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1.
BMC Geriatr ; 22(1): 836, 2022 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-36333652

RESUMEN

BACKGROUND: Frail cardiac surgery patients have an increased risk of worse postoperative outcomes. The purpose of this study was to evaluate the implementation of a novel Telehealth Home monitoring Enhanced-Frailty And Cardiac Surgery (THE-FACS) intervention and determine its impact on clinical outcomes in frail patients post-cardiac surgery. METHODS: Frail/vulnerable patients defined by Edmonton Frailty Scale (EFS > 4) undergoing cardiac surgery were prospectively enrolled (November 2019 -March 2020) at the New Brunswick Heart Centre. Exclusion criteria included age < 55 years, emergent status, minimally invasive surgery, lack of home support, and > 10-days postoperative hospital stay. Following standard training on THE-FACS, participants were sent home with a tablet device to answer questions about their health/recovery and measure blood pressure for 30-consecutive days. Transmitted data were monitored by trained cardiac surgery follow-up nurses. Patients were contacted only if the algorithm based on the patient's self-collected data triggered an alert. Patients who completed the study were compared to historical controls. The primary outcome of interest was to determine the number of patients that could complete THE-FACS; secondary outcomes included participant/caregiver satisfaction and impact on hospital readmission. RESULTS: We identified 86 eligible (EFS > 4), out of 254 patients scheduled for elective cardiac surgery during the study period (vulnerable: 34%). The patients who consented to participate in THE-FACS (64/86, 74%) had a mean age of 69.1 ± 6.4 years, 25% were female, 79.7% underwent isolated Coronary Artery Bypass Graft (CABG) and median EFS was 6 (5-8). 29/64 (45%) were excluded post-enrollment due to prolonged hospitalization (15/64) or requirement for hospital-to-hospital transfer (12/64). Of the remaining 35 patients, 21 completed the 30-day follow-up (completion rate:60%). Reasons for withdrawal (14/35, 40%) were mostly due to technical difficulties with the tablet. Hospital readmission, although non-significant, was reduced in THE-FACS participants compared to controls (0% vs. 14.3%). A satisfaction survey revealed > 90% satisfaction and ~ 67% willingness to re-use a home monitoring device. CONCLUSIONS: THE-FACS intervention can be used to successfully monitor vulnerable patients returning home post-cardiac surgery. However, a significant number of frail patients could not benefit from THE-FACS given prolonged hospitalization and technological challenges. Our findings suggest that despite overall excellent satisfaction in participants who completed THE-FACS, there remain major challenges for wide-scale implementation of technology-driven home monitoring programs as only 24% completed the study.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Fragilidad , Telemedicina , Humanos , Femenino , Anciano , Masculino , Fragilidad/diagnóstico , Anciano Frágil , Proyectos Piloto , Procedimientos Quirúrgicos Cardíacos/efectos adversos
2.
Epigenomes ; 6(2)2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35645252

RESUMEN

Although few in number, studies on epigenome of the heart of COVID-19 patients show that epigenetic signatures such as DNA methylation are significantly altered, leading to changes in expression of several genes. It contributes to pathogenic cardiac phenotypes of COVID-19, e.g., low heart rate, myocardial edema, and myofibrillar disarray. DNA methylation studies reveal changes which likely contribute to cardiac disease through unknown mechanisms. The incidence of severe COVID-19 disease, including hospitalization, requiring respiratory support, morbidity, and mortality, is disproportionately higher in individuals with co-morbidities. This poses unprecedented strains on the global healthcare system. While their underlying conditions make patients more susceptible to severe COVID-19 disease, strained healthcare systems, lack of adequate support, or sedentary lifestyles from ongoing lockdowns have proved detrimental to their underlying health conditions, thus pushing them to severe risk of congenital heart disease (CHD) itself. Prophylactic vaccines against COVID-19 have ushered new hope for CHD. A common connection between COVID-19 and CHD is SARS-CoV-2's host receptor ACE2, because ACE2 regulates and protects organs, including the heart, in various ways. ACE2 is a common therapeutic target against cardiovascular disease and COVID-19 which damages organs. Hence, this review explores the above regarding CHDs, cardiovascular damage, and cardiac epigenetics, in COVID-19 patients.

