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BACKGROUND: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine. METHODS: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases. RESULTS: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%). CONCLUSIONS: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.).
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Adjuvantes de Vacinas , Vacinas contra COVID-19 , COVID-19 , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes de Vacinas/administração & dosagem , Adjuvantes de Vacinas/efeitos adversos , Adjuvantes de Vacinas/uso terapêutico , Adulto , Anticorpos Antivirais , COVID-19/genética , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , Método Duplo-Cego , Humanos , Injeções Intramusculares , SARS-CoV-2/genética , VacinaçãoRESUMO
BACKGROUND: RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is an autosomal recessive hypomyelinating leukodystrophy characterized by neurological dysfunction, hypodontia and hypogonadotropic hypogonadism. The disease is caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C or POLR3K. Craniofacial abnormalities reminiscent of Treacher Collins syndrome have been originally described in patients with POLR3-HLD caused by biallelic pathogenic variants in POLR1C. To date, no published studies have appraised in detail the craniofacial features of patients with POLR3-HLD. In this work, the specific craniofacial characteristics of patients with POLR3-HLD associated with biallelic pathogenic variants in POLR3A, POLR3B and POLR1C are described. METHODS: The craniofacial features of 31 patients with POLR3-HLD were evaluated, and potential genotype-phenotype associations were evaluated. RESULTS: Various craniofacial abnormalities were recognized in this patient cohort, with each individual presenting at least one craniofacial abnormality. The most frequently identified features included a flat midface (61.3%), a smooth philtrum (58.0%) and a pointed chin (51.6%). In patients with POLR3B biallelic variants, a thin upper lip was frequent. Craniofacial anomalies involving the forehead were most commonly associated with biallelic variants in POLR3A and POLR3B while a higher proportion of patients with POLR1C biallelic variants demonstrated bitemporal narrowing. CONCLUSION: Through this study, we demonstrated that craniofacial abnormalities are common in patients with POLR3-HLD. This report describes in detail the dysmorphic features of POLR3-HLD associated with biallelic variants in POLR3A, POLR3B and POLR1C.
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Doenças Desmielinizantes , Doenças Neurodegenerativas , Humanos , RNA Polimerase III/genética , Padrões de Herança , RNA Polimerases Dirigidas por DNA/genéticaRESUMO
BACKGROUND: Humeral component retroversion (HcRV) can be customized to match native humeral retroversion (RV) during reverse total shoulder arthroplasty (RTSA). However, assessing postoperative individualized HcRV using computed tomography (CT) scans without an elbow can be challenging. Therefore, we developed a new method to obtain the HcRV and evaluated its reliability. METHODS: A total of 106 patients underwent RTSA using a single implant, in which the humeral component was implanted based on the preoperative humeral RV (Pre_HRV) using a bilateral CT scan of the elbow. Intraoperatively, a retroversion guide with version hole at 10° intervals was used; Pre_HRV was converted to 5° increments and applied for humeral component implantation. The axis of intertubercular sulcus (ITS) was defined as the line perpendicular to the intertubercular line, and the angle between the axis of ITS and the trans-epicondylar axis was defined as the bicipital groove rotation (BGR). ITS orientation was defined as the angle between the axis of ITS and the central axis of the humeral head. Since the BGR does not change, the postoperative implanted HcRV (Post_HcRV)f is calculated as the BGR minus the value of the postoperative ITS orientation. An agreement analysis was performed between Post_HcRV and both the intraoperatively applied humeral RV (I_HRV) and Pre_HRV, as well as between the pre- and postoperative ITS orientations. The humeral component's insertional errors were also evaluated. RESULTS: All radiologic measurements exhibited excellent inter- and intra-observer reliabilities. The reliabilities between Post_HcRV and both I_HRV and Pre_HRV, as well as between pre- and postoperative ITS orientations, showed excellent agreement (intraclass correlation coefficients: 0.953, 0.952, and 0.873, respectively). The humeral component was inserted within 5° in 86.8% of the planned humeral RV cases. CONCLUSIONS: The HcRV measured using the BGR and ITS orientations achieved good accuracy for restoring the planned humeral RV using a retroversion guide with the forearm axis. Therefore, this new radiological measurement method can aid orthopedic surgeons in confirming Post_HcRV on CT scans without an elbow.
