RESUMO
Mitochondrial single-stranded DNA-binding protein (mtSSB) is essential for mitochondrial DNA (mtDNA) replication. Recently, several mtSSB variants have been associated with autosomal dominant mitochondrial optic atrophy and retinal dystrophy. Here, we have studied at the molecular level the functional consequences of one of the most severe mtSSB variants, R107Q. We first studied the oligomeric state of this variant and observed that the mtSSBR107Q mutant forms stable tetramers in vitro. On the other hand, we showed, using complementary single-molecule approaches, that mtSSBR107Q displays a lower intramolecular ssDNA compaction ability and a higher ssDNA dissociation rate than the WT protein. Real-time competition experiments for ssDNA-binding showed a marked advantage of mtSSBWT over mtSSBR107Q. Combined, these results show that the R107Q mutation significantly impaired the ssDNA-binding and compacting ability of mtSSB, likely by weakening mtSSB ssDNA wrapping efficiency. These features are in line with our molecular modeling of ssDNA on mtSSB showing that the R107Q mutation may destabilize local interactions and results in an electronegative spot that interrupts an ssDNA-interacting-electropositive patch, thus reducing the potential mtSSB-ssDNA interaction sites.
Assuntos
DNA de Cadeia Simples , Proteínas de Ligação a DNA , Mutação , Humanos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/química , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/química , Modelos Moleculares , Ligação Proteica , Estrutura Quaternária de ProteínaRESUMO
OBJECTIVE: The International Commission on Radiological Protection has highlighted the large number of medical specialties that use fluoroscopy outside diagnostic imaging departments without radiation protection programmes for patients and staff. Vascular surgery is one of these specialties. Thoracic endovascular aortic repair (TEVAR) is a complicated procedure requiring radiation protection guidance and optimisation. The recent EU Basic Safety Standards Directive requires the use and periodic updating of diagnostic reference levels (DRLs) for interventional procedures. The aim of this study was to determine doses for patients undergoing TEVAR with mobile Xray systems and hybrid rooms (fixed Xray systems) to obtain national DRLs and to suggest optimisation actions. METHODS: This was a retrospective cross sectional study. The Spanish Chapter of Endovascular Surgery conducted a national survey in 11 autonomous communities representing around 77.6% of the Spanish population (47.33 million inhabitants). A total of 266 TEVAR procedures from 17 Spanish centres were analysed, of which 53.0% were performed in hybrid operating rooms. National DRLs were obtained and defined as the third quartile of the median values from the different participating centres. RESULTS: The proposed national DRLs are: for kerma area product (KAP), 113.81 Gy·cm2 for mobile Xray systems and 282.59 Gy·cm2 for hybrid rooms; and for cumulative air kerma (CAK) at the patient entry reference point, 228.38 mGy for mobile systems and 910.64 mGy for hybrid rooms. CONCLUSION: Based on the requirement to know radiation doses for standard endovascular procedures, this study of TEVARs demonstrated that there is an increased factor of 2.48 in DRLs for KAP when the procedure is performed in a hybrid room compared with mobile C-arm systems, and an increased factor of 3.98 in DRLs for CAK when the procedure is performed with hybrid equipment. These results will help to optimise strategies to reduce radiation doses during TEVAR procedures.
