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This systematic review assesses the relationship between climate induced coastal hazards and psychological well-being of communities in the Asia-Pacific region. The review synthesises findings from 13 peer-reviewed articles published between 2007 and 2020, encompassing data from seven countries: Bangladesh, India, Indonesia, Philippines, Solomon Islands, Tuvalu, and Vietnam. Results reveals a robust negative association between exposure to coastal hazards and psychological outcomes, notably stress, depression, anxiety, and distress. Most of the studies (77%) corroborate negative impacts of coastal hazards on psychological health. Additionally, 69% of the reviewed articles suggest a correlation between coastal hazards and negative outcomes for community livelihoods and essential resources. The review highlights increased psychological vulnerability among marginalised subpopulations, such as economically disadvantaged communities, a trend supported by 92% of the examined articles. The findings indicates that factors such as environmental vulnerability, resource availability, community traits, and coping methods are important in determining whether a community can effectively handle coastal hazards or face increased psychological health risks. This research aligns with international health frameworks, including the World Health Organization's Health Emergency and Disaster Risk Management guidelines. However, a notable research gap emerges - the absence of studies that specifically explore psychological responses of communities to ongoing climate-related coastal hazards, such as sea-level rise. These findings emphasise an urgent need for targeted research to guide comprehensive, multidisciplinary policy interventions aimed at mitigating the psychological and socio-economic repercussions of climate-related coastal hazards.
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Aves , Vírus da Influenza A , Influenza Aviária , Influenza Humana , Saúde Pública , Influenza Aviária/transmissão , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Influenza Humana/transmissão , Animais , Humanos , Aves/virologia , Vírus da Influenza A/patogenicidadeRESUMO
A 65-year-old woman presented to our hospital with 5 days of chest tightness, dyspnoea, and lower abdominal distension. Echocardiography revealed a mass in the right atrium. An emergency operation was carried out to prevent tumour shedding. The patient was discharged on the 4th day of tumour resection, without any complications At the 18 months follow-up, she suffered from kidney and lung tumours. She refused any treatment and passed away. scRNA-seq was applied to analyse the nature of the tumour. The cellular components of benign tumours include chondrocytes, smooth muscle cells, fibroblasts, mesenchymal stromal cells, and osteoblasts. Additionally, the cyclic guanosine monophosphate (cGMP-PKG) signalling pathway, transcriptional misregulation in cancer, and the p53 signalling pathway may be related to the growth of this tumour. scRNA-seq is a good approach to analyse growth patterns of cardiac tumours and helpful for distinguishing the nature of the tumour.
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Neoplasias Cardíacas , Feminino , Humanos , Idoso , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/genética , Análise de Sequência de RNARESUMO
Background: Pulmonary artery dissection (PAD) is an uncommon condition associated with high mortality rates. To date, a comprehensive examination of various underlying causes of PAD remains unexplored. Methods: We used the search words "pulmonary artery dissection," "pulmonary artery dilatation," and "pulmonary artery rupture" in the public database, and examined the medical records of PAD patients treated in our hospital. Data on demographics, aetiology, PAD locations, histopathology, treatments, and outcomes, were collected. Results: A total of 145 patients with PAD (135 cases from the literature and 10 cases from our hospital) were analysed. PAD aetiology was categorized into four groups: congenital heart diseases (CHD) associated with pulmonary arterial hypertension (PAH), non-CHD associated with pulmonary hypertension (PH), aortic dissection-related, and miscellaneous causes. The most frequent cause, accounting for 32.4 % of PAD cases, was congenital heart disease, followed by idiopathic PAH (13 %) and chronic obstructive pulmonary disease (6 %). Patients with CHD were typically younger at the time of PAD diagnosis (median age: 35 years old) when compared with those suffering from aortic dissection, PH-associated conditions, or other causes (median age: 45, 55, and 56 years old, respectively). Imaging of the pulmonary artery proved effective in diagnosing PAD. The outcomes were generally poor. 44.7 % (21/47) of patients with CHD associated with PAH and 47.7 % (21/44) of non-CHD PH-associated diseases died during follow-up. Multidisciplinary team consultations are crucial when making decisions on management of PAD. Characteristic PAD histopathology features included thickened intima and hypertrophied media with atheromatous degeneration, disrupted elastic fibres, and lymphocytic infiltration. Conclusions: PAD aetiology can be divided into four main categories, with CHD associated with PAH being the leading cause. Despite the similar histopathology features, clinical manifestations and outcomes vary according to the aetiology.
