Therapeutic potential of Buddleja Polystachya Fresen (stem and leaves) extracts: antimicrobial and cytotoxic properties for ocular disease management.

This study on Buddleja polystachya highlights its phytochemical composition, antimicrobial activity, and cytotoxic impacts. The study emphasizes the plant's potential to treat ocular diseases by identifying important compounds involved in the bioactivity through GC-MS analysis. This study explores the antimicrobial and cytotoxic potential of Buddleja polystachya (stem and leaves) extracts, with a focus on their application in treating bacterial ocular infections and their efficacy against MCF7, HT29, and HepG2 cancer cells. Through comprehensive GC-MS analysis, a diverse array of phytochemicals was identified within Buddleja polystachya stem and leaves extracts, including carbohydrates, phenolic derivatives, fatty acids, and steroidal components. The extracts were then evaluated for their biological activities, revealing significant antimicrobial properties against a range of bacterial strains implicated in ocular infections. The research findings demonstrate that stem extracts derived from Buddleja polystachya demonstrated high to moderate cytotoxic effects on cancer cell lines MCF7, HT29, and HepG2. Notably, these effects were characterized by varying IC50 values, which suggest distinct levels of sensitivity. In contrast, leaf extracts exhibited reduced cytotoxicity when tested against all these cell lines, although they did so with a significantly higher cytotoxicity aganist HepG2 cells. The results of this investigation highlight the potential therapeutic utilization of Buddleja polystachya extracts in the management of ocular infections and cancer. These results support the need for additional research to elucidate the underlying mechanisms of action of these extracts and explore their potential as drugs.

Rare germline disorders implicate long non-coding RNAs disrupted by chromosomal structural rearrangements.

In recent years, there has been increased focus on exploring the role the non-protein-coding genome plays in Mendelian disorders. One class of particular interest is long non-coding RNAs (lncRNAs), which has recently been implicated in the regulation of diverse molecular processes. However, because lncRNAs do not encode protein, there is uncertainty regarding what constitutes a pathogenic lncRNA variant, and thus annotating such elements is challenging. The Developmental Genome Anatomy Project (DGAP) and similar projects recruit individuals with apparently balanced chromosomal abnormalities (BCAs) that disrupt or dysregulate genes in order to annotate the human genome. We hypothesized that rearrangements disrupting lncRNAs could be the underlying genetic etiology for the phenotypes of a subset of these individuals. Thus, we assessed 279 cases with BCAs and selected 191 cases with simple BCAs (breakpoints at only two genomic locations) for further analysis of lncRNA disruptions. From these, we identified 66 cases in which the chromosomal rearrangements directly disrupt lncRNAs. Strikingly, the lncRNAs MEF2C-AS1 and ENSG00000257522 are each disrupted in two unrelated cases. Furthermore, in 30 cases, no genes of any other class aside from lncRNAs are directly disrupted, consistent with the hypothesis that lncRNA disruptions could underly the phenotypes of these individuals. To showcase the power of this genomic approach for annotating lncRNAs, here we focus on clinical reports and genetic analysis of two individuals with BCAs and additionally highlight six individuals with likely developmental etiologies due to lncRNA disruptions.

Evaluation of [18F]fluoroestradiol and ChRERα as a gene expression PET reporter system in rhesus monkey brain.

Positron emission tomography (PET) reporter systems are a valuable means of estimating the level of expression of a transgene in vivo. For example, the safety and efficacy of gene therapy approaches for the treatment of neurological and neuropsychiatric disorders could be enhanced via the monitoring of exogenous gene expression levels in the brain. The present study evaluated the ability of a newly developed PET reporter system [18F]fluoroestradiol ([18F]FES) and the estrogen receptor-based PET reporter ChRERα, to monitor expression levels of a small hairpin RNA (shRNA) designed to suppress choline acetyltransferase (ChAT) expression in rhesus monkey brain. The ChRERα gene and shRNA were expressed from the same transcript via lentivirus injected into monkey striatum. In two monkeys that received injections of viral vector, [18F]FES binding increased by 70% and 86% at the target sites compared with pre-injection, demonstrating that ChRERα expression could be visualized in vivo with PET imaging. Post-mortem immunohistochemistry confirmed that ChAT expression was significantly suppressed in regions in which [18F]FES uptake was increased. The consistency between PET imaging and immunohistochemical results suggests that [18F]FES and ChRERα can serve as a PET reporter system in rhesus monkey brain for in vivo evaluation of the expression of potential therapeutic agents, such as shRNAs.

