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PURPOSE: Stereotactic radiosurgery (SRS) for brain metastases is frequently prescribed to the maximum tolerated dose to minimize the probability of local progression. However, many patients die from extracranial disease prior to local progression and may not require maximally aggressive treatment. Recently, improvements in models of SRS tumor control probability (TCP) and overall survival (OS) have been made. We predicted that by combining models of OS and TCP, we could better predict the true risk of local progression after SRS than by using TCP modeling alone. METHODS AND MATERIALS: Records of patients undergoing SRS at a single institution were reviewed retrospectively. Using established TCP and OS models, for each patient, the probability of 1-year survival [p(OS)] was calculated, as was the probability of 1-year local progression [p(LP)]) for each treated lesion. Joint-probability was used to combine the models [p(LP,OS)=p(LP)*p(OS)]. Analyses were conducted at the individual metastasis and whole-patient levels. Fine-Gray regression was used to model p(LP) or p(LP,OS) on the risk of local progression after SRS, with death as a competing risk. RESULTS: At the patient level, 1-year local progression was 0.08 (95% CI, 0.03-0.15), median p(LP,OS) was 0.13 (95% CI, 0.07-0.2), and median p(LP) was 0.29 (95% CI, 0.22-0.38). At the metastasis level, 1-year local progression was 0.02 (95% CI, 0.01-0.04), median p(LP,OS) was 0.05 (95% CI, 0.02-0.07), and median p(LP) was 0.10 (95% CI, 0.07-0.13). p(LP,OS) was found to be significantly associated with the risk of local progression at the patient level (P = .048) and metastasis level (P = .007); however, p(LP) was not (P = .16 and P = .28, respectively). CONCLUSIONS: Simultaneous modeling of OS and TCP more accurately predicted local progression than TCP modeling alone. Better understanding which patients with brain metastases are at risk of local progression after SRS may help personalize treatment to minimize risk without sacrificing efficacy.

Abstract Objective Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for assessing myocardial infarction lesions, offering precise myocardial tissue characterization. Elevated transverse relaxation time (T2) serves as a specific indicator of increased myocardial water content, thus becoming a valuable index for myocardial edema. However, conventional T2-weighted CMR sequence exhibits several limitations, primarily providing qualitative information. In contrast, recently developed quantitative T2 mapping techniques overcome these limitations, enabling a more reliable assessment of myocardial edema. These techniques offer the advantage of diagnosing and monitoring myocardial injury without the necessity of contrast agents. Our study aims to add to a growing literature demonstrating the efficacy of quantitative T2 mapping technique to detect and quantify regions of myocardial edema post-myocardial infarction. Result Native T1 and T2 mapping accurately identified myocardial edema in all patients enrolled in the study. Notably, native T1 and T2 values exhibited a significant elevation in the infarcted myocardium compared to the remote myocardium (for T1: 1295.50 ± 87.65 vs. 1074.95 ± 92.86 ms, respectively; and for T2: 74.63 ± 6.51 vs. 52.53 ± 6.26 ms, respectively; p

Abstract The current study was assigned to determine the putative preventive role of vinpocetine (VIN) in cervical hyperkeratosis (CHK) in female rats. Estradiol Benzoate (EB) was utilized in a dose f (60 μg/100 g, i.m) three times/week for 4 weeks to induce cervical hyperkeratosis. VIN was administered alone in a dose of (10 mg/kg/day, orally) for 4 weeks and in the presence of EB. Levels of malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), interleukin-18 (IL-18), IL-1β, tumor necrosis factor-alpha (TNF-α) were measured in cervical tissue. The expression of NLRP3/GSDMD/Caspase-1, and SIRT1/Nrf2 was determined using ELISA. Cervical histopathological examination was also done. EB significantly raised MDA, NOx, TNF-α, IL-18, IL-1β, and GSDMD and up-regulated NLRP3/Caspase-1 proteins. However, GSH, SIRT1, and Nrf2 levels were reduced in cervical tissue. VIN significantly alleviates all biochemical and histopathological abnormalities. VIN considerably mitigates EB-induced cervical hyperkeratosis via NLRP3-induced pyroptosis and SIRT1/Nrf2 signaling pathway.

