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1.
Vet Sci ; 11(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38393078

RESUMO

Real-time quaking-induced conversion (RT-QuIC) assays have become a common tool to detect chronic wasting disease (CWD) and are very sensitive provided the assay duration is sufficient. However, a prolonged assay duration may lead to non-specific signal amplification. The wide range of pre-defined assay durations in current RT-QuIC applications presents a need for methods to optimize the RT-QuIC assay. In this study, receiver operating characteristic (ROC) analysis was applied to optimize the assay duration for CWD screening in obex and retropharyngeal lymph node (RLN) tissue specimens. Two different fluorescence thresholds were used: a fixed threshold based on background fluorescence (Tstdev) and a max-point ratio (maximum/background fluorescence) threshold (TMPR) to determine CWD positivity. The optimal assay duration was 33 h for obex and 30 h for RLN based on Tstdev, and 29 h for obex and 32 h for RLN based on TMPR. The optimized assay durations were then evaluated for screening CWD in white-tailed deer from an affected farm. At a replicate level, using the optimized assay durations with TStdev and TMPR, the level of agreement with enzyme-linked immunosorbent assay (ELISA) was significantly higher (p < 0.05) than that when using a 40 h assay duration. These findings demonstrate that the optimization of assay duration via a ROC analysis can improve RT-QuIC assays for screening CWD in white-tailed deer.

2.
J Vet Pharmacol Ther ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38033195

RESUMO

The aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that Vdss decreased and C0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 µg/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of ≥1 mg/kg in sheep.

3.
Biomacromolecules ; 24(11): 5142-5151, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37792545

RESUMO

RNA delivery has been demonstrated to be a potent method of vaccine delivery, as demonstrated by the recent success of the COVID-19 vaccines. Polymers have been shown to be effective vehicles for RNA delivery, with poly(ethylene imine) (PEI) being the current gold standard for delivery. Nonetheless, PEI has toxicity concerns, and so finding alternatives is desirable. Poly(2-oxazoline)s are a promising alternative to PEI, as they are generally biocompatible and offer a high degree of control over the polymer structure. Here, we have synthesized an ionizable primary amine 2-oxazoline and combined it with a double bond containing oxazoline to synthesize a small library of charged statistical and block copolymers. The pendant double bonds were reacted further to decorate the polymers with glucose via a thiol-ene click reaction. All polymers were shown to have excellent cell viability, and the synthesized block polymers showed promising complexation efficiencies for the saRNA, demonstrating a clear structure-property relationship. The polymer transfection potential was tested in various cell lines, and a polymer composition with an amine/glucose ratio of 9:27 has demonstrated the best transfection potential across all cell lines tested. Overall, the results suggest that block polymers with a cationic segment and high levels of glycosylation have the best complexation efficiency and RNA expression levels.


Assuntos
Vacinas contra COVID-19 , Polímeros , Humanos , Polímeros/química , Aminas , RNA , Glucose
4.
Biomacromolecules ; 24(4): 1924-1933, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-36976928

RESUMO

Glycopolymers are potent candidates for biomedical applications by exploiting multivalent carbohydrate-lectin interactions. Owing to their specific recognition capabilities, glycosylated polymers can be utilized for targeted drug delivery to certain cell types bearing the corresponding lectin receptors. A fundamental challenge in glycopolymer research, however, is the specificity of recognition to receptors binding to the same sugar unit (e.g., mannose). Variation of polymer backbone chirality has emerged as an effective method to distinguish between lectins on a molecular level. Herein, we present a facile route toward producing glycopolymers with a defined tacticity based on a step-growth polymerization technique using click chemistry. A set of polymers have been fabricated and further functionalized with mannose moieties to enable lectin binding to receptors relevant to the immune system (mannose-binding lectin, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin, and dendritic and thymic epithelial cell-205). Surface plasmon resonance spectrometry was employed to determine the kinetic parameters of the step-growth glycopolymers. The results highlight the importance of structural complexity in advancing glycopolymer synthesis, yet multivalency remains a main driving force in lectin recognition.


