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1.
Vet Surg ; 51(7): 1070-1077, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35834384

RESUMO

OBJECTIVE: To determine the ability of a commercial cryotherapy system (Game Ready Equine) to cool the metacarpal subcutaneous tissue and the superficial digital flexor tendon (SDFT) in horses. STUDY DESIGN: Experimental study. ANIMALS OR SAMPLE POPULATION: Six healthy adult horses. METHODS: Thermocouples were implanted into the metacarpal subcutaneous tissues and the SDFT of six horses. Two treatments (cryotherapy or cryotherapy with 5-50 mmHg intermittent compression) were randomly assigned to forelimbs and performed for 20 minutes. Temperatures were compared to the target range of 10-19°C and between groups. RESULTS: Only one limb in the cryotherapy/compression group reached the target range after cryotherapy. Temperatures did not differ between treatment groups at time 0. Lowest temperatures achieved in the subcutaneous tissue (p = .0043) and SDFT (p = .005) were 4.9 and 7.6°C lower when intermittent compression was applied. Similarly, applying compression induced a maximum change in temperature of approximately 7.0°C in the subcutaneous tissue (p = .014) and 10.2°C in the SDFT (p = .0001). CONCLUSION: The cryotherapy system did not cool equine subcutaneous tissue or SDFT to the target temperature range, except in one limb. Combining cryotherapy with intermittent compression did result in lower temperatures and a greater change in temperature of the subcutaneous tissue and SDFT. CLINICAL SIGNIFICANCE: When using this cryotherapy system, the addition of intermittent compression should be considered to achieve lower temperatures and potentially greater reduction in inflammation. Further studies are warranted to determine the effect of longer treatment times, higher compression settings, and the optimal temperature for benefits in normal and diseased equine tissues.


Assuntos
Ossos Metacarpais , Metacarpo , Animais , Crioterapia/veterinária , Membro Anterior , Cavalos , Tendões
2.
Anat Histol Embryol ; 51(4): 484-491, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35608253

RESUMO

The aim of the study was to perform the morphometric analyses on metacarpi of Hamdani sheep via different measurement methods and to compare the methods. Thus, metacarpal bones of 15 females and 15 males were used in the study. Measurements were taken from the measurement points determined on metacarpus via four methods, and their statistical analyses were performed. When both male and female metacarpal bones were examined in the De parameter in the comparison with the methods, it was observed that the four measurement methods were different from one another (p < 0.01). When DEM and DEL measurement parameters were examined in male metacarpus, the highest value was measured in ImageJ and the smallest value was measured in 3D Slicer software; however, it was found that the statistical difference was not significant when compared numerically (p > 0.05). As a result, while it was observed that the measurements made by using digital calliper measurements, photometric analysis, and 3D software were similar in some of the parameters but there was no statistically significant difference; whereas, Statistical difference was detected in some parameters.


Assuntos
Ossos Metacarpais , Metacarpo , Animais , Feminino , Masculino , Ovinos
3.
Nucleic Acids Res ; 50(10): 5850-5863, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35580046

RESUMO

DDX58 encodes RIG-I, a cytosolic RNA sensor that ensures immune surveillance of nonself RNAs. Individuals with RIG-IE510V and RIG-IQ517H mutations have increased susceptibility to Singleton-Merten syndrome (SMS) defects, resulting in tissue-specific (mild) and classic (severe) phenotypes. The coupling between RNA recognition and conformational changes is central to RIG-I RNA proofreading, but the molecular determinants leading to dissociated disease phenotypes remain unknown. Herein, we employed hydrogen/deuterium exchange mass spectrometry (HDX-MS) and single molecule magnetic tweezers (MT) to precisely examine how subtle conformational changes in the helicase insertion domain (HEL2i) promote impaired ATPase and erroneous RNA proofreading activities. We showed that the mutations cause a loosened latch-gate engagement in apo RIG-I, which in turn gradually dampens its self RNA (Cap2 moiety:m7G cap and N1-2-2'-O-methylation RNA) proofreading ability, leading to increased immunopathy. These results reveal HEL2i as a unique checkpoint directing two specialized functions, i.e. stabilizing the CARD2-HEL2i interface and gating the helicase from incoming self RNAs; thus, these findings add new insights into the role of HEL2i in the control of antiviral innate immunity and autoimmunity diseases.


