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1.
Int J Med Microbiol ; 314: 151595, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38159514

RESUMEN

The rapid increase of OXA-244-producing Escherichia coli, predominantly driven by genetically clustered isolates of sequence type (ST)38, has been observed in at least nine European countries, including Germany. However, the reasons for the spread of OXA-244-producing E. coli remain unclear. Here, we aim to evaluate the possibility of prolonged carriage. We identified a total of six different patients with repeated detection of OXA-244-producing E. coli isolates, which were subjected to both short and long-read whole-genome sequencing (WGS). Besides allelic differences using core genome multilocus sequence typing (cgMLST) analyses, we obtained numbers of single-nucleotide polymorphisms (SNPs) to calculate individual base-pair substitution (BPS) rates. To assess possible re-exposure and risk factors for prolonged carriage, case interviews were conducted. The time between detections ranged from eleven months to more than three years. Initial isolates originated in three+ out of six cases from clinical samples, whereas remaining samples were from screening, mostly in the inpatient setting. As expected, cgMLST analyses showed low numbers of allelic differences between isolates of each case ranging from 1 to 4, whereas numbers of SNPs were between 2 and 99 (mean = 36), thus clearly highlighting the discrepancy between these different bacterial typing approaches. For five out of six cases, observed BPS rates suggest that patients can be colonized with OXA-244-producing E. coli, including ST38 cluster isolates, for extensively long times. Thus, we may have previously missed the epidemiological link between cases because exposure to OXA-244-producing E. coli could have occurred in a time frame, which has not been evaluated in previous investigations. Our results may help to guide future epidemiological investigations as well as to support the interpretation of genetic diversity of OXA-244-producing E. coli, particularly among ST38 cluster isolates.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli , Humanos , Escherichia coli/genética , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Tipificación de Secuencias Multilocus/métodos , Antibacterianos , Pruebas de Sensibilidad Microbiana
2.
J Exp Bot ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38804905

RESUMEN

Complete panicle exsertion (CPE) is an economically important quantitative trait that contributes to grain yield in rice. We deployed an integrated approach for understanding the molecular mechanism of CPE using a stable EMS mutant line, CPE-109 of Samba Mahsuri (SM) exhibiting CPE. Two consistent genomic regions have been identified for CPE through QTL mapping [qCPE-4 (28.24-31.22 Mb) and qCPE-12 (2.30-3.18 Mb)] and QTL-sequencing [Chr-4 (31.21-33.69 Mb) and Chr-12 (0.12-3.15 Mb)]. Two non-synonymous SNPs, viz; KASP 12-12 (T→C; Chr12:1269983) in Os12g0126300; AP2/ERF transcription factor and KASP 12-16 (G→A; Chr12:1515198) in Os12g0131400; F-box domain-containing protein explained 81.05 and 59.61% phenotypic variance respectively and exhibited strong co-segregation with CPE in F2 mapping populations, advanced generation lines and CPE exhibiting SM mutants through KASP assays. The downregulation of these genes in CPE-109 compared to SM was observed in transcriptome sequencing of flag leaves which was validated through qRT-PCR. We propose that the abrogation of Os12g0126300 and Os12g0131400 in CPE-109 combinatorially influences the downregulation of ethylene biosynthetic genes viz. ACC synthase, ethylene-responsive factor-2, and up-regulation of gibberellic acid synthetic genes viz. ent-kaurene synthase and two cytokinin biosynthesis genes viz. cytokinin-O-glucosyltransferase 2, carboxy-lyase which result in complete panicle exsertion.

3.
Exp Dermatol ; 33(6): e15120, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38886965

RESUMEN

Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.


Asunto(s)
Biomarcadores , Senescencia Celular , Biología Computacional , Fibroblastos , Envejecimiento de la Piel , Humanos , Envejecimiento de la Piel/genética , Fibroblastos/metabolismo , Biomarcadores/metabolismo , Aprendizaje Automático , Transcriptoma , Colágeno/metabolismo , Regulación hacia Abajo , Piel/metabolismo , Rayos Ultravioleta , Peróxido de Hidrógeno/metabolismo
4.
Subcell Biochem ; 106: 197-210, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38159228

RESUMEN

The cytopathic effect comprises the set of cellular alterations produced by a viral infection. It is of great relevance since it constitutes a direct marker of infection. Likewise, these alterations are often virus-specific which makes them a phenotypic marker for many viral species. All these characteristics have been used to complement the study of the dynamics of virus-cell interactions through the kinetic study of the progression of damage produced by the infection. Various approaches have been used to monitor the cytopathic effect, ranging from light microscopy, immunofluorescence assays, and direct labeling with fluorescent dyes, to plaque assay for the characterization of the infection over time. Here we address the relevance of the study of cytopathic effect and describe different experimental alternatives for its application.


