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1.
Inorg Chem ; 63(40): 18797-18808, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39315947

RESUMEN

A cobalt(II)-containing polyoxometalate, [H3O]5[{Co(H2O)4}3{Na(H2O)4}W12O42]·3H2O (Co-POM), has been isolated in a one-step facile aqueous synthesis and characterized unambiguously using single-crystal X-ray crystallography along with routine spectral analysis. The paratungstate cluster anion [W12O42]12- coordinates with {CoII(H2O)4}2+ and {Na(H2O)4}+ complex cations resulting in the formation of the water-insoluble Co-POM compound having three-dimensional (3-D) extended structure. Motivated by the protonated water molecules existing as the counter cations in Co-POM, herein, we demonstrate the detailed proton conductivity studies of the Co-POM, reaching a value of 1.04 × 10-2 S cm-1 at 80 °C and 98% relative humidity (RH). The temperature- and humidity-dependent proton conductivity in Co-POM is governed by Grotthus mechanism with Ea = 0.25 eV. In addition, we examined the electrochemical behavior of Co-POM, in an alkaline borate buffer where it is found to be electrochemically unstable and acts as a precatalyst (and not a true catalyst) for oxygen evolution reaction (OER). We also discuss the "post-mortem" analysis of the postelectrolysis sample to identify the active species which turns out to be a cobalt oxide material (Co3O4) incorporating small amounts of tungsten. Thus, in the present electrocatalysis work, the Co-POM molecule transforms into an efficient water oxidation catalyst (WOC).

2.
Mol Divers ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775995

RESUMEN

The remarkable conservation of the FtsZ among Gram-positive and Gram-negative bacteria, a crucial GTPase in bacterial cell division, has emerged as a promising antibacterial drug target to combat antibacterial resistance. There have been several coordinated efforts to develop inhibitors against FtsZ which can also serve as potential candidates for future antibiotics. In the present study, a natural product-like library (≈50,000 compounds) was employed to conduct HTVS against Staphylococcus aureus FtsZ protein (PDB Id: 6KVP). Additionally, molecular docking was carried out in two modes, SP and XP docking, using the Schrödinger suite. The glide scores of ligands obtained by XP docking were further summarized and compared with the control ligands (ZI1- co-crystal and PC190723-a compound undergoing clinical trial). Using the Prime-MM-GBSA approach, BFE calculations were performed on the top XP-scored ligands (≈598 compounds). These hits were also evaluated for ADMET parameters using the Qikprop algorithm, SwissADME, and in silico carcinogenicity testing using Carcinopred-El. Based on the results, ligand 4-FtsZ complex was considered for the 300 ns MDS analysis to get insights into its binding modes within the catalytic pocket of FtsZ protein. The analysis revealed that the amide linkage sandwiched between the triazole and 1-oxa-8-azaspirodecan-8-ium moiety (Val203) as well as the aminoethyl group present at 1st position on the triazole moiety (Leu209, Leu200, Asp210, and Ala202) were responsible for the FtsZ inhibitory activity, owing to their crucial interactions with key amino acid residues. Further, the complex also displayed good protein-ligand stability, ultimately predicting ligand 4 as a potent lead compound for the inhibition of FtsZ. Thus, our in silico findings will serve as a framework for in-depth in-vitro and in-vivo investigations encouraging the development of FtsZ inhibitors as a new generation of antibacterial agents.