Assuntos
Doenças Autoimunes , Odontodisplasia , Doenças Autoimunes/genética , Proteína DEAD-box 58/química , Proteína DEAD-box 58/genética , RNA Helicases DEAD-box/química , RNA Helicases DEAD-box/genética , Humanos , Imunidade Inata/genética , Metacarpo , RNA/química
4.
Pediatr Rheumatol Online J ; 20(1): 24, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410415

RESUMO

BACKGROUND: Singleton-Merten syndrome 1 (SGMRT1) is a rare type I interferonopathy caused by heterozygous mutations in the IFIH1 gene. IFIH1 encodes the pattern recognition receptor MDA5 which senses viral dsRNA and activates antiviral type I interferon (IFN) signaling. In SGMRT1, IFIH1 mutations confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation. CASE PRESENTATION: We report the case of a nine year old child who initially presented with a slowly progressive decline of gross motor skill development and muscular weakness. At the age of five years, he developed osteoporosis, acro-osteolysis, alveolar bone loss and severe psoriasis. Whole exome sequencing revealed a pathogenic de novo IFIH1 mutation, confirming the diagnosis of SGMRT1. Consistent with constitutive type I interferon activation, patient blood cells exhibited a strong IFN signature as shown by marked up-regulation of IFN-stimulated genes. The patient was started on the Janus kinase (JAK) inhibitor, ruxolitinib, which inhibits signaling at the IFN-α/ß receptor. Within days of treatment, psoriatic skin lesions resolved completely and the IFN signature normalized. Therapeutic efficacy was sustained and over the course muscular weakness, osteopenia and growth also improved. CONCLUSIONS: JAK inhibition represents a valuable therapeutic option for patients with SGMRT1. Our findings also highlight the potential of a patient-tailored therapeutic approach based on pathogenetic insight.


Assuntos
Interferon Tipo I , Osteoporose , Doenças da Aorta , Criança , Pré-Escolar , Hipoplasia do Esmalte Dentário , Humanos , Helicase IFIH1 Induzida por Interferon/genética , Masculino , Metacarpo/anormalidades , Debilidade Muscular , Doenças Musculares , Nitrilas , Odontodisplasia , Osteoporose/genética , Pirazóis , Pirimidinas , Calcificação Vascular
5.
Anat Rec (Hoboken) ; 305(12): 3385-3397, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35338614

RESUMO

Racehorses are exposed to repetitive overload during training and competition, causing joint hyperextension, tissue fatigue, and ultimately skeletal failure. Some degree of bone changes, such as sclerosis, are expected in equine athletes, as adaptation to the biomechanical rigors of training and racing. Understanding the imaging characteristics of the equine joint surface and subchondral bone would allow earlier detection of injuries or adaptation, improving prognosis and training programs. This study sought to describe the joint surface structural patterns and the periarticular structures of the third metacarpal bone (MC3). Both forelimbs of eight horses engaged in daily training programs, aged 3-5 years, which were euthanized for reasons unrelated to the metacarpophalangeal (MCP) joints, were collected. Specimens were evaluated through macroscopic inspection, radiography, ultrasonography, and microscopic examinations, such as optical microscopy and microtomography. Analysis of the microtomography images showed that 50% of the samples had higher trabecular thickness in the lateral condyle. Comparison of each imaging examination revealed that ultrasound images were most closely related to the histological examination (p = .29) in terms of sensitivity, while macroscopic and radiographic examinations differed most between evaluators. Finally, the irregularities and modifications observed in the articular cartilage surface and subchondral bone were normal adaptations of the anatomical structures of trained racehorses, which should be considered during clinical examination.


Assuntos
Cartilagem Articular , Doenças dos Cavalos , Ossos Metacarpais , Condicionamento Físico Animal , Cavalos , Animais , Ossos Metacarpais/diagnóstico por imagem , Metacarpo/lesões , Metacarpo/patologia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/patologia
6.
Sensors (Basel) ; 22(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35161452

RESUMO

The development of on-board technologies has enabled the development of quantification systems to monitor equine locomotion parameters. Their relevance among others relies on their ability to determine specific locomotor events such as foot-on and heel-off events. The objective of this study was to compare the accuracy of different methods for an automatic gait events detection from inertial measurement units (IMUs). IMUs were positioned on the cannon bone, hooves, and withers of seven horses trotting on hard and soft straight lines and circles. Longitudinal acceleration and angular velocity around the latero-medial axis of the cannon bone, and withers dorso-ventral displacement data were identified to tag the foot-on and a heel-off events. The results were compared with a reference method based on hoof-mounted-IMU data. The developed method showed bias less than 1.79%, 1.46%, 3.45% and -1.94% of stride duration, respectively, for forelimb foot-on and heel-off, and for hindlimb foot-on and heel-off detection, compared to our reference method. The results of this study showed that the developed gait-events detection method had a similar accuracy to other methods developed for straight line analysis and extended this validation to other types of exercise (circles) and ground surface (soft surface).


