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1.
Cell Mol Bioeng ; 16(5-6): 443-457, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38099214

RESUMEN

Introduction: Cell proliferation represents a major hallmark of cancer biology, and manifests itself in the assessment of tumor growth, drug resistance and metastasis. Tracking cell proliferation or cell fate at the single-cell level can reveal phenotypic heterogeneity. However, characterization of cell proliferation is typically done in bulk assays which does not inform on cells that can proliferate under given environmental perturbations. Thus, there is a need for single-cell approaches that allow longitudinal tracking of the fate of a large number of individual cells to reveal diverse phenotypes. Methods: We fabricated a new microfluidic architecture for high efficiency capture of single tumor cells, with the capacity to monitor cell divisions across multiple daughter cells. This single-cell proliferation (SCP) device enabled the quantification of the fate of more than 1000 individual cancer cells longitudinally, allowing comprehensive profiling of the phenotypic heterogeneity that would be otherwise masked in standard cell proliferation assays. We characterized the efficiency of single cell capture and demonstrated the utility of the SCP device by exposing MCF-7 breast tumor cells to different doses of the chemotherapeutic agent doxorubicin. Results: The single cell trapping efficiency of the SCP device was found to be ~ 85%. At the low doses of doxorubicin (0.01 µM, 0.001 µM, 0.0001 µM), we observed that 50-80% of the drug-treated cells had undergone proliferation, and less than 10% of the cells do not proliferate. Additionally, we demonstrated the potential of the SCP device in circulating tumor cell applications where minimizing target cell loss is critical. We showed selective capture of breast tumor cells from a binary mixture of cells (tumor cells and white blood cells) that was isolated from blood processing. We successfully characterized the proliferation statistics of these captured cells despite their extremely low counts in the original binary suspension. Conclusions: The SCP device has significant potential for cancer research with the ability to quantify proliferation statistics of individual tumor cells, opening new avenues of investigation ranging from evaluating drug resistance of anti-cancer compounds to monitoring the replicative potential of patient-derived cells. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00773-z.

2.
Mymensingh Med J ; 32(4): 1064-1072, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37777903

RESUMEN

Approximately 10.0% of tuberculosis (TB) Infected individuals develop clinical disease in the absence of immune suppression suggests that individual factors may play a role in the response to infection. Body's immune function is boosted by micronutrient and also plays a major role in response to tubercular infection. Someone, may argue that cell mediated immunity is compromised in iron deficiency before anemia becomes apparent. This descriptive observational study intended to assess serum iron profile in patients suffering from pulmonary tuberculosis. This study included 56 newly diagnosed sputum smear positive and negative pulmonary tuberculosis patients as per inclusion and exclusion criteria and was conducted at the department of the Internal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh with the collaboration of the Biochemistry department, BSMMU, Bangladesh from February 2017 to January 2018. Collected data were recorded in a structured questionnaire and compiled and appropriate analyses were done by using computer-based software Statistical Package for Social Sciences (SPSS) version 23.0. Out of 56 patients, majority was young and at reproductive age, male was predominant (78.6%) with a male to female ratio of 3.7:1. More than three fourth 43(81.0%) patients were found to have low serum iron concentration. Majority 45(80.4%) patients had normal serum TIBC, 6(10.7%) had low serum total iron binding capacity (TIBC) and 5(8.9%) had high serum TIBC. Almost two third 36(64.3%) patients had low serum transferrin saturation and 20(35.7%) had normal serum transferrin saturation. Majority 31(55.4%) patients had normal serum ferritin, 2(3.6%) had low serum ferritin and 23(41.1%) had high serum ferritin. Serum iron concentration and serum ferritin were significantly associated with chest x-ray abnormalities (p<0.01). Half of the patients were smear positive for acid fast bacilli (AFB) (50.0%). No significant association was found between sputum positive for AFB with iron profile status. In smear positive pulmonary tuberculosis patients, more than three fourth (78.6%) patients had low serum iron concentration at baseline and majority 20(80.0%) patients had normal serum iron concentration after 2(two) months. Mean serum iron concentration was 41.8±17.6mcg/l in baseline and 70.4±29.7mcg/l in at 2(two) month. More than sixty percent (60.7%) patients had low serum transferrin saturation at baseline and 20(80.0%) patients had normal serum transferrin saturation after 2(two) months. Mean serum transferrin saturation was 18.1±7.6% at baseline and 31.2±19.4% in at 2(two) months. After 2(two) months follow up serum iron concentration and serum transferrin saturation had significant improvement (p<0.05). Significant iron deficiency status occurred in pulpmonary tuberculosis and which improved after anti-tubercular treatment without iron supplementation.


