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1.
J Virol ; 95(23): e0061021, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34523972

RESUMO

Plasmablasts represent a specialized class of antibody-secreting effector B cells that transiently appear in blood circulation following infection or vaccination. The expansion of these cells generally tends to be massive in patients with systemic infections such as dengue or Ebola that cause hemorrhagic fever. To gain a detailed understanding of human plasmablast responses beyond antibody expression, here, we performed immunophenotyping and RNA sequencing (RNA-seq) analysis of the plasmablasts from dengue febrile children in India. We found that plasmablasts expressed several adhesion molecules and chemokines or chemokine receptors that are involved in endothelial interactions or homing to inflamed tissues, including skin, mucosa, and intestine, and upregulated the expression of several cytokine genes that are involved in leukocyte extravasation and angiogenesis. These plasmablasts also upregulated the expression of receptors for several B-cell prosurvival cytokines that are known to be induced robustly in systemic viral infections such as dengue, some of which generally tend to be relatively higher in patients manifesting hemorrhage and/or shock than in patients with mild febrile infection. These findings improve our understanding of human plasmablast responses during the acute febrile phase of systemic dengue infection. IMPORTANCE Dengue is globally spreading, with over 100 million clinical cases annually, with symptoms ranging from mild self-limiting febrile illness to more severe and sometimes life-threatening dengue hemorrhagic fever or shock, especially among children. The pathophysiology of dengue is complex and remains poorly understood despite many advances indicating a key role for antibody-dependent enhancement of infection. While serum antibodies have been extensively studied, the characteristics of the early cellular factories responsible for antibody production, i.e., plasmablasts, are only beginning to emerge. This study provides a comprehensive understanding of the transcriptional profiles of human plasmablasts from dengue patients.


Assuntos
Dengue/imunologia , Imunofenotipagem/métodos , Plasmócitos/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Facilitadores , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Citocinas/genética , Vírus da Dengue/imunologia , Humanos , Índia , Plasmócitos/metabolismo
2.
Arch Virol ; 166(7): 1913-1920, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33907861

RESUMO

Chikungunya virus (CHIKV) infection is endemic in many different countries. CHIKV outbreaks are emerging in new areas and re-emerging in previously exposed geographical regions, thus making it a significant public health concern. CHIKV infections are often clinically inapparent, especially in children, which poses a challenge to testing and evaluating any vaccine. During CHIKV infection, CHIKV-specific antibodies are produced, and some of these antibodies can neutralize viruses released from infected cells before they can enter uninfected cells. In this study, we evaluated IgG binding and neutralizing antibody responses in paired serum samples from CHIKV-infected children and those with other febrile illness, using a recombinant truncated E2 protein and whole CHIKV particles as test antigens. Antibody detection using the truncated E2 protein showed a significant overlap between CHIKV-infected subjects and those with other febrile illnesses. This overlap was greater when binding antibody titers were determined using fixed CHIKV particles as the test antigen. Acute- and convalescent-phase sera collected from children after CHIKV infection showed significant differences in their neutralizing capacity. The neutralizing and binding antibody response showed a significant positive correlation. We detected IgG antibodies in most cases during the acute phase of infection. This was observed at two different geographical locations, one of which is not considered highly endemic. Conventional wisdom would suggest this to be a marker of re-infection (secondary infection). However, dissenting opinions have been voiced in other viral diseases (such as Ebola) where studies have detected IgG in acute illness. In the absence of any significant body of work documenting secondary CHIKV infections, we believe further work is needed to understand the early IgG response that we observed.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Imunoglobulina G/imunologia , Febre de Chikungunya/virologia , Criança , Feminino , Humanos , Índia , Masculino , Proteínas do Envelope Viral/imunologia
3.
RNA Biol ; 18(sup2): 604-611, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34747322

RESUMO

By analysis of lncRNA expression profiles of macrophages in response to Mycobacterium tuberculosis (Mtb) infection, we identified novel highly expressed transcripts, unique in encompassing a protein coding transcript- Cytidine Monophosphate Kinase 2 (CMPK2) and a previously identified lncRNA- Negative Regulator of Interferon Response (NRIR). While these transcripts (TILT1, 2,3 - TLR4 and Infection induced Long Transcript) are induced by virulent Mtb as well as lipopolysaccharide (LPS) early, lack of/delayed expression in non-viable Mtb/BCG infected cells, respectively, suggest an important role in macrophage responses. The elevated expression by 3 hr in response to fast growing bacteria further emphasizes the importance of these RNAs in the macrophage infection response. Overall, we provide evidence for the presence of multiple transcripts that form a part of the early infection response programme of macrophages.Abbreviations: IFN: Interferon; NRIR: negative regulator of interferon response; CMPK2: cytidine/ uridine monophosphate kinase; LPS: lipopolysaccharide; LAM: Lipoarabinomannan; PIMs: Phosphatidylinositol Mannosides; TILT1, 2,3: TLR4 and Infection induced Long Transcript; TLR4: Toll-like receptor 4; Mtb: Mycobacterium tuberculosis; BCG: Mycobacterium bovis BCG; MDMs: human monocyte derived macrophages.


