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BACKGROUND: Human parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021-2022. METHODS: A cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing. RESULTS: The highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643). CONCLUSION: In conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.
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Vírus da Parainfluenza 1 Humana , Filogenia , Humanos , China/epidemiologia , Pré-Escolar , Criança , Vírus da Parainfluenza 1 Humana/genética , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Masculino , Feminino , Lactente , Adolescente , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Nasofaringe/virologia , Infecções por Respirovirus/epidemiologia , Infecções por Respirovirus/virologia , Recém-NascidoRESUMO
Highly enantioselective formal [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with aurone derivatives of low reactivity using chiral dinuclear zinc catalysts has been developed via a Brønsted base and Lewis acid cooperative activation model. These transformations involving a domino Michael/Mannich reaction sequence led to efficient construction of a range of chiral spiro[benzofuran-pyrrolidine] scaffolds bearing three biologically relevant heterocyclic moieties and two adjacent spiro quaternary stereocenters in high yields (up to 95%) and with good enantioselectivities (up to 99% ee).
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An asymmetric Michael/hemiketalization and Fridel-Crafts reaction has been reported through a one-pot reaction. A number of structurally novel tetrahydrofuran spirooxindoles are synthesized in the presence of a 10 mol % dinuclear zinc catalyst with diastereomer ratios (dr) of 3:1-13:1 and an enantiomeric excess (ee) of 75-99%. The reaction can be performed on a gram scale without impacting its efficiency. The absolute configuration of products is confirmed by X-ray single crystal structure analysis, and a possible mechanism is proposed.
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The antimicrobial peptide PaDef was isolated from Mexican avocado fruit and was reported to inhibit the growth of Escherichia coli and Staphylococcus aureus in 2013. In this study, an N-terminal 6 × His tagged recombinant PaDef (rPaDef) with a molecular weight of 7.5 KDa, for the first time, was expressed as a secreted peptide in Pichia pastoris. The optimal culture condition for rPaDef expression was determined to be incubation with 1.5% methanol for 72 h at 28 °C under pH 6.0. Under this condition, the amount of the rPaDef accumulation reached as high as 79.6 µg per 1 ml of culture medium. Once the rPaDef peptide was purified to reach a 95.7% purity using one-step nickel affinity chromatography, its strong and concentration-dependent antimicrobial activity was detected to be against a broad-spectrum of bacteria of both Gram-negative and Gram-positive. The growth of these bacterial pathogens was almost completely inhibited when the rPaDef peptide was at a concentration of as low as 90 µg/ml. In summary, our data showed that rPaDef derived from Mexican avocado fruit can be expressed and secreted efficiently when P. pastoris was used as a cell factory. This is the first report on heterologous expression of PaDef in P. pastoris and the approach described holds great promise for antibacterial drug development.
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Peptídeos Catiônicos Antimicrobianos , Escherichia coli/crescimento & desenvolvimento , Persea/genética , Pichia/metabolismo , Proteínas de Plantas , Staphylococcus aureus/crescimento & desenvolvimento , Peptídeos Catiônicos Antimicrobianos/biossíntese , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/farmacologia , Persea/química , Pichia/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/farmacologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologiaRESUMO
Mytichitin-A is an antimicrobial peptide isolated from the serum of Mytilus coruscus and is reported to inhibit bacterial growth as tested on several Gram-positive bacteria. To produce large quantity of Mytichitin-A to further investigate its biological activity, nucleotide sequence encoding a recombinant 6 × His-Mytichitin-A (rMytichitin-A) peptide was synthesized and inserted into the inducible yeast expression vector pPICZαA. With the availability of such an expression vector called pPICZαA-Mytichitin-A, we transformed Pichia pastoris GS115 cells with a SacI-linearized pPICZαA-Mytichitin-A by electroporation. Transgenic strains secreting rMytichitin-A with a molecular weight of approximate 10 KDa as expected were obtained. The optimal culture condition for rMytichitin-A expression was determined to be 1.0% methanol induction, 96 h incubation at 28 °C and the amount of rMytichitin-A reached 45.5 µg/ml. The percentage of rMytichitin-A was estimated to be 73.6% of the total protein. After rMytichitin-A was purified using nickel ions affinity chromatography, approximate 9.1 mg pure rMytichitin-A was obtained from 500 ml of cell culture medium with 97.8% purity. More importantly, both the culture supernatant and purified rMytichitin-A inhibited the growth of Gram-positive bacteria, especially Staphylococcus aureus and Bacillus subtilis with a minimum inhibition concentration of as low as 31 and 48 µg/ml, respectively. Differently from the native protein, however, the rMytichitin-A is not active against Gram-negative bacteria. Taken together, this is the first report on the heterologous expression of Mytichitin-A in P. pastoris. Our study showed that P. pastoris is an effective expression system for producing large quantities of biologically active Mytichitin-A for both research and application purposes.