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PURPOSES: The purpose of this study was to present and analyze the etiologic factors, clinical manifestations, bacteriology, and treatment outcomes of nasal septal abscess in a large cohort of adult patients. MATERIAL AND METHODS: Retrospective analysis. RESULTS: 36 adult patients, age from 19 to 85 (mean age, 51.83), with nasal septal abscesses were treated at Ear Nose Throat Hospital of Ho Chi Minh City from January 2020 to August 2022. The most common symptoms were nasal obstruction (75 %), headache/facial pain (58.33 %). Etiologic factors were found in 83.33 % of cases with the most common were diabetes mellitus (47.22 %), nose-picking (44.44 %). 75 % of cases had positive bacterial culture, of which 70.37 % were Staphylococcus aureus. Septal abscess was successfully treated in all cases using our treatment protocol, which involved an extended modified Killian's incision, irrigation with 1 % poviodine, placement of gauze in the abscess pocket, and nasal packing with Merocels. CONCLUSIONS: Diabetes and nose-picking were the most common etiologic factors; Staphylococcus aureus was the most common organism of nasal septal abscess in our study. Our treatment protocol is safe and effective.
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Diabetes Mellitus , Obstrução Nasal , Doenças dos Seios Paranasais , Doenças Faríngeas , Infecções Respiratórias , Infecções Estafilocócicas , Humanos , Adulto , Pessoa de Meia-Idade , Septo Nasal , Abscesso/etiologia , Abscesso/terapia , Abscesso/diagnóstico , Estudos Retrospectivos , Obstrução Nasal/complicações , Doenças dos Seios Paranasais/complicações , Staphylococcus aureus , Infecções Respiratórias/complicações , Celulite (Flegmão) , Infecções Estafilocócicas/terapia , Infecções Estafilocócicas/complicações , Doenças Faríngeas/complicaçõesRESUMO
Cockayne syndrome is a rare inherited DNA repair multisystemic disorder. Here, we aim to raise awareness of the phenotypic resemblances between Cockayne syndrome and the neurodevelopmental disorder caused by pathogenic variants in MORC2, a gene also involved in DNA repair. Using exome sequencing, we identified a de novo pathogenic variant in MORC2 in our patient. Our patient's phenotype was characterized by multiple features evocative of Cockayne syndrome. Based on our patient's phenotype, in addition to the phenotypic description of patients with pathogenic variants in MORC2 reported in the literature, we suggest that pathogenic variants in this gene are associated with a Cockayne-like phenotype.
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Síndrome de Cockayne , Transtornos do Neurodesenvolvimento , Humanos , Síndrome de Cockayne/genética , Fenótipo , Transtornos do Neurodesenvolvimento/genética , Sequenciamento do Exoma , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: Surgical treatment for posterior ethmoid diseases has historically been performed through a trans-ethmoid approach which usually required medialization of the middle turbinate, a middle meatal antrostomy and total ethmoidectomy. This can destabilize the basal lamella of the middle turbinate and also sacrifices the integrity of ostiomeatal complex and the healthy bulla if the patient has the disease only in the posterior ethmoid sinus. The aim of this study is to present of a novel minimally disruptive approach for the management of isolated posterior ethmoid diseases. METHODS: Retrospective case series analysis. RESULTS: 19 patients with isolated posterior ethmoid fungal balls were operated on via a trans-superior meatal approach. The most common signs and symptoms were headache (78.9%), and purulent/mucoid discharge from the superior meatus (89.5%). The technique is described in detail with the preservation of the ostiomeatal complex and bulla ethmoidalis. Complete removal of the disease was achieved in all cases through this access, with no intra-operative complications. The posterior ethmoid cavity remained patent postoperatively in all patients. No recurrence was noted during the follow-up period which ranged from 6 to 12 months. CONCLUSION: This is a minimally invasive approach, which is safe and effective for the surgical management of isolated posterior ethmoid diseases.
