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1.
Mol Neurobiol ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254911

RESUMEN

Alzheimer's disease (AD) presents a significant challenge to global health. It is characterized by progressive cognitive deterioration and increased rates of morbidity and mortality among older adults. Among the various pathophysiologies of AD, mitochondrial dysfunction, encompassing conditions such as increased reactive oxygen production, dysregulated calcium homeostasis, and impaired mitochondrial dynamics, plays a pivotal role. This review comprehensively investigates the mechanisms of mitochondrial dysfunction in AD, focusing on aspects such as glucose metabolism impairment, mitochondrial bioenergetics, calcium signaling, protein tau and amyloid-beta-associated synapse dysfunction, mitophagy, aging, inflammation, mitochondrial DNA, mitochondria-localized microRNAs, genetics, hormones, and the electron transport chain and Krebs cycle. While lecanemab is the only FDA-approved medication to treat AD, we explore various therapeutic modalities for mitigating mitochondrial dysfunction in AD, including antioxidant drugs, antidiabetic agents, acetylcholinesterase inhibitors (FDA-approved to manage symptoms), nutritional supplements, natural products, phenylpropanoids, vaccines, exercise, and other potential treatments.

2.
ACS Omega ; 9(35): 37253-37264, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39246478

RESUMEN

Unconventional hydrocarbon reservoirs are challenging media to exploit and develop for energy due to very low permeability. As such, unconventional means, such as horizontal drilling and hydraulic fracturing, are typically practiced. During hydraulic fracturing, the formation breakdown pressure is of great importance and determines the fluid pumping cost. Less attention has been given to breakdown pressure reduction for a cost-effective and enhanced hydraulic fracturing operation. The objective of this study is to explore the application of thermochemical fluids to induce thermal shock with the purpose of generating microcracks and reducing the breakdown pressure in high-temperature unconventional reservoirs. For this, thermochemical fluids of an endothermic nature (reduces the temperature when mixed) and Kentucky Sandstone and Eagle Ford Shale were utilized. In particular, we investigated the effect of endothermic reactions between ammonium chloride (NH4Cl) and sodium hydroxide (NaOH) on the strength and breakdown pressure of both samples by applying multiple cycle treatments. The obtained results indicated a significant reduction in both the strength and breakdown pressure of the rocks, with Kentucky Sandstone showing a reduction of 53.07% and Eagle Ford Shale by 34.71% in breakdown pressure. This novel approach not only provides a promising alternative to traditional fracturing methods in high-temperature reservoirs but also could bring a significant reduction in fluid pumping requirements as well as the operational cost of hydraulic fracturing.

3.
AMB Express ; 14(1): 104, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285019

RESUMEN

Developing a potent antiviral agent to combat Coronavirus Disease-19 (COVID-19) is of critical importance as we may be at risk of the emergence of new virus strains or another pandemic recurrence. The interaction between the SARS-CoV-2 spike protein and Angiotensin Converting Enzyme 2 (ACE2) is the main protein-protein interaction (PPI) implicated in the virus entry into the host cells. Spike-ACE2 PPI represents a major target for drug intervention. We have repurposed a previously described protein-protein interaction detection method to be utilized as a drug screening assay. The assay was standardized using Chitosan nanoparticles (CNPs) as the drug and SARS-CoV-2 spike-ACE2 interaction as the PPI model. The assay was then used to screen four natural bioactive compounds: Curcumin (Cur), Gallic acid (GA), Quercetin (Q), and Silymarin (Sil), and their cytotoxicity was evaluated in vitro. Production of the spike protein and the evaluation of its activity in comparison to a standard commercial protein was part of our work as well. Here we describe a novel simple immunofluorescent screening assay to identify potential SARS-CoV-2 inhibitors that could assess the inhibitory effect of any ligand against any PPI.