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BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , China/epidemiologia , Infecções por Helicobacter/epidemiologia , Estilo de Vida , Nomogramas , CháRESUMO
The 25 million Australians today are identified with more than 300 ancestries. People's home language use and shift patterns had demonstrated great variations as more immigrants from Asia-Pacific regions entered Australia. The ethnolinguistic composition of Australia's population had undergone substantial changes in the last few decades. Based on the statistics from Australian censuses, the present paper aims to analyze the changes of people's home language use and the shift patterns in the new Millennium. Five sets of census data released by Australian Bureau of Statistics were adopted as the secondary data source and descriptive analysis was conducted to disclose the dynamic picture of different home languages in Australia after 2000. The results suggest that the number of home language speakers in Australia has soared up quickly in the last two decades and great variations have been found between the traditional European migrant groups and the newly Asian arrivers. Mandarin has overtaken Italian and Greek to become the most populous home language other than English used in Australia since 2011 and great regional differences were also found to exist among different states and territories. Moreover, the ranking order of different home language speakers had changed considerably as compared with that in the last century. The language shift rates of different language communities and their cross-tabulations with generations, gender, age, and duration of residence in the latest available censuses after 2000 also revealed diverse developmental directions. The findings give us a glimpse of the current status of different home languages in Australia and help us to identify the potential factors impacting the shifting trends of different language communities. A better understanding of the language needs of different migrant communities may further help policymakers set more effective plans to accommodate an increasingly diverse Australian society.
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The endosymbiont Wolbachia manipulates host reproduction by several strategies, one of the most important of which is cytoplasmic incompatibility (CI). CI can be rescued when Wolbachia-infected males mate with females infected with the same Wolbachia strain. However, the potential rescue mechanism of CI in the small brown planthopper Laodelphax striatellus is unclear. In this study, comparative transcriptome analysis was applied to explore the effect of Wolbachia on L. striatellus eggs. A total of 1387 differentially expressed genes were identified. RNA interference of 7 Wolbachia-upregulated key planthopper genes reduced egg reproduction, suggesting that Wolbachia might improve fecundity in L. striatellus by affecting these 7 genes. Suppressing the expression of another upregulated gene, NDUFA8 (encoding NADH dehydrogenase [ubiquinone] 1 α subcomplex subunit 8-like) by RNA interference significantly increased the mortality of early embryos without affecting the number of deposited eggs. Wolbachia infection upregulated the mRNA level of NDUFA8, and dsNDUFA8 treatment of Wolbachia-infected females recreated CI-like symptoms, suggesting that NDUFA8 is associated with the rescue phenotype. Because all L. striatellus populations worldwide are infected with Wolbachia, NDUFA8 is a potential pest control target.
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Hemípteros , Wolbachia , Feminino , Masculino , Animais , Wolbachia/genética , Hemípteros/genética , Hemípteros/metabolismo , Fertilidade , Reprodução , Perfilação da Expressão GênicaRESUMO
Nucleoprotein (NP) functions crucially in the replicative cycle of influenza A virus (IAV) via forming the ribonucleoprotein complex together with PB2, PB1, and PA proteins. As its high conservation, NP ranks one of the hot targets for design of universal diagnostic reagents and antiviral drugs for IAV. Here, we report an anti-NP murine monoclonal antibody (mAb) 5F10 prepared from traditional lymphocyte hybridoma technique with the immunogen of a clade 2.3.4.4 H5N1 subtype avian influenza virus. The specificity of mAb 5F10 to NP protein was confirmed by immunofluorescence assay and western blotting, and the mAb 5F10 could be used in immunoprecipitation and immunohistochemistry assays. Importantly, mAb 5F10 possessed broad-spectrum reactivity against H1~H11 subtypes of avian influenza viruses, including various HA clades of H5Nx subtype. In addition, mAb 5F10 also showed good affinity with H1N1 and H3N2 subtype influenza viruses of swine and human origin. Furthermore, the recognized antigenic epitope of mAb 5F10 was identified to consist of the conserved amino acid motif 81EHPSA85 in the second flexible loop region of NP protein through screening the phage display peptide library. Collectively, the mAb 5F10 which recognizes the novel universal NP linear B-cell epitope of IAV with diverse origins and subtypes will be a powerful tool for NP protein-based structural, functional, and mechanistic studies, as well as the development of detection methods and universal vaccines for IAV. KEY POINTS: ⢠A broad-spectrum mAb against various subtypes and sources of IAV was developed ⢠The mAb possessed good reactivity in IFA, western blot, IP, and IHC assays ⢠The mAb targeted a novel conserved linear B-cell epitope involving 81EHPSA85 on NP protein.
