Deciphering molecular mechanisms underlying the inhibition of ß-glucuronidase by xanthones from Centaurium spicatum.

Herein, we scrutinized the inhibitory potential of five xanthones and a flavonoid, sourced from Centaurium spicatum, against ß-glucuronidase activity. The results showed that gentisin and azaleatin emerged as the most potent inhibitors, with significantly lower IC50 values of 0.96 ± 0.10 and 0.57 ± 0.04 µM, respectively. The evaluation of enzyme kinetics unveiled that the isolated xanthones manifested inhibition of ß-glucuronidase through a mixed inhibition mode, whereas azaleatin exhibited a noncompetitive inhibition mechanism. The findings from molecular docking analysis unveiled that the compounds under investigation, particularly azaleatin, displayed comparatively diminished binding affinities towards ß-glucuronidase. Furthermore, the tested drugs were shown to occupy a common binding site as the employed reference drug. Our comprehensive Molecular Dynamics (MD) simulations analysis revealed consistent trajectories for the investigated drugs, wherein azaleatin and gentisin demonstrated notable stabilization of energy levels. Analysis of various MD parameters revealed that drugs with the lowest IC50 values maintained relatively stable interactions with ß-glucuronidase. These drugs were shown to exert notable alterations in their conformation or flexibility upon complexation with the target enzyme. Conversely, the flexibility and accessibility of ß-glucuronidase was reduced upon drug binding, particularly with azaleatin and gentisin, underscoring the stability of the drug-enzyme complexes. Analysis of Coul-SR and LJ-SR interaction energies unveiled consistent and stable interactions between certain isolated drugs and ß-glucuronidase. Azaleatin notably displayed the lowest average Coul-SR interaction energy, suggesting strong electrostatic interactions with the enzyme's active site and significant conformational variability during simulation. Remarkably, LJ-SR interaction energies across different xanthones complexes were more negative than their Coul-SR counterparts, emphasizing the predominant role of van der Waals interactions, encompassing attractive dispersion and repulsive forces, in stabilizing the drug-enzyme complexes rather than electrostatic interactions.

The Role of Alternative Medicine in Managing Type 2 Diabetes: A Comprehensive Review.

Diabetes, a chronic metabolic disorder marked by elevated blood glucose levels, is increasingly prevalent globally, significantly impacting health-related quality of life. Type 2 diabetes (T2DM), characterized by insulin resistance and inadequate insulin production, presents a substantial public health challenge, necessitating comprehensive management strategies. Conventional treatments, including lifestyle modifications and pharmacotherapy, are essential for glycemic control and preventing complications. However, adherence to these treatments is often limited, highlighting the need for alternative strategies. Complementary and alternative medicine (CAM) offers potential cost-effective and accessible approaches for managing T2DM. Key herbal remedies like cinnamon, fenugreek, and bitter melon, along with dietary supplements like chromium, magnesium, and vanadium, have shown promise in glycemic control. Mind-body therapies, including yoga, tai chi, and meditation, contribute to improved hemoglobin A1c and fasting blood glucose levels. Research supports the integration of CAM with conventional therapies, demonstrating enhanced clinical efficacy and reduced economic burden. However, challenges such as standardization, quality control, and potential risks of herbal medicines need careful consideration. Regulatory frameworks and ethical considerations are essential to ensure patient safety and informed decision-making. Patient education and effective communication between healthcare providers and patients are crucial for integrating CAM into diabetes management. Empowerment-based interventions and collaborative approaches can enhance self-management skills and clinical outcomes. Overall, integrating CAM with conventional treatments offers a holistic approach to managing T2DM, potentially improving patient outcomes and reducing healthcare costs.

Impact of adding zeolite to broilers' diet and litter on growth, blood parameters, immunity, and ammonia emission.