Asunto(s)
Deficiencias de Hierro , Tuberculosis Pulmonar , Tuberculosis , Humanos , Masculino , Femenino , Ferritinas , Hierro , Tuberculosis Pulmonar/diagnóstico , Transferrinas , Transferrina/metabolismo
3.
World Neurosurg ; 178: 172-180.e3, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37473863

RESUMEN

OBJECTIVE: Traumatic spine injury (TSI) leads to significant morbidity and mortality in children. However, the global epidemiology of pediatric TSI is currently unknown. We conducted a systematic review and meta-analysis to estimate the global incidence of pediatric TSI and the burden of cases. METHODS: PubMed, Embase, and Scopus were searched for reports in June 2021 and updated in March 2023 with no restrictions on language or year of publication. A meta-analysis was conducted to estimate the global incidence of pediatric TSI and, subsequently, the number of cases of pediatric TSI worldwide and the proportion requiring spine surgery. RESULTS: Of 6557 studies, 25 met the inclusion criteria. Road traffic accidents (64%) were responsible for most cases reported in the literature, followed by falls (18%). The global incidence of TSI in children aged ≤20 years was estimated to be 14.24 of 100,000 children, or 375,734 children, with an estimated 114,975 requiring spine surgery. Across the World Bank income classification groups, lower middle-income countries had the highest pediatric TSI case burden (186,886 cases, with 57,187 requiring spine surgery). Across the World Health Organization regions, countries in the Southeast Asia region had the largest number of projected cases at 88,566, with 27,101 requiring surgical management, followed closely by the African region, with 87,235 projected cases and 26,694 requiring surgical management. CONCLUSIONS: Pediatric TSI represents a large healthcare burden globally. Interventions targeting both injury prevention and strengthening of neurosurgical capacity, especially in low resource settings, are needed to address this global health challenge.

4.
J Med Case Rep ; 16(1): 407, 2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36345015

RESUMEN

BACKGROUND: Abacavir is a nucleoside reverse transcriptase inhibitor that is used as a component of the antiretroviral treatment regimen in the management of the human immunodeficiency virus for both adults and children. It is efficacious, but its use may be limited by a hypersensitivity reaction linked with the HLA-B*57:01 genotype. HLA-B*57:01 has been reported to be rare in African populations. Because of the nature of its presentation, abacavir hypersensitivity is prone to late diagnosis and treatment, especially in settings where HLA-B*57:01 genotyping is not routinely done. CASE REPORT: We report a case of a severe hypersensitivity reaction in a 44-year-old Kenyan female living with the human immunodeficiency virus and on abacavir-containing antiretroviral therapy. The patient presented to the hospital after recurrent treatment for a throat infection with complaints of fever, headache, throat ache, vomiting, and a generalized rash. Laboratory results evidenced raised aminotransferases, for which she was advised to stop the antiretrovirals that she had recently been started on. The regimen consisted of abacavir, lamivudine, and dolutegravir. She responded well to treatment but was readmitted a day after discharge with vomiting, severe abdominal pains, diarrhea, and hypotension. Her symptoms disappeared upon admission, but she was readmitted again a few hours after discharge in a hysterical state with burning chest pain and chills. Suspecting abacavir hypersensitivity, upon interrogation she reported that she had taken the abacavir-containing antiretrovirals shortly before she was taken ill. A sample for HLA-B*57:01 was taken and tested positive. Her antiretroviral regimen was substituted to tenofovir, lamivudine, and dolutegravir, and on subsequent follow-up she has been well. CONCLUSIONS: Clinicians should always be cognizant of this adverse reaction whenever they initiate an abacavir-containing therapy. We would recommend that studies be done in our setting to verify the prevalence of HLA-B*57:01.