3.
J Am Chem Soc ; 144(26): 11859-11869, 2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35749229

RESUMEN

The well-known limitation of alkaline fuel cells is the slack kinetics of the cathodic half-cell reaction, the oxygen reduction reaction (ORR). Platinum, being the most active ORR catalyst, is still facing challenges due to its corrosive nature and sluggish kinetics. Many novel approaches for substituting Pt have been reported, which suffer from stability issues even after mighty modifications. Designing an extremely stable, but unexplored ordered intermetallic structure, Pd2Ge, and tuning the electronic environment of the active sites by site-selective Pt substitution to overcome the hurdle of alkaline ORR is the main motive of this paper. The substitution of platinum atoms at a specific Pd position leads to Pt0.2Pd1.8Ge demonstrating a half-wave potential (E1/2) of 0.95 V vs RHE, which outperforms the state-of-the-art catalyst 20% Pt/C. The mass activity (MA) of Pt0.2Pd1.8Ge is 320 mA/mgPt, which is almost 3.2 times better than that of Pt/C. E1/2 and MA remained unaltered even after 50,000 accelerated degradation test (ADT) cycles, which makes it a promising stable catalyst with its activity better than that of the state-of-the-art Pt/C. The undesired 2e- transfer ORR forming hydrogen peroxide (H2O2) is diminished in Pt0.2Pd1.8Ge as visible from the rotating ring-disk electrode (RRDE) experiment, spectroscopically visualized by in situ Fourier transform infrared (FTIR) spectroscopy and supported by computational studies. The effect of Pt substitution on Pd has been properly manifested by X-ray absorption spectroscopy (XAS) and X-ray photoelectron spectroscopy (XPS). The swinging of the oxidation state of atomic sites of Pt0.2Pd1.8Ge during the reaction is probed by in situ XAS, which efficiently enhances 4e- transfer, producing an extremely low percentage of H2O2.


Asunto(s)
Peróxido de Hidrógeno , Platino (Metal) , Catálisis , Electrones , Oxígeno/química , Platino (Metal)/química
4.
Adv Mater ; 34(30): e2202294, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35609013

RESUMEN

The discovery of novel materials for industrial-standard hydrogen production is the present need considering the global energy infrastructure. A novel electrocatalyst, Pt3 Ge, which is engineered with a desired crystallographic facet (202), accelerates hydrogen production by water electrolysis, and records industrially desired operational stability compared to the commercial catalyst platinum is introduced. Pt3 Ge-(202) exhibits low overpotential of 21.7 mV (24.6 mV for Pt/C) and 92 mV for 10 and 200 mA cm-2 current density, respectively in 0.5 m H2 SO4 . It also exhibits remarkable stability of 15 000 accelerated degradation tests cycles (5000 for Pt/C) and exceptional durability of 500 h (@10 mA cm-2 ) in acidic media. Pt3 Ge-(202) also displays low overpotential of 96 mV for 10 mA cm-2 current density in the alkaline medium, rationalizing its hydrogen production ability over a wide pH range required commercial operations. Long-term durability (>75 h in alkaline media) with the industrial level current density (>500 mA cm-2 ) has been demonstrated by utilizing the electrochemical flow reactor. The driving force behind this stupendous performance of Pt3 Ge-(202) has been envisaged by mapping the reaction mechanism, active sites, and charge-transfer kinetics via controlled electrochemical experiments, ex situ X-ray photoelectron spectroscopy, in situ infrared spectroscopy, and in situ X-ray absorption spectroscopy further corroborated by first principles calculations.

