Clinical Characteristics and Mortality of Intensive Care Patients With Intracerebral Hemorrhage and COVID-19: A Retrospective Cohort Analysis.

BACKGROUND: Since the COVID-19 pandemic, many studies have reported severe neurologic effects of the infection on the brain. Intracerebral hemorrhage (ICH) is a particular pathology that can result in these devastating neurologic effects. OBJECTIVES: The primary aim of our study is to investigate the possible difference in the clinical and laboratory characteristics of ICH between patients with positive COVID-19 tests and those with negative tests. The potential effect of this difference on the prognosis of the patients during their stay in the intensive care unit (ICU) is a secondary aim of the study. METHODS: In this retrospective cohort review, our data were collected from the electronic medical database of the Benghazi Medical Center (BMC) for the period from January 2021 to June 2022. We depended mainly on the admission paper information documented by emergency doctors, and mortality was measured depending on the clinical status after discharge from the ICU. RESULTS: This study included a sample of 72 patients, 34 patients (47.2%) were considered COVID-19 positive, and 38 patients (52.8%) were COVID-19 negative. The difference between groups was significant in ICH score ≥3 (higher in positive patients), INR (lower in positive patients), the incidence of new-onset hypertension (higher in positive patients), location of hematoma (infratentorial in positive patients), and intraventricular hemorrhage (IVH) extension (more in positive patients). Also, COVID-19 was significantly associated with ICH score ≥3 (OR 4.6, 95% CI 1.2 - 18.6, p = 0.03, R2 = 0.16), INR (𝛃 = 0.35, 95% CI 0.09 - 0.62, p < 0.003, R2 = 0.136), risk of ventilation (OR 14.1, 95% CI 3.5 - 56.9, p < 0.001, R2 = 0.26), hydrocephalus (OR 9.41, 95% CI 2.72 - 32.5, p = 0.001, R2 = 0.19), infratentorial location (OR 3.7, 95% CI 1.1 - 12.5, p = 0.04, R2 = 0.14), IVH extension (OR 3.5, 95% CI 1.2 - 10.4, p = 0.03, R2 = 0.09), new-onset hypertension (OR 4.2, 95% CI 1.5 - 11.9, p = 0.007, R2 = 0.10), and mortality (OR 4.9, 95% CI 1.6 - 15.3, p = 0.04, R2 = 0.15). The difference in survivability between groups was statistically insignificant (X2 = 0.41, log-rank, P = 0.53). CONCLUSION: The current study demonstrates, with sufficient evidence, that COVID-19 infection causes a significant change in some critical baseline characteristics like INR values, location, and IVH extension that influence the prognosis of ICH in ICU patients.

Anterior Column Release: With Great Lordosis Comes Great Risk of Complications-A Case Series.

STUDY DESIGN: Retrospective review. OBJECTIVE: We sought to characterize complications associated with anterior column release (ACR). SUMMARY OF BACKGROUND DATA: Correction of positive sagittal imbalance was traditionally completed with anterior column grafts or posterior osteotomies. ACR is a minimally invasive technique for addressing sagittal plane deformity by restoring lumbar lordosis. METHODS: We conducted a retrospective review of consecutive patients who underwent ACR in a prospectively kept database at a tertiary care academic center from January 2012 to December 2018. The prespecified complications were hardware failure (rod fracture, hardware loosening, or screw fracture), proximal junctional kyphosis, ipsilateral thigh numbness, ipsilateral femoral nerve weakness, arterial injury requiring blood transfusion, bowel injury, and abdominal pseudohernia. RESULTS: Thirty-eight patients were identified. Thirty-five patients had ACR at L3-4, 1 had ACR at L4-5, and 1 patient had ACR at L2-3 and L3-4. Eighteen patients (47.4%) had one of the prespecified complications (10 patients had multiple). Ten patients developed hardware failure (26.3%); 8 patients (21.1%) had rod fracture, 4 (10.5%) had screw fracture, and 1 (2.6%) had screw loosening. At discharge, rates of ipsilateral thigh numbness (37.8%) and hip flexor (37.8%)/quadriceps weakness (29.7%) were the highest. At follow-up, 6 patients (16.2%) had ipsilateral anterolateral thigh numbness, 5 (13.5%) suffered from ipsilateral hip flexion weakness, and 3 patients (5.4%) from ipsilateral quadriceps weakness. Arterial injury occurred in 1 patient (2.7%). Abdominal pseudohernia occurred in 1 patient (2.7%). There were no bowel injuries observed. CONCLUSIONS: ACR is associated with a higher than initially anticipated risk of neurological complications, hardware failure, and proximal junctional kyphosis.