Assuntos
Casco e Garras , Metacarpo , Animais , Fenômenos Biomecânicos , Membro Anterior , Marcha , Cavalos
7.
Am J Med Genet A ; 188(1): 249-252, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34453469

RESUMO

Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Goutières (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Interferons , Doenças da Aorta , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/patologia , Hipoplasia do Esmalte Dentário , Humanos , Helicase IFIH1 Induzida por Interferon/genética , Japão , Masculino , Metacarpo/anormalidades , Doenças Musculares , Malformações do Sistema Nervoso , Odontodisplasia , Osteoporose , Calcificação Vascular
8.
J Med Genet ; 59(3): 294-304, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33495304

RESUMO

BACKGROUND: Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in DDX58 (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2. METHODS: Families underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed. RESULTS: We have identified a novel DDX58 variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the DDX58 variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin. CONCLUSIONS: These results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.


Assuntos
Exantema , Glaucoma de Ângulo Aberto , Odontodisplasia , Proteína DEAD-box 58/genética , Exantema/patologia , Glaucoma de Ângulo Aberto/patologia , Humanos , Interferons/genética , Metacarpo/patologia , Odontodisplasia/genética , Odontodisplasia/patologia , Receptores Imunológicos
9.
J Equine Vet Sci ; 105: 103693, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34607693

RESUMO

A 20-year-old British Warmblood gelding was presented for a progressively worsening right forelimb lameness which developed following an intense dressage training session. Initial ultrasound examination revealed a triangular, intrathecal, hypoechoic region within the superficial digital flexor tendon (SDFT) in the proximal, palmar carpal region distal to the accessory carpal bone (ACB), extending 7cm distally into the proximal metacarpal region. No significant improvement in clinical presentation was observed following an eight-week rehabilitation programme. Repeat ultrasound examination revealed an enlarged cross-sectional area of affected tendon. Due to a poor clinical response to conservative treatment, combined with increasingly marked severity of the lameness, the horse was humanely euthanised and the affected SDFT was submitted for macroscopic and histopathological examination at the University of Liverpool. This revealed an approximately 70mm-elongated, focally extensive mass located within the SDFT. On cross-section, the mass was poorly delineated, irregularly triangular, focally haemorrhagic, firm, 15 × 12mm wide and eccentrically placed towards the palmar aspect of the tendon. Histopathological examination identified a moderately to highly cellular, infiltrative, poorly demarcated mesenchymal neoplasm comprised of streams of moderately atypical spindloid cells including bizarre mitoses. Intratendinous fibroma is an uncommonly recorded human neoplasm and this case represents the third reported case of this entity in the horse, the first in an adult horse and the first to be identified in the SDFT.


Assuntos
Ossos do Carpo , Fibroma , Doenças dos Cavalos , Animais , Fibroma/diagnóstico por imagem , Fibroma/veterinária , Doenças dos Cavalos/diagnóstico por imagem , Cavalos , Masculino , Metacarpo , Tendões/diagnóstico por imagem
10.
Biomolecules ; 11(8)2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34439917

RESUMO

Melanoma differentiation-associated protein 5 (MDA5) is a crucial RIG-I-like receptor RNA helicase enzyme encoded by IFIH1 in humans. Single nucleotide polymorphisms in the IFIH1 results in fatal genetic disorders such as Aicardi-Goutières syndrome and Singleton-Merten syndrome, and in increased risk of type I diabetes in humans. In this study, we chose four different amino acid substitutions of the MDA5 protein responsible for genetic disorders: MDA5L372F, MDA5A452T, MDA5R779H, and MDA5R822Q and analyzed their structural and functional relationships using molecular dynamic simulations. Our results suggest that the mutated complexes are relatively more stable than the wild-type MDA5. The radius of gyration, interaction energies, and intra-hydrogen bond analysis indicated the stability of mutated complexes over the wild type, especially MDA5L372F and MDA5R822Q. The dominant motions exhibited by the wild-type and mutant complexes varied significantly. Moreover, the betweenness centrality of the wild-type and mutant complexes showed shared residues for intra-signal propagation. The observed results indicate that the mutations lead to a gain of function, as reported in previous studies, due to increased interaction energies and stability between RNA and MDA5 in mutated complexes. These findings are expected to deepen our understanding of MDA5 variants and may assist in the development of relevant therapeutics against the disorders.