This work was designed to assess the impact of varying zeolite concentrations in diet and litter to enhance broiler's growth performance, immunity, and litter quality. A complete random arrangement was used for distributing 525 unsexed "Cobb 500" broiler chicks into seven treatments (75 chick / treatment), each treatment divided into 3 replicates (25 chicks / replicate). The 1st group (control one) received the recommended basal diet. Zeolite has been introduced to the basal diet (ZD) of the second, third, and fourth groups at concentrations of 5, 10, and 15 g/kg, respectively. The 5th, 6th and 7th groups used zeolite mixed with litter (ZL) at 0.5, 1, and 1.5 kg/m2 of litter, respectively. Due to the obtained results, adding zeolite with levels 15 g/kg of diet and 1.5 kg/1 m2 of litter, a significant improvement occurred in live body weight (LBW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR) and European production efficiency factor (EPEF). Also, transaminase enzymes (ALT and AST), creatinine, white blood cells (WBCs) and different Immunoglobulins were significantly increased with different zeolite levels, except urea concentrations which showed reduced due to different zeolite treatments. In addition, spleen relative weight hasn't been affected by zeolite treatments, even though thymus and bursa relative weights had been affected significantly. Moreover, the antibodies' production to Newcastle disease virus (NDV) and Avian influenza virus (AIV) had increased significantly with adding zeolite with levels 10 g/kg of diet and 1.5 kg/1m2 of litter. Litter quality traits (NH3 concentration, pH values, and Moisture content) were improved with zeolite addition. So, zeolite could be employed in both feed and litter of broilers to maximize their production, immunity and improve farm's climate.

Fetal gender prediction by monitoring circulating steroid hormones and some biochemical parameters in maternal dromedary camels.

To predict the sex of the foetus, healthy pregnant dromedary camels (n = 24) were included. Blood samples were collected for measurements of progesterone, estradiol, testosterone, and cortisol as well as total proteins, albumin, glucose, creatinine, blood urea nitrogen, phosphorus, calcium, creatine kinase, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), calcium, phosphorus, and magnesium. Statistical analysis revealed differences between pregnant camels and pregnant camels in terms of female or male foetuses depending on the actual sex of the born calf. The results revealed that testosterone and ALP concentrations were significantly (P < 0.001) greater in camels given to males than in those given to calves. There were strong positive correlations between male calf birth and testosterone and ALP concentrations (r = 0.864; P < 0.0001 and r = 0.637; P < 0.001, respectively). On the other hand, the cortisol, glucose and creatinine concentrations were significantly lower (P lower in camel calved males than in females). There were significant negative correlations between male calf birth and the cortisol, glucose and creatinine concentrations (r =-0.401; P = 0.052; r =-0.445; P = 0.029 and r =-0.400; P = 0.053, respectively). The concentrations of calcium, phosphorus, calcium/phosphorus ratio, magnesium, and albumin and the albumin/globulin ratio were not significantly different (P > 0.05) between the two groups. In conclusion, testosterone could be used as a biomarker to determine the sex of foetuses in dromedary camels.

Red Cell Alloimmunisation Among Sickle Cell Disease and Thalassemia Patients Following Rh- and K-Matched Red Cell Transfusion in Southwestern Saudi Arabia: A Multicenter Study.

Background: Alloimmunisation remains a major consequence of blood transfusion among sickle cell disease (SCD) and thalassemia patients due to the exposure to non-self-red blood cell (RBC) antigen. The complication is associated with transfusion reactions and delayed transfusion procedure because of the difficulty of finding compatible blood. This study aims to determine the prevalence of alloimmunisation to RBC and alloantibody specificities among SCD and thalassemia patients in, an endemic area of SCD and thalassemia, Jazan province of Saudi Arabia, from three major hospitals. Methods: This is a retrospective, multicenter cross-sectional study conducted on 1027 patients with SCD and thalassemia, which received Rh/K matched transfusions in 2019 in the three centers. Demographic data and medical records of participants from three transfusion institutions were collected and analysed. Results: A total of 1027 were enrolled in the cohort; 906 (88.2%) and 121 (11.8%) patients with SCD and thalassemia, respectively. There were 483 (47%) males and 544 (53%) females with median age of 15 (range 1-48). Among the studied population, 78 were alloimmunised with an overall alloimmunisation rate of 7.6%. These patients developed a total of 108 alloantibodies, and anti-E was the most detected antibody (25.9%) followed by anti-K (24.1%). Conclusion: The overall rate of alloimmunisation to RBC antigen among the studied population in Jazan was low compared to other areas in the country. Most alloantibodies detected were against E and K antigens. The knowledge of most encountered alloantibodies in our population will aid in selecting the most appropriate antigen-negative red cells. Further research, however, is needed to explore factors associated with residual risk of alloimmunisation in these patients.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Experimental and computational assessment of Antiparkinson Medication effects on meiofauna: Case study of Benserazide and Trihexyphenidyl.