Asunto(s)
Virus , Efecto Citopatogénico Viral
5.
BMC Med Educ ; 24(1): 343, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38539186

RESUMEN

BACKGROUND: In the dynamic field of pharmacy amongst a diverse array of countries with disparate income levels, pharmacists play a pivotal role in integrating emerging scientific knowledge into their practice while adapting to evolving therapeutic interventions and expanding service delivery responsibilities. Lifelong Learning (LLL) is cultivated through continuing professional education (CPE) and continuing professional development (CPD), indispensable components ensuring sustained professional competence and heightened patient care quality. The global landscape witnesses diverse LLL activities tailored to pharmacists' learning needs and preferences. This scoping review maps and synthesises a comprehensive global perspective on the existing knowledge regarding CPE/CPD models, statutory requirements, and pharmacists' preferences for LLL activities. OBJECTIVE: To comprehensively investigate global models of CPE/CPD for pharmacists' and examine the statutory requirements governing pharmacists' registration and licensure. METHOD: A literature search of PubMed, Google Scholar, Web of Science, and the University of KwaZulu-Natal library search engine was undertaken for studies between January 2012 and February 2023. The article selection and reporting followed the recommendations made by PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) guidelines. The articles were tabulated based on their respective country's income level, continuing education models employed, country-specific statutory requirements, and pharmacists' preferences for LLL activities. RESULTS: Of the initial 3974 publications identified through the database search, 24 studies met the review criteria. The majority of the articles originated from high-income countries (HICs) (14/24, 58.3%), and most employed the mandatory CPD points system (21/24, 87.5%). However, in some HICs and upper-middle income countries (UMICs), the CPE/CPD is non-mandatory. While most countries (19/24, 79.2%) offer various LLL formats, the preference of pharmacists remains primarily face-to-face learning (13/24, 54.2%). However, workplace learning (3/24, 12.5%) and blended learning (7/24, 29.1%) are mentioned in some studies. CONCLUSION: Diverse models of CPE/CPD alongside statutory requirements persist globally and evolve, shaped by varied implementation experiences. HICs lead in CPD models, while the implementation in low- and middle-income countries (LMICs) and low-income countries (LICs) requires further exploration for inclusivity and effectiveness. A few UMICs are either initiating or in early stages of implementing the CPD models. Structured planning for LLL activities is increasingly a global requirement for pharmacists' licensure. The essential progression of pharmacy practice in developing healthcare systems necessitates a mandatory CPD model. Ongoing research is crucial to fortify the implementation, align and unify the CPD model with evolving pharmacy profession needs.


Asunto(s)
Educación Continua en Farmacia , Farmacéuticos , Humanos , Modelos Educacionales
6.
Sensors (Basel) ; 24(4)2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38400369

RESUMEN

Amyloid plays a critical role in the pathogenesis of Alzheimer's disease (AD) and can aggregate to form oligomers and fibrils in the brain. There is increasing evidence that highly toxic amyloid-ß oligomers (AßOs) lead to tau protein aggregation, hyperphosphorylation, neuroinflammation, neuronal loss, synaptic loss, and dysfunction. Although the effects of AßOs on neurons have been investigated using conventional biochemical experiments, there are no established criteria for electrical evaluation. To this end, we explored electrophysiological changes in mouse hippocampal neurons (HT22) following exposure to AßOs and/or naringenin (Nar, a flavonoid compound) using electrical impedance spectroscopy (EIS). AßO-induced HT22 showed a decreased impedance amplitude and increased phase angle, and the addition of Nar reversed these changes. The characteristic frequency was markedly increased with AßO exposure, which was also reversed by Nar. The AßOs decreased intranuclear and cytoplasmic resistance and increased nucleus resistance and extracellular capacitance. Overall, the innovative construction of the eight-element CPE-equivalent circuit model further reflects that the pseudo-capacitance of the cell membrane and cell nucleus was increased in the AßO-induced group. This study conclusively revealed that AßOs induce cytotoxic effects by disrupting the resistance characteristics of unit membranes. The results further support that EIS is an effective technique for evaluating AßO-induced neuronal damage and microscopic electrical distinctions in the sub-microscopic structure of reactive cells.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Ratones , Animales , Péptidos beta-Amiloides/química , Impedancia Eléctrica , Enfermedad de Alzheimer/patología , Neuronas/metabolismo , Sinapsis/metabolismo , Sinapsis/patología
7.
Dev Biol ; 481: 160-171, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34666023