Asunto(s)
Fármacos Anti-VIH , Hipersensibilidad a las Drogas , Infecciones por VIH , Adulto , Niño , Femenino , Humanos , Lamivudine/efectos adversos , Kenia , Didesoxinucleósidos/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Vómitos , Fármacos Anti-VIH/efectos adversos , Hipersensibilidad a las Drogas/etiología
5.
Case Rep Ophthalmol Med ; 2022: 3614225, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36404806

RESUMEN

Purpose: To report a rare case of left-sided metastatic optic nerve infiltration and right-sided choroidal mass with exudative retinal detachment caused by EGFR exon 19 deletion positive non-small-cell lung adenocarcinoma that responded to targeted therapy with osimertinib (EGFR-TKI). Our patient demonstrated an excellent response with reduced size of the metastatic choroidal mass of the right orbit and improved visual acuity, in addition to systemic disease control. Case: A 66-year-old male patient with a history of diabetes mellitus, hypertension, and tobacco use presented with sudden vision loss in the left eye secondary to optic nerve infiltration and subacute vision loss in the right eye secondary to exudative retinal detachment from a choroidal metastasis. He was found to have a right lung mass, multiple metastatic pulmonary nodules, and liver and bone metastases. Biopsy from a mediastinal lymph node confirmed the diagnosis of metastatic lung adenocarcinoma. He was found to have exon 19 deletion on next-generation sequencing. We treated him with local radiation therapy to the left eye and systemic osimertinib (EGFR-TKI). Conclusion: To our knowledge, our case is the first report of a patient who initially presented with acute vision loss and was found to have metastatic retrobulbar optic nerve infiltration in one eye and metastatic choroidal lesion with exudative retinal detachment in the fellow eye secondary to lung adenocarcinoma. Due to the rarity of this condition, literature regarding effective treatment is scarce. Our patient demonstrated significant improvement in visual acuity and resolution of exudative retinal detachment in the right eye following osimertinib treatment and radiation therapy to the left eye. Further investigation into the role of tyrosine kinase inhibitors and radiation therapy in treating intraocular metastasis involving the optic nerve is needed.

6.
Sci Rep ; 11(1): 20978, 2021 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-34697331

RESUMEN

Due to complexity of smallholder farms, many times technologies with great potential fail to achieve the desired impact in leveraging productivity and profitability of the farming community. In the Indo-Gangetic Plains there is an urgent need to understand the diversity of farm households, identifying the main drivers deciding their system thus, classifying them into homogenous groups. In the present study, the diversity of smallholder farms was assessed using crop, livestock and income related characteristics and associated farm mechanization. Using principal component analysis and cluster analysis for 252 farm households, 4 farm types were identified i.e. Type 1. Small Farm households with cereal-based cropping system and subsistence livestock (39%), Type 2. Small Farm households with diversified cropping system dominated by cereal and fodder crops with only cattle herd (9%), Type 3. Marginal Farm household with diversified cropping system dominated by cash crop and herd comprising of only cattle (39%), Type 4. Marginal Farm household with diversified cropping system dominated by cereal crops and herd dominated by small ruminants (12%). Based on the constraints identified for different components of farming systems, low-cost interventions were planned for each farm type. These interventions have resulted in 84.8-103.2 per cent increase in the income of the farm HH under study suggesting usefulness of typology-based intervention planning in increasing income of small farm holders.