The ultrastructure of peroxisomes in the kidney of the camel (Camelus dromedarius).

Dromedary camels can survive and reproduce in desert areas. The unique anatomical structure of the kidney enables the camel to prevent water loss. The present study aimed to investigate the ultrastructure of the peroxisomes in the normal kidney of the adult dromedary camel. Tissue samples were taken from the cortex and outer medulla of the kidney of eight camels. The samples were then processed for histological and ultrastructural investigations. The epithelial cells of the proximal tubules displayed peroxisomes with varying sizes and shapes. The peroxisomes were observed in either dispersed or clustered arrangement. Each peroxisome exhibited a homogenous matrix enveloped by a single membrane. Several peroxisomes exhibited one or more dark marginal plates that were always strongly associated with the smooth endoplasmic reticulum. The intensity of the peroxisomal matrix differed significantly, either within the same cell or across different cells. The intensity was light or dark, with a few peroxisomes presenting a similar intensity to that of the mitochondria. Some peroxisomes contained nucleoids within their matrix. The peroxisomes in the first and second sections of proximal convoluted tubules were scattered and primarily located in the region between the microvilli and the underlying mitochondria. The peroxisomes in the third region were abundant and frequently aggregated in clusters throughout the cytoplasm. In the fourth region, the number of peroxisomes was low. The proximal straight tubule had a limited quantity of peroxisomes. In conclusion, peroxisomes in the proximal tubule in kidney of normal dromedary camel were similar in shape and size to other mammals; however, heterogeneity exists as a result of differences in species-specific peroxisomal proteins. Peroxisomes are suggested to be a major source of metabolic energy and act as hydrogen peroxide (H2O2) scavengers, resulting in the release of water and oxygen.

Tailored portable electrochemical sensor for dopamine detection in human fluids using heteroatom-doped three-dimensional g-C3N4 hornet nest structure.

BACKGROUND: There is widespread interest in the design of portable electrochemical sensors for the selective monitoring of biomolecules. Dopamine (DA) is one of the neurotransmitter molecules that play a key role in the monitoring of some neuronal disorders such as Alzheimer's and Parkinson's diseases. Facile synthesis of the highly active surface interface to design a portable electrochemical sensor for the sensitive and selective monitoring of biomolecules (i.e., DA) in its resources such as human fluids is highly required. RESULTS: The designed sensor is based on a three-dimensional phosphorous and sulfur resembling a g-C3N4 hornet's nest (3D-PS-doped CNHN). The morphological structure of 3D-PS-doped CNHN features multi-open gates and numerous vacant voids, presenting a novel design reminiscent of a hornet's nest. The outer surface exhibits a heterogeneous structure with a wave orientation and rough surface texture. Each gate structure takes on a hexagonal shape with a wall size of approximately 100 nm. These structural characteristics, including high surface area and hierarchical design, facilitate the diffusion of electrolytes and enhance the binding and high loading of DA molecules on both inner and outer surfaces. The multifunctional nature of g-C3N4, incorporating phosphorous and sulfur atoms, contributes to a versatile surface that improves DA binding. Additionally, the phosphate and sulfate groups' functionalities enhance sensing properties, thereby outlining selectivity. The resulting portable 3D-PS-doped CNHN sensor demonstrates high sensitivity with a low limit of detection (7.8 nM) and a broad linear range spanning from 10 to 500 nM. SIGNIFICANCE: The portable DA sensor based on the 3D-PS-doped CNHN/SPCE exhibits excellent recovery of DA molecules in human fluids, such as human serum and urine samples, demonstrating high stability and good reproducibility. The designed portable DA sensor could find utility in the detection of DA in clinical samples, showcasing its potential for practical applications in medical settings.

Occult Intertrochanteric Fracture Detected by Bone Scan Imaging: A Case Report.

Femoral intertrochanteric fractures can be occult and not visible on plain radiographs, even when there is a high clinical suspicion. This case study reports an occult intertrochanteric fracture that was diagnosed using a bone scan rather than an MRI or CT scan. A 91-year-old woman arrived at the emergency room with a complaint of left hip pain after slipping at home. Clinical examination revealed tenderness, mild swelling, limited range of motion, and an inability to bear weight. Radiographs and CT scans of the hip and pelvis showed no evidence of a fracture. An MRI was planned, but the patient's agitation resulted in improper images. Consequently, a bone scan identified an ill-defined focal area with slightly increased activity, consistent with an intertrochanteric femur fracture. In such challenging scenarios, bone scans can still serve as an alternative diagnostic tool, aiding in clinical decision-making.