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Vesícula , Seios Paranasais , Endoscopia/métodos , Osso Etmoide/cirurgia , Seio Etmoidal/cirurgia , Humanos , Estudos RetrospectivosRESUMO
PURPOSE: As the burden of surgical care and the associated outreach trips to low- and middle-income countries increases, it is important to collect postoperative data to assess and improve the quality, safety, and efficacy of the care provided. In this pilot study, we aimed to evaluate the feasibility of short message service (SMS)-based mobile phone follow up to obtain patient-reported outcome measures after hand surgery during a surgical outreach trip to Vietnam. METHODS: Patients undergoing surgery during a week-long outreach trip to Hospital 175 in Ho Chi Minh City, Vietnam, who owned a mobile phone, were included in this study. Eight eligible patients elected to participate and were sent an SMS-based, Health Insurance Portability and Accountability Act-compliant text message with a link to a contextualized shortened Disabilities of the Arm, Shoulder and Hand questionnaire at 1 day, 1 week, 2 weeks, 4 weeks, and 12 weeks after the surgery. The patient characteristics and instrument completion rates were reported. RESULTS: The 8 patients had a mean age of 45.4 years and lived at a mean distance of 72.7 km from the hospital. Seven (87.5%), 7 (87.5%), 8 (100%), 6 (75%), and 8 (100%) patients completed the follow-up questionnaires at 1 day, 1 week, 2 weeks, 4 weeks, and 12 weeks after the surgery, respectively. CONCLUSIONS: This pilot study demonstrates that the collection of patient-reported outcome measures after hand surgery outreach trips to low- and middle-income countries via SMS-based messaging is feasible for up to 12 weeks after the surgery. CLINICAL RELEVANCE: Short message service-based messaging can be used to obtain postoperative outcome measures for up to 12 weeks after surgical outreach trips to low- and middle-income countries. This technology can be scaled and contextualized based on location to ensure that patient care during outreach trips is safe and effective.
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Envio de Mensagens de Texto , Estudos de Viabilidade , Mãos/cirurgia , Humanos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Projetos PilotoRESUMO
Hypomyelinating leukodystrophies are genetic disorders characterized by insufficient myelin deposition during development. They are diagnosed on the basis of both clinical and MRI features followed by genetic confirmation. Here, we report on four unrelated affected individuals with hypomyelination and bi-allelic pathogenic variants in EPRS, the gene encoding cytoplasmic glutamyl-prolyl-aminoacyl-tRNA synthetase. EPRS is a bifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. It is a subunit of a large multisynthetase complex composed of eight aminoacyl-tRNA synthetases and its three interacting proteins. In total, five different EPRS mutations were identified. The p.Pro1115Arg variation did not affect the assembly of the multisynthetase complex (MSC) as monitored by affinity purification-mass spectrometry. However, immunoblot analyses on protein extracts from fibroblasts of the two affected individuals sharing the p.Pro1115Arg variant showed reduced EPRS amounts. EPRS activity was reduced in one affected individual's lymphoblasts and in a purified recombinant protein model. Interestingly, two other cytoplasmic aminoacyl-tRNA synthetases have previously been implicated in hypomyelinating leukodystrophies bearing clinical and radiological similarities to those in the individuals we studied. We therefore hypothesized that leukodystrophies caused by mutations in genes encoding cytoplasmic aminoacyl-tRNA synthetases share a common underlying mechanism, such as reduced protein availability, abnormal assembly of the multisynthetase complex, and/or abnormal aminoacylation, all resulting in reduced translation capacity and insufficient myelin deposition in the developing brain.