Assuntos
Doenças da Aorta/genética , Doenças Autoimunes do Sistema Nervoso/genética , Hipoplasia do Esmalte Dentário/genética , Helicase IFIH1 Induzida por Interferon/genética , Metacarpo/anormalidades , Doenças Musculares/genética , Mutação , Malformações do Sistema Nervoso/genética , Odontodisplasia/genética , Osteoporose/genética , Calcificação Vascular/genética , Biologia Computacional , Humanos , Ligação de Hidrogênio , Helicase IFIH1 Induzida por Interferon/fisiologia , Conformação Molecular , Simulação de Dinâmica Molecular , Proteínas Mutantes/genética , Mutação de Sentido Incorreto , Fenótipo , Análise de Componente Principal , RNA/metabolismo , Termodinâmica
11.
Am J Med Genet A ; 185(10): 3170-3175, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34189824

RESUMO

Singleton-Merten syndrome (SMS) is a type I interferonopathy. In this report, we disclose the first-to the best of our knowledge-direct association of SMS with femoral head necrosis (FHN). The following case report presents the condition of a 38-year-old male suffering from SMS with FHN, characterized by acute symptoms and rapid disease progression. As per the recommendations of the Association Research Circulation Osseous (ARCO) and the S3-guidelines, we successfully treated the FHN with core decompression. Our histological results correlate with the changes described in medical literature in patients with SMS and MDA5-knockout in vivo experiments such as osteopenia, widened medullary cavity, and thin cortical bone. Moreover, the conducted immunohistochemistry shows strong CD56 positivity of the osteoblasts and osteocytes, as well as significant CD68 and CD163 positivity of the middle-sized osteoclasts. Collectively, these findings suggest an underlying syndrome in the FHN. A six-month post-operative follow-up revealed complete recovery with the absence of the initial symptoms and ability to resume normal daily activities. Taken together, our findings suggest that SMS is an additional cause of FHN in young adults. Early detection and adequate treatment using well-established joint-preserving techniques demonstrate a favorable improvement of the patient's clinical condition.


Assuntos
Doenças da Aorta/genética , Hipoplasia do Esmalte Dentário/genética , Necrose da Cabeça do Fêmur/genética , Interferons/genética , Metacarpo/anormalidades , Doenças Musculares/genética , Odontodisplasia/genética , Osteoporose/genética , Anormalidades da Pele/genética , Calcificação Vascular/genética , Adulto , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Doenças da Aorta/complicações , Doenças da Aorta/patologia , Antígeno CD56/genética , Hipoplasia do Esmalte Dentário/complicações , Hipoplasia do Esmalte Dentário/patologia , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/complicações , Necrose da Cabeça do Fêmur/patologia , Humanos , Masculino , Metacarpo/patologia , Doenças Musculares/complicações , Doenças Musculares/patologia , Odontodisplasia/complicações , Odontodisplasia/patologia , Osteoporose/complicações , Osteoporose/patologia , Receptores de Superfície Celular/genética , Anormalidades da Pele/patologia , Resultado do Tratamento , Calcificação Vascular/complicações , Calcificação Vascular/patologia
12.
Medicine (Baltimore) ; 100(20): e26083, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011129

RESUMO

RATIONALE: Avascular necrosis (AVN) of the metacarpal head is rare, and there is no clear consensus on treatment. The main aim of this study was to discuss the possible pathologic-mechanics of its development, epidemiology, radiographic features, and outcome after conservative treatment. PATIENT CONCERNS: A 14-year-old male with a history of fractures in little finger complained of right-hand pain with a limited range of motion for 1 month. Diagnosis: Imaging examination confirmed the diagnosis of AVN in the long metacarpal finger and ring finger. INTERVENTIONS: The patient was treated using non-surgical management, such as splint immobilization, non-steroidal anti-inflammatory drugs, and physiotherapy. OUTCOMES: At the last follow-up 26 months later, the patient was in complete remission with no residual symptoms. Magnetic resonance imaging (MRI) confirmed excellent remodeling and regeneration in the metacarpal head. LESSONS: Metacarpal head necrosis typically occurs in adolescent patients with a history of trauma. Conservative treatment may sometimes have an excellent prognosis.