4.
Am J Transl Res ; 16(7): 3259-3272, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114700

RESUMEN

OBJECTIVE: Anemia is a pathological condition characterized by reduced oxygen bioavailability and/or changes in hematological parameters. This study investigated the anti-anemic activities of Carica papaya (CP) phytoconstituents in aluminium-chloride-induced anemic rats. METHOD: Twenty-seven rats were randomized into nine groups of three rats as follows; group 1 was the normal (non-induced) group, 2-9 were anemic rats administered 1 mL distilled water, standard drug (3 mg/kg body weight (bw) ferrous sulphate), 100, 300 and 500 mg/kg bw of crude methanolic extract of CP (CMECP) of the leaf and 100, 300 and 500 mg/kg bw of CMECP of the seed respectively in the first stage of the study. In the second stage, thirty-three rats were randomized into eleven groups of three rats as follows; group 1 was the normal group, 2-11 were anemic rats treated with 1 mL distilled water, standard drug, 75 mg/kg bw, 150 mg/kg of alkaloid fraction of CP seed, 75 mg/kg bw, 150 mg/kg bw of flavonoid fraction of CP seed, 75 mg/kg bw and 150 mg/kg of alkaloid fraction of CP leaf, 75 mg/kg bw and 150 mg/kg bw of flavonoid fraction of CP leaf respectively. RESULTS: Treatment of anemic rats with CP extracts and fractions of the seed and leaf significantly reversed the hematological parameters and body weight of anemic rats in a dose independent fashion. The CMECP leaf at 100 and 500 mg/kg gave PCV of 42.50±0.50 and 47.00±0.50, while the seed gave 49.50±0.50 and 42.50±0.50 respectively after 2 weeks of treatment. However, the alkaloid and flavonoid fraction of CP presented better anti-anemic properties probably due to constituents' synergism. CONCLUSION: This study concluded that CP possesses phytoconstituents which potentiates it as a safe anti-anemic drug candidate.

6.
Biomater Adv ; 165: 214005, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39208497

RESUMEN

Bacterial vaginosis (BV) is an imbalance of the vaginal microbiome in which there are limited lactobacilli and an overgrowth of anaerobic and fastidious bacteria such as Gardnerella. The propensity for BV recurrence is high, and therapies involving multiple treatment modalities are emerging to meet this need. However, current treatments requiring frequent therapeutic administration are challenging for patients and impact user compliance. Three-dimensional (3D)-printing offers a novel alternative to customize platforms to facilitate sustained therapeutic delivery to the vaginal tract. This study designed a novel vehicle intended for dual sustained delivery of both antibiotic and probiotic. 3D-printed compartmental scaffolds consisting of an antibiotic-containing silicone shell and a core containing probiotic Lactobacillus were developed with multiple formulations including biomaterials sodium alginate (SA), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyethylene oxide (PEO), and kappa-carrageenan (KC). The vehicles were loaded with 50 µg of metronidazole/mg polymer and 5 × 107 CFU of L. crispatus/mg scaffold. Metronidazole-containing shells exhibited cumulative drug release of 324.2 ± 31.2 µg/mL after 14 days. Multiple polymeric formulations for the probiotic core demonstrated cumulative L. crispatus recovery of >5 × 107 CFU/mg scaffold during this timeframe. L. crispatus-loaded polymeric formulations exhibited ≥2 log CFU/mL reduction in free Gardnerella in the presence of VK2/E6E7 vaginal epithelial cells. As a first step towards the goal of facilitating patient compliance, this study demonstrates in vitro effect of a novel 3D-printed dual antibiotic and probiotic delivery platform to target BV.


Asunto(s)
Lactobacillus crispatus , Metronidazol , Impresión Tridimensional , Probióticos , Siliconas , Humanos , Siliconas/química , Metronidazol/farmacología , Metronidazol/administración & dosificación , Metronidazol/química , Femenino , Probióticos/administración & dosificación , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/terapia , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/química , Preparaciones de Acción Retardada , Liberación de Fármacos , Sistemas de Liberación de Medicamentos/métodos
7.
Brain Netw Modul ; 3(2): 52-60, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119588

RESUMEN

Chronic neuropathic pain (CNP) remains a significant clinical challenge, with complex neurophysiological underpinnings that are not fully understood. Identifying specific neural oscillatory patterns related to pain perception and interference can enhance our understanding and management of CNP. To analyze resting electroencephalography data from individuals with chronic neuropathic pain to explore the possible neural signatures associated with pain intensity, pain interference, and specific neuropathic pain characteristics. We conducted a secondary analysis from a cross-sectional study using electroencephalography data from a previous study, and Brief Pain Inventory from 36 patients with chronic neuropathic pain. For statistical analysis, we modeled a linear or logistic regression by dependent variable for each model. As independent variables, we used electroencephalography data with such brain oscillations: as delta, theta, alpha, and beta, as well as the oscillations low alpha, high alpha, low beta, and high beta, for the central, frontal, and parietal regions. All models tested for confounding factors such as age and medication. There were no significant models for Pain interference in general activity, walking, work, relationships, sleep, and enjoyment of life. However, the model for pain intensity during the past four weeks showed decreased alpha oscillations, and increased delta and theta oscillations were associated with decreased levels of pain, especially in the central area. In terms of pain interference in mood, the model showed high oscillatory Alpha signals in the frontal and central regions correlated with mood impairment due to pain. Our models confirm recent findings proposing that lower oscillatory frequencies, likely related to subcortical pain sources, may be associated with brain compensatory mechanisms and thus may be associated with decreased pain levels. On the other hand, higher frequencies, including alpha oscillations, may disrupt top-down compensatory mechanisms.

