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1.
Emerg Infect Dis ; 30(2): 262-269, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38181800

RESUMEN

We evaluated the population-level benefits of expanding treatment with the antiviral drug Paxlovid (nirmatrelvir/ritonavir) in the United States for SARS-CoV-2 Omicron variant infections. Using a multiscale mathematical model, we found that treating 20% of symptomatic case-patients with Paxlovid over a period of 300 days beginning in January 2022 resulted in life and cost savings. In a low-transmission scenario (effective reproduction number of 1.2), this approach could avert 0.28 million (95% CI 0.03-0.59 million) hospitalizations and save US $56.95 billion (95% CI US $2.62-$122.63 billion). In a higher transmission scenario (effective reproduction number of 3), the benefits increase, potentially preventing 0.85 million (95% CI 0.36-1.38 million) hospitalizations and saving US $170.17 billion (95% CI US $60.49-$286.14 billion). Our findings suggest that timely and widespread use of Paxlovid could be an effective and economical approach to mitigate the effects of COVID-19.


Asunto(s)
COVID-19 , Lactamas , Leucina , Nitrilos , Prolina , Salud Pública , Ritonavir , Humanos , Estados Unidos/epidemiología , SARS-CoV-2 , Antivirales/uso terapéutico , Combinación de Medicamentos
2.
Lancet ; 402 Suppl 1: S39, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37997080

RESUMEN

BACKGROUND: The RSVpreF vaccines have breakthrough progress. The respiratory syncytial virus (RSV) vaccine for older adults from GlaxoSmithKline was the first RSV vaccine approved by the US Food and Drug Administration (FDA) in early May 2023, followed by the subsequent FDA approval of Pfizer's RSV vaccines for older adults and pregnant women. We aimed to estimate the public health impact of the potential population-level administrations of the RSVpreF vaccine in the UK. METHODS: In this modelling study, we used national census and contact survey data to construct an individual-based mathematical model, with interpersonal connections characterising household structure, social settings, and age-specific contact patterns. We considered both within-host viral-load dynamics and between-host RSV transmission. We modelled the coverages of RSV vaccines for older people (age ≥60 years) and pregnant women, using influenza vaccination data from the 2018-19 season. We explored a range of possible transmissibility and estimated the health burden averted by RSVpreF vaccine over a 300-day period as compared with the control scenario without vaccines. FINDINGS: In a low-transmission scenario (Re=1·2), RSVpreF would avert a total population of 2·35 (95% credible interval [CrI] 1·24-3·77) million infections, 12.80 (95% CrI 8·60-17·06) thousand hospital admissions, and 0·93 (95% CrI 0·69-1·25) thousand deaths, with 1·82 (1·41-2·33) million infections, 12·44 (8·50-16·38) thousand hospital admissions, and 0·93 (0·67-1·23) thousand deaths averted for people aged 60 years and older. In a high-transmission scenario (Re=2·0), RSVpreF would avert 2·01 (1·37-2·68) million infections, 14·67 (10·05-18·33) thousand hospital admissions, and 1·12 (0·80-1·35) thousand deaths. The majority averted would still be among older adults. INTERPRETATION: Our mathematical models will help improve the vaccine schedules of RSVpreF. Future work will address several limitations when data become available, including the incorporation of population immunity, potential vaccine hesitancy, and other factors affecting vaccine uptake and effectiveness. FUNDING: Government of the Hong Kong Special Administrative Region, the European Research Council, and Ministry of Science and Technology of the People's Republic of China.


Asunto(s)
COVID-19 , Vacunas contra Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , Femenino , Embarazo , Persona de Mediana Edad , Anciano , Pandemias , Reino Unido/epidemiología
3.
Appl Environ Microbiol ; 90(4): e0000724, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38501861

RESUMEN

With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.