Mechanical Recycling of Carbon Fiber-Reinforced Polymer in a Circular Economy.

This review thoroughly investigates the mechanical recycling of carbon fiber-reinforced polymer composites (CFRPCs), a critical area for sustainable material management. With CFRPC widely used in high-performance areas like aerospace, transportation, and energy, developing effective recycling methods is essential for tackling environmental and economic issues. Mechanical recycling stands out for its low energy consumption and minimal environmental impact. This paper reviews current mechanical recycling techniques, highlighting their benefits in terms of energy efficiency and material recovery, but also points out their challenges, such as the degradation of mechanical properties due to fiber damage and difficulties in achieving strong interfacial adhesion in recycled composites. A novel part of this review is the use of finite element analysis (FEA) to predict the behavior of recycled CFRPCs, showing the potential of recycled fibers to preserve structural integrity and performance. This review also emphasizes the need for more research to develop standardized mechanical recycling protocols for CFRPCs that enhance material properties, optimize recycling processes, and assess environmental impacts thoroughly. By combining experimental and numerical studies, this review identifies knowledge gaps and suggests future research directions. It aims to advance the development of sustainable, efficient, and economically viable CFRPC recycling methods. The insights from this review could significantly benefit the circular economy by reducing waste and enabling the reuse of valuable carbon fibers in new composite materials.

Predictors of early and late postoperative seizures in meningioma patients: a systematic review and meta-analysis.

Meningioma is the most common type of primary brain tumor which presents with a variety of neurological manifestations. Surgical resection tends to be the preferred treatment. The occurrence of seizures after resection is common, which occur either early, within seven days of operation, or late. Our meta-analysis investigated the possible predictors of early and late postoperative seizures. We assessed the relevant observational studies on predictors of postoperative seizures published in PubMed, Scopus, and Web of Science from January 2000 to September 2022, and those that met inclusion criteria were included. We calculated the association between potential predicting factors and postoperative seizures, odds ratios (ORs) with 95% confidence intervals (CIs) applying either random or fixed-effect models. The early and late postoperative seizures were evaluated individually. Thirteen observational studies involving 4176 patients were included. Seizures occurred in 250 (6%) and 584 (14%) patients, respectively, in the early and late postoperative phases. Shared predictors for early and late seizures included tumors involving the motor cortex (OR = 2.7; 95% CI: 1.67-4.38, OR = 2.46; 95% CI: 1.68-3.61), postoperative neurological deficit (OR = 4.68; 95% CI: 2.67-8.22, OR = 2.01; 95% CI: 1.39-2.92), and preoperative seizures (OR = 2.52; 95% CI: 1.82-3.49, OR = 4.35; 95% CI: 3.29-5.75). Peritumoral edema (OR = 1.99; 95% CI: 1.49-2.64) was a significant factor only among late postoperative seizure patients while surgical complications (OR = 3.77; 95% CI: 2.39-5.93) was a significant factor solely for early postoperative seizures. Meningioma patients commonly experience early and late postoperative seizures. Identifying predictors of postoperative seizures is essential to diagnose and manage them effectively.

Epidemiology of healthcare-associated Pseudomonas aeruginosa in intensive care units: are sink drains to blame?

