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1.
Oncol Res ; 32(6): 1037-1045, 2024.
Article in English | MEDLINE | ID: mdl-38827324

ABSTRACT

Background: The dysregulation of Isocitrate dehydrogenase (IDH) and the subsequent production of 2-Hydroxyglutrate (2HG) may alter the expression of epigenetic proteins in Grade 4 astrocytoma. The interplay mechanism between IDH, O-6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation, and protein methyltransferase proteins-5 (PRMT5) activity, with tumor progression has never been described. Methods: A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors. Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis. Inter-cohort statistical significance was evaluated. Results: Both IDH-mutant WHO grade 4 astrocytomas (n = 22, 64.7%) and IDH-wildtype glioblastomas (n = 12, 35.3%) had upregulated PRMT5 gene expression except in one case. Out of the 22 IDH-mutant tumors, 10 (45.5%) tumors showed MGMT-promoter methylation and 12 (54.5%) tumors had unmethylated MGMT. All IDH-wildtype tumors had unmethylated MGMT. There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma (p-value = 0.006). Statistically significant differences in progression-free survival (PFS) were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide (TMZ) or TMZ plus other chemotherapies, regardless of their IDH or MGMT-methylation status (p-value=0.0014). Specifically, IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation, who received only TMZ, have exhibited longer PFS. Conclusions: The relationship between PRMT5, MGMT-promoter, and IDH is not tri-directional. However, accumulation of D2-hydroxyglutarate (2-HG), which partially activates 2-OG-dependent deoxygenase, may not affect their activities. In IDH-wildtype glioblastomas, the 2HG-2OG pathway is typically inactive, leading to PRMT5 upregulation. TMZ alone, compared to TMZ-plus, can increase PFS in upregulated PRMT5 tumors. Thus, using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.


Subject(s)
Astrocytoma , DNA Methylation , DNA Modification Methylases , DNA Repair Enzymes , Disease Progression , Isocitrate Dehydrogenase , Mutation , Promoter Regions, Genetic , Protein-Arginine N-Methyltransferases , Tumor Suppressor Proteins , Humans , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , DNA Modification Methylases/genetics , DNA Modification Methylases/metabolism , Isocitrate Dehydrogenase/genetics , Male , Female , Astrocytoma/genetics , Astrocytoma/pathology , Middle Aged , Adult , Retrospective Studies , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Neoplasm Grading , Aged , Temozolomide/therapeutic use , Temozolomide/pharmacology , Gene Expression Regulation, Neoplastic
2.
ACS Omega ; 9(21): 23001-23012, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38826538

ABSTRACT

The literature does not provide any "high-performance thin-layer chromatographic (HPTLC)" techniques for the determination of a novel antidiabetic medicine, ertugliflozin (ERZ). Additionally, there are not many environmentally friendly analytical methods for ERZ measurement in the literature. A rapid, sensitive, and eco-friendly reversed-phase-HPTLC (RP-HPTLC) method was designed and validated in an attempt to analyze ERZ in marketed pharmaceutical tablets more precisely, accurately, and sustainably over the traditional normal-phase HPTLC (NP-HPTLC) method. The stationary phases used in the NP- and RP-HPTLC procedures were silica gel 60 NP-18F254S and 60 RP-18F254S plates, respectively. For NP-HPTLC, a chloroform/methanol (85:15 v/v) mobile phase was used. However, ethanol-water (80:20 v/v) was the preferred method for RP-HPTLC. Four distinct methodologies, including the National Environmental Method Index (NEMI), Analytical Eco-Scale (AES), ChlorTox, and Analytical GREEnness (AGREE) approaches, were used to evaluate the greenness of both procedures. For both approaches, ERZ detection was carried out at 199 nm. Using the NP- and RP-HPTLC techniques, the ERZ measurement was linear in the 50-600 and 25-1200 ng/band ranges. The RP-HPTLC method was found to be more robust, accurate, precise, linear, sensitive, and eco-friendly compared to the NP-HPTLC approach. The results of four greenness tools demonstrated that the RP strategy was greener than the NP strategy and all other reported HPLC techniques. The fact that both techniques can assess ERZ when its degradation products are present implies that they both have characteristics that point to stability-indicating features. 87.41 and 99.28%, respectively, were the assay results for ERZ in commercial tablets when utilizing the NP and RP procedures. Based on several validation and greenness metrics, it was determined that the RP-HPTLC approach was better than the NP-HPTLC method. As a result, it is possible to determine ERZ in pharmaceutical products using the RP-HPTLC approach.

