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Mutations truncating a single copy of the tumor suppressor, BRCA2, cause cancer susceptibility. In cells bearing such heterozygous mutations, we find that a cellular metabolite and ubiquitous environmental toxin, formaldehyde, stalls and destabilizes DNA replication forks, engendering structural chromosomal aberrations. Formaldehyde selectively depletes BRCA2 via proteasomal degradation, a mechanism of toxicity that affects very few additional cellular proteins. Heterozygous BRCA2 truncations, by lowering pre-existing BRCA2 expression, sensitize to BRCA2 haploinsufficiency induced by transient exposure to natural concentrations of formaldehyde. Acetaldehyde, an alcohol catabolite detoxified by ALDH2, precipitates similar effects. Ribonuclease H1 ameliorates replication fork instability and chromosomal aberrations provoked by aldehyde-induced BRCA2 haploinsufficiency, suggesting that BRCA2 inactivation triggers spontaneous mutagenesis during DNA replication via aberrant RNA-DNA hybrids (R-loops). These findings suggest a model wherein carcinogenesis in BRCA2 mutation carriers can be incited by compounds found pervasively in the environment and generated endogenously in certain tissues with implications for public health.
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Proteína BRCA2/genética , Aberrações Cromossômicas/efeitos dos fármacos , Formaldeído/toxicidade , Instabilidade Genômica/efeitos dos fármacos , Toxinas Biológicas/toxicidade , Dano ao DNA , Replicação do DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Haploinsuficiência , Células HeLa , Humanos , Proteína Homóloga a MRE11 , Proteoma , Ribonuclease H/metabolismoRESUMO
Menopausal hormone therapy (MHT) is known to increase the risk of venous thromboembolism (VTE), which includes deep vein thrombosis, pulmonary embolism, and less frequently cerebral vein thrombosis, but the absolute risk for a given patient is very low. After starting MHT, the risk of VTE seems to be at its highest, declining to the non-HRT user baseline level of risk after stopping. Whether estrogen-only or estrogen-progestin HRT combination is linked to a similar risk of VTE is unclear from the available evidence. The aim of this study is to evaluate the risks of developing VTE in relation to different types as well as different modes of administration of MHT through a database search including PubMed, MEDLINE, Google Scholar, Cochrane Library, and others in order to provide the women carers with the up-to-date and evidence-based guidelines and recommendations while counseling the post-menopausal women enquiring on use of hormonal therapies either to alleviate the menopausal symptoms or to prevent the long-term sequelae of estrogen deficiency.
On sait que l'hormonothérapie ménopausique (MHT) augmente le risque de thromboembolie veineuse (TEV), qui comprend la thrombose veineuse profonde, l'embolie pulmonaire et, moins fréquemment, la thrombose veineuse cérébrale, mais le risque absolu pour un patient donné est très faible. Après le début du MHT, le risque de TEV semble être à son plus haut niveau, diminuant jusqu'au niveau de risque de base des non-utilisatrices de THS après l'arrêt. Les preuves disponibles ne permettent pas de savoir si un THS à base d'Åstrogène seul ou d'association Åstroprogestative est lié à un risque similaire de TEV. Le but de cette étude est d'évaluer les risques de développer une TEV par rapport à différents types ainsi qu'à différents modes d'administration du MHT grâce à une recherche dans des bases de données comprenant PubMed, MEDLINE, Google Scholar, Cochrane Library et autres afin de fournir aux femmes les soignants avec les lignes directrices et recommandations à jour et fondées sur des preuves tout en conseillant les femmes ménopausées qui se renseignent sur l'utilisation de thérapies hormonales, soit pour soulager les symptômes de la ménopause, soit pour prévenir les séquelles à long terme d'une carence en Åstrogènes.
