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1.
Sci Rep ; 14(1): 7675, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561470

RESUMO

A serine protease called prolyl endopeptidase (PEP) hydrolyses the peptide bonds on the carboxy side of the proline ring. The excessive PEP expression in brain results in neurodegenerative illnesses like dementia, Alzheimer's disease, and Parkinson's disease. Results of the prior studies on antioxidant activity, and the non-cytotoxic effect of bi-carbazole-linked triazoles, encouraged us to extend our studies towards its anti-diabetic potential. Hence, for this purpose all compounds 1-9 were evaluated to reveal their anti-prolyl endo peptidase activity. Fortunately, seven compounds resulted into significant inhibitory capability ranging from 26 to 63 µM. Among them six compounds 4-9 exhibited more potent inhibitory activity with IC50 values 46.10 ± 1.16, 42.30 ± 1.18, 37.14 ± 1.21, 26.29 ± 0.76, 28.31 ± 0.64 and 31.11 ± 0.84 µM respectively, while compound 3 was the least active compound in the series with IC50 value 63.10 ± 1.58 µM comparing with standard PEP inhibitor bacitracin (IC50 = 125 ± 1.50 µM). Moreover, mechanistic study was performed for the most active compounds 7 and 8 with Ki values 24.10 ± 0.0076 and 23.67 ± 0.0084 µM respectively. Further, the in silico studies suggested that the compounds exhibited potential interactions and significant molecular conformations, thereby elucidating the structural basis for their inhibitory effects.


Assuntos
Peptídeo Hidrolases , Triazóis , Triazóis/farmacologia , Triazóis/química , Prolil Oligopeptidases , Serina Endopeptidases , Carbazóis , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular
2.
Int J Biol Macromol ; 267(Pt 2): 131629, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631585

RESUMO

Current management of HCV infection is based on Direct-Acting Antiviral Drugs (DAAs). However, resistance-associated mutations, especially in the NS3 and NS5B regions are gradually decreasing the efficacy of DAAs. Among the most effective HCV NS3/4A protease drugs, Sofosbuvir also develops resistance due to mutations in the NS3 and NS5B regions. Four mutations at positions A156Y, L36P, Q41H, and Q80K are classified as high-level resistance mutations. The resistance mechanism of HCV NS3/4A protease toward Sofosbuvir caused by these mutations is still unclear, as there is less information available regarding the structural and functional effects of the mutations against Sofosbuvir. In this work, we combined molecular dynamics simulation, molecular mechanics/Generalized-Born surface area calculation, principal component analysis, and free energy landscape analysis to explore the resistance mechanism of HCV NS3/4A protease due to these mutations, as well as compare interaction changes in wild-type. Subsequently, we identified that the mutant form of HCV NS3/4A protease affects the activity of Sofosbuvir. In this study, the resistance mechanism of Sofosbuvir at the atomic level is proposed. The proposed drug-resistance mechanism will provide valuable guidance for the design of HCV drugs.

3.
Sci Rep ; 14(1): 4947, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418484

RESUMO

Internet of Things (IoT) paves the way for the modern smart industrial applications and cities. Trusted Authority acts as a sole control in monitoring and maintaining the communications between the IoT devices and the infrastructure. The communication between the IoT devices happens from one trusted entity of an area to the other by way of generating security certificates. Establishing trust by way of generating security certificates for the IoT devices in a smart city application can be of high cost and expensive. In order to facilitate this, a secure group authentication scheme that creates trust amongst a group of IoT devices owned by several entities has been proposed. The majority of proposed authentication techniques are made for individual device authentication and are also utilized for group authentication; nevertheless, a unique solution for group authentication is the Dickson polynomial based secure group authentication scheme. The secret keys used in our proposed authentication technique are generated using the Dickson polynomial, which enables the group to authenticate without generating an excessive amount of network traffic overhead. IoT devices' group authentication has made use of the Dickson polynomial. Blockchain technology is employed to enable secure, efficient, and fast data transfer among the unique IoT devices of each group deployed at different places. Also, the proposed secure group authentication scheme developed based on Dickson polynomials is resistant to replay, man-in-the-middle, tampering, side channel and signature forgeries, impersonation, and ephemeral key secret leakage attacks. In order to accomplish this, we have implemented a hardware-based physically unclonable function. Implementation has been carried using python language and deployed and tested on Blockchain using Ethereum Goerli's Testnet framework. Performance analysis has been carried out by choosing various benchmarks and found that the proposed framework outperforms its counterparts through various metrics. Different parameters are also utilized to assess the performance of the proposed blockchain framework and shows that it has better performance in terms of computation, communication, storage and latency.