Assuntos
Aorta Torácica , Correção Endovascular de Aneurisma , Doses de Radiação , Feminino , Humanos , Masculino , Aorta Torácica/cirurgia , Aorta Torácica/diagnóstico por imagem , Estudos Transversais , Correção Endovascular de Aneurisma/efeitos adversos , Correção Endovascular de Aneurisma/normas , Fluoroscopia/normas , Exposição à Radiação/prevenção & controle , Exposição à Radiação/efeitos adversos , Proteção Radiológica/normas , Radiografia Intervencionista/efeitos adversos , Radiografia Intervencionista/normas , Valores de Referência , Estudos Retrospectivos , EspanhaRESUMO
Background: The aim of this study is to determine the atheromatous plaques' prevalence in orthopantomography and their relationship with periodontal disease and missing teeth. Material and Methods. Orthopantomographs of 1,254 patients over 18 years of age from Clínica Arlanza in Lerma, Burgos, were examined between 2017 and 2021. A Planmeca ProOne® orthopantomograph (68 kV, 7 mA, and 10 sg) was used. Statistical analysis was carried out using SPSS Statistics® version 25. The results of the categorical variables were described as frequencies (%). Contingency tables were made with the qualitative variables, and the chi-square test was applied to study the relationship among them. The measure of statistical power used was the relative risk (RR), which was described with its respective 95% confidence interval (CI). Student's t-test was applied to study the relationship between the qualitative variable "presence or absence of atheroma plaque" and the quantitative variable "number of teeth." Results: A 6.2% prevalence of atheroma plaques was obtained from 1,079 selected X-rays. The risk in patients with periodontal disease increased as periodontal disease worsened. The risk in patients with periodontal disease increased as periodontal disease worsened as follows: healthy patients vs. periodontal patients with less than 30% bone loss in radiography: RR 0.434, 95% CI 0.181-1.041, p = 0.053 healthy patients vs. patients with between 30%-60% bone loss: RR 0.177, 95% CI 0.075-0.418, p < 0.05 healthy patients vs. patients with more than 60% bone loss: RR 0.121, 95% CI 0.041-0.355, p < 0.05. Patients with calcifications on their orthopantomograms had a lower mean teeth number (20.9 teeth) compared to patients without calcifications (24 teeth), which was statistically significant, t (1077) = -3.125, p < 0.05. Conclusions: Orthopantomography can be considered a screening method to detect patients at increased cardiovascular risk who are referred for individualized study. It is important to continue research to know the real significance of these findings. Dentists should be aware of the importance of our work in our patients' systemic health.
RESUMO
INTRODUCTION: Cat-scratch disease (CSD) is caused by Bartonella henselae and it is under-recognized in adults because it mainly affects children. Clinical course is commonly benign and self-limited; occasionally, there may be systemic involvement. METHODS: Case-series study carried out in a tertiary care hospital in Buenos Aires suburbs. Patients older than 15 years diagnosed with CSD over a 5-year period were included (2016-2021). RESULTS: 30 adult patients were analyzed, with a median age of 20.5 years (IQR 17-29), 73% (n = 22) were male; 96% (n = 27) had history of exposure to cats. The most common clinical presentation of CSD was peripheral lymphadenopathy (90%), the average complication rate was 33% (n = 10), 86.7% (n = 26) received antimicrobial therapy, with a median duration of 5 days (IQR 5-10). Outcome was favorable in 83% (n = 25), 16% (n = 5) were lost to follow-up. DISCUSSION: Clinical features of CSD in adults are poorly described in the worldwide literature. Diagnosis can be challenging because the clinical hallmark is regional lymphadenopathy.
Introducción: La enfermedad por arañazo de gato (EAG) es producida por Bartonella henselae y debido a que afecta principalmente niños, es poco reconocida en adultos. El cuadro evolutivo es generalmente benigno y autolimitado, aunque ocasionalmente puede haber compromiso sistémico. Métodos: Estudio observacional, descriptivo y retrospectivo realizado en un hospital de tercer nivel del conurbano bonaerense. Se incluyeron pacientes mayores de 15 años con diagnóstico de EAG en un período de 5 años (2016-2021). Resultados: Se analizaron 30 pacientes adultos, con una mediana de edad de 20.5 años (17-29), el 73% (n = 22) fueron varones. El 96% (n = 27) presentó contacto estrecho con gatos. La presentación clínica más frecuente fue adenopatías periféricas (90%); el porcentaje de complicaciones fue de 33% (n = 10). La indicación de antibioticoterapia fue de 86.7% (n = 26), con una mediana de duración de 5 días (5-10). La evolución fue favorable en el 83% (n = 25), en el 16% (n = 5) se perdió seguimiento. Discusión: La EAG es poco reconocida en adultos; las características clínicas de este grupo etario se encuentran poco descriptas en la literatura. Es un desafío diagnóstico debido a que su forma de presentación más frecuente es la adenopatía localizada.