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Peptídeos Catiônicos Antimicrobianos , Bacillus subtilis/crescimento & desenvolvimento , Bactérias Gram-Negativas/crescimento & desenvolvimento , Mytilus/genética , Pichia/metabolismo , Staphylococcus aureus/crescimento & desenvolvimento , Animais , Peptídeos Catiônicos Antimicrobianos/biossíntese , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/farmacologia , Mytilus/metabolismo , Pichia/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacocinéticaRESUMO
BACKGROUND: Prenatal cardiac screening is of great importance as it contributes to appropriate neonatal management and helps parents to make a decision regarding their pregnancy. The aim of our study was to evaluate the efficiency of a newly proposed screening protocol in the detection of fetal congenital heart disease (CHD). METHODS: This was a prospective study. A total of 52 cases of confirmed CHD fetuses and 248 cases of randomly selected normal fetuses were included in the study. Two sonographers with similar experience performed the cardiac screenings under two different protocols independently. The conventional protocol (Protocol A) paid greater attention to the four-chamber view and the outflow tract views. A 6-month training program was provided to sonographers performing scans under the new protocol (Protocol B), which emphasized systematically evaluating fetal cardiac anatomy and hemodynamics. Color Doppler was mandatory and some ultrasonic signs for special cardiac anomalies were also introduced into this protocol. RESULTS: Protocol B detected more cardiac anomalies than did Protocol A (96.2 % vs. 61.5 %, P < 0.01). Specifically, Protocol B was superior to Protocol A in detecting cardiac malpositions, abnormal systemic and pulmonary venous connection, right aortic arch, transposition of the great arteries, and congenital corrected transposition of the great arteries. By visualizing flow disturbance and retrograde flow with color Doppler, Protocol B was better than Protocol A in screening valvular associated malformations, such as pulmonary atresia, pulmonary stenosis, tricuspid dysplasia, etc. For the normal fetuses, Protocol B was better than Protocol A in reducing the false-positive detection of septal defects. CONCLUSIONS: The current study introduces an enhanced protocol for fetal cardiac screening, under which the obstetric screening sonographers systematically identify fetal cardiac anatomy and hemodynamics. A short-term training program makes it possible for the screening sonographers to become familiar with the new protocol, and its value has been confirmed due to improvements made in screening efficiency.
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Ecocardiografia Doppler em Cores/métodos , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Estudos de Casos e Controles , Protocolos Clínicos , Reações Falso-Negativas , Feminino , Coração Fetal/anatomia & histologia , Coração Fetal/fisiopatologia , Cardiopatias Congênitas/embriologia , Hemodinâmica , Humanos , Gravidez , Estudos ProspectivosRESUMO
PURPOSE: To evaluate the effectiveness of presence of desmopressin in treating primary enuresis (PE) for children with attention deficit-hyperactivity disorder (ADHD) symptoms. MATERIALS AND METHODS: Children aged from 5 to 12 years with the chief complaint of PE treated with desmopressin were enrolled in pediatric urology clinics. The parent-reported SNAP-IV questionnaire was used to evaluate ADHD symptoms (cut-off value: 90th percentile). Voiding symptoms were assessed by the Dysfunctional Voiding Scoring System (DVSS) questionnaire. The responses to desmopressin were analyzed in children with and without ADHD symptoms. RESULTS: The study sample comprised 68 children; 27 (39.7%) presented with ADHD symptoms and 41 (60.3%) with non-ADHD symptoms. The children collected from a tertiary referral center may explain the high prevalence of ADHD symptoms in the present study. The total DVSS score in the ADHD symptoms group was significantly higher than in the non-ADHD symptoms group (7.72 versus 5.65, P=0.05). In the ADHD symptoms group, there were significantly higher score in the "pee 1-2 times/day" and "can't wait" subscales of DVSS and lower sleep quality based on the Pediatric Sleep Quality questionnaire, as well as significantly lower peak flow rate and voided volume. The responses to desmopressin for enuresis were comparable between children with ADHD and non-ADHD symptoms. CONCLUSIONS: Approximately 39.7% of PE children presented with ADHD symptoms at urologic clinics. PE children with ADHD symptoms had higher risk of daytime LUTS and comparable response to desmopressin treatment for PE. To evaluate ADHD symptoms and daytime voiding symptoms is important in children with PE.