Assuntos
Interações Hospedeiro-Patógeno/genética , Macrófagos/metabolismo , Macrófagos/microbiologia , Mycobacterium tuberculosis , Transcriptoma , Tuberculose/genética , Tuberculose/microbiologia , Linhagem Celular , Epistasia Genética , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Macrófagos/imunologia , RNA Longo não Codificante/genética , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Tuberculose/imunologia
4.
J Food Sci Technol ; 57(10): 3903-3912, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32903915

RESUMO

The present work was undertaken with an objective to evaluate the impact of temperature on respiration rate of fresh black carrot using a non-linear enzyme kinetics approach. Two different models viz. Arrhenius equation (temperature effect) and enzyme kinetics (effect of temperature and headspace concentration) have been compared for predicting the respiration rate of black carrot. The respiratory behavior of black carrot was assessed using closed system technique at 5, 10 and 15 °C (± 1 °C) temperature and constant relative humidity (RH) of 85%. The O2 consumption and CO2 evolution rate values were 39.17, 58.88 and 68.08 ml kg-1 h-1; 22.15, 34.63 and 41.86 ml kg-1 h-1 after the attainment of steady-state condition at 5, 10 and 15 °C, respectively. The inhibition by evolved CO2 was found to be predominantly competitive at all temperatures. The average absolute deviation in O2 consumption and CO2 evolution rate for Arrhenius model was 3.5% and 5.3% while for enzyme kinetics model was 8.8% and 6.3%, respectively. Dependency of respiration rate of black carrot on temperature was well defined by Arrhenius model. The outcomes of the study can be further utilized to design the MAP (modified atmosphere packages) for fresh black carrot storage at 5 °C with 85% RH.

5.
J Med Virol ; 90(7): 1222-1231, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29575050

RESUMO

B-cells play an important role in defending children against various infections. In view of scare data, we undertook this prospective cohort study to describe B cell compartment in HIV infected children (<5 years of age) and the effect of HAART on B cell subpopulations. HIV infected children (<5 years) from Pediatric HIV services of the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, were recruited (April 2012-December 2015). The enrolled HIV-1 infected children (n = 59) were followed up regularly for 12 months; healthy controls (n = 51) included HIV uninfected children with no major illness. Flow cytometry was performed on fresh EDTA-treated blood samples to characterize B cell subpopulations. In HIV-infected children, marked depletion of naive (P = 0.003), non-switched memory (P = 0.02), mature (P = 0.0005), resting memory (P < 0.0001) B cells, and expansion of double negative memory (P < 0.0001), activated memory (P < 0.0001) and tissue like memory (P < 0.0001) B cells were observed as compared to healthy controls. In children started on HAART, at the end of 12 months of therapy, frequencies of non-switched memory (P = 0.04), switched memory (P = 0.01), and resting memory (P = 0.003) B cells were lower; activated memory (P = 0.04), and tissue-like memory (P = 0.0001) B cells were still higher than healthy controls. HIV infection resulted in reduced memory B cells in HIV infected children. Following HAART, there was normalization of some B cell subpopulations. The study emphasizes the need of re-vaccination in HIV infected children to maintain the memory B cell pool and adequate humoral immune response against infections.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Pré-Escolar , Feminino , Citometria de Fluxo , Seguimentos , HIV-1/isolamento & purificação , Humanos , Índia , Lactente , Masculino , Estudos Prospectivos , Resultado do Tratamento
6.
J Gen Virol ; 98(7): 1879-1891, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28696188