Asunto(s)
Equol , Isoflavonas , Animales , Humanos , Ratones , Ratas , Porcinos , Equol/genética , Equol/metabolismo , Racemasas y Epimerasas , Pollos/metabolismo , Isoflavonas/metabolismo , Oxidorreductasas/metabolismo
4.
FASEB J ; 37(5): e22906, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37052859

RESUMEN

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which may cause right heart failure and even death. Accumulated evidence confirmed that microRNA-26 family play critical roles in cardiovascular disease; however, their function in PAH remains largely unknown. Here, we investigated the expression of miR-26 family in plasma from PAH patients using quantitative RT-PCR, and identified miR-26a-5p as the most downregulated member, which was also decreased in hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) autophagy models and lung tissues of PAH patients. Furthermore, chromatin immunoprecipitation (ChIP) analysis and luciferase reporter assays revealed that hypoxia-inducible factor 1α (HIF-1α) specifically interacted with the promoter of miR-26a-5p and inhibited its expression in PASMCs. Tandem mRFP-GFP-LC3B fluorescence microscopy demonstrated that miR-26a-5p inhibited hypoxia-induced PAMSC autophagy, characterized by reduced formation of autophagosomes and autolysosomes. In addition, results showed that miR-26a-5p overexpression potently inhibited PASMC proliferation and migration, as determined by cell counting kit-8, EdU staining, wound-healing, and transwell assays. Mechanistically, PFKFB3, ULK1, and ULK2 were direct targets of miR-26a-5p, as determined by dual-luciferase reporter gene assays and western blots. Meanwhile, PFKFB3 could further enhance the phosphorylation level of ULK1 and promote autophagy in PASMCs. Moreover, intratracheal administration of adeno-miR-26a-5p markedly alleviated right ventricular hypertrophy and pulmonary vascular remodeling in hypoxia-induced PAH rat models in vivo. Taken together, the HIF-1α/miR-26a-5p/PFKFB3/ULK1/2 axis plays critical roles in the regulation of hypoxia-induced PASMC autophagy and proliferation. MiR-26a-5p may represent as an attractive biomarker for the diagnosis and treatment of PAH.


Asunto(s)
Hipertensión Pulmonar , MicroARNs , Hipertensión Arterial Pulmonar , Ratas , Animales , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Remodelación Vascular/genética , Hipoxia/metabolismo , Hipertensión Arterial Pulmonar/genética , MicroARNs/genética , MicroARNs/metabolismo , Arteria Pulmonar/metabolismo , Miocitos del Músculo Liso/metabolismo , Autofagia , Proliferación Celular/genética , Movimiento Celular/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo
5.
Emerg Infect Dis ; 29(10): 2121-2124, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37640373

RESUMEN

China announced a slight easing of its zero-COVID rules on November 11, 2022, and then a major relaxation on December 7, 2022. We estimate that the ensuing wave of SARS-CoV-2 infections caused 1.41 million deaths in China during December 2022-February 2023, substantially higher than that reported through official channels.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , China/epidemiología
6.
BMC Med ; 21(1): 48, 2023 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-36765349