Total Hip Arthroplasty Following the Girdlestone Procedure in a Sickle Cell Disease Patient.

Sickle cell disease often leads to avascular necrosis (AVN) of the hip joint, resulting in joint pain and restricted range of motion. In cases where traditional treatments like total hip arthroplasty or core decompression may not suffice, the Girdlestone procedure, involving the resection of the femoral head, is considered. This case study centers on a 19-year-old male nursing student with sickle cell disease who underwent a Girdlestone procedure at 16 years of age, seeking relief from hip pain and limited mobility. However, the procedure led to leg length discrepancy and reduced hip function. Subsequent total hip arthroplasty successfully converted the prior procedure into a stable joint, improving the patient's range of motion and eliminating pain. The comprehensive surgical approach, including soft tissue releases and postoperative rehabilitation, significantly enhanced the patient's quality of life, emphasizing the importance of total hip arthroplasty as a superior intervention post-Girdlestone procedure.

Unveiling the potency of FDA-approved oxidopamine HBr for cervical cancer regulation and replication proteins.

Cervical Cancer remains a women's health concern worldwide and ranks among the most prevalent cancers, particularly in developing countries. Many women are diagnosed with cervical cancer, with a substantial number succumbing to the disease even after the availability of vaccines and drugs. The tumour microenvironment often exhibits immune evasion, including suppression of T-cell activity and altered cytokine, impacting the efficacy of therapeutic interventions and highlighting the need for treatments to modulate the immune response. Despite efforts to promote HPV vaccination and regular screenings, it causes many deaths, underscoring the urgent need for continued research, healthcare access, and rapid drug development or repurposing. In this study, we identified various proteins involved in cervical cancer cell cycle regulation and DNA replication proteins, performed the multitargeted docking with an FDA-approved library, and identified Oxidopamine HBr as a multitargeted drug. Studies extended with pharmacokinetics and compared with the standard values followed by DFT, which supported the compound as a multitargeted inhibitor. Further, the docked complexes were taken for the interaction fingerprints, and it was identified that there are many 9 polar, 5 hydrophobic, 2 aromatic, and 2 basic residues. We extended our studies for 100ns MD Simulation in water, and the computations explored the deviation and fluctuations under 2Å and many intermolecular interactions; the same trajectory files were used for the MM\GBSA studies. All the studies have supported the Oxidopamine HBr as a cervical cancer multitargeted inhibitor-however, experimental studies are needed before human use.

Targeted therapeutic management based on phytoconstituents for sickle cell anemia focusing on molecular mechanisms: Current trends and future perspectives.

The global epidemic of Sickle cell anemia (SCA) is causing thousands of children to die. SCA, a genetic disorder affecting the hemoglobin-globin chain, affects millions globally. The primary physiological issue in these patients is the polymerization of sickle hemoglobin within their red blood cells (RBCs) during their deoxygenating state. The RBC undergoes a sickle shape due to the polymerization of mutant hemoglobin within it and membrane deformation during anoxic conditions. To prevent complications, it is essential to effectively stop the sickling of RBCs of the patients. Various medications have been studied for treating SCA patients, focusing on antisickling, γ-globulin induction, and antiplatelet action. Natural and synthetic anti-sickling agents can potentially reduce patient clinical morbidity. Numerous clinical trials focused on using natural remedies for the symptomatic therapy of SCA. Medicinal plants and phytochemical agents have antisickling properties. Recent studies on plant extracts' natural compounds have primarily focused on in vitro RBCs sickling studies, with limited data on in vivo studies. This review discussed the potential role of phytoconstituents in the management of SCA.

From Traditional Use to Modern Evidence: The Medicinal Chemistry of Antimalarials from Genus Artemisia.