8.
Medicina (Kaunas) ; 60(8)2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39202581

RESUMEN

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.


Asunto(s)
Gonadotropina Coriónica , Clomifeno , Infertilidad Femenina , Inducción de la Ovulación , Síndrome del Ovario Poliquístico , Humanos , Femenino , Clomifeno/uso terapéutico , Clomifeno/administración & dosificación , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/fisiopatología , Inducción de la Ovulación/métodos , Gonadotropina Coriónica/administración & dosificación , Gonadotropina Coriónica/uso terapéutico , Gonadotropina Coriónica/sangre , Adulto , Embarazo , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/etiología , Fármacos para la Fertilidad Femenina/uso terapéutico , Fármacos para la Fertilidad Femenina/administración & dosificación , Índice de Embarazo , Resultado del Tratamiento
9.
Heliyon ; 10(15): e35876, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170179

RESUMEN

The increasing incidence of resistance extended spectrum-beta lactamase (ESBL) producing Klebsiella pneumonia become worldwide issue. The current study aimed to determine the genomic diversity of ESBL-producing K. pneumoniae in milk samples collected from cows with mastitis as well as their antibiotic sensitivity profiles and genetic identification in Peshawar, Pakistan. The california mastitis test (CMT) was initially used to verify the presence for mastitis in 700 collected milk samples. The molecular identification of the 16SrRNA gene confirmed 120/700 (17.14 %) propagation of K. pneumonia. Out of these isolates MDR ESBL-producing isolates were 60/120 (50 %). The lactose were found (M = 3.96 ± 0.28, SD = 2.19), followed by fats (M = 3.12 ± 0.11, SD = 0.90), protein (M = 5.97 ± 0.24, SD = 1.84), sodium (M = 55.74 ± 2.07, SD = 15.81), potassium (M = 138.5 ± 1.53, SD = 11.71), chloride (M = 0.74 ± 0.03, SD = 0.24), calcium (M = 10.27 ± 0.31, SD = 2.42), and chlorine (M = 2.80 ± 0.22, SD = 1.70), respectively. Amikacin (80 %), ceftazidime (71 %), and tetracycline (71 %) were shown to be the most effective antimicrobials against all of the isolates. The occurrence of the blaSHV gene was observed at 56.00 % whereas the blaTEM gene and blaCTX-M gene were 36.00 %, and 30.00 %. The distribution of blaCTX-M subgroup genes was followed by blaCTX-M-1 (38.00 %), blaCTX-M-9 (22.20 %), and blaCTX-M-15 (61.10 %). Co-occurrence of blaCTX-M+ blaSHV was (15.00 %), blaCTX-M+ blaTEM were (6.60 %), and blaSHV + blaTEM were (10.00 %), respectively. The inappropriate, prolonged and common use of antibiotics may apply selective pressure for propagation and the occurrence of resistant isolates.

10.
Indian J Orthop ; 58(9): 1272-1277, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39170658

RESUMEN

Purpose: Treatment of osteomyelitis (OM) is challenging. Ilizarov bone transport is a commonly used technique for management of OM. The recently introduced limb reconstruction system (LRS) has been effectively used for management of OM. It was suggested to be easier in use and less invasive. The present retrospective study aimed to compare LRS and Ilizarov bone transport in management of femoral OM using a propensity score matched analysis. Methods: The present retrospective study included 80 consecutive patients with femoral OM. The studied patients were managed either using Ilizarov external fixator (n = 40) or Orthofix LRS (n = 40). The clinical outcome measurements included union time, limb length discrepancy, additional operative procedures, refracture and infection. Results: Patients in the LRS group were exposed to significantly higher frequency of bone transport (30.0 versus 15.0%) and lower frequency of acute compression and lengthening (10.0 versus 32.5%). Patients in Ilizarov group had significantly higher frequency of tobramycin pellets as compared to their counterparts. The studied groups were comparable regarding the operative complications including pin-tract infection, non-union at docking site and refracture. Patients in the Ilizarov had significantly shorter time to union (8.2 ± 3.2 versus 11.0 ± 5.6 months, p = 0.012). No statistically significant differences were found between the studied groups regarding the quality-of-life domains. Conclusions: Use of Ilizarov external fixator and Orthofix LRS devices proved to be effective and reliable. Their influences on patients' quality appear to be comparable.