RESUMEN

BACKGROUND: Regarding primary and secondary cervical cancer prevention, the World Health Organization proposed the cervical cancer elimination strategy that requires countries to achieve 90% uptake of human papillomavirus (HPV) vaccines and 70% screening uptake. The optimal cervical screening strategy is likely different for unvaccinated and vaccinated cohorts upon national HPV immunization. However, health authorities typically only provide a one-size-fits-all recommendation for the general population. We aimed to evaluate the cost-effectiveness for determining the optimal screening strategies for vaccinated and unvaccinated cohorts. METHODS: We considered the women population in Hong Kong which has a unique HPV infection and cervical cancer epidemiology compared to other regions in China and Asia. We used mathematical models which comprise a deterministic age-structured compartmental dynamic component and a stochastic individual-based cohort component to evaluate the cost-effectiveness of screening strategies for cervical screening. Following the recommendations in local guidelines in Hong Kong, we considered strategies that involved cytology, HPV testing, or co-testing as primary cervical screening. We also explored the impacts of adopting alternative de-intensified strategies for vaccinated cohorts. The 3-year cytology screening was used as the base comparator while no screening was also considered for vaccinated cohorts. Women's lifetime life years, quality-adjusted life years, and costs of screening and treatment were estimated from the societal perspective based on the year 2022 and were discounted by 3% annually. Incremental cost-effectiveness ratios (ICERs) were compared to a willingness to pay (WTP) threshold of one gross domestic product per capita (US $47,792). Probabilistic and one-way sensitivity analyses were conducted. RESULTS: Among unvaccinated cohorts, the strategy that adds reflex HPV to triage mild cytology abnormality generated more life years saved than cytology-only screening and could be a cost-effective alternative. Among vaccinated cohorts, when vaccine uptake was 85% (based on the uptake in 2022), all guideline-based strategies (including the cytology-only screening) had ICERs above the WTP threshold when compared with no screening if the vaccine-induced protection duration was 20 years or longer. Under the same conditions, HPV testing with genotyping triage had ICERs (compared with no screening) below the WTP threshold if the routine screening interval was lengthened to 10 and 15 years or screening was initiated at ages 30 and 35 years. CONCLUSIONS: HPV testing is a cost-effective alternative to cytology for vaccinated cohorts, and the associated optimal screening frequency depends on vaccine uptake. Health authorities should optimize screening recommendations by accounting for population vaccine uptake.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Análisis Costo-Beneficio , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/complicaciones , Detección Precoz del Cáncer/métodos , Vacunación , Tamizaje Masivo/métodos , Hong Kong/epidemiología
7.
J Virol ; 96(20): e0131822, 2022 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-36173190

RESUMEN

Pseudorabies virus (PRV), which is extremely infectious and can infect numerous mammals, has a risk of spillover into humans. Virus-host interactions determine viral entry and spreading. Here, we showed that neuropilin-1 (NRP1) significantly potentiates PRV infection. Mechanistically, NRP1 promoted PRV attachment and entry, and enhanced cell-to-cell fusion mediated by viral glycoprotein B (gB), gD, gH, and gL. Furthermore, through in vitro coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays, NRP1 was found to physically interact with gB, gD, and gH, and these interactions were C-end Rule (CendR) motif independent, in contrast to currently known viruses. Remarkably, we illustrated that the viral protein gB promotes NRP1 degradation via a lysosome-dependent pathway. We further demonstrate that gB promotes NRP1 degradation in a furin-cleavage-dependent manner. Interestingly, in this study, we generated gB furin cleavage site (FCS)-knockout PRV (Δfurin PRV) and evaluated its pathogenesis; in vivo, we found that Δfurin PRV virulence was significantly attenuated in mice. Together, our findings demonstrated that NRP1 is an important host factor for PRV and that NRP1 may be a potential target for antiviral intervention. IMPORTANCE Recent studies have shown accelerated PRV cross-species spillover and that PRV poses a potential threat to humans. PRV infection in humans always manifests as a high fever, tonic-clonic seizures, and encephalitis. Therefore, understanding the interaction between PRV and host factors may contribute to the development of new antiviral strategies against PRV. NRP1 has been demonstrated to be a receptor for several viruses that harbor CendR, including SARS-CoV-2. However, the relationships between NRP1 and PRV are poorly understood. Here, we found that NRP1 significantly potentiated PRV infection by promoting PRV attachment and enhanced cell-to-cell fusion. For the first time, we demonstrated that gB promotes NRP1 degradation via a lysosome-dependent pathway. Last, in vivo, Δfurin PRV virulence was significantly attenuated in mice. Therefore, NRP1 is an important host factor for PRV, and NRP1 may be a potential target for antiviral drug development.