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Terapia de Reposição de Estrogênios , Menopausa , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/prevenção & controle , Feminino , Terapia de Reposição de Estrogênios/efeitos adversos , Fatores de Risco , Estrogênios/efeitos adversos , Estrogênios/administração & dosagem , Terapia de Reposição Hormonal/efeitos adversos , Progestinas/efeitos adversos , Progestinas/administração & dosagem , Pessoa de Meia-IdadeRESUMO
This review aims to provide the mother carers with the most recent evidence-based guidelines in the context of managing of pregnancy-associated VTE, where an extensive search through the medical journals addressing the topic including the medical database such as Pubmed, Medline, Sience direct,Embase and others using the title and key-words in order to gather the most concerned as well as the up-to-date publications concerned with the problem under research, the search resulted in recognising pregnancy as a significant risk factor for the development of VTE, both during the prenatal and postnatal periods, with an estimated increased likelihood risk of five and sixty times, respectively and concluded that venous thromboembolism (VTE) is one of the leading causes of maternal mortality hence, all pregnant women should be assessed for the risk of developing the condition as early as possible (when scheduling a booking antenatal appointment) or even in the pre-pregnancy clinic.
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Tromboembolia Venosa , Feminino , Gravidez , Humanos , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Fatores de Risco , Mortalidade MaternaRESUMO
Intrahepatic cholestasis of pregnancy (ICP) is the commonest among the specific dermatoses of pregnancy. The disease is characterised by intense pruritus and specifically by elevated bile acid levels and owing to the rarity of data published in this context, the disease carries a great challenge in both diagnosis and management. The disease is associated with significant maternal as well as perinatal adverse effects, hence, this article aims at improving the knowledge of the women's health carers with the up-to-date and evidence-based, whenever possible, recommendations while managing patients with ICP.
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Colestase Intra-Hepática , Complicações na Gravidez , Gravidez , Feminino , Humanos , Obstetra , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , Complicações na Gravidez/induzido quimicamente , Ácidos e Sais Biliares , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/terapia , Ácido Ursodesoxicólico/efeitos adversos , Resultado da GravidezRESUMO
The X-ray free-electron lasers that became available during the last decade, like the European XFEL (EuXFEL), place high demands on their instrumentation. Especially at low photon energies below 1â keV, detectors with high sensitivity, and consequently low noise and high quantum efficiency, are required to enable facility users to fully exploit the scientific potential of the photon source. A 1-Megapixel pnCCD detector with a 1024â ×â 1024 pixel format has been installed and commissioned for imaging applications at the Nano-Sized Quantum System (NQS) station of the Small Quantum System (SQS) instrument at EuXFEL. The instrument is currently operating in the energy range between 0.5 and 3â keV and the NQS station is designed for investigations of the interaction of intense FEL pulses with clusters, nano-particles and small bio-molecules, by combining photo-ion and photo-electron spectroscopy with coherent diffraction imaging techniques. The core of the imaging detector is a pn-type charge coupled device (pnCCD) with a pixel pitch of 75â µmâ ×â 75â µm. Depending on the experimental scenario, the pnCCD enables imaging of single photons thanks to its very low electronic noise of 3â e- and high quantum efficiency. Here an overview on the EuXFEL pnCCD detector and the results from the commissioning and first user operation at the SQS experiment in June 2019 are presented. The detailed descriptions of the detector design and capabilities, its implementation at EuXFEL both mechanically and from the controls side as well as important data correction steps aim to provide useful background for users planning and analyzing experiments at EuXFEL and may serve as a benchmark for comparing and planning future endstations at other FELs.
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OBJECTIVE: The goal of administering preoperative systemic prophylactic antibiotics is to have the concentration in the tissues at its optimum level at the start and throughout the surgery. The rationale for the use of antibiotics is not well accepted; possible side effects and development of microbial resistance patterns are potential risks along with the financial burden. Therefore, the present study was conducted with the aim to clinically evaluate the serum and tissue concentration of single-dose prophylactic ceftriaxone during an ongoing laparoscopic cholecystectomy (LC) and to find out risk factors for post operative surgical site infections (SSI). METHOD: It was an open labelled prospective study in 50 consecutive patients who underwent elective laparoscopic cholecystectomy under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by High Performance Liquid Chromatography during the ongoing surgery. Subjects were observed for any post-operative complications including SSI. RESULTS: Serum and tissue concentrations of ceftriaxone were significant at test value of 4 milligrams/Litre. Body mass index was significantly correlated with the tissue concentration of ceftriaxone at the time of incision. The rate of SSI was 2%. It significantly correlated with age more than 60 years, diabetes and infected bile. CONCLUSION: A single prophylactic intra-venous dose of 1 g ceftriaxone immediately prior to skin incision in LC is good enough for prevention of SSI in Indian patients.
