Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Am J Hum Genet ; 110(4): 648-662, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-36977412

RESUMEN

Several breast cancer susceptibility genes have been discovered, but more are likely to exist. To identify additional breast cancer susceptibility genes, we used the founder population of Poland and performed whole-exome sequencing on 510 women with familial breast cancer and 308 control subjects. We identified a rare mutation in ATRIP (GenBank: NM_130384.3: c.1152_1155del [p.Gly385Ter]) in two women with breast cancer. At the validation phase, we found this variant in 42/16,085 unselected Polish breast cancer-affected individuals and in 11/9,285 control subjects (OR = 2.14, 95% CI = 1.13-4.28, p = 0.02). By analyzing the sequence data of the UK Biobank study participants (450,000 individuals), we identified ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR = 3.28, 95% CI = 1.76-6.14, p < 0.001). Immunohistochemistry and functional studies showed the ATRIP c.1152_1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress. We showed that tumors of women with breast cancer who have a germline ATRIP mutation have loss of heterozygosity at the site of ATRIP mutation and genomic homologous recombination deficiency. ATRIP is a critical partner of ATR that binds to RPA coating single-stranded DNA at sites of stalled DNA replication forks. Proper activation of ATR-ATRIP elicits a DNA damage checkpoint crucial in regulating cellular responses to DNA replication stress. Based on our observations, we conclude ATRIP is a breast cancer susceptibility gene candidate linking DNA replication stress to breast cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Neoplasias de la Mama , Proteínas de Unión al ADN , Femenino , Humanos , Proteínas Adaptadoras Transductoras de Señales/genética , Bancos de Muestras Biológicas , Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , Daño del ADN , Proteínas de Unión al ADN/genética , Polonia/epidemiología , Proteína de Replicación A/genética , Proteína de Replicación A/metabolismo , Reino Unido/epidemiología
2.
J Clin Immunol ; 43(8): 1941-1952, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37584719

RESUMEN

PURPOSE: Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4 + T cells results in combined immunodeficiency (CID). Patients typically present with severe respiratory and gastrointestinal tract infections at early ages. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy. METHODS: We describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency. RESULTS: Consanguinity was present in all affected families. The median age at the initial presentation was 5.5 months (range 7 days to 18 years). The main symptoms included failure to thrive, persistent diarrhea, and pneumonia. Autoimmune and neurologic features were also documented in about one-third of the patients, respectively. Thirteen patients carried RFXANK gene mutations, two carried RFX5 gene mutations, and three carried a RFXAP gene mutation. Six patients shared the same RFXANK founder mutation (c.162delG); limited to the Iranian population and dated to approximately 1296 years ago. Four of the patients underwent HSCT; three of them are alive. On the other hand, nine of the fourteen patients who did not undergo HSCT had a poor prognosis and died. CONCLUSION: MHC-II deficiency is not rare in Iran, with a high rate of consanguinity. It should be considered in the differential diagnosis of CID at any age. With the limited access to HSCT and its variable results in MHC-II deficiency, implementing genetic counseling and family planning for the affected families are mandatory. We are better determined to study the c.162delG RFXANK heterozygous mutation frequency in the Iranian population.


Asunto(s)
Proteínas de Unión al ADN , Inmunodeficiencia Combinada Grave , Factores de Transcripción , Humanos , Recién Nacido , Proteínas de Unión al ADN/genética , Antígenos de Histocompatibilidad Clase II/genética , Irán , Mutación/genética , Inmunodeficiencia Combinada Grave/genética , Factores de Transcripción/genética
3.
BMC Pediatr ; 23(1): 116, 2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36890496