Abstract Sepsis is a pathological and biochemical disorder induced by numerous infections, leading to critical illness and a high mortality rate worldwide. Vincamine is an indole alkaloid compound obtained from the leaves of Vinca minor. The present study aims to investigate the hepato-protective activity of vincamine during colon ligation puncture (CLP)-induced sepsis at the molecular level. Sepsis was induced using the CLP model. Liver function enzymes such as ALT and AST were analyzed. The hepatic antioxidant status (SOD and GSH), lipid peroxidation (MDA), the pro-inflammatory cytokines (TNFα, IL-6, and IL-1β), bax, bcl2, and cleaved caspase 3 proteins were estimated. Nrf-2 and Keap-1 protein expression was evaluated using western blotting. Histopathological investigation of liver tissues was also performed. CLP-induced sepsis led to liver injury through the elevation of ALT and AST liver enzymes. Oxidative stress was initiated during CLP via the suppression of hepatic GSH content and SOD activity and the elevation of MDA. The inflammatory condition was activated by the upregulation of TNFα, IL-6, IL-1β, and Keap-1 and the downregulation of Nrf-2 proteins. The apoptosis was initiated through the activation of bax and cleaved caspase 3 protein expression and inhibition of bcl2 protein expression. However, vincamine significantly improved the hepatic histological abnormalities and decreased liver enzymes (ALT and AST). It ameliorated oxidative stress, as evidenced by reducing the hepatic MDA content and increasing the SOD activity and GSH content. Moreover, vincamine reduced the hepatic content of TNFα, IL-6, IL-1β, and Keap-1 and increased Nrf-2 protein expression. Additionally, it upregulated bcl2 protein expression and downregulated bax and cleaved caspase 3 protein expression. Vincamine exhibited hepato-protective potential during CLP-induced sepsis via the cross-connection of antioxidant, anti-inflammatory, and anti-apoptotic activities by modulating TNFα/IL-6/IL-1β/Nrf-2/Keap-1 and regulating bax/bcl2/cleaved caspase 3 signaling pathways.

Therapeutic Area: CVD Prevention – Primary and Secondary Background: The non-linear correlation between peak metabolic workload and cardiovascular disease incidence is under scrutiny in this study, particularly within the low socioeconomic residents of South Bronx. Methods: A retrospective examination of 190 patients subjected to cardiac graded treadmill stress testing and MET level evaluation between January 2007 and July 2023 was performed. Patients with incomplete testing, known heart disease, prior strokes, peripheral artery disease, severe systemic conditions, and pregnancy were excluded. Participants were segregated into low (8) MET groups. The primary outcome was cardiovascular morbidity incidence. Data analysis was controlled for age, sex, cardiac disease family history, BMI, smoking, and DM, HTN, and HLD histories. Results: Of the 190 participants, (47.9% females, 52.1% males, mean age 53 ± 14) 20 (11%) had at least one CV morbidity during the study period. Adjusted models demonstrated that patients with MET >5 had 0.14 lower odds of a cardiovascular event than MET 5-8 patients (OR 0.86; 95% CI 0.20-3.82), whereas METS >8 patients had 1.8 times higher odds (OR 1.8, CI 95% 0.51-6.46). Conclusions: Among the low-income population, our findings challenge previous studies, suggesting a linear relationship between higher METs and increased cardiovascular events. This warrants further investigation to validate our findings.