Asunto(s)
COVID-19 , Herpesvirus Suido 1 , Seudorrabia , Ratones , Humanos , Animales , Herpesvirus Suido 1/metabolismo , Neuropilina-1/genética , Neuropilina-1/metabolismo , Furina/metabolismo , SARS-CoV-2 , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Replicación Viral , Proteínas Virales/metabolismo , Antivirales/metabolismo , Mamíferos
8.
Bioprocess Biosyst Eng ; 46(11): 1539-1567, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37540309

RESUMEN

Enzymes with industrial significance are typically used in biological processes. However, instability, high sensitivity, and impractical recovery are the major drawbacks of enzymes in practical applications. In recent years, the immobilization technology has attracted wide attention to overcoming these restrictions and improving the efficiency of enzyme applications. Chitosan (CS) is a unique functional substance with biocompatibility, biodegradability, non-toxicity, and antibacterial properties. Chitosan composites are anticipated to be widely used in the near future for a variety of purposes, including as supports for enzyme immobilization, because of their advantages. Therefor this review explores the effects of the chitosan's structure, molecular weight, degree of deacetylation on the enzyme immobilized, effect of key factors, and the enzymes immobilized on chitosan based composites for numerous applications, including the fields of biosensor, biomedical science, food industry, environmental protection, and industrial production. Moreover, this study carefully investigates the advantages and disadvantages of using these composites as well as their potential in the future.


Asunto(s)
Quitosano , Quitosano/química , Enzimas Inmovilizadas/química
9.
Clin Infect Dis ; 75(1): e293-e295, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35171991

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic continues to pose substantial risks to public health, worsened by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that may have a higher transmissibility and reduce vaccine effectiveness. We conducted a systematic review and meta-analysis on reproduction numbers of SARS-CoV-2 variants and provided pooled estimates for each variant.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Humanos , Pandemias , Reproducción , SARS-CoV-2/genética
10.
BMC Med ; 20(1): 359, 2022 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-36266654

RESUMEN

BACKGROUND: The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. METHODS: The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. RESULTS: Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.


Asunto(s)
Anidulafungina , Infecciones por Bunyaviridae , Virosis , Animales , Ratones , Anidulafungina/farmacología , Anidulafungina/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Infecciones por Bunyaviridae/tratamiento farmacológico , Clatrina , Receptor de Interferón alfa y beta , SARS-CoV-2 , Proteínas Virales , Virosis/tratamiento farmacológico
11.
Small ; 18(14): e2108091, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35187811

RESUMEN

Converting the mechanical energy of human motion into electricity is considered an ideal energy supply solution for portable electronics. However, low-frequency human movement limits conversion efficiency of conventional energy harvesting devices, which is difficult to provide sustainable power for portable electronic devices. Herein, a fitness gyroscope nanogenerator (fg-NG) based on a triboelectric nanogenerator (TENG) and electromagnetic generator (EMG) is developed that can convert low-frequency wrist motion into high-frequency rotation by using the frequency up-conversion effect of the gyroscope. Remarkably, the fg-NG can reach a rotational speed of over 8000 rpm by hand, increasing the frequency by more than 280 times. The fg-NG can continuously and stably output a current of 17 mA and a voltage of 70 V at frequency of 220-230 Hz. The fg-NG is demonstrated to consistently power a hygrothermograph, smart bracelet, and mobile phone. Also, it can be applicated to a self-powered intelligent training system, showing its immense application potential in portable electronics and wireless Internet of Things devices.


Asunto(s)
Suministros de Energía Eléctrica , Nanotecnología , Electricidad , Electrónica , Humanos , Movimiento (Física)
12.
Pain Manag Nurs ; 23(6): 861-870, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35934662