BACKGROUND: Pseudomonas aeruginosa (PA) is a common cause of healthcare-associated infection (PA-HAI) in the intensive care unit (ICU). AIM: To describe the epidemiology of PA-HAI in ICUs in Ontario, Canada, and to identify episodes of sink-to-patient PA transmission. METHODS: This was a prospective cohort study of patients in six ICUs from 2018 to 2019, with retrieval of PA clinical isolates, and PA-screening of antimicrobial-resistant organism surveillance rectal swabs, and of sink drain, air, and faucet samples. All PA isolates underwent whole-genome sequencing. PA-HAI was defined using US National Healthcare Safety Network criteria. ICU-acquired PA was defined as PA isolated from specimens obtained ≥48 h after ICU admission in those with prior negative rectal swabs. Sink-to-patient PA transmission was defined as ICU-acquired PA with close genomic relationship to isolate(s) previously recovered from sinks in a room/bedspace occupied 3-14 days prior to collection date of the relevant patient specimen. FINDINGS: Over ten months, 72 PA-HAIs occurred among 60/4263 admissions. The rate of PA-HAI was 2.40 per 1000 patient-ICU-days; higher in patients who were PA-colonized on admission. PA-HAI was associated with longer stay (median: 26 vs 3 days uninfected; P < 0.001) and contributed to death in 22/60 cases (36.7%). Fifty-eight admissions with ICU-acquired PA were identified, contributing 35/72 (48.6%) PA-HAIs. Four patients with five PA-HAIs (6.9%) had closely related isolates previously recovered from their room/bedspace sinks. CONCLUSION: Nearly half of PA causing HAI appeared to be acquired in ICUs, and 7% of PA-HAIs were associated with sink-to-patient transmission. Sinks may be an under-recognized reservoir for HAIs.

Robust Quantification of Phosphodiesterase-4D in Monkey Brain with PET and 11C-Labeled Radioligands That Avoid Radiometabolite Contamination.

Phosphodiesterase-4D (PDE4D) has emerged as a significant target for treating neuropsychiatric disorders, but no PET radioligand currently exists for robustly quantifying human brain PDE4D to assist biomedical research and drug discovery. A prior candidate PDE4D PET radioligand, namely [11C]T1650, failed in humans because of poor time stability of brain PDE4D-specific signal (indexed by total volume of distribution), likely due to radiometabolites accumulating in brain. Its nitro group was considered to be a source of the brain radiometabolites. Methods: We selected 5 high-affinity and selective PDE4D inhibitors, absent of a nitro group, from our prior structure-activity relationship study for evaluation as PET radioligands. Results: All 5 radioligands were labeled with 11C (half-time, 20.4 min) in useful yields and with high molar activity. All displayed sizable PDE4D-specific signals in rhesus monkey brain. Notably, [11C]JMJ-81 and [11C]JMJ-129 exhibited excellent time stability of signal (total volume of distribution). Furthermore, as an example, [11C]JMJ-81 was found to be free of radiometabolites in ex vivo monkey brain, affirming that this radioligand can provide robust quantification of brain PDE4D with PET. Conclusion: Given their high similarity in structures and metabolic profiles, both [11C]JMJ-81 and [11C]JMJ-129 warrant further evaluation in human subjects. [11C]JMJ-129 shows a higher PDE4D specific-to-nonspecific binding ratio and will be the first to be evaluated.

Transcriptome analysis in mouse skin after exposure to ultraviolet radiation from a canopy sunbed.

Exposure to ultraviolet radiation (UV-R), from both natural and artificial tanning, heightens the risk of skin cancer by inducing molecular changes in cells and tissues. Despite established transcriptional alterations at a molecular level due to UV-R exposure, uncertainties persist regarding UV radiation characterization and subsequent genomic changes. Our study aimed to mechanistically explore dose- and time-dependent gene expression changes, that may drive short-term (e.g., sunburn) and long-term actinic (e.g., skin cancer) consequences. Using C57BL/6N mouse skin, we analyzed transcriptomic expression following exposure to five erythemally weighted UV-R doses (0, 5, 10, 20, and 40 mJ/cm2 ) emitted by a UV-R tanning device. At 96 h post-exposure, 5 mJ/cm2 induced 116 statistically significant differentially expressed genes (DEGs) associated with structural changes from UV-R damage. The highest number of significant gene expression changes occurred at 6 and 48 h post-exposure in the 20 and 40 mJ/cm2 dose groups. Notably, at 40 mJ/cm2 , 13 DEGs related to skin barrier homeostasis were consistently perturbed across all timepoints. UV-R exposure activated pathways involving oxidative stress, P53 signaling, inflammation, biotransformation, skin barrier maintenance, and innate immunity. This in vivo study's transcriptional data offers mechanistic insights into both short-term and potential non-threshold-dependent long-term health effects of UV-R tanning.