RESUMEN

The corpuscles of Stannius (CS) represent a unique endocrine organ of teleostean fish that secrets stanniocalcin-1 (Stc1) to maintain calcium homeostasis. Appearing at 20-25 somite stage in the distal zebrafish pronephros, stc1-expressing cells undergo apical constriction, and are subsequently extruded to form a distinct gland on top of the distal pronephric tubules at 50 â€‹h post fertilization (hpf). Several transcription factors (e.g. Hnf1b, Irx3b, Tbx2a/b) and signaling pathways (e.g. Notch) control CS development. We report now that Fgf signaling is required to commit tubular epithelial cells to differentiate into stc1-expressing CS cells. Inhibition of Fgf signaling by SU5402, dominant-negative Fgfr1, or depletion of fgf8a prevented CS formation and stc1 expression. Ablation experiments revealed that CS have the ability to partially regenerate via active cell migration involving extensive filopodia and lamellipodia formation. Activation of Wnt signaling curtailed stc1 expression, but had no effect on CS formation. Thus, our observations identify Fgf signaling as a crucial component of CS cell fate commitment.


Asunto(s)
Diferenciación Celular , Glándulas Endocrinas/embriología , Factores de Crecimiento de Fibroblastos , Pronefro/embriología , Vía de Señalización Wnt , Proteínas de Pez Cebra , Pez Cebra , Animales , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Pez Cebra/embriología , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
8.
Transpl Infect Dis ; 25(2): e14036, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36880576

RESUMEN

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.


Asunto(s)
Trasplante de Hígado , Trasplante de Órganos , Masculino , Humanos , Persona de Mediana Edad , Femenino , Trasplante de Órganos/efectos adversos , Trasplante de Hígado/efectos adversos , Carbapenémicos , Estudios Retrospectivos , Factores de Riesgo , Receptores de Trasplantes
9.
Mol Breed ; 43(9): 69, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37622088

RESUMEN

Complete panicle exsertion (CPE) in rice is an important determinant of yield and a desirable trait in breeding. However, the genetic basis of CPE in rice still remains to be completely characterized. An ethyl methane sulfonate (EMS) mutant line of an elite cultivar Samba Mahsuri (BPT 5204), displaying stable and consistent CPE, was identified and named as CPE-110. MutMap and RNA-seq were deployed for unraveling the genomic regions, genes, and markers associated with CPE. Two major genomic intervals, on chromosome 8 (25668481-25750456) and on chromosome 11 (20147154-20190400), were identified to be linked to CPE through MutMap. A non-synonymous SNP (G/A; Chr8:25683828) in the gene LOC_Os08g40570 encoding pyridoxamine 5'-phosphate oxidase with the SNP index 1 was converted to Kompetitive allele-specific PCR (KASP) marker. This SNP (KASP 8-1) exhibited significant association with CPE and further validated through assay in the F2 mapping population, released varieties and CPE exhibiting BPT 5204 mutant lines. RNA-seq of the flag leaves at the booting stage, 1100 genes were upregulated and 1305 downregulated differentially in CPE-110 and BPT 5204. Metabolic pathway analysis indicated an enrichment of genes involved in photosynthesis, glyoxylate, dicarboxylate, porphyrin, pyruvate, chlorophyll, carotenoid, and carbon metabolism. Further molecular and functional studies of the candidate genes could reveal the mechanistic aspects of CPE. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01412-1.