3.
J Neurosurg ; : 1-9, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701530

ABSTRACT

OBJECTIVE: Postoperative thrombotic complications represent a unique challenge in cranial neurosurgery as primary treatment involves therapeutic anticoagulation. The decision to initiate therapy and its timing is nuanced, as surgeons must balance the risk of catastrophic intracranial hemorrhage (ICH). With limited existing evidence to guide management, current practice patterns are subjective and inconsistent. The authors assessed their experience with early therapeutic anticoagulation (≤ 7 days postoperatively) initiation for thrombotic complications in neurosurgical patients undergoing cranial surgery to better understand the risks of catastrophic ICH. METHODS: Adult patients treated with early therapeutic anticoagulation following cranial surgery were considered. Anticoagulation indications were restricted to thrombotic or thromboembolic complications. Records were retrospectively reviewed for demographics, surgical details, and anticoagulation therapy start. The primary outcome was the incidence of catastrophic ICH, defined as ICH resulting in reoperation or death within 30 days of anticoagulation initiation. As a secondary outcome, post-anticoagulation cranial imaging was reviewed for new or worsening acute blood products. Fisher's exact and Wilcoxon rank-sum tests were used to compare cohorts. Cumulative outcome analyses were performed for primary and secondary outcomes according to anticoagulation start time. RESULTS: Seventy-one patients satisfied the inclusion criteria. Anticoagulation commenced on mean postoperative day (POD) 4.3 (SD 2.2). Catastrophic ICH was observed in 7 patients (9.9%) and was associated with earlier anticoagulation initiation (p = 0.02). Of patients with catastrophic ICH, 6 (85.7%) had intra-axial exploration during their index surgery. Patients with intra-axial exploration were more likely to experience a catastrophic ICH postoperatively compared to those with extra-axial exploration alone (OR 8.5, p = 0.04). Of the 58 patients with postoperative imaging, 15 (25.9%) experienced new or worsening blood products. Catastrophic ICH was 9 times more likely with anticoagulation initiation within 48 hours of surgery (OR 8.9, p = 0.01). The cumulative catastrophic ICH risk decreased with delay in initiation of anticoagulation, from 21.1% on POD 2 to 9.9% on POD 7. Concurrent antiplatelet medication was not associated with either outcome measure. CONCLUSIONS: The incidence of catastrophic ICH was significantly increased when anticoagulation was initiated within 48 hours of cranial surgery. Patients undergoing intra-axial exploration during their index surgery were at higher risk of a catastrophic ICH.

4.
ACS Omega ; 9(18): 20322-20330, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38737024

ABSTRACT

This study addresses the pivotal challenge of hydrogen production through methane decomposition, offering a pathway to achieving clean energy goals. Investigating the utilization of titania-modified zirconia dual redox supports (10TiZr) in iron or doped iron-based catalysts for the CH4 decomposition reaction, our research involves a thorough characterization process. This includes analyses of the surface area porosity, X-ray diffraction, Raman-infrared spectroscopy, and temperature-programmed reduction/oxidation. The observed sustained enhancement in catalytic activity over extended durations suggests the in situ formation of catalytically active sites. The introduction of Co or Ni into the 30Fe/10TiZr catalyst leads to the generation of a higher density of reducible species. Furthermore, the Ni-promoted 30Fe/10TiZr catalyst exhibits a lower crystallinity, indicating superior dispersion. Notably, the cobalt-promoted 30Fe/10TiZr catalyst achieves over 80% CH4 conversion and H2 yield within 3 h. Additionally, the Ni-promoted 30Fe/10TiZr catalyst attains a remarkable 87% CH4 conversion and 82% H2 yield after 3 h of the continuous process.