5.
ACS Nano ; 16(4): 6185-6196, 2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35377140

RESUMEN

Electrochemical reduction of CO2 into valuable fuels and chemicals is a promising route of replacing fossil fuels by reducing CO2 emissions and minimizing its adverse effects on the climate. Tremendous efforts have been carried out for designing efficient catalyst materials to selectively produce the desired product in high yield from CO2 by the electrochemical process. In this work, a strategy is reported to enhance the electrochemical CO2 reduction reaction (ECO2RR) by constructing an interface between a metal-based alloy (PdIn) nanoparticle and an oxide (In2O3), which was synthesized by a facile solution method. The oxide-derived PdIn surface has shown excellent eCO2RR activity and enhanced CO selectivity with a Faradaic efficiency (FE) of 92.13% at -0.9 V (vs RHE). On the other hand, surface PdO formation due to charge transfer on the bare PdIn alloy reduces the CO2RR activity. With the support of in situ (EXAFS and IR) and ex situ (XPS, Raman) spectroscopic techniques, the optimum presence of the Pd-In-O interface has been identified as a crucial parameter for enhancing eCO2RR toward CO in a reducing atmosphere. The influence of eCO2RR duration is reported to affect the overall performance by switching the product selectivity from H2 (from water reduction) to CO (from eCO2RR) on the oxide-derived alloy surface. This work also succeeded in the multifold enhancement of the current density by employing the gas diffusion electrode (GDE) and optimizing its process parameters in a flow cell configuration.

6.
Sensors (Basel) ; 22(3)2022 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-35161576

RESUMEN

Many patients affected by breast cancer die every year because of improper diagnosis and treatment. In recent years, applications of deep learning algorithms in the field of breast cancer detection have proved to be quite efficient. However, the application of such techniques has a lot of scope for improvement. Major works have been done in this field, however it can be made more efficient by the use of transfer learning to get impressive results. In the proposed approach, Convolutional Neural Network (CNN) is complemented with Transfer Learning for increasing the efficiency and accuracy of early detection of breast cancer for better diagnosis. The thought process involved using a pre-trained model, which already had some weights assigned rather than building the complete model from scratch. This paper mainly focuses on ResNet101 based Transfer Learning Model paired with the ImageNet dataset. The proposed framework provided us with an accuracy of 99.58%. Extensive experiments and tuning of hyperparameters have been performed to acquire the best possible results in terms of classification. The proposed frameworks aims to be an efficient tool for all doctors and society as a whole and help the user in early detection of breast cancer.


Asunto(s)
Neoplasias de la Mama , Aplicaciones Móviles , Neoplasias de la Mama/diagnóstico , Detección Precoz del Cáncer , Femenino , Humanos , Aprendizaje Automático , Redes Neurales de la Computación
7.
ChemSusChem ; 14(15): 3074-3083, 2021 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-34038021

RESUMEN

A facile microwave-assisted strategy was employed to synthesize Ni3 Bi2 S2 nanocrystals. Variation in the synthesis conditions tuned the composition of monoclinic and orthorhombic phases of Ni3 Bi2 S2 . The electrochemical hydrogen evolution activity of the catalyst with highest percentage of monoclinic phase demonstrated a negligible onset potential of only 24 mV close to that of state-of-the-art Pt/C with an overpotential as low as 88 mV. Density functional theory calculations predicted the monoclinic phase exhibit the lowest adsorption free energy corresponding to hydrogen adsorption ( Δ G ads H * ) and, therefore, the highest hydrogen evolution activity amongst the considered phases. The quasi-2D structure of monoclinic phase facilitated an increased charge-transfer between Ni and Bi, favoring the downward shift of the d-band center to enhance the catalytic activity.

8.
Chem Asian J ; 16(10): 1184-1197, 2021 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-33749999

RESUMEN

The activity of Pt towards oxygen reduction reaction (ORR) can be enhanced by alloying it with secondary metals. They can be grouped into three different classes: alloys, bimetallics and intermetallics. Although alloys and bimetallics exhibit enhanced performance, often they are limited by metal dissolution and resulted in poor durability. This invokes the need on the development of ordered intermetallics. In this minireview we comprehensively present the recent progress and developments of Pt3 X alloys and intermetallics towards ORR. Additionally, major technical challenges and possible future research directions to overcome these challenges are discussed to facilitate further research in this area.

9.
Chem Commun (Camb) ; 57(22): 2824, 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33660727

RESUMEN

Correction for 'Conductive interface promoted bifunctional oxygen reduction/evolution activity in an ultra-low precious metal based hybrid catalyst' by Shreya Sarkar et al., Chem. Commun., 2021, 57, 1951-1954, DOI: 10.1039/D0CC08225B.