11.
ACS Omega ; 9(28): 31081-31092, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39035882

RESUMEN

Liquid loading significantly hinders gas production in unconventional shale wells, restricting flow and causing productivity decline. This study presents a novel approach to address this challenge, utilizing thermochemical fluids to generate in situ pressure and heat and effectively mitigating liquid loading issues. Laboratory experiments were conducted using a specially designed flow loop system to evaluate the performance of thermochemical fluids in alleviating liquid loading. The key treatment parameters such as thermochemical volumes, injection rate, number of cycles, and optimum injection time were optimized to improve the removal efficiency. In addition, PIPESIM software (pipe simulation program) was used to validate the effectiveness of the thermochemical approach for removing the liquid loading issue. Both laboratory results and PIPESIM outcomes confirmed the efficiency of thermochemical fluids in handling liquid loading. Removal efficiency of more than 90% can be achieved using thermochemical injection. The liquid removal efficiency increases with the number of cycles due to the generation of more pressure and heat at later injection cycles. Increasing injection cycles from 1 to 3 resulted in liquid removal efficiency rising from 17 to 95%. Also, PIPESIM results indicated that the gas production rate can be improved by around 74% after applying thermochemical treatment. Overall, this study introduces an effective treatment for liquid loading mitigation with significant potential to enhance gas production. The proposed method offers several advantages, including ease of application and extended well life.

12.
Noncoding RNA Res ; 9(4): 1249-1256, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39036602

RESUMEN

Background: Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, ß-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients. Aim: Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction. Patients & methods: Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA. Results: Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity. Conclusion: Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes.

13.
Polymers (Basel) ; 16(14)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39065357

RESUMEN

Since buildings are designed to endure over time, it is crucial to comprehend how laminated glass (LG) windows, and consequently, the polymer interlayer materials, respond to weathering. This paper explores the impact of accelerated humidity on the mechanical properties of several polymer interlayer materials and LG sections. The study specifically focuses on three polymer interlayer materials of industrial interest: polyvinyl butyral (PVB), ethylene-vinyl acetate (EVA), and ionomer (SG). To examine the environmental effects, testing setups were devised to subject the polymeric materials and LG panels to specific conditions. Uniaxial tension coupons and LG disks were submerged in a water bath to simulate the environmental effect. A dedicated testing fixture was designed and manufactured for the LG disks. The results showed that the properties of EVA, including strength, maximum strain, and toughness, were not significantly affected by the environmental conditions. However, the properties of SG5000 were notably impacted, with a significant reduction in its bond strength due to water immersion.

14.
Arab J Gastroenterol ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39079824

RESUMEN

BACKGROUND AND STUDY AIM: Helicobacter Pylori (H. pylori), a widespread gastric pathogen, can have a range of presentations necessitating population based tailored treatment strategies. We aimed to study the clinical and demographic profile of patients with H pylori in Qatar, to determine the best treatment strategy for Qatar's population. PATIENTS AND METHODS: Retrospective data collection of all patients diagnosed with H pylori from January 2017 to December 2019 in Hamad Medical Corporation (HMC) and Primary Health Care Corporation (PHCC), Qatar was done. The demographic, clinical, endoscopic and histologic characteristics of patients and H. Pylori directed therapies were documented and compared. Pearson's Chi-square test, independent samples ttest or analysis of variance (ANOVA) was used as appropriate to compare various parameters between patients. RESULTS: 2217 patients tested positive for H. Pylori over 3 yrs. of which 837 (37.8 %) were Qatari nationals. Dyspepsia was the most common indication for testing (44.6 % patients) which was positively associated with gastric erythema and atrophy on endoscopy (P = 0.000 and 0.004, respectively) and negatively associated with a normal endoscopy (p = 0.038). Most of the patients had chronic active gastritis (98.2 %). Other pre-malignancies were seen in only 85 (14.3 %) patients. Mean (SD) age of patients with premalignancies was significantly more than those without [ 53.25 (17.6) vs. 44.77 (14.8), p = 0.000]. Only 11(0.6 %) patients had a malignancy of the stomach. CONCLUSION: H pylori infection may be quite prevalent amongst Qatari nationals. Since prevalence of gastric premalignancies and incidence of gastric malignancy in patients with H pylori in Qatar may be low, generalized test and treat strategy is not economically and practically meaningful in Qatar. Symptomatic patients should be tested and treated, with endoscopy reserved for those with alarming symptoms, failure of proton pump inhibitors and older patients.