Assuntos
Tratamento Conservador , Metacarpo/anormalidades , Osteonecrose/diagnóstico , Osteonecrose/terapia , Adolescente , Humanos , Masculino , Osteonecrose/etiologia
13.
Rev. bras. ortop ; 56(2): 198-204, Apr.-June 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1251347

RESUMO

Abstract Objective The present study aims to analyze the clinical results of the surgical treatment of metacarpal neck fractures with retrograde intramedullary fixation using cannulated headless screws (Herbert type). Methods Retrospective study of 21 closed fractures deviated from the metacarpal neck in 21 patients operated between April 2015 and November 2018. Results The sample included 19 men and 2 women. The mechanisms that caused the trauma were punching, falling to the ground and motor vehicle accident (n = 14, 5 and 2). The affected metacarpals were the 5th, 3rd, and 2nd (n = 19, 1 and 1). Surgical indications were neck-shaft diaphysis of the metacarpal > 30º for the 2nd and 3rd metacarpals and > 40º for the 5th metacarpal, shortening ≥ 5mm, rotational deviation, and the desire of the patient not to use plaster cast. In the immediate postoperative period, patients remained without immobilization and were instructed to mobilize their fingers according to tolerance. All patients had total active mobility > 240º and returned to their former occupations. All fractures consolidated and there were no reinterventions. Discussion The great advantages of the headless screw technique are its low morbidity, sufficient stability to avoid external immobilization, and reproducibility at low cost. Conclusion This is an easy, fast technique that has excellent results for the surgical treatment of displaced fractures of the neck of the metacarpals.


Resumo Objetivo O presente estudo visa analisar os resultados clínicos do tratamento cirúrgico das fraturas de colo do metacarpo com fixação intramedular retrógrada utilizando parafusos canulados sem cabeça (tipo Herbert). Métodos Estudo retrospectivo de 21 fraturas fechadas desviadas do colo do metacarpo em 21 pacientes operados entre abril de 2015 e novembro de 2018. Resultados A casuística incluiu 19 homens e 2 mulheres. Os mecanismos causadores do trauma foram soco, queda ao solo e acidente com veículo motorizado (n = 14, 5 e 2). Os metacarpos acometidos foram o V, III e II (n = 19, 1 e 1). As indicações cirúrgicas foram angulação colo-diáfise do metacarpo > 30º para os II e III metacarpos e > 40º para o V metacarpo, encurtamento ≥ 5mm, desvio rotacional e o desejo do paciente de não utilizar imobilização gessada. No pós-operatório imediato, os pacientes permaneceram sem imobilização e orientados a mobilizar os dedos conforme tolerância. Todos os pacientes ficaram com mobilidade ativa total > 240º e retornaram às suas antigas ocupações. Todas fraturas consolidaram e não houve reintervenções. Discussão As grandes vantagens da técnica com parafuso sem cabeça são sua baixa morbidade, estabilidade suficiente para não precisar de imobilização externa e reprodutibilidade com baixo custo. Conclusão Esta é uma técnica fácil, rápida, e que apresenta ótimos resultados para o tratamento cirúrgico das fraturas deslocadas do colo dos metacarpos.


Assuntos
Humanos , Masculino , Feminino , Período Pós-Operatório , Estudos Retrospectivos , Ossos Metacarpais , Fraturas Ósseas , Fixação Interna de Fraturas , Metacarpo/cirurgia , Metacarpo/lesões
14.
Hum Brain Mapp ; 42(7): 2262-2277, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33621380