Therapeutic Area: Peripheral Artery Disease Background: Peripheral artery disease (PAD) is a debilitating condition characterized by atherosclerosis in the peripheral arteries, affecting approximately 200 million people worldwide. Current treatment options for PAD, such as statins, have limitations in terms of efficacy and tolerability. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown promise in reducing cardiovascular events in hypercholesterolemic patients. This review focuses on the efficacy, safety, and clinical outcomes of PCSK9 inhibitors in PAD based on recent trials and literature. Methods: A comprehensive literature search was conducted using PubMed to identify relevant trials and studies evaluating PCSK9 inhibitors in PAD patients. Key trials including FOURIER and ODYSSEY were analyzed for efficacy in reducing LDL cholesterol levels and cardiovascular events, including myocardial infarction, stroke, coronary revascularization, and major adverse limb events. Safety data was compiled from multiple trials. Cost-effectiveness studies were also reviewed. Results: The FOURIER trial demonstrated that evolocumab significantly reduced LDL cholesterol by 59% (p$500,000 per QALY in some analyses), PCSK9 inhibitors may be cost-effective in specific high-risk populations. Conclusions: PCSK9 inhibitors demonstrate significant efficacy in lowering LDL cholesterol and reducing cardiovascular events in PAD patients, with a favorable safety profile. However, cost remains a barrier to widespread utilization. Current PAD treatment guidelines do not yet incorporate PCSK9 inhibitors. Further research is needed on long-term outcomes, cost-effectiveness, and the role of PCSK9 inhibitors in the context of current PAD management. PCSK9 inhibitors represent a promising therapeutic option for select high-risk PAD patients not at goal with statins alone.

Therapeutic Area: ASCVD/CVD Risk Factors Background: Cardiovascular disease remains a leading cause of morbidity and mortality worldwide. Identifying modifiable risk factors is crucial for risk stratification and prevention strategies. This study aimed to investigate the association between various metabolic parameters and the occurrence of cardiovascular events in a cohort of patients, with the goal of informing targeted interventions and risk assessment approaches. Methods: We conducted a retrospective analysis of 190 patients, evaluating the impact of metabolic equivalents (METs), history of chronic kidney disease (CKD), diabetes mellitus (DM), hyperlipidemia (HLD), hypertension (HTN), body mass index (BMI), and mean pulmonary hypertension resistance (MPHR) on the incidence of cardiac events, including myocardial infarction, unstable angina, and cardiac death. Logistic regression models were employed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Chi-square tests and tests for equality of variances were performed to assess statistical significance. Results: Patients with METs >8 had a higher incidence of cardiac events compared to those with METs ≤5 (56.3% vs. 12.5%, p=0.032). DM (46.9% vs. 22.2%, p=0.0026) and HTN (87.5% vs. 67.7%, p=0.0212) were also significantly associated with cardiac events. Mean BMI was higher in the cardiac event group (31.87 vs. 29.30, p=0.0168). After adjusting for confounders, the OR for METs >8 was 1.82 (95% CI 0.51-6.46, p=0.36). No significant associations were observed for HLD, CKD, family history of coronary artery disease, or peripheral vascular disease. Conclusions: Our findings underscore the importance of metabolic factors, particularly METs levels, DM, and HTN, in predicting cardiovascular risk. Elevated BMI was also associated with increased event occurrence. These results highlight the need for comprehensive management of metabolic disorders to mitigate cardiovascular disease burden. Future studies should explore targeted interventions and risk assessment strategies incorporating these metabolic parameters to optimize cardiovascular disease prevention and management.