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Antibacterianos/farmacocinética , Antibioticoprofilaxia/métodos , Ceftriaxona/farmacocinética , Colecistectomia Laparoscópica/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Administração Intravenosa , Adolescente , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Ceftriaxona/administração & dosagem , Ceftriaxona/sangue , Esquema de Medicação , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Centros de Atenção Terciária , Adulto JovemRESUMO
BACKGROUND: Warts, or verrucae, are mucosal human papilloma virus (HPV) infections that are very challenging to treat. OBJECTIVE: To compare the safety and efficacy of intralesional injection of vitamin D3 versus intralesional injection of candida albicans antigen for plantar warts. METHODS: Forty patients were included in the study and were divided into two groups (A&B) with 20 patients each. Group A received intralesional vitamin D3 while Group B received intralesional Candida antigen. Injection was done every 3 weeks until clearance of warts or a maximum of three treatments. RESULTS: Nine patients showed complete clearance in group A (45%), while 6 patients (30%) showed partial response and no response in 5 patients (25%) of group (A). As for group (B), complete clearance of the treated warts was observed in 8 patients (40%), partial response in 6 patients (30%) while no response was observed in 6 patients (30%). No superiority of one treatment to the other was observed nor was any statistical significance in both groups’ responses noted. CONCLUSION: Treatment of multiple warts by intralesional injection of candida antigen or vitamin D3 is safe and effective, with good cure rates, has an excellent safety profile, with minimal recurrences and statistically equivalent. J Drugs Dermatol. 2021;20(5):546-549. doi:10.36849/JDD.5264.
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Antígenos de Fungos/administração & dosagem , Candida albicans/imunologia , Colecalciferol/administração & dosagem , Imunoterapia/métodos , Verrugas/tratamento farmacológico , Adulto , Antígenos de Fungos/efeitos adversos , Antígenos de Fungos/imunologia , Colecalciferol/efeitos adversos , Feminino , Seguimentos , Humanos , Imunoterapia/efeitos adversos , Injeções Intralesionais , Masculino , Resultado do Tratamento , Verrugas/imunologia , Adulto JovemRESUMO
The pro-arrhythmic triggers in Brugada and early repolarization syndromes (BrS, ERS) have not been analyzed systematically except for case reports. We clinically investigated the circumstances which precede/predispose to arrhythmic events in these syndromes during long-term follow-up. A detailed history from the patients/witnesses was taken to investigate the antecedent events in the last few hours that preceded syncope/ventricular fibrillation (VF); medical records, ECG and blood test from the emergency room (ER) were reviewed. 19 patients that fulfilled the investigation criteria were followed up for 71 ± 49 months (34-190 months). Prior to the event (syncope/VF), the patients were partaking different activities in the following decreasing order; drinking alcoholic beverage, having meal, and getting up from sleep, exercise. 3 patients reported mental/physical stress prior to the event and 2 patients developed VF several days after starting oral steroid for treatment of bronchial asthma. In the ER, elevated J-wave amplitude (0.27 ± 0.15 mV) was found with 58 % of the patients having hypokalemia. After electrolyte correction and cessation of steroids, the following day plasma K+ (4.2 ± 0.3 mEq/L, P < 0.001) was significantly increased and J-wave amplitude (0.13 ± 0.1 mV, P < 0.001) was remarkably reduced. Three patients were kept on oral spironolactone/potassium supplements. During follow-up for 71 ± 49 (34-190) months, among 4 patients with VF recurrence, one patient developed VF after taking oral steroid. In ERS and BrS, hypokalemia and corticosteroid therapy add substantial pro-arrhythmic effects, but potentially treatable. Stopping steroid therapy and avoiding hypokalemia had excellent long-term outcome.
