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1.
BMC Infect Dis ; 20(1): 188, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122317

RESUMO

BACKGROUND: In recent times, Plasmodium vivax (P. vivax) has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes. Its unique biology makes it resilient to control measures that are otherwise effective against P. falciparum. A deeper understanding of P. vivax biology and pathogenesis is, therefore, essential for developing the right control strategies. Proteomics of P. falciparum has been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. However, unlike P. falciparum, proteomics data for P. vivax infection is minimal due to the absence of a continuous culture system. The dependence on clinical samples and animal models has drastically limited P. vivax research, creating critical knowledge gaps in our understanding of the disease. This study describes an in-depth proteomics analysis of P. vivax-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets for P. vivax malaria. METHODS: A mass-spectrometry- (MS) based proteomics approach (Q Exactive) was applied to analyze human plasma and parasite isolates from vivax malaria patients visiting a primary health centre in India. Additionally, a targeted proteomics assay was standardized for validating unique peptides of most recurring parasite proteins. RESULTS: Thirty-eight P. vivax proteins were detected in human plasma with high confidence. Several glycolytic enzymes were found along with hypothetical, cytoskeletal, ribosomal, and nuclear proteins. Additionally, 103 highly abundant P. vivax proteins were detected in parasite isolates. This represents the highest number of parasite proteins to be reported from clinical samples so far. Interestingly, five of these; three Plasmodium exported proteins (PVX_003545, PVX_003555 and PVX_121935), a hypothetical protein (PVX_083555) and Pvstp1 (subtelomeric transmembrane protein 1, PVX_094303) were found in both plasma and parasite isolates. CONCLUSIONS: A parasite proteomics investigation is essential to understand disease pathobiology and design novel interventions. Control strategies against P. vivax also depend on early diagnosis. This work provides deeper insights into the biology of P. vivax by identifying proteins expressed by the parasite during its complex life-cycle within the human host. The study also reports antigens that may be explored as diagnostic candidates.


Assuntos
Malária Vivax/sangue , Plasmodium vivax/isolamento & purificação , Proteínas de Protozoários/sangue , Ontologia Genética , Interações Hospedeiro-Parasita/fisiologia , Humanos , Índia , Estágios do Ciclo de Vida , Malária Vivax/parasitologia , Plasmodium vivax/fisiologia , Proteômica/métodos , Proteínas de Protozoários/análise , Proteínas de Protozoários/genética , Espectrometria de Massas em Tandem
2.
J Virol ; 92(16)2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29769349

RESUMO

TREX1 has been reported to degrade cytosolic immune-stimulatory DNA, including viral DNA generated during HIV-1 infection; but the dynamic range of its capacity to suppress innate immune stimulation is unknown, and its full role in the viral life cycle remains unclear. A main purpose of our study was to determine how the intracellular level of TREX1 affects HIV-1 activation and avoidance of innate immunity. Using stable overexpression and CRISPR-mediated gene disruption, we engineered a range of TREX1 levels in human THP-1 monocytes. Increasing the level of TREX1 dramatically suppressed HIV-1 induction of interferon-stimulated genes (ISGs). Productive infection and integrated proviruses were equal or increased. Knocking out TREX1 impaired viral infectivity, increased early viral cDNA, and caused 10-fold or greater increases in HIV-1 ISG induction. Knockout of cyclic GMP-AMP synthase (cGAS) abrogated all ISG induction. Moreover, cGAS knockout produced no increase in single-cycle infection, establishing that HIV-1 DNA-triggered signaling is not rapid enough to impair the initial ISG-triggering infection cycle. Disruption of the HIV-1 capsid by PF74 also induced ISGs, and this was TREX1 level dependent, required reverse transcriptase catalysis, and was eliminated by cGAS gene knockout. Thus, the intracellular level of TREX1 pivotally modulates innate immune induction by HIV-1. Partial HIV-1 genomes are the TREX1 target and are sensed by cGAS. The nearly complete lack of innate immune induction despite equal or increased viral integration observed when the TREX1 protein level is experimentally elevated indicates that integration-competent genomes are shielded from cytosolic sensor-effectors during uncoating and transit to the nucleus.IMPORTANCE Much remains unknown about how TREX1 influences HIV-1 replication: whether it targets full-length viral DNA versus partial intermediates, how intracellular TREX1 protein levels correlate with ISG induction, and whether TREX1 digestion of cytoplasmic DNA and subsequent cGAS pathway activation affects both initial and subsequent cycles of infection. To answer these questions, we experimentally varied the intracellular level of TREX1 and showed that this strongly determines the innate immunogenicity of HIV-1. In addition, several lines of evidence, including time-of-addition experiments with drugs that impair reverse transcription or capsid integrity, showed that the pathogen-associated molecular patterns sensed after viral entry contain DNA, are TREX1 and cGAS substrates, and are derived from incomplete reverse transcriptase (RT) products. In contrast, the experiments demonstrate that full-length integration-competent viral DNA is immune to TREX1. Treatment approaches that reduce TREX1 levels or facilitate release of DNA intermediates may advantageously combine enhanced innate immunity with antiviral effects.