5.
Mol Biol Rep ; 51(1): 659, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748061

ABSTRACT

BACKGROUND: Mitochondrial DNA (mtDNA) has become a significant tool for exploring genetic diversity and delineating evolutionary links across diverse taxa. Within the group of cold-water fish species that are native to the Indian Himalayan region, Schizothorax esocinus holds particular importance due to its ecological significance and is potentially vulnerable to environmental changes. This research aims to clarify the phylogenetic relationships within the Schizothorax genus by utilizing mitochondrial protein-coding genes. METHODS: Standard protocols were followed for the isolation of DNA from S. esocinus. For the amplification of mtDNA, overlapping primers were used, and then subsequent sequencing was performed. The genetic features were investigated by the application of bioinformatic approaches. These approaches covered the evaluation of nucleotide composition, codon usage, selective pressure using nonsynonymous substitution /synonymous substitution (Ka/Ks) ratios, and phylogenetic analysis. RESULTS: The study specifically examined the 13 protein-coding genes of Schizothorax species which belongs to the Schizothoracinae subfamily. Nucleotide composition analysis showed a bias towards A + T content, consistent with other cyprinid fish species, suggesting evolutionary conservation. Relative Synonymous Codon Usage highlighted leucine as the most frequent (5.18%) and cysteine as the least frequent (0.78%) codon. The positive AT-skew and the predominantly negative GC-skew indicated the abundance of A and C. Comparative analysis revealed significant conservation of amino acids in multiple genes. The majority of amino acids were hydrophobic rather than polar. The purifying selection was revealed by the genetic distance and Ka/Ks ratios. Phylogenetic study revealed a significant genetic divergence between S. esocinus and other Schizothorax species with interspecific K2P distances ranging from 0.00 to 8.87%, with an average of 5.76%. CONCLUSION: The present study provides significant contributions to the understanding of mitochondrial genome diversity and genetic evolution mechanisms in Schizothoracinae, hence offering vital insights for the development of conservation initiatives aimed at protecting freshwater fish species.


Subject(s)
Phylogeny , Animals , Mitochondrial Proteins/genetics , Base Composition/genetics , DNA, Mitochondrial/genetics , Codon Usage/genetics , Trout/genetics , Trout/classification , Codon/genetics , Genome, Mitochondrial/genetics , Evolution, Molecular , Fish Proteins/genetics , Genomics/methods , Genetic Variation/genetics , Cyprinidae/genetics , Cyprinidae/classification
6.
Sci Rep ; 14(1): 11275, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760415

ABSTRACT

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels.


Subject(s)
Hepatitis B , Hepatitis C , Transients and Migrants , Humans , Qatar/epidemiology , Hepatitis B/epidemiology , Hepatitis B/virology , Hepatitis B/blood , Female , Transients and Migrants/statistics & numerical data , Hepatitis C/epidemiology , Adult , Male , Prevalence , Cross-Sectional Studies , Middle Aged , Hepacivirus/immunology , Hepacivirus/isolation & purification , Hepatitis B virus/isolation & purification , Hepatitis B virus/immunology , Young Adult , COVID-19/epidemiology , COVID-19/virology , Adolescent , Hepatitis B Surface Antigens/blood , Hepatitis C Antibodies/blood
7.
Article in English | MEDLINE | ID: mdl-38797498