15.
Front Microbiol ; 15: 1399466, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827146

RESUMEN

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.

16.
Front Chem ; 12: 1419242, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911996

RESUMEN

DNA gyrase and topoisomerase IV show great potential as targets for antibacterial medicines. In recent decades, various categories of small molecule inhibitors have been identified; however, none have been effective in the market. For the first time, we developed a series of disalicylic acid methylene/Schiff bases hybrids (5a-k) to act as antibacterial agents targeting DNA gyrase and topoisomerase IV. The findings indicated that the new targets 5f-k exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria, with efficacy ranging from 75% to 115% of the standard ciprofloxacin levels. Compound 5h demonstrated the greatest efficacy compared to the other compounds tested, with minimum inhibitory concentration (MIC) values of 0.030, 0.065, and 0.060 µg/mL against S. aureus, E. coli, and P. aeruginosa. 5h had a MIC value of 0.050 µg/mL against B. subtilis, which is five times less potent than ciprofloxacin. The inhibitory efficacy of the most potent antibacterial derivatives 5f, 5h, 5i, and 5k against E. coli DNA gyrase was assessed. The tested compounds demonstrated inhibitory effects on E. coli DNA gyrase, with IC50 values ranging from 92 to 112 nM. These results indicate that 5f, 5h, 5i, and 5k are more effective than the reference novobiocin, which had an IC50 value of 170 nM. Compounds 5f, 5h, 5i, and 5k were subjected to additional assessment against E. coli topoisomerase IV. Compounds 5h and 5i, which have the highest efficacy in inhibiting E. coli gyrase, also demonstrated promising effects on topoisomerase IV. Compounds 5h and 5i exhibit IC50 values of 3.50 µM and 5.80 µM, respectively. These results are much lower and more potent than novobiocin's IC50 value of 11 µM. Docking studies demonstrate the potential of compound 5h as an effective dual inhibitor against E. coli DNA gyrase and topoisomerase IV, with ADMET analysis indicating promising pharmacokinetic profiles for antibacterial drug development.

17.
J Clin Med ; 13(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38930113

RESUMEN

Background: Gastric fluid volume has been used as a surrogate marker for pulmonary aspiration risk in studies evaluating fasting protocol safety. This study measured residual gastric fluid volume in children using a protocol in which diluted oral contrast medium was administered up until one hour before anesthesia. Methods: This was a single-center prospective observational cohort trial of 70 children for elective abdominal/pelvic computed tomography (CT). Imaging was performed after diluted enteral contrast medium administration, beginning two hours before and ending at least one hour before induction. For each patient, gastric fluid volume was calculated using an image region of interest. The primary outcome measure was gastric fluid volume measured using the computed tomography image. Results: The median time from the end of contrast administration to imaging was 1.5 h (range: 1.1 to 2.2 h). Residual gastric volume, measured using CT was <0.4 mL/Kg in 33%; ≥0.4 mL/Kg in 67%; and ≥1.5 mL/Kg in 44% of patients. Residual gastric volumes measured using CT and aspiration were moderately correlated (Spearman's correlation coefficient = 0.41, p = 0.0003). However, the median residual gastric volume measured using CT (1.17, IQR: 0.22 to 2.38 mL/Kg) was higher than that of aspiration (0.51, IQR: 0 to 1.58 mL/Kg, p = 0.0008 on differences in paired measures). Three cases of vomiting were reported. No evidence of pulmonary aspiration was identified. Conclusions: Children who receive large quantities of clear fluid up to one hour before anesthesia can have a significant gastric residual volume.