7.
Cell Rep Med ; 2(1): 100188, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33521702

RESUMEN

Chordomas are rare spinal tumors addicted to expression of the developmental transcription factor brachyury. In chordomas, brachyury is super-enhancer associated and preferentially downregulated by pharmacologic transcriptional CDK inhibition, leading to cell death. To understand the underlying basis of this sensitivity, we dissect the brachyury transcription regulatory network and compare the consequences of brachyury degradation with transcriptional CDK inhibition. Brachyury defines the chordoma super-enhancer landscape and autoregulates through binding its super-enhancer, and its locus forms a transcriptional condensate. Transcriptional CDK inhibition and brachyury degradation disrupt brachyury autoregulation, leading to loss of its transcriptional condensate and transcriptional program. Compared with transcriptional CDK inhibition, which globally downregulates transcription, leading to cell death, brachyury degradation is much more selective, inducing senescence and sensitizing cells to anti-apoptotic inhibition. These data suggest that brachyury downregulation is a core tenet of transcriptional CDK inhibition and motivates developing strategies to target brachyury and its autoregulatory feedback loop.


Asunto(s)
Biomarcadores de Tumor/genética , Cordoma/genética , Quinasas Ciclina-Dependientes/genética , Proteínas Fetales/genética , Proteínas de Neoplasias/genética , Neoplasias de la Columna Vertebral/genética , Proteínas de Dominio T Box/genética , Secuencia de Bases , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Cordoma/metabolismo , Cordoma/patología , Quinasas Ciclina-Dependientes/metabolismo , Proteínas Fetales/metabolismo , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Células HEK293 , Histonas/genética , Histonas/metabolismo , Humanos , Queratina-18/genética , Queratina-18/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Proteínas de Neoplasias/metabolismo , Proteolisis , Transducción de Señal , Neoplasias de la Columna Vertebral/metabolismo , Neoplasias de la Columna Vertebral/patología , Proteínas de Dominio T Box/metabolismo
8.
Clin Infect Dis ; 73(11): e4166-e4174, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-32706859

RESUMEN

BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. CLINICAL TRIALS REGISTRATION: NCT04292899 and EUPAS34303.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Adulto , Alanina/análogos & derivados , Antivirales/uso terapéutico , Estudios de Cohortes , Humanos , Saturación de Oxígeno , Estudios Retrospectivos , SARS-CoV-2 , Nivel de Atención , Resultado del Tratamiento
10.
AACE Clin Case Rep ; 6(6): e357-e360, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33244503

RESUMEN

OBJECTIVE: To shed light on a unique presentation of duplication of the pituitary gland (DPG)-plus syndrome. METHODS: We present the case report gathered from the patient. RESULTS: This patient uniquely had DPG-plus syndrome with a concurrent dermoid cyst. CONCLUSION: DPG is a very rare developmental anomaly and there are not many case reports published in the literature. The presence of DPG with dermoid cyst in our patient has not been reported previously. This case report discusses the various presentations of the syndrome and also provides an overview of investigations and management of these patients.

11.
Indian J Tuberc ; 67(3): 423-425, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32825886

RESUMEN

Moxifloxacin is a third-generation fluoroquinolone antibiotic with broad spectrum activity and also used as component of anti-tubercular therapy (ATT). Though frequently prescribed, moxifloxacin induced encephalopathy is uncommonly seen. Here we describe a forty four year old male, with features of disseminated tuberculosis (TB) and suspected case of multi-drug resistance (MDR), who developed acute encephalopathy. Extensive laboratory investigations, neuroimaging of brain, cerebrospinal fluid analysis was unremarkable. On stopping moxifloxacin, which was being administerd as part of ATT for MDR TB, encephalopathy resolved completely, thereby proving it to be a case of moxifloxacin induced encephalopathy. To conclude, by presenting this case, we wish to raise awareness about moxifloxacin induced encephalopathy among healthcare providers.


Asunto(s)
Antituberculosos/efectos adversos , Discitis/tratamiento farmacológico , Encefalitis/inducido químicamente , Moxifloxacino/efectos adversos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis de la Columna Vertebral/tratamiento farmacológico , Adulto , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Deprescripciones , Electroencefalografía , Encefalitis/fisiopatología , Humanos , Masculino , Síndromes de Neurotoxicidad/etiología
12.
Eur J Nucl Med Mol Imaging ; 47(13): 3118-3129, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32483653

RESUMEN

BACKGROUND: Initial studies of tuberculosis (TB) in macaques and humans using 18F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure. PATIENTS AND METHODS: HIV-negative adults with EPTB from eight sites across six countries had three 18F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. 18F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5-5.0 MBq/kg of 18F-FDG. FINDINGS: One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma. INTERPRETATION: Current 18F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways.