10.
BMC Public Health ; 23(1): 2331, 2023 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-38001464

RESUMEN

BACKGROUND: The current study integrates brand management literature with food consumption research and develops an integrative framework by combining food safety trust, consumer perceived ethicality, brand evangelism, and brand passion into a single conceptual model. METHOD: This quantitative study included 228 ready-to-eat consumers in China using purposive sampling. Data were collected at two periods in time, resulting in a time-lag study in which respondents provided data on independent and moderating variables at time 1 and mediating and dependent variables at time 2 with the same respondents from time 1. The hypothesized correlations were tested using SEM and PROCESS Macro techniques. RESULTS: According to the findings, trust in food safety has a significant impact on brand evangelism and passion. Furthermore, consumer perceived ethicality (CPE) found to have a substantial moderating role between food safety-FS and brand passion. Moreover, we validated the brand passion role as a mediator between brand evangelism and food safety trust, and investigated whether consumer perceived ethicality conditionally affects the strength of the indirect relationship among food safety trust and brand evangelism through brand passion, indicating a moderated-mediation mechanism. ORIGINALITY: Drawing on Sternberg theory of love, current study is the first of its kind to evaluate the boundary role as well as the conditional indirect influence of customer perceived ethicality among the study's variables and provides useful information for ready-to-eat food brand managers on how to keep them interested in their risk-free food products.


Asunto(s)
Comportamiento del Consumidor , Confianza , Humanos , Inocuidad de los Alimentos , Alimentos , Emociones
11.
Differentiation ; 124: 52-59, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35182852

RESUMEN

Claudins are a family of tight junction proteins expressed in epithelial tissues during development and in postnatal life. We hypothesized that claudins are required for branching morphogenesis in the developing chick lung. To test this hypothesis, we exposed cultured chick lung explants at embryonic day 5 to a truncated non-toxic form of the Clostridium perfringens enterotoxin known as C-CPE that removes C-CPE-sensitive claudins from tight junctions. Using in situ hybridization and immunofluorescence studies, we established that only one C-CPE-sensitive claudin, Claudin-3, was expressed in the chick lung at this stage. C-CPE treated lung explants did not exhibit any defect in lung branching compared to controls. However, they did exhibit a significantly smaller lumen area, suggesting that paracellular permeability was perturbed. The decrease in lumen area was associated with a loss of Claudin-3 expression within tight junctions of the respiratory epithelium and an increase in permeability of the respiratory epithelium. When C-CPE-treated lung explants were treated with forskolin, lumen area was restored. In summary, removal of a sealing claudin, Claudin-3, from tight junctions in embryonic lung epithelium results in a decrease in lumen area and in hydrostatic pressure needed for lung development.


Asunto(s)
Pollos , Claudinas , Animales , Claudina-3/genética , Claudinas/genética , Epitelio , Pulmón
12.
Knee Surg Sports Traumatol Arthrosc ; 31(3): 1082-1088, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36409325

RESUMEN

PURPOSE: Highly crosslinked polyethylene (HXLPE) was introduced in total knee arthroplasty (TKA) to reduce wear and consequent revisions for loosening due to conventional polyethylene (CPE) wear. This study aims to analyse whether HXLPE is as safe as CPE and could improve the TKA clinical and radiological results in a long-term follow-up. METHODS: This retrospective study included all consecutive starting series of 223 patients with severe primary knee osteoarthritis (OA), with a minimum follow-up of 10 years treated between July 1st, 2007, and July 31st, 2010. After excluding patients who did not respect the inclusion and exclusion criteria, 128 patients were included in the analysis of this study. The patients were then divided into two groups according to the type of polyethylene (PE) implanted: CPE or HXLPE liners. All patients were evaluated for clinical and radiological parameters, causes and revision rates related to the type of PE implanted. RESULTS: HXLPE appears to be as safe as CPE in TKA, reporting no higher revisions for osteolysis, prosthesis loosening, infection, and mechanical failure. Nevertheless, no statistically significant differences were found between the two groups in the clinical and radiological outcomes evaluated. CONCLUSIONS: Clinical, radiological results, and revision rates are similar between HXLPE and CPE in TKA after 10 years of follow-up, although HXLPE benefits remain controversial. LEVEL OF EVIDENCE: III.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Prótesis de Cadera , Humanos , Polietileno , Artroplastia de Reemplazo de Rodilla/métodos , Estudios de Seguimiento , Estudios Retrospectivos , Diseño de Prótesis , Falla de Prótesis
13.
Anaerobe ; 79: 102687, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36549463

