greater distress, presence of suicidal ideation, greater body dysmorphic concerns, lower appearance satisfaction) variables. To conclude, perceived stigmatization is common in patients with skin diseases. Factors have been identified that will help clinicians and policymakers to target vulnerable patient groups, offer adequate patient management, and to ultimately develop evidence-based interventions.


Assuntos
Psoríase , Dermatopatias , Humanos , Masculino , Estereotipagem , Pacientes Ambulatoriais , Qualidade de Vida/psicologia , Dermatopatias/diagnóstico , Dermatopatias/psicologia , Psoríase/diagnóstico , Psoríase/psicologia , Inquéritos e Questionários
8.
Molecules ; 28(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37375331

RESUMO

Melanoma incidence, a type of skin cancer, has been increasing worldwide. There is a strong need to develop new therapeutic strategies to improve melanoma treatment. Morin is a bioflavonoid with the potential for use in the treatment of cancer, including melanoma. However, therapeutic applications of morin are restrained owing to its low aqueous solubility and limited bioavailability. This work investigates morin hydrate (MH) encapsulation in mesoporous silica nanoparticles (MSNs) to enhance morin bioavailability and consequently increase the antitumor effects in melanoma cells. Spheroidal MSNs with a mean size of 56.3 ± 6.5 nm and a specific surface area of 816 m2/g were synthesized. MH was successfully loaded (MH-MSN) using the evaporation method, with a loading capacity of 28.3% and loading efficiency of 99.1%. In vitro release studies showed that morin release from MH-MSNs was enhanced at pH 5.2, indicating increased flavonoid solubility. The in vitro cytotoxicity of MH and MH-MSNs on human A375, MNT-1 and SK-MEL-28 melanoma cell lines was investigated. Exposure to MSNs did not affect the cell viability of any of the cell lines tested, suggesting that the nanoparticles are biocompatible. The effect of MH and MH-MSNs on reducing cell viability was time- and concentration-dependent in all melanoma cell lines. The A375 and SK-MEL-28 cell lines were slightly more sensitive than MNT-1 cells in both the MH and MH-MSN treatments. Our findings suggest that MH-MSNs are a promising delivery system for the treatment of melanoma.


Assuntos
Melanoma , Nanopartículas , Humanos , Dióxido de Silício , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos , Melanoma/tratamento farmacológico , Flavonoides/farmacologia , Porosidade
9.
Hum Mutat ; 43(7): 900-918, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35344616

RESUMO

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.


Assuntos
Anormalidades Craniofaciais , Nanismo , Deformidades Congênitas dos Membros , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Anormalidades Urogenitais , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/genética , Nanismo/diagnóstico , Nanismo/genética , Genes Recessivos , Humanos , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/genética , Masculino , Fenótipo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/genética
10.
Br J Dermatol ; 187(1): 115-125, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35041211

RESUMO

BACKGROUND: Body dysmorphic disorder (BDD) is a common psychiatric disorder associated with high costs for healthcare systems as patients may repeatedly ask for different, often not effective, interventions. BDD symptoms are more prevalent in patients with dermatological conditions than in the general population, but there are no large sample studies comparing the prevalence of BDD symptoms between patients with dermatological conditions and healthy skin controls. OBJECTIVES: To compare the prevalence of BDD symptoms between patients with different dermatological conditions and healthy skin controls and to describe sociodemographic, physical and psychological factors associated with BDD symptoms to identify patients who may have a particularly high chance of having this condition. METHODS: This observational, cross-sectional, comparative multicentre study included 8295 participants: 5487 consecutive patients with different skin diseases (56% female) recruited among dermatological outpatients at 22 clinics in 17 European countries, and 2808 healthy skin controls (66% female). BDD symptoms were assessed by the Dysmorphic Concern Questionnaire. Sociodemographic data and information on psychological factors and physical conditions were collected. Each patient was given a dermatological diagnosis according to ICD-10 by a dermatologist. The study was registered with number DRKS00012745. RESULTS: The average participation rate of invited dermatological patients was 82.4% across all centres. BDD symptoms were five times more prevalent in patients with dermatological conditions than in healthy skin controls (10.5% vs. 2.1%). Patients with hyperhidrosis, alopecia and vitiligo had a more than 11-fold increased chance (adjusted Odds Ratio (OR) > 11) of having BDD symptoms compared with healthy skin controls, and patients with atopic dermatitis, psoriasis, acne, hidradenitis suppurativa, prurigo and bullous diseases had a more than sixfold increased chance (adjusted OR > 6) of having BDD symptoms. Using a logistic regression model, BDD symptoms were significantly related to lower age, female sex, higher psychological stress and feelings of stigmatization. CONCLUSIONS: Clinical BDD symptoms are significantly associated with common dermatological diseases. As such symptoms are associated with higher levels of psychological distress and multiple unhelpful consultations, general practitioners and dermatologists should consider BDD and refer patients when identified to an appropriate service for BDD screening and management.


