Glucagon-like peptide-1 (GLP-1) agonists are gaining attention as a potential treatment for obesity. While studies have shown that these medications greatly impact dietary habits, their relationship to consumer food waste is unexplored. We analyzed data from 505 U.S. consumers who self-report GLP-1 medication use and found that 25% agree that they waste more food since beginning the medication with 61% disagreeing with this statement. Respondents are less likely to agree with this statement if they have been on the medication a longer time and more likely to agree if they report experiencing nausea since beginning the medication. Several dietary changes are also significantly associated with self-reported changes in food waste since starting the medication. With previous literature finding GLP-1’s significant impact on individual food consumption and dietary choices, our findings suggest that the effects of this novel class of anti-obesity medications may cast a significant impact on food waste patterns. With the potential for widespread adoption of these medications, and given that approximately one-third of food in the United States is wasted by consumers, understanding the interaction of these two consumer trends is critical for projecting their joint impact on the food system.

Nuclear magnetic resonance (NMR) is a technique used for many years by chemists for elucidation of molecular structure. Technological progress over the years has enabled this technique, making it easier to use. Thus, the LF-NMR (low-field NMR) was introduced as side technique, characterized by low man-agement costs and shorter analysis time than its main counterpart. The application of 1H LF-NMR for the quantification of ethyl alcohol in different alcoholic matrices is herein described, comparing results ob-tained with this technique with those determined by a reference gascromatographic method.

In this very personal hunt for the meaning of the bacterial cell cycle, the snark, I briefly revisit and update some of the mechanisms we and many others have proposed to regulate the bacterial cell cycle. These mechanisms, which include the dynamics of calcium, membranes, hyperstructures and networks, are based on physical and physico-chemical concepts such as ion condensation, phase transition, crowding, liquid crystal immiscibility, collective vibrational modes, reptation, and water availability. I draw on ideas from subjects such as the ‘prebiotic ecology’ and phenotypic diversity to help with the hunt. Given the fundamental nature of the snark, I would expect that its capture would make sense of other parts of biology. The route therefore followed by the hunt has involved trying to answer questions like “why do cells replicate their DNA?”, “why is DNA replication semi-conservative?”, “why is DNA a double helix?”, “why do cells divide?”, “is cell division a spandrel?” and “how are catabolism and anabolism balanced?”. Here, I propose some relatively unexplored, experimental approaches to testing snark-related hypotheses and, finally, I propose some possibly original ideas about DNA packing, about phase separations, and about computing with populations of virtual bacteria.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

Astragalus plants belong to the legume family and have obvious rhizosphere effect. The northwestern area of Yunnan China is the main distribution region of Astragalus plants with high application value, but low recognition and resource reserves. The aim of this research is to explore the species diversity of cultivable rhizosphere fungi derived from A. acaulis, A. forrestii, and A. ernestii growing in special high-cold environment of northwest Yunnan, and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fungus Aspergillus calidoustus AA12 from A. acaulis fermentation substance showed a broad antibacterial spectrum and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the species of A. calidoustus, including a sesterterpine 6-epi-ophiobolin G (1), two sesquiterpenes penicisochroman A (2), pergillin (3) and 7-methyl-2-(1-methylethylethlidene)-furo[3,2-H]isoquinoline-3-one (4), and three polyketides trypacidin (5), 1,2-seco-trypacidin (6) and questin (7). Compound 1 exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL, and prominent inhibitory effect on the biofilm of Streptococcus agalactiae at MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity against Plasmodium falciparum strains 3D7 and chloroquine-resistant Dd2 at the half maximal inhibitory concentration (IC50) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizosphere fungi Astragalus-derived in special high-cold environment and further increased the library of fungi available for natural anti-infectious products screening.

This review explores the nuanced decision-making surrounding postoperative radiotherapy for diffuse low-grade glioma (DLGG) patients, emphasizing the need for personalized treatment to balance the benefits of tumor control with the risks of long-term side effects. Radiotherapy is a cornerstone of DLGG treatment, offering significant improvements in progression-free survival, but its potential for cognitive decline and vascular lesions necessitates careful consideration of individual patient factors. The review delves into the complexities of radiotherapy timing, revealing that while early radiotherapy enhances progression-free survival, it does not significantly impact overall survival and may lead to earlier onset of cognitive decline. Conversely, delayed radiotherapy may mitigate cognitive decline but may result in shorter progression-free survival and the onset of neurological symptoms. The review advocates for a patient-centered approach, emphasizing the importance of weighing individual risks and benefits, and highlights the potential of artificial intelligence in predicting cognitive decline and the need to revisit previous research findings in light of the 2021 WHO (World Health Organization) classification update, underscoring the evolving nature of DLGG treatment and the ongoing quest for optimal therapeutic strategies.

In volleyball, the jump serve is a fundamental and crucial skill that is one of the most commonly used serving techniques. This study aimed to examine the kinematic differences between straight line (SL) and diagonal line (DL) in volleyball jump serves by focusing on torso and attack arm joint motions. Three-dimensional coordinate data were captured using a motion capture system (200 Hz) in 14 right-handed male professional volleyball players who performed SL and DL jump serves. This result suggests that the pelvis and torso backward rotation angles during the arm-clocking phase were smaller when performing DL serves. During ball contact, the servers exhibited greater forward rotation angles of the pelvis and torso to control the upper body facing the diagonal direction of the target zone. In addition, lowering the forward tilt angle of the trunk helped the servers maintain body balance in the air and increased their wrist flexion angle, preventing the ball from flying out of bounds when performing DL. These findings highlight the importance of controlling pelvic and torso rotations in the transverse plane when adjusting for different serving lines. These insights can guide volleyball athletes and coaches in refining their serving techniques.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

This study evaluates audiogenic epilepsy in Krushinsky-Molodkina rats using a wireless EEG system to overcome the limitations of traditional methods that restrict animal movement. Nine male KM rats, prone to audiogenic seizures, were implanted with electrodes in areas critical for seizure activity (inferior colliculus, ventrolateral periaqueductal gray, dorsal area of the secondary auditory cortex, and motor cortex). This setup allowed for the observation of seizures without movement restriction. Results showed that targeted neural intervention via electrode implantation reduced the intensity of convulsive seizures in half of the subjects, suggesting a potential therapeutic approach. The severity of seizures was influenced by the pre-phonostimulation EEG background activity in specific brain regions, identifying them as key in the genesis and generalization of seizures. Observations of dual generalized seizure waves and induced hyperkinesis challenge conventional epilepsy models and suggest new directions for research and therapy development.

Background: The practice of self-medication is common worldwide and is an important component of medical self-care. However, the practice can be dangerous and is linked to various risks for the patients and the entire community. This study aimed to estimate the prevalence and factors associated with self-medication among Bangladeshi adults. Methods: A cross-sectional survey was conducted between April and June 2021 among Bangladeshi adults (aged >19 years) using convenient sampling. A total of 1320 data were collected through face-to-face interviews using a standardized questionnaire. Multivariable logistic regression analysis was used to identify factors associated with self-medication practice (SMP). Results: Overall, 41% of adults in our survey reported SMP. The most common illnesses that prompted SMP were common cold/flu (66.4%), gastric problems (65%), and headache (64.4%). The most frequent reasons for SMP were to get better services (30.59%), perceive SMP without side effects (23.28%), and save time with effectiveness (14.56%). Potential risk factors included 10 years (AOR = 1.91; 95% CI: 1.04 - 3.50) and >12 years of schooling (AOR = 5.03; 95% CI: 2.27 - 11.15), being a businessman (AOR = 4.64; 95% CI: 1.74 - 12.37), having ≤6 family members (AOR = 2.13; 95% CI: 1.40 - 3.24), being a member of a social group (AOR = 1.53; 95% CI: 1.10 - 2.12), a health status check after every six months (AOR = 1.52; 95% CI: 1.08 - 2.13), and current ill-health (AOR = 1.41; 95% CI: 1.06 - 1.87). Protective factors identified included ≤30 years of age (AOR = 0.40; 95% CI: 0.17 - 0.93), and practice of modern (AOR = 0.39; 95% CI: 0.22- 0.69) and herbal (AOR = 0.45; 95% CI: 0.21- 0.97) healing types. Conclusion: More than one-third of the study participants reported practicing self-medication. Increasing the community’s awareness of the extreme consequences of SMP and not just the average experience might sway individuals away from SMP, and implementing strict jurisdiction could be a way to minimize the SMP.

The study of the pathogenesis of febrile seizures and their consequences frequently necessitates gene expression analysis. The primary methodology employed for such analysis is reverse transcription with quantitative polymerase chain reaction (RT-qPCR). To guarantee the accuracy of data obtained by RT-qPCR, it is crucial to utilize stably expressed reference genes. The objective of this study was to identify the most suitable reference genes for use in the analysis of mRNA production in various brain regions of rats following prolonged neonatal febrile seizures. The expression stability of eight housekeeping genes was evaluated using the online tool RefFinder in the dorsal and ventral hippocampal regions and in the temporal and medial prefrontal cortex of the brain. The Ppia gene exhibited the greatest stability of expression. Conversely, the genes with the least stable expression level are Actb and Ywhaz; thus, it is not recommended to use them for normalization in a febrile seizure model. Additionally, the majority of housekeeping genes demonstrate age-related, region-specific fluctuations. Therefore, it is crucial to employ the appropriate housekeeping genes for each brain structure under investigation when examining the expression dynamics of genes of interest in a febrile seizure model.