Assuntos
DNA Viral/imunologia , Exodesoxirribonucleases/metabolismo , HIV-1/imunologia , HIV-1/fisiologia , Imunidade Inata , Nucleotidiltransferases/metabolismo , Fosfoproteínas/metabolismo , Transcrição Reversa , DNA Viral/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Monócitos/imunologia , Monócitos/virologia , Células THP-1
3.
J Prosthodont ; 28(1): e1-e5, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28122401

RESUMO

Prosthetic rehabilitation of a completely edentulous patient should never be restricted to the replacement of missing teeth. The ultimate aim of complete denture treatment should be restoration of the full range of oral functions and esthetics. Slumped cheeks are always a concern for esthetically demanding complete denture patients. This article describes a simple, scientific, cost-effective technique to improve facial esthetics in a completely edentulous patient with the help of a cheek plumper. The technique used here implements the concept of neutral zone to precisely determine the amount of space available for the cheek plumper. The simple friction lock attachments that retained the cheek plumpers on the prosthesis were also fabricated after determining the space available in the appropriate areas. Thus an effort was made to keep the cheek plumpers unobtrusive yet effective to ensure complete integration of the prosthesis into the stomatognathic system.


Assuntos
Bochecha , Retenção de Dentadura/instrumentação , Prótese Total , Estética Dentária , Boca Edêntula/reabilitação , Bochecha/anatomia & histologia , Técnica de Fundição Odontológica , Planejamento de Dentadura/instrumentação , Planejamento de Dentadura/métodos , Retenção de Dentadura/métodos , Humanos , Masculino , Pessoa de Meia-Idade
4.
J Prosthodont ; 28(1): e13-e17, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28383131

RESUMO

The success of removable prostheses ultimately depends on a number of factors such as retention, stability, support, esthetics, and masticatory function. Increased intraoral inter-arch distance leads to an increase in the weight of the prosthesis. This may compromise the retention and resistance, which are key for a successful removable prosthesis. Various methods, techniques, and materials have been reported to minimize the weight of a prosthesis. This article describes a simple, unique, precise single-flask technique for the fabrication of a lightweight maxillary prosthesis using caramel as a 3D spacer, which was "indexed" to obtain a uniform thickness of acrylic around the hollow cavity.


Assuntos
Planejamento de Dentadura , Prótese Total Superior , Retenção de Dentadura , Estética Dentária , Humanos
5.
J Virol ; 88(11): 6158-67, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24648460

RESUMO

UNLABELLED: The measles virus (MeV) membrane fusion apparatus consists of a fusion protein trimer and an attachment protein tetramer. To trigger membrane fusion, the heads of the MeV attachment protein, hemagglutinin (H), bind cellular receptors while the 96-residue-long H stalk transmits the triggering signal. Structural and functional studies of the triggering mechanism of other paramyxoviruses suggest that receptor binding to their hemagglutinin-neuraminidase (HN) results in signal transmission through the central segments of their stalks. To gain insight into H-stalk structure and function, we individually replaced its residues with cysteine. We then assessed how stable the mutant proteins are, how efficiently they can be cross-linked by disulfide bonds, whether cross-linking results in loss of function, and, in this case, whether disulfide bond reduction restores function. While many residues in the central segment of the stalk and in the spacer segment above it can be efficiently cross-linked by engineered disulfide bonds, we report here that residues 59 to 79 cannot, suggesting that the 20 membrane-proximal residues are not engaged in a tetrameric structure. Rescue-of-function studies by disulfide bond reduction resulted in the redefinition and extension of the central fusion-activation segment as covering residues 84 to 117. In particular, we identified four residues located between positions 92 and 99, the function of which cannot be restored by disulfide bond reduction after cysteine mutagenesis. These mutant H proteins reached the cell surface as complex oligomers but could not trigger membrane fusion. We discuss these observations in the context of the stalk exposure model of membrane fusion triggering by paramyxoviruses. IMPORTANCE: Measles virus, while being targeted for eradication, still causes significant morbidity and mortality. Here, we seek to understand how it enters cells by membrane fusion. Two viral integral membrane glycoproteins (hemagglutinin tetramers and fusion protein trimers) mediate the concerted receptor recognition and membrane fusion processes. Since previous studies have suggested that the hemagglutinin stalk transmits the triggering signal to the fusion protein trimer, we completed an analysis of its structure and function by systematic Cys mutagenesis. We report that while certain residues of the central stalk segment confer specificity to the interaction with the fusion protein trimer, others are necessary to allow folding of the H-oligomer in a standard conformation conducive to fusion triggering, and still other residues sustain the conformational change that transmits the fusion-triggering signal.