While the use of plants in traditional medicine dates back to 1500 B.C., modern advancements led to the development of innovative therapeutic techniques. On the other hand, in the field of anti-infective agents, lack of efficacy and the onset of resistance stimulate the search for novel agents. Genus Artemisia is one of the most diverse among perennial plants with a variety of species, properties, and chemical components. The genus is known for its therapeutic values and, in particular, for its role in the origin of antimalarial agents derived from artemisinin. In this review, we aim to provide an updated overview of the evolution of natural and natureinspired compounds related to the genus Artemisia that have been proven, in vitro and in vivo, to possess antimalarial properties. An overview of the chemical composition and a description of the ethnopharmacological aspects will be presented, as well as an updated report on in vitro and in vivo evidence that allowed the translation of artemisinin and its derivatives from traditional chemistry into modern medicinal chemistry. The biological and structural properties will be discussed, also dedicating attention to the challenging tasks that still are open, such as the identification of optimal combination strategies, the routes of administration, and the full assessment of the mechanism of action.

Dissecting molecular mechanisms underlying the inhibition of ß-glucuronidase by alkaloids from Hibiscus trionum: Integrating in vitro and in silico perspectives.

ß-Glucuronidase, a crucial enzyme in drug metabolism and detoxification, represents a promising target for therapeutic intervention due to its potential to modulate drug pharmacokinetics and enhance therapeutic efficacy. Herein, we assessed the inhibitory potential of phytochemicals from Hibiscus trionum against ß-glucuronidase. Grossamide and grossamide K emerged as the most potent ß-glucuronidase inhibitors with IC50 values of 0.73 ± 0.03 and 1.24 ± 0.03 µM, respectively. The investigated alkaloids effectively inhibited ß-glucuronidase-catalyzed PNPG hydrolysis through a noncompetitive inhibition mode, whereas steppogenin displayed a mixed inhibition mechanism. Molecular docking analyses highlighted grossamide and grossamide K as inhibitors with the lowest binding free energy, all compounds successfully docked into the same main binding site occupied by the reference drug Epigallocatechin gallate (EGCG). We explored the interaction dynamics of isolated compounds with ß-glucuronidase through a 200 ns molecular dynamics (MD) simulation. Analysis of various MD parameters revealed that grossamide and grossamide K maintained stable trajectories and demonstrated significant energy stabilization upon binding to ß-glucuronidase. Additionally, these compounds exhibited the lowest average interaction energies with the target enzyme. The MM/PBSA calculations further supported these findings, showing the lowest binding free energies for grossamide and grossamide K. These computational results are consistent with experimental data, suggesting that grossamide and grossamide K could be potent inhibitors of ß-glucuronidase.

Galangin attenuates chlorpyrifos-induced kidney injury by mitigating oxidative stress and inflammation and upregulating Nrf2 and farnesoid-X-receptor in rats.

Chlorpyrifos (CPF) is a highly toxic commonly used pesticide and can seriously harm human health. This study assessed the potential of galangin (GAL), an antioxidant flavonoid, to attenuate oxidative stress, inflammation and kidney injury caused by CPF, emphasizing the role of farnesoid-x-receptor (FXR) and Nrf2. Rats were supplemented with CPF and GAL for 28 days. CPF increased serum creatinine, urea and Kim-1, provoked several tissue alterations, and increased kidney ROS, malondialdehyde (MDA), NF-κB p65, TNF-α, iNOS, and caspase-3. GAL effectively ameliorated serum kidney injury markers, ROS, MDA, and TNF-α, suppressed NF-κB p65, iNOS, and caspase-3, and enhanced antioxidants. GAL suppressed Keap1 and upregulated FXR, Nrf2, HO-1 and NQO-1 in CPF-administered rats. GAL exhibited binding affinity with Keap1, FXR, caspase-3, iNOS, HO-1, and NF-κB. In conclusion, GAL is effective in preventing CPF nephrotoxicity by attenuating oxidative stress and inflammation. This protection is linked to upregulation of antioxidants, Nrf2/HO-1 signaling and FXR.

Association Between Baseline Macular Morphologic Features on Optical Coherence Tomography and Visual Outcomes in Patients with Vogt-Koyanagi-Harada Disease.