Medication adherence is a vexing challenge with nonadherence at 50% or greater among US adults. With most medications self-administered by patients in the home, home medication management practices, especially where patients store medication in the home and receptivity to guidance from healthcare providers, need to be better understood to improve adherence. We designed and deployed a survey to investigate home medication management. The 1,673 survey respondents reported that the most common home storage locations for medications were nightstand drawers (28%) and atop nightstands (27%). Kitchen cabinets and bathroom vanities were significantly associated with increased odds of having ever forgotten to take a medication. Desks, dining room tables, and nightstand drawers were associated with the greatest statistically significant decrease in odds of having ever forgotten to take a medication. Almost all (96%) respondents were receptive to guidance on medication storage from a healthcare provider. Patients are largely on their own to devise home medication management practices, yet some home storage locations are significantly associated with decreased odds of having forgotten to take a medication. Knowing which practices are associated with adherence may lead to better guidance for patients from healthcare providers and to innovation in the design of medication adherence interventions.

The enormous potential of renewable bioresources is expected to play a key role in the development of the EU’s sustainable circular economy. In this context, inexhaustible, biodegradable, non-toxic and carbon-neutral forest-origin resources are very attractive for the development of novel sustainable products. The main structural component of wood is cellulose, which, in turn, is the feedstock of nanocellulose, one of the most explored nanomaterials. Different applications of nanocellulose have been proposed, including packaging, functional coatings, insulating materials, nanocomposite fields among others. However, the intrinsic flammability of nanocellulose restricts its use in some industries where fire risk is a concern. This paper overviews the most recent studies of the fire resistance of nanocellulose-based materials, focusing on thin films, coatings and aerogels. Along with effectiveness, increased attention to sustainable approaches is considered in developing novel fire-resistant coatings. The great potential of bio-based fire-resistant materials, combined with conventional non-halogenated fire retardants FRs, has been established. The formulation methods, types of fire retardants and their action modes, and methods used for analysing fire retardancy are discussed in the frame of this overview.

(1) Background: As part of the Scottish Governments five-year recovery plan to address the backlog in NHS care following the COVID-19 pandemic, community pharmacies in Scotland are planned to provide a Hospital Discharge Medicines Supply and Medicines Reconciliation Service. We aimed to qualitatively explore patients’ experience of this new service; (2) Method: Adult patients (≥18yrs age) who consented to participate in the Community Pharmacy Hospital Dis-charge and Medicines Reconciliation Service were invited for interview within 21 days of dis-charge from hospital. Qualitative, one-to-one, semi-structured, patient interviews were conducted by telephone and audio-recorded using Microsoft Teams®. The interview audio recordings were transcribed verbatim and underwent thematic analysis; (3) Results: 12 patients were inter-viewed, evenly split by sex and with a median age of 62 years (range; 36 to 88 years). Analysis generated main five themes; Patient Engagement, Stakeholder Communication, Practical Factors, Human Factors, and Comparative Experiences. Many of these were interdependent; (4) Con-clusions: Patients appreciated that the service ensured a quicker discharge from hospital. Good stakeholder communication, practical factors (including choice, location, and the realities of ob-taining their medication from the community pharmacy), and a pre-existing and trusted rela-tionship in their usual community pharmacy were the key factors that regulated the patient ex-perience. In the main, patients were positive about the introduction of this new service. However, a lack of previous relationship or trust with a community pharmacy, and previous experiences with medication supply problems were factors which had the potential to negatively impact on patient experiences.

Background/Objectives: Habituation and sensitization are opposite phenomena that play a role in the pathophysiology of episodic migraine and its progression to chronic migraine (CM). There have been just a few studies that have investigated these phenomena in patients with medication overuse headache (MOH) in comparison to those with chronic migraine (CM) and healthy controls (HCs), and the findings have been inconsistent. Methods: We measured and examined visual evoked potentials (VEPs) in 81 patients with MOH and 24 patients with CM, as well as 24 HCs. The VEPs were used to assess sensitization by analyzing the amplitude of the first block (100 sweeps), and to evaluate habituation by measuring the amplitude response decrement after 6 blocks. We further examined patients diagnosed with MOH based on their acute medication type and after a 3-week acute medication withdrawal program. Results: There were no significant differences between groups in terms of the first N1-P1 VEP amplitude block and its habituation. It was found that patients with MOH had a greater drop in the amplitude of the VEP P1-N2 complex after repeated stimulation than patients with CM or HC. The VEPs parameters showed no significant differences based on the specific overused drug and after a 3-week acute medication off. Conclusions: We propose that the results obtained in patients with MOH indicate an abnormal activation of inhibitory circuits in the parieto-occipital region in response to repeated modulatory stimuli.

This article encapsulates an exploration of seizure dynamics through the lens of computational modeling in epilepsy. Starting with a foundational understanding of the FitzHugh-Nagumo model, asimplified representation of neuronal activity, we try to understand the intricacies of epileptic seizures. We methodically demonstrated the transition from normal neuronal activity to a seizure-like state by altering key parameters in the model, such as external current and coupling strength. This was followed by an extension of the model to a network of neurons, simulating the complex interactions and synchronization patterns indicative of seizure propagation. Numerical simulations were conducted to visualize the impact of varying coupling strengths on network dynamics, offering insights into the mechanisms of seizure initiation and spread. The study was complemented by a discussion on the implications of these findings for understanding epilepsy, highlighting the bridging of theoretical models with clinical understanding. Our approach not only illuminates the potential of computational models in epilepsy research but also underscores the significance of interdisciplinary collaboration in advancing our comprehension of neurological disorders. Through this article, we aim to provide a nuanced perspective on the modeling of epileptic seizures, offering a valuable resource for researchers and clinicians in the field.

Electroencephalography (EEG) is essential for tracking brain activity and identifying seizure effects. However, epileptic behaviour can only be detected after a specialist has carefully analysed all EEG recordings along with a proper history of the patient. A skilled physician is required for the right epilepsy diagnosis and therapy. But most of the time, patients visit the clinician in the interictal stage with no proper history documented. Therefore, it was essential to the automatic prediction of stages of seizure. K nearest neighbours (KNN) and random forest (RF) models using raw EEG signals, preictal, ictal, postictal, and interictal stages were identified in this study. The possibility of these characteristics is explored by examining how well time-domain signals work in the prediction of epileptic stages using intracranial EEG datasets from Freiburg Hospital (FH), Children's Hospital Boston-Massachusetts Institute of Technology (CHB-MIT), and Temple University Hospital (TUHEEG). To test the viability of this approach, two different types of simulations were carried out on three binary classifications (interictal vs. preictal, interictal vs. ictal, preictal vs. postictal, and interictal vs. postictal), and one four-class problem (interictal vs. preictal vs. ictal vs. postictal) was performed for each model. The average accuracy when using time-domain signals in the FH database was 90.5% and 75.0%; CHB-MIT was 92.87% and 75.9%; and TUHEEG was 94.46% and 76.8%, respectively, for the KNN and RF models.

Institutionalized older adults often face complex medication regimens, increasing their risk of adverse drug events due to polypharmacy, overprescribing, medication interactions or the use of Potentially Inappropriate Medications (PIM). However, data on medication use and associated risks in this population remain scarce. This pilot study aimed to characterize the sociodemographic, clinical and pharmacotherapeutic profiles and the use of PIM among institutionalized elders residing in Residential Structures for Elderly People (ERPI) in the Faro municipality, located in the Portuguese region of the Algarve. We conducted a cross-sectional study in a non-randomized sample of 96 participants (mean age: 86.6 ±7.86 years) where trained researchers reviewed medication profiles and identified potentially inappropriate medications using the EU(7)-PIM list. Over 90% of participants exhibited polypharmacy (≥5 medications), with an average of 9.1 ± 4.15 medications per person. About 92% had potential drug interactions, including major and moderate interactions. More than 86% used at least one potentially inappropriate medication, most commonly central nervous system drugs. This pilot study demonstrates that institutionalized older adults may be at high risk of potential medication-related problems. Implementing comprehensive medication review programs and promoting adapted prescribing practices are crucial to optimize medication use and improve the well-being of this vulnerable population.

It is not new in medical history to propose a global concern to be classified as a disease. Defining a concern into disease allows to assign ethical responsibilities to develop powerful and effective interventions. It also allow to appropriate distribute the resources uniformly economically and morally. In 2003, World Health Organization report stated that 30-50 % of patients do not take their medications as prescribed associated with morbidity, mortality and health cost. It was considered a global concern, however, irrespective of decades of researches conducted on medication adherence, we are still unable to state that medication adherence issues are being resolved. In this review, we have described few apprehensions in current understandings of medication adherence that have limited its research. We have also proposed medication adherence as disorder and provided its’ definition and classification

Background and Aim: Patients with Type 2-diabetes condition tend to have multiple medications in various dosage which leads to complex medication regimens. Complexity of regimen results in poor adherence, uncontrolled glycemic value and treatment failure. The research aimed to investigate medication regimen complexity index, medication adherence, and impact of medication regimen complexity on glycemic control and medication adherence.Materials and Methods: A Crossectional Study methods was conducted at Bheri Hospital Nepalgunj, among 145 Diabetes patients. Medication adherence was assessed by using a General Medication Adherence Scale (GMAS Nep-Tool). Medication regimen complexity was assessed by using a Medication Regimen Complexity Index (MRCI) tool. Chi-square test, One-way ANOVA, Paired t-test, and binary logistic regression were used for inferential statistics. Results: This study shows that most of the participants were female and aged group 50-59 years. Hypertension was the most common comorbidity, followed by hypothyroidism. The majority of participants exhibited partial adherence 90 (62.1%) to their medication regimen. It was seen that medications prescribed for diabetes were more complex than non-diabetes medications (Mean±SD MRCI: 8.28±3.155 vs. 4.57±2.107). The negative correlation was seen with diabetes MRCI and medication adherence (r=-0.090). There was statistically significant association between diabetes MRCI and glycemic control, (p<0.05). Binary logistic regression revealed that females had lower odds of high MRCI compared to males ( multivariate p-value: 0.014, AOR: 0.403, 95% CI: 0.195-0.832), while sedentary lifestyle showed high Diabetes MRCI (COR: 4.709, 95% CI: 0.962-23.05) and abnormal BMI were associated with higher MRCI (binary p-value: 0.067, COR: 2.30, 95% CI: 0.942-5.65; multivariate p-value: 0.092, AOR: 2.323, 95% CI: 0.878-5.67). Conclusion: Diabetes medications are more complex, reducing adherence and worsening A1C outcomes. Simplifying regimens improves results, with MRCI being valuable for healthcare providers. The medication adherence and therapeutic outcomes can be improved by the improved by the involvement of clinical pharmacist using MRCI.