Asunto(s)
Fluorodesoxiglucosa F18 , Tuberculosis , Adulto , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Radiofármacos , Tuberculosis/diagnóstico por imagen
13.
Eur Respir J ; 55(2)2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31831584

RESUMEN

BACKGROUND: A large proportion of the huge global burden of extrapulmonary tuberculosis (EPTB) cases are treated empirically without accurate definition of disease sites and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 2-deoxy-2-(fluorine-18) fluoro-d-glucose (18F-FDG) in tuberculosis could be a useful imaging technique for localising disease sites and extent of disease. METHODS: We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across eight centres located in six countries: India, Pakistan, Thailand, South Africa, Serbia and Bangladesh, to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/computed tomography (CT) scans were performed within 2 weeks of presentation. FINDINGS: 358 patients with EPTB (189 females; 169 males) were recruited over 45 months, with an age range of 18-83 years (females median 30 years; males median 38 years). 350 (98%) out of 358 patients (183 female, 167 male) had positive scans. 118 (33.7%) out of 350 had a single extrapulmonary site and 232 (66.3%) out of 350 had more than one site (organ) affected. Lymph nodes, skeleton, pleura and brain were common sites. 100 (28%) out of 358 EPTB patients had 18F-FDG PET/CT-positive sites in the lung. 110 patients were 18F-FDG PET/CT-positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. INTERPRETATION: 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies.


Asunto(s)
Fluorodesoxiglucosa F18 , Tuberculosis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bangladesh , Estudios Transversales , Femenino , Humanos , India , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pakistán , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Radiofármacos , Sudáfrica , Tuberculosis/diagnóstico por imagen , Adulto Joven
15.
Pediatrics ; 141(6)2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29728429

RESUMEN

BACKGROUND: Interferon-γ release assays (IGRAs) are important adjunctive tests for diagnosing tuberculosis (TB) disease in children. METHODS: We analyzed California TB registry data for patients ≤18 years with laboratory-confirmed TB disease during 2010-2015 to identify case characteristics associated with test selection and performance and measure IGRA sensitivity. RESULTS: In total, 778 cases of TB were reported; 360 were laboratory confirmed. Indeterminate IGRAs were associated with being <1 year old (prevalence rate ratio 9.23; 95% confidence interval 2.87 to 29.8) and having central nervous system disease (prevalence rate ratio 2.69; 95% confidence interval 1.06 to 6.86) on multivariable analysis. Ninety-five children had both an IGRA and tuberculin skin test (TST) performed. Among those, the sensitivity of IGRA in 5- to 18-year-olds was 96% (66 out of 69) vs 83% (57 out of 69) for TST (P = .01); IGRA sensitivity compared with TST in children ages 2 to 4 was 91% (10 out of 11) vs 91% (10 out of 11) (P > .99), and the sensitivity compared with TST in children aged <2 years was 80% (12 out of 15) vs 87% (13 out of 15) (P > .99). CONCLUSIONS: This is the largest North American analysis of IGRA use and performance among children with TB disease. In children <5 years old, IGRA sensitivity is similar to TST, but sensitivity of both tests are reduced in children <2 years old. Indeterminate results are higher in children <1 year old and in central nervous system disease. In children ≥5 years old with laboratory-confirmed TB, IGRA has greater sensitivity than TST and should be considered the preferred immunodiagnostic test..