RESUMEN

BACKGROUND: Evidence shows the increase of anti-tissue transglutaminase (tTG) levels in various conditions, including infectious agents, independently of celiac disease (CD). The aim of this study was to investigate the effect of helicobacter pylori (H.pylori) infection eradication on serum level of tTG in children with CD. METHODS: This study was conducted on children aged 2 to 18 who referred to reference hospitals for diagnosis of CD. After upper endoscopy and biopsy to confirm CD and H.pylori infection, the children were divided into three groups (including group one: 16 CD patients with positive H. pylori; group two: 16 non-CD patients with positive H. pylori; and group three: 56 CD patients with negative H. pylori), respectively. The tTG level in study groups were compared after the eradication of H.pylori. RESULTS: The mean age of the subjects in the group one, two, and three was 9.7 ± 3.33, 11.8 ± 3.14, and 7.6 ± 3.32 years, respectively. Our results showed that in group one, mean tTG increased after eradication of H.pylori infection, however, these changes were not significant (182.43 vs. 157.18, P = 0.121). In the second group, although unlike the first group, mean tTG decreased after eradication of the infection, but still these changes were not significant (9.56 vs. 22.18, P = 0.449). Furthermore, at the baseline level, the mean tTG in the group three was closer to the mean tTG in the first group. CONCLUSION: Our findings showed that the eradication of H.pylori infection does not have a significant effect on tTG levels in children with and without CD.


Asunto(s)
Enfermedad Celíaca , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Niño , Enfermedad Celíaca/diagnóstico , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Biopsia , Endoscopía
4.
Neuroimage ; 242: 118457, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34363959

RESUMEN

Interactions between different brain regions can be revealed by dependencies between their neuronal oscillations. We examined the sensitivity of different oscillatory connectivity measures in revealing interhemispheric interactions between primary motor cortices (M1s) during unilateral finger movements. Based on frequency, amplitude, and phase of the oscillations, a number of metrics have been developed to measure connectivity between brain regions, and each metric has its own strengths, weaknesses, and pitfalls. Taking advantage of the well-known movement-related modulations of oscillatory amplitude in M1s, this study compared and contrasted a number of leading connectivity metrics during distinct phases of oscillatory power changes. Between M1s during unilateral movements, we found that phase-based metrics were effective at revealing connectivity during the beta (15-35 Hz) rebound period linked to movement termination, but not during the early period of beta desynchronization occurring during the movement itself. Amplitude correlation metrics revealed robust connectivity during both periods. Techniques for estimating the direction of connectivity had limited success. Granger Causality was not well suited to studying these connections because it was strongly confounded by differences in signal-to-noise ratio linked to modulation of beta amplitude occurring during the task. Phase slope index was suggestive but not conclusive of a unidirectional influence between motor cortices during the beta rebound. Our findings suggest that a combination of amplitude and phase-based metrics is likely required to fully characterize connectivity during task protocols that involve modulation of oscillatory power, and that amplitude-based metrics appear to be more sensitive despite the lack of directional information.


Asunto(s)
Magnetoencefalografía/métodos , Corteza Motora/diagnóstico por imagen , Adulto , Femenino , Dedos , Humanos , Masculino , Movimiento , Sensibilidad y Especificidad , Adulto Joven
5.
Int Wound J ; 16(6): 1339-1346, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31418528

RESUMEN

The aim of this study was to identify diabetic foot ulcer (DFU) patients at risk for the development of a hard-to-heal wound. This is a post-hoc analysis of a prospective cohort study including a total of 208 patients with a DFU. The primary endpoints were time to healing and the development of a hard-to-heal-wound. Univariable and multivariable logistic and Cox regression analysis were used to study the associations of patient characteristics with the primary endpoints. The number of previous DFUs [odds ratio (OR): 1.42, 95% confidence interval (CI): 1.01-1.99, P = .04], University of Texas (UT) classification grade 2 (OR: 2.93, 95% CI: 1.27-6.72, P = .01), UT classification grade 3 (OR: 2.80, 95% CI: 1.17-6.71, P = .02), and a diagnosis of foot stand deformation (OR: 1.54, 95% CI: 0.77-3.08, P = .05) were significantly associated with the development of a hard-to-heal wound. Only UT classification grade 3 (HR: 0.61, 95% CI: 0.41-0.90, P = .01) was associated with time to healing. The number of previous DFUs, UT classification grade, and a diagnosis of foot deformation are significantly associated with development of a hard-to-heal wound in patients with a DFU. The only predictor significantly associated with time to healing was UT classification grade 3. These patient characteristics can be used to identify patients at risk for the development of hard-to-heal wounds, who might need an early intervention to prevent wound problems.