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Síndrome de Brugada/etiologia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Síncope/etiologia , Fibrilação Ventricular/etiologia , Potenciais de Ação , Corticosteroides/efeitos adversos , Adulto , Idoso , Antiarrítmicos/uso terapêutico , Biomarcadores/sangue , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/tratamento farmacológico , Síndrome de Brugada/fisiopatologia , Eletrocardiografia , Feminino , Seguimentos , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipopotassemia/sangue , Hipopotassemia/complicações , Hipopotassemia/terapia , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Prognóstico , Estudos Prospectivos , Fatores de Risco , Síncope/diagnóstico , Síncope/tratamento farmacológico , Síncope/fisiopatologia , Fatores de Tempo , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: The distribution of late gadolinium enhancement (LGE) on the cardiac MRI (CMR) indicates myocardial fibrosis and provides information of possible reentry substrates. QT dynamicity reflecting repolarization abnormalities has gained attention as a potential prognostic predictive factor. OBJECTIVE: To clarify the correlation between the LGE distribution on CMR and QT dynamicity represented by the QT/RR relationship. METHODS: CMR and QT/RR analyses using Holter monitoring were performed in 34 patients (24 males, 60 ± 11 years) with ventricular tachycardia (VT) and/or ventricular fibrillation (VF). The LGE on CMR was scored using a 4-point score in 17 left ventricular segments. The sum of the LGE scores was calculated for each patient. The QT/RR slope and daytime/nighttime QT/RR ratio (day/night ratio) were calculated. The correlation between the slope or the day/night QT/RR ratio and late enhancement findings was analyzed. RESULTS: All patients were divided into 23 LGE positive (LGE(+)) and 11 LGE negative (LGE(-)) patients. The slopes of the QTe/RR and QTa /RR were significantly steeper in the LGE(+) than in LGE(-) patients (0.21 ± 0.03 vs 0.13 ± 0.02; P < 0.001, 0.19 ± 0.03 vs 0.13 ± 0.02; P < 0.001, respectively), and both slopes were significantly correlated with the total LGE scores (r = 0.83, P < 0.001; r = 0.71, P < 0.001, respectively). In the LGE(+) patients, the QTe day/night (1.37 ± 0.38 vs 0.91 ± 0.33; P = 0.002) and QTa day/night ratios (1.33 ± 0.26 vs 1.06 ± 0.30; P = 0.011) were significantly greater than those in the LGE(-) patients. CONCLUSION: The LGE distribution was closely related to the QT dynamicity, suggesting that a combination of these markers can be a powerful tool for understanding the background pathophysiology.
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Meios de Contraste , Gadolínio , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Taquicardia Ventricular/diagnóstico por imagem , Fibrilação Ventricular/diagnóstico por imagem , Eletrocardiografia Ambulatorial , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/fisiopatologiaRESUMO
AIMS: There are many reports on the ECG characteristics of idiopathic outflow tract ventricular arrhythmias (OT-VAs) to predict their origin. However, differentiating near regions using 12-lead ECGs is still complicated. The synthesized 18-lead ECG derived from the 12-lead ECG can provide virtual waveforms of the right-sided chest leads (V3R, V4R, and V5R) and back leads (V7, V8, and V9). The aim of this study was to develop a simple and useful parameter for differentiating OT-VA origins using the 18-lead ECG. METHODS AND RESULTS: We studied 28 and 73 patients with idiopathic VAs in a pacemapping study and validation cohort, respectively. In the pacemapping study, several sites out of five different sites were paced in each patient: the anterior and posterior right ventricular OT (RVOT-ant and RVOT-post), right and left coronary cusps (RCC and LCC), and junction of both cusps (RLJ). The 18-lead ECGs during pacemapping among the five sites were compared for establishing a simple parameter to predict VA origins. A novel parameter using 18-lead ECGs was tested prospectively in 73 patients. In the pacemapping study, the dominant QRS morphology pattern in the synthesized V5R significantly differed among those sites (RVOT-ant:Rs, RVOT-post:rS, RCC:QS, RLJ:qR, and LCC:R). The patients in the validation cohort were divided into five groups depending on those QRS morphology patterns during VAs in the synthesized V5R. Each V5R QRS morphology pattern could predict a precise origin of the OT-VAs with an overall accuracy of 75%. CONCLUSION: The QRS morphology pattern in V5R was a simple and useful parameter for differentiating detailed OT-VA origins.