PURPOSE: The choroidal thickening and serous retinal detachments that characterize Vogt-Koyanagi-Harada (VKH) disease can be imaged in detail using spectral domain optical coherence tomography (SD-OCT). Whether specific qualitative and quantitative SD-OCT features at presentation were associated with visual outcomes in a randomized controlled trial comparing methotrexate to mycophenolate for steroid-sparing control of uveitis were evaluated. METHODS: An exploratory subanalysis of data from the FAST trial in which SD-OCT images from VKH participants were analyzed for presence/absence of bacillary detachments, retinal pigment epithelium (RPE) folds, and internal limiting membrane (ILM) fluctuations was performed. A modified RPE undulation index was calculated to provide a quantifiable surrogate marker for choroidal folds. RESULTS: SD-OCT images were available from 158 eyes with VKH. At baseline, bacillary detachments were present in 23.5% of eyes, RPE folds in 22.8% of eyes, and ILM fluctuations in 35.2% of eyes. For each 0.1 unit increase in modified RPE undulation index, there was an associated 0.13 increase in mean logMAR BSCVA at baseline. None of the SD-OCT features were associated with BSCVA at the 6-month primary endpoint. Indeed, mean final BSCVA was similar in those with and without the SD-OCT features of interest at baseline, and was between 0.1 and 0.2 logMAR (Snellen visual acuity 20/25 to 20/30). CONCLUSIONS: While eyes with VKH may present with a variety of SD-OCT imaging pathology prior to starting immunosuppression with methotrexate or mycophenolate mofetil, final visual outcome in our study was excellent. With appropriate immunosuppression, good visual outcomes are possible in VKH.ClinicalTrials.gov Identifier NCT01829295Date of Registration: April 11, 2013.

Clinical Performance of Computer-Aided Design (CAD)/Computer-Aided Manufacturing (CAM) Resin Nanoceramic Endocrowns in Restoring Molars: An In Vivo Study.

Background It is difficult to determine the optimal method for restoring endodontically treated teeth, as several factors affect this decision. Functional requirements and the amount of remaining coronal tissue are considered the most important factors in choosing the best restoration for those teeth. Endocrown was introduced as a conservative alternative for endodontically treated and coronally damaged teeth. Aim The aim of this study is to assess the clinical performance of the nanoceramic system for molar endocrowns by evaluating color change, gingival condition, prosthesis integrity, and the presence of secondary caries. Materials and methods The sample consisted of 20 endocrowns. The teeth were prepared with at least 2 mm of wall thickness and a cavity depth of 4 mm from the occlusal surface. The final impression was taken, and the prostheses were adhered using dual-cure resin cement. It was clinically evaluated according to clinical success criteria (United States Public Health Service) in terms of color stability, gingival indexes, integrity of the restoration, and the presence of secondary caries after a week, three months, six months, and a year. The statistical study was conducted using IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, NY, USA), and the results were considered statistically significant at the 95% level of significance. The Friedman test was used to study the significance of the differences in the average values of color change, plaque index, and the integrity of the prostheses during follow-up periods. Results The study showed a gradual increase in the degree of color change with follow-up periods. Furthermore, there was no significant difference in the incidence of gingival changes, the integrity of the prosthetic margins, or the occurrence of secondary caries during the follow-up periods. Conclusions Within the limitations of this study, an endocrown made of CeraSmart nanoceramic is an acceptable option for crowning decayed and endodontic-treated molars with acceptable clinical performance.

Public Awareness and Knowledge of Sleeve Gastrectomy in the Southwest Region of Saudi Arabia.

Background Obesity is a major global health concern, causing significant health dilemmas. Large groups of Saudi individuals are considered obese, with significant implications for medical practice. Bariatric surgery, including sleeve gastrectomy, is a crucial intervention for severe obesity, although it is associated with potential complications. This study aims to investigate the public knowledge about the indications and consequences of sleeve gastrectomy in the Southwest region of Saudi Arabia and assess their general awareness of sleeve gastrectomy. Methodology This descriptive, cross-sectional, online-based study included 347 individuals from the Southwest region of Saudi Arabia. Data were collected via an online questionnaire and analyzed using SPSS version 27 (IBM Corp., Armonk, NY, USA). Results This study included 347 participants, with a majority being females (88.5%, n = 307) and Saudis (98.6%, n = 342). The most common age group was 21-25 years (34%, n = 118), followed by those over 40 years of age (26.5%, n = 92). Most participants resided in Al-Qunfudhah (66.3%, n = 230) and held a bachelor's degree (75.8%, n = 263). Nearly half were students (48.7%, n = 169), and 56.2% (n = 195) earned less than 5,000 per month. The prevalent weight range was 40-60 kg (46.1%, n = 160), and most participants' height was 150-160 cm (58.5%, n = 203). Overall, 61% (x̄ = 211.6) of the respondents had good knowledge about sleeve gastrectomy, with 70.3% (x̄ = 244) understanding its general aspects, 56.1% (x̄ = 194.5) knowing the indications, and 60.1% (x̄ = 208.7) aware of the complications. Conclusions The majority of residents of the Southwest region of Saudi Arabia have moderate levels of knowledge regarding sleeve gastrectomy. However, the study demonstrated substantial gaps in knowledge and awareness regarding sleeve gastrectomy, mainly about its indications and potential.