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Antidiuréticos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Desamino Arginina Vasopressina/uso terapêutico , Enurese/fisiopatologia , Micção , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Criança , Enurese/complicações , Enurese/tratamento farmacológico , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Malaria and schistosomiasis are endemic and co-exist in the same geographic areas, even co-infecting the same host. Previous studies have reported that concomitant infection with Schistosoma japonicum could offer protection against experimental cerebral malaria (ECM) in mice. This study was performed to evaluate whether alterations in parasite density could alter this protective effect. METHODS: Mice were inoculated with 100 or 200 S. japonicum cercariae followed by infection with high or low density of Plasmodium berghei ANKA strain eight weeks after the first infection. Then, parasitaemia, survival rate and blood-brain-barrier (BBB) damage were assessed. Interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, IL-13, IL-10, and TGF-ß levels were determined in splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA). Cell surface/intracellular staining and flow cytometry were used to analyse the level of CD4(+)/CD8(+) T cells, CD4(+)CD25(+)Foxp3(+) Tregs, IL-10-secreting Tregs, and IL-10(+)Foxp3-CD4(+) T cells in the spleen, and CD4(+)/CD8(+) T cells infiltrating the brain. RESULTS: Co-infection with low density P. berghei and increased S. japonicum cercariae significantly increased the levels of IL-4, IL-5, IL-13, TGF-ß and Tregs, but significantly decreased the levels of IFN-γ and the percentage of CD4(+) T cells and CD8(+) T cells in the spleen and CD8(+) T cell infiltration in the brain. Increased worm loads also significantly decreased mortality and BBB impairment during ECM. When challenged with higher numbers of P. berghei and increased cercariae, the observed cytokine changes were not statistically significant. The corresponding ECM mortality and BBB impairment also remained unchanged. CONCLUSIONS: This study demonstrates that protection for ECM depends on the numbers of the parasites, S. japonicum and P. berghei, during co-infection. Alterations in the regulatory response appear to play a key role in this adaptation.
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Coinfecção/imunologia , Malária Cerebral/imunologia , Plasmodium berghei/imunologia , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Animais , Coinfecção/parasitologia , Coinfecção/patologia , Citocinas/imunologia , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/parasitologia , Suscetibilidade a Doenças/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Tolerância Imunológica , Malária Cerebral/parasitologia , Malária Cerebral/patologia , Camundongos , Camundongos Endogâmicos C57BL , Parasitemia/imunologia , Parasitemia/parasitologia , Parasitemia/patologia , Esquistossomose Japônica/parasitologia , Esquistossomose Japônica/patologia , Baço/imunologiaRESUMO
BACKGROUND: We previously reported the use of a catheter system to damage the tricuspid valve and create infectious endocarditis (IE) in an animal model. The current study aims to create a faint IE model suitable for antibiotic prophylaxis using a low bacterial inoculum. We also aim to explore a way to quantitatively assess valvular impairment and to predict the success of the IE models during catheterization. METHODS: Ninety rabbits were assigned to two groups according to the density of bacteria inoculated (1 × 10(5) CFU for Group A and 1 × 10(4) CFU for Group B). A catheter system consisting of a polyethylene catheter and a guide wire were used to damage the valve. The catheter system was passed through the rabbits' tricuspid valves under echocardiographic guidance. A pressure transducer was used to assess right atrial pressure (P(RA)) before and just after valvular damage to calculate the pressure alterations (ΔP(RA)). The animals in group A and B were divided into 3 subgroups according to the ΔP(RA) (0-5 mmHg for Groups A1 and B1; 5-10 mmHg for Groups A2 and B2; 10-15 mmHg for Groups A3 and B3). Staphylococcus aureus (ATCC 29213) inoculation was performed 24 hr after cardiac catheterization. RESULTS: Faint IE was confirmed in 20%, 93.3%, 26.7%, 6.7%, 20%, and 33.3% of the rabbits in Groups A1, A2, A3, B1, B2, and B3, respectively. There was no difference in the LV/RV ratio and VTR of the No-IE, faint-IE, and severe IE animals. Faint IE rabbits had a larger ΔPRA than No-IE rabbits (7.81 ± 1.21 vs. 2.48 ± 1.0, P < 0.01, for Group A; 7.60 ± 1.32 vs. 2.98 ± 1.08, P < 0.01, for Group B). The ΔPRA of severe IE and faint IE rabbits was significantly different (13.11 ± 1.31 vs. 7.81 ± 1.21, P < 0.01, for Group A; 12.73 ± 1.44 vs.7.60 ± 1.32, P < 0.01, for Group B). CONCLUSION: ΔP(RA) could be used to assess valvular impairment. Controlling the value of ΔP(RA) during catheterization and inoculating of an appropriate dose of bacteria was associated with a successful IE model.