ABSTRACT

INTRODUCTION: Cardiac substructure dose metrics are more strongly linked to late cardiac morbidities than whole-heart metrics. MR-guided radiation therapy (MRgRT) enables substructure visualization during daily localization, allowing potential for enhanced cardiac sparing. We extend a publicly available state-of-the-art deep learning (DL) framework, nnU-Net, to incorporate self-distillation (nnU-Net.wSD) for substructure segmentation for MRgRT. METHODS: Eighteen (Institute A) patients who underwent thoracic or abdominal radiation therapy on a 0.35 T MR-guided linac were retrospectively evaluated. On each image, one of two radiation oncologists delineated reference contours of 12 cardiac substructures (chambers, great vessels, and coronary arteries) used to train (n=10), validate (n=3), and test (n=5) nnU-Net.wSD leveraging a teacher-student network and comparing to standard 3D U-Net. The impact of using simulation data or including 3-4 daily images for augmentation during training was evaluated for nnU-Net.wSD. Geometric metrics (Dice similarity coefficient (DSC), mean distance to agreement (MDA), and 95% Hausdorff distance (HD95)), visual inspection, and clinical dose volume histograms (DVHs) were evaluated. To determine generalizability, Institute A's model was tested on an unlabeled dataset from Institute B (n=22) and evaluated via consensus scoring and volume comparisons. RESULTS: nnU-Net.wSD yielded a DSC (reported mean ± standard deviation) of 0.65±0.25 across the 12 substructures (Chambers: 0.85±0.05, Great Vessels: 0.67±0.19, and Coronary Arteries 0.33±0.16, mean MDA <3 mm, and mean HD95 <9 mm) while outperforming the 3D U-Net (0.583±0.28, p<0.01). Leveraging fractionated data for augmentation improved over a single MR-SIM timepoint (0.579±0.29, p<0.01). Predicted contours yielded DVHs that closely matched the clinical treatment plans where mean and D0.03cc doses deviated by 0.32±0.5 Gy and 1.42±2.6 Gy respectively. No statistically significant differences between Institute A and B volumes (p>0.05) for 11 of 12 substructures with larger volumes requiring minor changes and coronary arteries exhibiting more variability. CONCLUSIONS: This work is a critical step to rapid and reliable cardiac substructure segmentation to improve cardiac sparing in low-field MRgRT.

8.
Nanotechnology ; 35(32)2024 May 20.
Article in English | MEDLINE | ID: mdl-38697039

ABSTRACT

In the current study, the effect of rGO ratio on the N-dopped TiO2has been synthesized through sol-gel method. The prepared N-doped TiO2/rGO composites were examined for humidity sensing applications. The relationship between optical properties and the humidity sensing properties was studied. The structure, morphology, and bonding interaction have been examined using XRD, FT-IR, PL and HRTEM respectively. The average particle size as estimated from XRD and HRTEM was found to be about 9 nm. The optical properties have been studied using UV/ Vis. Spectroscopy. Further, optical parameters including refractive index and optical band gap energy have been estimated. The humidity sensing behavior of the resultant composites were evaluated in a wide range of humidity (7%-97% RH) at different testing frequencies. The optical band gap was found to be decreased as the amount of rGO increase. Among all prepared samples, both the optical parameters and humidity sensing experiments confirmed that the 0.5% rGO@N-dopped TiO2sample is the best candidate for the humidity sensing applications. The best optimum testing frequency was demonstrated to be 50 Hz. The sensor demonstrates a fast response and recovery times of 13 s and 33 s with low hysteresis and large sensitivity. The humidity sensing mechanism was studied using complex impedance spectroscopy at different RH levels under testing frequency range from 50 Hz to 5 MHz and testing voltage of 1 VAC. The produced structure demonstrated a promising material for humidity measuring devices.

9.
Poult Sci ; 103(7): 103799, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38759566

ABSTRACT

This study investigated the effect of different levels of zeolite in laying hen (Silver Montazah) diet and litter on productive performance, egg quality criteria, and economics during the second stage of production (40-56 wk of age). An experiment with a 3 × 4 factorial design was performed to study the effects of four levels of zeolite (0, 10, 15, and 20 g/kg feed) in the diet and three levels of zeolite (0, 1.5, and 2 kg/m2) in the litter. Adding zeolite to diet and litter significantly improved final BW and BW change, egg number, egg weight, egg mass, laying rate, feed consumption (FC), and feed conversion ratio (FCR), as well as egg quality criteria when compared to the unsupplemented group. Additionally, adding zeolite at a level of 2 kg /m2 litter and 20 g/kg diet achieved the greatest enhancement in productive performance features. Therefore, it can be suggested that the greatest results were obtained in laying farms when zeolite was added as a litter addition and as a supplement to feed.