Assuntos
Hemaglutininas Virais/metabolismo , Vírus do Sarampo/fisiologia , Fusão de Membrana/fisiologia , Modelos Biológicos , Transdução de Sinais/fisiologia , Animais , Chlorocebus aethiops , Cisteína , Dissulfetos/metabolismo , Citometria de Fluxo , Células HEK293 , Hemaglutininas Virais/fisiologia , Humanos , Mutagênese , Estabilidade Proteica , Células Vero
6.
PLoS Pathog ; 8(7): e1002805, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22807681

RESUMO

Accumulating evidence suggests an important role for Natural Killer (NK) cells in the control of HIV-1 infection. Recently, it was shown that NK cell-mediated immune pressure can result in the selection of HIV-1 escape mutations. A potential mechanism for this NK cell escape is the selection of HLA class I-presented HIV-1 epitopes that allow for the engagement of inhibitory killer cell immunoglobulin-like receptors (KIRs), notably KIR2DL2. We therefore investigated the consequences of sequence variations within HLA-Cw*0102-restricted epitopes on the interaction of HLA-Cw*0102 with KIR2DL2 using a large panel of overlapping HIV-1 p24 Gag peptides. 217 decameric peptides spanning the HIV-1 p24 Gag consensus sequence were screened for HLA-Cw*0102 stabilization by co-incubation with Cw*0102⁺/TAP-deficient T2 cells using a flow cytometry-based assay. KIR2DL2 binding was assessed using a KIR2DL2-IgG fusion construct. Function of KIR2DL2⁺ NK cells was flow cytometrically analyzed by measuring degranulation of primary NK cells after co-incubation with peptide-pulsed T2 cells. We identified 11 peptides stabilizing HLA-Cw*0102 on the surface of T2 cells. However, only one peptide (p24 Gag209₋218 AAEWDRLHPV) allowed for binding of KIR2DL2. Notably, functional analysis showed a significant inhibition of KIR2DL2⁺ NK cells in the presence of p24 Gag209₋218-pulsed T2 cells, while degranulation of KIR2DL2⁻ NK cells was not affected. Moreover, we demonstrated that sequence variations in position 7 of this epitope observed frequently in naturally occurring HIV-1 sequences can modulate binding to KIR2DL2. Our results show that the majority of HIV-1 p24 Gag peptides stabilizing HLA-Cw*0102 do not allow for binding of KIR2DL2, but identified one HLA-Cw*0102-presented peptide (p24 Gag209₋218) that was recognized by the inhibitory NK cell receptor KIR2DL2 leading to functional inhibition of KIR2DL2-expressing NK cells. Engagement of KIR2DL2 might protect virus-infected cells from NK cell-mediated lysis and selections of sequence polymorphisms that increase avidity to KIR2DL2 might provide a mechanism for HIV-1 to escape NK cell-mediated immune pressure.