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Pressão Atrial/fisiologia , Cateterismo Cardíaco/métodos , Ecocardiografia/métodos , Endocardite Bacteriana/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Animais , Função do Átrio Direito/fisiologia , Modelos Animais de Doenças , Endocardite Bacteriana/microbiologia , Feminino , Masculino , Valor Preditivo dos Testes , Coelhos , Infecções Estafilocócicas/diagnóstico por imagem , Staphylococcus aureus , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/microbiologiaRESUMO
In order to improve the biocompatibility of metallic implants, bioactive components are often used as coatings so that a real bond with the surrounding bone tissue can be formed. We prepared ethyl cellulose/carbonated hydroxyapatite composite coatings (ECHCs) on Ti6Al4V substrates with carbonated hydroxyapatite coatings (CHACs) without ethyl cellulose as controls. The inorganic constituent on the CHACs and ECHCs is calcium-deficient carbonated hydroxyapatite with a flaky texture and a low degree of crystallinity. The flaky carbonated hydroxyapatite plates aggregate to form macropores with an aperture size of around 0.5-2.0 µm. The presence of ethyl cellulose provides superior morphology, contact angle, and biocompatibility characteristics. In comparison to CHACs, ECHCs exhibit a smoother, crack-free surface because the cracks are filled by ethyl cellulose. Moreover, the contact angle of ECHCs is 37.3°, greater than that of CHACs (13.0°). Surface biocompatibility was investigated by using human bone mesenchymal stem cells (hBMSCs). The attachment, spreadability, viability and proliferation of hBMSCs on ECHCs are superior to those on CHACs. Thus, the crack-free ECHCs have excellent biocompatibility and are appropriate for use as biological implants.
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Materiais Biocompatíveis , Carbonatos/química , Celulose/análogos & derivados , Durapatita , Titânio , Ligas , Células Cultivadas , Celulose/química , Humanos , Microscopia Eletrônica de Varredura , Difração de PóRESUMO
BACKGROUND: Since the outbreak of COVID-19, China has undertaken a variety of preventative and control measures, effectively reducing the incidence of numerous infectious diseases among the pediatric population in Hangzhou. We aim to investigate the genetic and epidemiological characteristics of Human parainfluenza virus-3 (HPIV-3) in pediatric patients during this period. METHODS: A total of 1442 pharyngeal swab samples were collected from outpatients and inpatients with a diagnosis of acute respiratory tract infections (ARTIs) from November 2020 to March 2021. HPIV-3 was detected by quantitative real time polymerase chain reaction (qRT-PCR). The L gene of HPIV-3 positive samples was amplified and sequenced. RESULTS: Among 1442 children with ARTI, the positive rate of HPIV-3 was 7.07% (102/1442). The positive detection rate was the highest in the 6-month to 1-year age group. Coinfection was observed in 36 HPIV-3-positive samples (35.29%, 36/102), and adenovirus (ADV) was the most common coinfecting virus (63.89%, 23/36). The L gene of 48 HPIV-3 positive samples was sequenced. The nucleotide sequence analysis showed high consistency (92.10%-99.40%), and all strains belonged to C3a. CONCLUSIONS: During study periods, the positive detection rate of HPIV-3 among children is high, and the highest proportion of coinfection was observed in HPIV-3 mixed ADV infection. Phylogenetic analysis revealed that the nucleotide sequence of the L gene of HPIV-3 was highly consistent, and the main epidemic strain in this area was the C3a subtype.