10.
J Am Heart Assoc ; 13(11): e033447, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38780160

ABSTRACT

BACKGROUND: Coronary microvascular function and hemodynamics may play a role in coronary circulation and myocardial remodeling in patients with aortic stenosis (AS). We aimed to evaluate the relationship between myocardial blood flow and myocardial function in patients with AS, no AS, and aortic valve sclerosis. METHODS AND RESULTS: We included consecutive patients who had resting transthoracic echocardiography and clinically indicated positron emission tomography myocardial perfusion imaging to capture their left ventricular ejection fraction, global longitudinal strain (GLS), and myocardial flow reserve (MFR). The primary outcome was major adverse cardiovascular event (all-cause mortality, myocardial infarction, or late revascularization). There were 2778 patients (208 with aortic sclerosis, 39 with prosthetic aortic valve, 2406 with no AS, and 54, 49, and 22 with mild, moderate, and severe AS, respectively). Increasing AS severity was associated with impaired MFR (P<0.001) and GLS (P<0.001), even when perfusion was normal. Statistically significant associations were noted between MFR and GLS, MFR and left ventricular ejection fraction, and MFR and left ventricular ejection fraction reserve. After a median follow-up of 349 (interquartile range, 116-662) days, 4 (7.4%), 5 (10.2%), and 6 (27.3%) patients experienced a major adverse cardiovascular event in the mild, moderate, and severe AS groups, respectively. In a matched-control analysis, patients with mild-to-moderate AS had higher rates of impaired MFR (52.9% versus 39.9%; P=0.048) and major adverse cardiovascular event (11.8% versus 3.0%; P=0.002). CONCLUSIONS: Despite lack of ischemia, as severity of AS increased, MFR decreased and GLS worsened, reflecting worse coronary microvascular health and myocardial remodeling. Positron emission tomography-derived MFR showed a significant independent correlation with left ventricular ejection fraction and GLS. Patients with prosthetic aortic valve showed a high prevalence of impaired MFR.


Subject(s)
Aortic Valve Stenosis , Fractional Flow Reserve, Myocardial , Microcirculation , Myocardial Perfusion Imaging , Stroke Volume , Ventricular Function, Left , Ventricular Remodeling , Humans , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/diagnostic imaging , Female , Male , Ventricular Remodeling/physiology , Aged , Ventricular Function, Left/physiology , Myocardial Perfusion Imaging/methods , Fractional Flow Reserve, Myocardial/physiology , Stroke Volume/physiology , Microcirculation/physiology , Coronary Circulation/physiology , Echocardiography , Severity of Illness Index , Aged, 80 and over , Middle Aged , Retrospective Studies , Aortic Valve/physiopathology , Aortic Valve/diagnostic imaging , Aortic Valve/surgery
11.
Pharmaceuticals (Basel) ; 17(5)2024 May 06.
Article in English | MEDLINE | ID: mdl-38794159

ABSTRACT

Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) are classified as high-risk infections that can lead to death, particularly among older individuals. Nowadays, plant nanoparticles such as glycyrrhizic acid are recognized as efficient bactericides against a wide range of bacterial strains. Recently, scientists have shown interest in plant extract nanoparticles, derived from natural sources, which can be synthesized into nanomaterials. Interestingly, glycyrrhizic acid is rich in antioxidants as well as antibacterial agents, and it exhibits no adverse effects on normal cells. In this study, glycyrrhizic acid nanoparticles (GA-NPs) were synthesized using the hydrothermal method and characterized through physicochemical techniques such as UV-visible spectrometry, DLS, zeta potential, and TEM. The antimicrobial activity of GA-NPs was investigated through various methods, including MIC assays, anti-biofilm activity assays, ATPase activity assays, and kill-time assays. The expression levels of mecA, mecR1, blaR1, and blaZ genes were measured by quantitative RT-qPCR. Additionally, the presence of the penicillin-binding protein 2a (PBP2a) protein of S. aureus and MRSA was evaluated by a Western blot assay. The results emphasized the fabrication of GA nanoparticles in spherical shapes with a diameter in the range of 40-50 nm. The data show that GA nanoparticles exhibit great bactericidal effectiveness against S. aureus and MRSA. The treatment with GA-NPs remarkably reduces the expression levels of the mecA, mecR1, blaR1, and blaZ genes. PBP2a expression in MRSA was significantly reduced after treatment with GA-NPs. Overall, this study demonstrates that glycyrrhizic acid nanoparticles have potent antibacterial activity, particularly against MRSA. This research elucidates the inhibition mechanism of glycyrrhizic acid, which involves the suppressing of PBP2a expression. This work emphasizes the importance of utilizing plant nanoparticles as effective antimicrobial agents against a broad spectrum of bacteria.