Two concentrations (6.25 and 1.25 mg/L) were used for two Parkinson's disease medications, Benserazide, and Trihexyphenidyl, to test their effects on the meiobenthic nematofauna. It is predicted that these highly hydrosoluble drugs will end up in marine environments. The results showed that both medications when added alone, induced (i) important changes in the numbers and (ii) taxonomic composition. The impact of Benserazide and Trihexyphenidyl was also reflected in the (iii) functional traits of nematofauna, with the most affected categories following exposure being the trophic group 1B, the clavate tails, the circular amphids, the c-p2 life history, and the body length of 1-2 mm. These results were supported by the molecular interactions of the studied drugs with both GLD-3 and SDP proteins of Caenorhabditis elegans. (iv) The mixtures of both drugs did not show any changes in the nematode communities, suggesting that no synergistic or antagonistic interactions exist between them.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Objective sonographic measurements of renal pelvic diameter and renal parenchymal thickness can identify renal hypofunction and poor drainage in patients with antenatally detected unilateral ureteropelvic junction obstruction.

INTRODUCTION: Hydronephrosis grading systems risk stratify patients with potential ureteropelvic junction obstruction, but only some criteria are measured objectively. Most notably, there is no consensus definition of renal parenchymal thinning. OBJECTIVES: The objective of this study was to assess the association between sonographic measures of renal length, renal pelvic diameter, and renal parenchymal thickness and the outcomes of a)renal hypofunction(differential renal function{DRF} <40%) and b)high-risk renal drainage(T1/2 > 40 min). STUDY DESIGN: An institutional database of patients who had diuretic renograms(DR) for unilateral hydronephrosis was reviewed. Only infants with Society for Fetal Urology(SFU) grades 3/4 hydronephrosis without hydroureter on postnatal sonogram and had a DR within 120 days were included. The following measurement variables were analyzed: anterior posterior renal pelvic diameter(APRPD), renal length(RL), renal parenchymal thickness(PT), minimal renal parenchymal thickness(MPT = shortest distance from mid-pole calyx to parenchymal edge), and renal pyramidal thickness(PyrT). RL, PT, MPT, PyrT measurements were expressed as ratios (hydronephrotic kidney/contralateral kidney). Multivariate logistic regression was performed for each outcome by comparing three separate renal measurement models. Model 1: RLR, APRPD, MPTR; Model 2: RLR, APRPD, PTR, Model 3: RLR, APRPD, PyrTR. Individual performance of variables from the best performing model were assessed via ROC curve analysis. RESULTS: 196 patients were included (107 with SFU grade 3, 89 with SFU grade 4) hydronephrosis. Median patient age was 29[IQR 16,47.2] days. 10% had hypofunction, and 20% had T1/2 > 40 min 90% with hypofunction and 87% with high-risk drainage had SFU4 hydronephrosis. Model 1 exhibited the best performance, but on multivariate analysis, only APRPD and MPTR were independently associated with both outcomes. No other measure of parenchymal thickness reached statistical significance. The odds of hypofunction and high-risk drainage increase 10% per 1 mm increase in APRPD(aOR 1.1 [CI 1.03-1.2], p = 0.005; aOR 1.1 [CI 1.03-1.2], p = 0.003). For every 0.1unit increase in MPTR the odds of hypofunction decrease by 40%(aOR 0.6 [CI 0.4-0.9], p = 0.019); and the odds of high-risk drainage decrease by 30%(aOR 0.7 [CI 0.5-0.9], p = 0.011). Optimal statistical cut-points of APRPD >16 mm and/or MPTR <0.36 identified patients at risk for obstructive parameters on DR. DISCUSSION AND CONCLUSION: Of the sonographic hydronephrosis measurement variables analyzed, only APRPD and MPTR were independently associated with objective definitions of obstruction based on renal function and drainage categories. Patients who maintain APRPD <16 mm and/or MPTR >0.36 can potentially be monitored with renal sonograms as there is >90% chance that they will not have DRF<40% or T1/2 > 40 min.

The impact of different imaging modalities in diagnosis and management of patient with dural arteriovenous fistula: A rare case report.