Abstract Gemigliptin-Rosuvastatin single-pill combination is a promising therapeutic tool in the effective control of hyperglycemia and hypercholesterolemia. Organic sensors with high quantum yields have profoundly significant applications in the pharmaceutical industry, such as routine quality control of marketed formulations. Herein, the fluorescence sensor, 2-Morpholino-4,6-dimethyl nicotinonitrile 3, (λex; 226 nm, λem; 406 nm), was synthesized with a fluorescence quantum yield of 56.86% and fully characterized in our laboratory. This sensor showed high efficiency for the determination of Gemigliptin (GEM) and Rosuvastatin (RSV) traces through their stoichiometric interactions and simultaneously fractionated by selective solvation. The interaction between the stated analytes and sensor 3 was a quenching effect. Various experimental parameters and the turn-off mechanism were addressed. The adopted approach fulfilled the ICH validation criteria and showed linear satisfactory ranges, 0.2–2 and 0.1–1 μg/mL for GEM and RSV, respectively with nano-limits of detection less than 30 ng/mL for both analytes. The synthesized sensor has been successfully applied for GEM and RSV co-assessment in their synthetic polypill with excellent % recoveries of 98.83 ± 0.86 and 100.19 ± 0.64, respectively. No statistically significant difference between the results of the proposed and reported spectrophotometric methods in terms of the F- and t-tests. Ecological and whiteness appraisals of the proposed study were conducted via three novel approaches: the Greenness Index via Spider Diagram, the Analytical Greenness Metric, and the Red–Green–Blue 12 model. The aforementioned metrics proved the superiority of the adopted approach over the previously published one regarding eco-friendliness and sustainability. Our devised fluorimetric turn-off sensing method showed high sensitivity, selectivity, feasibility, and rapidity with minimal cost and environmental burden over other sophisticated techniques, making it reliable in quality control labs.

This work introduces an n-D algorithm to generate multi-dimensional Sigma Shift Matrix (nD-SSM) code sequences is proposed, which is based on spectral/temporal/spatial incoherent optical code division multiple access (OCDMA) system. Our proposed system is capable of generating code in accordance with the value of n, where $n=1$ , 2 and 3 for 1D, 2D, and 3D respectively. The nD-SSM codes improve system cardinality by eliminating multiple access interference and its accompanied phase induced intensity noise (PIIN). Additionally, the nD-SSM technique permits various users with different dimensions of codewords to send their data. The data will be sent with the lowest probability of interference. The design of transmitter-receiver structure of nD-SSM OCDMA system is described. Gaussian approximation is used to analyze performance of the proposed nD-SSM OCDMA system by investigating signal to noise ratio (SNR) and bit error rate (BER) under different conditions of transmission. The maximum allowable number of users with BER ~10-9 is 43, 108, 140, 158 and 600, respectively for 1D-SSM, 2D-SSM, 2D-DEU, 3D-PD and 3D-SSM codes, respectively at 622 Mbps. These numbers of users with the same value of BER decreased to 18 for 1D-SSM, 46 for 2D-SSM, 2 for 2D-DEU, 82 for 3D-PD, and 237 for 3D-SSM at 2.5 Gbps. At 10 Gbps, the maximum allowable number of users are 9, 24, 40, and 97 for 1D-SSM, 2D-SSM, 3D-PD, and 3D-SSM, respectively. Accordingly, the proposed 3D-SSM code supports the larger number of users at different data rates when compared to other codes.

PURPOSEEarly-onset colorectal cancer (EOCRC) is a rising health problem. The incidence of EOCRC has increased over the past 2 decades all over the world. Reports from Egypt since the 1990s have reported a higher incidence among young populations with no identifiable risk factors. The aim of this study was to assess EOCRC in Egypt regarding incidence, characteristics, treatment pattern, and survival compared with average age onset and elderly patients.MATERIALS AND METHODSThis was a retrospective, record-based, cohort study combining data from four different cancer centers in Egypt. We grouped patients according to age into three categories: the EOCRC group for patients age ≤45 years and the average age onset and elderly cancer group (for patients age ≥65 years).RESULTSThe study included 1,310 patients with histopathologically proven colorectal cancer, representing four different geographical areas in Egypt. Patients with EOCRC represented 42.4% of the study population. Female patients were 50.6% among the EOCRC group and 52.5% among the average age group. Rectal tumors were significantly higher in EOCRC (54.7% v 40.6%; P < .001). There was no significant difference between both groups regarding the tumor stage at presentation, obstruction, or presence of metastases at presentation. Patients with EOCRC had a significantly higher rate of peritoneum/adnexa metastases than the average age ones (12.3% in EOCRC v 6.9% in the average age group; P < .001). No statistically significant differences between EOCRC and average age groups in both disease-free survival and overall survival were reported.CONCLUSIONA comprehensive framework for the study of EOCRC is required in Egypt as well as a genomic analysis to identify possible underlying genetic alterations responsible for the high incidence of EOCRC.