3.
Prostate ; 83(15): 1395-1414, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37555617

RESUMEN

BACKGROUND: Radical prostatectomy is the standard of care for prostate cancer. Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) is being widely adopted due to positive functional outcomes compared to conventional robotic-assisted radical prostatectomy (c-RARP). Concerns regarding potency, oncological outcomes, and learning curve are still a matter of debate. METHODS: Following Preferred Instrument for Systematic Reviews and Meta-Analysis guidelines and PROSPERO registration CRD42023398724, a systematic review was performed in February 2023 on RS-RARP compared to conventional c-RARP. Outcomes of interest were continence recovery, potency, positive surgical margins (PSM), biochemical recurrence (BCR), estimated blood loss (EBL), length of stay (LOS), operation time and complications. Data were analyzed using R version 4.2.2. RESULTS: A total of 17 studies were included, totaling 2751 patients, out of which 1221 underwent RS-RARP and 1530 underwent c-RARP. Continence was analyzed using two definitions: zero pad and one safety pad. Cumulative analysis showed with both definitions statistical difference in terms of continence recovery at 1 month (0 pad odds ratio [OR] = 4.57; 95% confidence interval [CI] = [1.32-15.77]; Safety pad OR = 13.19; 95% CI = [8.92-19.49]), as well as at 3 months (0 pad OR, 2.93; 95% CI = [1.57-5.46]; Safety pad OR = 5.31; 95% CI = [1.33-21.13]). Continence recovery at 12 months was higher in the one safety pad group after RS-RARP (OR = 4.37; 95% CI = [1.97-9.73]). The meta-analysis revealed that overall PSM rates without pathologic stage classification were not different following RS-RARP (OR = 1.13; 95% CI = [0.96-1.33]. Analysis according to the tumor stage revealed PSM rates in pT2 and pT3 tumors are not different following RS-RARP compared to c-RARP (OR = 1.46; 95% CI = [0.84-2.55]) and (OR = 1.41; 95% CI = [0.93-2.13]), respectively. No difference in potency at 12 months (OR = 0.98; 95% CI = [0.69-1.41], BCR at 12 months (OR = 0.99; 95% CI = [0.46-2.16]), EBL (standardized mean difference [SMD] = -0.01; 95% CI = [-0.31 to 0.29]), LOS (SMD = -0.01; 95% CI = [-0.48 to 0.45]), operation time (SMD = -0.14; 95% CI = [-0.41 to 0.12]) or complications (OR = 0.9; 95% CI = [0.62-1.29]) were observed. CONCLUSIONS: Our analysis suggests that RS-RARP is safe and feasible. Faster continence recovery rate is seen after RS-RARP. Potency outcomes appear to be similar. PSM rates are not different following RS-RARP regardless of pathologic stage. Further quality studies are needed to confirm these findings.


Asunto(s)
Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del Tratamiento , Neoplasias de la Próstata/patología , Prostatectomía/efectos adversos , Biopsia , Márgenes de Escisión
4.
Eur J Clin Microbiol Infect Dis ; 41(1): 87-97, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34599708

RESUMEN

Prosthetic joint infection (PJI) is a feared and challenging to diagnose complication after arthroplasty, with Staphylococcus epidermidis as the major pathogen. One important criteria to define PJI is the detection of phenotypically indistinguishable microorganisms with identical antibiotic susceptibility pattern in at least two different samples. However, owing to phenotypical variation within genetic clones and clonal variation within a phenotype, the criteria may be ambiguous. We investigated the extent of diversity among coagulase-negative staphylococci (CoNS) in PJI and characterised S. epidermidis isolates from PJI samples, specifically multiple S. epidermidis isolates identified in individual PJI patients. We performed a retrospective cohort study on 62 consecutive patients with PJI caused by CoNS from two hospitals in Northern Sweden. In 16/62 (26%) PJIs, multiple S. epidermidis isolates were available for whole-genome analyses. Hospital-adapted multidrug-resistant genetic clones of S. epidermidis were identified in samples from 40/62 (65%) of the patients using a combination of pulsed-field gel electrophoresis and multilocus sequence typing. Whole-genome sequencing showed the presence of multiple sequence types (STs) in 7/16 (44%) PJIs where multiple S. epidermidis isolates were available. Within-patient phenotypical variation in the antibiotic susceptibility and/or whole-genome antibiotic resistance gene content was frequent (11/16, 69%) among isolates with the same ST. The results highlight the ambiguity of S. epidermidis phenotypic characterisation as a diagnostic method in PJI and call for larger systematic studies for determining the frequency of CoNS diversity in PJIs, the implications of such diversity for microbiological diagnostics, and the therapeutic outcomes in patients.