Assuntos
Proteína do Núcleo p24 do HIV/imunologia , HIV-1/imunologia , Antígenos HLA-C/imunologia , Células Matadoras Naturais/imunologia , Receptores KIR2DL2/metabolismo , Linhagem Celular , Citotoxicidade Imunológica , Variação Genética , Proteína do Núcleo p24 do HIV/genética , Proteína do Núcleo p24 do HIV/metabolismo , Infecções por HIV/imunologia , HIV-1/genética , HIV-1/metabolismo , Humanos , Evasão da Resposta Imune , Ligação Proteica , Alinhamento de Sequência
7.
Clin Microbiol Rev ; 25(2): 344-61, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22491775

RESUMO

The menu of diagnostic tools that can be utilized to establish a diagnosis of influenza is extensive and includes classic virology techniques as well as new and emerging methods. This review of how the various existing diagnostic methods have been utilized, first in the context of a rapidly evolving outbreak of novel influenza virus and then during the different subsequent phases and waves of the pandemic, demonstrates the unique roles, advantages, and limitations of each of these methods. Rapid antigen tests were used extensively throughout the pandemic. Recognition of the low negative predictive values of these tests is important. Private laboratories with preexisting expertise, infrastructure, and resources for rapid development, validation, and implementation of laboratory-developed assays played an unprecedented role in helping to meet the diagnostic demands during the pandemic. FDA-cleared assays remain an important element of the diagnostic armamentarium during a pandemic, and a process must be developed with the FDA to allow manufacturers to modify these assays for detection of novel strains in a timely fashion. The need and role for subtyping of influenza viruses and antiviral susceptibility testing will likely depend on qualitative (circulating subtypes and their resistance patterns) and quantitative (relative prevalence) characterization of influenza viruses circulating during future epidemics and pandemics.


Assuntos
Técnicas de Laboratório Clínico/métodos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/virologia , Virologia/métodos , Humanos , Orthomyxoviridae/classificação , Orthomyxoviridae/isolamento & purificação
8.
Front Oral Health ; 4: 1292332, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098979

RESUMO

Inflammation of the gingiva is one of the most common and routine findings in dental practice. These routine appearances of inflammatory gingivae can show peculiarity when associated with an underlying systemic condition or because of reactive, benign, or malignant pathologies. This case highlights minute clinical signs of the gingiva that deviate from the routine presentation and warrant further investigations. A 63-year-old woman presented with a chief complaint of severe pain in relation to the lower front teeth region for 1 month. Intraoral examination revealed a gingival lesion on the labial aspect of 41, 42, and 43, and an intraoral periapical radiograph showed mild bone loss. The lesion persisted despite oral prophylaxis, and a biopsy was advised. The final diagnosis was stage 1 gingival squamous cell carcinoma (GSCC). It is important to note that the non-descript presentation of GSCC in early stages often mimics benign traumatic or inflammatory lesions of the gingiva. Peculiar clinical features of GSCC of note include the lack of traditionally associated risk factors and localized red or ulcerative lesions with increased bleeding tendencies that do not respond to routine periodontal treatment within 2 weeks.

9.
Neurotherapeutics ; 20(4): 1229-1240, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37296356

RESUMO

Recent evidence suggests that the glucagon-like peptide-1 receptor (GLP-1R) agonists have neuroprotective activities in the CNS in animal models of Parkinson's disease, Alzheimer's disease, and multiple sclerosis (MS). This study aimed to investigate whether a novel long-acting GLP-1R agonist, NLY01, could limit demyelination or improve remyelination as occurs in MS using the cuprizone (CPZ) mouse model. Herein, we assessed the expression of GLP-1R on oligodendrocytes in vitro and found that mature oligodendrocytes (Olig2+PDGFRa-) express GLP-1R. We further confirmed this observation in the brain by immunohistochemistry and found that Olig2+CC1+ cells express GLP-1R. We next administered NLY01 twice per week to C57B6 mice while on CPZ chow diet and found that NLY01 significantly reduced demyelination with greater weight loss than vehicle-treated controls. Because GLP-1R agonists are known to have anorexigenic effect, we then administered CPZ by oral gavage and treated the mice with NLY01 or vehicle to ensure the dose consistency of CPZ ingestion among mice. Using this modified approach, NLY01 was no longer effective in reducing demyelination of the corpus callosum (CC). We next sought to examine the effects of NLY01 treatment on remyelination after CPZ intoxication and during the recovery period using an adoptive transfer-CPZ (AT-CPZ) model. We found no significant differences between the NLY01 and vehicle groups in the amount of myelin or the number of mature oligodendrocytes in the CC. In summary, despite the promising anti-inflammatory and neuroprotective effects of GLP-1R agonists that have been previously described, our experiments provided no evidence to support a beneficial effect of NLY01 on limiting demyelination or enhancing remyelination. This information may be useful in selecting proper outcome measures in clinical trials of this promising class of drugs in MS.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Remielinização , Camundongos , Animais , Cuprizona/toxicidade , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Bainha de Mielina , Esclerose Múltipla/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
10.
J Virol ; 85(12): 5970-4, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21471246