Traditional elderly monitoring systems may misdiagnose and treat senior citizens due to inaccurate results, resulting in higher care costs and poorer health outcomes. Thus, the Internet of Things (IoT) was introduced to provide accurate, real-time monitoring data to improve overall performance. The IoT health system connects devices wirelessly to collect and analyze health data, monitor vital signs and physical activity, and provide real-time insights to improve health management. This paper aims to monitor real-time conditions as well as ensure the safety of senior citizens by developing a low-cost wearable prototype device to measure heart pulses, detect falls, and determine their actual location in an indoor space. The data is uploaded to IoT platforms like Blynk, Firebase, and Google Assistant, providing frequent updates on the elderly's health status and conditions and sending emergency messages, if necessary, to an Android application. A home control system is also developed to control the home appliances using mobile phones or voice control. A demonstration has been conducted to showcase the operation and functionality of the prototype. The proposed system has the capability to simplify the daily routines of the elderly while also granting caregivers greater control over their health and well-being.

BACKGROUND: Cholesteatomas are growths of squamous epithelium that can form inside the middle ear and mastoid cavity and damage nearby structures causing hearing loss when located at the petrous apex. The primary goal of petrous apex cholesteatoma resection is gross total removal with tympanoplasty and canal-wall up or canal-wall down tympanomastoidectomy. At present, there is no definitive surgical approach supported by greater than level 4 evidence in the literature to date. METHODS: A systematic review was conducted utilizing PubMed, Embase, and Scopus databases. Articles were screened and selected to be reviewed in full text. The articles that met inclusion criteria were reviewed for relevant data. Data analysis, means, and standard deviations were calculated using Microsoft Excel. RESULTS: After screening, five articles were included in the systematic review. There were a total of eight pediatric patients with nine total cholesteatomas removed. Conductive hearing loss was the most common (77%) presenting symptom. Perforations were noted in seven ears (86%). Recurrence was noted in 50% of patients with an average recurrence rate of 3.5 years (SD = 1.73). Average length of follow-up was 32.6 months (SD = 21.7). Canal-wall up was the most utilized technique (60%) and there were zero noted surgical complications. Five of the seven (71%) patients that experienced hearing loss from perforation noted improved hearing. CONCLUSION: Due to its rarity, diagnostic evaluation and treatment can vary. Further, multi-institutional investigation is necessary to develop population-level management protocols for pediatric patients affected by petrous apex cholesteatomas.

Wound healing, one of the most intricate and dynamic processes of the body, maintains skin integrity following trauma. One of the main issues that still exists is impaired wound healing, particularly for immunosuppressed patients. Recently, natural products from marine environments have been employed in wound-repairing activities. This work investigates the mesenchymal stem cells in the combined capacity of the bone marrow (BMMSC) for wound healing and Cystoseira sp. Algae extract in immunosuppressed rats. High-resolution liquid chromatography / MS investigation of Cystoseira extract revealed the prevalence of fatty acids that have wound-soothing potential. From constructed PPI network for wound healing and further analysis through molecular docking and molecular dynamics (MD) simulation experiments suggested that cystalgerone metabolite may be responsible for the wound healing-promoting effect of Cystoseira extract. According to the CD marker characterization of the BMMSC, 98.21% of them expressed CD90, and 97.1% expressed CD105. Sixteen d after immunity suppression (by 40 mg/kg hydrocortisone daily), an incision was made in the dorsal skin of the rat. The treatments were applied for 16 d and samples were taken from the tested groups on the 8th, 14th, and 16th days. The BMMSCs / Cystoseira group showed significantly improved wound closure, thickness, density of new layers, and skin elasticity than the control group (p < 0.001). The BMMSCs / Cystoseira combination significantly reduced the oxidative indicators, pro-inflammatory cytokines, and immune markers, according to the RT-PCR gene expression study. In order to delve deeper into the complex interconnections among wound healing-related biological targets and pinpoint key factors in this complex process, we engaged in network pharmacology and computational research. Subsequently, we conducted a comprehensive computational analysis, including reverse docking, free energy (ΔG) computation, and molecular dynamics simulations, on the molecular structures of the annotated compounds. The purpose of this investigation was to identify potential new targets for these chemicals as well as any potential interactions they may have with different signaling pathways related to the wound healing process. Our research indicates that the primary compounds of Cystoseira holds potential wound healing therapeutic activity. Although more safety testing and clinical studies are required, the combination has great potential for regenerative medicine and could be a revolutionary advance in the healing of the wounds of immunosuppressed patients.