RESUMO

Delineating the factors leading to the development of broadly neutralizing antibodies (bnAbs) during natural HIV-1 infection and dissecting their epitope specificities generates useful information for vaccine design. This is the first longitudinal study to assess the plasma-neutralizing antibody response and neutralizing determinants in HIV-1-infected children from India. We enrolled 26 and followed up 20 antiretroviral therapy (ART)-naïve, asymptomatic, chronic HIV-1-infected children. Five (19.2 %) baseline and 10 (50 %) follow-up plasma samples neutralized ≥50 % of subtypes A, B and C tier 2 viruses at an ID50 titre ≥150. A modest improvement in neutralization breadth and potency was observed with time. At baseline, subtype C-specific neutralization predominated (P=0.026); interestingly, follow-up samples exhibited cross-neutralizing activity. Epitope mapping revealed V3C reactive antibodies with significantly increased Max50 binding titres in follow-up samples from five infected children; patient #4's plasma antibodies exhibited V3-directed neutralization. A salient observation was the presence of CD4 binding site (CD4bs)-specific NAbs in patient #18 that improved with time (1.76-fold). The RSC3 wild-type (RSC3WT) protein-depleted plasma eluate of patient #18 demonstrated a more than 50% ID50 decrease in neutralization capacity against five HIV-1 pseudoviruses. Further, the presence of CD4bs-neutralizing determinants in patient #18's plasma was confirmed by the neutralizing activity demonstrated by the CD4bs-directed IgG fraction purified from this plasma, and competition with sCD4 against JRFLgp120, identifying this paediatric donor as a potential candidate for the isolation of CD4bs-directed bnAbs. Overall, we observed a relative increase in plasma-neutralizing activity with time in HIV-1-infected children, which suggests that the bnAbs evolve.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Proteção Cruzada/imunologia , Epitopos/imunologia , Anticorpos Anti-HIV/sangue , HIV-1/classificação , HIV-1/imunologia , Adolescente , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Mapeamento de Epitopos , Feminino , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Índia , Estudos Longitudinais , Masculino , Fragmentos de Peptídeos/imunologia
7.
J Virol ; 90(24): 11259-11278, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27707928

RESUMO

Epidemiological studies suggest that India has the largest number of dengue virus infection cases worldwide. However, there is minimal information about the immunological responses in these patients. CD8 T cells are important in dengue, because they have been implicated in both protection and immunopathology. Here, we provide a detailed analysis of HLA-DR+ CD38+ and HLA-DR- CD38+ effector CD8 T cell subsets in dengue patients from India and Thailand. Both CD8 T cell subsets expanded and expressed markers indicative of antigen-driven proliferation, tissue homing, and cytotoxic effector functions, with the HLA-DR+ CD38+ subset being the most striking in these effector qualities. The breadth of the dengue-specific CD8 T cell response was diverse, with NS3-specific cells being the most dominant. Interestingly, only a small fraction of these activated effector CD8 T cells produced gamma interferon (IFN-γ) when stimulated with dengue virus peptide pools. Transcriptomics revealed downregulation of key molecules involved in T cell receptor (TCR) signaling. Consistent with this, the majority of these CD8 T cells remained IFN-γ unresponsive even after TCR-dependent polyclonal stimulation (anti-CD3 plus anti-CD28) but produced IFN-γ by TCR-independent polyclonal stimulation (phorbol 12-myristate 13-acetate [PMA] plus ionomycin). Thus, the vast majority of these proliferating, highly differentiated effector CD8 T cells probably acquire TCR refractoriness at the time the patient is experiencing febrile illness that leads to IFN-γ unresponsiveness. Our studies open novel avenues for understanding the mechanisms that fine-tune the balance between CD8 T cell-mediated protective versus pathological effects in dengue. IMPORTANCE: Dengue is becoming a global public health concern. Although CD8 T cells have been implicated both in protection and in the cytokine-mediated immunopathology of dengue, how the balance is maintained between these opposing functions remains unknown. We comprehensively characterized CD8 T cell subsets in dengue patients from India and Thailand and show that these cells expand massively and express phenotypes indicative of overwhelming antigenic stimulus and tissue homing/cytotoxic-effector functions but that a vast majority of them fail to produce IFN-γ in vitro Interestingly, the cells were fully capable of producing the cytokine when stimulated in a T cell receptor (TCR)-independent manner but failed to do so in TCR-dependent stimulation. These results, together with transcriptomics, revealed that the vast majority of these CD8 T cells from dengue patients become cytokine unresponsive due to TCR signaling insufficiencies. These observations open novel avenues for understanding the mechanisms that fine-tune the balance between CD8-mediated protective versus pathological effects.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Citotoxicidade Imunológica , Vírus da Dengue/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Transcriptoma/imunologia , ADP-Ribosil Ciclase 1/genética , ADP-Ribosil Ciclase 1/imunologia , Adolescente , Anticorpos/farmacologia , Antígenos CD28/antagonistas & inibidores , Antígenos CD28/genética , Antígenos CD28/imunologia , Complexo CD3/genética , Complexo CD3/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/virologia , Proliferação de Células/efeitos dos fármacos , Criança , Pré-Escolar , Vírus da Dengue/genética , Vírus da Dengue/crescimento & desenvolvimento , Vírus da Dengue/metabolismo , Feminino , Regulação da Expressão Gênica , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Humanos , Imunidade Celular , Índia , Lactente , Interferon gama/genética , Interferon gama/imunologia , Ionomicina/farmacologia , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Cultura Primária de Células , RNA Helicases/genética , RNA Helicases/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Serina Endopeptidases/genética , Serina Endopeptidases/imunologia , Transdução de Sinais , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/virologia , Acetato de Tetradecanoilforbol/farmacologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia
8.
BMC Infect Dis ; 15: 126, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25887748