Assuntos
Lectinas , Manose , Lectinas/química , Manose/química , Carboidratos , Ressonância de Plasmônio de Superfície , Polímeros/química
5.
J Interprof Care ; 37(1): 66-72, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34978245

RESUMO

Despite extensive research having been carried out on nurse-physician collaboration, there remains a paucity of evidence on how collaboration interacts with organizational commitment and its effect on turnover intention. This study aims to determine the mediating role of nurse-physician collaboration on the effect of organizational commitment on turnover intention. We used a cross-sectional design based on voluntary paper surveys from the inpatient clinics of six public hospitals in the north of Turkey. Data including measures of nurse-physician collaboration, organizational commitment, and turnover intention were collected from a convenience sample of the nurses (n = 212) and physicians (n = 109). Pearson's correlation analysis was used to determine the relationships between variables, and the mediating effect was analyzed with PROCESS Macro "Model 4" for IBM SPSS. Statistical significance was specified at 95% confidence intervals and two-tailed P values of <0.05 for all tests. While most of the participants were nurses (66%), 34% were physicians. For both nurses and physicians, organizational commitment and nurse-physician collaboration negatively affected the turnover intention. However, the mediating role of nurse-physician collaboration was only significant for nurses (b = -0.025). The results demonstrate the importance of harmony, joint decision-making, and responsibility-sharing between nurses and physicians concerning dedication, engagement, and job satisfaction, especially for nurses.


Assuntos
Relações Interprofissionais , Recursos Humanos de Enfermagem Hospitalar , Humanos , Intenção , Estudos Transversais , Reorganização de Recursos Humanos , Satisfação no Emprego , Inquéritos e Questionários
6.
Anatol J Cardiol ; 26(12): 886-892, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35949121

RESUMO

BACKGROUND: Several previous studies have suggested that sublethal doses of Escherichia coli lipopolysaccharide (endotoxin) and monophosphoryl lipid A Re595, a nonpyrogenic derivative of Salmonella minnesota lipopolysaccharide, exhibit antiarrhythmic effects in the rat model of ischemia-reperfusion arrhythmias. METHODS: In this study, the protective effect of lipopolysaccharide derivatives was also further investigated in drug (aconitine or ouabain)-induced arrhythmia models, and conclusions were drawn with particular emphasis on the molecular characteristics of different types of lipopolysaccharide. RESULTS: The importance of the molecular structure for the antiarrhythmic effect of monophosphoryl lipid A and E. coli lipopolysaccharide was tested in the ischemia-reperfusion arrhythmia model. In contrast to monophosphoryl lipid A from Salmonella typhimurium SL 684 which has only monophosphoryl residue in its structure, monophosphoryl lipid A Re595, obtained from S. minnesota, and E. coli lipopolysaccharide which have both mono and diphosphoryl residue reduced the duration of ventricular tachycardia (e.g., during reperfusion: vehicle: 176 ± 22.8; monophosphoryl lipid A Re595: 132.83 ± 12.1, as second, n=8-10, P < .05) and the incidence of ventricular fibrillation. The antiarrhythmic effects of E. coli lipopolysaccharide and monophosphoryl lipid A Re595 in ischemia-reperfusion arrhythmia model were absent in either aconitine- (e.g., onset time for ventricular ectopic beats: saline 25.3 5.0, E. coli lipopolysaccharide 24.3 ± 7.1; vehicle: 24.0 ± 4.5, monophosphoryl lipid A SL684 23.8 ± 4.3, as second, n=6, P > .05) or ouabain-induced arrhythmia models in mice. CONCLUSION: Therefore, we conclude that lipopolysaccharide derivatives exhibit antiarrhythmic effect only in ischemia-reperfusion arrhythmias, and lipopolysaccharide should possess diphosphoryl groups in its subcomponent composition for this antiarrhythmic effect.