Background: Seizures in the early postoperative period may impair patient recovery and increase risk of complication. The aim of this study is to determine whether there is any advantage in postoperative seizure prophylaxis following meningioma resection. Methods: This systematic review was conducted in accordance with PRISMA guidelines. PUBMED, Web of Science, Embase, Science Direct, and Cochrane were searched for papers until April 2023. Results: Among 9 studies, a total of 3,249 were evaluated patients, of which 984 patients received antiepileptic drugs (AEDs). A comparison between patients who received AEDs and those who did not showed a non-significant differences between both groups (RR 1.22, 95% CI 0.66 to 2.40; I² = 57%). Postoperative seizures occurred in 5% (95% CI: 1% to 9%) within the early time period (<7 days), and 9% (95% CI: 1% to 17%) in the late time period (>7 days), with significant heterogeneity (I² = 91% and 97% respectively). In seizure-naive patients, the rate of postoperative seizures was 2% (95% CI: 0% to 6%) in the early period and increased to 6% (95% CI: 0% to 15%) in the late period. High heterogeneity led to the use of random-effects models in all analyses. Conclusion: The current evidence does not provide sufficient support for the effectiveness of prophylactic AED medications in preventing postoperative seizures in patients undergoing meningioma resection. This underscores the importance of considering diagnostic criteria and conducting individual patient analysis to guide clinical decision-making in this context.

Epilepsy is a neurological disorder that affects approximately 1% of the world's population. To diagnose and estimate the occurrence of epilepsy, the analysis of recorded brain activity is performed by a neurologist, which is not only time-consuming and tedious but also occasionally accompanied by human error. Therefore, in recent decades, researchers have aimed to unravel an approach for designing and building an automated method for diagnosing and estimating the occurrence of epilepsy. Accordingly, the present study proposed two new-fangled ways based on brain signals and a convolutional neural network (CNN). Moreover, this research implements a CNN with a sequential three-layer structure. Numerous experiments were performed, and the accuracy of estimating epilepsy using the developed methods was achieved at 95% without feedback and 97% with feedback. The proposed methods were proven to be more accurate than the previous techniques and can be employed as a physician's assistant once entering the field of operation.

Elemental sulfur, commonly known for its wide range of biological activity, has a long history of being used to protect all garden and vegetable crops from a range of pests and diseases, including powdery mildew, ascochyta blight, clubroot, plant mites, oidium, anthracnose, and scab. In the present study, a quick and environmentally friendly approach has been developed for the synthesis of sulfur nanoparticles with antibacterial activity. Sulfur nanoparticles (SNPs) were prepared by modifying the surface of elemental sulfur using various polyelectrolyte-surfactant mixtures (PSM) including NaCMC-SDBS and PHMG-CTAB. The SNPs were characterized by UV–visible spectrophotometry, X-ray diffraction (XRD), and thermogravimetric analysis (TG/DSC), scanning electron microscopy (SEM), with the SNPs showing an almost spherical shape with an average size in the range of 150-200 nm. The antibacterial activity of the sulfur nanoparticles was tested using against gram-positive S. aureus and E. faecium and gram-negative E. coli and P. aeruginosa bacteria. From this, it could be seen that SNPs exhibited significant antimicrobial activity against gram-positive bacteria, i.e., S. aureus and E. faecium. The in vitro cytotoxicity of the SNPs-1 and SNPs-2 studied to normal (MeT-5A) and tumorous (MCF-7) human cell lines was assessed in the concentration range from 500 μg/ml to 0.12 mg/ml, from which it was determined as being non-cytotoxic. The received products can be considered for potential application in agriculture and medicine.

Abstract Epilepsy is a disorder of the brain and a seriously debilitating condition, which has been associated with injury, social stigmatisation and in some cases, sudden unexpected and premature death. A sense of profound isolation is felt by many individuals with epilepsy, and this community has expressed an urgent desire for an early warning system to allow them time to prepare for seizure onset. Surveys of dog owners with epilepsy have previously reported that some dogs can predict the onset of a seizure. The current study used an experimental design to investigate the alleged propensity of untrained pet dogs to react to human epileptic seizures. We hypothesised that seizures are associated with specific volatile organic compounds resulting in detectable odours which are the biomarker that triggers these reported behavioural changes in the dogs. Here we provide details of the first empirical test to demonstrate that pet dogs display several significant behavioural changes when they are exposed to seizure-related odours that apparently emanate from their owners. Using a repeated measures design experiment, recordings were made of the reactions of 19 untrained pet dogs to odours from sweat samples provided by three people with epilepsy and by two people without epilepsy (controls). The seizure-associated sweat samples were captured pre-seizure, during seizure and post-seizure. All samples were randomly delivered to individual dogs in a test area, using two bespoke pieces of apparatus called Remote Odour Delivery Mechanisms (RODM). One RODM delivered only experimental odours, the other delivered only control odours. Behavioural changes by the dogs on encountering the odour samples were recorded by video for later analysis. Consistent with our hypothesis, seizure-associated odours evoked significant behavioural changes in the dogs which were affiliative in nature and directed at their owners.

A large core size and bending resistance are very important properties of mid-infrared energy transfer fibers, but large core sizes usually lead to a deterioration of bending properties. A negative-curvature nested node-free anti-resonant hollow-core fiber (AR-HCF) based on quartz is proposed. It was made by adding a nested layer to a previous AR-HCF design to provide an additional anti-resonance region while keeping the gap between adjacent tubes strictly correlated to the core diameter to produce a node-free structure. These features improve the fiber’s bending resistance while achieving a larger core diameter. The simulation results show that the radial air-glass anti-resonant layer is increased by the introduction of the nested anti-resonant tube, and the weak interference overlap between the fiber core and the cladding mode is reduced, so the fiber core’s limiting loss and the sensitivity to bending are effectively reduced. When the capillary wall thickness t of the fiber is 0.71 μm, the core diameter D is 70 μm, the ratio of the inner diameter of the cladding capillary to the core diameter d/D is 0.62, and the diameter of the nested tube is d0=29 μm, the fiber has a lower limiting loss at the wavelength of 2.79 μm, and the limiting loss is 3.28×10-4 dB/m. At the same time, the optimized structure also has good bending resistance. When the bending radius is 30 mm, the bending loss is only 4.72×10-2 dB/m. To our knowledge, this is the first research to achieve an anti-bending low-loss micro-structure hollow fiber with a bending radius of less than 30 mm in the 2.79 μm band. An anti-bending low-loss anti-resonant hollow-core fiber with this structure constitutes a reliable choice for the light guiding system of a 2.79 μm band erbium laser therapy instrument.

Wearable technology will become available and allow prolonged electroencephalography (EEG) monitoring in the home environment of patients with epilepsy. Neurologists analyse the EEG visually and annotate all seizures, which patients often under report. Visual analysis of a 24 hour EEG recording typically takes one to two hours. Reliable automated seizure detection algorithms will be crucial to reduce this analysis. We study a dataset of behind-the-ear EEG measurements. Our first aim was to develop a methodology to reduce the EEG dataset by classifying part of the data automatically, while retaining 100% detection sensitivity (DS). Prediction confidences are determined by temperature scaling of the classification model outputs and trust scores. A DS of approximately 90% (99%) can be achieved when automatically classifying around 90% (60%) of the data. Perfect DS can be achieved when automatically classifying 50% of the data. Our second contribution demonstrates that a common modelling strategy, where predictions from several short EEG segments are used to obtain a final prediction, can be improved by filtering out untrustworthy segments with low trust scores. The false detection rate shows a relative decrease between 21% and 43%, and the DS shows a small increase or decrease.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

In order to tackle the issue of severe rocking phenomenon under seismic conditions in structures equipped with steel spring isolation bearings, this paper investigates a novel type of anti-rocking bearing. Firstly, the structural configuration and working principle of the novel anti-rocking bearing are introduced, and a design method for bearing parameters is proposed. Secondly, a finite element analysis model is established using SAP2000 software to conduct nonlinear dynamic time history analysis under seismic loading. The analysis results show that the structural arrangement of the novel anti-rocking bearing reduces both the vertical displacement difference and the rocking angle of the isolation layer. The bearing exhibits a certain level of anti-rocking effect, but it may cause significant tensile forces in some bearings, necessitating the installation of anti-tensile reinforcement. The effectiveness of the anti-rocking effect improves as the stiffness of the steel tension rod in the bearing increases; however, it also leads to higher maximum tension in individual bearings as well as the total tension in all bearings. For structures equipped with the novel anti-rocking bearing, the acceleration amplifies under most cases, with amplification coefficients ranging from 0.82 to 1.55. The performance of the novel anti-rocking bearing varies significantly for different seismic waves. The stiffness of the steel tension rod should be determined considering the reference pressure of the bearing and the maximum designed tension of the bearing. Through the finite element simulation of the bearing, the mechanical properties of the bearing are basically the same as the theoretical analysis results. For the cylinder and the joint bearing, certain structural measures need to be taken to ensure its strength and stiffness.