In vascular neurosurgery, dural arteriovenous fistulas (DAVFs) are a difficult, challenging condition whose natural history and therapy are still debated. This case report presented a 30-year-old male patient who experienced intermittent headaches for two months, along with gradual weakness in all four limbs, resulting in quadriplegia. Magnetic resonance imaging (MRI), computed tomography (CT), and digital subtraction angiography (DSA) played a significant role in the diagnosis of the patient, in which the final diagnosis was vascular myelopathy due to Dural arteriovenous fistula (DAVF). A successful embolization procedure of arteriovenous fistula using balloon-assisted liquid embolic agents, through branches of the right occipital artery was performed, resulting in complete obliteration of the fistula. In order to improve the neurovascular symptoms that had previously been reported, the patient was effectively undergoing rehabilitation, with notable progress.

σ-Hole, lone-pair-hole, and π-hole site-based interactions in aerogen-comprising complexes: a comparative study.

Herein, the potential of ZO3 and ZF2 aerogen-comprising molecules (where Z = Ar, Kr, and Xe) to engage in σ-, lp-, and π-hole site-based interactions was comparatively studied using various ab initio computations. For the first time, a premier in-depth elucidation of the external electric field (EEF) influence on the strength of the σ-, lp-, and π-hole site-based interactions within the ZO3/ZF2⋯NH3 and ⋯NCH complexes was addressed using oriented EEF with disparate magnitude. Upon the energetic features, σ-hole site-based interactions were noticed with the most prominent preferability in comparison to lp- and π-hole analogs. This finding was ensured by the negative interaction energy values of -11.65, -3.50, and -2.74 kcal mol-1 in the case of σ-, lp-, and π-hole site-based interactions within the XeO3⋯ and XeF2⋯NH3 complexes, respectively. Detailedly, the strength of the σ- and lp-hole site-based interactions directly correlated with the atomic size of the aerogen atoms and the magnitude of the positively oriented EEF. Unexpectedly, an irregular correlation was noticed for the interaction energies of the π-hole site-based interactions with the size of the π-hole. Interestingly, the π-hole site-based interactions within Kr-comprising complexes exhibited higher negative interaction energies than the Ar- and Xe-comprising counterparts. Notwithstanding, a direct proportion between the interaction energies of the π-hole site-based interactions and π-hole size was obtained by employing EEF along the positive orientation with high strength. The present outcomes would be a fundamental basis for forthcoming progress in studying the σ-, lp-, and π-hole site-based interactions within aerogen-comprising complexes and their pertinent applications in materials science and crystal engineering.

Identifying the origin of delayed electroluminescence in a polariton organic light-emitting diode.

Modifying the energy landscape of existing molecular emitters is an attractive challenge with favourable outcomes in chemistry and organic optoelectronic research. It has recently been explored through strong light-matter coupling studies where the organic emitters were placed in an optical cavity. Nonetheless, a debate revolves around whether the observed change in the material properties represents novel coupled system dynamics or the unmasking of pre-existing material properties induced by light-matter interactions. Here, for the first time, we examined the effect of strong coupling in polariton organic light-emitting diodes via time-resolved electroluminescence studies. We accompanied our experimental analysis with theoretical fits using a model of coupled rate equations accounting for all major mechanisms that can result in delayed electroluminescence in organic emitters. We found that in our devices the delayed electroluminescence was dominated by emission from trapped charges and this mechanism remained unmodified in the presence of strong coupling.

The Burden of Stroke Mimics Among Hyperacute Stroke Unit Attendees with Special Emphasis on Migraine: A 10-Year Evaluation.