Asunto(s)
Articulaciones/microbiología , Infecciones Relacionadas con Prótesis/microbiología , Staphylococcus epidermidis/fisiología , Anciano , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Articulaciones/cirugía , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Prótesis e Implantes/microbiología , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Estudios Retrospectivos , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/aislamiento & purificación
5.
Sensors (Basel) ; 22(23)2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36502020

RESUMEN

In recent years, detecting credit card fraud transactions has been a difficult task due to the high dimensions and imbalanced datasets. Selecting a subset of important features from a high-dimensional dataset has proven to be the most prominent approach for solving high-dimensional dataset issues, and the selection of features is critical for improving classification performance, such as the fraud transaction identification process. To contribute to the field, this paper proposes a novel feature selection (FS) approach based on a metaheuristic algorithm called Rock Hyrax Swarm Optimization Feature Selection (RHSOFS), inspired by the actions of rock hyrax swarms in nature, and implements supervised machine learning techniques to improve credit card fraud transaction identification approaches. This approach is used to select a subset of optimal relevant features from a high-dimensional dataset. In a comparative efficiency analysis, RHSOFS is compared with Differential Evolutionary Feature Selection (DEFS), Genetic Algorithm Feature Selection (GAFS), Particle Swarm Optimization Feature Selection (PSOFS), and Ant Colony Optimization Feature Selection (ACOFS) in a comparative efficiency analysis. The proposed RHSOFS outperforms existing approaches, such as DEFS, GAFS, PSOFS, and ACOFS, according to the experimental results. Various statistical tests have been used to validate the statistical significance of the proposed model.


Asunto(s)
Algoritmos , Aprendizaje Automático
6.
Chem Zvesti ; 76(2): 1107-1117, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34690413

RESUMEN

COVID-19 is an unprecedented pandemic threatening global health, and variants were discovered rapidly after the pandemic. The two variants, namely the SARS-CoV-2 B.1.1.7 (Alpha) and P.1 (Gamma), were formed by the mutations in the receptor binding domain of spike glycoprotein (SGP). These two variants are known to possess a high binding affinity with the angiotensin-converting enzyme 2. Amidst the rapid spread of these mutant strains, research and development of novel molecules become tedious and labour-intensive. Imidazole and benzimidazole scaffolds were selected in this study based on their unique structural features and electron-rich environment, resulting in increased affinity against a variety of therapeutic targets. In the current study, imidazole- and benzimidazole-based anti-parasitic drugs are repurposed against SARS-CoV-2 Alpha and Gamma variant spike glycoproteins using computational strategies. Out of the screened 15 molecules, flubendazole and mebendazole have exhibited promising binding features to the two receptors (PDB ID: 7NEH and 7NXC), as evidenced by their glide score and binding free energy. The results are compared with that of the two standard drugs, remdesivir and hydroxychloroquine. Flubendazole and mebendazole have become convenient treatment options against mutant lineages of SARS-CoV-2. The edge of the flubendazole was further established by its stability in MD simulation conducted for 100 ns employing GROMACS software. Further, in vitro and in vivo studies are essential to understand, if flubendazole and mebendazole indeed hold the promise to manage SARS-CoV-2 mutant stains. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-021-01900-8.

7.
J Minim Access Surg ; 18(2): 230-234, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33605934

RESUMEN

BACKGROUND: This study aims at describing the feasibility and safety of video-assisted thoracic surgery (VATS) in benign diseases such as pulmonary sequestrations (PSs) and report the surgical outcomes. MATERIALS AND METHODS: This is a retrospective analysis of prospectively maintained data of 25 patients who were operated for PS over 7 years at a dedicated thoracic surgery centre in India. Pre-operative details, operative technique and details, post-operative details and complications were recorded and analysed. RESULTS: There were 15 (60%) males and 10 (40%) females, with a median age of 22.28 years (range, 16-28 years). All patients had intra-lobar type of sequestration. The most commonly involved was left lower lobe (n = 15 patients, 60%) followed by the right lower lobe (n = 10 patients, 40%). The origin of blood supply was from the descending thoracic aorta in 18 patients (72%), the abdominal aorta in 5 (20%) and the coeliac trunk and the inferior phrenic artery in one patient (4%) each. All patients underwent complete lobar resection. One patient was converted because of dense hilar adhesion. The average duration of surgery was 179 min and the average blood loss was 204 ml. The median hospital stay and chest tube duration were 4 and 3 days, respectively. One patient was re-explored because of post-operative bleeding. Only one patient had an air leak for >7 days. The median follow-up was 42 months (range, 6-90 months) without any recurrence. CONCLUSIONS: VATS is a safe, feasible and effective option for PS at experienced centres.