12.
Polymers (Basel) ; 16(10)2024 May 10.
Article in English | MEDLINE | ID: mdl-38794547

ABSTRACT

Approximately 50% of global plastic wastes are produced from plastic packaging, a substantial amount of which is disposed of within a few minutes of its use. Although many plastic types are designed for single use, they are not always disposable. It is now widely acknowledged that the production and disposal of plastics have led to a plethora of negative consequences, including the contamination of both groundwater and soil resources and the deterioration of human health. The undeniable impact of excessive plastic manufacturing and waste generation on the global plastic pollution crisis has been well documented. Therefore, degradable polymers are a crucial solution to the problem of the non-degradation of plastic wastes. The disadvantage of degradable polymers is their high cost, so blending them with natural polymers will reduce the cost of final products and maximize their degradation rate, making degradable polymers competitive with industrial polymers that are currently in use daily. In this work, we will delineate various degradable polymers, including polycaprolactone, starch, and cellulose. Furthermore, we will elucidate several aspects of polyvinyl alcohol (PVA) and its blends with natural polymers to show the effects of adding natural polymers on PVA properties. This paper will study cost-effective and ecologically acceptable polymers by combining inexpensive natural polymers with readily accessible biodegradable polymers such as polyvinyl alcohol (PVA).

13.
Science ; 384(6695): 584-590, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38696583

ABSTRACT

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl, one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 22 , Meningomyelocele , Animals , Female , Humans , Male , Mice , Chromosomes, Human, Pair 22/genetics , DiGeorge Syndrome/genetics , Exome Sequencing , Folic Acid/administration & dosage , Folic Acid Deficiency/complications , Folic Acid Deficiency/genetics , Meningomyelocele/epidemiology , Meningomyelocele/genetics , Penetrance , Spinal Dysraphism/genetics , Risk , Adaptor Proteins, Signal Transducing/genetics
14.
Neurol Sci ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38565747

ABSTRACT

Alzheimer's disease, prevalent in individuals aged 60 and above, constitutes most dementia cases and significantly impairs memory and cognitive functions. With global Alzheimer's cases projected to triple by 2050, there is a pressing need for effective interventions. Lecanemab, a monoclonal antibody targeting amyloid-beta plaques, shows promise in slowing Alzheimer's progression. Positive clinical trial results have instilled hope in patients, prompting ongoing research to advance understanding and intervention possibilities. To contribute to this knowledge base, we conducted a systematic review and meta-analysis, focusing on lecanemab's efficacy and safety at a dosage of 10 mg/kg. This comprehensive approach aimed to address gaps in the current literature, scrutinize research disparities, and guide future investigations. Applying strict inclusion/exclusion criteria, we assessed study details, participant information, and intervention specifics, using the Cochrane risk of bias tool for quality evaluation. Statistical analyses, conducted with R software, included risk ratios and mean differences, assessing heterogeneity and publication bias. The meta-analysis reveals a significant positive effect of lecanemab (10 mg/kg biweekly) on cognitive outcomes in Alzheimer's disease. Consistent reductions in ADCOMS, CDR-SB, and ADAS-cog14 scores across studies indicate drug efficacy with narrow confidence intervals and no significant heterogeneity. While TEAE shows no significant difference, heightened risks of ARIA-E and ARIA-H associated with lecanemab underscore the need for vigilant safety monitoring in clinical practice. Despite the drug efficacy, the study emphasizes a balanced assessment of benefits and potential risks associated with lecanemab, providing critical insights for clinicians evaluating its use in addressing cognitive impairment in individuals with Alzheimer's disease.