RESUMEN

OBJECTIVE: We aimed to examine the surface-attached soil of commercially available potatoes in Japan to determine the association between foodborne infection and the circulation of Clostridium perfringens through vegetables, soil, and environments. METHODS: C. perfringens spores were isolated from 30 surface-attached soil samples of potatoes obtained from six regions in Japan. We performed multiplex polymerase chain reaction (PCR) and sequencing to detect the presence of six toxin and plasmid-related genes in the isolates. RESULTS: Sulfite-reducing clostridial spores were detected in 28 (93%) of 30 potato samples, and toxin gene PCR was performed using 613 isolates. The C. perfringens α toxin gene (cpa) was detected in 288 isolates (288/613; 47%) from 25 potato samples (83%), and these isolates were presumed to be the strains of C. perfringens. The toxin types of C. perfringens were classified into type A, in which 73% of isolates had only cpa, followed by type F in 20%, type C in 6%, and type E in 0.003% (1 isolate). The enterotoxin gene (cpe) related to food poisoning was detected in 64 isolates from 9 potato samples (3%). Of these, 59 isolates had cpa and cpe, whereas five had cpa, C. perfringens ß toxin gene, and cpe. All tested cpe-positive isolates had plasmid-type cpe. CONCLUSIONS: The isolation of culturable cpe-positive C. perfringens from the surface-attached soil of commercially available potatoes indicates that potatoes are a potential source of foodborne transmission of C. perfringens.


Asunto(s)
Infecciones por Clostridium , Enfermedades Transmitidas por los Alimentos , Solanum tuberosum , Clostridium perfringens/genética , Prevalencia , Enterotoxinas/genética , Enfermedades Transmitidas por los Alimentos/epidemiología
14.
Angew Chem Int Ed Engl ; 62(21): e202301259, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36918357

RESUMEN

The synthesis, characterization, and catalytic performance of an iridium(III) catalyst with an electron-deficient cyclopentadienyl ligand ([CpE IrI2 ]2 ) are reported. The [CpE IrI2 ]2 catalyst was synthesized by complexation of a precursor of the CpE ligand with [Ir(cod)OAc]2 , followed by oxidation, desilylation, and removal of the COD ligand. The electron-deficient [CpE IrI2 ]2 catalyst enabled C-H amidation reactions assisted by a weakly coordinating ether directing group. Experimental mechanistic studies and DFT calculations suggested that the high catalytic performance of [CpE IrI2 ]2 is due to its electron-deficient nature, which accelerates both C-H activation and IrV -nitrenoid formation.

15.
Arch Microbiol ; 204(10): 625, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36112247

RESUMEN

The present study described the cytopathic effect of PPR virus presently being used in serial passages at the level of 60th in Vero cells and infected tissue culture fluid was used in this study as viral inoculum. Vero cells were grown on cover slip & were infected with tissue culture fluid at a fixed multiplicity of infection (MOI) 0.01. The infected cover slip along with control were stained with H&E stain at periodic intervals and cytopathic effect was studied with microscope. The cytopathic effect (CPE) was visible at first from 24 hpi and the Vero cells showed initial cell rounding, aggregation, and syncytial development. Development of inclusion bodies and cell degradation was noticed by 72 hpi. Complete detachment of the cell monolayer was observed by 84 hpi. It is concluded that, development of numerous inclusion bodies are the indication of well adaptation & extensive multiplication of PPRV in Vero cells.


Asunto(s)
Peste de los Pequeños Rumiantes , Virus de la Peste de los Pequeños Rumiantes , Animales , Técnicas de Cultivo de Célula , Chlorocebus aethiops , Células Vero
16.
J Pept Sci ; 28(8): e3406, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35043501

RESUMEN

A peptide containing a cysteinyl prolyl ester (CPE) moiety at the C-terminus (CPE peptide) was transformed into a diketopiperazine (DKP) thioester via an intramolecular N-S acyl shift reaction and was then used for peptide ligation. The difference in reactivity between the CPE peptide stereoisomers was examined. In reactions of the CPE peptides that contained L-Cys-L-Pro or D-Cys-D-Pro, the desired DKP thioester was formed at the preceding amino acid residue. On the other hand, in reactions of the CPE peptides that contained D-Cys-L-Pro or L-Cys-D-Pro, a thiolactone was formed at the C-terminal prolyl ester, and the ligation occurred at the C-terminal Pro residue. Using this reaction, it was possible to efficiently prepare a cyclic peptide.