Assuntos
Aconitina , Lipopolissacarídeos , Ratos , Camundongos , Animais , Aconitina/efeitos adversos , Roedores , Ouabaína/efeitos adversos , Escherichia coli , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Antiarrítmicos/efeitos adversos
7.
J Coll Physicians Surg Pak ; 32(8): 1051-1055, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35932132

RESUMO

OBJECTIVE: To determine the indications of early and late complications in 224 patients who underwent Percutaneous Endoscopic Gastrostomy (PEG) procedure. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of General Surgery, Karatay University and Medipol University, Turkey, from January 2014 to December 2020. METHODOLOGY: Patients' age, gender, primary diseases, PEG indications, morbidity, mortality, and complications were recorded by performing the PEG procedure. Hospitalisation, follow-up periods of the patients, and the re-insertion of PEG were evaluated. RESULTS: The most common indication for PEG tube insertion was nutritional disorder associated with cerebrovascular diseases in 81 (37%) patients. No mortality was perceived due to the PEG tube insertion. However, mortality was observed in 84 (38.4%) patients in the first six months, in 6 (2.7%) patients between the sixth and twelfth month, and in 8 (3.7%) patients after the twelfth month. All these mortalities were attributed to the primary disease. In the early and late periods, complications were observed in the total of 45 (20.4%) patients. Among them, 17 (7.7%) patients experienced early period complications, whereas 28 (12.7%) patients experienced late period complications. CONCLUSION: Enteral nutrition should be preferred in order to avoid complications of parenteral nutrition in the patients who need long-term nutrition. In enteral nutrition, PEG should be preferred to surgical gastrostomy because it has less morbidity and mortality, can be done at the bedside and outpatiently when necessary, does not require general anesthesia, and is cheaper and practical. KEY WORDS: Gastrostomy, Percutaneous Endoscopic gastrostomy, Enteral nutrition, PEG complications.


Assuntos
Nutrição Enteral , Gastrostomia , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Gastrostomia/efeitos adversos , Gastrostomia/métodos , Humanos , Estado Nutricional , Nutrição Parenteral , Estudos Retrospectivos , Turquia
8.
Surg Technol Int ; 412022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36017960

RESUMO

BACKGROUND: Laparoscopic surgery for colorectal cancer is mostly performed in university hospitals or experienced centers. This study aimed at determining the learning curve of laparoscopic surgery for colorectal cancer at a new regional state hospital. PATIENTS AND METHODS: Clinico-pathological data of 106 consecutive patients who underwent laparoscopic surgery for colorectal cancer at a new regional state hospital between August 2018 and September 2021 were prospectively recorded and analyzed. All surgeries were performed by a single inexperienced surgeon without supervision. The primary outcome of the study was the operative time, which was used for a Cumulative Sum (CUSUM) analysis of the learning curve. The secondary outcomes included a comparison of preoperative, intraoperative, and postoperative outcomes during the learning curve period. RESULTS: According to the CUSUM analysis, the learning curve consisted of three unique phases: phase 1 [the initial learning period (cases 1-53)], phase 2 [the consolidation period (cases 54-68)], and phase 3 [the experienced period (cases 69-106)]. Of the intraoperative outcomes, operative time and estimated blood loss were significantly reduced from phase 1 to phase 3 (p<0.001). Of the postoperative outcomes, time to pass stool (p<0.05), time to oral feeding (p=0.001), drain removal time (p<0.001), and length of hospital stay (p=0.042) were shorter in phase 3 compared to phases 1 and 2. Of the histopathological results, the specimen length and the number of harvested lymph nodes increased with experience (p=0.001). CONCLUSIONS: The present results suggest that a surgeon at a new regional state hospital must experience 53-68 cases to achieve competence in laparoscopic colorectal cancer surgery.