Asunto(s)
Pie Diabético/fisiopatología , Cicatrización de Heridas/fisiología , Estudios de Cohortes , Pie Diabético/clasificación , Femenino , Estudio Históricamente Controlado , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Índice de Severidad de la Enfermedad
6.
Gut ; 65(7): 1151-64, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26033966

RESUMEN

OBJECTIVE: Colorectal cancer remains the fourth most common cause of cancer-related mortality worldwide. Here we investigate the role of nuclear factor-κB (NF-κB) co-factor B-cell CLL/lymphoma 3 (BCL-3) in promoting colorectal tumour cell survival. DESIGN: Immunohistochemistry was carried out on 47 tumour samples and normal tissue from resection margins. The role of BCL-3/NF-κB complexes on cell growth was studied in vivo and in vitro using an siRNA approach and exogenous BCL-3 expression in colorectal adenoma and carcinoma cells. The question whether BCL-3 activated the AKT/protein kinase B (PKB) pathway in colorectal tumour cells was addressed by western blotting and confocal microscopy, and the ability of 5-aminosalicylic acid (5-ASA) to suppress BCL-3 expression was also investigated. RESULTS: We report increased BCL-3 expression in human colorectal cancers and demonstrate that BCL-3 expression promotes tumour cell survival in vitro and tumour growth in mouse xenografts in vivo, dependent on interaction with NF-κB p50 or p52 homodimers. We show that BCL-3 promotes cell survival under conditions relevant to the tumour microenvironment, protecting both colorectal adenoma and carcinoma cells from apoptosis via activation of the AKT survival pathway: AKT activation is mediated via both PI3K and mammalian target of rapamycin (mTOR) pathways, leading to phosphorylation of downstream targets GSK-3ß and FoxO1/3a. Treatment with 5-ASA suppressed BCL-3 expression in colorectal cancer cells. CONCLUSIONS: Our study helps to unravel the mechanism by which BCL-3 is linked to poor prognosis in colorectal cancer; we suggest that targeting BCL-3 activity represents an exciting therapeutic opportunity potentially increasing the sensitivity of tumour cells to conventional therapy.


Asunto(s)
Neoplasias Colorrectales/química , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas/metabolismo , Transducción de Señal , Factores de Transcripción/análisis , Factores de Transcripción/metabolismo , Animales , Antiinflamatorios no Esteroideos/farmacología , Apoptosis , Proteínas del Linfoma 3 de Células B , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Colon/química , Neoplasias Colorrectales/patología , Células HCT116 , Humanos , Mesalamina/farmacología , Ratones , Ratones Desnudos , FN-kappa B/análisis , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas/genética , ARN Interferente Pequeño/farmacología , Recto/química , Serina-Treonina Quinasas TOR/metabolismo , Factores de Transcripción/genética , Carga Tumoral
7.
Tumour Biol ; 35(4): 3827-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24338767

RESUMEN

Osteopontin (OPN) is a multifunctional glycophosphoprotein that was detected in many carcinomas, and it may have a prognostic role. The aim of this study was to determine osteopontin serum levels in patients with oral squamous cell carcinoma (OSCC) and investigated its correlation with clinicopathological features of tumor. Using an ELISA kit, we assessed and compared the circulating levels of OPN in blood serum of 45 oral squamous cell carcinoma patients with 45 healthy control samples. The serum osteopontin level in patients with OSCC was significantly higher (145.8 ± 14.6 ng/ml, n = 45) compared with the healthy controls (53.9 ± 9.6 ng/ml, n = 45, p < 0.001). Mean serum osteopontin level was significantly higher in patients with nodal metastasis (p = 0.03) and higher stage (p = 0.02). Findings of the present study suggest that OPN may have a potential role in pathogenesis of OSCC and it may be used as a tool for monitoring tumor progression.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Osteopontina/fisiología , Adulto , Anciano , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/etiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/sangre , Neoplasias de la Boca/etiología , Osteopontina/sangre , Pronóstico
8.
BMC Pregnancy Childbirth ; 14: 278, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-25128406