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Epidemiologia Molecular , Vírus da Parainfluenza 3 Humana , Filogenia , Infecções Respiratórias , Infecções por Respirovirus , Humanos , Vírus da Parainfluenza 3 Humana/genética , Vírus da Parainfluenza 3 Humana/isolamento & purificação , Vírus da Parainfluenza 3 Humana/classificação , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , China/epidemiologia , Pré-Escolar , Lactente , Masculino , Criança , Feminino , Infecções por Respirovirus/epidemiologia , Infecções por Respirovirus/virologia , Coinfecção/epidemiologia , Coinfecção/virologia , Adolescente , Recém-NascidoRESUMO
Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.
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Regulação Neoplásica da Expressão Gênica , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , ÍntronsRESUMO
Accumulating evidence has demonstrated that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of cells, play an important role in the subversion, inhibition, and downregulation of the immune response to cancer. However, the characteristics of these cells, particularly clinical relevance, in malignant tumors remain unclear due to a lack of specific markers. In this study, we characterized peripheral CD14(+)HLA-DR(-/low) cells, a new human MDSC subpopulation, in 89 patients with non-small cell lung cancer (NSCLC). As expected, both frequency and absolute number of CD14(+)HLA-DR(-/low) cells were significantly increased in the peripheral blood of NSCLC patients compared with that of the healthy controls and indicated an association with metastasis, response to chemotherapy, and progression-free survival. These cells showed decreased expression of CD16 and CD86 compared with HLA-DR(+) monocytes. Unlike classical monocytes, these populations showed significantly decreased allostimulatory activity and showed the ability to inhibit autologous T cell proliferation and IFN-γ production in a cell-contact-dependent manner. Furthermore, we demonstrated that CD14(+)HLA-DR(-/low) cells expressed the NADPH oxidase component gp91(phox) and generated high level of reactive oxygen species (ROS). Moreover, inactivation of ROS reversed their immunosuppressive capacity on T cell response. These results prove, for the first time, the existence of ROS-producing CD14(+)HLA-DR(-/low) myeloid-derived suppressor cells in NSCLC patients, which mediate tumor immunosuppression and might thus represent a potential target for therapeutic intervention.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Antígenos HLA-DR/imunologia , Receptores de Lipopolissacarídeos/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Células Mieloides/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Processos de Crescimento Celular/imunologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Feminino , Citometria de Fluxo , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Células Mieloides/patologia , Pemetrexede , Taxoides/administração & dosagem , GencitabinaRESUMO
BACKGROUND: Since helminths and malaria parasites are often co-endemic, it is important to clarify the immunoregulatory mechanism that occurs during the process of co-infection. A previous study confirmed that dendritic cells (DCs) are involved in the establishment and regulation of the T-cell-mediated immune response to malaria infection. In the current study, distinct response profiles for splenic DCs and regulatory T cell (Treg) responses were assessed to evaluate the effects of a pre-existing Schistosoma japonicum infection on malaria infection. METHODS: Malaria parasitaemia, survival rate, brain histopathology and clinical experimental cerebral malaria (ECM) were assessed in both Plasmodium berghei ANKA-mono-infected and S. japonicum-P. berghei ANKA-co-infected mice. Cell surface/intracellular staining and flow cytometry were used to analyse the level of splenic DC subpopulations, toll-like receptors (TLRs), DC surface molecules, Tregs (CD4âºCD25âºFoxp3âº), IFN-γ/IL-10-secreting Tregs, and IFN-γâº/IL-10âº-Foxp3â»CD4⺠T cells. IFN-γ, IL-4, IL-5, IL-10 and IL-13 levels were determined in splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA). RESULTS: The co-infected mice had significantly higher malaria parasitaemia, compared with the mono-infected mice, on days 2, 3, 7 and 8 after P. berghei ANKA infection. Mono-infected mice had a slightly lower survival rate, while clinical ECM symptoms, and brain pathology, were significantly more severe during the period of susceptibility to ECM. On days 5 and 8 post P. berghei ANKA infection, co-infected mice had significantly lower levels of CD11câºCD11bâº, CD11câºCD45R/B220âº, CD11câºTLR4âº, CD11câºTLR9âº, CD11câºMHCIIâº, CD11câºCD86âº, IFN-γ-secreting Tregs, and IFN-γâºFoxp3â»CD4⺠T cells in single-cell suspensions of splenocytes when compared with P. berghei ANKA-mono-infected mice. Co-infected mice also had significantly lower levels of IFN-γ and higher levels of IL-4, IL-5, and IL-13 in splenocyte supernatants compared to mono-infected mice. There were no differences in the levels of IL-10-secreting Tregs or IL-10âºFoxp3â»CD4⺠T cells between co-infected and mono-infected mice. CONCLUSIONS: A Tregs-associated Th2 response plays an important role in protecting against ECM pathology. Pre-existing S. japonicum infection suppressed TLR ligand-induced DC maturation and had an anti-inflammatory effect during malaria infection not only by virtue of its ability to induce Th2 responses, but also by directly suppressing the ability of DC to produce pro-inflammatory mediators.