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Algoritmos , Mapeamento Potencial de Superfície Corporal/métodos , Diagnóstico por Computador/métodos , Eletrocardiografia/métodos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
INTRODUCTION: We reported impaired QT-rate dependence in early repolarization syndrome (ERS); however, contemporary data have shown peak incidence of sudden cardiac death (SCD) in ERS and Brugada syndrome (BrS) at mid-night and early morning. Taken together, we analyzed the nocturnal QT-rate dependence in both syndromes. METHODS AND RESULTS: A total of 172 subjects were enrolled: 11 ERS, 11 BrS patients, 50 subjects with an uneventful ER pattern (ERP), and 100 non-J-wave control subjects. Ambulatory ECG-derived parameters (QT, QTc, and QT/RR slope) and day-night QT difference were analyzed and compared. Among the groups, there was no significant difference in the average QT or QTc; however, the 24-hour QT/RR slope was significantly smaller in ERS and BrS patients (0.103 ± 0.01 and 0.106 ± 0.01, respectively) than in the control group (0.156 ± 0.03, P < 0.001). Detailed analysis showed a lower day-night QT difference in ERS and BrS patients (19 ±18.7 and 24 ±14 milliseconds, respectively) than in the controls (40 ± 22 milliseconds, P = 0.007) with the lowest QT/RR slopes seen in the ERS and BrS groups from 0 to 3:00 am (QT/RR; 0.076 ± 0.02 vs. 0.092 ± 0.04 vs. 0.117 ± 0.04, for the ERS, BrS, and controls, respectively, P = 0.004) and from 3 to 6 am (QT/RR 0.074 ± 0.03 vs. 0.079 ± 0.02 vs. 0.118 ± 0.04, P < 0.001). CONCLUSION: In a large population of age- and gender-matched groups, both ERS and BrS patients showed attenuated QT-rate dependence and impaired QT day-night modulation that may provide a baseline reentrant substrate. Importantly, QT/RR maladaptation was most evident at mid-night and early morning, which may explain the propensity of such patients to develop SCD during this critical period.
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Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/mortalidade , Morte Súbita Cardíaca/epidemiologia , Eletrocardiografia Ambulatorial/estatística & dados numéricos , Distribuição por Idade , Ritmo Circadiano , Comorbidade , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por Sexo , Taxa de SobrevidaRESUMO
We describe three cases of J-wave syndrome in which ventricular fibrillation (VF) was probably induced by corticosteroid therapy. The patients involved were being treated with prednisolone for concomitant bronchial asthma. One of the three patients had only one episode of VF during her long follow-up period (14 years). Two patients had hypokalemia during their VF episodes. Corticosteroids have been shown to induce various types of arrhythmia and to modify cardiac potassium channels. We discuss the possible association between corticosteroid therapy and VF in J-wave syndrome based on the cases we have encountered.
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Antiarrítmicos/administração & dosagem , Reanimação Cardiopulmonar/métodos , Desfibriladores Implantáveis , Glucocorticoides/efeitos adversos , Hipopotassemia , Fibrilação Ventricular , Adulto , Asma/tratamento farmacológico , Eletrocardiografia/métodos , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hipopotassemia/induzido quimicamente , Hipopotassemia/complicações , Hipopotassemia/diagnóstico , Masculino , Síndrome , Resultado do Tratamento , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapiaRESUMO
Objectives: Reinforcement of polymethylmethacrylate (PMMA) denture base resins (DBRs) with inorganic fillers with superior properties and accepted aesthetics are favored and still a big dilemma. This study was undertaken to evaluate the color change, flexural strength, and modulus of elasticity of heat-polymerized DBR material modified with silver nanoparticles (AgNPs) and zirconium dioxide nanoparticles (ZNPs). Methods: Sixty acrylic specimens (30/color test, 30/flexural properties) were fabricated and divided according to nanoparticles type and addition into 3 groups (n = 10). Group-I; unmodified specimens, Group-II; modified specimens with 0.5wt% AgNPs (PMMA/AgNPs), and Group-III; modified specimens with 7.5wt% ZNPs (PMMA/ZNPs). Disc-shape (20 × 3 mm) and bar-shape (65 × 10 × 2.5 mm) specimens were fabricated for color and flexural properties, respectively. The spectrophotometer was used for evaluation of the color change (∆E). The flexural strength and elastic modulus evaluation was carried out using a 3-point bending test (5 mm/min). Tukey's post hoc and one-way ANOVA were used to analyze the data at a significant level P ≤ 0.05. Results: PMMA/AgNPs group exhibited a significant increase in color change when compared with PMMA/ZNPs. PMMA/ZNPs showed significantly the highest flexural strength value when compared with unmodified and PMMA/AgNPs groups (P < 0.001), however, there was an absence of significant differences in terms of flexural strength values between PMMA/AgNPs and unmodified groups (P > 0.05). PMMA/AgNPs insignificantly increased its modulus of elasticity strength (P = 0.09410) while PMMA/ZNPs significantly increased its modulus of elasticity strength (P = 0.00396). Conclusion: The AgNPs and ZNPs addition to PMMA increased the color change and AgNPs change the color of DBRs. The flexural attributes of DBRs have been increased by ZNPs.