RESUMEN

OBJECTIVES: This study aimed to evaluate the effectiveness of cognitive behavioral therapy (CBT) and mindfulness therapy (MT) for pain relief and quality of life (QOL) in patients with diabetic neuropathy. REVIEW/ANALYSIS METHODS: Four databases were systematically searched from their respective inception dates to 29 June 2021. Relevant randomized controlled trials (RCTs) were screened and assessed for risk of bias. Eight RCTs evaluating CBT or MT were included. Statistical analysis was performed using Review Manager 5.4. RESULTS: Eight RCTs involving 384 patients with painful diabetic neuropathy (PDN) tested psychological interventions, including three CBT and five MT studies. The results showed that patients' pain severity (standardized mean difference [SMD] = -0.60, 95% confidence interval [CI; -0.93 to -0.27], P = .0003) and QOL (SMD = -0.43, 95% CI [-0.83 to -0.04], p = .03) were improved immediately after treatment. Besides, the pain intensity (SMD = -0.67, 95% CI [-1.37 to 0.03], p = .06), pain interference (SMD = -0.75, 95% CI [-1.20 to -0.30], p = .001) and depressive symptoms (SMD = -0.62, 95% CI [-0.96 to -0.28], p = .0003) were superior to the control group after follow up. The subgroup analysis results of different intervention type showed that the CBT group could immediately improve pain (SMD = -0.44, 95% CI [-0.78 to -0.10], p = .01) after treatment. However, there was no statistically significant difference in the CBT group after follow-up (SMD = -0.15, 95% CI [-0.52 to 0.22], p = .42). CONCLUSIONS: Cognitive behavioral therapy or MT is effective for treating pain in patients with diabetic peripheral neuropathy, improving the QOL, and reducing depressive symptoms. However, large-scale, multi-centre, rigorously designed RCTs are needed to further verify the long-term effects.


Asunto(s)
Terapia Cognitivo-Conductual , Diabetes Mellitus , Neuropatías Diabéticas , Atención Plena , Humanos , Neuropatías Diabéticas/terapia , Terapia Cognitivo-Conductual/métodos , Calidad de Vida , Dolor
13.
Int Heart J ; 63(3): 492-497, 2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35569965

RESUMEN

Atrial fibrillation (AF) is highly prevalent in patients with mitral stenosis (MS), but the efficacy of left atrial appendage occlusion (LAAO) in these patients remains unclear.The aim of this study was to evaluate the efficacy and safety of LAAO in patients with MS complicated by AF at high risk of bleeding.We recruited patients from September 2015 to September 2018. We compared the 3-year outcomes of LAAO in 21 patients with AF complicated by MS and 42 sex- and age-matched patients with AF without MS.The MS group had more cases of peripheral arterial embolism (28.6% versus 2.4%, P = 0.004), more spontaneous echo contrast (47.6% versus 9.5%, P = 0.001), a larger LAA orifice diameter (P < 0.01), and a slower LAA flow (P < 0.05) than the Non-MS group. The mean size of the selected occluder device was bigger for patients with MS than for patients with Non-MS (29.2 ± 3.7 versus 26.9 ± 3.1 mm, P = 0.014). In the first 45 follow-up days, 2 (9.5%) patients with MS had device-related thrombi (DRT); one of them had transient ischemic attack 24 hours postoperatively. From 45 days to 6 months, one patient in each group had DRT. After 6 months, two patients in the Non-MS group still had residual leaks; one of them had a stroke, with a small DRT. The proportion of dual antiplatelet therapy was higher in the Non-MS group than in the MS group (33.3% versus 4.8%, P = 0.012), but this population had an increased bleeding risk.LAAO is relatively effective and safe for preventing embolic events in patients with MS complicated by AF, at high risk of bleeding.


Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Embolia , Estenosis de la Válvula Mitral , Accidente Cerebrovascular , Trombosis , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/cirugía , Fibrilación Atrial/complicaciones , Fibrilación Atrial/cirugía , Embolia/complicaciones , Hemorragia/complicaciones , Humanos , Estenosis de la Válvula Mitral/complicaciones , Estenosis de la Válvula Mitral/cirugía , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento
14.
Small ; 17(29): e2101430, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34145752