BACKGROUND AND OBJECTIVES: Stroke and migraine are common neurological illnesses that cause tremendous suffering for patients. Certain diseases can mimic the clinical manifestations of an actual stroke. Migraine is one of the most commonly reported stroke mimics. The main goals of this study are to look at the prevalence of stroke mimics on the stroke pathway of Sheffield Teaching Hospitals and how many of them are migraines. MATERIALS AND METHODS: A retrospective service evaluation was conducted at the hyperacute stroke unit (HASU) of the Royal Hallamshire Hospital (RHH) in the United Kingdom. The total admissions from 2013 to 2022 were collected from the Sentinel Stroke National Audit Programme database, and the number of stroke mimics was evaluated each year. The burden of migraine stroke mimics was also evaluated. Then, a one-year sample of stroke mimics was extracted to look for the types of each mimic. RESULTS: From 2013 to 2022, 45.75% (n = 12156) of the stroke pathway patients (n = 26573) were stroke mimics, with an increment of up to 55% in the years 2021 and 2022. During these 10 years, migraine stroke mimics accounted for 10.21% of admissions (n = 1240). The three most common mimics in a one-year sample of stroke pathway patients were migraine (14.70%) (n = 373), functional neurological disorders (FNDs) (7.17%) (n = 182), and Guillain-Barré syndrome (6.66%) (n = 169). Seizures, syncope, and metabolic derangements were reported as mimics in 4.17% (n = 106), 3.14% (n = 80), and 1.77% (n = 45), respectively. CONCLUSIONS: About half of the HASU attendees were stroke mimics rather than actual strokes, and the most common mimics were migraines.

Outcomes in Patients with Vogt-Koyanagi-Harada Disease from the First-line Antimetabolites for Steroid-sparing Treatment Uveitis Trial.

PURPOSE: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). RESULTS: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. CONCLUSIONS: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929.

Acridinedione-phthalimide conjugates: Intramolecular electron transfer and singlet oxygen generation studies for optical and photodynamic therapy applications.

We reported herein the synthesis, characterization of hybrid conjugates composed of phthalimide (Phth) and acridine-1,8-diones (Acr) for optical and medical applications. For the synthetic procedure, a three-step synthetic strategy has been utilized. The optical properties of the examined 1,8-acridinedione-phthalimide connected molecules (AcrPhth 1-5) have been examined utilizing various spectroscopic techniques, e.g., steady-state absorption and fluorescence, and time-correlated single photon counting. The steady-state absorption studies showed that AcrPhth 1-5 absorbs the light in the UV and visible region. The fluorescence studies of AcrPhth 1-5 exhibited significant fluorescence quenching compared to the acridinedione control compounds (Acr 1-5) suggesting the occurrence of electron-transfer reactions from the electron donating acridinedione moiety (Acr) to the electron accepting phthalimide moiety (Phth). The rate and efficiency of the electron-transfer reactions were determined from the fluorescence lifetime measurements indicating the fast electron-transfer processes of the covalently connected AcrPhth 1-5 conjugates. Computational studies supported the intramolecular electron-transfer reaction of AcrPhth conjugates using ab initio B3LYP/6-311G methods. In the optimized structures, the HOMO was found to be entirely located on the Acr entity, while the LUMO was found to be entirely on the Phth entity. Further, the synthesized compounds were tested as photosensitizers for generating the singlet oxygen species, which is a key factor in the photodynamic therapy (PDT) applications. The nanosecond laser flash measurements enable us to detect the triplet-excited states of examined Acr and AcrPhth conjugates, determining the triplet quantum yields, and direct detecting the singlet oxygen in an accurate way. From this observation, the singlet quantum yields were found to be in the range of 0.12-0.27 (for Acr 1-5) and 0.07-0.19 (for AcrPhth 1-5 conjugates). The molecular docking studies revealed that compound AcrPhth 2 exhibited high binding affinity with for key genes (p53, TOP2B, p38, and EGFR) suggesting its potential as a targeted anticancer therapy.

Biological Control of Tomato Bacterial Leaf Spots and Its Impact on Some Antioxidant Enzymes, Phenolic Compounds, and Pigment Content.

