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1.
J Am Soc Cytopathol ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35589508

RESUMO

INTRODUCTION: In lung cancer patients presenting with malignant pleural effusion (MPE), cytology might represent the only source of tumor tissue for diagnosis and predictive biomarker testing. Programmed death ligand 1 (PD-L1) expression in tumor cells is a predictive biomarker for immunotherapy in non-small cell lung carcinomas and is tested using immunohistochemistry. However, knowledge of the validity of PD-L1 testing on MPE samples is limited. We evaluated the feasibility of immunocytochemistry (ICC) for PD-L1 in MPE cell blocks (CBs) and assessed the concordance in expression with patient-matched histologic samples. MATERIALS AND METHODS: ICC for PD-L1 was performed on formalin-fixed paraffin-embedded CBs of MPE and patient-matched histologic samples, if available, using the automated Ventana PD-L1 SP263 assay. The tumor proportion score (TPS), based on partial or complete membranous tumor cell staining, was categorized as negative (<1%), low (≥1% to <50%), and high (≥50%). In CBs with any degree of PD-L1 expression, ICC for CD163 highlighting macrophages was performed to exclude nonspecific PD-L1 expression in macrophages. The CB PD-L1 TPS was compared with the TPS obtained from the patient-matched histologic samples. RESULTS: Of 43 MPE CBs available, 25 were positive for PD-L1 (25 of 42; 59%), and 1 sample was inadequate. Of the 11 patient-matched histologic samples tested, the PD-L1 TPS categories were concordant for 10 of the 11 (91% concordance) cases. CONCLUSIONS: PD-L1 expression in MPE CBs showed good concordance with expression in histologic samples and is feasible as a source for PD-L1 testing. The concurrent use of CD163 immunostains will aid in the manual assessment of PD-L1 TPS.

2.
Am J Dermatopathol ; 44(5): 376-379, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35234192

RESUMO

ABSTRACT: Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a cutaneous CD30-positive lymphoproliferative disorder. The patients usually present with single or multiple cutaneous nodules or papules and about 10% cases present with extracutaneous manifestations, which are predominantly in the form of regional lymph nodal involvement. Visceral involvement especially pulmonary or hepatic involvement in C-ALCL is only rarely described in the scientific literature. Approximately 20%-42% cases show spontaneous regression, about 50% cases may recur; however, C-ALCL generally carries a good prognosis. We present a rare case of primary C-ALCL in a 66-year-old man with regional lymph nodal and hepatic involvement. Differential diagnostic entities are discussed in this report with the review of the literature.


Assuntos
Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico Cutâneo Primário de Células Grandes , Transtornos Linfoproliferativos , Dermatopatias , Neoplasias Cutâneas , Idoso , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico Cutâneo Primário de Células Grandes/diagnóstico , Linfoma Anaplásico Cutâneo Primário de Células Grandes/patologia , Transtornos Linfoproliferativos/patologia , Masculino , Recidiva Local de Neoplasia , Receptores Proteína Tirosina Quinases , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia
3.
J Infect ; 84(3): 383-390, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34974056

RESUMO

BACKGROUND: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. METHODS: We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify independent predictors. RESULTS: A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95% CI 1.1-11), use of systemic steroids (aOR 7.7, 95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6, 95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. CONCLUSION: Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.


Assuntos
COVID-19 , Mucormicose , Estudos de Casos e Controles , Humanos , Mucormicose/epidemiologia , Fatores de Risco , SARS-CoV-2
4.
JAMA Netw Open ; 5(1): e2142210, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34994793

RESUMO

Importance: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. Objective: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. Design, Setting, and Participants: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Exposures: Vaccination with 0, 1, or 2 doses of BBV152. Main Outcomes and Measures: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Results: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. Conclusions and Relevance: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.


Assuntos
COVID-19/epidemiologia , Pessoal de Saúde , Reinfecção , SARS-CoV-2 , Adulto , COVID-19/etiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Imunogenicidade da Vacina , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Centros de Atenção Terciária , Vacinas de Produtos Inativados/administração & dosagem , Vírion/imunologia , Adulto Jovem
5.
Am J Blood Res ; 11(5): 472-497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824881