RESUMO

BACKGROUND: The available pharmacokinetic data on anti-tubercular drugs in children raises the concern of suboptimal plasma concentrations attained when doses extrapolated from adult studies are used. Also, there is lack of consensus regarding the effect of malnutrition on pharmacokinetics of anti-tubercular drugs in children. We conducted this study with the aims of determining the plasma concentrations of isoniazid, rifampicin, pyrazinamide and ethambutol achieved with different dosage of the anti-tubercular drugs so as to provide supportive evidence to the revised dosages and to evaluate the effects of malnutrition on the pharmacokinetics of these drugs in children. We also attempted to correlate the plasma concentrations of these drugs with clinical outcome of therapy. METHOD: Prospective drug estimation study was conducted in two groups of children, age 6 months to 15 years, with tuberculosis, with or without severe malnutrition, receiving different dosage of daily anti- tubercular therapy. The dosage (range) of isoniazid was 5 (4-6) and 10 (7-15) mg/kg in the two groups, respectively, that of rifampicin-10 (8-12) and 15 (10-12) mg/kg, respectively, both the groups received same dose of pyrazinamide (30-35 mg/kg) and ethambutol (20-25 mg/kg). All four drugs were simultaneously estimated by liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS AND CONCLUSION: The median (IQR) Cmax of isoniazid increased significantly from 0.6 (0.3,1.2) µg/mL to 3.4 (1.8, 5.0) µg/mL with increase in the dose. Plasma rifampicin concentrations increased only marginally on increasing the dose [median (IQR) Cmax: 10.4 (7.2, 13.9) µg/mL vs. 12.0 (6.1, 24.3) µg/mL, p=0.08]. For ethambutol, 55.9% of the children had inadequate 2-hour concentrations. Two-hour plasma concentrations of at least one drug were low in 59 (92.2%) and 54 (85.7%) children in the two dosing regimen, respectively. We did not observe any effect of malnutrition on pharmacokinetic parameters of the drugs studied. We did not observe an association between low plasma drug concentrations and poor outcome. We may have to be cautious while increasing the doses and strive to asses other factors influencing the drug concentrations and treatment outcomes in children.


Assuntos
Antituberculosos/farmacocinética , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Antituberculosos/administração & dosagem , Área Sob a Curva , Criança , Pré-Escolar , Etambutol/administração & dosagem , Etambutol/farmacocinética , Etnicidade , Feminino , Humanos , Índia , Lactente , Isoniazida/administração & dosagem , Isoniazida/farmacocinética , Masculino , Estudos Prospectivos , Pirazinamida/administração & dosagem , Pirazinamida/farmacocinética , Análise de Regressão , Rifampina/administração & dosagem , Rifampina/farmacocinética , Espectrometria de Massas em Tandem , Resultado do Tratamento , Tuberculose Pulmonar/metabolismo
9.
Cutan Ocul Toxicol ; 33(4): 289-93, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24517496

RESUMO

CONTEXT: Medication-related adverse events, apart from causing significant morbidity and mortality, increase the healthcare cost burden and lead to early treatment discontinuations. OBJECTIVES: Knowing the fact that cutaneous adverse drug reactions (cADRs) are most frequent, this study was conducted with an aim to describe their clinical profiles and preventive strategies. METHODS: All adverse drug reaction (ADR) forms filled from January 2012 to January 2013 were scrutinised and forms with cADRs analysed and assessed for causality, preventability and severity. RESULTS: Of 400 ADR forms, 109 included cADRs. Sixty-eight percent patients were males and mean ± SD age was 35 ± 18 years. Rash, Steven-Johnson syndrome and toxic epidermal necrolysis were the most common presentations. Most frequent culprit drugs included antibiotics and anti-inflammatory agents. Causality was probable or possible in majority. Ninety percent cases were "not preventable". Majority of the patients had mild to moderate reactions and recovered completely after medical management. CONCLUSIONS: Pharmacovigilance, with special attention to monitoring and reporting of cADRs must be encouraged. As major bulk of cADRs result from physician prescribed drugs, awareness on part of the physician can help in their timely detection and management, thereby restricting the associated damage.