9.
Eur Arch Otorhinolaryngol ; 279(12): 5707-5714, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35723731

RESUMO

PURPOSE: The current studies in the literature report that periostin contributes to the formation of nasal polyps and may be a molecular biomarker for chronic rhinosinusitis with nasal polyps (CRSwNP). This study aims to investigate the effect of periostin in determining polyp burden in CRSwNP patients and evaluate its impact on postoperative surgical results and its functionality as a biomarker. METHODS: The study included 26 patients who underwent endoscopic sinus surgery due to CRSwNP and 30 patients who were scheduled to undergo septoplasty due to isolated nasal septum deviation. We performed preoperative Lund-Mackay scoring and preoperative and postoperative SNOT-22 and Modified Lund-Kennedy scoring for the patients. Tissue and serum samples were collected from all patients in surgery and another serum sample was taken from CRSwNP patients at postoperative month 6. RESULTS: Tissue eosinophil (p < 0.001), preoperative serum (p < 0.001), and tissue (p = 0.002) periostin were significantly higher in the CRSwNP group. We observed a statistically significant positive correlation between tissue eosinophil values and tissue periostin values in CRSwNP patients (p = 0.004). We found a statistically significant positive correlation between the tissue periostin values and postoperative SNOT-22 scores of the CRSwNP group patients (p = 0.005). CONCLUSION: According to the results of our study, we think that periostin can be used as a biomarker in the prediction, determination of disease severity, and prognosis of CRSwNP. Comprehensive cohort studies with larger patient series are needed to provide more information on the role and effects of periostin in cases of CRSwNP undergoing surgical treatment.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/diagnóstico , Pólipos Nasais/cirurgia , Rinite/complicações , Rinite/diagnóstico , Rinite/cirurgia , Sinusite/complicações , Sinusite/diagnóstico , Sinusite/cirurgia , Eosinófilos , Doença Crônica , Biomarcadores
10.
Biomacromolecules ; 23(3): 543-575, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-34982551

RESUMO

Carbohydrates bearing a distinct complexity use a special code (Glycocode) to communicate with carbohydrate-binding proteins at a high precision to manipulate biological activities in complex biological environments. The level of complexity in carbohydrate-containing macromolecules controls the amount and specificity of information that can be stored in biomacromolecules. Therefore, a better understanding of the glycocode is crucial to open new areas of biomedical applications by controlling or manipulating the interaction between immune cells and pathogens in terms of trafficking and signaling, which would become a powerful tool to prevent infectious diseases. Even though a certain level of progress has been achieved over the past decade, synthetic glycomacromolecules are still lagging far behind naturally existing glycans in terms of complexity and precision because of insufficient and inefficient synthetic techniques. Currently, specific targeting at a cellular level using synthetic glycomacromolecules is still challenging. It is obvious that multidisciplinary collaborations are essential between different specialized disciplines to enhance the carbohydrate receptor-targeting paradigm for new biomedical applications. In this Perspective, recent developments in the synthesis of sophisticated glycomacromolecules are highlighted, and their biological and biomedical applications are also discussed in detail.


Assuntos
Carboidratos , Polissacarídeos , Carboidratos/química , Glicoproteínas , Substâncias Macromoleculares , Polissacarídeos/química
11.
J Coll Physicians Surg Pak ; 32(12): SS95-SS97, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36597302

RESUMO

Trauma is one of the causes of acute myocardial infarction (AMI). In the literature, coronary dissection or vasospasm is thought to play a role in the aetiology of AMI, but the presence of coronary thrombosis without coronary dissection is uncommon. If bleeding pathologies occur in addition to traumatic coronary thrombosis, this may make the situation more complicated. A 32-year male patient was brought to a tertiary emergency service due to a car accident. We detected femoral shaft fracture, hemothorax, subdural haemorrhage, and coronary thrombosis without dissection in the patient. A chest tube was inserted and emergency coronary angiography was performed. Total occlusion of the left anterior descending artery (LAD) was detected. Balloon angioplasty was done and a stent was applied to the LAD. Acetyl salicylic acid and clopidogrel were started despite his bleeding pathologies. In trauma patients, coronary thrombosis without coronary dissection may occur with bleeding pathologies. Electrocardiography should be performed in patients with chest trauma. Thrombosis-bleeding balance should be carefully evaluated during treatment and treatment should be determined by taking this situation into consideration. Key Words: Coronary thrombosis, Multiple trauma, Bleeding, Angioplasty, Antiplatelet therapy.