RESUMEN

BACKGROUND: Pre-eclampsia remains a dominant cause of maternal and fetal mortality in developed countries. In a previous prospective study we identified a fall in the VEGF-A isoform VEGF-A165b in the plasma of patients in the first trimester to be a predictor of later pre-eclampsia. VEGF-A165b has been shown to have potent cytoprotective properties in many cell types. We therefore tested the hypothesis that VEGF-A165b may be cytoprotective for placental trophoblasts. METHODS: We used an immortalised first trimester trophoblast cell line exposed to chemical toxicity, and physiological (<2% O2) and atmospheric oxygen (21% O2) in the presence or absence of VEGF-A165b, angiogenic VEGF-A165a, a non-specific anti-VEGF-A blocking antibody (bevacizumab), or a specific anti-VEGF-A165b antibody. Cell viability and cytotoxicity were measured by trypan blue and LDH assay respectively. RESULTS: Under high (21%) levels of oxygen, trophoblast viability was increased, and cytotoxicity reduced by exogenous recombinant VEGF-A165b (p < 0.05, n = 10) or VEGF-A165a. The cytoprotective effect was not seen under lower (<2%) oxygen conditions, where VEGF-A165b was upregulated. However inhibition of VEGF-A with blocking antibodies (bevacizumab or anti-VEGF-A165b) had marked cytotoxic effects under low oxygen conditions presumably through the blockade of autocrine survival pathways. CONCLUSIONS: These results show that when trophoblasts are exposed to lower oxygen tensions (as they are early in the 1st trimester) endogenous VEGF-A165b contributes to their survival through an autocrine pathway. In contrast in high oxygen conditions exogenous VEGF-A isoforms have a greater effect on trophoblast survival.


Asunto(s)
Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Oxígeno/farmacología , Trofoblastos/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/fisiología , Inhibidores de la Angiogénesis/farmacología , Bevacizumab/farmacología , Hipoxia de la Célula/fisiología , Línea Celular , Supervivencia Celular/fisiología , Humanos , Isoformas de Proteínas/farmacología , Isoformas de Proteínas/fisiología , Trofoblastos/fisiología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología
9.
ScientificWorldJournal ; 2014: 272949, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24563629

RESUMEN

The primary goal of this work is to provide a general optimal three-step class of iterative methods based on the schemes designed by Bi et al. (2009). Accordingly, it requires four functional evaluations per iteration with eighth-order convergence. Consequently, it satisfies Kung and Traub's conjecture relevant to construction optimal methods without memory. Moreover, some concrete methods of this class are shown and implemented numerically, showing their applicability and efficiency.


Asunto(s)
Modelos Teóricos
10.
Vet Med Sci ; 10(2): e1404, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38454742