10.
Chem Commun (Camb) ; 57(15): 1951-1954, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33502398

RESUMEN

Ultra low PtPd alloy deposited on Ni12P5 nanostructures (PtPd/Ni12P5) exhibited enhanced ORR activity (onset: 1.003 V and E1/2:0.95 V) on par with commercial Pt/C and superior OER activity with 81% reduction of the precious metal compared to the commercial catalyst.

11.
JTCVS Open ; 8: 491-502, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36004086

RESUMEN

Background: Globally, an increasing number of vulnerable or frail patients are undergoing cardiac surgery. However, large-scale frailty data are often limited by the need for time-consuming frailty assessments. This study aimed to (1) create a retrospective registry-based frailty score (FS), (2) determine its effect on outcomes and age, and (3) health care costs. Methods: Retrospective data were obtained from the New Brunswick Heart Centre registry for all cardiac surgery patients between 2012 and 2017. A 20-point FS was created using available binary risk variables. The primary outcomes of interest most relevant to vulnerable patients were prolonged hospitalization, failure to be discharged home, and hospitalization bed cost. Composite outcome of prolonged hospitalization (>8 days) and/or non-home discharge were analyzed using multivariate analysis. Results: A total of 3463 patients (mean age, 66 ± 10 years) were included in the final analysis. Tercile-based FSs were: low (0-4; n = 856), medium (5-7; n = 1709), high (≥8; n = 898). In unadjusted data, frail patients were older with more comorbidities. High FS patients had greater risks of prolonged hospitalization (median 7 vs 5 days; P < .001), lower home-discharge rates (51% vs 83%; P < .001), higher 30-day readmission rates (18% vs 10%; P < .001), and increased 30-day mortality rates (≤0.7% [low], >0.7% to ≤1.2% [medium], and >1.2% to 4.8% [high]; P < .001). After statistical adjustment, the FS was an independent predictor of composite outcome (odds ratio, 1.3: 95% CI, 1.26-1.35), and increased hospital bed costs. Conclusions: A registry-based FS can be used to identify vulnerable or frail patients undergoing cardiac surgery and was associated with poor outcomes independent of age. This highlights that although frailty defined by increased vulnerability is often associated with older age, it is not a surrogate for aging, thereby having important implications in reducing health system costs and efforts to provide streamlined care to the most vulnerable.

12.
Nanoscale ; 12(44): 22718-22734, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33170196

RESUMEN

We report a novel s-tetrazine based covalent organic framework (TZA-COF) and its hybrid nanocomposites with reduced graphene oxide (TZA-COF-rGO) and Co metal to illustrate novel structure-activity relationships in this class of compounds for electrocatalytic oxygen reduction reaction (ORR). The Co-impregnated hybrid composites (TZA-COF-rGO-Co) were further annealed to yield Co-encapsulated nitrogen doped graphitic carbon (Co@NC-600), which exhibited excellent ORR activity comparable to that of the state-of-the art Pt/C in terms of onset potential, E1/2 (half-wave potential), 4e- reduction selectivity and methanol tolerance. Sequential mechanistic analyses of activity enhancement and electron transfer pathways for the ORR, at different stages of controlled catalyst engineering, elucidated the crucial role of active sites and overall catalyst nature in tuning the ORR mechanism. Co@NC-600 also exhibited high oxygen evolution reaction (OER) activity under alkaline conditions which makes it one of the most efficient non-precious metal bifunctional catalysts, capable of catalyzing complex 4e- reduction processes like the ORR and OER.