Assuntos
Angioplastia Coronária com Balão , Trombose Coronária , Traumatismo Múltiplo , Infarto do Miocárdio , Humanos , Masculino , Trombose Coronária/etiologia , Infarto do Miocárdio/etiologia , Angioplastia Coronária com Balão/efeitos adversos , Angiografia Coronária , Traumatismo Múltiplo/complicações
12.
Drug Deliv Transl Res ; 12(8): 1788-1810, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34841492

RESUMO

Carbohydrate-based materials are increasingly investigated for a range of applications spanning from healthcare to advanced functional materials. Synthetic glycopolymers are particularly attractive as they possess low toxicity and immunogenicity and can be used as multivalent ligands to target sugar-binding proteins (lectins). Here, we utilised RAFT polymerisation to synthesize two families of novel diblock copolymers consisting of a glycopolymers block containing either mannopyranose or galactopyranose pendant units, which was elongated with sodium 2-acrylamido-2-methyl-1-propanesulfonate (AMPS) to generate a polyanionic block. The latter enabled complexation of cationic aminoglycoside antibiotic tobramycin through electrostatic interactions (loading efficiency in the 0.5-6.3 wt% range, depending on the copolymer). The resulting drug vectors were characterized by dynamic light scattering, zeta-potential, and transmission electron microscopy. Tobramycin-loaded complexes were tested for their ability to prevent clustering or disrupt biofilm of the Pseudomonas aeruginosa Gram-negative bacterium responsible for a large proportion of nosocomial infection, especially in immunocompromised patients. P. aeruginosa possesses two specific tetrameric carbohydrate-binding adhesins, LecA (PA-IL, galactose/N-acetyl-D-galactosamine-binding) and LecB (PA-IIL, fucose/mannose-binding), and the cell-associated and extracellular adhesin CdrA (Psl/mannose-binding) thus ideally suited for targeted drug delivery using sugar-decorated tobramycin-loaded complexes here developed. Both aliphatic and aromatic linkers were utilised to link the sugar pendant units to the polyacrylamide polymer backbone to assess the effect of the nature of such linkers on bactericidal/bacteriostatic properties of the complexes. Results showed that tobramycin-loaded complexes efficiently suppressed (40 to 60% of inhibition) in vitro biofilm formation in PAO1-L P. aeruginosa and that preferential targeting of PAO1-L biofilm can be achieved using mannosylated glycopolymer-b-AMPSm.


Assuntos
Pseudomonas aeruginosa , Tobramicina , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes , Humanos , Manose , Tobramicina/química
13.
NPJ Biofilms Microbiomes ; 7(1): 87, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34880222

RESUMO

Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of polysaccharides, nucleic acids and proteins. We hypothesised that carbohydrates could contribute to immune recognition of Pseudomonas aeruginosa biofilms by engaging C-type lectins. Here we show binding of Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN, CD209), mannose receptor (MR, CD206) and Dectin-2 to P. aeruginosa biofilms. We also demonstrate that DC-SIGN, unlike MR and Dectin-2, recognises planktonic P. aeruginosa cultures and this interaction depends on the presence of the common polysaccharide antigen. Within biofilms DC-SIGN, Dectin-2 and MR ligands appear as discrete clusters with dispersed DC-SIGN ligands also found among bacterial aggregates. DC-SIGN, MR and Dectin-2 bind to carbohydrates purified from P. aeruginosa biofilms, particularly the high molecular weight fraction (HMW; >132,000 Da), with KDs in the nM range. These HMW carbohydrates contain 74.9-80.9% mannose, display α-mannan segments, interfere with the endocytic activity of cell-associated DC-SIGN and MR and inhibit Dectin-2-mediated cellular activation. In addition, biofilm carbohydrates reduce the association of the DC-SIGN ligand Lewisx, but not fucose, to human monocyte-derived dendritic cells (moDCs), and alter moDC morphology without affecting early cytokine production in response to lipopolysaccharide or P. aeruginosa cultures. This work identifies the presence of ligands for three important C-type lectins within P. aeruginosa biofilm structures and purified biofilm carbohydrates and highlights the potential for these receptors to impact immunity to P. aeruginosa infection.