4.
Eur J Heart Fail ; 26(2): 373-382, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38235936

RESUMO

AIMS: The therapeutic mechanism of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on left cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF) is not well-established. This study meta-analysed the impact of SGLT2i on left cardiac structure and function in patients with HFrEF. METHODS AND RESULTS: Online databases were queried up to April 2023 for trials reporting indicators of left cardiac structure and function in patients with HFrEF treated with SGLT2i. Data from studies were pooled using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). Six trials were included (n = 555). Compared with control, SGLT2i significantly improved left ventricular end-diastolic volume (LVEDV; WMD: -17.07 ml [-23.84, -10.31]; p < 0.001), LVEDV index (WMD: -5.62 ml/m2 [-10.28, -0.97]; p = 0.02), left ventricular end-systolic volume (LVESV; WMD: -15.63 ml [-26.15, -5.12]; p = 0.004), LVESV index (WMD: -6.90 ml/m2 [-10.68, -3.11]; p = 0.001), left ventricular ejection fraction (WMD: 2.71% [0.70, 4.72]; p = 0.008), and left atrial volume index (WMD: -2.19 ml/m2 [-4.26, -0.11]; p = 0.04) in patients with HFrEF. SGLT2i use was associated with a non-significant trend towards a reduction in left ventricular mass index (WMD: -6.25 g/m2 [-12.79, 0.28]; p = 0.06). No significant impact on left ventricular global longitudinal strain was noted (WMD: 0.21% [-0.25, 0.67]; p = 0.38). CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitors improve cardiac structure and function in patients with HFrEF.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico , Função Ventricular Esquerda , Remodelação Ventricular , Glucose , Sódio
5.
Pediatr Neurol ; 152: 4-10, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171084

RESUMO

BACKGROUND: Erythropoietin (EPO) is a proposed drug for the treatment of neonatal hypoxic-ischemic encephalopathy (HIE). Multiple studies have linked its use, either as a monotherapy or in conjunction with therapeutic hypothermia (TH), with improved neonatal outcomes including death and neurodisability. However, there is also evidence in the literature that raises concerns about its efficacy and safety for the treatment of neonatal encephalopathy (NE). METHODS: We searched MEDLINE, Cochrane CENTRAL, and Embase for both observational studies and randomized controlled trials (RCTs) investigating the effectiveness of EPO in treating NE. Only studies in which at least 300 U/kg of EPO was used and reported any one of the following outcomes: death, death or neurodisability, and cerebral palsy, were included. RESULTS: Seven studies with 903 infants with the diagnosis of NE were included in our meta-analysis. EPO did not reduce the risk of death or neurodisability (risk ratio 0.68 [95% confidence interval [CI]: 0.43 to 1.09]) (P = 0.11). Similarly, the risk of cerebral palsy was not reduced by the administration of EPO (risk ratio 0.68 [95% CI: 0.33 to 1.40]) (P = 0.30). The risk of death was also not reduced at any dose of EPO regardless of the use of TH. CONCLUSIONS: The results of our meta-analysis do not support the use of EPO for the treatment of neonatal encephalopathy. However, future large-scale RCTs are needed to strengthen these findings.