8.
Drug Dev Res ; 82(4): 503-522, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33432634

RESUMEN

Diabetes mellitus (DM) is an endocrine disorder that causes increased blood glucose than usual due to insulin impairment. In DM, several complications arise in which diabetic wound (DW) is the most devastating complication. About 25% of patients with DM expected to develop DWs in their lifetime and undergo limb amputations. Even though several treatments such as surgery, debridement, wound dressings, advanced therapies were available, the overall conclusion has been that with very few exceptions, patients still suffer from limitations like pain, frequent dress changing, high rates of failure, and cost involvement. Further, the treatments involving the delivery of therapeutic agents in treating DWs have limited success due to abnormal levels of proteases in the DW environment. In this backdrop, in situ gelling injectable hydrogels have gained special attention due to their easy encapsulation of therapeutic medications and prolonged release, filling the wound defect areas, ease of handling, and minimally invasive surgical procedures. Though the in situ gelling injectable hydrogels are developed a couple of decades ago, their use for treating DW has not yet been explored thoroughly. Thus, in this review, we have covered the sequential events of DW healing, pathophysiology, current treatments, and its limitations, along with a particular emphasis on the mechanism of action of these in situ gelling injectable hydrogels treating DWs.


Asunto(s)
Complicaciones de la Diabetes/tratamiento farmacológico , Hidrogeles/administración & dosificación , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Vendajes , Proliferación Celular/efectos de los fármacos , Desbridamiento , Hemostasis/efectos de los fármacos , Humanos , Oxigenoterapia Hiperbárica , Control de Infecciones , Inflamación/tratamiento farmacológico , Inyecciones , Péptidos y Proteínas de Señalización Intercelular/farmacología , Terapia de Presión Negativa para Heridas , Piel Artificial
9.
Photochem Photobiol Sci ; 18(6): 1540-1555, 2019 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-31020956

RESUMEN

In this study, Cu doped ZnO photo-catalysts were used for the degradation of the heterocyclic compounds, pyridine and quinoline. Three ZnO based photo-catalysts with different amounts of Cu doping (1%, 5% and 10%) were synthesized by precipitation method. The characterization of the catalyst was done using field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Brunauer Emmett Teller (BET), diffuse reflectance spectroscopy (DRS) and photo-luminescence (PL) techniques. The band gaps of the pure ZnO, and 1%, 5% and 10% Cu doped ZnO photo-catalysts were found to be 3.27 eV, 3.21 eV, 3.17 eV and 2.91 eV, respectively. The effects of pH, photo-catalyst dose and irradiation time were studied. Under optimum conditions (5% Cu doped ZnO, dose of 1.2 g L-1 for pyridine and 1.6 g L-1 for quinoline, pH = 11 and time = 5 h), the maximum pyridine and quinoline mineralization efficiencies were found to be 92.4% and 74.3%, respectively. The mineralization process followed first-order kinetics. The in situ formation of singlet oxygen, hydroxyl radicals and superoxide radicals was confirmed by reactive oxygen species (ROS) scavenger studies. Catalyst reusability studies showed excellent mineralization up to four consecutive cycles. The enhanced photo-catalytic mechanism was studied by comparing the band structure with respect to the potential of highly reactive species (˙OH and O2˙-). A possible mineralization pathway was proposed on the basis of the intermediates detected by gas chromatography coupled with mass spectrometry (GC-MS) analysis.