Asunto(s)
Cisteína , Ésteres , Cisteína/química , Dicetopiperazinas , Dipéptidos/química , Péptidos/química
17.
Mol Ther ; 29(2): 873-885, 2021 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-33333292

RESUMEN

Antiviral drug development for coronavirus disease 2019 (COVID-19) is occurring at an unprecedented pace, yet there are still limited therapeutic options for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2, thus generating better antiviral efficacy. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Sixteen synergistic and eight antagonistic combinations were identified; among 16 synergistic cases, combinations of the US Food and Drug Administration (FDA)-approved drug nitazoxanide with remdesivir, amodiaquine, or umifenovir were most notable, all exhibiting significant synergy against SARS-CoV-2 in a cell model. However, the combination of remdesivir and lysosomotropic drugs, such as hydroxychloroquine, demonstrated strong antagonism. Overall, these results highlight the utility of drug repurposing and preclinical testing of drug combinations for discovering potential therapies to treat COVID-19.


Asunto(s)
Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2/efectos de los fármacos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Combinación de Medicamentos , Sinergismo Farmacológico , Humanos , Hidroxicloroquina/uso terapéutico
18.
Euro Surveill ; 27(50)2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36695467

RESUMEN

Since March 2022, there has been an emergence of multidrug-resistant organisms (MDRO) in the Netherlands in patients originating from Ukraine (58 patients, 75 isolates). For about half of these patients, recent hospitalisation in Ukraine was reported. Genomic surveillance revealed that the majority of the MDRO represent globally spread epidemic lineages and that 60% contain New Delhi metallo-ß-lactamase (NDM) genes. Professionals should be aware of an increase in such MDRO associated with migration and medical evacuation of people from Ukraine.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Humanos , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Países Bajos/epidemiología , Ucrania/epidemiología , Bacterias Gramnegativas , beta-Lactamasas/genética , Pruebas de Sensibilidad Microbiana
19.
Euro Surveill ; 27(43)2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36305334

RESUMEN

A nosocomial outbreak by cefiderocol (FDC)-resistant NDM-1-producing Klebsiella pneumoniae (NDM-Kp) occurred in a large tertiary care hospital from August 2021-June 2022 in Florence, Italy, an area where NDM-Kp strains have become endemic. Retrospective analysis of NDM-Kp from cases observed in January 2021-June 2022 revealed that 21/52 were FDC-resistant. The outbreak was mostly sustained by clonal expansion of a mutant with inactivated cirA siderophore receptor gene, which exhibited high-level resistance to FDC (MIC ≥ 32 mg/L) and spread independently of FDC exposure.


Asunto(s)
Infección Hospitalaria , Infecciones por Klebsiella , Humanos , Klebsiella pneumoniae/genética , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Estudios Retrospectivos , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Brotes de Enfermedades , Antibacterianos , Pruebas de Sensibilidad Microbiana , Cefiderocol
20.
Knee Surg Sports Traumatol Arthrosc ; 30(9): 3120-3130, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35182171

RESUMEN

PURPOSE: Total knee arthroplasty (TKA) has experienced exponential growth over the last decade, including increasingly younger patients with high functional demands. Highly crosslinked polyethylene (HXLPE) has been proven effective in reducing osteolysis and loosening revisions while improving long-term survival and performance in total hip arthroplasty; nevertheless, this superiority is not demonstrated in TKA. The aim of this systematic review and meta-analysis was to examine whether HXLPE improved overall survival and postoperative functional and radiological outcomes compared to conventional polyethylene (CPE) in TKA. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a literature search of five databases (PubMed, Medline, Scopus, Science Direct and Embase) was made. A PICOS model was performed. The initial screening identified 2541 studies. Each eligible clinical article was analysed according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (LoE). Only randomised clinical trials (RCTs) of LoE 1 and 2 were included. The methodological quality of the articles was assessed using the Risk of Bias 2 (RoB 2) tool. RESULTS: Six clinical studies were included in the final study. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO). A total of 2285 knees were included. Eight outcomes (total reoperations, reoperations for prosthesis loosening and infections, radiolucent lines, osteolysis, mechanical failure, postoperative KSS knee score and function score) were analysed. For none of them, a statistically significant difference was found about the superiority of HXLPE over CPE (p > 0.05). CONCLUSIONS: There were no statistically significant differences between HXLPE and CPE for TKA concerning clinical, radiological, and functional outcomes; nevertheless, HXLPE did not show higher failure rates or complications and can be safely used for TKA. LEVEL OF EVIDENCE: II.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteólisis , Humanos , Polietileno , Polietilenos , Diseño de Prótesis , Falla de Prótesis , Ensayos Clínicos Controlados Aleatorios como Asunto
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