Assuntos
Paralisia Cerebral , Eritropoetina , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Recém-Nascido , Lactente , Humanos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Eritropoetina/efeitos adversos , Doenças do Recém-Nascido/terapia , Paralisia Cerebral/tratamento farmacológico , Hipotermia Induzida/efeitos adversos
6.
Saudi Med J ; 45(1): 74-78, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38220229

RESUMO

OBJECTIVES: To evaluate the effect of the presence of a physician in the triage area on the number of patients who leave without being seen (LWBS) and some of the factors affecting emergency department (ED) crowding. METHODS: This was a pre-post study carried out at King Fahad Specialist Hospital, Dammam, Saudi Arabia. The 3-month study, consisting of 7826 patients, was split into pre-physician and post-physician periods. Variables compared across these periods were the number of LWBS patients, length of hospital stay, time to physician, and time to disposition decision. Statistical analysis was carried out using R version 4.3.0. RESULTS: Our results showed that the presence of a triage physician significantly decreased the number of LWBS patients (p<0.001) and the time taken to encounter an ED physician (p<0.001). However, it did not have any significant impact on the length of hospital stay (p=0.5) or time to disposition decision (p=0.9). CONCLUSION: The appointment of a triage physician has streamlined patient flow and decreased LWBS rates in the ED, demonstrating the need for more thorough research in this area.


Assuntos
Médicos , Melhoria de Qualidade , Humanos , Triagem/métodos , Fatores de Tempo , Serviço Hospitalar de Emergência , Hospitais Especializados , Tempo de Internação , Aglomeração , Estudos Retrospectivos
7.
Water Res ; 250: 121035, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38154339

RESUMO

Membrane bioreactors (MBRs) play a crucial role in wastewater treatment, but they face considerable challenges due to fouling. To tackle this issue, innovative strategies are needed. This study investigated the effectiveness of membrane reciprocation and quorum quenching (QQ) to control fouling in MBRs. The study compared MBRs using membrane reciprocation (30 rpm) and QQ (injecting media containing 100 or 200 mg/L BH4) with conventional MBRs employing different air-scouring intensities. The results demonstrated that combining membrane reciprocation (30 rpm) with QQ (200 mg/L BH4) significantly extended the service time of MBRs, making it approximately six times longer than conventional methods. Moreover, this approach reduced physically reversible resistance. The reduction in signal molecules related to biofouling due to QQ showcased its critical role in controlling biofouling, even under high shear caused by membrane reciprocation. However, the impact of QQ on microbial community structure appeared relatively insignificant when compared to factors such as operation time, aeration intensity, and membrane reciprocation. By combining membrane reciprocation and QQ, the study achieved a remarkable 81 % energy saving compared to extensive aeration (103 s-1 in velocity gradient), in addition to the extended service time. Importantly, this combined antifouling approach did not negatively affect microbial characteristics and wastewater treatment, emphasizing its effectiveness in MBRs. Overall, the findings of this study offer valuable insights for developing synergistic fouling control strategies in MBRs, significantly improving the energy efficiency of the wastewater treatment process.


Assuntos
Incrustação Biológica , Purificação da Água , Percepção de Quorum , Membranas Artificiais , Incrustação Biológica/prevenção & controle , Reatores Biológicos , Purificação da Água/métodos
8.
Curr Probl Cardiol ; 49(1 Pt C): 102148, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37863458

RESUMO

There is a lack of mortality data on rheumatic heart disease (RHD) in the United States (US). In light of this, a retrospective analysis was conducted to investigate the temporal, sex-based, racial, and regional trends in RHD-related mortality in the US, ranging from 1999 to 2020. The Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER) dataset was analyzed, where crude and age-adjusted mortality rates (AAMR) were identified, along with annual percentage changes (APCs) determined by Joinpoint regression. Through the period of 1999 to 2020, there were 141,137 RHD-related deaths reported, with a marginal decline from 4.05/100,000 in 1999 to 3.12/100,000 in 2020. However, the recent rise in AAMR from 2017 to 2020 has created a source of concern (APC: 6.62 [95% CI, 3.19-8.72]). Similar trends were observed in the Black or African American race from 2017 to 2020 (APC: 10.58 [95% CI, 6.29-17.80]). Moreover, the highest percentage change from 2018 to 2020 was observed in residents of large metropolitan areas (APC: 7.6 [95% CI, 2.8-10.5]). A prominent disparity was observed among states, with values ranging from 1.74/100,000 in Louisiana to 5.27/100,000 in Vermont. States within the top 90th percentile of RHD-related deaths included Alaska, Minnesota, Washington, Wyoming, and Vermont. In conclusion, it is imperative to delve deeper into the evidently rising trends of RHD-related mortality and outline the possible sources of social determinants within US healthcare in order to provide equal and quality medical care throughout the nation.