10.
BMC Med Educ ; 19(1): 303, 2019 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-31391042

RESUMEN

BACKGROUND: A two-year optometry technician (OT) training was started in Eritrea in 2009 to fulfill the immediate human resource needs in providing refractive, dispensing and primary eye care services in vision centers. This study aimed to assess the current practice pattern and confidence level among the OTs. METHODS: A self-administered questionnaire was developed and administered to all available OTs in January 2017. The OTs were identified through the Ministry of Health's database. The questionnaire included questions on demographics, scope of practice and confidence level in the clinical practice areas. RESULTS: A total of 94 OTs had graduated by the end of 2016 and 71 (75.5%) of them were involved in the country's eye care services. All the 70 OTs who completed the survey were working under the Ministry of Health in various regions of the country. The mean age of the OTs was 25.6 ± 4.7 years (range: 20 to 48 years) and 43 (61.4%) of them were male. Four out of six regions in the country lacked the required number of OTs for the recommended ratio of one refractionist to 50,000 population. All the OTs provided refraction services; however, they lacked experience in dispensing (62.9%), clinical examination of patients (35.7%) and low vision care (4.3%). While the OTs expressed confidence in refractive procedures, low levels of confidence were expressed for dispensing and primary eye care services. CONCLUSION: OTs contributed to the primary eye care sector in Eritrea. However, high attrition rate, imbalanced distribution, a limited practice in core areas and low clinical confidence were the key challenges for this profession in this country. With better facilities, improved infrastructure and extended education and career opportunities, the two-year trained OTs could potentially serve further in the Eritrean eye care system. Further studies to evaluate the competency, job satisfaction and effectiveness OTs are recommended.


Asunto(s)
Técnicos Medios en Salud/educación , Competencia Clínica , Optometría/educación , Alcance de la Práctica , Autoimagen , Adulto , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Adulto Joven
11.
Drug Dev Ind Pharm ; 44(10): 1650-1658, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29848103

RESUMEN

5-Aminosalicylic acid (5-ASA) is an aminosalicylate anti-inflammatory drug, which is also known as mesalazine or mesalamine. Currently employed in treating inflammatory bowel disease, ulcerative colitis, inflamed anus or rectum, and maintain remission in Crohn's disease. Evidence from the researchers highlighted its significant re-epithelization in allergic asthma, aphthous, and gastric ulcerative conditions. The objective of the study was to formulate the pluronic lecithin organogel (PLO) containing 5-ASA and evaluate its wound-healing ability in a full thickness excision wound rat model. The data obtained from in silico docking studies revealed 5-ASA is having an affinity towards the transforming growth factor-beta (TGF-ß) specifically towards beta1. Among various formulations prepared (F1 to F8), F1, and F6 have shown a maximum in vitro drug release with optimum pH and viscosity. From MTT assay it was found that selected PLO formulations showed no toxicity and enhanced cell proliferation in HaCaT cell lines. In vivo wound-healing studies in albino Wistar rats has revealed that PLO accelerates wound closure and reepithelization to the statistically significant level on day 3 (p < .05) in comparison with untreated wounds. In conclusion, the overall results suggest that 5-ASA PLO gel is a potential therapeutic option for the treatments of wounds, however, further studies are highly warrened to determine the various mechanisms of 5-ASA in regulating the cell migration and reepithelization in wound healing to outspread its use in clinics.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Lecitinas/farmacología , Mesalamina/farmacología , Poloxámero/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/química , Línea Celular , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Femenino , Geles , Humanos , Lecitinas/química , Masculino , Mesalamina/química , Poloxámero/química , Conejos , Ratas , Tensoactivos/química , Tensoactivos/farmacología , Cicatrización de Heridas/fisiología
12.
BMC Ophthalmol ; 17(1): 209, 2017 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-29166895