Three years after its emergence, coronavirus disease 2019 (COVID-19) continues to be a leading cause of worldwide morbidity and mortality. This systematic review comprises relevant case reports that discuss non-multisystem inflammatory syndrome in children (non-MIS-C) and postacute sequalae of COVID-19 (PASC) in the paediatric population, also known as long COVID syndrome. The study aims to highlight the prevalent time interval between COVID-19 and the development of non-MIS-C post-infectious sequalae (PIS). Databases were searched for studies that met our inclusion and exclusion criteria. The final screening revealed an equal sex distribution where the commonest age intervals were school-age and adolescence, with 38% of the patients being older than six years. Interestingly, hospital admission during the course of COVID-19 was not a predictor of the subsequent PASC; forty-nine patients (44.9%) were hospitalized while sixty patients (55.1%) were not hospitalized. Moreover, the most predominant time interval between COVID-19 and the developing PASC was within 14 days from the start of COVID-19 infection (61%). These findings suggest a crucial link between COVID-19 and immune PIS in the paediatric population, especially those older than six years. Accordingly, follow-up and management are encouraged in case of unusual symptoms and signs following COVID-19 infection, regardless of the COVID-19 infection severity.

Clivia miniata (Lindl) is a member of the family Amaryllidaceae known for its chemically diverse alkaloids with a wide range of biological activities. Many reports revealed a direct role of oxidative stress in the early stage of Alzheimer’s disease (AD). Meanwhile, β-site amyloid precursor protein cleavage enzyme 1 (BACE-1) is a molecular target for the treatment of AD. We aimed to investigate C. miniata root, bulb, and aerial part chemical profiling, antioxidant, BACE-1, and AChE enzyme inhibitory activities. Results showed that the total root had the most potent radical scavenging activity as compared to the total bulb and aerial part, respectively. Ethanol root extract had the most potent BACE-1 inhibitory activity (IC50 = 0.02 ± 0.001 µg/mL) as compared to the bulb and aerial part (IC50 = 0.93 ± 0.13, 1.80 ± 0.24 µg/mL), respectively. Moreover, the total root extract mitigated AChE enzyme activity more than total bulb and aerial fractions with IC50 values of (0.06 ± 0.02, 0.58 ± 0.3, and 1.89 ± 0.42 µg/mL, respectively. Bioassay-guided acid-base fractionation confirmed superior BACE-1 inhibitory activity of the root fractions particularly, methylene chloride and ethyl acetate fractions with (IC50 values of 0.21 ± 0.60 and 0.01 ± 0.001 µg/mL), respectively. UPLC-MS analysis of ethyl acetate and methylene chloride fractions of C. miniata root led to the identification of eight phenolics and thirteen alkaloids, respectively. Molecular docking studies against BACE-1 protein revealed that lycorine di-hexoside, miniatine, and cliviaaline were the most promising hits. Further investigation of anti-AD potential of the aforementioned small molecules is required.

Cardiac arrest is a medical emergency affecting many adults around the world. The quality and efficacy of cardiopulmonary resuscitation [CPR] are associated with improved survival. Reported differences in CPR performance and survival among centres have motivated the resuscitation community to develop guidelines and tools to improve CPR outcomes.Many tools are proposed for the assessment of cardiac arrest aiming for identifying the underlying cause, especially reversible ones, assessing the response of the patient to resuscitation in order to restore the normal circulation. Each of these tools have its own limitations and even failure of improving survival rates.Point of care ultrasound [POCUS] is increasingly used in the emergency department. The application and utilization of POCUS is still below what is expected. This may be attributed to the fact that ultrasound is operator-dependent. However, in presence of a well-trained expert, POCUS may improve outcomes of cardiopulmonary resuscitation. This review will highlight the role of POCUS in cardiac arrest.