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Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Humana , Animais , Humanos , Camundongos , Suínos , Anticorpos Monoclonais , Nucleoproteínas , Epitopos de Linfócito B , Vírus da Influenza A Subtipo H3N2 , Anticorpos AntiviraisRESUMO
Janus particles for oil-water separation have attracted widespread attention in recent years. Herein, we prepared a bowl-shaped Janus particle that could rapidly separate oil and water through a thiol-ene click reaction and selective etching. Firstly, snowman-like composite microspheres based on silica and mercaptopropyl polysilsesquioxane (SiO2@MPSQ) were prepared by a hydrolytic condensation reaction and phase separation, and the effects of the rotational speed and molar ratios on their microscopic morphologies were investigated. Subsequently, bowl-shaped Janus particles with convex hydrophilic and concave oleophilic surfaces were prepared via a thiol-ene click reaction followed by HF etching. Our amphiphilic bowl-shaped Janus particles could remarkably separate micro-sized oil droplets from an n-heptane-water emulsion with a separation efficiency of >98% within 300 s. Based on the experimental and theoretical results, we proposed the underlying mechanism for the coalescence of oil droplets upon the addition of the amphiphilic bowl-shaped Janus particles.
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BACKGROUND: Liver cirrhosis (LC) is a prevalent and severe disease in China. The burden of LC is changing with widespread vaccination of hepatitis B virus (HBV) and antiviral therapy. However, the recent transition in etiologies and clinical features of LC cases requiring hospitalization is unclear. AIM: To identify the transition in etiologies and clinical characteristics of hospitalized LC patients in Southern China. METHODS: In this retrospective, cross-sectional study we included LC inpatients admitted between January 2001 and December 2020. Medical data indicating etiological diagnosis and LC complications, and demographic, laboratory, and imaging data were collected from our hospital-based dataset. The etiologies of LC were mainly determined according to the discharge diagnosis, and upper gastrointestinal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma (HCC), portal vein thrombosis, hepatorenal syndrome, and acute-on-chronic liver failure (ACLF) were considered LC-related complications in our study. Changing trends in the etiologies and clinical characteristics were investigated using logistic regression, and temporal trends in proportions of separated years were investigated using the Cochran-Armitage test. In-hospital prognosis and risk factors associated with in-hospital mortality were also investigated. RESULTS: A total of 33143 patients were included in the study [mean (SD) age, 51.7 (11.9) years], and 82.2% were males. The mean age of the study population increased from 51.0 years in 2001-2010 to 52.0 years in 2011-2020 (P < 0.001), and the proportion of female patients increased from 16.7% in 2001-2010 to 18.2% in 2011-2020 (P = 0.003). LC patients in the decompensated stage at diagnosis decreased from 68.1% in 2001-2010 to 64.6% in 2011-2020 (P < 0.001), and the median score of model for end-stage liver disease also decreased from 14.0 to 11.0 (P < 0.001). HBV remained the major etiology of LC (75.0%) and the dominant cause of viral hepatitis-LC (94.5%) during the study period. However, the proportion of HBV-LC decreased from 82.4% in 2001-2005 to 74.2% in 2016-2020, and the proportion of viral hepatitis-LC decreased from 85.2% in 2001-2005 to 78.1% in 2016-2020 (both P for trend < 0.001). Meanwhile, the proportions of LC caused by alcoholic liver disease, autoimmune hepatitis and mixed etiology increased by 2.5%, 0.8% and 4.5%, respectively (all P for trend < 0.001). In-hospital mortality was stable at 1.0% in 2011-2020, whereas HCC and ACLF manifested the highest increases in prevalence among all LC complications (35.8% to 41.0% and 5.7% to 12.4%, respectively) and were associated with 6-fold and 4-fold increased risks of mortality (odds ratios: 6.03 and 4.22, respectively). CONCLUSION: LC inpatients have experienced changes in age distribution and etiologies of cirrhosis over the last 20 years in Southern China. HCC and ACLF are associated with the highest risk of in-hospital mortality among LC complications.