Assuntos
Bartonella henselae , Doença da Arranhadura de Gato , Humanos , Doença da Arranhadura de Gato/diagnóstico , Doença da Arranhadura de Gato/tratamento farmacológico , Masculino , Adulto , Feminino , Adulto Jovem , Adolescente , Bartonella henselae/isolamento & purificação , Antibacterianos/uso terapêutico , Linfadenopatia , Estudos Retrospectivos , Argentina , Animais , GatosRESUMO
INTRODUCTION: In the clinical medicine's immediate assistance unit, care is focused on outpatients with diseases that require early diagnosis, such as tuberculous adenitis (TA). The aim was to describe clinical features, complementary studies and procedures performed in patients with a diagnosis confirmed by bacteriology or pathological anatomy of TA. METHODS: Observational, descriptive, retrospective. PERIOD: 2017-2023. RESULTS: Fourty nine patients were included, with a median age of 31 years, 59% were female, 22% with comorbidities. 40% had localized lymphadenopathy, most of them cervical. HIV serology was positive in 3 cases (6.1%). Samples for bacteriology were submitted in 73%, with isolation of M. tuberculosis in 71%. Nodal fine needle aspiration (FNA) was performed in 79%, and in 48% the cytology results were suggestive of tuberculosis. Nodal biopsy was performed in 77%, with granulomatous adenitis as result in 62%. The term between admission and diagnosis ranged from a median of 40 days. Most treatments were started after the biopsy result, followed by culture, bacilloscopy, FNA, and GeneXpert. One patient died. DISCUSSION: TA predominates in the female sex in the studied group, coinciding with the local experience, the average age of presentation is 30 to 40 years, can affect any lymph node region, although the cervical location predominates, which coincides with the findings of this work. In our series, the diagnostic delay from the first consultation was shorter than reported in the literature.
Introducción: En el consultorio de atención inmediata de clínica se concentra la atención de pacientes ambulatorios con enfermedades que requieren diagnóstico precoz, como la adenitis tuberculosa (AT). El objetivo fue describir las características clínicas, estudios complementarios y procedimientos realizados a pacientes con diagnóstico confirmado por bacteriología o anatomía patológica de AT. Métodos: Estudio observacional, descriptivo, retrospectivo. Período: 2017-2023. Resultados: Se incluyeron 49 pacientes, con una mediana de edad de 31 años; 59% de sexo femenino, 22% con comorbilidades El 40% presentó adenopatías localizadas, la mayoría cervicales. La serología para HIV era positiva en 3 (6.1%). Al 73% se le ingresaron muestras para bacteriología, con aislamiento de M. tuberculosis en 71%. Al 79% se le realizó punción aspiración con aguja fina (PAAF) ganglionar; en el 48% los resultados de la citología fueron sugestivos de tuberculosis (TB). Al 77% se le realizó biopsia ganglionar, resultando en el 62% adenitis granulomatosa. Desde la primera consulta hasta el diagnóstico transcurrieron una mediana de 40 días. La mayoría de los tratamientos se iniciaron luego del resultado de la biopsia, seguido de cultivos, baciloscopia, PAAF y GeneXpert. Un paciente falleció. Discusión: La AT predominó en el sexo femenino en el grupo estudiado, coincidente con la experiencia local, la edad promedio de presentación fue 30 a 40 años. Puede afectar cualquier cadena ganglionar, aunque predomina la localización cervical, que coincide con los hallazgos de este trabajo. En nuestra serie, la demora diagnóstica desde la primera consulta fue menor a la referida en la bibliografía.
Assuntos
Tuberculose dos Linfonodos , Humanos , Feminino , Estudos Retrospectivos , Masculino , Adulto , Tuberculose dos Linfonodos/diagnóstico , Tuberculose dos Linfonodos/patologia , Pessoa de Meia-Idade , Adulto Jovem , Biópsia por Agulha Fina , Mycobacterium tuberculosis/isolamento & purificação , Adolescente , IdosoRESUMO
The type IX secretion system (T9SS) is a nanomachinery utilized by bacterial pathogens to facilitate infection. The system is regulated by a signaling cascade serving as its activation switch. A pivotal member in this cascade, the response regulator protein PorX, represents a promising drug target to prevent the secretion of virulence factors. Here, we provide a comprehensive characterization of PorX both in vitro and in vivo. First, our structural studies revealed PorX harbors a unique enzymatic effector domain, which, surprisingly, shares structural similarities with the alkaline phosphatase superfamily, involved in nucleotide and lipid signaling pathways. Importantly, such pathways have not been associated with the T9SS until now. Enzymatic characterization of PorX's effector domain revealed a zinc-dependent phosphodiesterase activity, with active site dimensions suitable to accommodate a large substrate. Unlike typical response regulators that dimerize via their receiver domain upon phosphorylation, we found that zinc can also induce conformational changes and promote PorX's dimerization via an unexpected interface. These findings suggest that PorX can serve as a cellular zinc sensor, broadening our understanding of its regulatory mechanisms. Despite the strict conservation of PorX in T9SS-utilizing bacteria, we demonstrate that PorX is essential for virulence factors secretion in Porphyromonas gingivalis and affects metabolic enzymes secretion in the nonpathogenic Flavobacterium johnsoniae, but not for the secretion of gliding adhesins. Overall, this study advances our structural and functional understanding of PorX, highlighting its potential as a druggable target for intervention strategies aimed at disrupting the T9SS and mitigating virulence in pathogenic species.