RESUMEN

BACKGROUND: Anaplasma ovis (A. ovis) is the predominant causative agent of anaplasmosis in goats and sheep in most tropical and subtropical regions of the world. However, there is considerable variation in reported infection rates, breed susceptibility, and controversial findings regarding the haemolytic effects of A. ovis infection in goats. OBJECTIVES: Thus, we investigated the molecular and haematological aspects of A. ovis infection in goats from Ahvaz city. METHODS: One hundred and fifty apparently healthy goats (74 blacks and 76 Najdi goats) were randomly sampled from six flocks in the Ahvaz suburb during ticks' activity season. Haematological evaluation, smear microscopic (SM) examination and PCR assay were performed to assess A. ovis infection. Additionally, the percentage of parasitemia was determined from blood smears. RESULTS: SM examination revealed that 25.7% of the goats displayed erythrocyte Anaplasma-like inclusion bodies. PCR analysis indicated that 54% of the goats were positive for A. ovis infection (44.6% of blacks and 63.2% of Najdi goats). No significant difference in haematological values was observed between healthy and infected goats based on PCR testing. However, a significant difference in haematological indices was observed between the group with parasitemia level of 0.01-0.02% (SM and PCR positive) compared to the healthy goats (SM and PCR negative), particularly concerning Hb, PCV and RBC count (p < 0.01). CONCLUSIONS: When the parasitemia exceeds 0.01%, A. ovis infection may disrupt haematological parameters in infected goats. The high prevalence of A. ovis infection (54%) among the studied goats underscores the importance of giving special attention to implementing necessary measures for disease control in the Ahvaz suburb.


Asunto(s)
Anaplasma ovis , Anaplasmosis , Enfermedades de las Cabras , Enfermedades de las Ovejas , Ovinos , Animales , Anaplasmosis/epidemiología , Cabras , Irán/epidemiología , Parasitemia/veterinaria , Enfermedades de las Cabras/epidemiología , Enfermedades de las Ovejas/epidemiología
11.
Front Neuroimaging ; 3: 1341732, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38379832

RESUMEN

Introduction: Protocols for noninvasive brain stimulation (NIBS) are generally categorized as "excitatory" or "inhibitory" based on their ability to produce short-term modulation of motor-evoked potentials (MEPs) in peripheral muscles, when applied to motor cortex. Anodal and cathodal stimulation are widely considered excitatory and inhibitory, respectively, on this basis. However, it is poorly understood whether such polarity-dependent changes apply for neural signals generated during task performance, at rest, or in response to sensory stimulation. Methods: To characterize such changes, we measured spontaneous and movement-related neural activity with magnetoencephalography (MEG) before and after high-definition transcranial direct-current stimulation (HD-TDCS) of the left motor cortex (M1), while participants performed simple finger movements with the left and right hands. Results: Anodal HD-TDCS (excitatory) decreased the movement-related cortical fields (MRCF) localized to left M1 during contralateral right finger movements while cathodal HD-TDCS (inhibitory), increased them. In contrast, oscillatory signatures of voluntary motor output were not differentially affected by the two stimulation protocols, and tended to decrease in magnitude over the course of the experiment regardless. Spontaneous resting state oscillations were not affected either. Discussion: MRCFs are thought to reflect reafferent proprioceptive input to motor cortex following movements. Thus, these results suggest that processing of incoming sensory information may be affected by TDCS in a polarity-dependent manner that is opposite that seen for MEPs-increases in cortical excitability as defined by MEPs may correspond to reduced responses to afferent input, and vice-versa.

12.
J Res Med Sci ; 18(10): 911-3, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24497866

RESUMEN

Duplication of inferior vena cava (IVC) is a rare finding in radiologic studies and its coincidence with thrombosis is even rarer. Here we described a rare case with duplication of IVC and symptomatic venous thrombosis of her lower extrimity.