13.
Asian Pac J Cancer Prev ; 21(9): 2493-2499, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32986344

RESUMEN

BACKGROUND: There is, till date no population-based data regarding cancer patterns in North- Eastern India, dictating the need to understand the epidemiology of cancer in this population for its effective management. METHODS: This is the first report of the Population Based Cancer Registry (PBCR) in Tripura (2010-2014). The protocol involves active collection of data on all cancer cases from Tripura through staff visit in more than 150 sources of incident and mortality registration, government and private hospitals, municipal corporation, etc. and scrutiny, corroboration with existing records. Data was analyzed statistically to understand cancer trends in terms of incidence and mortality across different sites, age groups affected and gender. RESULTS: A total of 10,251 cases were registered during the period, with overall age-adjusted incidence rates of 75.7 and 54.9 per 100,000 males and females respectively. Crude Incidence Rate (CR) and Age- Adjusted Rate (AAR) was among the lowest reported in India, probably due to associated socio-economic factors. The most prevalent cancers were lung (18.1%), esophageal (8.3%) for men and cervix uteri (17.6%), breast (13.8%) for females. Gall bladder cancer in females was one of the highest in the country. Rate of cancer mortality in the population was quite high and significantly increased with time, probably accounting for dearth in early detection and feasible treatment alternatives. CONCLUSION: The data suggests that high cancer incidence and mortality are prevalent in the population of Tripura, dictating the need of active tobacco control measures, early detection and awareness drives for effective cancer control.


Asunto(s)
Neoplasias/epidemiología , Neoplasias/mortalidad , Sistema de Registros/estadística & datos numéricos , Adolescente , Adulto , Anciano , Niño , Femenino , Estudios de Seguimiento , Humanos , Incidencia , India/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias/patología , Pronóstico , Tasa de Supervivencia , Adulto Joven
14.
Front Cardiovasc Med ; 7: 103, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32671100

RESUMEN

Background: Obesity is a risk factor that negatively impacts outcomes in patients undergoing heart surgery by mechanisms that are not well-defined nor predicated on BMI alone. This knowledge gap has fuelled a search for biomarkers associated with cardiovascular diseases that could provide clinical insight to surgeons. One such biomarker is growth differentiation factor15(GDF15), associated with inflammation, metabolism, and heart failure outcomes but not yet examined in the context of obesity and cardiac surgery outcomes. Methods: Patients undergoing open-heart surgery were consented and enrolled for blood and tissue (atria) sampling at the time of surgery. Biomarker analysis was carried out using ELISA and western blot/qPCR, respectively. Biomarker screening was classified by inflammation(NLR, GDF15, Galectin3, ST2, TNFR2), heart failure(HF)/remodeling(NT-proBNP) and metabolism(glycemia, lipid profile). Patients were categorized based on BMI: obese group (BMI ≥30.0) and non-obese group(BMI 20.0-29.9). Subsequent stratification of GDF15 high patients was conservatively set as being in the 75th percentile. Results: A total of 80 patients undergoing any open-heart surgical interventions were included in the study. Obese (mean BMI = 35.8, n = 38) and non-obese (mean BMI = 25.7, n = 42) groups had no significant differences in age, sex, or co-morbidities. Compared to other biomarkers, plasma GDF15 (mean 1,736 vs. 1,207 ng/l, p < 0.001) was significantly higher in obese patients compared to non-obese. Plasma GDF15 also displayed a significant linear correlation with BMI (R 2 = 0.097; p = 0.0049). Atria tissue was shown to be a significant source of GDF15 protein and tissue levels significantly correlated with plasma GDF15 (R 2 = 0.4, p = 0.0004). Obesity was not associated with early/late mortality at median follow-up >2years. However, patients with high GDF15 (>1,580 ng/l) had reduced survival (65%) compared to the remaining patients with lower GDF15 levels (95%) by Kaplan Meier Analysis (median >2 years; p = 0.007). Conclusions: Circulating GDF15 is a salient biomarker likely sourced from heart tissue that appears to predict higher risk obese patients for adverse outcomes. More importantly, elevated GDF15 accounted for more sensitive outcome association than BMI at 2 years post-cardiac surgery, suggesting it heralds links to pathogenicity and should be actively studied prospectively and dynamically in a post-operative follow-up. Trial number: NCT03248921.

15.
ACS Appl Mater Interfaces ; 11(41): 37602-37616, 2019 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-31545585

RESUMEN

Intermetallic compounds (IMCs) have diverse electronic and geometrical properties to offer. However, the synthesis of intermetallic nanoparticles is not always easy; developing new methodologies that are conventional for many systems can be challenging, especially when incorporating highly electropositive metals to reduce to IMCs using solution synthesis methodologies. In this study, we report a comprehensive approach to access nanocrystalline PdxMy (M = Cu, Zn, Ga, Ge, Sn, Pb, Cd, In) intermetallic (IM) via the coreduction method employing sodium borohydride as the reductant. A combination of diffraction, spectroscopic, and microscopic techniques were performed to characterize the formed nanoparticles in terms of their phase composition, purity, particle size distribution, and surface oxidation properties of metals, respectively. IMCs of Pd with the elements such as Cu, Zn, Ga, and Ge exhibited higher catalytic activity that with elements such as In, Sn, Pb, and Cd. The DFT studies on these compounds revealed that the adsorption of benzylamine at the Pd site and the dissociative adsorption of O2 on the IM surface play a significant effect on catalytic activity. Among them, PdCu IM exhibited an excellent conversion of benzylamine (94.0%), with 92.2% of dibenzylimine selectivity compared to other IMCs. Moreover, PdCu exhibited decent recyclability and activity for the oxidation of different substituted primary amines.

16.
ACS Appl Mater Interfaces ; 11(24): 21686-21696, 2019 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-31120729

RESUMEN

The present study reports the effect of Sn substitution on the structural and thermoelectric properties of synthetic tetrahedrite (Cu12Sb4S13) system. The samples were prepared with the intended compositions of Cu12Sb4- xSn xS13 ( x = 0.25, 0.35, 0.5, 1) and sintered using spark plasma sintering. A detailed structural characterization of the samples revealed tetrahedrite phase as the main phase with Sn substituting at both Cu and Sb sites instead of only Sb site. The theoretical calculations using density functional theory revealed that Sn at Cu(1) 12d or Cu(2) 12e site moves the Fermi level ( EF) toward the band gap, whereas Sn at Sb 8c site introduces hybridized hole states near EF. Consequently, a relatively high optimum power factor of 1.3 mW/mK2 was achieved by the x = 0.35 sample. The Sn-substituted samples exhibited a significant decrease in the total thermal conductivity (κT) compared to the pristine composition (Cu12Sb4S13), primarily because of reduced electronic thermal conductivity. Due to an optimum power factor (1.3 mW/mK2) and reduced thermal conductivity (0.9 W/mK), a maximum zT of 0.96 at 673 K was achieved for x = 0.35 sample, which is nearly 40% increment compared to that of the pristine (Cu12Sb4S13) sample.

17.
Inorg Chem ; 57(20): 12576-12587, 2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30281284

RESUMEN

In this work, we have discovered the anisotropic near-zero thermal expansion (NZTE) behavior in a family of compounds REAg xGa4- x ( RE = La-Nd, Sm, Eu, and Yb). The compounds adopt the CeAl2Ga2 structure type and were obtained as single crystals in high yield by metal flux growth technique using gallium as active flux. Temperature-dependent single crystal X-ray diffraction suggests that all the compounds exhibit near zero thermal expansion along c direction in the temperature range of 100-450 K. Temperature-dependent X-ray absorption near-edge spectroscopic study confirmed ZTE behavior is due to the geometrical features associated within the crystal structure. The anisotropic NZTE behavior was further established by anisotropic magnetic measurements on selected single crystals. The atomic displacement parameters, apparent bond lengths, bond angles, and structural distortion with respect to the temperature reveal that geometric features associated with the structural distortion cause the anisotropic NZTE along c-direction. The preliminary magnetic studies suggest all the compounds are paramagnetic at room temperature except LaAgGa3. Electrical resistivity study reveals that compounds from this series are metallic in nature.

18.
Cancer Biol Ther ; 19(7): 631-635, 2018 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-29624473

RESUMEN

Head and neck squamous cell carcinoma is one of the leading cancers in terms of incidence and mortality. However, no reliable marker till date accurately predicts its progression when altered in healthy tissues. The study aims to identify alleles of microsatellites adjacent to important cell cycle regulatory, tumor suppressor genes altered in early head and neck lesions, viz. RBSP3, LIMD1 and CDC25A, which undergo frequent deletion and can be used for population screening and early detection. DNA for tumors and normal tissues was isolated from 143 patients in different stages of head and neck squamous cell carcinoma. The size of microsatellite present in normal tissues and their deletion in the corresponding tumor was identified, along with the correlation of expression in normal epithelium with respect to allele size. The results revealed a range of alleles (CA9 to CA32) for the different microsatellites of the genes in normal tissues. The larger alleles were significantly deleted with differential deletion of alleles observed in tumors, except for LIMD1, in which the smaller allele was significantly deleted. In normal tissues, some alleles represented as stable alleles with high prevalence, while in tumours, specific sizes showed greater propensity for deletion. However, similar expression of the proteins in normal epithelium adjacent to tumors was observed despite variations in allele size, possibly due to the location of the microsatellites. Thus, those alleles when present in normal tissues and undergoing persistent deletion in tumours could be used as markers for screening and early identification of populations at risk of developing head and neck lesions.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de Cabeza y Cuello/diagnóstico , Repeticiones de Microsatélite/genética , Eliminación de Secuencia , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Alelos , Secuencia de Bases/genética , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Detección Precoz del Cáncer/métodos , Epitelio/patología , Femenino , Genoma Humano/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas con Dominio LIM/genética , Captura por Microdisección con Láser , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Mucosa Bucal/patología , Regiones Promotoras Genéticas/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Proteínas Supresoras de Tumor/genética , Fosfatasas cdc25/genética
19.
PLoS One ; 13(4): e0195937, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29672635

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is a global disease and mortality burden, necessitating the elucidation of its molecular progression for effective disease management. The study aims to understand the molecular profile of three candidate cell cycle regulatory genes, RBSP3, LIMD1 and CDC25A in the basal/ parabasal versus spinous layer of normal oral epithelium and during head and neck tumorigenesis. Immunohistochemical expression and promoter methylation was used to determine the molecular signature in normal oral epithelium. The mechanism of alteration transmission of this profile during tumorigenesis was then explored through additional deletion and mutation in HPV/ tobacco etiological groups, followed byclinico-pathological correlation. In basal/parabasal layer, the molecular signature of the genes was low protein expression/ high promoter methylation of RBSP3, high expression/ low methylation of LIMD1 and high expression of CDC25A. Dysplastic epithelium maintained the signature of RBSP3 through high methylation/ additional deletion with loss of the signatures of LIMD1 and CDC25A via deletion/ additional methylation. Similarly, maintenance and / or loss of signature in invasive tumors was by recurrent deletion/ methylation. Thus, differential patterns of alteration of the genes might be pre-requisite for the development of dysplastic and invasive lesions. Etiological factors played a key role in promoting genetic alterations and determining prognosis. Tobacco negative HNSCC patients had significantly lower alterations of LIMD1 and CDC25A, along with better survival among tobacco negative/ HPV positive patients. Our data suggests the necessity for perturbation of normal molecular profile of RBSP3, LIMD1 and CDC25A in conjunction with etiological factors for head and neck tumorigenesis, implying their diagnostic and prognostic significance.


Asunto(s)
Carcinoma de Células Escamosas/etiología , Transformación Celular Neoplásica/genética , Epitelio/metabolismo , Neoplasias de Cabeza y Cuello/etiología , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas con Dominio LIM/genética , Proteínas Supresoras de Tumor/genética , Fosfatasas cdc25/genética , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Metilación de ADN , Epitelio/patología , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas con Dominio LIM/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Regiones Promotoras Genéticas , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteínas Supresoras de Tumor/metabolismo , Flujo de Trabajo , Fosfatasas cdc25/metabolismo
20.
Ultramicroscopy ; 185: 1-4, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29136544

RESUMEN

The field enhancement factor at the emitter tip and its variation in a close neighbourhood determines the emitter current in a Fowler-Nordheim like formulation. For an axially symmetric emitter with a smooth tip, it is shown that the variation can be accounted by a cosθ˜ factor in appropriately defined normalized co-ordinates. This is shown analytically for a hemiellipsoidal emitter and confirmed numerically for other emitter shapes with locally quadratic tips.

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