Assuntos
Receptor de Manose , Pseudomonas aeruginosa , Biofilmes , Carboidratos , Células Dendríticas , Matriz Extracelular de Substâncias Poliméricas , Humanos , Lectinas Tipo C
14.
Cranio ; : 1-9, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34842057

RESUMO

OBJECTIVE: To examine the SCUBE1 level, a biomarker in vascular biology that could determine the prognosis of cardiovascular events during OSA treatment. METHODS: In total, 129 patients were included in the study. Thirty were diagnosed with simple snoring and 99 with OSA. RESULTS: In males, significant correlation was determined between SCUBE1 non-REM AHI, hypopnea index, total apnea index, mean SO2, minimum SO2, and < 90% saturation duration. CONCLUSION: Serum SCUBE1 levels increased more in male patients with severe OSA compared to other OSA levels, and high serum SCUBE1 levels were found to be associated with lower oxygen levels in OSA patients. The SCUBE1 biomarker can correlate with severe OSA in males. There was a statistically significant difference between OSA groups in terms of SCUBE1 score for male patients (p = 0.002) but not for females (p = 0.498). It is important that future SCUBE1 studies evaluate males vs. females.

15.
JACS Au ; 1(10): 1621-1630, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34723265

RESUMO

Carbohydrate-binding proteins (lectins) play vital roles in cell recognition and signaling, including pathogen binding and innate immunity. Thus, targeting lectins, especially those on the surface of immune cells, could advance immunology and drug discovery. Lectins are typically oligomeric; therefore, many of the most potent ligands are multivalent. An effective strategy for lectin targeting is to display multiple copies of a single glycan epitope on a polymer backbone; however, a drawback to such multivalent ligands is they cannot distinguish between lectins that share monosaccharide binding selectivity (e.g., mannose-binding lectins) as they often lack molecular precision. Here, we describe the development of an iterative exponential growth (IEG) synthetic strategy that enables facile access to synthetic glycomacromolecules with precisely defined and tunable sizes up to 22.5 kDa, compositions, topologies, and absolute configurations. Twelve discrete mannosylated "glyco-IEGmers" are synthesized and screened for binding to a panel of mannoside-binding immune lectins (DC-SIGN, DC-SIGNR, MBL, SP-D, langerin, dectin-2, mincle, and DEC-205). In many cases, the glyco-IEGmers had distinct length, stereochemistry, and topology-dependent lectin-binding preferences. To understand these differences, we used molecular dynamics and density functional theory simulations of octameric glyco-IEGmers, which revealed dramatic effects of glyco-IEGmer stereochemistry and topology on solution structure and reveal an interplay between conformational diversity and chiral recognition in selective lectin binding. Ligand function also could be controlled by chemical substitution: by tuning the side chains of glyco-IEGmers that bind DC-SIGN, we could alter their cellular trafficking through alteration of their aggregation state. These results highlight the power of precision synthetic oligomer/polymer synthesis for selective biological targeting, motivating the development of next-generation glycomacromolecules tailored for specific immunological or other therapeutic applications.