RESUMEN

BACKGROUND: Proper information on causes of childhood vision loss is essential in developing appropriate strategies and programs to address such causes. This study aimed at identifying the causes of vision loss in children attending the national referral eye hospital with the only pediatric ophthalmology service in Eritrea. METHODS: A retrospective data review was conducted for all the children (< 16 years of age) who attended Berhan Aiyni National Referral Eye Hospital in five years period from January 2011 to December 2015. Causes of vision loss for children with vision impairment (recorded visual acuity less than 6/18 for distance in the better eye) was classified by the anatomical site affected and by underlying etiology based on the timing of the insult and causal factor. RESULTS: The medical record cards of 22,509 children were reviewed, of whom 249 (1.1%) were visually impaired. The mean age of the participants was 7.82 ± 5.43 years (range: one month to 16 years) and male to female ratio was 1:0.65. The leading causes of vision loss were cataract (19.7%), corneal scars (15.7%), refractive error and amblyopia (12.1%), optic atrophy (6.4%), phthisis bulbi (6.4%), aphakia (5.6%) and glaucoma (5.2%). Childhood factors including trauma were the leading causes identified (34.5%) whereas other causes included hereditary factors (4%), intrauterine factors (2.0%) and perinatal factors (4.4%). In 55.0% of the children, the underlying etiology could not be attributed. Over two-thirds (69.9%) of vision loss was potentially avoidable in nature. CONCLUSION: This study explored the causes of vision loss in Eritrean children using hospital based data. Cataract corneal opacities, refractive error and amblyopia, globe damage due to trauma, infection and nutritional deficiency, retinal disorders, and other congenital abnormalities were the leading causes of childhood vision impairment in children attending the tertiary eye hospital in Eritrea. As majority of the causes of vision loss was due to avoidable causes, we recommended primary level public health strategies to prevent ocular injuries, vitamin A deficiency, perinatal infections and retinopathy of prematurity as well as specialist pediatric eye care facilities for cataract, refractive errors, glaucoma and rehabilitative services to address childhood vision loss in Eritrea.


Asunto(s)
Ceguera/etiología , Oftalmopatías/complicaciones , Baja Visión/etiología , Adolescente , Niño , Preescolar , Eritrea , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Riesgo
13.
Hereditas ; 153: 16, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28096778

RESUMEN

BACKGROUND: Simple Sequence Repeats or microsatellites are resourceful molecular genetic markers. There are only few reports of SSR identification and development in pineapple. Complete genome sequence of pineapple available in the public domain can be used to develop numerous novel SSRs. Therefore, an attempt was made to identify SSRs from genomic, chloroplast, mitochondrial and EST sequences of pineapple which will help in deciphering genetic makeup of its germplasm resources. RESULTS: A total of 359511 SSRs were identified in pineapple (356385 from genome sequence, 45 from chloroplast sequence, 249 in mitochondrial sequence and 2832 from EST sequences). The list of EST-SSR markers and their details are available in the database. CONCLUSIONS: PineElm_SSRdb is an open source database available for non-commercial academic purpose at http://app.bioelm.com/ with a mapping tool which can develop circular maps of selected marker set. This database will be of immense use to breeders, researchers and graduates working on Ananas spp. and to others working on cross-species transferability of markers, investigating diversity, mapping and DNA fingerprinting.


Asunto(s)
Ananas/genética , Bases de Datos de Ácidos Nucleicos , Genoma de Planta , Repeticiones de Microsatélite , ADN de Cloroplastos/genética , ADN Mitocondrial/genética , ADN de Plantas/genética , Etiquetas de Secuencia Expresada , Marcadores Genéticos , Interfaz Usuario-Computador
14.
Antimicrob Agents Chemother ; 58(7): 4123-30, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24798289

RESUMEN

The type VI secretion system (T6SS) is the most prevalent bacterial secretion system and an important virulence mechanism utilized by Gram-negative bacteria, either to target eukaryotic cells or to combat other microbes. The components show much variability, but some appear essential for the function, and two homologues, denoted VipA and VipB in Vibrio cholerae, have been identified in all T6SSs described so far. Secretion is dependent on binding of an α-helical region of VipA to VipB, and in the absence of this binding, both components are degraded within minutes and secretion is ceased. The aim of the study was to investigate if this interaction could be blocked, and we hypothesized that such inhibition would lead to abrogation of T6S. A library of 9,600 small-molecule compounds was screened for their ability to block the binding of VipA-VipB in a bacterial two-hybrid system (B2H). After excluding compounds that showed cytotoxicity toward eukaryotic cells, that inhibited growth of Vibrio, or that inhibited an unrelated B2H interaction, 34 compounds were further investigated for effects on the T6SS-dependent secretion of hemolysin-coregulated protein (Hcp) or of phospholipase A1 activity. Two compounds, KS100 and KS200, showed intermediate or strong effects in both assays. Analogues were obtained, and compounds with potent inhibitory effects in the assays and desirable physicochemical properties as predicted by in silico analysis were identified. Since the compounds specifically target a virulence mechanism without affecting bacterial replication, they have the potential to mitigate the virulence with minimal risk for development of resistance.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Sistemas de Secreción Bacterianos/efectos de los fármacos , Proteínas Hemolisinas/metabolismo , Fosfolipasas A1/antagonistas & inhibidores , Vibrio cholerae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Fosfolipasas A1/metabolismo , Vibrio cholerae/patogenicidad , Factores de Virulencia/antagonistas & inhibidores
15.
Opt Lett ; 39(16): 4966-9, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-25121920