Assuntos
Acne Vulgar , Transtornos Dismórficos Corporais , Acne Vulgar/psicologia , Transtornos Dismórficos Corporais/diagnóstico , Transtornos Dismórficos Corporais/epidemiologia , Transtornos Dismórficos Corporais/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , Prevalência , Inquéritos e Questionários
11.
Int J Mol Sci ; 23(5)2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35269997

RESUMO

After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs' biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs' properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.


Assuntos
Antineoplásicos , Complexos de Coordenação , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Cobre/química , Metais/química
12.
Am J Hum Genet ; 102(1): 27-43, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29276006

RESUMO

Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. Robinow syndrome is a skeletal disorder historically refractory to molecular diagnosis, potentially stemming from substantial genetic heterogeneity. All current known pathogenic variants reside in genes within the noncanonical Wnt signaling pathway including ROR2, WNT5A, and more recently, DVL1 and DVL3. However, ∼70% of autosomal-dominant Robinow syndrome cases remain molecularly unsolved. To investigate this missing heritability, we recruited 21 families with at least one family member clinically diagnosed with Robinow or Robinow-like phenotypes and performed genetic and genomic studies. In total, four families with variants in FZD2 were identified as well as three individuals from two families with biallelic variants in NXN that co-segregate with the phenotype. Importantly, both FZD2 and NXN are relevant protein partners in the WNT5A interactome, supporting their role in skeletal development. In addition to confirming that clustered -1 frameshifting variants in DVL1 and DVL3 are the main contributors to dominant Robinow syndrome, we also found likely pathogenic variants in candidate genes GPC4 and RAC3, both linked to the Wnt signaling pathway. These data support an initial hypothesis that Robinow syndrome results from perturbation of the Wnt/PCP pathway, suggest specific relevant domains of the proteins involved, and reveal key contributors in this signaling cascade during human embryonic development. Contrary to the view that non-allelic genetic heterogeneity hampers gene discovery, this study demonstrates the utility of rare disease genomic studies to parse gene function in human developmental pathways.


Assuntos
Anormalidades Craniofaciais/genética , Nanismo/genética , Heterogeneidade Genética , Deformidades Congênitas dos Membros/genética , Anormalidades Urogenitais/genética , Via de Sinalização Wnt/genética , Adolescente , Adulto , Sequência de Bases , Criança , Pré-Escolar , Segregação de Cromossomos/genética , Anormalidades Craniofaciais/diagnóstico , Diagnóstico Diferencial , Nanismo/diagnóstico , Feminino , Genes Dominantes , Estudos de Associação Genética , Humanos , Deformidades Congênitas dos Membros/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Fenótipo , Anormalidades Urogenitais/diagnóstico
13.
FASEB J ; 34(10): 13959-13977, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32851720

RESUMO

Growing evidence supports a central role of NADPH oxidases (NOXs) in the regulation of platelets, which are circulating cells involved in both hemostasis and thrombosis. Here, the use of Nox1-/- and Nox1+/+ mice as experimental models of human responses demonstrated a critical role of NOX1 in collagen-dependent platelet activation and pathological arterial thrombosis, as tested in vivo by carotid occlusion assays. In contrast, NOX1 does not affect platelet responses to thrombin and normal hemostasis, as assayed in tail bleeding experiments. Therefore, as NOX1 inhibitors are likely to have antiplatelet effects without associated bleeding risks, the NOX1-selective inhibitor 2-acetylphenothiazine (2APT) and a series of its derivatives generated to increase inhibitory potency and drug bioavailability were tested. Among the 2APT derivatives, 1-(10H-phenothiazin-2-yl)vinyl tert-butyl carbonate (2APT-D6) was selected for its high potency. Both 2APT and 2APT-D6 inhibited collagen-dependent platelet aggregation, adhesion, thrombus formation, superoxide anion generation, and surface activation marker expression, while responses to thrombin or adhesion to fibrinogen were not affected. In vivo administration of 2APT or 2APT-D6 led to the inhibition of mouse platelet aggregation, oxygen radical output, and thrombus formation, and carotid occlusion, while tail hemostasis was unaffected. Differently to in vitro experiments, 2APT-D6 and 2APT displayed similar potency in vivo. In summary, NOX1 inhibition with 2APT or its derivative 2APT-D6 is a viable strategy to control collagen-induced platelet activation and reduce thrombosis without deleterious effects on hemostasis. These compounds should, therefore, be considered for the development of novel antiplatelet drugs to fight cardiovascular diseases in humans.