Synthesis and preclinical evaluation of [11C]uPSEM792 for PSAM4-GlyR based chemogenetics.

Chemogenetic tools are designed to control neuronal signaling. These tools have the potential to contribute to the understanding of neuropsychiatric disorders and to the development of new treatments. One such chemogenetic technology comprises modified Pharmacologically Selective Actuator Modules (PSAMs) paired with Pharmacologically Selective Effector Molecules (PSEMs). PSAMs are receptors with ligand-binding domains that have been modified to interact only with a specific small-molecule agonist, designated a PSEM. PSAM4 is a triple mutant PSAM derived from the α7 nicotinic receptor (α7L131G,Q139L,Y217F). Although having no constitutive activity as a ligand-gated ion channel, PSAM4 has been coupled to the serotonin 5-HT3 receptor (5-HT3R) and to the glycine receptor (GlyR). Treatment with the partner PSEM to activate PSAM4-5-HT3 or PSAM4-GlyR, causes neuronal activation or silencing, respectively. A suitably designed radioligand may enable selective visualization of the expression and location of PSAMs with positron emission tomography (PET). Here, we evaluated uPSEM792, an ultrapotent PSEM for PSAM4-GlyR, as a possible lead for PET radioligand development. We labeled uPSEM792 with the positron-emitter, carbon-11 (t1/2 = 20.4 min), in high radiochemical yield by treating a protected precursor with [11C]iodomethane followed by base deprotection. PET experiments with [11C]uPSEM792 in rodents and in a monkey transduced with PSAM4-GlyR showed low peak radioactivity uptake in brain. This low uptake was probably due to high polarity of the radioligand, as evidenced by physicochemical measurements, and to the vulnerability of the radioligand to efflux transport at the blood-brain barrier. These findings can inform the design of a more effective PSAM4 based PET radioligand, based on the uPSEM792 chemotype.

Unveiling the Tapestry of Tobacco Consumption: Exploring the Sociodemographic Factors Impacting Smokers at Smoking Cessation Clinics in Jeddah.

Background The World Health Organization (WHO) has identified tobacco smoking as a global epidemic, causing an estimated three million deaths annually. This study aims to examine the sociodemographic characteristics and smoking-related behaviors among individuals attending smoking cessation clinics in Jeddah during 2022. By identifying these factors, appropriate interventions can be developed to combat the smoking epidemic. Methodology The study enrolled male and female participants who visited the Smoking Cessation Clinics in Jeddah from January 2022 to December 2022. Eligible participants were between 18 and 60 years old and agreed to take part in the study. Data on smoking status, medical history, previous attempts at quitting, and medication use were collected. Statistical analysis, including chi-square tests and P-values, was conducted to assess the associations between participants' medical history and smoking cessation attempts. Results A total of 5,869 participants were included in the study. The findings revealed that approximately one-fifth of the participants had previously attempted to quit smoking, while the majority 4,780 (81.4%) had not made any cessation attempts. Among those who had made quit attempts, the majority had tried quitting between one and four times 968 (16.5%). The duration of successful cessation reported by participants was generally short, with the majority 4,781 (81.5%) not experiencing any extended period of quitting. Common reasons for relapse included cravings, social influences, mood changes, stress, and withdrawal symptoms. The study also found significant associations between specific medical conditions and smoking cessation attempts. Conclusions The study identified significant associations between male gender, older age group (51-60 years), divorced marital status, intermediate educational levels, higher income levels, retired status, extreme body mass index (BMI) categories, and previous attempts at smoking cessation. Healthcare providers and policymakers should consider these findings when developing and implementing smoking cessation programs. The insights gained from this research can contribute to the development of targeted interventions to reduce smoking rates and improve public health outcomes.