15.
Open Vet J ; 14(1): 108-115, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38633168

ABSTRACT

Background: Biostimulation is a management practice that improves the reproductive parameters, potentiates the desire, and improves the reproductive efficiency during the short breeding season in camels. Aim: This study aims to investigate the concurrent changes in hormonal profiles in response to management and behavioral situations on camel farms in the Eastern region of Saudi Arabia. Methods: A total of 10 male and 50 female camels were used in this study. The hormonal profile of male camels was evaluated weekly starting from December to August. Results: The results show that both serum testosterone and cortisol levels increased (p < 0.01) from December to March compared to April to August. A strong negative correlation was observed between testosterone levels and temperature (r = -0.81, p < 0.05), and a similarly robust negative correlation was found between cortisol levels and temperature (r = -0.83, p < 0.05). The dominant rutting males showed higher levels of testosterone than the submissive males. Serum testosterone levels increased (p < 0.01) in males out of rutting after hearing the sounds of other couples before and during mating. Conclusion: Hearing sounds emitted during mating increases the testosterone output, and improves the libido of male camels during the nonrutting period. It is important to keep two individually housed males for mating purposes. One male joins the herd alone in winter (winter rutter), and the other joins in spring (spring rutter), this could keep the libido extended rutting and improve the reproductive performance in camel herds.


Subject(s)
Camelus , Testosterone , Male , Female , Animals , Camelus/physiology , Hydrocortisone , Reproduction/physiology
16.
Front Aging ; 5: 1373741, 2024.
Article in English | MEDLINE | ID: mdl-38605867

ABSTRACT

MicroRNAs (miRNAs) are short RNA molecules that are not involved in coding for proteins. They have a significant function in regulating gene expression after the process of transcription. Their participation in several biological processes has rendered them appealing subjects for investigating age-related disorders. Increasing data indicates that miRNAs can be influenced by dietary variables, such as macronutrients, micronutrients, trace minerals, and nutraceuticals. This review examines the influence of dietary factors and nutraceuticals on the regulation of miRNA in relation to the process of aging. We examine the present comprehension of miRNA disruption in age-related illnesses and emphasize the possibility of dietary manipulation as a means of prevention or treatment. Consolidating animal and human research is essential to validate the significance of dietary miRNA control in living organisms, despite the abundance of information already provided by several studies. This review elucidates the complex interaction among miRNAs, nutrition, and aging, offering valuable insights into promising areas for further research and potential therapies for age-related disorders.

17.
Ann R Coll Surg Engl ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563082

ABSTRACT

INTRODUCTION: Vascular access surgery (VAS) involves the creation and maintenance of arteriovenous access to facilitate haemodialysis. The prevalence of haemodialysis is rising despite increases in kidney transplants on a yearly basis. There is currently only one access surgery fellowship accredited by the Royal College of Surgeons of England. We aimed to establish the experience and perceived competence in access surgery of senior vascular surgery trainees. METHODS: A short questionnaire (SurveyMonkey) was used to survey all senior (ST6-ST8) vascular surgery trainees in Health Education England (HEE) vascular surgery training programmes. The short survey asked trainees to report their: (1) training grade; (2) training deanery; (3) experience of access surgery; and (4) whether senior trainees thought they would be able to independently undertake primary access surgery post-completion of training (post Certificate of Completion of Training). The survey was circulated via HEE deaneries and the vascular surgery trainees' society: the Rouleaux Club. RESULTS: Twenty-eight senior (ST6-ST8) vascular surgery trainees responded to the survey: 29.6% were ST6 level, 33.3% were ST7 and 37.1% were ST8. Deanery respondence was evenly spread, although London was overrepresented (37.1%). In total, 28.6% had been involved in fewer than 10 cases, 35.7% in 10-25 cases, and 35.7% in more than 25 cases. Almost 54% of senior vascular surgery trainees believed they would not be able to undertake independent access surgery once they had completed training. CONCLUSIONS: Competence in access surgery is an increasing requirement of a consultant vascular surgeon. More formalised training is required to adequately train the next generation of vascular surgeons.