RESUMO

Epidemiological studies have shown the protective effect of KIR3DL1/HLA-Bw4 genotypes in human immunodeficiency virus type 1 (HIV-1) infection; however, the functional correlates for the protective effect remain unknown. We investigated whether human leukocyte antigen (HLA)-Bw4-presented HIV-1 peptides could affect the interaction between the inhibitory natural killer (NK) cell receptor KIR3DL1 and its ligand HLA-Bw4. Distinct HIV-1 epitopes differentially modulated the binding of KIR3DL1 to HLA-Bw4. Furthermore, cytotoxic T lymphocyte (CTL) escape mutations within the immunodominant HLA-B57 (Bw4)-restricted Gag epitope TSTLQEQIGW abrogated KIR3DL1 binding to HLA-B57, suggesting that sensing of CTL escape variants by NK cells can contribute to the protective effect of the KIR3DL1/HLA-Bw4 compound genotype.


Assuntos
Epitopos de Linfócito T/imunologia , Produtos do Gene gag/genética , Variação Genética , HIV-1/imunologia , Antígenos HLA-B/metabolismo , Peptídeos/genética , Receptores KIR3DL1/metabolismo , Sequência de Aminoácidos , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Produtos do Gene gag/química , Produtos do Gene gag/imunologia , Produtos do Gene gag/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , Antígenos HLA-B/genética , Humanos , Evasão da Resposta Imune , Epitopos Imunodominantes , Células Jurkat , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Peptídeos/química , Peptídeos/imunologia , Peptídeos/metabolismo , Mutação Puntual , Ligação Proteica/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo
11.
J Virol ; 85(2): 828-34, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21068250

RESUMO

Spatial variation in the epidemiological patterns of successive waves of pandemic influenza virus in humans has been documented throughout the 20th century but never understood at a molecular level. However, the unprecedented intensity of sampling and whole-genome sequencing of the H1N1/09 pandemic virus now makes such an approach possible. To determine whether the spring and fall waves of the H1N1/09 influenza pandemic were associated with different epidemiological patterns, we undertook a large-scale phylogeographic analysis of viruses sampled from three localities in the United States. Analysis of genomic and epidemiological data reveals distinct spatial heterogeneities associated with the first pandemic wave, March to July 2009, in Houston, TX, Milwaukee, WI, and New York State. In Houston, no specific H1N1/09 viral lineage dominated during the spring of 2009, a period when little epidemiological activity was observed in Texas. In contrast, major pandemic outbreaks occurred at this time in Milwaukee and New York State, each dominated by a different viral lineage and resulting from strong founder effects. During the second pandemic wave, beginning in August 2009, all three U.S. localities were dominated by a single viral lineage, that which had been dominant in New York during wave 1. Hence, during this second phase of the pandemic, extensive viral migration and mixing diffused the spatially defined population structure that had characterized wave 1, amplifying the one viral lineage that had dominated early on in one of the world's largest international travel centers.


Assuntos
Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Pandemias , Filogenia , Análise por Conglomerados , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Epidemiologia Molecular , New York/epidemiologia , Filogeografia , RNA Viral/genética , Estações do Ano , Análise de Sequência de DNA , Texas/epidemiologia , Wisconsin/epidemiologia
13.
Mult Scler Relat Disord ; 66: 104036, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35858500

RESUMO

Moyamoya Angiopathy (MMA) is frequently not considered in differential diagnosis of Multiple Sclerosis (MS). This is the first study to prospectively analyze rate of misdiagnosis of MMA as MS and its clinical implications. Of the 160 angiographically proven MMA, 5 patients had an initial misdiagnosis of MS (3.13%). These 5 cases had female-predominance (80%).Out of the 5 cases, 4 cases (80%) presented with hemiparesis; 3 cases (60%) had an immediate precipitating factor. Radiologically, presence of both periventricular and juxtacortical white-matter-lesions was seen in 4 out of 5 cases (80%);none had infratentorial/spinal lesion, while all 5 cases had presence of "Ivy" sign and abnormal flow voids. Differentiation relies on careful evaluation of clinico-radiological features. MMA should be considered as a rare but important differential to MS.