A Multi-Classifiers Based Algorithm for Energy Efficient Tasks Offloading in Fog Computing.

The IoT has connected a vast number of devices on a massive internet scale. With the rapid increase in devices and data, offloading tasks from IoT devices to remote Cloud data centers becomes unproductive and costly. Optimizing energy consumption in IoT devices while meeting deadlines and data constraints is challenging. Fog Computing aids efficient IoT task processing with proximity to nodes and lower service delay. Cloud task offloading occurs frequently due to Fog Computing's limited resources compared to remote Cloud, necessitating improved techniques for accurate categorization and distribution of IoT device task offloading in a hybrid IoT, Fog, and Cloud paradigm. This article explores relevant offloading strategies in Fog Computing and proposes MCEETO, an intelligent energy-aware allocation strategy, utilizing a multi-classifier-based algorithm for efficient task offloading by selecting optimal Fog Devices (FDs) for module placement. MCEETO decision parameters include task attributes, Fog node characteristics, network latency, and bandwidth. The method is evaluated using the iFogSim simulator and compared with edge-ward and Cloud-only strategies. The proposed solution is more energy-efficient, saving around 11.36% compared to Cloud-only and approximately 9.30% compared to the edge-ward strategy. Additionally, the MCEETO algorithm achieved a 67% and 96% reduction in network usage compared to both strategies.

Isolation and Detection of Drug-Resistant Bacterial Pathogens in Postoperative Wound Infections at a Tertiary Care Hospital in Saudi Arabia.

Background: Surgical site infections (SSIs), especially when caused by multidrug-resistant (MDR) bacteria, are a major healthcare concern worldwide. For optimal treatment and prevention of antimicrobial resistance, it is important for clinicians to be aware of local drug-resistant bacterial pathogens that cause SSIs. Objective: To determine the frequency patterns of drug-resistant bacterial strains causing SSIs at a tertiary care hospital in Saudi Arabia. Methods: This retrospective study was conducted at the Microbiology laboratory of Al-Noor Specialist Hospital, Makkah, Saudi Arabia, and included wound swab samples from all cases of SSI between January 01, 2017, and December 31, 2021. The swabs were processed for the identification of bacterial strains and their resistance pattern to antibiotics according to the Clinical and Laboratory Standards Institute. Results: A total of 5409 wound swabs were analyzed, of which 3604 samples (66.6%) were from male. Most samples were from the Department of Surgery (43.3%). A total of 14 bacterial strains were isolated, of which 9 were Gram-negative bacteria. The most common isolates were Klebsiella pneumoniae, followed by Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and vancomycin-resistant S. aureus (VRSA). In terms of MDR in 2021, the highest rate of carbapenem-resistance was in A. baumannii (97%). MDR was as follows: A. baumannii, 97%; K. pneumoniae, 81%; E. coli, 71%; MRSA, 60%; P. aeruginosa, 33%; VRE, 22%; and VRSA, 2%. Conclusion: This study showed that in the city of Makkah, Saudi Arabia, the rates of MDR bacteria are high, with the majority being Gram-negative.

Integrated immunoinformatics and subtractive proteomics approach for multi-epitope vaccine designing to combat S. pneumoniae TIGR4.