RESUMO

Acute myeloid leukemia (AML) is a complex, aggressive myeloid neoplasm characterized by frequent somatic mutations that influence different functional categories' genes, resulting in maturational arrest and clonal expansion. AML can arise de novo (dn-AML) or can be secondary AML (s-AML) refers to a leukemic process which may arise from an antecedent hematologic disorder (AHD-AML), mostly from a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or can be the result of an antecedent cytotoxic chemotherapy or radiation therapy (therapy-related AML, t-AML). Clinical and biological features in secondary and therapy-related AML are distinct from de novo AML. Secondary and therapy-related AML occurs mainly in the elderly population and responds worse to therapy with higher relapse rates due to resistance to cytotoxic chemotherapy. Over the last decade, advances in molecular genetics have disclosed the sub-clonal architecture of secondary and therapy-related AML. Recent investigations have revealed that cytogenetic abnormalities and underlying genetic aberrations (mutations) are likely to be significant factors dictating prognosis and critical impacts on treatment outcome. Secondary and therapy-related AML have a poorer outcome with adverse cytogenetic abnormalities and higher recurrences of unfavorable mutations compared to de novo AML. In this review, we present an overview of the clinical features of secondary and therapy-related AML and address the function of genetic mutations implicated in the pathogenesis of secondary leukemia. Detailed knowledge of the pathogenetic mechanisms gives an overview of new prognostic markers, including targetable mutations that will presumably lead to the designing and developing novel molecular targeted therapies for secondary and therapy-related AML. Despite significant advances in knowing the genetic aspect of secondary and therapy-related AML, its influence on the disease's pathophysiology, standard treatment prospects have not significantly evolved during the past three decades. Thus, we conclude this review by summarizing the modern and developing treatment strategies in secondary and therapy-related acute myeloid leukemia.

6.
Med Sci (Basel) ; 9(4)2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34842758

RESUMO

Background Diabetes mellitus (DM) is a decisive risk factor for severe illness in coronavirus disease 2019 (COVID-19). India is home to a large number of people with DM, and many of them were infected with COVID-19. It is critical to understand the impact of DM on mortality and other clinical outcomes of COVID-19 infection from this region. Aims The primary objective of our study was to analyze the mortality rate in people with DM infected with COVID-19. The secondary objectives were to assess the effect of various comorbidities on mortality and study the impact of DM on other clinical outcomes. Methods This is a retrospective study of COVID-19 infected patients admitted to a tertiary care hospital in north India in the early phase of the pandemic. Results Of the 1211 cases admitted, 19 were excluded because of incomplete data, and 1192 cases were finally considered for analysis. DM constituted 26.8% of total patients. The overall mortality rate was 6.1%, and the rate was 10.7% in the presence of diabetes (p < 0.01, OR 2.55). In univariate analysis, increased age, chronic kidney disease (CKD), coronary artery disease (CAD), stroke, and cancer were associated with mortality. On multiple logistic regression, the independent predictors of mortality were CAD, CKD, and cancer. Breathlessness and low SpO2 at presentation, extensive involvement in CXR, and elevated ANC/ALC ratio were also significantly associated with mortality. Conclusions The presence of comorbidities such as DM, hypertension, CAD, CKD, and cancer strongly predict the risk of mortality in COVID-19 infection. Early triaging and aggressive therapy of patients with these comorbidities can optimize clinical outcomes.


Assuntos
COVID-19 , Diabetes Mellitus , COVID-19/mortalidade , Comorbidade , Doença da Artéria Coronariana/complicações , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Humanos , Neoplasias/complicações , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos
7.
Anal Bioanal Chem ; 413(13): 3455-3469, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33796931

RESUMO

Chromium contamination of soil and water is a serious environmental and public health concern as the hexavalent form of chromium [Cr(VI)] is readily soluble in water and is a confirmed carcinogen. There is an imminent need for a robust, low-cost, and simple analytical technique to facilitate in situ monitoring of Cr(VI) in water. Current quantitative methods of Cr(VI) detection are largely laboratory-based, time-consuming, expensive, and require training for implementation. In this contribution, a portable, easy-to-use, and compact measuring tool is presented that provides Cr(VI) concentration within 10 min of water sampling over a linear range of 0-3 mg L-1. This tool utilizes a relatively inexpensive camera-enabled smartphone with a custom-made test chamber attachment to seamlessly perform Cr(VI) measurements on water samples in the field. For analysis, an android-based software application was developed that directs the user to perform a simple series of steps following the diphenylcarbazide-based colorimetric method prescribed by the American Public Health Association. The tool was validated against a standard UV-visible spectrophotometer for a variety of synthetic and naturally contaminated water samples, with correlation factors greater than 0.993 (p < .001). The colorimetric method was also validated against a non-colorimetric Cr(VI) detection technique-ion chromatography-inductively coupled plasma mass spectrometry. Furthermore, Cr(VI) detection limits for the smartphone-enabled colorimetric method were found to be within 1.3-11.6 µg L-1, which were significantly better than reported for commercially available field test kits, and even surpassed the limits exhibited by a typical spectrophotometer (25-50 µg L-1). Finally, real-time mapping of source waters at a contaminated site was demonstrated by remote logging of Cr(VI) water quality data and corresponding GPS coordinates into a cloud server. This study highlights the potential role of smartphone-based monitoring tool in providing information to the affected community and enabling safe access to drinking water. An accurate, robust, simple-to-use, and economic method to measure hexavalent chromium in water within 10 min of sampling at site.