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Alelos , Aminoacil-tRNA Sintetases/genética , Mutação/genética , Adolescente , Criança , Pré-Escolar , Evolução Fatal , Feminino , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
PURPOSE: The distance between the anterior wall of the maxillary sinus and the nasolacrimal duct has been classified into three types by Simmen, in which type I (< 3 mm) is the least feasible for a prelacrimal approach. The aim of our study is to present a surgical technique which overcomes the anatomical limitation of the narrow lacrimal recess (type I) in the management of inverted papilloma in the maxillary sinus. METHODS: Case series. RESULTS: Eight patients with type I lacrimal recess underwent surgical resection for inverted papilloma in the maxillary sinus via a prelacrimal approach. The technique is described in detail in the article and essentially involves exposure of the nasolacrimal duct using a diamond burr. Complete tumor excision was achieved in all cases through this access, with no significant intra-operative complications. CONCLUSIONS: This prelacrimal approach technique is safe and effective for the management of inverted papilloma in maxillary sinuses with a type I lacrimal recess configuration.
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Aparelho Lacrimal , Ducto Nasolacrimal , Papiloma Invertido , Endoscopia , Humanos , Complicações Intraoperatórias , Aparelho Lacrimal/diagnóstico por imagem , Aparelho Lacrimal/cirurgia , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Ducto Nasolacrimal/diagnóstico por imagem , Ducto Nasolacrimal/cirurgia , Papiloma Invertido/diagnóstico por imagem , Papiloma Invertido/cirurgiaRESUMO
Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA's Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks and 1 year post-IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs γ) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss.
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Células da Medula Óssea/efeitos da radiação , Isótopos de Ferro/efeitos adversos , Fenômenos Fisiológicos Musculoesqueléticos/efeitos da radiação , Osteogênese/efeitos da radiação , Estresse Oxidativo , Exposição à Radiação/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Expressão Gênica/genética , Expressão Gênica/efeitos da radiação , Transferência Linear de Energia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteogênese/genética , Oxirredução/efeitos da radiação , Prótons/efeitos adversos , Doses de Radiação , Radiação IonizanteRESUMO
OBJECTIVE: This study aims to ascertain frequency of mutations in POLR3A or POLR3B, which are associated with 4H leukodystrophy, in a cohort of patients with unclassified hypomyelination. METHODS AND RESULTS: In a cohort of 22 patients with the magnetic resonance imaging (MRI) diagnosis of unclassified hypomyelination and without typical clinical signs, we evaluated clinical and MRI features. Developmental delay or intellectual disability, ataxia, and spasticity were frequent symptoms. POLR3A and POLR3B were sequenced. A compound heterozygote mutation in POLR3B was found in only one patient. Additional investigations allowed a definitive diagnosis in 10 patients. CONCLUSION: Mutations in POLR3A or POLR3B are rare in patients with unclassified hypomyelination, and alternative diagnoses should be considered first.
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Doenças Desmielinizantes/genética , Mutação/genética , RNA Polimerase III/genética , Adolescente , Adulto , Encéfalo/patologia , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/diagnóstico , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
We report a case of mild cavitating leukoencephalopathy associated with a homozygous c.755A > G (p.Asp252Gly) NDUFS1 mutation in a 7-year old boy. Biochemical analysis confirmed an isolated reduction in complex I activity. Magnetic resonance imaging of the brain showed a diffuse cystic leukoencephalopathy with the involvement of the corpus callosum and sparing of the gray matter. The clinical course was marked by an acute presentation of neurological deficits at 24 months followed by recurrent episodes of mild neurological deterioration, subsequent remissions, and prolonged periods of stability. This is one of the mildest known clinical presentations of complex I deficiency secondary to mutations in NDUFS1, expanding the clinical spectrum and natural history of this disorder. Consideration of clinical variability needs to be taken into account in patient management and family counseling.