Assuntos
Cardiopatia Reumática , Humanos , Grupos Raciais , Estudos Retrospectivos , Cardiopatia Reumática/mortalidade , Estados Unidos/epidemiologia , Masculino , Feminino
9.
Curr Probl Cardiol ; 49(1 Pt C): 102131, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37866417

RESUMO

BACKGROUND: Reduction of diastolic blood pressure (DBP) below 70 mmHg may decrease perfusion to the heart and worsen cardiovascular (CV) outcomes. AIMS: Explore the association between low DBP and CV outcomes. METHODS: We searched the online databases until August 2023 for studies reporting the risk of all-cause mortality (ACM) or CV outcomes in patients with low versus normal DBP (70-80mm Hg). RESULTS: Inclusion of 10 studies (n = 1,998,223 patients) found that a mean achieved DBP < 60 mmHg was associated with an increased risk of all-cause mortality (HR 1.48; 95 % CI [1.26-1.74]), especially in patients with pre-existing CV disease. It was also associated to a higher risk of major adverse cardiovascular events (HR 1.84; [1.28-2.65]) and myocardial infarction (HR 1.49; [1.13-1.97]). A DBP of 60-69 mmHg was associated with an increased risk of all-cause mortality (HR 1.11; [1.03-1.20]). CONCLUSION: Reduction of DBP, particularly below 60 mmHg, is associated with increased risk of ACM.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Hipertensão , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Pressão Sanguínea/fisiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Acidente Vascular Cerebral/etiologia , Infarto do Miocárdio/etiologia , Insuficiência Cardíaca/complicações , Doenças Cardiovasculares/epidemiologia
10.
Heliyon ; 9(11): e21041, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37928005

RESUMO

The main aim of this study is to figure out how well cryptand-2.2.1 (C 2.2.1) and cryptand-2.1.1 (C 2.1.1) macrocyclic compounds (MCs) work as novel extractants for scandium (Sc) by using an artificial neural network (ANN) models in MATLAB software. Moreover, C2.2.1 and C2.1.1 have never been evaluated to recover Sc. The independent variables impacting the extraction process (concentration of MC, concentration of Sc, pH, and time), and a nonlinear autoregressive network with exogenous input (NARX) and feed-forward neural network (FFNN) models were used to estimate their optimum values. The greatest obstacle in the selective recovery process of the REEs is the similarity in their physicochemical properties, specifically their ionic radius. The recovery of Sc from the aqueous solution was experimentally evaluated, then the non-linear relationship between those parameters was predictively modeled using (NARX) and (FFNN). To confirm the extraction and stripping efficiency, an atomic absorption spectrophotometer (AAS) was employed. The results of the extraction investigations show that, for the best conditions of 0.008 mol/L MC concentration, 10 min of contact time, pH 2 of the aqueous solution, and 75 mg/L Sc initial concentration, respectively, the C 2.1.1 and C 2.2.1 extractants may reach 99 % of Sc extraction efficiency. Sc was recovered from a multi-element solution of scandium (Sc), yttrium (Y), and lanthanum (La) under these circumstances. Whereas, at a concentration of 0.3 mol/L of hydrochloric acid, the extraction of Sc was 99 %, as opposed to Y 10 % and La 7 %. The Levenberg-Marquardt training algorithm had the best training performance with an mean-squared-error, MSE, of 5.232x10-6 and 6.1387x10-5 for C 2.2.1 and C 2.1.1 respectively. The optimized FFNN architecture of 4-10-1 was constructed for modeling recovery of Sc. The extraction process was well modeled by the FFNN with an R2 of 0.999 for the two MC, indicating that the observed Sc recovery efficiency consistent with the predicted one.