Asunto(s)
Ensayos de Liberación de Interferón gamma , Tuberculosis/diagnóstico , Adolescente , Factores de Edad , California/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Mycobacterium tuberculosis/inmunología , Sistema de Registros , Estudios Retrospectivos , Sensibilidad y Especificidad , Prueba de Tuberculina , Tuberculosis/epidemiología
16.
Biomicrofluidics ; 12(1): 014114, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29531635

RESUMEN

The transport of deformable objects, including polymer particles, vesicles, and cells, has been a subject of interest for several decades where the majority of experimental and theoretical studies have been focused on circular tubes. Due to advances in microfluidics, there is a need to study the transport of individual deformable particles in rectangular microchannels where corner flows can be important. In this study, we report measurements of hydrodynamic mobility of confined polymeric particles, vesicles, and cancer cells in a linear microchannel with a square cross-section. Our operating conditions are such that the mobility is measured as a function of geometric confinement over the range 0.3 < λ < 1.5 and at specified particle Reynolds numbers that are within 0.1 < Rep < 2.5. The experimental mobility data of each of these systems is compared with the circular-tube theory of Hestroni, Haber, and Wacholder [J. Fluid Mech. 41, 689-705 (1970)] with modifications made for a square cross-section. For polymeric particles, we find that the mobility data agrees well over a large confinement range with the theory but under predicts for vesicles. The mobility of vesicles is higher in a square channel than in a circular tube, and does not depend significantly on membrane mechanical properties. The mobility of cancer cells is in good agreement with the theory up to λ ≈ 0.8, after which it deviates. Comparison of the mobility data of the three systems reveals that cancer cells have higher mobility than rigid particles but lower than vesicles, suggesting that the cell membrane frictional properties are in between a solid-like interface and a fluid bilayer. We explain further the differences in the mobility of the three systems by considering their shape deformation and surface flow on the interface. The results of this study may find potential applications in drug delivery and biomedical diagnostics.

17.
Bioorg Med Chem Lett ; 28(7): 1198-1206, 2018 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-29525219

RESUMEN

Gram-positive bacteria are among the most common human pathogens associated with clinical infections which range from mild skin infections to sepsis. Resistance towards existing class of drugs by Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE) and vancomycin resistant enterococci (VRE) is a growing concern. There is an urgent need to discover new antibiotics which are active against resistant strains of Gram positive bacteria. We report herein a novel class of spiropyrimidinetrione oxazolidinone derivatives as novel antibacterial agents. Key step towards the synthesis of title compounds involved the use of tert-amino reaction with [1,5]-hydride shift leading to the new CC bond formation. Compound 30n has demonstrated potent antibacterial activity against a panel of Gram-positive microbial strains including MRSA, MRSE, and LNZ and vancomycin resistant strains of E. faecalis. Further, molecular docking studies suggest that 30n has binding mode similar to that of LNZ in 50S RNA ribosome.


Asunto(s)
Antibacterianos/farmacología , Diseño de Fármacos , Oxazolidinonas/farmacología , Pirimidinonas/farmacología , Compuestos de Espiro/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Oxazolidinonas/síntesis química , Oxazolidinonas/química , Pirimidinonas/síntesis química , Pirimidinonas/química , Compuestos de Espiro/síntesis química , Compuestos de Espiro/química , Staphylococcus epidermidis/efectos de los fármacos , Relación Estructura-Actividad , Enterococos Resistentes a la Vancomicina/efectos de los fármacos
18.
APL Bioeng ; 2(3): 032002, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31069319

RESUMEN

There is growing recognition that cell deformability can play an important role in cancer metastasis and diagnostics. Advancement of methods to characterize cell deformability in a high throughput manner and the capacity to process numerous samples can impact cancer-related applications ranging from analysis of patient samples to discovery of anti-cancer compounds to screening of oncogenes. In this study, we report a microfluidic technique called multi-sample deformability cytometry (MS-DC) that allows simultaneous measurement of flow-induced deformation of cells in multiple samples at single-cell resolution using a combination of on-chip reservoirs, distributed pressure control, and data analysis system. Cells are introduced at rates of O(100) cells per second with a data processing speed of 10 min per sample. To validate MS-DC, we tested more than 50 cell-samples that include cancer cell lines with different metastatic potential and cells treated with several cytoskeletal-intervention drugs. Results from MS-DC show that (i) the cell deformability correlates with metastatic potential for both breast and prostate cancer cells but not with their molecular histotype, (ii) the strongly metastatic breast cancer cells have higher deformability than the weakly metastatic ones; however, the strongly metastatic prostate cancer cells have lower deformability than the weakly metastatic counterparts, and (iii) drug-induced disruption of the actin network, microtubule network, and actomyosin contractility increased cancer cell deformability, but stabilization of the cytoskeletal proteins does not alter deformability significantly. Our study demonstrates the capacity of MS-DC to mechanically phenotype tumor cells simultaneously in many samples for cancer research.