Assuntos
Doença de Moyamoya , Esclerose Múltipla , Erros de Diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , Doença de Moyamoya/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia
14.
Cancer Epidemiol Biomarkers Prev ; 31(5): 1090-1102, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34810209

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development. METHODS: A literature search until August 2020 in MEDLINE, EMBASE, and Web of Science was performed. Studies were included if they assessed circulating blood, urine, or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk. RESULTS: A total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC [n = 4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22]. Additionally, an inverse association was seen with pyridoxal 5'-phosphate (PLP) levels (n = 4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D, and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched-chain amino acids with PDAC risk, but due to differences in measures reported, a meta-analysis could not be performed. CONCLUSIONS: Our pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC. IMPACT: Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Biomarcadores , Biomarcadores Tumorais , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Glucose , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Prognóstico , Neoplasias Pancreáticas
15.
J Pediatr Hematol Oncol ; 33(3): e127-31, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21399527

RESUMO

A 5.5-year-old asymptomatic Hispanic/African American male presented with matted lymph nodes in the neck and reticulonodular opacities in the right upper lung. An extensive diagnostic work up was performed to rule out infectious etiologies. Biopsies of the lymph node and lung tissue were diagnostic of nodular lymphocyte predominant Hodgkin lymphoma. Two weeks into the chemotherapy, gastric aspirates grew Mycobacterium avium intracellulare. This is the first case of nodular lymphocyte predominant Hodgkin lymphoma involving the lung with coexistent Mycobacterium avium intracellulare.


Assuntos
Doença de Hodgkin/complicações , Neoplasias Pulmonares/complicações , Linfonodos/patologia , Linfócitos/patologia , Infecção por Mycobacterium avium-intracellulare/complicações , Pré-Escolar , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/patologia , Tomografia por Emissão de Pósitrons
16.
Pediatr Emerg Care ; 27(9): 804-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21878831

RESUMO

STUDY OBJECTIVE: The 2009 H1N1 pandemic (H1N1pdm) virus has been associated with high rates of asymptomatic infections. Existing influenza infection control policies do not address potential transmission through exposure to asymptomatic infected individuals in health care settings. We conducted a seroprevalence study of H1N1pdm infection to determine whether health care workers (HCWs) in the emergency department showed increased evidence of infection during the first wave of the pandemic than that previously reported in adults in the community. METHODS: Blood samples and demographic and clinical data were collected from eligible emergency department HCWs. Subjects' sera were tested for presence of antibodies specific for seasonal H1N1 and H1N1pdm viruses by hemagglutination-inhibition assay. RESULTS: One hundred eight subjects were enrolled, of which 20 (18.5%) were seropositive for H1N1pdm and 52 (48%) for seasonal H1N1. The median age of H1N1pdm-seropositive subjects was 32 years (range, 24-59 years). Of H1N1pdm-seropositive subjects, 35% were asymptomatic. Rates of H1N1pdm detection in HCWs (18.5%) were significantly higher than those observed previously in an identical age cohort in the community (2.6%, n = 262). CONCLUSIONS: The higher serodetection rates in adults observed in the current study suggest potentially significantly more frequent infections in HCWs than in the general population. Further investigations are needed to ascertain the relative incidence of influenza infections in HCWs and non-HCWs, to study influenza transmission by asymptomatic infected subjects and ascertain the burden of such transmission in health care settings.


Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/epidemiologia , Doenças Profissionais/epidemiologia , Pandemias/estatística & dados numéricos , Recursos Humanos em Hospital/estatística & dados numéricos , Adolescente , Adulto , Idoso , Doenças Assintomáticas , Infecção Hospitalar/epidemiologia , Exposição Ambiental , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Hospitais Privados/estatística & dados numéricos , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vacinas contra Influenza , Influenza Humana/sangue , Influenza Humana/transmissão , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/sangue , Doenças Profissionais/virologia , Estudos Soroepidemiológicos , Wisconsin/epidemiologia , Adulto Jovem
17.
Acta Neurol Belg ; 121(5): 1165-1172, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33539002