RESUMO

Many studies focused on the cortical representations of fingers, while the palm is relatively neglected despite its importance for hand function. Here, we investigated palm representation (PR) and its relationship with finger representations (FRs) in primary somatosensory cortex (S1). Few studies in humans suggested that PR is located medially with respect to FRs in S1, yet to date, no study directly quantified the somatotopic organization of PR and the five FRs. Importantly, the link between the somatotopic organization of PR and FRs and their activation properties remains largely unexplored. Using 7T fMRI, we mapped PR and the five FRs at the single subject level. First, we analyzed the cortical distance between PR and FRs to determine their somatotopic organization. Results show that PR was located medially with respect to D5. Second, we tested whether the observed cortical distances would predict the relationship between PR and FRs activations. Using three complementary measures (cross-activations, pattern similarity and resting-state connectivity), we show that the relationship between PR and FRs activations were not determined by their somatotopic organization, that is, there was no gradient moving from D5 to D1, except for resting-state connectivity, which was predicted by the somatotopy. Instead, we show that the representational geometry of PR and FRs activations reflected the physical structure of the hand. Collectively, our findings suggest that the spatial proximity between topographically organized neuronal populations do not necessarily predicts their functional properties, rather the structure of the sensory space (e.g., the hand shape) better describes the observed results.


Assuntos
Mapeamento Encefálico , Dedos/fisiologia , Metacarpo/fisiologia , Córtex Somatossensorial/fisiologia , Adolescente , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Somatossensorial/diagnóstico por imagem , Adulto Jovem
15.
Hand (N Y) ; 16(4): 557-561, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33073608

RESUMO

Avascular necrosis of the metacarpal head, known as Dieterich disease, is rare. The underlying pathogenesis of the disease is not clearly understood, and there are few cases reported in the literature. Nonoperative treatment with rest and nonsteroidal anti-inflammatory drugs is often successful, but surgical management is sometimes indicated. The case outlined here describes a novel application of the known technique of metacarpophalangeal joint denervation to relieve pain while maintaining joint mechanics and grip strength.


Assuntos
Osteonecrose , Denervação , Humanos , Articulação Metacarpofalângica/cirurgia , Metacarpo/anormalidades , Osteonecrose/cirurgia
16.
Am J Med Genet A ; 185(3): 952-954, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33369046
17.
Arterioscler Thromb Vasc Biol ; 41(1): 35-47, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33176451

RESUMO

Arterial calcification is a common phenomenon in the elderly, in patients with atherosclerosis or renal failure and in diabetes. However, when present in very young individuals, it is likely to be associated with an underlying hereditary disorder of arterial calcification. Here, we present an overview of the few monogenic disorders presenting with early-onset cardiovascular calcification. These disorders can be classified according to the function of the respective disease gene into (1) disorders caused by an altered purine and phosphate/pyrophosphate metabolism, (2) interferonopathies, and (3) Gaucher disease. The finding of arterial calcification in early life should alert the clinician and prompt further genetic work-up to define the underlying genetic defect, to establish the correct diagnosis, and to enable appropriate therapy.


Assuntos
Doenças da Aorta/genética , Artérias/metabolismo , Hipoplasia do Esmalte Dentário/genética , Hereditariedade , Erros Inatos do Metabolismo/genética , Metacarpo/anormalidades , Doenças Musculares/genética , Odontodisplasia/genética , Osteogênese/genética , Osteoporose/genética , Calcificação Vascular/genética , Animais , Doenças da Aorta/complicações , Doenças da Aorta/metabolismo , Artérias/patologia , Hipoplasia do Esmalte Dentário/complicações , Hipoplasia do Esmalte Dentário/metabolismo , Doença de Gaucher/complicações , Doença de Gaucher/genética , Doença de Gaucher/metabolismo , Predisposição Genética para Doença , Humanos , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/metabolismo , Metacarpo/metabolismo , Doenças Musculares/complicações , Doenças Musculares/metabolismo , Odontodisplasia/complicações , Odontodisplasia/metabolismo , Osteoporose/complicações , Osteoporose/metabolismo , Fenótipo , Medição de Risco , Fatores de Risco , Calcificação Vascular/complicações , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia
18.
Int Immunol ; 33(4): 211-224, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33119735

RESUMO

Mutations in DDX58 (DExD/H-box helicase 58), which encodes the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I), were recently identified in the rare autoimmune disease Singleton-Merten syndrome (SMS). We report the spontaneous development of psoriasis-like skin lesions as an SMS-like symptom in transgenic mice harboring one of the RIG-I SMS variants, E373A. Histological analysis revealed typical characteristics of psoriasis, including the abnormal proliferation and differentiation of keratinocytes leading to epidermal hyperplasia, and infiltrates consisting of neutrophils, dendritic cells and T cells. Levels of the IL-23/IL-17 immune axis cytokines were high in the skin lesions. Rag2-/- transgenic mice showed partial amelioration of the phenotype, with down-regulation of inflammatory cytokines, including IL-17A, suggesting the importance of lymphocytes for the pathogenesis similar to that of human psoriasis. Of note, IL-17A deficiency abolished the skin phenotype, and treatment using the JAK inhibitor tofacitinib not only prevented onset, but also improved the skin manifestations even after onset. Our study provides further evidence for the involvement of RIG-I activation in the onset and progression of psoriasis via type I interferon signaling and the IL-23/IL-17 axis.