RESUMEN

Free-standing rotary triboelectric nanogenerators (rTENG) can accomplish special tasks which require both high voltage and high frequency. However, the reported high performance rTENG all have complex structures for output enhancement. In this work, an ultra-simple strategy to build high performance rTENG is developed. With only one small paper strip added to the conventional structure, the output of the TENG is promoted hugely. The voltage is triplicated to 2.3 kV, and the current and charge are quintupled to 133 µA and 197 nC, respectively. The small paper strip, with the merits of ultra-simplicity, wide availability, easy accessibility and low cost, functions as a super-effective charge supplement. This simple and delicate structure enables ultra-high durability with the 2.3 kV voltage output 100% maintained after 1 000 000 cycles. This charge supplementary strategy is universally effective for many other materials, and decouples the output enhancement from any friction or contact on the metal electrodes, emphasizing a critical working principle for the rTENG. Atmospheric cold plasma is generated using the paper strip rTENG (ps-rTENG), which demonstrates strong ability to do bacteria sterilization. This simple and persistent charge supplementary strategy can be easily adopted by other designs to promote the output even further.


Asunto(s)
Nanotecnología
15.
Pacing Clin Electrophysiol ; 44(7): 1253-1258, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33165978

RESUMEN

Atrial fibrillation (AF), the most common arrhythmia, is a major cause of stroke and systemic embolism. Patients with AF are at higher risk of stroke with the left atrial appendage (LAA) being the most common site for thrombus formation. Although oral anticoagulation (OAC) remains the standard of care for stroke prevention in AF patients, there are still several limitations, including increased risk of bleeding and noncompliance. LAA closure (LAAC) has been found to be non-inferior to OAC in preventing all-cause strokes and systemic embolisms in randomized clinical trials, and is increasingly performed for stroke prevention in patients with nonvalvular AF (NVAF). However, device-related thrombus (DRT) after LAAC and a potentially increased risk of stroke related to DRT were observed in several registered studies, and attract wide concern. This review provides a comprehensive update on the incidence, mechanism, risk factors, prevention, diagnosis, and treatment of DRT after LAAC in patients with NVAF.


Asunto(s)
Apéndice Atrial/cirugía , Fibrilación Atrial/cirugía , Complicaciones Posoperatorias/etiología , Prótesis e Implantes/efectos adversos , Trombosis/etiología , Procedimientos Quirúrgicos Cardíacos/instrumentación , Humanos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/terapia
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(1): 47-51, 2021 Jan 10.
Artículo en Zh | MEDLINE | ID: mdl-33423257

RESUMEN

OBJECTIVE: To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function. METHODS: Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization. RESULTS: The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene. CONCLUSION: The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.


Asunto(s)
Mutación del Sistema de Lectura , Riñón Poliquístico Autosómico Dominante , Proteínas Quinasas , Análisis Mutacional de ADN , Femenino , Células HEK293 , Células HeLa , Humanos , Masculino , Linaje , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/fisiopatología , Proteína Quinasa D2 , Proteínas Quinasas/genética , Transporte de Proteínas/genética , Secuenciación del Exoma
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(11): 1106-1109, 2021 Nov 10.
Artículo en Zh | MEDLINE | ID: mdl-34729753

RESUMEN

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION: The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.


Asunto(s)
Polidactilia , China , Femenino , Humanos , Mutación , Linaje , Polidactilia/genética , Pulgar , Secuenciación del Exoma
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(12): 1224-1227, 2021 Dec 10.
Artículo en Zh | MEDLINE | ID: mdl-34839512

RESUMEN

OBJECTIVE: To explore the genetic basis for a Chinese patient with amyotrophic lateral sclerosis (ALS). METHODS: Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Genetic variant was identified by whole exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and healthy controls. RESULTS: The patient was found to harbor a heterozygous c.420C>G (p.Asn140Lys) variant of the SOD1 gene. The same variant was not detected in his parents and 100 healthy controls. The variant has not been included in HGMD, dbSNP and other databases. CONCLUSION: The c.420C>G variant of the SOD1 gene may underlie the ALS in this patient. Above finding has enriched the spectrum of SOD1 gene variants.