(1) Background: This article reviews the available scientific literature on drug-related problems and negative outcomes associated with medications identified by medication review with follow-up for end-stage renal disease and discussed with the physicians; (2) Methods: A systematic review was conducted of the scientific literature retrieved from the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Cochrane Library: The Cochrane Central Register and Control Trials (CENTRAL) and Literatura Latinoamericana y del Caribe (LILACS), Medicina en Español (MEDES), and the SciELO bibliographic database (collection of scientific journals). The following terms were used as descriptors and searched in free text: "end-stage renal disease", "medication review", and "drug-related problems” and “negative outcomes associated with medication". The following limits were applied: "humans" and "adults (more than 18 years)”; (3) Results: A total of 59 references were recovered and after applying inclusion/exclusion criteria, 16 articles were selected. Of these selected articles, 15 provided information on drug-related problems and only 1 on negative outcomes associated with medications; (4) Conclusions: It can be concluded that drug-related problems and negative outcomes associated with medication affect patients with end-stage renal disease, mainly those receiving renal replacement therapy. More evidence is needed, especially on negative outcomes associated with medication.

Introduction: Medication overuse headache (MOH) is a secondary headache that occurs 15 or more days per month in patients with preexisting headache. This can result from the excessive (10 or 15 days/month) use of drugs for acute or symptomatic headache therapy. Aim: To examine the relationships between demographic parameters, illnesses and habits of life, clinical type and length of previous headache and MOH and clinical features of MOH. Materials and methods: This study was conducted at the Clinic of Neurology, Clinical Center of Niš, and included 83 patients (11 men and 72 women) who were first diagnosed with MOH. The mean age of the patients in the study cohort was 40.5 ± 11.6 years. The study was performed in strict accordance with the Declaration of Helsinki after informed consent was obtained from each participant in the study. The study was approved by the local ethics committee. Results: In the study cohort, there were more women (86.7%), nonsmokers (59%), those who did not consume alcohol (95.2%), those who were physically inactive (90.4%), those who consumed caffeinated beverages (89.2%), and those with diseases of the cardiovascular (12%) or osseous joint system (10.8%). MOH was most commonly generated by chronic migraine (64%). The duration of MOH until diagnosis was 5.1 ± 5.5 years. The following MOH characteristics were observed: moderate pain (45.8%), bilateral localization (56.6%), temporal presentation (65.1%), and neck tightness (81.9%). Common (41%) and combination analgesics (48.2%) were used most frequently, 15 to 25 days per month. The impact of MOH on daily life was assessed as significant (HIT - 65.4 ± 5.5), correlating with the duration of earlier chronic headaches (r = 0.327, p = 0.003). Conclusion: MOH can be generated by the transformation of a previous chronic headache due to overuse of analgesic therapy. The MOH significantly affects all aspects of a patient's life. MOH can be prevented by educating patients by limiting the use of analgesic therapy, especially in the at-risk group (middle-aged women with chronic migraines).

Electroencephalography (EEG) signals are the primary source for discriminating the preictal from the interictal stage, enabling early warnings before the seizure onset. The epileptic seizure prediction models face significant challenges due to data scarcity, diversity, and privacy. This paper proposes a three-tier architecture for epileptic seizure prediction associated with the Federated Learning (FL) model that enhances the capability by utilizing the significant amount of seizure patterns from globally distributed patients with data privacy. The determination of the preictal state is influenced by global and local model-assisted decision-making by modeling the two-level edge layer. Integrating the Spiking Encoder (SE) with Graph Convolutional Neural Network (Spiking-GCNN) works as the local model trained using the bi-timescale approach. Each local model utilizes the aggregated seizure knowledge from the different medical centers through FL and determines the preictal probability in the coarse-grained personalization. The Adaptive Neuro-Fuzzy Inference System (ANFIS) is utilized in fine-grained personalization to recognize epileptic seizure patients by examining the outcomes of the FL model, heart rate variability features, and patient-specific clinical features. The proposed seizure prediction is evaluated using benchmark datasets by comparing them with the existing works to demonstrate the potential results.

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

This study aimed to investigate the knowledge of patients with hypertension about their condition, adherence to antihypertensive medication, and the factors influencing it. A cross-sectional study was conducted in two cardiology outpatient clinics of two tertiary hospitals, in Greece. The study included 188 patients diagnosed with hypertension. The patient’s knowledge about their disease and adherence to medication were assessed by using the HK-LS and A-14 scales, respectively. Patients had sufficient knowledge levels about their disease, but significantly low levels of adherence to medication. Patients with higher knowledge levels were more adherent to medications [r(188) = 0.885, p &lt; 0.001]. By using multivariate analysis, higher age (p = 0.018), residence in a more populous area (p = 0.041), more years with the disease (p = 0.012), and a lower number of medications (p = 0.03) were associated with higher levels of knowledge. Conversely, younger age (p = 0.036), lower educational levels (p = 0.048), fewer years with the disease (p = 0.001), and a higher number of medications (p = 0.003) were associated with lower adherence to medication. The Greek patients' hypertension knowledge was sufficient, however, adherence to medication was significantly low. Healthcare managers could utilize our findings to design targeted interventions for improving adherence to medication for these patients.

Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

Febrile seizure (FS), which occurs as a response to fever, is the most common seizure that occurs in infants and young children. FS is usually accompanied by diverse neuropsychiatric symptoms including impaired social behaviors; however, no causative link between FS and autism spectrum disorder (ASD) has yet been established. Here, we provide evidence linking FS occurrence with ASD pathogenesis in rats. We developed an FS juvenile rats model and found ASD-like abnormal behaviors including deficits in social novelty, repetitive behaviors, and hyperlocomotion. In addition, FS model juvenile rats showed enhanced levels of gliosis and inflammation in the hippocampal CA2 region and cerebellum. Furthermore, abnormal levels of social and repetitive behaviors persisted in adults FS model rats. These findings suggest that occurrence of FS in infants can cause behavioral endophenotypes of ASD.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted health care worldwide. As the pandemic has been prolonged, quarantine restrictions have been lightened gradu-ally, which can influence outcomes of pediatric patients with chronic disease such as epi-lepsy by increase of susceptibility of the COVID-19 infection. The aim of this study was to determine impacts of COVID-19 pandemic on seizure control and identify potential risk factors that might worsen seizure attacks during the pandemic in children with epilepsy. We performed a retrospective chart review of 48 pediatric patients with epilepsy during the COVID-19 pandemic from January 2016 to July 2022. During the COVID-19 pandemic period, 25% of pediatric patients experienced sei-zure worsening, showing an increase in seizure frequency or duration or both. Factors associated with worsening seizures during pandemic were: diagnosis of epi-lepsy less than one year, comorbid conditions with cerebral palsy or having a tracheosto-my or a PEG, and infection with other viruses (respiratory syncytial virus, influenza virus A, influenza virus B) rather than COVID-19 infection. Our finding highlights the need to proactively monitor and regularly follow up (es-pecially short period of time) patients after they are diagnosed with epilepsy. It is also important to properly manage those who are susceptible to serious illness and keep sea-sonal viral infections under surveillance to manage exacerbated seizure in children with epilepsy. Furthermore, pediatric physicians should not overlook surveillance of seasonal respiratory viruses since quarantine restrictions are getting eased.

Epilepsy is a prevalent neurological disorder with considerable risks, including physical impairment and irreversible brain damage from seizures. Given these challenges, the urgency for prompt and accurate seizure detection cannot be overstated. Traditionally, experts have relied on manual EEG signal analyses for seizure detection, which is labor-intensive and prone to hu-man error. Recognizing this limitation, the rise of deep learning methods has been heralded as a promising avenue, offering more refined diagnostic precision. On the other hand, the prevailing challenge in many models is their constrained emphasis on specific domains, potentially diminishing their robustness and precision in complex real-world environments. This paper presents a novel model that seamlessly integrates the salient features from the time-frequency domain alongside pivotal statistical attributes derived from EEG signals. This fusion process involves the integration of essential statistics, including the mean, median, and variance, combined with the rich data from compressed time-frequency (CWT) images processed using auto-encoders. This multidimensional feature set provides a robust foundation for subsequent analytic steps. A long short-term memory (LSTM) network, meticulously optimized for the renowned Bonn Epilepsy dataset, was used to enhance the capability of the proposed model. Preliminary evaluations underscore the prowess of the proposed model: remarkable 100% accuracy in most of the binary classifications, impressive performance exceeding 95% for three-class and four-class challenges, and a commendable rate exceeding 93.5% for the five-class classification.