Assuntos
Proteína DEAD-box 58/genética , Proteína DEAD-box 58/metabolismo , Interferon Tipo I/imunologia , Interleucina-17/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Psoríase/patologia , Animais , Doenças da Aorta/genética , Proteínas de Ligação a DNA/genética , Células Dendríticas/imunologia , Hipoplasia do Esmalte Dentário/genética , Epiderme/patologia , Hiperplasia/genética , Hiperplasia/patologia , Inibidores de Janus Quinases/farmacologia , Janus Quinases/antagonistas & inibidores , Queratinócitos/citologia , Queratinócitos/patologia , Metacarpo/anormalidades , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças Musculares/genética , Neutrófilos/imunologia , Odontodisplasia/genética , Osteoporose/genética , Piperidinas/farmacologia , Psoríase/genética , Pirimidinas/farmacologia , Linfócitos T/imunologia , Calcificação Vascular/genética
19.
Methods Mol Biol ; 2181: 269-286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32729086

RESUMO

The type I interferonopathies comprise a heterogenous group of monogenic diseases associated with a constitutive activation of type I interferon signaling.The elucidation of the genetic causes of this group of diseases revealed an alteration of nucleic acid processing and signaling.ADAR1 is among the genes found mutated in patients with this type of disorders.This enzyme catalyzes the hydrolytic deamination of adenosines in inosines within a double-stranded RNA target (RNA editing of A to I). This RNA modification is widespread in human cells and deregulated in a variety of human diseases, ranging from cancers to neurological abnormalities.In this review, we briefly summarize the knowledge about the RNA editing alterations occurring in patients with mutations in ADAR1 gene and how these alterations might cause the inappropriate IFN activation.


Assuntos
Doenças Genéticas Inatas/genética , Interferon Tipo I/genética , Edição de RNA/fisiologia , Adenosina Desaminase/genética , Doenças da Aorta/genética , Doenças Autoimunes do Sistema Nervoso/genética , Hipoplasia do Esmalte Dentário/genética , Humanos , Imunidade Inata/genética , Interferon Tipo I/metabolismo , Metacarpo/anormalidades , Doenças Musculares/genética , Malformações do Sistema Nervoso/genética , Odontodisplasia/genética , Osteoporose/genética , RNA de Cadeia Dupla/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Calcificação Vascular/genética
20.
Clin Imaging ; 67: 7-10, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32497998

RESUMO

Osteochondroses is a well-known entity and typically affecting immature skeleton with few common locations involved are femoral head epiphysis, tibial tubercle apophysis, calcaneal apophysis, humeral capitellum and anterior vertebral end plates. We report a rare case of osteochondroses showing avascular necrosis involving metacarpal heads known as Dieterich disease, involving the head of the third metacarpal and probably the first case with a history of rock climbing as an etiology. Chronic repetitive microtrauma plays a significant role in the disease, as is seen in our patient. Imaging plays a crucial role in diagnosing, as well as monitoring progress, with MRI being a critical modality. The fact that this entity is rare does not necessarily make it difficult to detect. It may be clinical underdiagnosed due to lack of familiarity with this entity and radiographic findings may be subtle or inapparent. Bone scan is likely sensitive but not specific. MRI also likely has a role for early detection. This article is written with educational intent for the reader for the benefit of the patients with this rare disease.


Assuntos
Metacarpo/anormalidades , Osteocondrose/diagnóstico por imagem , Osteonecrose/diagnóstico por imagem , Epífises , Fêmur , Cabeça , Humanos , Imageamento por Ressonância Magnética , Masculino , Ossos Metacarpais , Metacarpo/diagnóstico por imagem , Osteocondrose/diagnóstico , Coluna Vertebral , Tíbia
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