11.
J Biomol Struct Dyn ; : 1-19, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37965722

RESUMO

The severity of the influenza virus infection is largely determined by its ability to invade the human host receptor. This critical step is conducted by utilizing hemagglutinin (HA) due to its binding with sialic acid 2,6 (SA). Though 18 subtypes (H1-H18) of HA have been identified, the most efficient one for conducting the host entry has not yet been resolved. This study aims to assess the severity of infections for HA variants by conducting a comparative docking of H1-H18 with the human SA receptor. Eighteen viral 3D structures were retrieved, minimized, and optimized for docking with human SA. In all retrieved structures, five conserved amino acid residues were selected for docking with human SA. Special protein grids were prepared by locating these five residues in the 18 selected subtypes. Results showed that H3 and H8 exerted the highest standard precision and extra precision docking scores, and the highest binding affinities with the human SA, respectively. Phylogenetic analyses confirmed the actual positioning of the selected 3D structures and showed these docked structures belonged to their usual classes due to the extremely close distances found in each docked subtype compared with its corresponding non-docked structures. H8-SA showed slightly better RMSD and SASA values than H3-SA, while H3-SIA showed more favourable radius of gyration scores than H8-SIA in the majority of the simulation period. Due to the highest affinity of binding of H3 and H8 with the human receptor, special caution should be exercised regarding any possible outbreak mediated by these subtypes in human populations. However, it is important to acknowledge a limitation inherent to the computational approach; it may hold relative rather than absolute significance. Further research is needed to deepen our understanding of the intricate interplay between HA variants and the host receptor, taking into account the broader context of viral infection dynamics.Communicated by Ramaswamy H. Sarma.

12.
Retina ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37972977

RESUMO

PURPOSE: Evaluate preoperative bilateral eye patching (BEP) on subretinal fluid (SRF) and vision in acute primary rhegmatogenous retinal detachments (RRD). METHODS: Retrospective non-randomized interventional study of 335 RRD patients undergoing BEP until surgery (BEP cohort) and separated by % full-time compliance: high (≥ 90%), medium (> 90% but ≥ 50%), and low (< 50%). Those declining BEP were included (control). All underwent surgery and followed for ≥ 3 months. Imaging was obtained immediately prior to surgery (iPTS). Best-corrected visual acuity (BCVA) was measured at longest follow-up and iPTS. SRF and foveal status iPTS were analyzed. RESULTS: 240 and 95 patients were in BEP and control cohorts, respectively. 30 patients presented iPTS for analysis. High (64%) and medium (35%) compliance showed significantly greater (P < 0.01) SRF reduction compared to low (4%) and control (3%). Mac-off RRD showed significantly greater (P < 0.01) foveal reattachment with high (29%) and medium (8%) compliance compared to low (2%) and control (1%). Mac-on RRD demonstrated no significant differences (P ≥ 0.51) in final BCVA among high (0 logMAR [median], 20/20 Snellen), medium (0.10 logMAR, 20/25 Snellen), low (0.10 logMAR), and control cohorts (0.10 logMAR). Mac-off RRD demonstrated significantly better final BCVA with high compliance (0.30 logMAR, 20/40 Snellen) compared to low (0.40 logMAR, 20/50 Snellen; P = 0.04) and control (0.60 logMAR, 20/80 Snellen; P = 0.02). CONCLUSIONS: Preoperative BEP can stabilize or improve SRF in acute primary RRD. Patients with BEP >50% of time experienced greatest benefits.