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Malária/imunologia , Plasmodium berghei/imunologia , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Animais , Encéfalo/patologia , Células Dendríticas/imunologia , Modelos Animais de Doenças , Feminino , Histocitoquímica , Tolerância Imunológica , Imunofenotipagem , Malária/parasitologia , Malária/patologia , Camundongos , Camundongos Endogâmicos C57BL , Parasitemia/parasitologia , Esquistossomose Japônica/complicações , Esquistossomose Japônica/patologia , Baço/imunologia , Análise de Sobrevida , Linfócitos T Reguladores/imunologiaRESUMO
BACKGROUND: Fetal unilateral lung agenesis, complicated with cardiac shifting, is a rare anomaly, the diagnosis of which remains a challenge for many sonographers in routine screening programs. The present study describes a systematic approach for the diagnosis of fetal unilateral lung agenesis and cardiac malpositions in routine prenatal screening. METHODS: A total of 18 cases of fetal unilateral lung agenesis complicated with cardiac malposition were reviewed. A systematic method was proposed to identify the fetal left side and right side according to the fetal head position and posture by acquiring a long axis and transverse view of the fetus. Fetal unilateral lung agenesis was diagnosed by evaluation of the ipsilateral pulmonary artery. The diagnosis was confirmed by postnatal echocardiography, digital radiology, and computed tomography after birth or by autopsy findings. RESULTS: The left-sided fetal heart with the cardiac apex rotating to the left and posterior were confirmed in all 7 left lung agenesis cases, while the rightward shifting of the fetal heart together with the cardiac axis deviating to the right were confirmed in all 11 cases of right lung agenesis. The disappearance of the ipsilateral pulmonary artery was confirmed in all 18 cases of unilateral lung agenesis. Cardiac anomalies were present in a total of 7 of the 18 cases of lung agenesis with 4 of 7 in cases of left lung agenesis and 3 of 11 in cases of right agenesis. CONCLUSIONS: The systematic approach introduced in the current report is helpful in the diagnosis of fetal unilateral lung agenesis complicated with cardiac malposition. The information provided by this study may be helpful to better understand unilateral lung agenesis anatomically and to facilitate its potential examination.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Levocardia/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pulmão/anormalidades , Ultrassonografia Pré-Natal/métodos , Ecocardiografia Doppler em Cores , Feminino , Humanos , Pulmão/diagnóstico por imagem , Gravidez , Artéria Pulmonar/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: The most widely used experimental models of infective endocarditis (IE) are the rabbit and rat models, in which cardiac valve lesions are induced by a polyethylene catheter introduced into the left ventricle through the aortic valve. Our study was designed to create a rabbit model of IE right-sided with echocardiographic guidance. METHODS: Thirty rabbits underwent both catheterization and inoculation (group A). These were divided into three subgroups of ten based on the time of catheter removal (immediately, after 24 h, and after death or moribundity for groups, A(1), A(2), and A(3), respectively). Ten inoculated-only and ten catheterized-only rabbits served as controls. A catheter system consisted of a polyethylene catheter and a guide wire inside it. This system was passed through the rabbits' tricuspid valves under echocardiographic guidance to damage them. The ratio of left ventricle to right ventricle (LV/RV) was measured in a four-chamber view before catheterization and at the time of death or moribundity. The peak velocity of tricuspid regurgitation (V(TR)) was measured in a four-chamber view at the time of catheterization and at the time of death or moribundity. Staphylococcus aureus (ATCC 29213) inoculation was performed 24 h after right heart catheterization to produce IE. RESULTS: IE was confirmed in 28 of 30 rabbits by macroscopic and histologic examination of tricuspid valves, blood cultures, and bacterial count in cardiac vegetations. Cardiac vegetations were confirmed in 25 of 28 IE rabbits by echocardiography. Enlargement of right ventricle dimension with a significantly decreased LV/RV ratio was confirmed in all IE rabbits at the time of death or moribundity than at the initial state (1.11 ± 0.35 vs. 1.95 ± 0.39, P < 0.01; 1.21 ± 0.34 vs. 1.98 ± 0.35, P < 0.01; 1.04 ± 0.31 vs. 2.00 ± 0.41, P < 0.01 for groups A(1), A(2), and A(3), respectively). V(TR) was significantly higher in all the IE rabbits at the time of death or moribundity than at the time of catheterization (1.89 ± 0.46 vs 0.76 ± 0.45, P < 0.01; 2.04 ± 0.73 vs 0.68 ± 0.66, P < 0.01; 2.24 ± 0.51 vs 0.87 ± 0.55, P < 0.01 for group A(1), A(2), and A(3), respectively). CONCLUSION: The models described herein closely reproduced the pathogenesis and pathophysiology of right heart catheter-induced endocarditis in humans. Echocardiographic guidance is helpful in the process of right heart catheterization. Some echocardiographic parameters, such as V(TR) and the LV/RV ratio could be used to assess the success or failure of the IE models.