Streptococcus pneumoniae is one of the major precarious pathogens accountable for over 1.2 million fatalities annually. The key drivers for pneumococcal vaccine development involve high morbidity and mortality in over one million cases, especially in very young children and the elderly. In this study, immunoinformatics was integrated with subtractive proteomics to find antigenic proteins for designing a multi-epitope vaccine against S. pneumoniae. As prospective vaccine targets, the developed pipeline identified two antigenic proteins, i.e., penicillin-binding protein and ATP synthase subunit. Several immunoinformatics and bioinformatics resources were used to forecast T- and B-cell epitopes from specific proteins. By employing a mixture of five cytotoxic T-cell lymphocytes, six helper T-cell lymphocytes, and seven linear B-cell lymphocyte epitopes, a 392 amino acid-long vaccine was designed. To enhance immune responses, the designed vaccine was coupled with a cholera enterotoxin subunit B adjuvant. The designed vaccine was highly antigenic, non-allergenic, and stable for human usage. The stability of the vaccine with toll-like receptor-4 was evaluated by molecular docking and molecular dynamic simulation. In addition, immunological simulation was performed to test its real-world potency. The vaccine codon was then cloned in silico. Overall, this study paves the way for the development of a multi-epitope S. pneumoniae vaccine under laboratory conditions. Furthermore, the current findings warrant for the experimental validation of the final multi-epitope vaccine construct to demonstrate its immunological reinforcing capability and clinical applicability.

Antimicrobial Resistance Pattern of Pseudomonas aeruginosa: An 11-Year Experience in a Tertiary Care Hospital in Makkah, Saudi Arabia.

Purpose: Pseudomonas aeruginosa (P. aeruginosa) is a common causative pathogen in healthcare settings and displays increasing levels of resistance to common antimicrobial drugs. Its capacity to resist has been reported in multiple locations across the world. This study evaluates current levels of antibiotic resistance and seeks to understand antibiotic resistance patterns in the context of the clinical isolates of P. aeruginosa. Methods: All clinical isolates were cultured at 37 °C for 24 h in different media: blood sheep agar, McConkey agar, and cystine-lactose-electrolyte-deficient agar (CLED), bacterial identification and antibiotic susceptibility patterns were determined using the Vitek-2 (bioMérieux) automated system. Results: In total, there were 61,029 patient specimens, of which 5534 were identified as non-duplicated P. aeruginosa clinical isolates, most being from males aged over 60 years. The research findings revealed that the maximum antibiotic resistance associated with P. aeruginosa isolates was found in colistin (97%), which was followed by piperacillin/tazobactam (75.8%). The maximum resistance rates in P. aeruginosa isolates were found in relation to cefepime (42.7%,) which was followed by ciprofloxacin (34.3%). Conclusion: The antibiotic resistance rate during the first six years of the research period was notably higher than in the last years, due to the application of infection control protocols and strict policies to control antibiotic prescriptions in all Saudi hospitals.

A Rare Case of Central Retinal Artery Occlusion in the Setting of Patent Foramen Ovale.

Patent foramen ovale (PFO) is a congenital heart anomaly with persistent non-closure of the atrial septum that generally closes six to 12 months after birth in the majority of adults. While remaining asymptomatic in the majority of cases, PFO could lead to paradoxical embolism and cryptogenic strokes in most symptomatic cases. The incidence of small arterial occlusion due to paradoxical emboli is quite uncommon. In this report, we present a case of a 51-year-old man who presented with acute left-sided painless visual loss due to central retinal artery occlusion (CRAO). Stroke work-up and hypercoagulability evaluations were negative. The patient was found to have PFO with the initial presentation as CRAO, a rather rare presentation in the setting of PFO. In this report also, we discuss the clinical presentation, pathogenesis, and the current evidence-based therapeutic options in the management of PFO in adults, highlighting the importance of considering this diagnostic entity in the setting of acute visual loss, as with our case presentation.

Quadricuspid Aortic Valve: An Incidental Finding in an Elderly Man.

Quadricuspid aortic valve (QAV) is a very rare congenital abnormality. Here, we present a rare case of QAV incidentally noted in a patient at an advanced age during transthoracic echocardiography (TTE). A 73-year-old man with a history of hypertension, hyperlipidemia, diabetes, and treated prostate cancer was admitted to the hospital with palpitations. An electrocardiogram (ECG) showed T-wave inversion in V5-V6, with initial troponin levels mildly elevated. Acute coronary syndrome was ruled out by serial ECGs that were unchanged, and troponins downtrended. TTE showed a rare and incidental finding of type A QAV with four equal cusps with mild aortic regurgitation.