18.
Sci Total Environ ; 943: 173836, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38866157

RESUMEN

To mitigate anthropogenic CO2 emissions and address the climate change effects, carbon capture and storage by mineralization (CCSM) and industrial mineral carbonation are gaining attraction. Specifically, in-situ carbon mineralization in the subsurface geological formations occurs due to the transformation of silicate minerals into carbonates (e.g., CaCO3, MgCO3) while ex-situ carbon mineralization at the surface undergoes chemical reactions with metal cations - thus leading to permanent storage. However, both processes are complex and require a rigorous investigation to enable large-scale mineralization. This paper, therefore, aims to provide an overreaching review of the in-situ and ex-situ methods for carbon mineralization for different rock types, various engineered processes, and associated mechanisms pertinent to mineralization. Furthermore, the factors influencing in-situ and ex-situ processes, e.g., suitable minerals, optimal operating conditions, and technical challenges, have also been inclusively reviewed. Our findings suggest that in-situ carbon mineralization, i.e., subsurface permanent storage of CO2 by mineralization, arguably is more promising than ex-situ mineralization due to energy efficiency and large-scale storage potential. Furthermore, the effect of rock type can be ranked as igneous (basalt) > carbonates (sedimentary) > sandstone (sedimentary) to consider for rapid and large-scale CCSM. The findings of this review will, therefore, help towards a better understanding of carbon mineralization, which contributes towards large-scale CO2 storage to meet the global net-zero targets.

19.
Epilepsy Behav Rep ; 27: 100653, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841319

RESUMEN

This is a retrospective and comparative pilot study to investigate the role of vagus nerve stimulation (VNS) in improving cognitive functions in the pediatric age group with drug resistant epilepsy (DRE). It was conducted from January 2018 to February 2023. Children between the ages of 4 and 18 years were divided into two groups, the "VNS group" and the "best medical treatment (BMT) group". Follow up period was 12 months. Demographic, clinical, etiological and investigational data were recorded. Cognitive assessment using the Modified Mini-Mental State Examination for children (MMSE) was recorded at baseline and 12 months later for each group. 76.4 % of patients were classified as epilepsy secondary to cerebral palsy. 75 % of patients showed ≥ 50 % seizure frequency reduction among the VNS group as compared to 12.5 % in the BMT group. None of both groups achieved seizure freedom. At 12 months, both BMT and VNS groups showed statistically significantly improved overall cognitive score from baseline records (p = 0.027) and (p = 0.012), respectively, with a significantly higher improvement in VNS group. Also, statistical sub-analysis of cognitive subscales in cerebral palsy patients in both groups was conducted and revealed a significant improvement (p = 0.02) in the VNS group. We concluded that there is a potential role of VNS in improving cognitive functions which was shown by using a cost-effective screening tool. A significant effect was observed specially in cerebral palsy patients. This is very beneficial in limited-resources countries since VNS has good safety profile, high seizure control, and added value to cognitive functions.

20.
J Sports Sci Med ; 23(2): 425-435, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38841632

RESUMEN

Non-local muscle fatigue (NLMF) refers to a transient decline in the functioning of a non-exercised muscle following the fatigue of a different muscle group. Most studies examining NLMF conducted post-tests immediately after the fatiguing protocols, leaving the duration of these effects uncertain. The aim of this study was to investigate the duration of NLMF (1-, 3-, and 5-minutes). In this randomized crossover study, 17 recreationally trained participants (four females) were tested for the acute effects of unilateral knee extensor (KE) muscle fatigue on the contralateral homologous muscle strength, and activation. Each of the four sessions included testing at either 1-, 3-, or 5-minutes post-test, as well as a control condition for non-dominant KE peak force, instantaneous strength (force produced within the first 100-ms), and vastus lateralis and biceps femoris electromyography (EMG). The dominant KE fatigue intervention protocol involved two sets of 100-seconds maximal voluntary isometric contractions (MVIC) separated by 1-minute of rest. Non-dominant KE MVIC forces showed moderate and small magnitude reductions at 1-min (p < 0.0001, d = 0.72) and 3-min (p = 0.005, d = 0.30) post-test respectively. The KE MVIC instantaneous strength revealed large magnitude, significant reductions between 1-min (p = 0.021, d = 1.33), and 3-min (p = 0.041, d = 1.13) compared with the control. In addition, EMG data revealed large magnitude increases with the 1-minute versus control condition (p = 0.03, d = 1.10). In summary, impairments of the non-exercised leg were apparent up to 3-minutes post-exercise with no significant deficits at 5-minutes. Recovery duration plays a crucial role in the manifestation of NLMF.


Asunto(s)
Estudios Cruzados , Electromiografía , Contracción Isométrica , Rodilla , Fatiga Muscular , Fuerza Muscular , Humanos , Fatiga Muscular/fisiología , Femenino , Masculino , Contracción Isométrica/fisiología , Fuerza Muscular/fisiología , Adulto Joven , Rodilla/fisiología , Factores de Tiempo , Adulto , Músculo Cuádriceps/fisiología , Músculo Esquelético/fisiología , Músculos Isquiosurales/fisiología
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