Assuntos
Trombose das Artérias Carótidas/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , NADPH Oxidase 1/antagonistas & inibidores , Fenotiazinas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Animais , Trombose das Artérias Carótidas/prevenção & controle , Células Cultivadas , Colágeno/metabolismo , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Fibrinogênio/metabolismo , Hemorragia/etiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fenotiazinas/efeitos adversos , Fenotiazinas/uso terapêutico , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Trombina/metabolismo
14.
Neurobiol Learn Mem ; 168: 107157, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31927084

RESUMO

Differences in motor learning can be partially explained by differences in genotype. The catechol-O-methyltransferase (COMT) Val158Met polymorphism regulates the dopamine (DA) availability in the prefrontal cortex modulating motor learning and performance. Given the differences in tonic and phasic DA transmission, this study aimed to investigate whether the greater cognitive flexibility associated with the Val allele would favor the learning of movement parametrization, while the greater cognitive stability associated with the Met allele favors the acquisition of the movement pattern. Furthermore, we investigated if the genotypic characteristics impact visual scanning of information related to parametrization and to the movement pattern, and the level of cortical connectivity associated with motor planning and control. Performance and learning of a sequential motor task were compared among three genotypes (Val/Val, Val/Met, and Met/Met), as well as their oculomotor behavior and level of cortical coherence. The findings show that the cognitive flexibility promoted by the Val allele is associated with a better parametrization. The search for information through visual scanning was specific to each genotype. Also, a greater cortical connectivity associated with the Val allele was found. The combined study of behavioral, electrophysiological and molecular levels of analysis showed that the cognitive stability and flexibility associated with the COMT alleles, influence specific aspects of motor learning.


Assuntos
Encéfalo/fisiologia , Catecol O-Metiltransferase/fisiologia , Movimentos Oculares/fisiologia , Aprendizagem/fisiologia , Atividade Motora/fisiologia , Adulto , Catecol O-Metiltransferase/genética , Eletroencefalografia , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto Jovem
15.
Dermatol Ther ; 33(6): e13969, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32621633

RESUMO

Psychodermatology is a growing specialty which is gaining momentum in different parts of the world. It focuses on the connection between skin and psyche. Psychocutaneous conditions are characterized by those disorders where stress is the key element in exacerbating skin conditions or flare ups of dermatoses like psoriasis and atopic dermatitis. There is a direct relationship of stress with the course, and prognosis of the skin disease. In some situations, there is no skin condition but the lesions are self-inflicted and such disorders are always associated with underlying psychopathology or psychological conflicts. Sometimes emotional problems are more prominent as a result of having skin disease, and the psychological consequences may be more severe than the physical symptoms. Management of these conditions require a combination of psychpharmacology, psychotherapy, and liaison clinics of psychiatry and dermatology. This review focuses on the common management approach which can be adopted by dermatologists in treating patients with psychodermatological disorders, improving doctor-patient relationship and therapeutic bond.


Assuntos
Dermatologia , Psiquiatria , Dermatopatias , Dermatologistas , Humanos , Relações Médico-Paciente , Dermatopatias/diagnóstico , Dermatopatias/terapia
16.
Arch Toxicol ; 93(9): 2617-2634, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31468101