RESUMEN

This Letter presents the essence of our recent experimental study on generic singularities carrying spatially partially coherent, polychromatic dark hollow beams (PDHBs). To the best of our knowledge, this is the first experimental demonstration of generic singularities-induced wavefront tearing in focused polychromatic beams.

16.
World J Surg ; 38(12): 3235-47, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25189439

RESUMEN

INTRODUCTION: Tropical pancreatitis is a form of chronic pancreatitis originally described in the tropics. Prospective studies in Western countries have shown improved quality of life (QOL) following surgery in alcoholic chronic pancreatitis. In studies on Frey's pancreaticojejunostomy for tropical pancreatitis, improvement in pain was considered the endpoint, and there is a paucity of data in the literature with regard to QOL with tropical pancreatitis following surgery. OBJECTIVE: Our objective was to prospectively analyze the outcome of Frey's pancreaticojejunostomy in tropical pancreatitis and health-related QOL following surgery by administering the Short Form 36-item health survey (SF-36). MATERIALS AND METHODS: A total of 25 patients underwent Frey's pancreaticojejunostomy between 2010 and 2012 and were included in the study; data were collected prospectively. The visual analog scale (VAS) for pain and the SF-36 form were used to record health-related QOL preoperatively, and at 3 and 12 months post-surgery, comparing the same with the general population. RESULTS: Patients with tropical pancreatitis experience poor QOL (26.71 ± 15.95) compared with the general population (84.54 ± 12.42). Post-operative QOL scores (78.54 ± 15.84) were better than the pre-operative scores (26.71 ± 15.95) at 12-month post-surgery follow-up. The VAS score for pain improved at 12 months post-surgery (1.58 ± 1.41 vs. 8.21 ± 1.64). Two of the three patients (12.5 %) who had diabetes were free from anti-diabetes medication at 12 months post-surgery. Steatorrhea was seen in five patients (20.8 %) before surgery and increased to eight (33.3 %) at 12 months post-surgery. Mean body weight increased from 45.75 kg pre-operatively to 49.25 kg at 12 months post-operatively. CONCLUSIONS: Frey's pancreaticojejunostomy effectively reduces pain in tropical pancreatitis, with significant improvement in health-related QOL, which is comparable with the general population in most aspects.


Asunto(s)
Dolor Abdominal/etiología , Pancreatoyeyunostomía/métodos , Pancreatitis Alcohólica/cirugía , Pancreatitis Crónica/cirugía , Calidad de Vida , Adolescente , Adulto , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dimensión del Dolor , Pancreatitis Alcohólica/complicaciones , Pancreatitis Crónica/complicaciones , Estudios Prospectivos , Esteatorrea/etiología , Resultado del Tratamiento , Aumento de Peso , Adulto Joven
17.
Materials (Basel) ; 17(19)2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39410346

RESUMEN

Recycling's value in conserving scarce resources, avoiding environmental damage to the land, and reducing energy consumption is well known. This research aims to develop a composite that uses recycled reinforcement that was formed through an in situ method to build confidence in the usage of recycled materials. Thus, in connection with defense and aerospace industry applications, aluminum composite alloys receive more interest due to their light weight and high strength with improved mechanical properties; therefore, this research focuses on the fabrication of in situ-developed recycled TiC (r-TiC)-reinforced AlZnMgCu composites, i.e., new recycled materials. Experiments were conducted to determine the synthesized composites' microstructural, mechanical, tribological, and corrosion properties. The microstructural study showed that r-TiC was distributed uniformly along the grain boundaries until the addition of 12% r-TiC. However, the accumulation of reinforcements began at 14% r-TiC addition and became more aggregated with subsequent increases in the percentage addition of r-TiC. The mechanical and tribological tests showed that the composite with 14% r-TiC was superior to all other compositions, with 60% improved mechanical qualities and the lowest wear rate of 0.0007 mm3/m. Composites containing 2% r-TiC showed the best corrosion resistance, an increase of 22% over AlZnMgCu, without reinforcement.