Abstract Background On the staggering emergence of the Omicron variant, numerous questions arose about the evolution of virulence and transmissibility in microbes. Main body of the abstract The trade-off hypothesis has long speculated the exchange of virulence for the sake of superior transmissibility in a wide array of pathogens. While this certainly applies to the case of the Omicron variant, along with influenza virus, various reports have been allocated for an array of pathogens such as human immunodeficiency virus (HIV), malaria, hepatitis B virus (HBV) and tuberculosis (TB). The latter abide to another form of trade-off, the invasion–persistence trade-off. In this study, we aim to explore the molecular mechanisms and mutations of different obligate intracellular pathogens that attenuated their more morbid characters, virulence in acute infections and invasion in chronic infections. Short conclusion Recognizing the mutations that attenuate the most morbid characters of pathogens such as virulence or persistence can help in tailoring new therapies for such pathogens. Targeting macrophage tropism of HIV by carbohydrate-binding agents, or targeting the TMPRSS2 receptors to prevent pulmonary infiltrates of COVID-19 is an example of how important is to recognize such genetic mechanisms.

Inflammation is a critical defensive mechanism mainly arising due to the production of prostaglandins via cyclooxygenase enzymes. This study aimed to examine the anti-inflammatory activity of fatty acid glucoside (FAG), which is isolated from Ficus benghalensis against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic activity of the FAG on RAW 264.7 macrophages was evaluated with an MTT assay. The levels of PGE2 and NO and the activity of iNOS, COX-1, and COX-2 enzymes in LPS-stimulated RAW 264.7 cells were evaluated. The gene expression of IL-6, TNF-α, and PGE2 was investigated by qRT-PCR. The expression of epidermal growth factor receptor (EGFR), Akt, and PI3K proteins was examined using Western blotting analysis. Furthermore, molecular docking of the new FAG against EGFR was investigated. A non-cytotoxic concentration of FAG increased NO release and iNOS activity, inhibited COX-1 and COX-2 activities, and reduced PGE2 levels in LPS-stimulated RAW 264.7 cells. It diminished the expression of TNF-α, IL-6, PGE2, EGFR, Akt, and PI3K. Furthermore, the molecular docking study proposed the potential direct binding of FAG with EGFR with a high affinity. This study showed that FAG is a natural EGFR inhibitor, NO-releasing, and COX-inhibiting anti-inflammatory agent via EGFR/Akt/PI3K pathway inhibition.

The fish market in Wuhan, China was the epicenter of Covid-19 pandemic, brought about by SARS-Co-V-2. The latter has radiated worldwide, resulting in significant economic and social disruption “Covid Crisis”. Although numerous drugs have been indicated for treating the viral infection and/or its symptoms, U.S. FDA has granted approvals for only three therapeutic agents; Remdesivir, Baricitinib and Monoclonal Antibodies (Bamlanivimab/Etesevimab, Casirivimab/Imdevimab). This review assigns the approved drug entities with respect to their chemical and pharmacological aspects as well as their reported analyses in marketed formulations and biological matrices. Furthermore, it offers a comparative study between the cited analytical methodologies for each drug separately. A comprehensive, detailed, yet an instant message of Coronavirus authorized cure is delivered throughout the presented review.