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Volatile organic compounds (VOCs) in urine are valuable biomarkers for noninvasive disease diagnosis. Herein, a facile coordination-driven modular assembly strategy is used for developing a library of gas-sensing materials based on porous MXene frameworks (MFs). Taking advantage of modules with diverse composition and tunable structure, our MFs-based library can provide more choices to satisfy gas-sensing demands. Meanwhile, the laser-induced graphene interdigital electrodes array and microchamber are laser-engraved for the assembly of a microchamber-hosted MF (MHMF) e-nose. Our MHMF e-nose possesses high-discriminative pattern recognition for simultaneous sensing and distinguishing of complex VOCs. Furthermore, with the MHMF e-nose being a plug-and-play module, a point-of-care testing (POCT) platform is modularly assembled for wireless and real-time monitoring of urinary volatiles from clinical samples. By virtue of machine learning, our POCT platform achieves noninvasive diagnosis of multiple diseases with a high accuracy of 91.7%, providing a favorable opportunity for early disease diagnosis, disease course monitoring, and relevant research.
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Grafite , Materiais Inteligentes , Compostos Orgânicos Voláteis , Nariz Eletrônico , BiomarcadoresRESUMO
Background: Deep learning (DL) could predict isocitrate dehydrogenase (IDH) mutation status from MRIs. Yet, previous work focused on CNNs with refined tumor segmentation. To bridge the gap, this study aimed to evaluate the feasibility of developing a Transformer-based network to predict the IDH mutation status free of refined tumor segmentation. Methods: A total of 493 glioma patients were recruited from two independent institutions for model development (TCIA; N = 259) and external test (AHXZ; N = 234). IDH mutation status was predicted directly from T2 images with a Swin Transformer and conventional ResNet. Furthermore, to investigate the necessity of refined tumor segmentation, seven strategies for the model input image were explored: (i) whole tumor slice; (ii-iii) tumor mask and/or not edema; (iv-vii) tumor bounding box of 0.8, 1.0, 1.2, 1.5 times. Performance comparison was made among the networks of different architectures along with different image input strategies, using area under the curve (AUC) and accuracy (ACC). Finally, to further boost the performance, a hybrid model was built by incorporating the images with clinical features. Results: With the seven proposed input strategies, seven Swin Transformer models and seven ResNet models were built, respectively. Based on the seven Swin Transformer models, an averaged AUC of 0.965 (internal test) and 0.842 (external test) were achieved, outperforming 0.922 and 0.805 resulting from the seven ResNet models, respectively. When a bounding box of 1.0 times was used, Swin Transformer (AUC = 0.868, ACC = 80.7%), achieved the best results against the one that used tumor segmentation (Tumor + Edema, AUC = 0.862, ACC = 78.5%). The hybrid model that integrated age and location features into images yielded improved performance (AUC = 0.878, Accuracy = 82.0%) over the model that used images only. Conclusions: Swin Transformer outperforms the CNN-based ResNet in IDH prediction. Using bounding box input images benefits the DL networks in IDH prediction and makes the IDH prediction free of refined glioma segmentation feasible.