RESUMO

Moyamoya disease (MMD) is a progressive steno-occlusive vasculopathy at the circle of Willis, characteristically involving the supra-clinoid segment of internal carotid arteries and their proximal branches with prominent collateral artery formation. Here we present, a series of imaging findings and varied clinical presentation of eight cases (n = 8) of MMD in the pediatric population (aged 0-18 years) after a retrospective review and detailed clinical evaluation. Detailed clinical history and examination were performed of eight pediatric patients of MMD with varied presentations. Magnetic resonance imaging (MRI) of the brain along with time of flight (TOF) sequence magnetic resonance angiography (MRA) was performed for all patients with a 3 T ((T) SEIMENS MRI scanner. Three out of eight cases (37.5%) presented with imaging findings of acute parenchymal infarction involving one or more major vascular territories showing diffusion restriction on DWI (diffusion-weighted image) sequence. Two of the patients (25%) showed chronic infarction with areas of gliosis and encephalomalacia. One child presented with watershed areas of infarction involving bilateral parieto-occipital region. In one of the patients (12.5%) being evaluated for dystonia, the only parenchymal finding detected was that of asymmetric ventriculomegaly. A solitary patient being evaluated for intermittent focal seizure followed by Todd's hemiparesis had normal parenchymal brain imaging. Leptomeningeal pattern of enhancement was noted in one patient (12.5%). Although predominantly an intracranial vasculopathy, MMD may have myriad presentations apart from stroke, some of which are highlighted in this series.


Assuntos
Encéfalo/diagnóstico por imagem , Doença de Moyamoya/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos
18.
Metallomics ; 13(2)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33595653

RESUMO

The organo-osmium complex [OsII(ɳ6-p-cym)(PhAzPy-NMe2)I]+ (FY26) exhibits promising in vitro antitumour activity against mouse hepatocarcinoma Hepa1-6 and other mouse or human cancer cell lines. Here, we drastically enhance water solubility of FY26 through the replacement of the PF6- counter-anion with chloride using a novel synthesis method. FY26⋅PF6 and FY26⋅Cl displayed similar in vitro cytotoxicity in two cancer cell models. We then show the moderate and late anticancer efficacy of FY26⋅PF6 and FY26⋅Cl in a subcutaneous murine hepatocarcinoma mouse model. Both efficacy and tolerability varied according to FY26 circadian dosing time in hepatocarcinoma tumour-bearing mice. Tumour and liver uptake of the drug were determined over 48 h following FY26⋅Cl administration at Zeitgeber time 6 (ZT6), when the drug is least toxic (in the middle of the light span when mice are resting). Our studies suggest the need to administer protracted low doses of FY26 at ZT6 in order to optimize its delivery schedule, for example through the use of chrono-releasing nanoparticles.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Complexos de Coordenação/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Complexos de Coordenação/administração & dosagem , Complexos de Coordenação/efeitos adversos , Complexos de Coordenação/farmacocinética , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Distribuição Tecidual
19.
Pharmacol Ther ; 214: 107610, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32585232

RESUMO

The Inhibitor of Apoptosis proteins (IAPs) are a family of proteins that are mainly known for their anti-apoptotic activity and ability to directly bind and inhibit caspases. Recent research has however revealed that they have extensive roles in governing numerous other cellular processes. IAPs are known to modulate ubiquitin (Ub)-dependent signaling pathways through their E3 ligase activity and influence activation of nuclear factor κB (NF-κB). In this review, we discuss the involvement of IAPs in individual hallmarks of cancer and the current status of therapies targeting these critical proteins.


Assuntos
Apoptose , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias/metabolismo , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Humanos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Mimetismo Molecular , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Transdução de Sinais
20.
Minerva Stomatol ; 69(5): 302-308, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32407059

RESUMO

BACKGROUND: Chronic kidney disease (CKD-HD) patients undergoing routine hemodialysis have been reported to have oral signs and symptoms due to disease process or various comorbidities like diabetes mellitus (DM). Both CKD and DM can cause oral changes. Hence this study aimed to evaluate the prevalence of oral symptoms and signs in CKD-HD patients and to rule out DM as possible confounding factor for the oral findings. METHODS: Oral manifestations were assessed in 102 CKD-HD patients, and compared with 100 DM patients and 101 non-diabetic patients with no renal impairment. RESULTS: Most common symptom reported by patients with CKD-HD were xerostomia, altered taste. The most prevalent objective findings were oral dryness. There was statistically significant difference in symptoms and signs between CKD-HD and non-CKD patients. However, no significant difference between CKD-HD with and without DM. CONCLUSIONS: This study showed increased prevalence of oral findings in CKD patients. It also revealed that Diabetes mellitus cannot be a contributing factor for increased prevalence of oral manifestations in CKD patients.


Assuntos
Diabetes Mellitus , Insuficiência Renal Crônica , Comorbidade , Diabetes Mellitus/epidemiologia , Humanos , Prevalência , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia
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