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Complexo I de Transporte de Elétrons/deficiência , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/genética , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/genética , Mutação de Sentido Incorreto , NADH Desidrogenase/genética , Encéfalo/patologia , Criança , Complexo I de Transporte de Elétrons/genética , Homozigoto , Humanos , MasculinoRESUMO
Excitotoxicity and disruption of Ca(2+) homeostasis have been implicated in amyotrophic lateral sclerosis (ALS) and limiting Ca(2+) entry is protective in models of ALS caused by mutation of SOD1. Lomerizine, an antagonist of L- and T-type voltage-gated calcium channels and transient receptor potential channel 5 transient receptor potential channels, is well tolerated clinically, making it a potential therapeutic candidate. Lomerizine reduced glutamate excitotoxicity in cultured motor neurons by reducing the accumulation of cytoplasmic Ca(2+) and protected motor neurons against multiple measures of mutant SOD1 toxicity: Ca(2+) overload, impaired mitochondrial trafficking, mitochondrial fragmentation, formation of mutant SOD1 inclusions, and loss of viability. To assess the utility of lomerizine in other forms of ALS, calcium homeostasis was evaluated in culture models of disease because of mutations in the RNA-binding proteins transactive response DNA-binding protein 43 (TDP-43) and Fused in Sarcoma (FUS). Calcium did not play the same role in the toxicity of these mutant proteins as with mutant SOD1 and lomerizine failed to prevent cytoplasmic accumulation of mutant TDP-43, a hallmark of its pathology. These experiments point to differences in the pathogenic pathways between types of ALS and show the utility of primary culture models in comparing those mechanisms and effectiveness of therapeutic strategies.
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Bloqueadores dos Canais de Cálcio/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Neurônios Motores/efeitos dos fármacos , Fármacos Neuroprotetores , Piperazinas/farmacologia , Superóxido Dismutase/genética , Superóxido Dismutase/fisiologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Cálcio/metabolismo , Cálcio/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Técnicas de Transferência de Genes , Homeostase/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Corpos de Inclusão/metabolismo , Camundongos , Mitocôndrias/enzimologia , Mitocôndrias/genética , Neurônios Motores/metabolismo , Mutação/genética , Mutação/fisiologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Superóxido Dismutase-1RESUMO
Aicardi-Goutières syndrome (AGS) is a rare genetic disorder with inflammatory immune-mediated pathogenesis. Disease onset is most commonly marked by recurrent fevers, irritability, and developmental regression in the 1st year of life. A stable phase characterized by severe spastic quadriparesis and cognitive deficit follows. Brain calcifications, leukoencephalopathy, and cerebral atrophy are the radiological hallmarks of AGS and often show progression over time. We present an atypical patient with late-onset AGS characterized by spastic paraparesis and a leukoencephalopathy that markedly improved during follow-up, demonstrating a nonprogressive disease course and the exceptional amelioration of the white matter abnormalities.