18.
Ann R Coll Surg Engl ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563594

ABSTRACT

INTRODUCTION: Vascular access surgery (VAS) involves the creation and maintenance of arteriovenous access to facilitate haemodialysis. The prevalence of haemodialysis is rising despite increases in kidney transplants on a yearly basis. There is currently only one access surgery fellowship accredited by the Royal College of Surgeons of England. We aimed to establish the experience and perceived competence in access surgery of senior vascular surgery trainees. METHODS: A short questionnaire (SurveyMonkey) was used to survey all senior (ST6-ST8) vascular surgery trainees in Health Education England (HEE) vascular surgery training programmes. The short survey asked trainees to report their: (1) training grade; (2) training deanery; (3) experience of access surgery; and (4) whether senior trainees thought they would be able to independently undertake primary access surgery post-completion of training (post Certificate of Completion of Training). The survey was circulated via HEE deaneries and the vascular surgery trainees' society: the Rouleaux Club. RESULTS: Twenty-eight senior (ST6-ST8) vascular surgery trainees responded to the survey: 29.6% were ST6 level, 33.3% were ST7 and 37.1% were ST8. Deanery respondence was evenly spread, although London was overrepresented (37.1%). In total, 28.6% had been involved in fewer than 10 cases, 35.7% in 10-25 cases, and 35.7% in more than 25 cases. Almost 54% of senior vascular surgery trainees believed they would not be able to undertake independent access surgery once they had completed training. CONCLUSIONS: Competence in access surgery is an increasing requirement of a consultant vascular surgeon. More formalised training is required to adequately train the next generation of vascular surgeons.

19.
RSC Adv ; 14(15): 10445-10451, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38567336

ABSTRACT

Avapritinib (AVA) is the first medication authorized by the US-FDA in 2020 for the management of gastrointestinal stromal tumours (GISTs) that can't be treated by surgery. Cancer is among the most common causes of death worldwide and is the second most common cause of death after cardiovascular disease. Therefore, a quick, easy, sensitive, and straightforward fluorimetric approach was used to analyse AVA in pharmaceutical materials and blood plasma (pharmacokinetic). The suggested technique relies on 2% sodium dodecyl sulphate (SDS, pH 4) micellar system augmentation of the fluorescence of the tested drug. The technique demonstrated high relative fluorescence intensity (RFI) at 430 nm after excitation at 340 nm. Concentrations ranging from 20.0-400.0 ng mL-1 with a limit of quantitation of 9.47 ng mL-1 were used to obtain luminescence data for the studied medicine. In addition, the quantum yield of the AVA fluorescence was increased with the gradual addition of a surfactant at a concentration above its critical micellar level. This knowledge has been exploited to enhance the effectiveness of a spectrofluorometric technique for the estimation of AVA in human plasma (98.95 ± 1.22%) and uniformity tests with greenness assessments. The conditions for enhanced fluorescence were optimized and fully validated using US-FDA and International Conference on Harmonization (ICH) rules. This innovative strategy was expanded for AVA stability research in human plasma across various circumstances. This approach is an eco-friendly solution compared to traditional testing methods that use hazardous chemicals.

20.
Regul Toxicol Pharmacol ; 149: 105626, 2024 May.
Article in English | MEDLINE | ID: mdl-38636774

ABSTRACT

The healthcare systems of African nations heavily rely on importing and repackaging biological medicine. More than 70% of the pharmaceutical products consumed in Africa are imported. The localization of biosimilar production can have a positive impact on the availability and cost of these products by reducing the expenses for African governments and making essential healthcare products more accessible to the population. However, it is evident that the developing countries, particularly African nations, face various obstacles and difficulties in localizing biosimilar production. These challenges encompass development, manufacturing, evaluation, and registration processes. In this review, we will highlight the significant hurdles and achievements encountered during the localization process of biosimilars.


Subject(s)
Biosimilar Pharmaceuticals , Africa , Developing Countries , Drug Industry
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