13.
J Patient Saf ; 19(3): 173-179, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36849451

RESUMEN

INTRODUCTION: Central line-associated bloodstream infections (CLABSIs) are associated with significant patient harm and health care costs. Central line-associated bloodstream infections are preventable through quality improvement initiatives. The COVID-19 pandemic has caused many challenges to these initiatives. Our community health system in Ontario, Canada, had a baseline rate of 4.62 per 1000 line days during the baseline period. OBJECTIVES: Our aim was to reduce CLABSIs by 25% by 2023. METHODS: An interprofessional quality aim committee performed a root cause analysis to identify areas for improvement. Change ideas included improving governance and accountability, education and training, standardizing insertion and maintenance processes, updating equipment, improving data and reporting, and creating a culture of safety. Interventions occurred over 4 Plan-Do-Study-Act cycles. The outcome was CLABSI rate per 1000 central lines: process measures were rate of central line insertion checklists used and central line capped lumens used, and balancing measure was the number of CLABSI readmissions to the critical care unit within 30 days. RESULTS: Central line-associated bloodstream infections decreased over 4 Plan-Do-Study-Act cycles from a baseline rate of 4.62 (July 2019-February 2020) to 2.34 (December 2021-May 2022) per 1000 line days (51%). The rate of central line insertion checklists used increased from 22.8% to 56.9%, and central line capped lumens used increased from 72% to 94.3%. Mean CLABSI readmissions within 30 days decreased from 1.49 to 0.1798. CONCLUSIONS: Our multidisciplinary quality improvement interventions reduced CLABSIs by 51% across a health system during the COVID-19 pandemic.


Asunto(s)
COVID-19 , Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Infección Hospitalaria , Sepsis , Humanos , Cateterismo Venoso Central/efectos adversos , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/prevención & control , Mejoramiento de la Calidad , Pandemias/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control
14.
Biochem Soc Trans ; 40(4): 831-5, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22817743

RESUMEN

SRPK1 (serine-arginine protein kinase 1) is a protein kinase that specifically phosphorylates proteins containing serine-arginine-rich domains. Its substrates include a family of SR proteins that are key regulators of mRNA AS (alternative splicing). VEGF (vascular endothelial growth factor), a principal angiogenesis factor contains an alternative 3' splice site in the terminal exon that defines a family of isoforms with a different amino acid sequence at the C-terminal end, resulting in anti-angiogenic activity in the context of VEGF165-driven neovascularization. It has been shown recently in our laboratories that SRPK1 regulates the choice of this splice site through phosphorylation of the splicing factor SRSF1 (serine/arginine-rich splicing factor 1). The present review summarizes progress that has been made to understand how SRPK1 inhibition may be used to manipulate the balance of pro- and anti-angiogenic VEGF isoforms in animal models in vivo and therefore control abnormal angiogenesis and other pathophysiological processes in multiple disease states.


Asunto(s)
Proteínas Serina-Treonina Quinasas/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Empalme Alternativo/genética , Animales , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Humanos , Degeneración Macular/genética , Degeneración Macular/metabolismo , Proteínas Serina-Treonina Quinasas/genética
15.
Curr Med Mycol ; 8(3): 18-22, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37051553

RESUMEN

Background and Purpose: Candidiasis is regarded as one of the most important fungal infections and a cause of disease and mortality in patients with hematological malignancy. Accordingly, antifungal prophylaxis is of significant importance in this regard. This study aimed to identify the epidemiology of Candida colonization and evaluate its antifungal susceptibility pattern in patients with hematological malignancy. Materials and Methods: In this study, the samples were collected from the oral cavity of 100 patients, and Candida colonization was confirmed by fungal culture. Candida strains were also identified by ITS-PCR. In vitro antifungal susceptibility tests against fluconazole, amphotericin B, and caspofungin were performed according to CLSI M60. Results: Demographic characteristics, comorbidities, distribution of Candida species (spp.), and antifungal susceptibility were analyzed in this study. The study participants included 100 patients with a mean age of 15.48%±48.74 years (age range: 17-84 years). Regarding gender distribution, the majority (64%) of the patients were male. In terms of the distribution of underlying hematologic malignancy, 27% of the cases had lymphoma. The most commonly isolated species among patients were C. albicans complex (49%; n=49), C. glabrata (39%; n=39), and co-colonization of C. albicans complex and C. with C. glabrata (10%; n=10). The overall resistance of C. albicans complex was 5% to fluconazole (n=5) and 2% to amphotericin B (n=2). Furthermore, C. glabrata showed 11% (n=11) resistance to fluconazole and was susceptible to amphotericin B. All Candida spp. isolated from patients who were susceptible to caspofungin. Conclusion: The high rate of colonization of Candida spp., especially the significant increase in the frequency of C. glabrata in patients with blood malignancies and the gradual increase in resistance to fluconazole, necessitate a change in the use of antifungal drugs for the prevention and experimental treatment of hematological malignancy.