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Doenças Autoimunes do Sistema Nervoso/patologia , Leucoencefalopatias/diagnóstico , Malformações do Sistema Nervoso/patologia , Paraparesia Espástica/diagnóstico , Fatores Etários , Doenças Autoimunes do Sistema Nervoso/complicações , Doenças Autoimunes do Sistema Nervoso/genética , Criança , Feminino , Humanos , Leucoencefalopatias/complicações , Mutação , Malformações do Sistema Nervoso/complicações , Malformações do Sistema Nervoso/genética , Paraparesia Espástica/complicações , Remissão Espontânea , Ribonuclease H/genéticaRESUMO
Background: Rhinoplasty in patients with previous unilateral cleft lip repair is a surgical challenge due to complex nasal deformities, including a horizontally positioned nasal wing, wide cleft side nostrils, nasal base defects, and a short and deviated nasal columella. To comprehensively address these complexities, we exclusively utilized autologous costal cartilage in rhinoplasty procedures, using various surgical techniques. Methods: This study presents a comprehensive case series of 39 patients who had previously undergone unilateral cleft lip surgery but still had nasal deformities. Rhinoplasty using autologous costal cartilage was performed at Cho Ray Hospital, Vietnam. Costal cartilage was partially crushed and then finely cut to shape the dorsal area and raise the nasal base on the cleft side. Partially crushed cartilage was also used to shape shield grafts, cap grafts, and alar batten grafts, whereas sliced cartilage was utilized for septal extension grafts. Evaluation was based on improvements in anthropometric indicators, patient satisfaction using Rhinoplasty Outcome Evaluation (ROE) scale and FACE-Q scores. Results: The average age of patients was 25.13 years. All postoperative anthropometric indicators showed significant improvements. Postsurgery, the total ROE score was three times higher than before surgery (P < 0.001), and the total FACE-Q score was 2.26 times higher (P < 0.001). No significant intraoperative or postoperative complications were observed. Conclusions: This procedure effectively addresses complex nasal deformities in patients with prior unilateral cleft lip repair, emphasizing the value of autologous costal cartilage in rhinoplasty for such individuals.
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Introduction Facial trauma can cause damage to the facial nerve, which can have negative effects on function, aesthetics, and quality of life if left untreated. Objective To evaluate the effectiveness of peripheral facial nerve direct end-to-end anastomosis and/or nerve grafting surgery for patients with facial nerve injury after facial trauma. Methods Fifty-nine patients with peripheral facial nerve paralysis after facial injuries underwent facial nerve rehabilitation surgery from November 2017 to December 2021 at Ho Chi Minh City National Hospital of Odontology. Results All 59 cases of facial trauma with damage to the peripheral facial nerve underwent facial nerve reconstruction surgery within 8 weeks of the injury. Of these cases, 25/59 (42.3%) had end-to-end anastomosis, 22/59 (37.3%) had nerve grafting, and 12/59 (20.4%) had a combination of nerve grafting and end-to-end anastomosis. After surgery, the rates of moderate and good recovery were 78.4% and 11.8%, respectively. All facial paralysis measurements showed statistically significant improvement after surgery, including the Facial Nerve Grading Scale 2.0 (FNGS 2.0) score, the Facial Clinimetric Evaluation (FaCE) scale, and electroneurography. The rate of synkinesis after surgery was 34%. Patient follow-up postoperatively ranged from 6 to > 36 months; 51 out of 59 patients (86.4%) were followed-up for at least 12 months or longer. Conclusion Nerve rehabilitation surgery including direct end-to-end anastomosis and nerve grafting is effective in cases of peripheral facial nerve injury following facial trauma. The surgery helps restore nerve conduction and improve facial paralysis.
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Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare cause of acute abdominal pain, but could potentially be fatal to patients, and should be recognized soon in the emergency department after excluding other common causes. Computed tomography (CT) is the modality of choice for initial diagnosis and follow-up. Currently there is no evidence-based guidelines for managing SISMAD. A 58-year-old man being suspected of a mesenteric artery dissection was referred to our emergergy department. The patient was monitored, treated conservatively with anticoagulant and discharged after 3 days. Follow-up CT scans at 6 month, 1 year and 1 year and a half post discharge showed a partially occluded false lumen, the diameter of true lumen had increased in size and no signs of bowel ischemia. SISMAD should be considered as part of differential diagnoses when patients in their fifth to seventh decades of life present with acute abdominal pain. Treatment includes conservative management, percutaneous endovascular interventions, or surgery, but most patients can be managed conservatively.