Modification of the Structure and Linear/Nonlinear Optical Characteristics of PVA/Chitosan Blend through CuO Doping for Eco-Friendly Applications.

The solution casting technique is utilized to fabricate blank and CuO-doped polyvinyl alcohol/chitosan (PVA/CS) blends for eco-friendly applications. The structure and surface morphologies of prepared samples were explored by Fourier transform infrared (FT-IR) spectrophotometry and scanning electron microscopy (SEM), respectively. FT-IR analysis reveals the incorporation of CuO particles within the PVA/CS structure. SEM analysis exposes the well-dispersion of CuO particles in the host medium. The linear/nonlinear optical characteristics were found on the basis of UV-visible-NIR measurements. The transmittance of the PVA/CS decreases upon CuO increasing to 20.0 wt%. The optical bandgap (Eg dir./Eg ind.) decreases from 5.38/4.67 eV (blank PVA/CS) to 3.72/3.12 eV (20.0 wt% CuO-PVA/CS). An obvious improvement in the optical constants of the PVA/CS blend is achieved by CuO doping. The Wemple-DiDomenico (WDD) and Sellmeier oscillator models were utilized to examine the CuO role dispersion behavior of the PVA/CS blend. The optical analysis shows clear enrichment of the optical parameters of the PVA/CS host. The novel findings in the current study nominate CuO-doped PVA/CS films for applications in linear/nonlinear optical devices.

In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18 kDa (TSPO) in monkey brain.

PURPOSE: [18F]SF51 was previously found to have high binding affinity and selectivity for 18 kDa translocator protein (TSPO) in mouse brain. This study sought to assess the ability of [18F]SF51 to quantify TSPO in rhesus monkey brain. METHODS: Positron emission tomography (PET) imaging was performed in monkey brain (n = 3) at baseline and after pre-blockade with the TSPO ligands PK11195 and PBR28. TSPO binding was calculated as total distribution volume corrected for free parent fraction in plasma (VT/fP) using a two-tissue compartment model. Receptor occupancy and nondisplaceable uptake were determined via Lassen plot. Binding potential (BPND) was calculated as the ratio of specific binding to nondisplaceable uptake. Time stability of VT was used as an indirect probe to detect radiometabolite accumulation in the brain. In vivo and ex vivo experiments were performed in mice to determine the distribution of the radioligand. RESULTS: After [18F]SF51 injection, the concentration of brain radioactivity peaked at 2.0 standardized uptake value (SUV) at ~ 10 min and declined to 30% of the peak at 180 min. VT/fP at baseline was generally high (203 ± 15 mL· cm-3) and decreased by ~ 90% after blockade with PK11195. BPND of the whole brain was 7.6 ± 4.3. VT values reached levels similar to terminal 180-min values by 100 min and remained relatively stable thereafter with excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated in the brain. Ex vivo experiments in mouse brain showed that 96% of radioactivity was parent. No significant uptake was observed in the skull, suggesting a lack of defluorination in vivo. CONCLUSION: The results demonstrate that [18F]SF51 is an excellent radioligand that can quantify TSPO with a good ratio of specific to nondisplaceable uptake and has minimal radiometabolite accumulation in brain. Collectively, the results suggest that [18F]SF51 warrants further evaluation in humans.

Green synthesis of MgO nanoparticles and its antibacterial properties.