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INTRODUCTION: Almost all current investigations on early repolarization syndrome (ERS) have focused on the J-wave characteristics and ST-segment configuration; however, few have reported on ventricular repolarization indexes in ERS. METHODS AND RESULTS: A total of 145 subjects were enrolled: 10 ERS patients, 45 uneventful ER pattern (ERP) subjects, and 90 healthy controls without J waves or ST-segment elevation. Ambulatory ECG-derived parameters (QT, QTc(B), QTc(F), T peak-Tend(Tpe), and QT/RR slope) were measured and statistically compared. Among the groups, there was no significant difference in the average QT and QTc(B); however, ERS patients had the shortest QTc(F) and longest Tpe (QTc(F): 396.2 ± 19 vs 410.4 ± 20 vs 419.2 ± 19 milliseconds, P = 0.036, Tpe: 84.9 ± 12 vs 70.4 ± 11 vs 66.9 ± 15 milliseconds, P < 0.001, for the ERS, ERP, and control groups, respectively). Importantly, the 24-hour QT/RR slope was significantly smaller in the ERS than ERP and control groups (QT/RR: 0.105 ± 0.01 vs 0.154 ± 0.02 vs 0.161 ± 0.03, respectively; P < 0.001). When analyzing the diurnal and nocturnal QT/RR slopes, ERS patients had small diurnal and nocturnal QT/RR slopes while the ERP and control groups had large diurnal and small nocturnal QT/RR slopes (diurnal QT/RR: 0. 077 ± 0.01 vs 0.132 ± 0.03 vs 0.143 ± 0.03, P < 0.001; nocturnal QT/RR: 0.093 ± 0.02 vs 0.129 ± 0.03 vs 0.130 ± 0.04, P = 0.02 in the ERS, ERP, and control groups, respectively). CONCLUSION: ERS patients had a continuously depressed diurnal and nocturnal adaptation of the QT interval to the heart rate. Such abnormal repolarization dynamics might provide a substrate for reentry and be an important element for developing ventricular fibrillation in the ERS cohort.
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Arritmias Cardíacas/fisiopatologia , Eletrocardiografia , Adulto , Idoso , Eletrocardiografia Ambulatorial , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome , Fibrilação Ventricular/etiologiaRESUMO
We present an in-depth investigation into the Radiation-Induced Segregation (RIS) phenomenon in Ni-Cr alloys. All the pivotal factors affecting RIS such as surface's absorption efficiency, grain size, production bias, dose rate, temperature, and sink density were systematically studied. Through comprehensive simulations, the individual and collective impacts of these factors were analyzed, enabling a refined understanding of RIS. A notable finding was the significant influence of production bias on point defects' interactions with grain boundaries/surfaces, thereby playing a crucial role in RIS processes. Production bias alters the neutrality of these interactions, leading to a preferential absorption of one type of point defect by the boundary and consequent establishment of distinct surface-mediated patterns of point defects. These spatial patterns further result in non-monotonic spatial profiles of solute atoms near surfaces/grain boundaries, corroborated by experimental observations. In particular, a positive production bias, signifying a higher production rate of vacancies over interstitials, drives more Cr depletion at the grain boundary. Moreover, a temperature-dependent production bias must be considered to recover the experimentally reported dependence of RIS on temperature. The severity of radiation damage and RIS becomes more pronounced with increased production bias, dose rate, and grain size, while high temperatures or sink density suppress the RIS severity. Model predictions were validated against experimental data, showcasing robust qualitative and quantitative agreements. The findings pave the way for further exploration of these spatial dependencies in subsequent studies, aiming to augment the comprehension and predictability of RIS processes in alloys.