16.
Int J Mol Cell Med ; 11(1): 78-87, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36397809

RESUMEN

Degeneration of dopaminergic (DA) neurons in the substantia nigra is known as the main cause of Parkinson's disease (PD). Preventing the loss of DA neurons alongside the cell-replacement therapy have brought tremendous hope for the treatment of PD. For this purpose, various studies have been done to find the specific DA neuro-protective compounds or progressing DA-differentiation methods. Ferulic acid (FA) has strong neuro-protective effects, but at this point its role on protection and differentiation of DA neurons is not well-defined. Mouse neural stem cells (mNSCs) were treated with FA and expressions of TH (tyrosine hydroxylase) and NURR1 as the DA neuron specific markers were determined using real time qRT-PCR and immunostaining assays . Finally, efficacy of FA on DA differentiation was evaluated in comparison with other methods using fibroblast growth factor 8b (FGF8b) and sonic hedgehog (SHH). Treatment with FA could increase the Th and Nurr1 gene expressions in mNSCs. Also, it enhanced ß - tubullin - III expression and increased the neurite length in treated groups. Real time qRT-PCR and immunostaining assays showed that FA could increase DA differentiation in mNSCs effectively. Also, gene expression profile in some groups showed that FA can raise the differentiation rate of other neuronal subtypes such as cholinergic neurons. FA effectively induces the DA differentiation in neural precursor cells by its ability to increase the expression of the NURR1 transcription factor, which is a known transcription factor for differentiation of midbrain DA neurons.

17.
Leadersh Health Serv (Bradf Engl) ; ahead-of-print(ahead-of-print)2021 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-34797039

RESUMEN

PURPOSE: Long-term care (LTC) organizations have struggled to protect their vulnerable clients from the ravages of the COVID-19 pandemic. Although various suggestions on containing outbreaks in LTC facilities have gained prominence, ensuring the safety of residents is not just a crisis issue. In that context, the authors must reasses the traditional management practices that were not sufficient for handling unexpected and demanding conditions. The purpose of this paper is to suggest rethinking the underlying attributes of LTC organizations and drawing insight from the parallels they have to high-reliability organizations (HROs). DESIGN/METHODOLOGY/APPROACH: The authors analyzed qualitative data collected from a Canadian LTC facility to shed light on the current state of reliability practices and culture of the LTC industry and to identify the strengths and weaknesses of the traditional management approaches. FINDINGS: To help the LTC industry develop the necessary crisis management capacity to tackle unexpected future challenges, there is an urgent need for adopting a more systemic top-down approach that cultivates mindfulness, learning and resilience. ORIGINALITY/VALUE: This study contributes by applying the HRO theoretical lens in the LTC context. The study provides the LTC leaders with insights into creating a unified effort at the industry level to give rise to a high-reliability-oriented industry.


Asunto(s)
COVID-19 , Cuidados a Largo Plazo , Canadá , Humanos , Pandemias , Reproducibilidad de los Resultados , SARS-CoV-2
18.
Cureus ; 13(7): e16666, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34458051