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BACKGROUND: Biallelic pathogenic variants in SLC17A5 cause three forms of free sialic acid storage disease categorized based on severity from least to most severe: Salla disease, intermediate-severe Salla disease, and infantile free sialic acid storage disease. Intermediate-severe Salla disease is the most recently described form. Here, we report a longitudinal characterization of intermediate-severe Salla disease progression in two sisters carrying the following biallelic variants in SLC17A5: c.406A>G (p.Lys136Glu) and c.819+1G>A. METHODS: A retrospective review of medical records was performed. A developmental questionnaire was completed to obtain further clinical information. For functional characterization of the predicted splice site variant, RNA was extracted from patient blood samples and sequenced. RESULTS: Disease onset occurred within the first six months of life in both patients. Early childhood development was delayed with achievement of some milestones followed by a developmental plateau in late childhood. After this, both patients began a slow and progressive neurological regression in adolescence. Functional studies confirmed the pathogenicity of the c.819+1G>A variant, resulting in a frameshift and deletion of exon 6. CONCLUSIONS: We present a detailed study describing the clinical course of intermediate-severe Salla disease with over 15 to 20 years of evolution and demonstrate the pathogenicity of the c.819+1G>A splice site variant.
Assuntos
Doença do Armazenamento de Ácido Siálico , Adolescente , Humanos , Criança , Pré-Escolar , Doença do Armazenamento de Ácido Siálico/genética , Mutação/genética , Ácido N-Acetilneuramínico , Progressão da DoençaRESUMO
RNA polymerase III-related leukodystrophy (POLR3-related leukodystrophy) is a rare, genetically determined hypomyelinating disease arising from biallelic pathogenic variants in genes encoding subunits of RNA polymerase III (Pol III). Here, we describe the first reported case of POLR3-related leukodystrophy caused by biallelic pathogenic variants in POLR3D, encoding the RPC4 subunit of Pol III. The individual, a female, demonstrated delays in walking and expressive and receptive language as a child and later cognitively plateaued. Additional neurological features included cerebellar signs (e.g., dysarthria, ataxia, and intention tremor) and dysphagia, while non-neurological features included hypodontia, hypogonadotropic hypogonadism, and dysmorphic facial features. Her MRI was notable for diffuse hypomyelination with myelin preservation of early myelinating structures, characteristic of POLR3-related leukodystrophy. Exome sequencing revealed the biallelic variants in POLR3D, a missense variant (c.541C > T, p.P181S) and an intronic splice site variant (c.656-6G > A, p.?). Functional studies of the patient's fibroblasts demonstrated significantly decreased RNA-level expression of POLR3D, along with reduced expression of other Pol III subunit genes. Notably, Pol III transcription was also shown to be aberrant, with a significant decrease in 7SK RNA and several distinct tRNA genes analyzed. Affinity purification coupled to mass spectrometry of the POLR3D p.P181S variant showed normal assembly of Pol III subunits yet altered interaction of Pol III with the PAQosome chaperone complex, indicating the missense variant is likely to alter complex maturation. This work identifies biallelic pathogenic variants in POLR3D as a novel genetic cause of POLR3-related leukodystrophy, expanding the molecular spectrum associated with this disease, and proposes altered tRNA homeostasis as a factor in the underlying biology of this hypomyelinating disorder.
RESUMO
Mindfulness is an intervention that was used in many psychiatry treatments. In this study, the subject experienced two different states: (1) attention (i.e., listening to a podcast) and (2) mindfulness (i.e., meditation). Twenty-two students were included in a Mindfulness-Based Stress Reduction (MBSR) course with EEG recording sessions on week four and week six. Brain dynamics were investigated to elucidate the complexity and connectivity of the brain. The alpha PSD increased in all brain areas during mindfulness in both weeks. For complexity, Fractal Dimension (FD) increased significantly during meditation in the week six recording. When comparing the FD in the mindfulness state of week four and week six, we also witnessed a significant increase in the following week. The coherence of the interhemispheric frontal and temporal regions increased significantly in both weeks. In conclusion, the subject successfully transferred from attention to mindfulness, demonstrated by the alpha changes when going from podcast to meditating. An enhancement in brain complexity was found, suggesting an augmentation in cognitive function. Finally, the coherence exhibits strengthened connections in the frontal area.