18.
Diseases ; 12(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39195171

RESUMEN

Diabetic wounds (DWs) are considered chronic complications observed in patients suffering from type 2 diabetes mellitus (DM). Usually, DWs originate from the interplay of inflammation, oxidation, impaired tissue re-epithelialization, vasculopathy, nephropathy, and neuropathy, all of which are related to insulin resistance and sensitivity. The conventional approaches available for the treatment of DWs are mainly confined to the relief of wound pressure, debridement of the wound, and management of infection. In this paper, we speculate that treatment of DWs with 5-aminosalicylic acid (5-ASA) and subsequent activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and transforming growth factor beta (TGF-ß) via the AhR pathway might be highly beneficial for DW patients. This estimation is based on several lines of evidence showing that 5-ASA and PPAR-γ activation are involved in the restoration of insulin sensitivity, re-epithelialization, and microcirculation. Additionally, 5-ASA and TGF-ß activate inflammation and the production of pro-inflammatory mediators. Suitable stabilized formulations of 5-ASA with high absorption rates are indispensable for scrutinizing its probable pharmacological benefits since 5-ASA is known to possess lower solubility profiles because of its reduced permeability through skin tissue. In vitro and in vivo studies with stabilized formulations and a control (placebo) are mandatory to determine whether 5-ASA indeed holds promise for the curative treatment of DWs.

19.
Life (Basel) ; 14(5)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38792564

RESUMEN

Chronic obstructive pulmonary disease (COPD) is a common condition with an estimated prevalence of 12% in adults over the age of 30 years worldwide. COPD is a leading cause of morbidity and mortality globally, with a substantial economic and social burden. There are an estimated 3 million deaths annually due to COPD. However, most of the patients with COPD respond to routine interventions like bronchodilator therapy, assessing supplemental oxygen needs, smoking cessation, vaccinations, and pulmonary rehabilitation. There is a significant number of patients who unfortunately progress to have persistent symptoms despite these interventions. Refractory COPD is not yet formally defined. Patients with severe persistent symptoms or exacerbations despite appropriate care can be considered to have refractory COPD. Managing refractory COPD needs a multidimensional approach. In this review article, we will discuss essential interventions like ensuring adequate inhaler techniques, exploring the need for non-invasive ventilatory support, use of chronic antibiotics and phosphodiesterase inhibitors to advanced therapies like bronchoscopic lung volume reduction surgery, and the upcoming role of anti-IL5 agents in managing patients with refractory COPD. We will also discuss non-pharmacologic interventions like psycho-social support and nutritional support. We will conclude by discussing the palliative care aspect of managing patients with refractory COPD. Through this review article, we aim to better the approach to managing patients with refractory COPD and discuss new upcoming therapies.

20.
Antibiotics (Basel) ; 13(7)2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-39061258

RESUMEN

Bacterial histidine kinase (BHK) is a constituent of the two-component signaling (TCS) pathway, which is responsible for the regulation of a number of processes connected to bacterial pathogenicity, virulence, biofilm development, antibiotic resistance, and bacterial persistence. As BHK regulation is diverse, inhibitors can be developed, such as antibiotic synergists, bacteriostatic/bactericidal agents, virulence inhibitors, and biofilm inhibitors. Inhibition of essential BHK has always been an amenable strategy due to the conserved binding sites of the domains across bacterial species and growth dependence. Hence, an inhibitor of BHK might block multiple TCS regulatory networks. This review describes the TCS system and the role of BHK in bacterial virulence and discusses the available inhibitors of BHK, which is a specific response regulator with essential structural features.

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