16.
RSC Chem Biol ; 2(2): 568-576, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34458800

RESUMO

Hyaluronic acid (HA), the only non-sulphated glycosaminoglycan, serves numerous structural and biological functions in the human body, from providing viscoelasticity in tissues to creating hydrated environments for cell migration and proliferation. HA is also involved in the regulation of morphogenesis, inflammation and tumorigenesis through interactions with specific HA-binding proteins. Whilst the physicochemical and biological properties of HA have been widely studied for decades, the exact mechanisms by which HA exerts its multiple functions are not completely understood. Glycopolymers offer a simple and precise synthetic platform for the preparation of glycan analogues, being an alternative to the demanding synthetic chemical glycosylation. A library of homo, statistical and alternating HA glycopolymers were synthesised by reversible addition-fragmentation chain transfer polymerisation and post-modification utilising copper alkyne-azide cycloaddition to graft orthogonal pendant HA monosaccharides (N-acetyl glucosamine: GlcNAc and glucuronic acid: GlcA) onto the polymer. Using surface plasmon resonance, the binding of the glycopolymers to known HA-binding peptides and proteins (CD44, hyaluronidase) was assessed and compared to carbohydrate-binding proteins (lectins). These studies revealed potential structure-binding relationships between HA monosaccharides and HA receptors and novel HA binders, such as Dectin-1 and DEC-205 lectins. The inhibitory effect of HA glycopolymers on hyaluronidase (HAase) activity was also investigated suggesting GlcNAc- and GlcA-based glycopolymers as potential HAase inhibitors.

17.
Cureus ; 13(5): e15356, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34094787

RESUMO

Objective This study aims to determine the factors that prolong cecal intubation time (CIT) and determine the effect of obesity on CIT measured using multiple indexes. Methods Patients who underwent elective colonoscopy between July 10, 2020, and January 20, 2021, were evaluated in this prospective observational study. Age, gender, constipation, bowel preparation, presence of diverticulosis, previous surgery history, auxiliary maneuver and additional analgesic requirement, cecum intubation length (CL) and obesity indices [body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR)] were analyzed. Factors affecting CIT were assessed by both univariate and multivariate logistic regression (LR) analyses. Results A total of 512 patients were analyzed. Mean CIT was 5.6 ± 1.6 min, and median CIT was 5.17 min. The CIT median was ≤5.17 min in 264 (51.5%) of the patients, and the CIT median was >5.17 min in 248 (48.5%). In the univariate LR results, young age, constipation, poor bowel preparation, increased CL, additional analgesic requirement, low WHtR, and low BMI (<25 kg/m2) were the factors that prolonged CIT (p <0.05). In the multivariate LR analysis results, WHtR >0.5 and BMI >30 kg/m2 were found to be independent factors that decrease CIT [OR: 0.01 (0.01 0.03) p <0.001; OR: 0.28 (0.13 0.57) p <0.001]. Conclusion Younger age, low WHtR, low BMI, increased CL, constipation, inadequate bowel preparation, and the use of extra analgesics were found to be associated with longer CIT. When all factors were evaluated together, obesity measured by only WHtR (>0.5) and BMI (>30 kg/m2) were the best predictors of decreased CIT.

18.
Wideochir Inne Tech Maloinwazyjne ; 16(2): 336-346, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34136029

RESUMO

INTRODUCTION: Studies with inexperienced surgeons in terms of the learning curve for laparoscopic totally extraperitoneal (TEP) inguinal hernia repair are limited. AIM: To compare three inexperienced surgeons in terms of the learning curve without supervision. MATERIAL AND METHODS: Patients' data, which were from consecutive laparoscopic TEP hernioplasties between December 2017 and February 2020, were analysed retrospectively. The primary outcome was to compare the learning curve of three surgeons (Surgeon A, B, and C) in terms of complications, conversion, and duration of surgery. Secondary outcomes were recurrence rates. RESULTS: A total of 299 patients were included in the study. Conversion and intraoperative complication rates decreased after the first 60 cases (from 10% to 2.5%, p = 0.013 and from 9% to 2.5%, p = 0.027, respectively). The mean operative time reached a plateau of less than 40 min after 51-81 cases (Surgeon A 51, B 71, and C 81 cases). Ageing was a risk factor for intraoperative complications and recurrence (p < 0.001, p = 0.008, respectively), and higher body mass index (BMI) was a risk factor for conversion (p = 0.004). Age ≥ 60 years compared to age < 60 years increased intraoperative complications five-fold and recurrence six-fold (p = 0.001). On the other hand, BMI ≥ 30 kg/m2 increased the possibility of conversion to open surgery nine-fold (p < 0.001). In addition, a positive correlation was found between the operative time and the BMI and VAS score (p = 0.004, p = 0.015, respectively). CONCLUSIONS: In order to reach the plateau in the operative time during the TEP learning curve period, more than 50 cases should be experienced, whereas more than 60 cases are needed for conversion, intraoperative complications, and recurrence.