Assuntos
Toxidermias , Farmacovigilância , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Toxidermias/epidemiologia , Toxidermias/patologia , Toxidermias/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Pele/patologia , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
10.
CJC Pediatr Congenit Heart Dis ; 3(2): 74-78, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38774680

RESUMO

Background: Electrocardiographic early repolarization (EER) is linked with idiopathic ventricular fibrillation in adults. It is frequently seen in children, with poorly understood significance. Some evidence suggests that it could be a vagally mediated phenomenon. A retrospective case-control study was undertaken to test the hypothesis that EER is more common among children with typical vasovagal syncope (VVS) than among their peers with nonvagal syncope (NVS) or with no syncope. Methods: Patients aged 4-18 years with syncope were identified by a single-centre database search followed by a review of history for features of VVS (n = 150) or NVS (n = 84). The first available electrocardiogram (ECG) for VVS or for NVS was retrieved. Age- and sex-matched children with no known syncope or heart disease were then identified (n = 216). ECGs were assessed separately for EER based on published criteria by 2 observers blinded to patients' clinical status. Results: Mean age was 12.3 ± 3.2 years, and heart rate was 74.2 ± 16.5 beats/min. EER was more prevalent in VVS (33.3%) than among patients with NVS (19.1%; odds ratio: 2.29; confidence interval: 1.32-5.50) or among those with no syncope (12.5%; odds ratio: 3.14; confidence interval: 1.81-5.46). Heart rates were significantly lower in VVS and NVS (heart rate: 70.1 ± 13.8 and 70.7 ± 12.4 beats/min, respectively) compared with children with no syncope (heart rate: 78.2 ± 18.0 beats/min), both P < 0.001. Conclusions: EER is more common in paediatric patients with VVS than those with NVS or without syncope, consistent with a possible vagal contribution to the ECG finding.


Contexte: La repolarisation précoce (RP) à l'électrocardiogramme (ECG) est liée à une fibrillation ventriculaire idiopathique chez les adultes. Fréquente chez les enfants, sa signification est toutefois nébuleuse. Certaines données laissent penser qu'il pourrait s'agir d'un phénomène d'origine vagale. Une étude rétrospective cas-témoins a donc été réalisée dans le but de vérifier l'hypothèse selon laquelle la RP à l'ECG est plus courante chez les enfants atteints de syncope vasovagale (SVV) typique que chez leurs pairs atteints de syncope non vagale (SNV) ou non atteints de syncope. Méthodologie: Des patients de 4 à 18 ans atteints de syncope ont été recensés au moyen d'une recherche dans la base de données d'un centre, suivie d'un examen des antécédents visant à retracer des manifestations de SVV (n = 150) ou de SNV (n = 84). Le premier ECG disponible traduisant une SVV ou une SNV a été récupéré. Un appariement selon l'âge et le sexe entre les sujets atteints et des enfants qui n'étaient pas atteints de syncope ni de maladie cardiaque (n = 216) a ensuite été effectué. Deux observateurs qui ne connaissaient pas l'état clinique des enfants ont évalué les ECG séparément, à la recherche d'une RP, en se basant sur les critères publiés. Résultats: L'âge moyen des sujets était de 12,3 ± 3,2 ans et la fréquence cardiaque moyenne, de 74,2 ± 16,5 battements/minute. La prévalence de la RP à l'ECG était plus élevée chez les patients atteints de SVV (33,3 %) que chez les patients atteints de SNV (19,1 %; rapport de cotes [RC] : 2,29; intervalle de confiance [IC] : 1,32-5,50) ou les enfants non atteints de syncope (12,5 %; RC : 3,14; IC : 1,81-5,46). La fréquence cardiaque (FC) était significativement plus faible chez les sujets atteints de SVV ou de SNV (FC : 70,1 ± 13,8 et 70,7 ± 12,4 battements/minute, respectivement), en comparaison des enfants non atteints de syncope (FC : 78,2 ± 18,0 battements/minute); p < 0,001 dans les deux cas. Conclusion: La repolarisation précoce à l'ECG est plus courante chez les enfants atteints de syncope vasovagale que chez les enfants atteints de syncope non vagale ou non atteints de syncope, ce qui concorde avec une possible composante vagale dans le tracé de l'ECG.

11.
J Orthop Surg Res ; 19(1): 135, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347592

RESUMO

BACKGROUND: In patients with COVID-19 infection and respiratory insufficiency, corticosteroid (CCS) administration is recommended. Among the wide range of complications and interactions, time-limited high-dose CCS administration might promote avascular necrosis (AVN) in a cumulative dose. This systematic review updated the current evidence and characterises the trend of AVN following time-limited high-dose CCS administration in patients who had severe COVID-19, discussing management strategies and outcomes. METHODS: This systematic review was conducted according to the 2020 PRISMA statement. In October 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Scopus restricting the search to the years 2019 to 2023. All the clinical studies which investigated the association between time-limited high-dose CCS administration in patients with severe COVID-19 infection and AVN were accessed. RESULTS: A total of 245 patients (9 studies) who experienced AVN following COVID-19 were included in the present investigation. 26% (63 of 245 included patients) were women. The mean age of the patients was 42.9 ± 17.7 years. Four studies focused on AVN of the hip and two on the knee, and the other studies included patients with AVN from mixed areas of the body (spine, pelvis, and shoulder). The mean time elapsed from COVID-19 infection to the development of symptomatic AVN was 79.4 ± 59.2 days (range, 14 to 166 days). CONCLUSION: It is possible that even time-limited high-dose CCS administration in patients with severe COVID-19 infection increased the incidence of AVN. The mean time elapsed from COVID-19 infection to the development of symptomatic AVN was approximately 80 days. Given the high risk of bias in all the included studies, the quality of recommendations of the present investigation is low, and no reliable conclusion can be inferred.