Assuntos
Ecocardiografia/métodos , Endocardite Bacteriana/diagnóstico por imagem , Infecções Estafilocócicas/diagnóstico por imagem , Staphylococcus aureus/isolamento & purificação , Animais , Cateterismo Cardíaco/efeitos adversos , Catéteres/microbiologia , Modelos Animais de Doenças , Endocardite Bacteriana/etiologia , Endocardite Bacteriana/microbiologia , Feminino , Masculino , Coelhos , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologiaRESUMO
BACKGROUND/PURPOSE: Children with attention deficit hyperactivity disorder (ADHD) tend to be more vulnerable to various forms of voiding dysfunction and nocturnal enuresis (NE). We attempt to compare the clinical manifestations and attentional performance between ADHD children with NE and those without NE. METHODS: We consecutively enrolled children diagnosed with ADHD in child and adolescent psychiatric clinics. The questionnaires for evaluation of ADHD symptoms and voiding dysfunction symptoms were administered to all study participants. All participants also received the Test Battery for Attention Performance (TAP) for assessment of attentional function. RESULTS: A total of 53 children were enrolled in this study, comprising 47 boys and six girls. The prevalence rate of NE was 28.3%. Children in the NE group had statistically significant higher dysfunctional voiding symptom score (5.40 ± 3.66 vs.3.16 ± 2.74; p = 0.018) and two subscales of "When I wet myself, my underwear is soaked" (p < 0.001) and "I miss having a bowel movement every day" (p = 0.047). There were no significant differences with regard to all psychiatric evaluations between the NE and non-NE groups. In the TAP test, the NE group showed a significantly shorter reaction time in the domain of inhibitory control, working memory, and auditory sustained attention than the non-NE group. CONCLUSION: Children with ADHD have a high prevalence of NE. ADHD children with NE had a significantly higher dysfunctional voiding symptom score and shorter reaction time in most domains of the TAP test. Further study is needed to discern the impact of NE on the neuropsychological function of ADHD children.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Atenção , Enurese Noturna/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Enurese Noturna/complicações , Análise e Desempenho de TarefasRESUMO
BACKGROUND/PURPOSE: Current guidelines recommend that hypospadias repair should be performed before age 18 months. This study aims to investigate the trends of surgical timing and to determine what factors are associated with age at surgery. METHODS: The present study utilized a subset of the National Health Insurance Research Database, known as Longitudinal Health Insurance Database 2005, which contains the data of all paid medical benefit claims over the period from 1997 to 2007 for a subset of one million beneficiaries randomly drawn from the population of 22.72 million individuals in NHI program during any part of calendar year 2005. We analyzed claims data for all subjects with the diagnoses of hypospadias. RESULTS: Among 52,705 live male newborns, 218 were diagnosed with hypospadias and thus were included as subjects in our study. Among them, 89 received repair surgery. Approximately 60.6% of the study subjects received repair after the age of 18 months. Multivariate analysis showed that several factors were significantly associated with age at hypospadias surgery: specialty of clinics where first diagnosis was made; specialty of physician making the first diagnosis, age of physician making the first diagnosis; specialty of surgeon performing the surgery; number of years since surgeon's board certification; urbanization level of subject's residence; modality of surgery; concomitant cryptorchidism; concomitant prematurity and low birth weight; age at diagnosis; and number of well-baby clinic visits. CONCLUSION: This study addresses an important issue of delayed hypospadias surgery in Taiwan, which provides a potential opportunity for improvement in quality of care.