Magnesium oxide nanostructured particles (NP) were prepared using a simple solution combustion technique using different leaf extracts such as Mangifera indica (Mango - Ma), Azadirachta indica (Neem-Ne), and Carica papaya (Papaya-Pa) as surfactants. The highly crystalline phase of MgO nanostructures was confirmed by PXRD and FTIR studies for 2 h 500°C calcined samples. To analyze the characteristics of obtained material-MaNP, NeNP, and PaNP for dosimetry applications, thermoluminescence (TL) studies were carried out for Co-60 gamma rays irradiated samples in the dose range 10-50 KGy; PaNP and NeNP exhibited well-defined glow curve when compared with MaNP samples. In addition, it was observed that the TL intensity decreases, with increase in gamma dose and the glow peak temperature is shifted towards the higher temperature with the increase in heating rate. The glow peak was segregated using glow curve deconvolution and thermal cleaning method. Kinetic parameters estimated using Chen's method, trap depth (E), and frequency factor (s) were found to be 0.699, 7.408, 0.4929, and 38.71, 11.008, and 10.71 for PaNP, NeNP, and MaNP respectively. The well-resolved glow curve, good linear behavior in the dose range of 10-50, KGy, and less fading were observed in PaNP as compared with MaNP and NeNP. Further, the antibacterial activity was checked against human pathogens such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A visible zone of clearance was observed at 200 and 100 µg/mL by the PaNP and NeNP, indicating the death of colonies by the nanoparticles. Therefore, PaNP nanomaterial is a potential phosphor material for dosimetry and antibacterial application compared to NeNP and MaNP.

Candidate 3-benzazepine-1-ol type GluN2B receptor radioligands (11C-NR2B-Me enantiomers) have high binding in cerebellum but not to σ1 receptors.

INTRODUCTION: We recently reported 11C-NR2B-SMe ([S-methyl-11C](R,S)-7-thiomethoxy-3-(4-(4-methyl-phenyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol) and its enantiomers as candidate radioligands for imaging the GluN2B subunit within rat N-methyl-D-aspartate receptors. However, these radioligands gave unexpectedly high and displaceable binding in rat cerebellum, possibly due to cross-reactivity with sigma-1 (σ1) receptors. This study investigated 11C-labeled enantiomers of a close analogue (7-methoxy-3-(4-(p-tolyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol; NR2B-Me) of 11C-NR2B-SMe as new candidate GluN2B radioligands. PET was used to evaluate these radioligands in rats and to assess potential cross-reactivity to σ1 receptors. METHODS: NR2B-Me was assayed for binding affinity and selectivity to GluN2B in vitro. 11C-NR2B-Me and its enantiomers were prepared by Pd-mediated treatment of boronic ester precursors with 11C-iodomethane. Brain PET scans were conducted after radioligand intravenous injection into rats. Various ligands for GluN2B receptors or σ1 receptors were administered at set doses in pre-blocking or displacement experiments to assess their impact on imaging data. 18F-FTC146 and enantiomers of 11C-NR2B-SMe were used for comparison. Radiometabolites from brain and plasma were measured ex vivo and in vitro. RESULTS: NR2B-Me enantiomers showed high GluN2B affinity and selectivity in vitro. 11C-NR2B-Me enantiomers gave high early whole rat brain uptake of radioactivity, including high uptake in cerebellum, followed by slower decline. Radioactivity in brain at 30 min ex vivo was virtually all unchanged radioligand. Only less lipophilic radiometabolites appeared in plasma. When 11C-(R)-NR2B-Me was used, three high-affinity GluN2B ligands-NR2B-SMe, Ro25-6981, and CO101,244-showed increasing pre-block of whole brain radioactivity retention with increasing dose. Two σ1 receptor antagonists, FTC146 and BD1407, were ineffective pre-blocking agents. Together, these results strongly resemble those obtained with 11C-NR2B-SMe enantiomers, except that 11C-NR2B-Me enantiomers showed faster reversibility of binding. When 18F-FTC146 was used as a radioligand, FTC146 and BD1407 showed strong pre-blocking effects whereas GluN2B ligands showed only weak blocking effects. CONCLUSION: 11C-NR2B-Me enantiomers showed specific binding to GluN2B receptors in rat brain in vivo. High unexpected specific binding in cerebellum was not due to σ1 receptors. Additional investigation is needed to identify the source of the high specific binding.