RESUMO

3-Methylmethcathinone (3-MMC or metaphedrone) has become one of the most popular recreational drugs worldwide after the ban of mephedrone, and was recently deemed responsible for several intoxications and deaths. This study aimed at assessing the hepatotoxicity of 3-MMC. For this purpose, Wistar rat hepatocytes were isolated by collagenase perfusion, cultured and exposed for 24 h at a concentration range varying from 31 nM to 10 mM 3-MMC. The modulatory effects of cytochrome P450 (CYP) inhibitors on 3-MMC hepatotoxicity were evaluated. 3-MMC-induced toxicity was perceived at the lysosome at lower concentrations (NOEC 312.5 µM), compared to mitochondria (NOEC 379.5 µM) and cytoplasmic membrane (NOEC 1.04 mM). Inhibition of CYP2D6 and CYP2E1 diminished 3-MMC cytotoxicity, yet for CYP2E1 inhibition this effect was only observed for concentrations up to 1.3 mM. A significant concentration-dependent increase of intracellular reactive species was observed from 10 µM 3-MMC on; a concentration-dependent decrease in antioxidant glutathione defences was also observed. At 10 µM, caspase-3, caspase-8, and caspase-9 activities were significantly elevated, corroborating the activation of both intrinsic and extrinsic apoptosis pathways. Nuclear morphology and formation of cytoplasmic acidic vacuoles suggest prevalence of necrosis and autophagy at concentrations higher than 10 µM. No significant alterations were observed in the mitochondrial membrane potential, but intracellular ATP significantly decreased at 100 µM. Our data point to a role of metabolism in the hepatotoxicity of 3-MMC, which seems to be triggered both by autophagic and apoptotic/necrotic mechanisms. This work is the first approach to better understand 3-MMC toxicology.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Metanfetamina/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Psicotrópicos/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Masculino , Metanfetamina/toxicidade , Cultura Primária de Células , Ratos Wistar
18.
Artigo em Inglês | MEDLINE | ID: mdl-30258484

RESUMO

OBJECTIVES: This study aims to identify the prevalence of burnout and associated factors in Brazilian medical students. METHODS: In the largest medical school from Central Brazil, the Maslach Burnout Inventory-Student Survey and a socio-demographic questionnaire were adopted in this cross-sectional study. Correlations among the three dimensions of burnout were verified. RESULTS: The evaluation of 399 students revealed a frequency of 12.0% of burnout. Women had a higher rate of burnout (8.0%) than men (4.0%). The fifth period had the higher frequency of burnout (27.1%), while the seventh grade had the lower frequency (2.1%). The students showed high scores only in emotional exhaustion (63.2%). Between the dimensions "emotional exhaustion" and "disbelief" found a significant correlation. CONCLUSION: The fifth period of the Medicine course and the female gender are the most affected by burnout syndrome and therefore, the preventive actions to reduce stress among medical students should be directed mainly at these higher risk categories. The low burnout rate found in our study can attest that the PBL methodology and medical schools strategically located to meet regional demand may represent strategies for the prevention of burnout among medical students.

19.
J Med Syst ; 41(2): 23, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28000117

RESUMO

Indoor environments are characterized by several pollutant sources. Because people spend more than 90% of their time in indoor environments, several studies have pointed out the impact of indoor air quality on the etiopathogenesis of a wide number of non-specific symptoms which characterizes the "Sick Building Syndrome", involving the skin, the upper and lower respiratory tract, the eyes and the nervous system, as well as many building related diseases. Thus, indoor air quality (IAQ) is recognized as an important factor to be controlled for the occupants' health and comfort. The majority of the monitoring systems presently available is very expensive and only allow to collect random samples. This work describes the system (iAQ), a low-cost indoor air quality monitoring wireless sensor network system, developed using Arduino, XBee modules and micro sensors, for storage and availability of monitoring data on a web portal in real time. Five micro sensors of environmental parameters (air temperature, humidity, carbon monoxide, carbon dioxide and luminosity) were used. Other sensors can be added for monitoring specific pollutants. The results reveal that the system can provide an effective indoor air quality assessment to prevent exposure risk. In fact, the indoor air quality may be extremely different compared to what is expected for a quality living environment. Systems like this would have benefit as public health interventions to reduce the burden of symptoms and diseases related to "sick buildings".


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental/instrumentação , Saúde Ocupacional , Tecnologia sem Fio , Dióxido de Carbono/análise , Monóxido de Carbono/análise , Humanos , Umidade , Armazenamento e Recuperação da Informação/métodos , Síndrome do Edifício Doente/prevenção & controle , Temperatura
20.
Wien Med Wochenschr ; 167(Suppl 1): 49-51, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28299553

RESUMO

"Morgellons disease" has been a controversial topic in the history of psychodermatology. The most consensual scientific opinion is that it is a primary psychiatric disorder, particularly, a delusional disorder, although others were also pointed out. Some authors have suggested that it may correspond to a common dermatosis with secondary psychopathology. The Morgellons Research Foundation has advocated that it is "an emerging infectious" entity. This paper intends to critically review the main ideas and controversies, since its first description.


Assuntos
Delírio de Parasitose/história , Dermatologia/história , Doença de Morgellons/história , Transtornos Neuróticos/história , Psiquiatria/história , Terminologia como Assunto , Criança , Pré-Escolar , Feminino , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Lactente , Masculino
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