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Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne febrile disease caused by SFTS virus (SFTSV), or Dabie bandavirus, in the Phenuiviridae family. Clinically neurological disorders in SFTS have been commonly reported, but their neuropathogenesis has rarely been studied. Microglia are a type of neuroglia accounting for 10 to 12% of all cells in the brain. As resident immune cells, microglial cells are the first line of immune defense present in the central nervous system (CNS). Here, we report that SFTSV was able to infect microglial cells and stimulate interleukin 1ß (IL-1ß) secretion in the brains of infected neonatal BALB/c mice. We characterized the cell death induced in infected human microglial HMC3 cells, also susceptible to SFTSV, and found that the NOD-like receptor protein 3 (NLRP3) inflammasome was activated, leading to secretion of IL-1ß and pyroptosis. Knockdown of NLRP3 or inhibition of the NLRP3 inflammasome activation suppressed the viral replication, suggesting that the activation of the NLRP3 inflammasome may support SFTSV replication in microglial cells. Viral nonstructural protein NSs, a known modulator of immune responses, interacted and colocalized with NLRP3 for the inflammasome activation. It appeared that the N-terminal fragment, amino acids 1 to 66, of NSs was critical to promote the assembly of the inflammasome complex by interacting with NLRP3 for its activation in microglial cells. Our findings provide evidence that SFTSV may cause neurological disorders through infecting microglia and activating the inflammasome through its nonstructural protein NSs for neural cell death and inflammation. This study may have revealed a novel mechanism of SFTSV NSs in dysregulating host response. IMPORTANCE Encephalitis or encephalopathy during severe fever with thrombocytopenia syndrome (SFTS) is considered a critical risk factor leading to high mortality, but there have been no studies to date on the pathogenesis of encephalitis or encephalopathy caused by SFTS virus. Here, we report that SFTSV infection can active the NLRP3 inflammasome and induce IL-1ß secretion in the brains of infected newborn mice. In infected human HMC3 microglia, SFTSV activated the NLRP3 inflammasome via the viral nonstructural protein NSs through interaction with its N-terminal fragment. Notably, our findings suggest that the activation of the NLRP3 inflammasome may promote SFTSV replication in infected microglial cells. This study may reveal a novel mechanism by SFTSV to dysregulate host responses through its nonstructural protein, which could help us understand viral neuropathogenesis in SFTS patients.
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Encefalite , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Phlebovirus , Piroptose , Proteínas não Estruturais Virais , Animais , Células Cultivadas , Humanos , Inflamassomos/metabolismo , Camundongos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Phlebovirus/metabolismo , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Proteínas não Estruturais Virais/metabolismoRESUMO
Zika virus (ZIKV) is a mosquito-borne flavivirus and can cause neurodevelopmental disorders in fetus. As a neurotropic virus, ZIKV persistently infects neural tissues during pregnancy but the viral pathogenesis remains largely unknown. ZIKV has a positive-sense and single-stranded RNA genome, which encodes 7 non-structural (NS) proteins, participating in viral replication and dysregulation of host immunity. Like those in many other viruses, NS proteins are considered to be products evolutionarily beneficiary to viruses and some are virulence factors. However, we found that some NS proteins encoded by ZIKV genome appeared to function against the viral replication. In this report we showed that exogenously expressed ZIKV NS2A and NS4A inhibited ZIKV infection by inhibiting viral RNA replication in microglial cells and astrocytes. To understand how viral NS proteins suppressed viral replication, we analyzed the transcriptome of the microglial cells and astrocytes and found that expression of NS4A induced the upregulation of ISGs, including MX1/2, OAS1/2/3, IFITM1, IFIT1, IFI6, IFI27, ISG15 or BST2 through activating the ISGF3 signaling pathway. Upregulation of these ISGs seemed to be related to the inhibition of ZIKV replication, since the anti-ZIKV function of NS4A was partially attenuated when the cells were treated with Abrocitinib, an inhibitor of the ISGF3 signaling pathway, or were knocked down with STAT2. Aborting the protein expression of NS4A, but not its nucleic acid, eliminated the antiviral activity of NS4A effectively. Dynamic expression of viral NS proteins was examined in ZIKV-infected microglial cells and astrocytes, which showed comparatively NS4A occurred later than other NS proteins during the infection. We hypothesize that NS4A may possess intrinsic features to serve as a unique type of pathogen associated molecular pattern (PAMP), detectable by the cells to induce an innate immune response, or function with other mechanisms, to restrict the viral replication to a certain level as a negative feedback, which may help ZIKV maintain its persistent infection in fetal neural tissues.
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Infecção por Zika virus , Zika virus , Animais , RNA Viral/metabolismo , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Zika virus/fisiologiaRESUMO
Background: Patent ductus arteriosus (PDA) can close on its own during childhood. Patent ductus arteriosus with left pulmonary artery (LPA) occlusion is rare. Here, we describe possible aetiologies of this condition and treatment strategies based on recent guidelines. Case summary: A 35-year-old man experienced shortness of breath for 20 years. Physical examination revealed pitting oedema, digital clubbing, and bi-phasic murmur along the left sternal border at the 2nd and 3rd intercostal space. Congenital heart disease was suspected. Echocardiography revealed a severely dilated pulmonary trunk and PDA; however, the LPA was not visible. The patient has undergone PDA ligation surgery >30 years ago, which may have caused accidental LPA ligation; however, extreme elevation of pulmonary pressure led to increased difficulties in performing LPA reconstruction and PDA division. Therefore, pulmonary arterial hypertension (PAH) initial combination therapy with parenteral prostanoids was prescribed. The patient's condition improved gradually. Discussion: Inadvertent ligation of the LPA instead of PDA is a rare and usually fatal complication during ductal ligation. Patients who survive this catastrophic complication usually develop the progressive pulmonary vascular disease with increased pulmonary pressure and impaired lung parenchyma resulting in right heart and respiratory failure. Early and regular follow-up with cardiac imaging studies is important to diagnose this complication. Reconstruction of the ligated LPA and PDA late in the disease course is difficult due to the development of pulmonary arterial hypertension. Initial PAH combination therapy may be valuable for relieving the patients' symptoms at that stage. Heart and lung transplantation can also be considered in suitable patients.