9.
Obstet Gynecol Sci ; 64(2): 174-189, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33499580

RESUMO

The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical characteristics and laboratory parameters of COVID-19 patients were compiled systematically, with special reference to pregnant women in order to understand the disease course. An extensive literature search on various scientific databases for relevant manuscripts was conducted, which yielded 7 manuscripts for final analysis. The most common symptoms were fever (85%), cough (70.63%), chest tightness (37.36%), expectoration (33.27%), fatigue (32%), dyspnea (31.95%), and shortness of breath (31.19%), while hemoptysis (1.0%) was the least common. The associated comorbidities were hypertension (21.6%) and diabetes (10.0%). In terms of hematological parameters, lower total leukocyte counts were observed in 65% of cases and biochemical parameters, patients demonstrated elevated levels of albumin (53.72%), lactate dehydrogenase (45.71%), and natriuretic peptide (34.84%); however, total bilirubin was elevated in only 8% of cases. In the acute inflammatory cytokine profile, C-reactive protein (59.0%), tumor necrosis factor (58.0%), erythrocyte sedimentation rate (57.0%), interleukin-2 (IL- 2, 54.0%), and IL-6 (52.0%) levels were increased, while prolactin levels (6.5%) were minimally elevated. The recovery rate was approximately 41%, and mortality was about 6.5%. The study also concluded that the clinical symptoms of COVID-19 were similar among pregnant and non-pregnant women. There was no evidence of vertical transmission of COVID-19 infection. This review critically analyzed COVID-19 as a public health hazard in order to help policy makers, health care givers, and primary physicians to promote early diagnosis and prevention.

10.
Neuron ; 107(3): 470-486.e11, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32592656

RESUMO

Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 µm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.


Assuntos
Encéfalo/diagnóstico por imagem , Cálcio/metabolismo , Corpo Celular/patologia , Neurônios/patologia , Imagem Óptica/métodos , Animais , Artefatos , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Ligação ao Cálcio , Corpo Celular/metabolismo , Proteínas de Fluorescência Verde , Camundongos , Neurônios/metabolismo , Neurópilo , Peixe-Zebra
11.
Brain Res ; 1687: 155-161, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29524437

RESUMO

The non-competitive glutamate antagonist, phencyclidine is used in rodents to model behavioural deficits see in schizophrenia. Importantly, these deficits endure long after the cessation of short-term chronic treatment (sub-chronic), indicating that the drug treatment causes long-term changes in the physiology and/or chemistry of the brain. There is evidence that this may occur through glutamatergic modulation of mesolimbic dopamine release, perhaps involving metabotropic glutamate receptors (mGluR). This study sought to investigate the effect of sub-chronic phencyclidine pretreatment on modulation of dopamine neurotransmission by metabotropic glutamate receptors 2 and 5 (mGluR2 and mGluR5) in the nucleus accumbens shell in vitro, with the hypothesis that phencyclidine pretreatment would disrupt the mGluR-mediated modulation of dopamine release. We showed that the orthosteric mGluR2 agonist LY379268 (0.1 µM, 1 µM and 10 µM) and mGluR5 positive allosteric modulator CDPPB (1 µM and 10 µM) both attenuated potassium-evoked dopamine release, underscoring their role in modulating dopamine neurotransmission in the nucleus accumbens. Sub-chronic PCP treatment, which caused cognitive deficits measured by performance in the novel object recognition task, modelling aspects of behavioral deficits seen in schizophrenia, induced neurobiological changes that enhanced dopamine release in the nucleus accumbens, but had no effect on mGluR2 or mGluR5 mediated changes in dopamine release. Therefore it is unlikely that schizophrenia-related behavioural changes seen after sub-chronic phencyclidine pre-treatment are mediated through mGluR modulation of dopamine release.


Assuntos
Dopamina/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Fenciclidina/uso terapêutico , Receptores de Glutamato Metabotrópico/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Técnicas Eletroquímicas , Feminino , Técnicas In Vitro , Potássio/farmacologia , Ratos , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos
12.
Part Part Syst Charact ; 34(1)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28804214

RESUMO

A simple strategy for making nanoparticles by sonofragmentation of high-aspect-ratio 1D substrates is introduced. With common laboratory equipment, ultra-thin nanowires are fragmented into nanoparticles of size determined by the nanowire width, resulting within hours in monodisperse, crystalline nanoparticles of < 10 nm. This strategy is applicable to a diversity of semiconductor, oxide and metal nanowires.

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