13.
Ocul Immunol Inflamm ; : 1-6, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37917881

RESUMO

PURPOSE: To describe ocular involvement in subjects with Whipple's disease (WD). METHODS: Retrospective review of documented WD cases seen at Mayo Clinic between 1980 and 2021 with ocular involvement. RESULTS: Of 217 patients with WD, 30 had eye exams and four (two female, median age 58.5 years) had ocular involvement. Findings included anterior/intermediate uveitis (n = 2), intermediate uveitis and phlebitis (n = 1), and chorioretinitis with vitritis (n = 1). The diagnosis was confirmed by vitreous biopsy in three of four cases. In two cases, WD diagnosis was unconfirmed prior to the ocular diagnosis. Systemic manifestations included gastrointestinal symptoms in all patients, synovitis (n = 3), weight loss (n = 2), and pericarditis (n = 1). Mean time from onset of ocular symptoms to ocular diagnosis was 11 months (range 2-28 months). Prior systemic symptoms were present as long as 3 years. CONCLUSIONS: WD is uncommon and ocular involvement is even more rare. However, WD should be considered in the differential for all patients with chronic recalcitrant uveitis, especially in the setting of polyarthralgias and/or gastrointestinal symptoms. Vitreous biopsy is a reliable method to diagnose ocular WD.Abbreviations and Acronyms: Whipple's disease (WD), intestinal lipodystrophy (IL), polymerase-chain reaction (PCR), periodic acid-Schiff (PAS), trimethoprim/sulfamethoxazole (TMP/SMX).

14.
Heliyon ; 9(11): e21345, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37954383

RESUMO

The lateritic ore drying in the Cuban nickel producing industry is realized within flighted rotary dryers. In this investigation, performance indicators in regards to transfer of momentum, heat and mass were evaluated. The dryers operate in a concurrent configuration with combustion gas, at a productivity between 40 t h-1 and 50 t h-1. The distribution function of the residence time (RTD) was best fitted to a model of a multi-branch tanks-in-series system, theoretical residence time was 51 ± 2 min and experimental mean residence time 61 min, at a rate of 45 t h-1 and hydraulic efficiency 1.23, due to the presence of dead-zoon. Mass and energy balance was made following a "black box" model, as results, the specific fuel consumption was 27.25 ± 0.25 kg fuel t-1 of wet ore, specific energy consumption 79.66 ± 0.95 kg fuel t-1 of H2O evaporated, energy efficiency 97.28 ± 0.01 %, thermal efficiency 66.88 ± 0.71 % and drying efficiency 98.77 ± 0.12 %. Mathematical modelling was made using a system of differential equations, the rate of drying in falling rate period was estimated by Arrhenius equation, then, temperature profile and ore moisture content along the dryer was simulated. The model provided a successful predictive performance; for an inlet gas temperature between 850 °C and 900 °C, the ore moisture was reduced form 33.0 % (wet basis) to a range depending on the dryer productivity, from 3.0 % to 7.1 %. Designing a computerized system that implements these algorithms can benefit on efficiency and productivity of the production plant.

15.
J Biomol Struct Dyn ; : 1-13, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37671847

RESUMO

Resistin is a cysteine-rich secretory hormone that induces resistance to insulin, and its elevated expression is correlated with the onset of diabetes and several related metabolic disorders. Resistin performs its inhibitory role by connecting three identical subunits through Cys22-based disulfide linkages. The necessity to inhibit the formation of resistin trimer is one of the essential means to prevent the aggravation of diabetes mellitus type 2, obesity, and atherosclerosis. This study was conducted to screen the clinically approved drugs to find the most potent one to inhibit resistin with the best pharmacokinetics and drug-likeness properties. A total of 4654 clinically approved drugs were docked against the Cys22 residue of resistin. The top ten drugs with the highest high-precision (XP) docking scores were selected. Ioversol and masoprocol showed the highest XP docking and Molecular Mechanics-Generalized Born Surface Area (MMGBSA) scores, respectively, with double hydrogen bonding with the targeted Cys22. Molecular dynamics (MD) simulations showed that the masoprocol-resistin complex exhibited lower root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) values than those observed in the ioversol-resistin complex. Both drugs induced drastic conformational changes in resistin monomer interactions. However, ioversol did not prove satisfying drug-likeness properties, while masoprocol showed the most favourable pharmacokinetic and drug-likeness properties. This study has demonstrated that masoprocol offers a novel inhibitory effect on resistin with the highest ligand affinity, making it a promising drug for combating insulin resistance.Communicated by Ramaswamy H. Sarma.