Assuntos
COVID-19 , Osteonecrose , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Pandemias , Fatores de Risco , COVID-19/epidemiologia , Corticosteroides/efeitos adversos , Osteonecrose/induzido quimicamente , Osteonecrose/epidemiologia , Estudos Retrospectivos
12.
Nat Med ; 30(3): 670-674, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321219

RESUMO

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.


Assuntos
Coinfecção , Vírus da Dengue , Dengue , Dengue Grave , Humanos , Criança , Dengue/epidemiologia , Dengue Grave/epidemiologia , Anticorpos Antivirais , Coinfecção/epidemiologia , Febre
13.
Pediatr Cardiol ; 34(8): 1941-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22926400

RESUMO

A ventriculoseptal defect (VSD) usually is present in patients with a double-outlet right ventricle. This report describes a case of double-outlet right ventricle with a completely shrouded inlet VSD and no interventricular shunting. This was associated with a severely regurgitant dysplastic mitral valve. The anatomy and clinical management of the patient is discussed together with an overview of the existing literature.


Assuntos
Anormalidades Múltiplas , Dupla Via de Saída do Ventrículo Direito/diagnóstico , Comunicação Interventricular/diagnóstico , Procedimentos Cirúrgicos Cardíacos , Diagnóstico Diferencial , Dupla Via de Saída do Ventrículo Direito/cirurgia , Ecocardiografia Doppler em Cores , Eletrocardiografia , Feminino , Comunicação Interventricular/cirurgia , Humanos , Recém-Nascido , Imagem Cinética por Ressonância Magnética
14.
Cureus ; 14(9): e29788, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36340544

RESUMO

INTRODUCTION: Giant cell tumor (GCT) is a benign but locally aggressive bone tumor. It has a peak incidence between 30-40 years with a predilection for the epiphyseal/metaphyseal region of bone. The most common locations for bone GCT are the distal femur, proximal tibia, distal radius, and sacrum in decreasing order. MATERIAL AND METHODS: In this retrospective study, 22 patients (13 females and nine males) with recurrent giant cell tumors around the knee joint between 2009-2022, with a mean age of 30.2 years (range: 18-55) were included. The patients were followed up monthly for three months, three-monthly for the next two years, six-monthly for the next five years, and thereafter, yearly. The mean follow-up period was 36.97 months (range 23-120 months). RESULTS: There were 19 recurrences after curettages and three after resections. Re-extended curettage was done in 17 cases and the resultant cavities were filled with autologous bone grafts in six and with polymethyl methacrylate (PMMA) cement in the other 11 cases. Reconstruction with megaprosthesis was done in two patients whereas knee arthrodesis was done in two patients after wide resection. The average Musculoskeletal Tumor Society (MSTS) score of our series of 22 patients was 23.1 (Range: 19-30). CONCLUSION: Campanacci grade 1 and 2 lesions can be successfully treated with extended curettage and bone grafting/bone cementing. For patients with grade 3 lesions, there are two options available according to the financial status of the patient; the first option is reconstruction with prosthesis and the other option is arthrodesis.

15.
Cureus ; 14(7): e27451, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36051721

RESUMO

INTRODUCTION: Distal end radius is the second most common location for giant cell tumours (GCTs) followed by the knee. Like at any other location, they are treated with extended curettage or resection but reportedly have an increased propensity for recurrence. This study aims to treat the recurrent distal end radius GCTs and their outcome after further surgeries. PATIENTS AND METHODS: This study was conducted retrospectively from 2009 to 2021 and included 32 patients with recurrent distal end radius GCTs with a mean age of 29.53 years (range: 18-45 years). Twenty-five recurrences occurred after curettage and seven after resection. Twelve lesions were treated with further extended curettage. Nineteen recurrent lesions were treated with resection and arthrodesis. One out of two soft tissue recurrences was treated with en bloc resection. The mean follow-up period was 45.25 months (range: 24-120). RESULTS: The patients with joint preservations treated with further curettage and those where resection of soft tissue recurrences was done with salvage of joint had better functional outcomes with a mean Musculoskeletal Tumor Society (MSTS) score of 26.53 (Range: 22-30). The cases with arthrodesis had an average score of 23.75 (Range: 20-26). The overall average MSTS score was 24.89. CONCLUSIONS: We conclude that local recurrence contained within the bone can be re-curetted. The isolated soft tissue recurrences can be re-excised. The bony lesions with extensive soft tissue extension should be treated with resection and reconstruction. The re-recurrence rate after further adequate treatment does not increase much.