Asunto(s)
Esclerosis Amiotrófica Lateral , Esclerosis Amiotrófica Lateral/genética , China , Heterocigoto , Humanos , Superóxido Dismutasa-1/genética , Secuenciación del Exoma
19.
Catheter Cardiovasc Interv ; 96(7): E755-E757, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-31696654

RESUMEN

Coronary sinus perforation is a life-threatening complication of transseptal puncture and needs to be repaired immediately. In this study, we report a case of a 74-year-old female patient with nonvalvular atrial fibrillation, who is a poor long-term anticoagulation candidate. During the manipulation of transseptal puncture, a perforation of the free right atrial wall at the coronary sinus ostium occurred, which was caused by the Brockenbrough needle and followed by the immediate advancement of an 8.5-French transseptal sheath. In consideration of the danger of cardiac tamponade after sheath removal, we decided to leave the 8.5-French sheath in the pericardial cavity. Then, we advanced a 6 mm ventricular septal occluder through the sheath. Finally, we achieved successful deployment of the device and closure of the perforation under the guidance of fluoroscopy and transthoracic echocardiography. Subsequently, the left atrial appendage orifice was occluded with a 21 mm Watchman device. This case illustrates that percutaneous device closure is feasible for inadvertent perforation of the free right atrial wall at the coronary sinus during transseptal puncture and should be considered as an alternative to surgery.


Asunto(s)
Fibrilación Atrial/terapia , Cateterismo Cardíaco/instrumentación , Seno Coronario/lesiones , Lesiones Cardíacas/terapia , Tabiques Cardíacos , Técnicas Hemostáticas/instrumentación , Dispositivo Oclusor Septal , Lesiones del Sistema Vascular/terapia , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Cateterismo Cardíaco/efectos adversos , Seno Coronario/diagnóstico por imagen , Femenino , Lesiones Cardíacas/diagnóstico por imagen , Lesiones Cardíacas/etiología , Tabiques Cardíacos/diagnóstico por imagen , Humanos , Diseño de Prótesis , Punciones , Resultado del Tratamiento , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/etiología
20.
Heart Vessels ; 34(8): 1360-1369, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30820642

RESUMEN

This study aimed to estimate the incidence and risk factors of device-related thrombus (DRT) following percutaneous left atrial appendage closure (LAAC) in real-world practices. Between February 2012 and December 2016, 319 consecutive patients with atrial fibrillation underwent percutaneous LAAC using WATCHMAN, WATCHMAN Flx, Amplatzer cardiac plug, and Amulet devices. All patients underwent transesophageal echocardiography (TEE) at a minimum of three time points; periprocedurally, at 45 days, and at 6 months. Other clinical parameters were also evaluated, and a comparison between patients with DRT and those not suffering from DRT was done. The percutaneous LAAC was successfully performed in 97.8% of the patients. DRT was detected in 14 (4.49%) patients; of the 14 patients, DRT was detected in 3 patients at acute phase, 8 patients at subacute phase, 2 patients at late phase and 1 patient at very late phase. Most of the DRT originated from the central screw of device. In 6 out of 14 patients, DRT was successfully resolved by oral anticoagulation. Higher HAS-BLED score (4.1 ± 1.2 vs. 3.5 ± 1.1, p = 0.042) was more frequent in patients with DRT. Multivariable analysis showed that residual peri-device leak may result in a predisposition to DRT (p = 0.023). The incidence of DRT after percutaneous LAAC was acceptable, as a part of the DRT was resolved with oral anticoagulation. Residual peri-device leak was associated with DRT. Optimal implantation without peri-device gap, individual antithrombotic regimens, and careful monitoring with TEE follow-up could be conducive to the prevention of DRT.


Asunto(s)
Apéndice Atrial/cirugía , Fibrilación Atrial/cirugía , Dispositivo Oclusor Septal/efectos adversos , Trombosis/diagnóstico por imagen , Trombosis/epidemiología , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Ecocardiografía Transesofágica , Femenino , Alemania/epidemiología , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento
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