17.
Heliyon ; 9(7): e17794, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37456018

RESUMO

Several conventional methods are employed to remove numerous pollutants from oily wastewater discharged from oil-field activities. The purpose of this study is to use a new design of an electrocoagulation reactor (ECR) to treat oily wastewater effluents from the Al-Muthanna petroleum plant to minimize a Total Dissolved Solids (TDS) to levels suitable for employment. In a continuous ECR, a One-Sided-Finned cathode tube (1SF) made of aluminum was inserted between a pair of aluminum-cylindrical anodes. The effects of the electrolysis period (4-60 min), current density (0.63-5.0 mA/cm2), and flow rate (50-150 ml/min) on Final TDS value were investigated. The increment of flow rate causes the final TDS value to be increased, while the extending of the electrolysis process and the raise in current density reduces it. The final TDS was 1842.54 mg/l (reduce by 307.46 mg/l) at optimum values of 1-h electrolysis, 5 mA/cm2 current density, and 50 ml/min flow rate, with an inner anode consumption of 0.13 g and an outer anode consumption of 0.43 g. Regression models with a p-value of 0.001 and F-value of 27.01 noted that the selected model components were important, and the estimated model is considered prominent. Furthermore, the regression coefficient (R2 = 97.99%) for the final TDS response revealed that the model fit the data well. This study confirmed the ability of the new electrocoagulation reactor to treat petroleum wastewater under significant conditions which overcomes the drawbacks of the conventional designs of electrocoagulation reactors.

18.
Healthcare (Basel) ; 11(14)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37510523

RESUMO

Coronavirus disease 2019, or COVID-19, still has a terrifying potential due to its continuous genetic variation. Although vaccines have been created, adherence to preventive measures remains a privileged choice to tackle the pandemic. This study aims to investigate the anxiety, attitudes, and practices (KAPs) towards COVID-19 infection in the Eastern Province of Saudi Arabia. In this cross-sectional study, data were collected from 400 participants via an online self-structured questionnaire. Anxiety, attitude, and practice scores were calculated by summing the points of the statements under the corresponding domain multiplied by 100 over 12, 21, or 15, respectively. Chi-square and one-way analysis of variance were used to investigate the relationships between vaccination, anxiety, attitude, practice scores, and demographic characteristics. More than half of the participants were female (58.5%; mean age of 29.5 years; the majority in the age groups of <20 years and 21-30 years). Only 21.5% of the participants were suffering from or previously had chronic diseases. Notably, 22.3% of the male participants were vaccinated (p = 0.000). The old age groups (41-50 years and >50 years) were more vaccinated (16.3% and 24.1%, respectively, p = 0.000), as well as the unemployed (36.4%; p = 0.000). The mean scores of anxiety, attitude, and practice were 66.8, 72.3, and 85.2, respectively. Females had an anxiety score of 68.5% (p = 0.008) and a higher attitude score of 68.5% (p = 0.008). Infected male participants had a lower practice score of 80% (p = 0.038), while females recorded higher practice scores (85.7 ± 11.6). The results highlight the importance of reliable communication from health representatives and legislators in educating the public and promoting their knowledge about non-therapeutic interventions. Efficient intervention approaches are required to fill the gap during the implementation of non-therapeutic measures. Also, it is recommended that awareness programs, during COVID-19 or any other similar pandemics, should be tailored to target Eastern Province inhabitants, especially males.