RESUMO
The Type-IX secretion system (T9SS) is a nanomachinery utilized by bacterial pathogens to facilitate infection. The system is regulated by a signaling cascade serving as its activation switch. A pivotal member in this cascade, the response regulator protein PorX, represents a promising drug target to prevent the secretion of virulence factors. Here, we provide a comprehensive characterization of PorX both in vitro and in vivo . First, our structural studies revealed PorX harbours a unique enzymatic effector domain, which, surprisingly, shares structural similarities with the alkaline phosphatase superfamily, involved in nucleotide and lipid signaling pathways. Importantly, such pathways have not been associated with the T9SS until now. Enzymatic characterization of PorX's effector domain revealed a zinc-dependent phosphodiesterase activity, with active site dimensions suitable to accommodate a large substrate. Unlike typical response regulators that dimerize via their receiver domain upon phosphorylation, we found that zinc can also induce conformational changes and promote PorX's dimerization via an unexpected interface. These findings suggest that PorX can serve as a cellular zinc sensor, broadening our understanding of its regulatory mechanisms. Despite the strict conservation of PorX in T9SS-utilizing bacteria, we demonstrate that PorX is essential for virulence factors secretion in Porphyromonas gingivalis and affects metabolic enzymes secretion in the non-pathogenic Flavobacterium johnsoniae , but not for the secretion of gliding adhesins. Overall, this study advances our structural and functional understanding of PorX, highlighting its potential as a druggable target for intervention strategies aimed at disrupting the T9SS and mitigating virulence in pathogenic species.
RESUMO
Resumen El síndrome de Nicolau es una complicación infrecuente de la aplicación parenteral de diversos fármacos. Se caracteriza por la aparición de dolor, seguido de edema, eritema y luego una placa necrótica. Se reporta el caso de un hombre de 31 años que presenta este síndrome luego de la aplicación de penicilina benzatínica intramuscular. La biopsia apoyó el diagnóstico. Recibió tratamiento con enoxaparina y cilostazol con posterior mejoría.
Abstract Nicolau syndrome is a rare complication of the parenteral application of various drugs. It is char acterized by the appearance of pain, followed by edema, erythema, and then a necrotic plaque. We present the case of a 31-year-old male with this syndrome, after the application of intramuscular benzathine penicillin. The diagnosis was supported by the biopsy. He received treatment with enoxaparin and cilostazol with subsequent improvement.
RESUMO
La hidatidosis o equinococosis quística es una zoonosis parasitaria endémica causada por el estadio larvario del cestode Echinococcus granulosus. El hígado y el pulmón son los órganos con afección más frecuente. Su ubicación subcutánea es una entidad rara, poco descrita, y por ende un reto diagnóstico. Describimos el caso de una mujer, de 18 años de edad, procedente de un área endémica, que presentó un quiste hidatídico primario supraclavicular.
Hydatid disease or cystic echinococcosis is an endemic parasitic zoonosis caused by the larval stage of the cestode Echinococcus granulosus, the liver and lung being the most frequently affected organs. Its subcutaneous location is a rare entity, little described, and therefore a diagnostic challenge. We describe the case of an 18-year-old woman from an endemic area who presented with a primary supraclavicular hydatid cyst.