Sepsis is a serious disease that can lead to mortality. The etiology of the disease is connected to how the body as a host reacts toward microbes such as bacteria, viruses, and fungi invasion. Current research shows that during sepsis, the reaction toward microbe attacks takes two main phases. The first is known as a cytokine storm, while the second is a vicious cycle of pro-inflammatory responses followed by a strict anti-inflammatory response led by CD4+ Tregs. Various immunomodulatory therapies have been proposed to break the cycle of pro- and anti-inflammatory reactions to sepsis. However, clinical trials did not show promising results, indicating further research into the mechanism that Treg uses to inhibit proinflammatory reactions. We used next-generation sequencing (NGS) analysis of bulk RNA-seq and single-cell RNA-seq data to examine the exact molecular pathways used by Treg to inhibit the immune response in sepsis. Our approach identified ACOD1 (Aconitate Decarboxylase 1) as a primary mediator of Treg suppression of immune cells. We identified and validated CD36 as a downstream target of ACOD1. CD36 is a known metabolite regulator in Tregs. Taken together, our results indicate that targeting ACOD1 could prove valuable in regulating Treg function during sepsis.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

Due to the large interest and need, there has been much recent work in epileptic seizure detection using machine learning models. Using un-intrusive measurements of brain activity such as electroencephalograms (EEG) has allowed for large datasets to be constructed and used for computational intelligence to identify seizure events within EEG data. In this paper, we use a publicly avaibale EEG dataset to develop a lightweight Machine learning supervised model (simple Decision Tree) to classify seizure events from brain waves. The performance of this developed model was compared with a complex ML model (Support Vector Machine). The cross-validated Decision Tree model performed better for seizure event classification with an overall accuracy of 91.17%. This lightweight model will allow for developing mobile applications and user comfort

Background and objective. Globally, disposing of unused medicines has become a source of concern, as pharmaceutical waste enters the ecosystem, posing a threat to human health and the environment. This study aimed to assess the disposal practice of unused medication among pharmacists in Libya. This study also seeks to determine if pharmacists plan to have their pharmacies serve as assembly points for potential take-back initiatives. Methods. A random sample of 150 pharmacists from various government and private pharmacies in Tripoli participated in a self-administered questionnaire about their disposal practices, and knowledge on pharmacies serving as collection points for ideal disposal of unused medicines. Descriptive statistics were used to interpret the data. Results. A total of 128 pharmacists completed the survey. The majority of respondents said that throwing discarded drugs in the trash bin was their preferred method of disposal (53.1%), followed by discarding via burn and drug wholesalers (17.2%, 14.8%, respectively). Only 2.1% of the respondents disposed unused medicines according to the WHO guidelines of drug disposal. Moreover, about 65.6% had poor knowledge about Take-Back program. Conclusion. Failure to follow the WHO guidelines for drug disposal raises the risk of contamination of our environment and the likelihood of humans and animals ingesting harmful pharmaceutical wastes.

The modulation of Nrf2 activity has been reported to be implicated in the pathology of various neurological disorders, including epilepsy. Previous studies have demonstrated that Nrf2 is activated in the post-status epilepticus rat model, however, the spatio-temporal, as well as cell type-specific expression of Nrf2 following brief epileptic seizures remains unclear. Here, we evaluated how an acute epileptic seizure affected the expression of Nrf2 and its downstream genes in the cortex and the hippocampus up to 1-week following the induced seizure. We found that after a pentylenetetrazol-induced seizure, Nrf2 significantly increased at 24 h at the mRNA level and 3 to 6 h at the protein level in the cortex. In the hippocampus, the Nrf2 mRNA level peaked at 3 h after the seizure, and no significant changes were observed in the protein level. Interestingly, the mRNA level of Nrf2 downstream genes peaked at 3-6 h after seizure in both the cortex and the hippocampus. A significant increase in the expression of Nrf2 was observed in the neuronal population of CA1 and CA3 regions of the hippocampus, as well as in the cortex. Moreover, we observed no change in the co-localization of Nrf2 with astrocytes neither in the cortex nor in CA1 and CA3. Our results revealed that following a brief acute epileptic seizure, the expression of Nrf2 and its downstream genes is transiently increased and peaked at early timepoints after seizure predominantly in the hippocampus, and this expression is restricted to the neuronal population.

With the increasing societal expectation that animals are afforded greater protection in emergencies, the legal process from entering a property to rescue a companion animal, through to how to dispose of such animals if they remain unclaimed has not been well examined in New Zealand. It is hypothesised that the legal framework for such response is flawed. In this study, each phase of animal disaster rescue is evaluated against four key statues that may apply in each phase, in that does any statute provide clear end to end provisions with clear legal authority to do so. The study found that all statutes evaluated contained flaws and that the current legal provisions are insufficient to provide clear authority for the sequential process of undertaking rescue of animals during emergencies. A major flaw was discovered in the Civil Defence Emergency Management Act 2002 a key statute, that provided for the seizure of property and animals but omitted a procedure for the disposal of such seized things leaving them all in legal limbo. It is recommended that animal disaster laws are updated to be more animal inclusive. The method also may be applicable to assist evaluating animal disaster management legal frameworks in other countries.

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Ice accumulation poses considerable challenges in transportation, notably in the domain of general aviation. The present study combines the strengths and limitations of conventional aircraft de-icing techniques with the emerging trend toward all-electric aircraft. The study aims to utilize laser-induced graphene (LIG) technology to create a multifunctional surface, seamlessly integrating hydrophobic properties with efficient electrical heating to mitigate surface icing effectively. We investigated the utilization of a 10.6 μm CO2 laser for direct writing on polyimide (PI), a widely-used insulating encapsulation material. From the thermomechanical perspective, our initial analysis using COMSOL Multiphysics software revealed that when the laser power P exceeds 5 W, the PI substrate experience ablative damage. The experimental results show that when P ≤ 5W, an increase in power has a positive impact on the quality, surface porosity, roughness reduction, line-spacing reduction, and water contact-angle enhancement of the graphene. Conversely, when P &gt; 5 W, higher power negatively affects both the substrate and the graphene structure by inducing excessive ablation. However, it influences the graphene line height positively and is consistent with overall experimental-simulation congruence. Furthermore, the incorporation of high-quality graphene resulted in a surface that exhibited higher contact angles (CA &gt; 120°), lower energy consumption, and higher heating efficiency compared to the use of traditional electrically heated materials for anti-icing applications. The potential applications of this one-step fabrication method extend across various industries, particularly aviation, marine engineering, and other ice-prone domains. Moreover, the method has extensive prospects for addressing pivotal challenges associated with ice formation and serves an innovative and efficient anti-icing technology.

The growing emphasis on sustainability and environmental stewardship in the pharmaceutical industry necessitates innovative solutions to manage pharmaceutical waste, particularly medication bottles. This research paper explores the potential of integrating Radio Frequency Identification (RFID) and blockchain technology to enhance the traceability, accountability, and efficiency of recycling empty medication bottles. By utilizing RFID for real-time tracking and blockchain for secure, immutable data storage, this proposed system improves transparency across the supply chain and incentivizes consumer participation in recycling programs. The solution provides benefits to pharmaceutical manufacturers, regulators, and consumers, contributing to sustainability, regulatory compliance, and environmental protection.

(1) Background: Asthma and Chronic Obstructive Pulmonary Disease (COPD ) are major global health issues, impacting morbidity, mortality, and healthcare costs. Despite the proven benefits of pharmacist involvement in managing these conditions, their potential in hospitals remains underused. This study aimed to identify patients at high risk of rehospitalisation post-exacerbation of asthma or COPD, to target pharmaceutical interventions. (2) Methods: Data from the University Hospital for January-December 2019 on adult admissions for asthma/COPD were analyzed, focusing on demographics, hospitalization, and clinical outcomes. (3) Results: Among the 140 patients enrolled, a significant majority (91%) underwent adjustments in their treatment regimens during their hospital stay, and nearly 59% faced readmission within six months. A survival analysis highlighted a notable disparity in the rates of rehospitalisation-free survival between patients with asthma and those with COPD, identifying COPD patients as having a higher susceptibility to rehospitalisation. (4) Conclusion: The study found COPD pa-tients at greater risk but didn't specify a priority profile, suggesting the necessity for broad, cus-tomized interventions to improve outcomes and reduce healthcare strain.

Objective: To evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011-December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. Results: 243 patients were included, ninety-five (44.2%) used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors the incidence of MRONJ and mean time to the occurrence of MRONJ was 6.6% (8/120) and 16.8 months (SD 7.8) respectively. In patients treated with denosumab and CDK4/6 inhibitor 13.7% (13/95) and 15.4 month (SD 8.7) respectively. The difference in the incidence was not significant (p=0.085). Conclusion: it suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab was higher and the onset of MRONJ occurred earlier in the presence of CDK4/6 inhibitors. Although the difference was not significant, given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association.

Background and Objectives: In Libya, prescription medicines can easily be dispensed without a prescription, as self-medication with the subsequent of potential misuse and unnecessary risk for patients. This systematic review and meta-analysis explored the prevalence of self-medication among citizens in Libya. Methods: We systematically searched PubMed, ISI Web of Knowledge, EMBASE, Medline, Scopus, google scholar and ResearchGate databases for studies published in Libya reporting the prevalence of non-prescription use of medicines in community pharmacies, targeting studies published from Jan 2008 until Dec 2019. A random meta-analysis was performed to analyze pooled estimates of non-prescription usage of medicines. Results: Out of 63 articles identified, a total of 13 papers from 7 cities were met the inclusion criteria and involved a total of 4741 subjects. The overall pooled proportion of self-medication of drugs was 53.6% (95% CI: 0.93% - 1.08%), with low heterogeneity and the P-value of the whole population tasted was found to be = 1.000 (df = 12). Seven out of the 13 studies reported data on self-medication for antibiotics without prescription. The records ranged from 15.3% (95% CI 0.61–1.65) in Misurata to 76.6% (95% CI 0.80–1.25) in Tripoli. Conclusion: Self-medication use of medicines among Libyan population is a common phenomenon involving a high proportion use of antibiotics. This misuse of medications could enhance the development and spread of antibiotic resistance.