Thermal disorder prevents the suppression of ultra-fast photochemistry in the strong light-matter coupling regime.

Strong coupling between molecules and confined light modes of optical cavities to form polaritons can alter photochemistry, but the origin of this effect remains largely unknown. While theoretical models suggest a suppression of photochemistry due to the formation of new polaritonic potential energy surfaces, many of these models do not account for the energetic disorder among the molecules, which is unavoidable at ambient conditions. Here, we combine simulations and experiments to show that for an ultra-fast photochemical reaction such thermal disorder prevents the modification of the potential energy surface and that suppression is due to radiative decay of the lossy cavity modes. We also show that the excitation spectrum under strong coupling is a product of the excitation spectrum of the bare molecules and the absorption spectrum of the molecule-cavity system, suggesting that polaritons can act as gateways for channeling an excitation into a molecule, which then reacts normally. Our results therefore imply that strong coupling provides a means to tune the action spectrum of a molecule, rather than to change the reaction.

Relationship among micro-pollutants, economic growth, renewable energy, nanotechnology and ecological foot prints of China: evidence from panel data analysis.

An important concern is the availability of clean drinking water, which is an essential need for human survival. This issue arises due to the existence of hazardous micropollutants originating from various emission sources. Nanotechnology aids in the mitigation of micropollutants by assimilating and counteracting their effects, hence diminishing their influence on water and other ecosystems. The study investigates the relationship between nanotechnological progress, the adoption of renewable energy, environmental consequences, and economic growth in China, using the Environmental Kuznets Curve theory as a conceptual framework. The study employs panel cointegration tests to analyze structural breaks from 2000 to 2020. Nanotechnology is expected to reduce environmental degradation and the presence of micro-pollutants by increasing the use of renewable energy and promoting energy conservation. Nanotechnology is crucial for mitigating micro-pollutants and advancing sustainable development in this specific context. However, the literature also highlights the harmful consequences of nanoparticle emissions caused by nanotechnology on human and environmental health for a long duration, requiring more examination. This research is the first empirical inquiry into the relationship between improvements in nanotechnology, the use of renewable energy, economic growth, and ecological effect, all within the context of the Environmental Kuznets Curve theory. The results confirm the successful incorporation of all components with a focus on long-term outcomes. The findings suggest that the EKC hypothesis is relevant in China. In China, advancements in nanotechnology have a moderating effect on environmental degradation. The use of renewable energy sources in China enhances environmental circumstances. Given the offered empirical evidence, it is advisable for the government to have a leading role in the development of innovative nanotechnologies that have low emissions of nanoparticles. By using this approach, it will be possible to encourage the conservation of energy and the use of renewable sources in a more secure way, hence improving the effectiveness of sustainable development initiatives.

Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of ß-glucuronidase by coumarins from Hibiscus trionum.

Unraveling the intricacies of ß-glucuronidase inhibition is pivotal for developing effective strategies in applications specific to gastrointestinal health and drug metabolism. Our study investigated the efficacy of some Hibiscus trionum phytochemicals as ß-glucuronidase inhibitors. The results showed that cleomiscosin A and mansonone H emerged as the most potent inhibitors, with IC50 values of 3.97 ± 0.35 µM and 10.32 ± 1.85 µM, respectively. Mechanistic analysis of ß-glucuronidase inhibition indicated that cleomiscosin A and the reference drug EGCG displayed a mixed inhibition mode against ß-glucuronidase, while mansonone H exhibited noncompetitive inhibition against ß-glucuronidase. Docking studies revealed that cleomiscosin A and mansonone H exhibited the lowest binding affinities, occupying the same site as EGCG, and engaged significant key residues in their binding mechanisms. Using a 30 ns molecular dynamics (MD) simulation, we explored the interaction dynamics of isolated compounds with ß-glucuronidase. Analysis of various MD parameters showed that cleomiscosin A and mansonone H exhibited consistent trajectories and significant energy stabilization with ß-glucuronidase. These computational insights complemented experimental findings, underscoring the potential of cleomiscosin A and mansonone H as ß-glucuronidase inhibitors.

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.

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.

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.