Assuntos
Humanos , Feminino , Adolescente , Equinococose/cirurgia , Equinococose/diagnóstico , Equinococose/tratamento farmacológico , Albendazol/uso terapêutico , Biópsia por Agulha Fina , Echinococcus granulosus , Anticestoides/uso terapêuticoRESUMO
Resumen La enfermedad de Still del adulto (ESA) es una enfermedad reumática e inflamatoria, infrecuente, de etiología desconocida. Su presentación clínica es variada y sus síntomas más frecuentes son fiebre, artralgias, exantema asalmonado evanescente, odinofagia, adenopatías, hepatoesplenomegalia, serositis y presencia en laboratorio de leucocitosis (neutrofilia), hiperferritinemia asociado a ausencia de anticuerpos. El diagnóstico es clínico y por exclusión. Existen criterios clasificatorios como son los de Yamaguchi1, Cush y Fautrel2,3 que ayudan a la orientación diagnóstica. El tratamiento se define según la presentación y la evolución clínica1. Se describen las características clínicas, diagnósticas, tratamiento y evolución de siete pacientes con ESA.
Abstract Adult Still's disease (ASD) is an uncommon rheumatic and inflammatory disorder of unknown etiology. The major clinical features include fever, arthralgia, transient salmon-pink rash, odynophagia, lymphadenopathy, hepatosplenomegaly, serositis, and laboratory findings such as leukocytosis with neutrophilia, hyperferritinemia, and negative immunologic laboratory testing. ASD diagnosis is reached by exclusion. Different classification criteria such as Yamaguchi, Cush and Fautrel have been developed for the identification of ASD. Treatment is based on the degree of disease activity and clinical response1. We describe clinical manifestations, diagnosis, treatment, and prognosis of seven patients with adult's Still disease.
Assuntos
Doença de Still de Início Tardio , Doenças Reumáticas , FebreRESUMO
El síndrome antisintetasa es una miopatía inflamatoria idiopática (MII) de origen autoinmune, poco frecuente, que se caracteriza por la presencia de autoanticuerpos antisintetasa ARNt (generalmente anti-Jo1), asociado frecuentemente a miositis, enfermedad pulmonar intersticial, poliartritis, manos de mecánico y fenómeno de Raynaud. Se reporta el caso de una mujer de 45 años de edad que presenta este síndrome con características fenotípicas de dermatomiositis y responde de forma favorable luego de la administración del tratamiento con glucocorticoides asociado a metotrexato.
Anti-synthetase syndrome is a rare autoimmune inflammatory myopathy characterized by autoantibodies against tRNA synthetases (most commonly anti-Jo1) with clinical features that include myositis, interstitial lung disease, polyarthritis, mechanic's hands and Raynaud's phenomenon. We report a 45-year-old woman who presented with dermatomyositis phenotypical features and a significant improvement with corticosteroids and metotrexate treatment.
Assuntos
Miosite , Doenças Pulmonares Intersticiais , LigasesRESUMO
Las enfermedades relacionadas con IgG4 (ER-IgG4) son entidades fibroinflamatorias e inmunomediadas, caracterizadas por la afección multiorgánica, con la formación de pseudotumores que provocan lesión tisular y daño orgánico subsecuente. Se describe el caso de un paciente de 43 años que presentó sialoadenitis esclerosante y cumplió todos los criterios diagnósticos de enfermedad relacionada con IgG4.
IgG4-related diseases (IgG4-RD) are fibroinflammatory immune-mediated entities characterized by multiorgan involvement with the development of pseudotumors that cause tissue injury and subsequent organ damage. We describe the case of a 43-year-old man who presented sclerosing sialadenitis and fulfilled the diagnostic criteria for IgG4-related disease.
Assuntos
Doença Relacionada a Imunoglobulina G4 , SialadeniteRESUMO
El síndrome antisintetasa es una miopatía inflamatoria idiopática (MII) de origen autoinmune, poco frecuente, que se caracteriza por la presencia de autoanticuerpos antisintetasa ARNt (generalmente anti-Jo1), asociado frecuentemente a miositis, enfermedad pulmonar intersticial, poliartritis, manos de mecánico y fenómeno de Raynaud. Se reporta el caso de una mujer de 45 años de edad que presenta este síndrome con características fenotípicas de dermatomiositis y responde de forma favorable luego de la administración del tratamiento con glucocorticoides asociado a metotrexato.
Anti-synthetase syndrome is a rare autoimmune inflammatory myopathy characterized by autoantibodies against tRNA synthetases (most commonly anti-Jo1) with clinical features that include myositis, interstitial lung disease, polyarthritis, mechanic's hands and Raynaud's phenomenon. We report a 45-year-old woman who presented with dermatomyositis phenotypical features and a significant improvement with corticosteroids and metotrexate treatment.