Tomato bacterial spots, caused by Xanthomonas campestris pv. vesicatoria (Xcv1) and X. euvesicatoria (Xe2), as well as bacterial specks, caused by two strains of Pseudomonas syringae pv. tomato (Pst1 and Pst2), represent significant threats to tomato production in the El-Sharkia governorate, often resulting in substantial yield losses. The objective of this study was to evaluate the efficacy of various biocontrol culture filtrates, including bacteria and fungi agents, in managing the occurrence and severity of these diseases, while also monitoring physiological changes in tomato leaves, including antioxidant enzymes, phenolics, and pigment content. The culture filtrates from examined Trichoderma species (T. viride, T. harzianum, and T. album), as well as the tested bacteria (Bacillus subtilis, Pseudomonas fluorescens, and Serratia marcescens) at concentrations of 25%, 50%, and 100%, significantly inhibited the proliferation of pathogenic bacteria In vitro. For the In vivo experiments, we used specific doses of 5 mL of spore suspension per plant for the fungal bioagents at a concentration of 2.5 × 107 spores/mL. The bacterial bioagents were applied as a 10 mL suspension per plant at a concentration of 1 × 108 CFU/mL. Spraying the culture filtrates of the tested bioagents two days before infection In vivo significantly reduced disease incidence and severity. Trichoderma viride exhibited the highest efficacy among the fungal bioagents, followed by T. harzianum and T. album. Meanwhile, the culture filtrate of B. subtilis emerged as the most potent among the bacterial bioagents, followed by P. fluorescens. Furthermore, applying these culture filtrates resulted in elevated levels of chitinase, peroxidase, and polyphenol oxidase activity. This effect extended to increased phenol contents, as well as chlorophyll a, chlorophyll b, and carotenoids in sprayed tomato plants compared to the control treatment. Overall, these findings underscore the potential of these biocontrol strategies to effectively mitigate disease incidence and severity while enhancing plant defense mechanisms and physiological parameters, thus offering promising avenues for sustainable disease management in tomato production.

Diagnostic Evaluation of Polycythemia Vera at High Altitude.

BACKGROUND: Polycythemia is a common medical problem, frequently acquired and reactive to secondary conditions. High-altitude-associated hypoxia contributes to the greater prevalence of polycythemia at altitude. Primary clonal polycythemia vera (PV), even though it is rare, requires a different therapeutic approach. Suspicion of PV usually drives the diagnostic workup of polycythemia. METHODS: In this retrospective lab record study, we collected all JAK2 tests requested over a three-year period. We analyzed requests that were made for the evaluation of polycythemia. Complete blood count (CBC) and imaging of the abdomen were collected. RESULTS: Out of 208 total requests, 136 were for the purpose of polycythemia evaluation. JAK2 mutation was positive (confirming the presence of PV) in 22 (16.7%) cases. PV patients have the usual demographics reported elsewhere. Additionally, PV patients exhibit distinct hemogram results featuring leukocytosis, thrombocytosis, and hypochromic microcytic red blood cells (RBCs) related to the associated iron deficiency. CONCLUSIONS: Many patients with polycythemia at altitude might be unnecessarily considered for an evaluation of PV, if hemoglobin/hematocrit is the sole deciding criterion. PV patients have a distinct CBC pattern that can be exploited to better select patients with polycythemia for further evaluation and thus reduce unnecessary workups.

Effects of immersing Japanese quail eggs in various doses of riboflavin on reproductive, growth performance traits, blood indices and economics.

This investigation aimed to evaluate the impact of immersion (IM) riboflavin treatment on the hatchability, production efficiency, and carcass characteristics of Japanese quail eggs. A total of 260 eggs of Japanese quail birds were used for hatching and were randomly divided into 4 treatments with 5 replicates (13 eggs/replicate) in a fully randomized design. Hatching eggs were immersed in riboflavin for 2 min before incubation. The experiment treatments were designed as follows: G1 control group with no treatment, G2 treated with 3 g/L vit. B2 (IM), G3 treated with 4 g/L vit. B2 (IM) and G4 were treated with 5 g/L vit. B2 (IM). After hatching, 128 Japanese quail chicks, aged 7 d, were randomly grouped into 4 treatment groups, with 32 birds in each group. When quails were given vitamin B2 via immersion, they demonstrated significant enhancements in live body weight, body weight gain, feed consumption, and feed conversion ratio at different stages compared to the control group. Compared to control and other groups, the carcass parameters of Japanese quails given a 4 g/L immersion solution showed a significant improvement (P < 0.05). Hatchability and fertility (%) were considerably raised by Vit.B2 treatments of 3, 4, and 5g; the group immersed in 5 g/L had the highest percentages compared to the other groups. Furthermore, treated chickens with all concentrations of vitamin B2 had significantly higher blood indices than the controls. During the exploratory phase (1-6 wk) of age, the highest returns were reported in G4 treated with 5g/L vit. B2 (IM). Treating Japanese quail eggs with different dosages of vitamin B2 by immersion may be recommended to improve their productive and reproductive performance, blood indices, carcass traits, and economic efficiency.