16.
Cureus ; 14(7): e27329, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36042997

RESUMO

Background Soft-tissue sarcomas (STSs) are a rare heterogeneous group of tumors. Good functional results can be achieved with tumor excision in combination with suitable supplemental adjuvant therapies if needed. This study aimed to investigate the outcomes of wide resection of STS of the extremities. Methodology In this retrospective study, a total of 139 patients diagnosed with STS of the extremities by radiological and/or histopathological study/biopsy were included. All patients irrespective of metastasis were included. Results The mean age of the patients in our study was 43.5 ± 18.89 years. Overall, the mean tumor size was found to be 11.81 ± 6.218 cm. Malignant fibrous histiocytoma was the most common histology encountered (41%). Synovial sarcoma was the second most common histology encountered (14.38%). Recurrence was observed in 14 (10.1%) patients. The overall survival was 64.7% in our study. Conclusions The surgical margin achieved during the surgery is the most detrimental factor in local tumor control, and the overall survival of the patient after resection mainly depends on the stage of the tumor.

17.
iScience ; 25(6): 104384, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35620424

RESUMO

Monocytes are known to play a critical role in dengue pathophysiology. However, which monocyte subset expresses what inflammatory mediator(s) and what transcriptional features distinguish each of the monocyte subset in vivo remain poorly understood. In this study we provide a detailed transcriptional analysis of the three human monocyte subsets in healthy children and in children with dengue febrile illness. Notably, we found that the CD14+ CD16high intermediate monocyte subset from dengue patients highly upregulated key genes involved in mediating inflammation, endothelial dysfunction, vascular permeability, tissue extravasation, and clot prevention compared to healthy children. The CD14+CD16low classical monocytes shared some of these features. These two subsets increased massively in patients with severe dengue. By contrast, the CD14-CD16high nonclassical monocyte subset upregulated key genes involved in vasoconstriction, endothelial barrier stability, and are involved in endothelial patrolling while showing a significant decline from circulation. These findings improve our understanding of monocyte responses in dengue.

18.
Ultrason Sonochem ; 73: 105506, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33714087

RESUMO

The use of non-thermal processing technologies has been on the surge due to ever increasing demand for highest quality convenient foods containing the natural taste & flavor and being free of chemical additives and preservatives. Among the various non-thermal processing methods, ultrasound technology has proven to be very valuable. Ultrasound processing, being used alone or in combination with other processing methods, yields significant positive results on the quality of foods, thus has been considered efficacious. Food processes performed under the action of ultrasound are believed to be affected in part by cavitation phenomenon and mass transfer enhancement. It is considered to be an emerging and promising technology and has been applied efficiently in food processing industry for several processes such as freezing, filtration, drying, separation, emulsion, sterilization, and extraction. Various researches have opined that ultrasound leads to an increase in the performance of the process and improves the quality factors of the food. The present paper will discuss the mechanical, chemical and biochemical effects produced by the propagation of high intensity ultrasonic waves through the medium. This review outlines the current knowledge about application of ultrasound in food technology including processing, preservation and extraction. In addition, the several advantages of ultrasound processing, which when combined with other different technologies (such as microwave, supercritical CO2, high pressure processing, enzymatic extraction, etc.) are being examined. These include an array of effects such as effective mixing, retention of food characteristics, faster energy and mass transfer, reduced thermal and concentration gradients, effective extraction, increased production, and efficient alternative to conventional techniques. Furthermore, the paper presents the necessary theoretical background and details of the technology, technique, and safety precautions about ultrasound.