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Zika virus (ZIKV) is a positive-sense RNA flavivirus and can cause serious neurological disorders including microcephaly in infected fetuses. As a mosquito-borne arbovirus, it enters the bloodstream and replicates in various organs. During pregnancy, it can be transmitted from the blood of the viremic mother to the fetus by crossing the placental barrier. Monocytes and macrophages are considered the earliest blood cell types to be infected by ZIKV. As a first line defense, these cells are crucial components in innate immunity and host responses and may impact viral pathogenesis in humans. Previous studies have shown that ZIKV infection can activate inflammasomes and induce proinflammatory cytokines in monocytes. In this report, we showed that ZIKV could infect and induce cell death in human and murine macrophages. In addition to the presence of cleaved caspase-3, indicating that apoptosis was involved, we identified the cleaved caspase-1 and gasdermin D (GSDMD) as well as increased secretion of IL-1ß and IL-18. This suggests that the inflammasome was activated and that may lead to pyroptosis in infected macrophages. The pyroptosis was NLRP3-dependent and could be suppressed in the macrophages treated with shRNA to target and knockdown caspase-1. It was also be inhibited by an inhibitor for caspase-1, indicating that the pyroptosis was triggered via a canonical approach. Our findings in this study demonstrate a concomitant occurrence of apoptosis and pyroptosis in ZIKV-infected macrophages, with two mechanisms involved in the cell death, which may have potentially significant impacts on viral pathogenesis in humans.
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Infecção por Zika virus , Zika virus , Animais , Apoptose , Caspase 1/metabolismo , Feminino , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Placenta/metabolismo , Gravidez , Piroptose , Zika virus/metabolismo , Infecção por Zika virus/metabolismoRESUMO
BACKGROUND: Arrhythmia is not uncommon among pulmonary hypertension (PH) population, and may be associated with disease severity. HYPOTHESIS: To investigate different spectrums and prevalence of arrhythmias in different clinical PH groups in Chinese population. METHODS: Patients diagnosed with PH between April 15, 2019, and August 2, 2021, were enrolled prospectively. The prevalence of different types of arrhythmias in PH patients were calculated. Logistic regression analyses were conducted to determine independent predictors for arrhythmia. RESULTS: One thousand patients were enrolled. The prevalence of any arrhythmia, sinus node dysfunction, sinus tachycardia, atrial fibrillation, atrial flutter, other types of atrial tachycardia, atrioventricular block, and ventricular tachycardia is 44.4%, 12.2%, 15.2%, 8.1%, 4.1%, 10.2%, 7.1%, and 2.5%. Logistic regression analyses revealed that older age and larger right ventricle (odds ratio: 1.111 and 1.095, p < .05) were independently related with higher probability of supraventricular arrhythmia; Complicating with coronary artery disease, larger right ventricle, and increased left ventricular end-diastolic diameter (odds ratio: 19.540, 1.106, and 1.085, p < .05) were independently correlated with sinus node dysfunction/atrioventricular block in patients with pulmonary arterial hypertension. CONCLUSIONS: Nearly half of PH patients experienced at least one type of arrhythmia. The most common seen arrhythmias were supraventricular arrhythmia, sinus tachycardia, and sinus node dysfunction. Older age and larger right ventricle were independently related with higher probability of supraventricular arrhythmia; Complicating with coronary artery disease, larger right ventricle and increased left ventricular end-diastolic diameter were independently correlated with higher probability of sinus node dysfunction/atrioventricular block in patients with pulmonary arterial hypertension.