RESUMEN

Background Self-assessment is a central skill in competency-based medical education (CBME) and should be fostered in order to promote life-long learning. One measure that will guide the development of self-assessment is the alignment between it and external expert assessment. In this study, we explored the qualitative themes in the self-assessment rationale among trainees with incongruent self and faculty-assigned entrustment scores. Methods A total of 40 postgraduate medical trainees completed a four-scenario summative objective structured clinical examination (OSCE) as part of a simulation-based resuscitation curriculum in December 2017. After each scenario, an assessment involving an entrustment score and narrative rationale was completed by both trainee (self) and faculty. The differences between the trainee and faculty scores were calculated for each scenario and summed to give a single "incongruence score". Trainees who consistently scored themselves higher than the faculty were said to have a "positive-incongruence score" and those scoring below the faculty were said to have a "negative-incongruence" score. Through this method, 10 trainees with the highest and lowest scores were assigned to each group and their narrative rationales were coded and thematically analyzed. Results The content of the self-assessment narrative rationale differed between the two groups. Trainees in the positive-incongruence group focused on the concepts of speed and situational management, while trainees in the negative-incongruence group commented on lack of support, and a need to improve communication, diagnosis, and code blue management. The quality of the self-assessment rationale also differed between groups. Trainees in the negative-incongruence group provided higher-quality comments that were more detailed and granular. Conclusion We found differences in the content and quality of the self-assessment rationale between trainees whose self and faculty-assigned assessment is incongruent. This provides insight into how these groups differ and has valuable implications for the development of curricula targeting self-assessment skills.

19.
J Taibah Univ Med Sci ; 13(3): 238-246, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31435330

RESUMEN

OBJECTIVES: Adults with disabilities are at a higher risk of malnutrition than are their non-disabled counterparts owing to feeding problems and associated medical conditions. We evaluated the prevalence of malnutrition in a group of institutionalized women and investigated any feeding difficulties and nutrition-related medical problems. METHODS: This study used two versions of the Mini Nutritional Assessment-Short Form (MNA-SF) to screen malnutrition: the MNA-SF1 which uses the body mass index, and the MNA-SF2 which uses the calf circumference. Data were collected from 53 women with intellectual and physical disabilities in a cross-sectional survey of residents of the Kuwait Rehabilitation Centre. RESULTS: Of all participants, 63.5% were found to be overweight or obese, while 11.5% were underweight. Using the MNA-SF1, 57.7% were found to be at risk of malnourishment while 11.5% were malnourished. More patients were identified to be at risk of malnutrition or to be actually malnourished using the MNA-SF2 (59.6% and 23.1%, respectively). Reported feeding problems included difficulties in maintaining a sitting position, manipulating food on a plate, conveying food to the mouth, and in swallowing. The presence of infections worsened the prognoses of malnourished women regardless of their weight status. CONCLUSIONS: Our findings suggest that MNA-SF2 is a more sensitive tool for identifying malnourishment than MNA-SF1. Obesity can obscure the identification of malnourished patients if clinicians rely solely on the MNA-SF1, which uses the body mass index.

20.
J Vis Exp ; (141)2018 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-30474636

RESUMEN

Neural stem cells (NSCs) are multipotent and can give rise to the three major cell types of the central nervous system (CNS). In vitro culture and expansion of NSCs provide a suitable source of cells for neuroscientists to study the function of neurons and glial cells along with their interactions. There are several reported techniques for the isolation of neural stem cells from adult or embryo mammalian brains. During the microsurgical operation to isolate NSCs from different regions of the embryonic CNS, it is very important to reduce the damage to the brain cells to obtain the highest ratio of live and expandable stem cells. A possible technique for stress reduction during isolation of these cells from the mouse embryo brain is the reduction of surgical time. Here, we demonstrate a developed technique for rapid isolation of these cells from the E13 mouse embryo ganglionic eminence. Surgical procedures include harvesting E13 mouse embryos from the uterus, cutting the frontal fontanelle of the embryo with a bent needle tip, extracting the brain from the skull, microdissection of the isolated brain to harvest the ganglionic eminence, dissociation of the harvested tissue in NSC medium to gain a single cell suspension, and finally plating cells in suspension culture to generate neurospheres.


Asunto(s)
Separación Celular/métodos , Células-Madre Neurales/citología , Cultivo Primario de Células/métodos , Animales , Encéfalo/citología , Encéfalo/embriología , Medio de Cultivo Libre de Suero , Ganglios/citología , Ganglios/embriología , Ratones , Microdisección
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA