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The tumor suppressor LKB1 is a serine/threonine protein kinase that is frequently mutated in human lung adenocarcinoma (LUAD). LKB1 regulates a complex signaling network that is known to control cell polarity and metabolism; however, the pathways that mediate the tumor-suppressive activity of LKB1 are incompletely defined. To identify mechanisms of LKB1-mediated growth suppression, we developed a spheroid-based cell culture assay to study LKB1-dependent growth. We then performed genome-wide CRISPR screens in spheroidal culture and found that LKB1 suppresses growth, in part, by activating the PIKFYVE lipid kinase. Finally, we used chemical inhibitors and a pH-sensitive reporter to determine that LKB1 impairs growth by promoting the internalization of wild-type EGFR in a PIKFYVE-dependent manner.
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Quinasas de la Proteína-Quinasa Activada por el AMP , Fosfatidilinositol 3-Quinasas , Proteínas Serina-Treonina Quinasas , Esferoides Celulares , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Quinasas de la Proteína-Quinasa Activada por el AMP/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP/genética , Esferoides Celulares/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proliferación Celular , Línea Celular Tumoral , Sistemas CRISPR-Cas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genéticaRESUMEN
Atezolizumab plus bevacizumab is the preferred first-line treatment regimen for patients with advanced hepatocellular carcinoma. Limited data have shown promising results with the use of immune checkpoint inhibitors like nivolumab to downstage these patients for liver transplantation (LT). Here, we describe the first case of successful downstaging with atezolizumab plus bevacizumab in a patient with multifocal hepatocellular carcinoma and main portal vein tumoral thrombosis, followed by ABO-incompatible live donor LT. This illustrated case highlights that atezolizumab plus bevacizumab therapy may be a potential bridging tool for curative LT.
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Anticuerpos Monoclonales Humanizados , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Vena Porta , Trombosis de la Vena , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/complicaciones , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/complicaciones , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Vena Porta/patología , Masculino , Trombosis de la Vena/etiología , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/terapia , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , PronósticoRESUMEN
OBJECTIVES: White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets. MATERIALS AND METHODS: Sixty commercially available stainless steel brackets were coated with TiO2 nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO2 nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO2 nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm. RESULTS: The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant. CONCLUSIONS: The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties. CLINICAL RELEVANCE: Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.
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Antibacterianos , Adhesión Bacteriana , Microscopía Electrónica de Rastreo , Nanotubos , Soportes Ortodóncicos , Fosforilcolina , Streptococcus mutans , Propiedades de Superficie , Titanio , Titanio/química , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Fosforilcolina/química , Streptococcus mutans/efectos de los fármacos , Antibacterianos/farmacología , Nanotubos/química , Adhesión Bacteriana/efectos de los fármacos , Microscopía de Fuerza Atómica , Ensayo de Materiales , Acero Inoxidable/química , Metacrilatos/farmacología , Metacrilatos/química , Biopelículas/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/químicaRESUMEN
AIM AND BACKGROUND: To compare the root canal volume in primary teeth using hand and rotary instruments and to evaluate root canal filling techniques and flow of root canal obturation materials in the postinstrumented root canal volume using spiral computed tomography (SCT). MATERIALS AND METHODS: Freshly extracted 16 primary molars were randomly divided into two groups and subjected to SCT analysis before and after instrumentation. For the manual technique (group I) with eight teeth were prepared using K files, and rotary (group II) eight teeth preparation was performed with ProTaper files. The filled volume in each canal was measured using SCT, and the percentage of obturated volume was calculated. The data were statistically analyzed using the Mann-Whitney U test. RESULTS: There was a statistically significant difference in both groups' volume of root canals enlarged. Even though both K files and the ProTaper system brought about enlarged canals after instrumentation, there was a statistically significant increase in volume after using K files in two canals. In three canals, there was a statistically significant increase in volume after using ProTaper. Irrespective of the obturation technique and materials used, there is no statistically significant difference in the volume after obturation. CONCLUSION: From the results of this study, the ProTaper file system shows suitable volumetric enlargement up to an optimum level, which is needed in primary root canal walls, and is better in canal shaping, as evidenced by good postobturation volume. CLINICAL SIGNIFICANCE: The traditional method of cleaning and shaping the root canals in permanent teeth using manual stainless-steel files can lead to undesirable curvatures in root canal morphology, making correctly filling the root canals difficult. It is also time-consuming and sometimes leads to iatrogenic errors. Rotary nickel-titanium (Ni-Ti) instrumentation techniques have been developed to overcome these problems. How to cite this article: Yadav DBUC, Varma RB, Kumar JS, et al. Volumetric Analysis of Hand and Rotary Instrumentation, Root Canal Filling Techniques, and Obturation Materials in Primary Teeth Using Spiral CT. J Contemp Dent Pract 2024;25(3):250-259.
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Cavidad Pulpar , Diente Molar , Materiales de Obturación del Conducto Radicular , Obturación del Conducto Radicular , Preparación del Conducto Radicular , Tomografía Computarizada Espiral , Diente Primario , Humanos , Obturación del Conducto Radicular/métodos , Diente Primario/diagnóstico por imagen , Preparación del Conducto Radicular/instrumentación , Preparación del Conducto Radicular/métodos , Cavidad Pulpar/diagnóstico por imagen , Cavidad Pulpar/anatomía & histología , Tomografía Computarizada Espiral/métodos , Diente Molar/diagnóstico por imagen , Instrumentos Dentales , Técnicas In VitroRESUMEN
Context: Pelvic-ureteric junction obstruction (PUJO) causes urine stasis in the renal pelvis and progressive kidney damage. Postpyeloplasty improvement of renal function and urinary drainage is assessed by diuretic isotope renogram and ultrasonography. Renograms are expensive and have radiation exposure. This study explores whether ultrasound parameters such as percentage improvement in anteroposterior pelvic diameter (PI-APD) is a valuable markers for successful pediatric pyeloplasties. Aims: The aim of this study was to identify patients who would benefit from ultrasound monitoring of PI-APD alone instead of diuretic isotope renal scan for postoperative follow-up of pyeloplasty. Settings and Design: This was a retrospective descriptive study. Subjects and Methods: We analyzed 127 pediatric pyeloplasties performed and under follow-up between June 2016 and May 2021. We recorded the postoperative ultrasound and isotope renogram parameters. PI-APD (preoperative AP diameter - postoperative AP diameter)/preoperative AP diameter × 100) was compared with improvement in renogram parameters (differential renal function, Tmax, curve pattern, and retention) to look for a correlation between them. Statistical Analysis Used: SPSS version 20.5, Chi-square and paired t-test were used for statistical analysis. Results: About 73.2% of patients were males, with most cases detected antenatally (76.4%). The majority was left-sided PUJO (67.7%). The mean age at surgery was 30.8 months. We identified a statistically significant correlation between the ultrasound parameter PI-APD and the renogram parameter Tmax. There is no significant correlation between PI-APD and other renogram parameters. Conclusions: In patients whose ultrasound parameter PI-APD is >40% and renal parenchymal thickness has increased, isotope renograms can be avoided for follow-up of postpyeloplasty patients.
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PURPOSE: There are limited studies in the literature comparing the alignment accuracy of the large console, imageless, computer-assisted navigation (CAN) and portable, hand-held, accelerometer-based navigation (ABN) in total knee arthroplasty (TKA). This study was aimed to compare the operative time, blood loss, radiological, clinical and functional outcomes between CAN- and ABN-guided bilateral TKA. METHODS: From Jan 2016 to Dec 2017, 50 patients who underwent bilateral TKA were randomized to undergo either CAN-guided or ABN-guided TKA. Tourniquet time and blood loss were recorded, and intra-op complications were noted. Post-op radiological outcomes at 2 weeks were compared between the groups. The clinical and functional outcomes using the American Knee Society Scores (KSS) and Oxford Knee Score (OKS) were recorded pre-operatively and post-operatively at 3, 6, 12 months and at the end of the study with a minimum follow-up of 48 months. RESULTS: Both groups were well-matched in terms of patient demographic parameters. The mean surgical time per knee was significantly lower in the ABN group (54.5 ± 5.6 min) compared to the CAN group (61.7 ± 13.7 min; p < 0.01). Mean blood loss per knee in the ABN group was 592.1 ± 245.3 mL compared to 682.8 ± 322.0 in the CAN group (p = 0.11). In the ABN group, the mean post-op mechanical axis was 1.2 ± 3.2° (vs 1.5 ± 2.2° in the CAN group, p 0.6), the frontal femoral angle was 88.8 ± 2.3° (vs 88.8 ± 1.8° in the CAN group, p 1.0) and frontal tibial angle was 90.1 ± 1.6° (vs 89.7 ± 1.1° in the CAN group, p 0.14). At 48 month follow-up, the mean functional KSS in the ABN group was 89.0 ± 5.7 (vs 88.1 ± 4.5 in the CAN group, p 0.37) and the mean OKS was 40.5 ± 2.8 (vs 39.6 ± 3.2 in the CAN group, p 0.12). CONCLUSION: Portable, hand-held ABN offers alignment accuracy and functional outcomes in TKA similar to that with CAN, with a reduced duration of surgery. There was no advantage of either of the techniques in terms of clinical or functional outcomes at 48 month follow-up. LEVEL OF EVIDENCE 1.
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Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Cirugía Asistida por Computador , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Cirugía Asistida por Computador/métodos , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Acelerometría/métodos , ComputadoresRESUMEN
Background and Aims: Preoperative anxiety is a common problem among children undergoing surgery. The aim of the study was to assess the incidence and identify various predictors of preoperative anxiety in Indian children. Material and Methods: A prospective, observational study was conducted on 60 children of the American Society of Anesthesiologists Physical status 1/2, aged 2-6 years and scheduled for elective surgery under general anesthesia in a tertiary care teaching hospital. Preoperative parental anxiety was assessed using the State-Trait Anxiety Inventory questionnaire. The children's anxiety was assessed in the preoperative room, at the time of parental separation, and at the induction of anesthesia using modified Yale Preoperative Anxiety Scale (mYPAS) scoring by an anesthesiologist and a psychologist. Sedative premedication was employed prior to parental separation. Logistic regression analysis was carried out to identify the possible predictors of anxiety. Results: The incidence of high preoperative anxiety among the studied children was 76% in the preoperative room, 93% during parental separation, and 96% during anesthetic induction. Among the nine possible predictors identified on univariate regression, the presence of siblings was found to be a significant independent predictor on multivariate regression analysis (P = 0.04). The inter-rater agreement was excellent for the assessment of preoperative anxiety using mYPAS by the anesthesiologist and psychologist (weighted Kappa, k = 0.79). Conclusion: The incidence of preoperative anxiety in Indian children in the age group of 2-6 years is very high. The preop anxiety escalates progressively at parental separation and induction of anesthesia despite sedative premedication. The presence of siblings is a significant predictor of preoperative anxiety.
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INTRODUCTION: A wearable cardioverter defibrillator (WCD) is indicated in appropriate patients to reduce the risk for sudden cardiac death. Challenges for patients wearing a WCD have been frequent false shock alarms primarily due to electrocardiogram noise and wear discomfort. The objective of this study was to test a contemporary WCD designed for reduced false shock alarms and improved comfort. METHODS: One hundred and thirty patients with left ventricular ejection fraction ≤40% and an active implantable cardioverter defibrillator (ICD) were fitted with the ASSURE WCD (Kestra Medical Technologies) and followed for 30 days. WCD detection was enabled and shock alarm markers recorded, but shocks and shock alarms were disabled. All WCD episodes and ICD ventricular tachycardia/ventricular fibrillation (VT/VF) episodes were adjudicated. The primary endpoint was the false-positive shock alarm rate with a performance goal of 1 every 3.4 days (0.29 per patient-day). RESULTS: Of 163 WCD episodes, 4 were VT/VF and 159 non-VT/VF (121 rhythms with noise, 32 uncertain with noise, 6 atrial flutter without noise). Only three false-positive shock alarm markers were recorded; one false-positive shock alarm every 1333 patient-days (0.00075 per patient-day, 95% confidence interval: 0.00015-0.00361; p < .001). No ICD recorded VT/VF episodes meeting WCD detection criteria (≥170 bpm for ≥20 s) were missed by the WCD during 3501 patient-days of use. Median wear was 31.0 days (interquartile range [IQR] 2.0) and median daily use 23.0 h (IQR 1.7). Adverse events were mostly mild: skin irritation (19.4%) and musculoskeletal discomfort (8.5%). CONCLUSION: The ASSURE WCD demonstrated a low false-positive shock alarm rate, low patient-reported discomfort, and no serious adverse events.
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Desfibriladores Implantables , Dispositivos Electrónicos Vestibles , Arritmias Cardíacas , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Desfibriladores , Cardioversión Eléctrica/efectos adversos , Electrocardiografía , Humanos , Volumen Sistólico , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/terapia , Función Ventricular IzquierdaRESUMEN
In the present work, a series of new 1-{5-[2,5-bis(2,2,2-trifluoroethoxy)phenyl]-1,3,4-oxadiazol-3-acetyl-2-aryl-2H/methyl derivatives were synthesized through a multistep reaction sequence. The compounds were synthesized by the condensation of various aldehydes and acetophenones with the laboratory-synthesized acid hydrazide, which afforded the Schiff's bases. Cyclization of the Schiff bases yielded 1,3,4-oxadiazole derivatives. By spectral analysis, the structures of the newly synthesized compounds were elucidated, and further, their anti-cancer and anti-diabetic properties were investigated. To examine the dynamic behavior of the candidates at the binding site of the protein, molecular docking experiments on the synthesized compounds were performed, followed by a molecular dynamic simulation. ADMET (chemical absorption, distribution, metabolism, excretion, and toxicity) prediction revealed that most of the synthesized compounds follow Lipinski's rule of 5. The results were further correlated with biological studies. Using a cytotoxic assay, the newly synthesized 1,3,4-Oxadiazoles were screened for their in vitro cytotoxic efficacy against the LN229 Glioblastoma cell line. From the cytotoxic assay, the compounds 5b, 5d, and 5m were taken for colony formation assay and tunnel assay have shown significant cell apoptosis by damaging the DNA of cancer cells. The in vivo studies using a genetically modified diabetic model, Drosophila melanogaster, indicated that compounds 5d and 5f have better anti-diabetic activity among the different synthesized compounds. These compounds lowered the glucose levels significantly in the tested model.
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Antineoplásicos , Oxadiazoles , Animales , Simulación del Acoplamiento Molecular , Estructura Molecular , Oxadiazoles/química , Drosophila melanogaster , Antineoplásicos/química , Hipoglucemiantes/farmacología , Relación Estructura-ActividadRESUMEN
Aim: Laparoscopic CBD exploration (LCBDE) for Common bile duct (CBD) stones with laparoscopic cholecystectomy (LC) is an alternative to open CBD exploration, in patients with failed endoscopic retrograde cholangio-pancreatography (ERCP). It is being performed at few centres with adequate surgical expertise. Herein, we present our experience of LCBDE with LC over a period of 10 years. Patients and Methods: A retrospective analysis of prospectively recorded data of 121 consecutive patients was performed from February 2010 to November 2019, who underwent LC and LCBDE by choledochotomy in a single surgical unit. These included all patients with failed pre-operative ERCP. Results: Out of 121 patients, LCBDE successfully cleared the CBD in 118, and three patients were converted to open surgery. All these patients underwent choledochotomy for adequate exploration of CBD. T-tube closure of CBD was performed in 103 patients and removed after a mean of 14.6 ± 2.4 days. Primary closure was performed in 15 patients. The mean hospital stay post-procedure was 3.4 ± 0.7 days. Complete ductal clearance was achieved in 115 patients, and residual stone fragments reported in three patients were removed by ERCP. None of the patients experienced biliary peritonitis, biliary fistula, pancreatitis or cholangitis. There was no 30-day mortality and no recurrent stones reported with a mean follow-up of 12.4 ± 3.9 months. Conclusion: With adequate surgical expertise, LCBDE is a feasible alternative to open surgery for CBD stones after failed ERCP with early recovery and low morbidity.
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Parallel to the development of new medications for various diseases run the threat of medication errors. These errors though common, very few are fatal and so goes unnoticed. Such errors occurring with pediatric population can be a major predicament. This review aims to address the various parametric variations and considerations in pediatric population so as to minimize medication errors. A detailing about various causes, types and levels of errors, ways of analysing the amount of error and the essential knowledge about prescription writing which could reduce the incidents have been paid attention to. The article also discusses possible recommendations to the stakeholders and caregivers that could encompass the reason of lack of information for the ever-increasing medication errors.
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Errores de Medicación , Odontología Pediátrica , Niño , Humanos , Errores de Medicación/prevención & controlRESUMEN
Graphene quantum dots (GQDs), impressive materials with enormous future potential, are reviewed from their inception, including different precursors. Considering the increasing burden of industrial and ecological bio-waste, there is an urgency to develop techniques which will convert biowaste into active moieties of interest. Amongst the various materials explored, we selectively highlight the use of potential carbon containing bioprecursors (e.g. plant-based, amino acids, carbohydrates), and industrial waste and its conversion into GQDs with negligible use of chemicals. This review focuses on the effects of different processing parameters that affect the properties of GQDs, including the surface functionalization, paradigmatic characterization, toxicity and biocompatibility issues of bioprecursor derived GQDs. This review also examines current challenges and s the ongoing exploration of potential bioprecursors for ecofriendly GQD synthesis for future applications. This review sheds further light on the electronic and optical properties of GQDs along with the effects of doping on the same. This review may aid in future design approaches and applications of GQDs in the biomedical and materials design fields.
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A set of new Schiff bases of N-aryl 3- and 4-substituted maleimides has been prepared via condensation of N-aryl 3- and 4- substituted maleimides with p-toluene sulfonyl hydrazide in acidic medium at room temperature. The structures of synthesized compounds were characterized by IR, 1H NMR, 13C NMR, MS spectral data, and further confirmed by single-crystal x-ray crystallography for 5c. The computational study was carried out using Gaussian 09 software by using the B3LYP/6-311+G(d,p) basis set. Single-crystal study results showed much closeness with computational study results. These novel compounds were screened for their antimicrobial activity against two pathogenic bacteria such as Escherichia coli (ATCC 8739) and Staphylococcus aureus (ATCC25923) and two pathogenic fungi such as Aspergillus niger (MCIM10231) and Candida albicans (MTCC6275). The investigation of antimicrobial screening data showed that the most of tested compounds are moderate to good microbial inhibitors.
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Antibacterianos/farmacología , Antifúngicos/farmacología , Teoría Funcional de la Densidad , Maleimidas/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Aspergillus niger/efectos de los fármacos , Candida albicans/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Maleimidas/síntesis química , Maleimidas/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Bases de Schiff/síntesis química , Bases de Schiff/química , Bases de Schiff/farmacología , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
In malignant mesothelioma (MM) cells, secreted frizzled-related protein 4 (SFRP4) expression is downregulated by promoter methylation. In this study, we evaluated the effect of encapsulated chitosan-dextran (CS-DS) nanoparticle formulations of SFRP4 and its cysteine-rich domain (CRD) and netrin-like domain (NLD) as means of SFRP4-GFP protein delivery and their effects in JU77 and ONE58 MM cell lines. CS-DS formulations of SFRP4, CRD, and NLD nanoparticles were prepared by a complex coacervation technique, and particle size ranged from 300 nm for empty particles to 337 nm for particles containing the proteins. Measurement of the zeta potential showed that all preparations were around 25 mV or above, suggesting stable formulation and good affinity for the DNA molecules. The CS-DS nanoparticle formulation maintained high integrity and entrapment efficiency. Gene delivery of SFRP4 and its domains showed enhanced biological effects in both JU77 and ONE58 cell lines when compared to the non-liposomal FUGENE® HD transfection reagent. In comparison to the CRD nanoparticles, both the SFRP4 and NLD nanoparticles significantly reduced the viability of MM cells, with the NLD showing the greatest effect. The CS-DS nanoparticle effects were observed at an earlier time point and with lower DNA concentrations. Morphological changes in MM cells were characterized by the formation of membrane-associated vesicles and green fluorescent protein expression specific to SFRP4 and the NLD. The findings from our proof-of-concept study provide a stepping stone for further investigations using in vivo models.
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Quitosano , Sulfato de Dextran , Expresión Génica , Técnicas de Transferencia de Gen , Mesotelioma/metabolismo , Nanopartículas , Proteínas Proto-Oncogénicas/biosíntesis , Línea Celular Tumoral , Quitosano/química , Quitosano/farmacología , Sulfato de Dextran/química , Sulfato de Dextran/farmacología , Humanos , Mesotelioma/genética , Mesotelioma/patología , Mesotelioma/terapia , Nanopartículas/química , Nanopartículas/uso terapéutico , Proteínas Proto-Oncogénicas/genéticaRESUMEN
A metamaterial consisting of an array of gold micro-disks, separated from a ground plane of indium tin oxide (ITO) by a thin film of vanadium dioxide (VO2), behaves as a perfect absorber at infrared (IR) frequencies at room temperature. This metamaterial, which is transparent to visible light, can be switched to a highly reflecting state for IR light by heating the metamaterial to temperatures larger than the metal-insulator phase transition temperature 68°C of VO2. For a disk diameter of 1.5 µm and VO2 film thickness of 320 nm, two absorption bands are obtained: one, that arises from the metamaterial resonance; and a second peak that arises principally from a Fabry-Pérot resonance. A large change (>78%) occurs in the reflectivity between the low and high temperature phases. IR emittance of the metamaterial was measured with IR cameras and shown to be switchable to result in low emittance at high temperature. Optical readout of the state of VO2 within the metamaterial is demonstrated.
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Nitric oxide (NO) plays a critical role in endothelial functions such as cellular migration, vascular permeability and angiogenesis. Angiogenesis, the formation of new blood vessels from "pre-existing" ones is a carefully regulated process and essential during reproduction, development and wound healing. Previously our lab group reported that Secreted Frizzled-Related Protein 4 (sFRP4) could inhibit angiogenesis in both in vitro and in vivo conditions. sFRP4 belongs to a family of secreted glycoproteins that function as antagonists of the canonical Wnt signalling pathway. Although the pro-apoptotic role of sFRP4 is well discussed in literature, little is known in regards to its anti-angiogenic property. The objective of this study was to elucidate sFRP4 implications in NO biology of the endothelium. Results demonstrate that sFRP4 causes endothelial dysfunction by suppressing NO-cGMP signaling and elevating corresponding ROS levels. The imbalance between NO and ROS levels results in apoptosis and subsequent leakiness of endothelium as confirmed in vivo (Texas red/Annxin - CAM assay) and in vitro (Monolayer permeability assay) conditions. Furthermore utilizing peptides synthesized from the CRD domain of sFRP4, our results showed that while these peptides were able to cause endothelial dysfunctions, they did not cause apoptosis of the endothelial cells. Thereby confirming that sFRP4 can mediate its anti-angiogenic effect independent of its pro-apoptotic property. In conclusion, the current study reports that sFRP4-mediated anti-angiogenesis occurs as a result of impaired NO-cGMP signaling which in turn allow for elevation of redox levels and promotion of apoptosis of endothelial cells.
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Apoptosis/fisiología , Permeabilidad de la Membrana Celular/fisiología , GMP Cíclico/metabolismo , Endotelio/metabolismo , Óxido Nítrico/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Línea Celular , Células Endoteliales/metabolismo , Humanos , Neovascularización Patológica/metabolismo , Especies Reactivas de Oxígeno , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Pre-diagnosis attrition needs to be addressed urgently if we are to make progress in improving MDR-TB case detection and achieve universal access to MDR-TB care. We report the pre-diagnosis attrition, along with factors associated, and turnaround times related to the diagnostic pathway among patient with presumptive MDR-TB in Bhopal district, central India (2014). METHODS: Study was conducted under the Revised National Tuberculosis Control Programme setting. It was a retrospective cohort study involving record review of all registered TB cases in Bhopal district that met the presumptive MDR-TB criteria (eligible for DST) in 2014. In quarter 1, Line Probe Assay (LPA) was used if sample was smear/culture positive. Quarter 2 onwards, LPA and Cartridge-based Nucleic Acid Amplification Test (CbNAAT) was used for smear positive and smear negative samples respectively. Pre-diagnosis attrition was defined as failure to undergo DST among patients with presumptive MDR-TB (as defined by the programme). RESULTS: Of 770 patients eligible for DST, 311 underwent DST and 20 patients were diagnosed as having MDR-TB. Pre-diagnosis attrition was 60% (459/770). Among those with pre-diagnosis attrition, 91% (417/459) were not identified as 'presumptive MDR-TB' by the programme. TAT [median (IQR)] to undergo DST after eligibility was 4 (0, 10) days. Attrition was more than 40% across all subgroups. Age more than 64 years; those from a medical college; those eligible in quarter 1; patients with presumptive criteria 'previously treated - recurrent TB', 'treatment after loss-to-follow-up' and 'previously treated-others'; and patients with extra-pulmonary TB were independent risk factors for not undergoing DST. CONCLUSION: High pre-diagnosis attrition was contributed by failure to identify and refer patients. Attrition reduced modestly with time and one factor that might have contributed to this was introduction of CbNAAT in quarter 2 of 2014. General health system strengthening which includes improvement in identification/referral and patient tracking with focus on those with higher risk for not undergoing DST is urgently required.
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Aceptación de la Atención de Salud , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Adolescente , Adulto , Anciano , Antituberculosos/uso terapéutico , Diagnóstico Precoz , Femenino , Accesibilidad a los Servicios de Salud , Humanos , India , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Investigación Operativa , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/prevención & control , Adulto JovenRESUMEN
Objective: We assessed uptake of isoniazid preventive therapy (IPT) among child contacts of smear-positive tuberculosis (TB) patients and its implementation challenges from healthcare providers' and parents' perspectives in Bhopal, India. Methods: A mixed-method study design: quantitative phase (review of programme records and house-to-house survey of smear-positive TB patients) followed by qualitative phase (interviews of healthcare providers and parents). Results: Of 59 child contacts (<6 years) of 129 index patients, 51 were contacted. Among them, 19 of 51 (37%) were screened for TB and one had TB. Only 11 of 50 (22%) children were started and 10 of 50 (20%) completed IPT. Content analysis of interviews revealed lack of awareness, risk perception among parents, cumbersome screening process, isoniazid stock-outs, inadequate knowledge among healthcare providers and poor programmatic monitoring as main barriers to IPT implementation. Conclusion: National TB programme should counsel parents, train healthcare providers, simplify screening procedures, ensure regular drug supply and introduce an indicator to strengthen monitoring and uptake of IPT.
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Antituberculosos/farmacología , Control de Enfermedades Transmisibles/métodos , Trazado de Contacto/métodos , Conocimientos, Actitudes y Práctica en Salud , Isoniazida/farmacología , Cooperación del Paciente/etnología , Tuberculosis/prevención & control , Tuberculosis/transmisión , Adolescente , Adulto , Anciano , Antituberculosos/provisión & distribución , Preescolar , Femenino , Personal de Salud , Accesibilidad a los Servicios de Salud , Humanos , India , Lactante , Entrevistas como Asunto , Isoniazida/provisión & distribución , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Cooperación del Paciente/psicología , Profilaxis Posexposición , Evaluación de Programas y Proyectos de Salud , Investigación Cualitativa , Esputo/microbiología , Tuberculosis/diagnóstico , Adulto JovenRESUMEN
BACKGROUND: The degradation of ceramic femoral heads made of yttria-stabilized zirconia (Y-TZP) because of tetragonal-to-monoclinic phase transformation in vivo is well-described, whereas magnesia-stabilized zirconia (Mg-PSZ) ceramics resist phase transformation in a warm aqueous environment. The purpose of this study was to evaluate phase transformation, changes in surface topography, and roughness parameters, including changes in surface polarity and abrasiveness, among retrieved zirconia femoral heads. METHODS: A total of 69 Y-TZP and 86 Mg-PSZ-retrieved femoral heads were examined, with 5 never-implanted heads of each type as controls. Selected heads were scanned by x-ray diffraction, to measure % monoclinic phase. All heads were scanned by optical profilometry to find visual evidence of degradation and to measure surface roughness, surface polarity, and the functional roughness parameters. Monoclinic phase % and roughness data were plotted vs time in vivo. RESULTS: Visual evidence of phase transformation was observed among Y-TZP femoral heads, and some exhibited pitting. Y-TZP femoral heads roughened and become more abrasive in vivo, although those made by CeramTec exhibited less degradation than those by Morgan and Saint Gobain. In contrast, Mg-PSZ heads did not exhibit pitting, undergo phase transformation, or roughen in vivo, and retained a negative surface polarity. CONCLUSION: All Y-TZP femoral heads exhibited increased phase transformation with time in vivo, although not all Y-TZP heads exhibited catastrophic roughening. No phase transformation was observed on Mg-PSZ femoral heads after up to 19.2 years in vivo. The lack of degradation among Mg-PSZ retrievals suggests a lower wear potential in joint replacement.
Asunto(s)
Cabeza Femoral/cirugía , Prótesis de Cadera , Óxido de Magnesio/química , Diseño de Prótesis , Falla de Prótesis , Circonio/química , Cerámica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Ensayo de Materiales , Persona de Mediana Edad , Propiedades de Superficie , Difracción de Rayos X , ItrioRESUMEN
PURPOSE: To compare the efficacy between supplementing ferrous fumarate and ferrous sulfate to carbonated beverages by recording the in vitro mineral loss and surface microhardness (SMH) changes in human enamel. METHODS: 120 enamel blocks each (from primary and permanent teeth) were uniformly prepared and the initial SMH was recorded. These enamel specimens were equally divided (n = 60) for their respective beverage treatment in Group 1 (2 mmol/L ferrous sulfate) and Group 2 (2 mmol/L ferrous fumarate). Each group was further divided into three subgroups as Coca-Cola, Sprite and mineral water (n= 10). The specimens were subjected to three repetitive cycles of respective treatment for a 5-minute incubation period, equally interspaced by 5-minute storage in artificial saliva. The calcium and phosphate released after each cycle were analyzed spectrophotometrically and the final SMH recorded. RESULTS: The results were tested using student's t-test, one-way ANOVA and Wilcoxon signed rank test (P < 0.05). The spectrophotometric assessment of calcium and phosphate withdrawal found more loss with the supplementation of 2 mmol/L ferrous sulfate than ferrous fumarate (P < 0.005). Similarly, the mean surface microhardness reduction was less with the supplementation of 2 mmol/L ferrous fumarate than with ferrous sulfate (P < 0.005). Statistical comparisons revealed the maximum surface microhardness and mineral loss with primary enamel and the maximum loss produced in all groups by Coca-Cola (P < 0.005).