19.
Retin Cases Brief Rep ; 17(5): 572-576, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37490925

RESUMO

PURPOSE: The purpose of this study was to describe an exceedingly rare presentation of secondary vitreoretinal involvement by the uncommon entity "indolent T-cell lymphoproliferative disorder of the gastrointestinal tract" and illustrate the utility of fluorescence in situ hybridization for diagnosis. METHODS: This is a case report. RESULTS: A 57-year-old woman with presumed iritis on chronic topical prednisolone acetate presented with increased vitreous opacities in the right eye. She had a history of biopsy-confirmed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract involving the stomach and duodenum, JAK2 -rearrangement positive, controlled on maintenance oral methotrexate. Vitreous biopsy was unremarkable with small CD3-positive and CD4-positive and CD20-negative lymphocytes, along with histiocytes and fibroblasts. Immunostains showed CD4 positivity, and fluorescence in situ hybridization revealed a JAK2 gene rearrangement, consistent with the patient's previously diagnosed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Intravitreal methotrexate injections were started in the right eye. MRI of the brain and lumbar puncture with cytology, MYD88 , IL10, and flow cytometry performed at the time of right eye vitreoretinal lymphoma diagnosis revealed no evidence of central nervous system lymphoma, but subsequent bone marrow biopsy demonstrated 5% involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, JAK2 -rearrangement positive, with a lung nodule on PET computed tomography. She returned 4 months later with fatigue, night sweats, and blurry vision in the left eye with vitreous and anterior chamber cellular infiltration and retinal vasculitis. CONCLUSION: T-cell vitreoretinal lymphoma is rare, and diagnosis can be challenging. Despite inconclusive cytology in this case, interphase fluorescence in situ hybridization detected a JAK2 gene rearrangement, which confirmed the involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and prompted appropriate treatment and workup for recurrent systemic or central nervous system lymphoma.


Assuntos
Linfoma de Células T , Neoplasias da Retina , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Retina/patologia , Metotrexato , Hibridização in Situ Fluorescente , Corpo Vítreo/patologia , Trato Gastrointestinal/patologia , Linfoma de Células T/diagnóstico , Linfócitos T/patologia
20.
Obes Surg ; 33(9): 2632-2639, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37470954

RESUMO

BACKGROUND: Childhood obesity is an important worldwide issue of serious medical and social concern. One anastomosis gastric bypass (OAGB) is an approved, effective, and long-lasting procedure for weight loss and the remission of obesity-associated medical problems in the adult patients, but its efficacy and safety in children and adolescents are still on debate. This study aimed to evaluate safety and efficacy of OAGB compare to SG and RYGB during a 5-year follow-up. METHODS: A retrospective cohort study on children and adolescents with severe obesity who underwent primary OAGB, sleeve gastrectomy (SG), and Roux-e-Y gastric bypass (RYGB) at an academic hospital, between March 2016 and December 2020. RESULTS: Two hundred twenty-eight patients with 24 to 60 months of follow-up including 107 SG, 37 RYGB, and 84 OAGB were included in the final analysis. The mean age, preoperative weight, and BMI were 15.71 ± 2.09 years (range, 9-18 years), 126.3 ± 22.0 kg (74.5-215 kg), and 45.1 ± 6.9 kg/ m2 (36.4-79.3 kg/m2), respectively. The mean of follow-up was 30.05 ± 19.98 months. The mean of ∆BMI was 30.2 ± 5.1, 30.0 ± 5.4, and 31.1 ± 6.8 at 12th, 36th, and 60th months postoperative. At the 60-month follow-up, there were statistically significant differences in ΔBMI between SG and OAGB and SG and RYGB. CONCLUSION: OAGB is a safe and effective procedure for the treatment of obesity in children and adolescents in 24 to 60 months follow-ups.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Obesidade Pediátrica , Adulto , Humanos , Criança , Adolescente , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Estudos de Coortes , Estudos Retrospectivos , Obesidade Pediátrica/cirurgia , Obesidade Pediátrica/complicações , Gastrectomia/métodos , Resultado do Tratamento
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