19.
Surg Technol Int ; 39: 191-195, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181239

RESUMO

INTRODUCTION: Transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) hernia repair are the two most commonly used techniques in laparoscopic inguinal hernia repair, and the results of comparative studies are conflicting. The objective of this study is to compare the two methods in unilateral inguinal hernia repair. MATERIALS AND METHODS: The data of consecutive patients who underwent TEP and TAPP due to unilateral inguinal hernia between December 7, 2017, and March 15, 2020, were analyzed retrospectively. The primary outcome was to compare the clinical outcomes of the two techniques in terms of complications, conversion, pain, and operative time. The secondary outcome was recurrence rates. RESULTS: A total of 301 (TEP n=234, TAPP n=67) patients were included in the study. The mean age was 43 years, and the follow-up period was two years. The groups were similar in terms of demographic characteristics and hernia type. The mean operative time was longer in the TAPP group than in the TEP group (67 min and 58 min, p=0.007). The recurrence rate was 4.3% in the TEP group and 5.9% in the TAPP group (p>0.05). The conversion rate was 6% in both groups. In total, 19 (6.3%) patients had intraoperative complications (TEP n=16, TAPP n=3), and 23 (7.6%) patients had postoperative complications (TEP n=16, TAPP n=7). Both intraoperative and postoperative complication rates were similar between the groups (p=0.31 and p=0.051, respectively). The early postoperative pain was less in the TEP group (p=0.004). CONCLUSION: Less early postoperative pain and shorter operative time were detected in patients who underwent TEP.


Assuntos
Hérnia Inguinal , Laparoscopia , Adulto , Hérnia Inguinal/epidemiologia , Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Humanos , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
20.
J Coll Physicians Surg Pak ; 30(6): 668-672, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34102778

RESUMO

OBJECTIVE: To evaluate the usability of electrocardiography (ECG) intervals in the diagnosis and treatment monitoring of acute carbon monoxide (CO) poisoning. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Emergency Medicine, Kayseri City Hospital, Turkey, from November 2018 to May 2019. METHODOLOGY: Each of 80 patients for study and control groups were prospectively included. For study group, pre- and post-treatment ECG intervals (P-wave and QRS complex periods, PP, PR, RR, QT, and QTc intervals) and carboxyhemoglobin (COHb) levels of the patients were evaluated. For control group, ECG intervals and COHb levels of the patients during admission to the Emergency Department were evaluated. RESULTS: As a result of the statistical analysis in which measurements of the study group and control group were compared, a statistically significant difference was found in the following values: pre-treatment group COHb level (p<0.001), PR interval (p=0.046), PP interval (p<0.001), QT interval (p<0.001), QTC interval (p=0.016), RR interval (p<0.001), and post-treatment group COHb level (p<0.001), PR interval (p=0.009), PP interval (p=0.041), QTC interval (p=0.010), and RR interval (p=0.036). QT interval values in the post-treatment group were similar to those of the control group (p=0.342). In the ROC analysis where the diagnostic performance of ECG intervals was evaluated, the area under the curve (AUC) scale was between 0.29 and 0.62. CONCLUSION: ECG intervals do not provide as much benefit as COHb measurement in the diagnosis of acute CO poisoning. However, the QT interval is a useful ECG interval in the treatment monitoring of acute CO poisoning. Key Words: Acute carbonmonoxide poisoning, ECG interval, QT interval, Emergency Department.


Assuntos
Intoxicação por Monóxido de Carbono , Monóxido de Carbono , Intoxicação por Monóxido de Carbono/diagnóstico , Intoxicação por Monóxido de Carbono/terapia , Eletrocardiografia , Humanos , Curva ROC , Turquia
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