Patient safety is fundamental to healthcare. Adverse events particulary medication errors, cause harm to patients specially paediatric population in the emergency departament. Aim: To explore paediatric emergency nurses' perceptions of medication administration errors. Method: A qualitative, ethnomethodological, descriptive study. Data were collected through in-depth individual interviews with paediatric emergency nurses and analysed using Taylor and Bogdan's proposal. Results: Main categories extracted: 1) Safety culture transmitted by supervisors and safety groups. 2) Teamwork with good communication and a positive relationship. 3) Error management, the lack of formal support and negative feelings despite an understanding of the multifactorial nature of errors. The study identifies several challenges in the healthcare system. Emphasis on the per-ception of errors in terms of patient harm, while near misses or dose delays or omissions are not treated as errors. Conclusions: Although institutions have implemented safety culture strategies, nurses have not fully embraced them. Negative emotions and coping strategies are reported. There is a need to promote a positive safety culture and a safe working environment that encourages communica-tion within the team. Protocols could be adapted according to feasibility and perceived risk. The hospital should provide training in safe management and patient safety. This study was not reg-istered.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

We provide representations for the generalized Drazin inverse of an anti-triangular matrix of the form $\left( \begin{array}{cc} a&b\\ 1&0 \end{array} \right)$ in a Banach algebra $\mathcal{A}$, under the condition that $ab=ba$. Specifically, we present the representation of Drazin inverse for these types of anti-triangular matrices in Banach algebras.

Background The increasing number of elderly individuals in South Korea, now entering a super-aging era, underscores the growing importance of understanding their specific oral health needs. This study investigated changes in oral health conditions, salivary parameters, halitosis, systemic diseases, and medication usage with aging. Methods This study was retrospectively conducted using the medical records of patients who presented with complaints of xerostomia or halitosis between August 2020 and May 2023. A total of 274 patients (66 males, 208 females, mean age 59.39 ± 16.10 years) were included in this study. Results Aging was found to be significantly associated with the presence of sticky saliva, poor oral hygiene, tongue coating, and halitosis (all p < 0.05). Correlation analyses further revealed significant associations between aging and several conditions, including hypertension (r = 0.495, p < 0.001), diabetes mellitus (r = 0.255, p < 0.001), amlodipine usage (r = 0.249, p = 0.001), osteoporosis (r = 0.195, p = 0.001), cardiovascular disease (r = 0.150, p = 0.013), and the presence of tongue coating (r = 0.205, p = 0.001). Conversely, none of the salivary parameters demonstrated a significant relationship with aging. Furthermore, halitosis did not exhibit significant differences across age groups (all p > 0.05), with the exception of methyl mercaptan levels, which were notably higher among patients in their 20s (p = 0.049). Conclusions The findings of this study can help clinicians develop targeted strategies to address specific oral health challenges associated with aging in elderly patients.

Currently, in some domestic and foreign mines, the backfill drilling pipeline experience a rupture phenomenon even when the wear degree is low. This results in a delay in production due to the filling becoming 'sick'. This paper presents, for the first time, the damage mechanism from a mechanical perspective and re-derives the anti-extrusion strength model of the backfill drilling pipeline. We investigate the influence of law on the anti-extrusion strength of pipelines from the perspective of stratum and cement ring. We then verify the theoretical and simulation results through engineering examples. The results demonstrate that the Mises stress criterion is a suitable modification principle for the anti-extrusion strength model of the backfill drilling pipeline. The anti-extrusion strength of the pipeline is related to the elastic modulus and Poisson's ratio of the stratum, and the thickness of the cement ring. It is negatively affected by the depth of the stratum. For hard strata, a cement ring with a smaller elastic modulus is suitable, while for soft stratum, a cement ring with a larger elastic modulus is recommended. When the missing angle of the cement ring is less than 60°, the stress concentration factor increases up to 2.2. The stress unloading capacity of the cement ring ranges from 32.7% to 37.8%, and optimal performance of the cement ring is achieved when it has high strength and low rigidity. The backfill filling pipeline of a copper mine abroad was destroyed due to external extrusion force exceeding its anti-extrusion strength value. The modified pipeline anti-extrusion strength model is 18.2% higher than the casing API strength value. This finding can inform the design of the backfill filling pipeline for China's kilometer-deep wells in the future.

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

Background: Interleukins play dual roles in breast cancer, acting as both promoters and 11 inhibitors of tumorigenesis within the tumor microenvironment, which is shaped by their 12 inflammatory functions. This study analyzed the subtype-specific prognostic significance 13 of anti-inflammatory and pro-inflammatory signatures using microarray-based gene ex- 14 pression analysis. Correlations between these interleukin signatures and immune cell 15 markers (CD8, IgKC, CD20) and immune checkpoints (PD-1) were also evaluated. 16 Materials and Methods: The study investigated the prognostic significance of an anti- 17 inflammatory interleukin signature (IL-12, IL-21, IFN-γ) and a pro-inflammatory interleu- 18 kin signature (IL-4, IL-5, IL-10, IL-13, IL-17, CXCL1) for metastasis-free survival (MFS) 19 using Kaplan-Meier curves and Cox regression analyses in a cohort of 461 patients with 20 early breast cancer. Correlations were analyzed using the Spearman-Rho correlation coef- 21 ficient. 22 Results: Kaplan-Meier curves revealed that the prognostic significance of the anti-inflam- 23 matory signature was specifically pronounced in the basal-like subtype (p=0.004, Log 24 Rank). This signature retained independent prognostic significance in multivariate Cox 25 regression analysis (HR 0.463, 95% CI 0.290-0.741; p=0.001). Higher expression of the anti- 26 inflammatory interleukin signature was associated with longer MFS. The pro-inflamma- 27 tory interleukin signature showed a significant prognostic effect in the whole cohort, with 28 higher expression associated with shorter MFS (p=0.034). Strong correlations were found 29 between the anti-inflammatory signature and CD8 expression (ρ=0.391; p<0.001) and be- 30 tween the pro-inflammatory signature and PD-1 expression (ρ=0.627; p<0.001).

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

In this follow-up study, we aimed to assess the effectiveness of the “I do not smoke, I exercise”, anti-smoking preventive health education program. The program was based on the Theory of Planned Behavior supplemented with life-skills teaching and targeted at high school students. The intervention comprised ten one-hour online sessions, administered by physical education instructors. The study cohort comprised 222 students (109 boys, 113 girls) from 11 secondary schools, with an average age of 16.42 ± 1.36 years. Data collection involved pre- and post-intervention self-assessment questionnaires. The examined variables included attitudes towards smoking, intention to smoke, subjective norm, perceived behavioral control (PBC), knowledge about smoking, smoking behavior, exercise behavior, attitudes toward the program's implementation, and satisfaction with the program. Separate paired samples t-test revealed a significant improvement in students' knowledge about smoking, perceived behavioral control, and overall program satisfaction following the intervention. However, no significant changes were observed in the remaining variables. These findings suggest that the health education smoking prevention intervention incorporates techniques and strategies that influence the Perceived Behavioral Control variable, emphasizing students' strong interest in educationally theorized programs integrating technology into their design. Future studies should consider further examination of tobacco control strategies within the high school context.

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

Objective: This research was aimed to estimate the anti-fatigue effects of arecoline and elucidate its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL/6 mice were randomly allocated into six groups: a control group, a SD-induced fatigue model group, a group receiving Rhodiola Rosea capsules (2.5 mg/kg), and arecoline groups administered low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on the mouse fatigue-related behaviors was assessed by the behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. Enzyme-linked immunosorbent assays (ELISAs) were utilized to measure the levels of the relevant biochemical markers. Western blotting was employed to quantify the expression of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline significantly reduced both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased serum levels of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol, while elevated total testosterone, lactate dehydrogenase, and immunoglobulin G levels. Furthermore, it significantly increased superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase activity in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels were significantly increased, cytokine levels were markedly reduced, and the expression of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissue was significantly upregulated. Conclusion: The current study for the first time demonstrated that arecoline has significant anti-fatigue activity, and its mechanism of action is related to elevate the levels of glucose and lipid metabolism, relieve oxidative stress damage, inhibit neuroinflammatory response, regulate neurotransmitter levels and Keap1/Nrf2/HO-1 signaling pathway. The current study provides a new insight into the potential of arecoline in prevention and improvement of fatigue.