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Of the monomorphic ventricular tachycardias, there are 4 specific tachycardias related to the Purkinje system: 1) idiopathic verapamil-sensitive fascicular ventricular tachycardia (FVT); 2) non-re-entrant FVT; 3) bundle branch re-entry and interfascicular re-entry; and 4) Purkinje-mediated VT in structural heart disease. Verapamil-sensitive FVT is classified into 4 types according to the location of the circuit: 1) left posterior type; 2) left anterior type; 3) left upper septal type;and 4) reverse type. And, in the left anterior and posterior types, there are septal and papillary muscle subtypes. Although macro-re-entry has been reported to be the mechanism underlying verapamil-sensitive FVT, recording the entire circuit is challenging. One possible reason is that the Purkinje-muscle junction may penetrate the myocardial layer as a part of the circuit. The Purkinje network may thus play an important role in the initiation and maintenance of ventricular fibrillation. Further, it has been reported that the development and the abnormalities of the Purkinje system are associated with the arrhythmogenesis of ventricular fibrillation. Furthermore, it has been reported that catheter ablation of trigger ventricular premature complexes, and/or "de-networking" of the Purkinje system, can be used as electrical bailout therapy. There is a hypothesis that the intramural Purkinje system is involved in the generation of J waves. Nevertheless, as there are still unresolved issues that must be debated and accurately analyzed, this review aims to discuss the solved and unsolved questions related to Purkinje-related arrhythmias.
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Taquicardia Ventricular , Complexos Ventriculares Prematuros , Humanos , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapia , Ramos Subendocárdicos , Taquicardia Ventricular/cirurgia , VerapamilRESUMO
Impetigo herpetiformis (IH) is a pregnancy-specific dermatosis that is currently considered a form of generalised pustular psoriasis and mainly occurs in late pregnancy during the third trimester. IH presents as erythematous patches and pustules and might have systemic involvement. The disease may be associated with severe maternal, fetal, and neonatal complications. IH treatment is very challenging, however, various therapeutic options are available and effective for disease treatment.
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Pemphigoid gestationis (PG), also known as gestational pemphigoid, as it is specifically associated with a pregnancy event, is among the rare pregnancy-related dermatoses, characterised by the formation of autoantibodies against Bullous Pemphigoid antigens 180 and 230 (BP180 and BP230), causing significant damage to the basement membrane of the skin, resulting in marked pruritus and blisters on the abdomen and extremities. Diagnosis of PG is basically made by the characteristic clinical picture and confirmed by immunofluorescence studies and histopathology of a skin biopsy. Treatment, just as for other autoimmune dermatoses, is achieved by corticosteroids with the risk of relapses in subsequent pregnancies. Fetal growth restriction and pre-maturity are potential fetal complications associated with the disease, hence the recommended combined antenatal care by a dermatologist as well as an obstetrician, however, this disease is unlikely to be a source of significant maternal morbidity or mortality.
Assuntos
Penfigoide Gestacional , Complicações na Gravidez , Autoanticorpos , Feminino , Humanos , Penfigoide Gestacional/diagnóstico , Penfigoide Gestacional/tratamento farmacológico , Gravidez , Complicações na Gravidez/diagnóstico , Cuidado Pré-Natal , PruridoRESUMO
Serial femtosecond crystallography is a rapidly developing method for determining the structure of biomolecules for samples which have proven challenging with conventional X-ray crystallography, such as for membrane proteins and microcrystals, or for time-resolved studies. The European XFEL, the first high repetition rate hard X-ray free electron laser, provides the ability to record diffraction data at more than an order of magnitude faster than previously achievable, putting increased demand on sample delivery and data processing. This work describes a publicly available serial femtosecond crystallography dataset collected at the SPB/SFX instrument at the European XFEL. This dataset contains information suitable for algorithmic development for detector calibration, image classification and structure determination, as well as testing and training for future users of the European XFEL and other XFELs.
RESUMO
Vitiligo is one of the dermatomes affecting the melanocytes resulting in their destruction and subsequent patchy depigmentation of the skin. It is postulated to occur due to an autoimmune problem. Despite being a disease with limited systemic involvement and lack of mortality, it has a severe psychological impact. It may have a powerfully negative effect on a patient's quality of life. The relationship between vitiligo and pregnancy is not widely acknowledged. It may be associated with adverse pregnancy outcomes such as recurrent miscarriage, prematurity, intrauterine growth retardation and pre-eclampsia. Herein, this review describes the disease's adverse effects on pregnancy outcomes and the influence of pregnancy itself on the clinical evolution and prognosis of vitiligo.