Assuntos
Manipulação de Alimentos/métodos , Tecnologia de Alimentos/métodos , Ondas Ultrassônicas
19.
mSphere ; 5(3)2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32461278

RESUMO

Zinc supplementation in cell culture has been shown to inhibit various viruses, like herpes simplex virus, rotavirus, severe acute respiratory syndrome (SARS) coronavirus, rhinovirus, and respiratory syncytial virus (RSV). However, whether zinc plays a direct antiviral role in viral infections and whether viruses have adopted strategies to modulate zinc homeostasis have not been investigated. Results from clinical trials of zinc supplementation in infections indicate that zinc supplementation may be beneficial in a pathogen- or disease-specific manner, further underscoring the importance of understanding the interaction between zinc homeostasis and virus infections at the molecular level. We investigated the effect of RSV infection on zinc homeostasis and show that RSV infection in lung epithelial cells leads to modulation of zinc homeostasis. The intracellular labile zinc pool increases upon RSV infection in a multiplicity of infection (MOI)-dependent fashion. Small interfering RNA (siRNA)-mediated knockdown of the ubiquitous zinc uptake transporter ZIP1 suggests that labile zinc levels are increased due to the increased uptake by RSV-infected cells as an antiviral response. Adding zinc to culture medium after RSV infection led to significant inhibition of RSV titers, whereas depletion of zinc by a zinc chelator, N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) led to an increase in RSV titers. The inhibitory effect of zinc was specific, as other divalent cations had no effect on RSV titers. Both RSV infection and zinc chelation by TPEN led to reactive oxygen species (ROS) induction, whereas addition of zinc blocked ROS induction. These results suggest a molecular link between RSV infection, zinc homeostasis, and oxidative-stress pathways and provide new insights for developing strategies to counter RSV infection.IMPORTANCE Zinc deficiency rates in developing countries range from 20 to 30%, and zinc supplementation trials have been shown to correct clinical manifestations attributed to zinc deficiency, but the outcomes in the case of respiratory infections have been inconsistent. We aimed at understanding the role of zinc homeostasis in respiratory syncytial virus (RSV) infection. Infection of lung epithelial cell lines or primary small-airway epithelial cells led to an increase in labile zinc pools, which was due to increased uptake of zinc. Zinc supplementation inhibited RSV replication, whereas zinc chelation had an opposing effect, leading to increases in RSV titers. Increases in labile zinc in RSV-infected cells coincided with induction of reactive oxygen species (ROS). Both zinc depletion and addition of exogenous ROS led to enhanced RSV infection, whereas addition of the antioxidant inhibited RSV, suggesting that zinc is part of an interplay between RSV-induced oxidative stress and the host response to maintain redox balance.


Assuntos
Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/metabolismo , Replicação Viral/efeitos dos fármacos , Zinco/metabolismo , Zinco/farmacologia , Células A549 , Adolescente , Proteínas de Transporte de Cátions/genética , Linhagem Celular , Criança , Pré-Escolar , Células Epiteliais/metabolismo , Etilenodiaminas/farmacologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Pulmão/citologia , Pulmão/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Interferência de RNA , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia
20.
PLoS Negl Trop Dis ; 14(6): e0008203, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32579555

RESUMO

BACKGROUND: Dengue virus (DENV) infections pose one of the largest global barriers to human health. The four serotypes (DENV 1-4) present different symptoms and influence immune response to subsequent DENV infections, rendering surveillance, risk assessments, and disease control particularly challenging. Early diagnosis and appropriate clinical management is critical and can be achieved by detecting DENV nonstructural protein 1 (NS1) in serum during the acute phase. However, few NS1-based tests have been developed that are capable of differentiating DENV serotypes and none are currently commercially available. METHODOLOGY/PRINCIPLE FINDINGS: We developed an enzyme-linked immunosorbent assay (ELISA) to distinguish DENV-1-4 NS1 using serotype-specific pairs of monoclonal antibodies. A total of 1,046 antibodies were harvested from DENV-immunized mice and screened for antigen binding affinity. ELISA clinical performance was evaluated using 408 polymerase chain reaction-confirmed dengue samples obtained from patients in Brazil, Honduras, and India. The overall sensitivity of the test for pan-DENV was 79.66% (325/408), and the sensitivities for DENV-1-4 serotyping were 79.1% (38/48), 80.41% (78/97), 100% (45/45), and 79.6% (98/123), respectively. Specificity reached 94.07-100%. SIGNIFICANCE: Our study demonstrates a robust antibody screening strategy that enabled the development of a serotype NS1-based ELISA with maximized specific and sensitive antigen binding. This sensitive and specific assay also utilized the most expansive cohort to date, and of which about half are from Latin America, a geographic region severely underrepresented in previous similar studies. This ELISA test offers potential enhanced diagnostics during the acute phase of infection to help guide patient care and disease control. These results indicate that this ELISA is a promising aid in early DENV-1-4 diagnosis and surveillance in regions of endemicity in addition to offer convenient monitoring for future vaccine interventions.


Assuntos
Vírus da Dengue/classificação , Vírus da Dengue/isolamento & purificação , Dengue/virologia , Ensaio de Imunoadsorção Enzimática/métodos , Sorogrupo , Proteínas não Estruturais Virais/análise , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Brasil , Estudos de Coortes , Honduras , Humanos , Índia , América Latina , Camundongos Endogâmicos C57BL , Sensibilidade e Especificidade
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