Purpose of review: Medication overuse headache (MOH) is an important problem worlwide areas of different controversy regarding its entity. This article reviews the risk factors, comorbidities, pathophysiology, clinical presentation, effective management and prognosis of MOH, by summaries and integrates the results and finding in previously performed more than 15000 studies (from the year of 2010 to 2023) available from the scientific database of the University Medical Library in the University Clinical centre of Niš, which aimed to investigate and define a complexcity of this type of headache. Recent finding: It has been proposed that all acute migraine medications can lead to MOH, with differences in the propensity of different agents to cause the problem. Early data suggests that triptans and other pain killers used for the acute treatment of migraine, may be an exception. Recent studies show that practicioners and the general public are still largely unaware of the problem of medication overuse and its damaging effects. Summary: Although it is likely that MOH does occur and restricting the amount of acute medications is necessary to prevent it. It is also possible that increasing amounts of acute medications are simply a reflection of poorly controlled headaches, rather than a couse. Further researches need to be developed to identify more precisious mechanism in MOH effecitive management and its evolution. Key word: medication overuse headache (MOH)

Purpose of review: Medication overuse headache (MOH) is an important problem worlwide areas of different controversy regarding its entity. This article reviews the risk factors, comorbidities, pathophysiology, clinical presentation, effective management and prognosis of MOH, by summaries and integrates the results and finding in previously performed more than 15000 studies (from the year of 2010 to 2023) available from the scientific database of the University Medical Library in the University Clinical centre of Niš, which aimed to investigate and define a complexcity of this type of headache. Recent finding: It has been proposed that all acute migraine medications can lead to MOH, with differences in the propensity of different agents to cause the problem. Early data suggests that triptans and other pain killers used for the acute treatment of migraine, may be an exception. Recent studies show that practicioners and the general public are still largely unaware of the problem of medication overuse and its damaging effects. Summary: Although it is likely that MOH does occur and restricting the amount of acute medications is necessary to prevent it. It is also possible that increasing amounts of acute medications are simply a reflection of poorly controlled headaches, rather than a couse. Further researches need to be developed to identify more precisious mechanism in MOH effecitive management and its evolution.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Chagas disease (CD) is a neglected tropical parasitic disease caused by the protozoan Trypanosoma cruzi. Unfortunately, the current etiological treatment for CD is unsatisfactory, due to the high toxicity and low cure efficacy of compounds, mainly during the chronic phase of this disease. Thus, the discovery of new drugs for the treatment of CD is urgent. In the present study, we report the synthesis of a series of guanidines and its evaluation in in vitro assays to determine the trypanocidal effects on the Tulahuen T. cruzi strain, transfected with a β-galactosidase reporter gene, in comparison to the cytotoxic effects on vertebrate cells. The most potent and selective compounds LQOF-G1 and LQOF-G29 were considered good drug prototypes and candidates for in vivo tests using mice. Both compounds possess an electron withdrawing group on the aniline moiety, namely a NO2 and Br group, respectively, which effectively decrease the electron density. LQOF-G29 stands out among the investigated compounds due to the replacement of the benzyl group by methyladamantane.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from 33 strains (including 20 dinoflagellates, 4 diatoms and 9 strains from other 7 algal classes), cultivated under identical conditions were examined for antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Wide differences were observed between species within the same class, in particular dinoflagellates which were better represented in this study. These preliminary findings pave the way for in-depth characterization of extracts with highest signals in each test, identification of compounds responsible of the biological activities found, and a further screening of the CCVIEO culture collection.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

Variable flow emitters are a new type of emitter for underground drip irrigation that are used in locations where soil moisture is difficult to transport to the surface, which leads to crop emer-gence difficulties. The flow channel structure parameters of emitters affect the hydraulic per-formance of the emitter and its anticlogging ability. In this study, the variable flow emitter at the conventional low–flow water supply stage is taken as the research object. A combination of CFD numerical simulation of a two–phase flow of water and sand and clear water testing of test samples is applied to study the influence laws of 10 groups of variable flow emitter structural combinations on the effluent flow rate (q), flow index (x), particle passage rate and flow field inside the flow channel. The results show that the Realizable k–ε turbulence model can be used to simulate the flow field inside the variable flow emitter flow channel. The nRMSE between the measured and simulated values of q is 11.23%, and the relative error between the measured and simulated values of x is 4.66%, which gives a high simulation accuracy. The polar analysis shows that the tooth angle A has the smallest effect on the effluent flow rate q0.1 under 0.1 MPa, x, and particle passage rate of the variable flow emitter. The depth of the flow channel D, the spacing of the teeth B, and the height of the teeth E have a different order of precedence in the influence of the three indices, which are D > B > E > A, B > E > D > A, and E > B > D > A, respectively. The value of particle passage rate is positively correlated with the mean flow velocity (v) and the mean turbulent kinetic energy (k) in the flow channel, and particle passage rate tends to increase and then decrease with the increase of x. The retention time (t) of the particles in the flow channel is closely related to the magnitude of v and k. Three multivariate linear regression equations (R2 = 0.883 ~ 0.995) were constructed for q0.1, x, and particle passage rate versus the flow channel structural parameters. Using the scipy.optimize.minimize function in Python, we de-termined the three optimal combinations of flow channel structural parameters corresponding to better hydraulic performance: q0.1 is 1.5 or 2 L/h (objective function y = min x), better clogging resistance (y = max particle passage rate), and both (y = min (0.5 x - 0.5 particle passage rate)). The research results can provide a ref-erence for the optimal design of variable flow emitters.

Leishmaniasis are neglected diseases that affect regions such as South Asia, South Africa and Latin America, less developed regions. Current treatment, for cutaneous, mucocutaneous and visceral leishmaniosis, which are the main forms of the disease, is based on the administration of pentavalent antimonial and amphotericin B. However, these drugs have low efficacy and high toxicity. For this reason, the search for new treatments for this disease is necessary, based on studies of new molecules and their conformations. The research proposed the conformational study of brominated guanidine compounds with potential antileishmanial activity using Nuclear Magnetic Resonance (NMR) and X-ray diffraction (XRD) techniques. The present study involves the bro-minated molecules, LQOF-G2, LQOF-G30, LQOF-G35 and LQOF-G35-Br. The later was synthesized by the reaction of LQOF-G35 with NBS under IR irradiation at 120 Watts of potency and dichloro-methane as solvent by 12-h of exposition. The obtained results demonstrated the efficiency of the bromination method, since two bromines atoms entered the molecule. Furthermore, NMR analysis showed the occurrence of a conformational change from Z to E when compound LQOF-G35 was brominated to LQOF-G35-Br. This feature was well confirmed by comparative DRX study of the LQOF-G35 and LQOF-G35-Br compounds. The antileishmanial activity of LQOF-G2 e LQOF-G35 motivated the synthesis of new brominated compounds LQOF-G30 e LQOF-G35-Br.

The combination of several therapeutic strategies is often seen as a good way to decrease the resistance rates, since bacteria overcome better single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and the safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked both by cytotoxicity assays and flow cytometry.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

Adherence with multidrug therapy (MDT) is one of the keys to successful treatment of leprosy. In order to understand the treatment behavior, reasons for non-adherence, and efforts to improve medication adherence, it is necessary to use a valid and reliable instrument to measure adherence to MDT in multibacillary leprosy patients on regular basis. This study used a mixed method de-sign. The instrument development phase involved 10 experts using 4 rounds of Delphi method. Assessment items that are considered relevant are those that meet 4-5 Likert scale by a minimum of 75% of experts or meet assessment score >3.75. We did the pilot testing and the questionnaire was revised if invalid. After obtaining a valid and reliable instrument, it was tested to 100 sub-jects in 4 health centers. For internal validity test, 9 valid assessment items were obtained, with the correlation coefficient values of each item >0.3, and -Cronbach's reliability of 0.723. The instru-ment produced had sensitivity of 88.46% and specificity of 78.37%. From 100 subjects enrolled, 61% had good adherence and 39% had poor adherence based on questionnaire assessment. A valid and reliable questionnaire for evaluating adherence with MDT in Indonesian patients has been composed.

Cellulose nanocrystals (CNCs) are cellulose-derived nanomaterials that can be easily obtained, e.g., from vegetable wastes produced by circular economies. They show promising antimicrobial activity and the absence of side effects and toxicity. This study investigated the ability of CNCs to reduce microbial adherence and biofilm formation using in vitro microbiological models reproducing the oral environment. Microbial adherence by microbial strains of oral interest, Streptococcus mutans and Candida albicans was evaluated on the surfaces of salivary pellicle-coated enamel disks in the presence of different aqueous solutions of CNCs. The antibiofilm activity of the same CNC solutions was tested against S. mutans and an oral microcosm model based on mixed plaque inoculum using a continuous-flow bioreactor. Results showed an excellent anti-adherent activity of the CNCs against the tested strains from the lowest concentration tested (0.032 wt.%). Such activity was significantly higher against S. mutans than C. albicans, suggesting a selective anti-adherent activity against pathogenic strains. At the same time, there was a minimal albeit significant antibiofilm activity (at least 0.5 and 4 wt.% CNC solution for S. mutans and oral microcosm, respectively). This makes CNCs particularly interesting as anticaries agents, encouraging their use in the oral field.

Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.

The aim of this study was to investigate the physicochemical characterization and biological activities of chitosan (CH) based composite films with the incorporation of chestnut flower essential oil (CFEO). The composite films were prepared by casting method and characterized in terms of structural, morphological and mechanical properties via FT-IR, XRD, UV, SEM and TGA. The results proved the significantly increased water vapor permeability (WVP), heat resistance, antibacterial and antioxidant capabilities of CH-CFEO films. The incorporation of CH and CFEO enhanced the UV blocking, which made the film shield almost all UV light. Films with the tensile strength of 6.37 ± 0.41 MPa and elongation at break of 22.57 ± 0.35% were got with 6 mg mL-1 CFEO. Subsequently, the fruit preservation experiments also confirmed that the composite films could effectively extend the shelf life of bananas through their excellent water vapor and oxygen barrier. These desirable performances enable our newly developed composite films to be a remarkable packaging material to solve the fresh fruit preservation dilemma.