Assuntos
Hipospadia/diagnóstico , Hipospadia/cirurgia , Médicos/estatística & dados numéricos , Tempo para o Tratamento/tendências , Fatores Etários , Peso ao Nascer , Competência Clínica , Criptorquidismo/complicações , Cirurgia Geral/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Humanos , Hipospadia/complicações , Lactente , Masculino , Pediatria/estatística & dados numéricos , Nascimento Prematuro , Especialização/estatística & dados numéricos , Taiwan , Urologia/estatística & dados numéricosRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is one of the main pathogens that causes acute lower respiratory tract infection (ARTI) in infants. During the Coronavirus Disease 2019 (COVID-19) pandemic, although strict interventions have been implemented, RSV infection has not decreased. OBJECTIVES: To study the epidemiological and genetic characteristics of RSV circulating in Hangzhou after the peak of COVID-19. METHODS: A total of 1225 nasopharyngeal swabs were collected from outpatients with ARTIs from July 2021 to January 2022 in The Children's Hospital, Zhejiang University School of Medicine. RESULTS: A total of 267 (21.79%) of the 1225 samples were RSV positive. There was no gender bias. However, an obvious age preference for infection was observed, and children aged 3-6 years were more susceptible, which was very different from previous RSV pandemic seasons. Phylogenetic analysis of 115 sequenced RSV isolates showed that all the RSV-A viruses belong to the ON1 subtype, which could be clustered into three clusters. While all the RSV-B viruses belong to BA9. Further analysis of the mutations highlights the fixation of ten mutations, which should be given extra attention regarding their biological properties. CONCLUSION: The incidence of RSV infection in preschool children reported in this study is high. Phylogenetic analysis showed that the subtype A ON1 genotype was the dominant strain in Hangzhou from July 2021 to January 2022.
Assuntos
COVID-19 , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Lactente , Pré-Escolar , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Filogenia , COVID-19/epidemiologia , GenótipoRESUMO
PURPOSE: We clarified correlations between symptoms of attention deficit disorder with hyperactivity and voiding dysfunction in children. MATERIALS AND METHODS: The study sample consisted of 92 boys and 38 girls 4 to 14 years old who presented at pediatric urology clinics with untreated lower urinary tract symptoms. Parents completed the Swanson, Nolan and Pelham-IV scale. Each subject with a combined score in the first 2 subscales (inattention, hyperactivity/impulsivity) at or above the 90th percentile was classified as having symptoms of attention deficit disorder with hyperactivity. All other cases were classified as nonattention deficit disorder. Voiding dysfunction symptoms were assessed by the Dysfunctional Voiding Symptom Scale. Sleep quality was assessed by the Pediatric Sleep Questionnaire. We then analyzed correlations between Dysfunctional Voiding Symptom Scale and symptoms of attention deficit disorder with hyperactivity. RESULTS: The group with symptoms of attention deficit disorder with hyperactivity had significantly higher scores on the Dysfunctional Voiding Symptom Scale overall and in the "cannot wait" subscale compared to the group without attention deficit disorder, as well as poorer sleep quality and lower voiding volumes. Overall Dysfunctional Voiding Symptom Scale scores were significantly correlated with overall Swanson, Nolan and Pelham-IV scale scores and also significantly correlated with each of the 3 Swanson, Nolan and Pelham-IV subscales (inattention, hyperactivity/impulsivity and oppositional defiant). Overall Dysfunctional Voiding Symptom Scale scores and scores on the "cannot wait" and "hurt when pee" subscales were significantly higher for males than for females. CONCLUSIONS: Boys with higher scores of attention deficit disorder with hyperactivity symptoms tend to have higher Dysfunctional Voiding Symptom Scale scores. Lower urinary tract symptoms were significantly correlated with overall Swanson, Nolan and Pelham-IV scores and significantly correlated with each of the 3 subscales. Evaluation of concomitant symptoms of attention deficit disorder with hyperactivity in children with lower urinary tract symptoms is an important clinical concern.