19.
Cell Mol Biol (Noisy-le-grand) ; 63(6): 38-43, 2017 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-28968207

RESUMEN

Blackgram is an important pulse crop of the tropic and sub-tropic area and has been identified as a potential crop in many countries. In the south-East Asia arsenic toxicity in soil and water is one of the most environmental problems. Crop productivity is highly affected by cultivation in arsenic polluted soil or irrigation through arsenic polluted water. The present study was conducted to evaluate the effect of arsenic (As) on fresh shoot length, fresh shoot weight, fresh root length, fresh shoot weight and total fresh biomass, The results indicate that root length is more affected than shoot length due to arsenic toxicity. The fresh shoot weight observed was more affected than fresh root weight. This study indicates that arsenic toxicity causes the deleterious effect on blackgram growth. The toxic effect of blackgram depends on the genotypic variability. Some blackgram genotypes show very less toxic effect of arsenic due to its genetic makeup. Experimental findings of study indicate that longer root length and more shoot weight in arsenic stress condition may be tolerant blackgram genotype to arsenic toxicity.


Asunto(s)
Arsénico/toxicidad , Vigna/efectos de los fármacos , Biomasa , Genotipo , Raíces de Plantas/efectos de los fármacos , Suelo/química , Agua/química
20.
Eur Urol ; 70(4): 649-660, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27234997

RESUMEN

CONTEXT: Radical cystectomy (RC) is associated with frequent morbidity and prolonged length of stay (LOS) irrespective of surgical approach. Increasing evidence from colorectal surgery indicates that minimally invasive surgery and enhanced recovery programmes (ERPs) can reduce surgical morbidity and LOS. ERPs are now recognised as an important component of surgical management for RC. However, there is comparatively little evidence for ERPs after robot-assisted radical cystectomy (RARC). Due to the multimodal nature of ERPs, they are not easily validated through randomised controlled trials. OBJECTIVE: To provide a European Association of Urology (EAU) Robotic Urology Section (ERUS) policy on ERPs to guide standardised perioperative management of RARC patients. EVIDENCE ACQUISITION: The guidance was formulated in four phases: (1) systematic literature review of evidence for ERPs in robotic, laparoscopic, and open RC; (2) an online questionnaire survey formulated and sent to ERUS Scientific Working Group members; (3) achievement of consensus from an expert panel using the Delphi process; and (4) a standardised reporting template to audit compliance and outcome designed and approved by the committee. EVIDENCE SYNTHESIS: Consensus was reached in multiple areas of an ERP for RARC. The key principles include patient education, optimisation of nutrition, RARC approach, standardised anaesthetic, analgesic, and antiemetic regimens, and early mobilisation. CONCLUSIONS: This consensus represents the views of an expert panel established to advise ERUS on ERPs for RARC. The ERUS Scientific Working Group recognises the role of ERPs and endorses them as standardised perioperative care for patients undergoing RARC. ERPs in robotic surgery will continue to evolve with technological and pharmaceutical advances and increasing understanding of the role of surgery-specific ERPs. PATIENT SUMMARY: There is currently a lack of high-level evidence exploring the benefits of enhanced recovery programmes (ERPs) in patients undergoing robot-assisted radical cystectomy (RARC). We reported a consensus view on a standardised ERP specific to patients undergoing RARC. It was formulated by experts from high-volume RARC hospitals in Europe, combining current evidence for ERPs with experts' knowledge of perioperative care for robotic surgery.


Asunto(s)
Cistectomía/métodos , Atención Perioperativa/métodos , Complicaciones Posoperatorias/prevención & control , Recuperación de la Función , Procedimientos Quirúrgicos Robotizados , Consenso , Ambulación Precoz , Humanos
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