Abstract Recurrence and biochemical remission rates vary widely among different histological subtypes of pituitary adenoma. In this prospective study, we evaluated 107 consecutive primary pituitary adenomas operated on by a single neurosurgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 17 lactotroph, 5 null-cell and 6 plurihormonal. In each case, we performed direct endoscopic intraoperative inspection of the medial wall of the cavernous sinus, which was surgically removed when invasion was visualized. This was performed irrespective of tumor functional status. Medial wall resection was performed in 47% of pituitary adenomas, and 39/50 walls confirmed pathologic evidence of invasion, rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 78%. We show for the first-time dramatic disparities in the frequency of medial wall invasion among pathological subtypes. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 81% intraoperatively and 69% histologically, followed by plurihormonal tumors (40%) and gonadotroph cell tumors (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph adenomas, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the cavernous sinus medial wall was not associated with permanent cranial nerve morbidity nor carotid artery injury, although 4 patients (all Knosp 3-4) experienced transient diplopia. Medial wall resection in acromegaly resulted in the highest potential for biochemical remission ever reported, with an average postoperative day 1 GH levels of 0.96 ug/L and surgical remission rates of 92% based on normalization of IGF-1 levels after surgery (mean = 15.56 months; range 3–30 months). Our findings suggest that tumor invasion of the medial wall of the cavernous sinus may explain the relatively low biochemical remission rates currently seen for acromegaly and illustrate the relevance of advanced intradural surgical approaches for successful and durable outcomes in endonasal pituitary surgery for functional adenomas.

Objective: the albumin to fibrinogen ratio (AFR) and the C-reactive protein (CRP) to albumin ratio (CAR) have been proposed as markers of systemic inflammation. The goal of this study was to differentiate rheumatoid arthritis (RA) patients from healthy people and to study the association between AFR/CAR and DAS28 in RA.Patients and methods. A case control study including 30 RA patients and 30 healthy controls was performed. Fibrinogen, albumin, CRP and erythrocyte sedimentation rate (ESR) were measured. We calculated CAR and AFR in each group and compared them. Correlations of AFR, and CAR with disease activity were examined. Receiver operation characteristic (ROC) curves of AFR and CAR were also used to detect cutoffs for disease activity assessment.Results and discussion. CAR was higher while AFR was lower in RA patients than in control group. ROC curve analyses showed that CAR can be used to detect disease activity of RA at cut off 2.66 with sensitivity 81.3% and specificity 64.3% with an area under the curve (AUC) 0.78. So, CAR was a fair parameter to discriminate disease activity among RA patients. AFR has AUC 0.62, sensitivity 87.5% and specificity 42.9% at cutoff value 5.96. So, in our group AFR was a poor indicator to discriminate disease activity among RA patients.Conclusion. AFR and CAR have been recently proposed as inflammatory markers for assessment of disease activity in RA. AFR and CAR are simple, and inexpensive biomarkers, they also can be rapidly evaluated. CAR was found to be a fair parameter to depict disease activity in RA patients. AFR poorly depicted RA activity.

Abstract Marine algae have served as a treasure trove of structurally variable and biologically active metabolites. The present study emphasizes on UPLC–MS metabolites fingerprinting for the first systematic broad scale metabolites characterization of three different phyla of marine seaweeds; Ulva fasciata, Pterocladia capillacea and Sargassum hornschuchii along with Spirulina platensis harvested from the Mediterranean Sea. A total of 85 metabolites belonging to various classes including mostly fatty acids and their derivatives, terpenoids, amino acids and dipeptides with considerable amounts of polyphenolic compounds. OPLS-DA model offered a better overview of phylum-based discrimination rapidly uncovering the compositional heterogeneity in metabolite profiles of algae extracts. An OPLS model was constructed using the cytotoxic activities against PC3 and MDA-MB-231 tumor cells to succinctly screen cytotoxic discriminatory metabolites among the tested algae species. The coefficient plot revealed that unsaturated fatty acids as stearidonic acid and linolenic acid, terpenoids namely as rosmanol, campestanol, dipeptides primarily glutamylglycine, glycyltyrosine along with polyphenolic compounds being abundantly present in S. platensis and U. fasciata samples with relatively marked cytotoxic potential might be the significant contributors synergistically meditating their anti-proliferative activity against PC3 and MDA-MB-231 tumor cells. Such results serve as baseline for understanding the chemistry of these species and performing strict correlation between metabolite and activity where a lack of information in this regard is observed.