As the adoption of deep learning models continues to surge across various applications, the need for efficient deployment architectures becomes increasingly critical. This paper presents a novel approach to enhance the deployment of deep learning models by leveraging serverless architecture. Serverless computing has been popular for its auto-scaling, cost-effectiveness, and simplified management characteristics. However, the intense resource demands of deep learning models pose challenges in maintaining low response times and effective load balancing within serverless environments. The proposed architecture addresses these challenges by integrating principles from both deep learning model optimization and serverless computing. Through systematic experimentation and analysis, we demonstrate that by appropriately designing and tuning the deployment architecture, significant improvements in response time, performance, resource utilization, and load distribution can be achieved.

The exposure of employees to specific risks is usually due to increasing levels of work-related stress, which negatively affects their skills and effectiveness in their job duties, lead-ing to the onset of physical/mental illnesses, mistakes, or even accidents. The aim of this study is to investigate the psychosocial risks experienced by nurses in tertiary hospitals in Greece and their association with their attitudes towards safety and the occurrence of medication errors. The research was conducted in four tertiary hospitals in Greece, with the participation of 514 nurses of all educational levels. Questionnaires were used to collect data on work-related stress, professional burnout, and medication errors. The results highlighted that psychosocial risks, such as high work pressure and lack of support, are directly linked to professional burnout and an increased likelihood of medication errors. The necessity of social support, job autonomy, and work-life balance are underscored as critical factors for reducing stress and improving the quality of care. Specific strategies are proposed to enhance the mental health of nurses and improve working conditions.

This narrative review provides a thorough examination of medication-related osteonecrosis of the jaw (MRONJ), encompassing its etiology, the role of drug holidays, and contemporary treatment approaches. By systematically analyzing literature from 2022 to 2023, this paper synthesizes the latest findings and trends in MRONJ research. The study emphasizes the importance of a holistic understanding of MRONJ, beginning with its etiological factors, assessing the therapeutic implications of drug holidays, and evaluating the efficacy of current treatment modalities. This review aims to offer clinicians and researchers a consolidated resource, highlighting the intricacies of MRONJ management and proposing directions for future research. Through this comprehensive approach, the paper seeks to advance the understanding and treatment of MRONJ, ensuring an evidence-based, patient-centric approach in clinical practice.

Cacalol (C), a sesquiterpene isolated from Psacalium decompositum, has demonstrated anti-inflammatory and antioxidant activities. Its cytotoxic, antiproliferative, and pro-apoptotic effects have been previously shown in an in vitro breast cancer model. A derivative, Cacalol Acetate (CA), shows potential in regulating these processes, which had not been previously reported. This study focused on an in vitro cervical cancer model, assessing CA's anti-proliferative, pro-apoptotic, cytostatic, and anti-migratory activities using the HeLa cell line. The natural anticancer agent I3C was used as a control for comparison. CA demonstrated significant antitumor activities, including inhibiting cell growth, inducing apoptosis, arresting cells in the G2 phase of the cell cycle, and inhibiting cell migration. These effects were notably greater compared to I3C. I3C, while following a similar trend, did not induce Cas-3 expression, suggesting a different apoptotic pathway. Neither CA nor I3C increased p62 and LC3B levels, indicating they do not stimulate autophagy marker expression. Both compounds inhibited HeLa cell migrate on and induced cell cycle arrest. Despite both holding promise as anticancer agents for cervical cancer, CA's lower cytotoxicity and stronger regulation of tumor phenotypes make it a more promising agent compared to I3C.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Aiming at the APF algorithm in the collision-free path planning and LQR algorithm tracking process, there are problems such as unreachable target points, local optimization, low safety coefficient of autonomous lane change collision avoidance tracking control and poor stability, this paper proposes an optimized APF method, which solves the defects of the traditional artificial potential field method by adding the distance adjustment factor, the safety distance protection model and the sub-target virtual potential field, and at the same time generates the autonomous driving car collision-free path. The path tracking control system is designed based on feed-forward control and DLQR controller, in which the vehicle dynamics state space model is used as the basis, the model is linearized and discretized, and the corresponding constraint variables are set to minimize the control command objective cost function under the constraints, and the objective of the DLQR controller.The objective is to accurately determine the steering angle in order to achieve path tracking and eliminate the lateral error between the reference path and the actual path caused by external interference.Finally, the simulink model and CarSim parameter configuration joint simulation platform are built, and different obstacle scenarios and different speeds are selected for collision-free path planning and tracking motion simulation research and analysis, which verifies the accuracy and practicability of the algorithm, and shows more obvious advantages in obstacle avoidance ability, path smoothing degree, and collision avoidance safety stability. The ideas proposed in this paper are expected to be further extended and popularized to actual path planning problems, which has important practical significance and engineering value.

The effects of hypothermia on neonatal encephalopathy may vary regionally, spatially, and cytopathologically in the gyrencephalic neocortex with manifestations potentially influenced by seizures that alter the severity and distribution of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia with continuous encephalographic (cEEG) monitoring for seizures to study injury in neocortex. Neonatal piglets were randomized to naïve, HI-normothermia (NT), overnight hypothermia (HT) initiated 2 hours after HI, sham-NT, or sham-HT treatments. Some piglets within sham and HI groups received cEEG monitoring during recovery. Survival was 2-7 days (piglets were unmedicated and those with poor recovery and unresolving seizures were euthanized early); there was no differences in survival among groups (p&gt;0.078). Neuropathology was assessed by hematoxylin and eosin staining and immunohistochemistry for RNA Binding FOX-1 Homolog 3 (Rbfox3/NeuN). Normal and ischemic-necrotic neurons were counted (layers II-VI collectively) in somatosensory, motor, and prefrontal cortices, identified by cytoarchitecture and connectomics, and in inferior parietal cortex by layer. Seizure burden was determined. HI-NT piglets had reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to naïve, sham-NT, and sham-HT piglets in anterior and posterior motor and somatosensory cortices. Frontal cortex was vulnerable in the prefrontal lateral bank after HI-NT with ischemic-necrosis. HI-HT piglets had higher normal/total neuron ratios and lower ischemic-necrotic/total neuron ratios than HI-NT piglets in anterior/posterior motor and somatosensory cortices. Total normal neuron density in layer III of inferior parietal cortex was reduced in HI-NT piglets compared to sham piglets and was protected by HT. Laminar analysis of Rbfox3 in somatosensory cortex revealed three types of neurons: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT. Cortical neuron Rbfox3-depletion was partly rescued by HT. Seizure burden was more severe in HI piglets compared to sham piglets, but HI-NT and HI-HT piglets were similar. We conclude that 1) the neonatal piglet neocortex has a suprasylvian spatial vulnerability to HI and seizures; 2) HT protects against neuropathology in functionally different regions of the neonatal gyrencephalic neocortex; 3) neurons in neonatal neocortex have a limited cytopathology repertoire seen by H&amp;E staining; 4) higher seizure burden correlates with more ischemic-necrotic neurons in somatosensory cortex; 5) seizure presence associates with damage spread to inferior parietal cortex; 6) seizure presence is insensitive to HT, and 7) Rbfox3 immunophenotyping identifies a novel neuronal RNA splicing protein nuclear-depletion pathology that appears reversible by HT. This work demonstrates that HT protection of neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores depleted neuronal RNA splicing factor.

The effective dissemination and implementation of health service interventions into practice requires a range of strategic and systematic approaches. This paper applies a conceptual implementation framework to the evaluation of a hospital-wide clinical pharmacy initiative, a redesign of the discharge medication prescription pathway. The influencing factors and strategies used to overcome potential negative influences are described and assessed.

Cirsium japonicum, a traditional herb, exhibits significant anti-inflammatory activity; however, the main components and potential mechanisms of C. japonicum remain unclear. The aim of this study is to investigate the anti-inflammatory mechanism of Cirsium japonicum through network pharmacology and cellular experiments. The effective components and potential targets for anti-inflammatory activity of C. japonicum were identified using traditional Chinese medicine systematic pharmacology database, TCMSP analysis platform, and GeneCards database. The drug-component-target-disease network diagram was constructed using Cytoscape3.8.0 software, while the protein interaction network diagram was created using STRING database and Cytoscape3.8.0 software. Gene ontology (GO) enrichment and KEGG pathway enrichment analysis were carried out using DAVID database. Molecular docking between key targets and active components was constructed with AutoDock software to determine the best binding target. Results revealed that 14 active components of C. japonicum targeted 171 anti-inflammatory proteins. GO function enrichment analysis yielded 173 items, while KEGG pathway enrichment analysis identified 48 signaling pathways related to inflammation regulation. Molecular docking showed that strong affinity between sitosterol, stigmasterol, and other components with key targets such as peroxisome proliferator-activated receptor α recombinant protein (PPARA) and cyclooxygenase-2 (PTGS2). Vanillin, one active ingredient of C. japonicum, inhibited the release of lipopolysaccharide (LPS)-induced inflammatory factors in RAW264.7 cells. These findings suggest that C. japonicum may exert its anti-inflammatory effects by modulating the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt) signal pathway (PI3K-Akt) and apoptin signal pathway, highlighting the multi-component, multi-target, and multi-channel molecular mechanism underlying its anti-inflammatory properties. Finally, the anti-inflammatory effect of vanillin, an effective component in C. japonicum, was verified by cell experiments. This study provides a new understanding of the pharmacological mechanisms of C. japonicum in treatment of inflammatory conditions.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

Bosentan, an endothelin-receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male apoE-/- mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin and mice were randomized into 4 groups: 1) Control/COG: no intervention. 2) ΒΟG: bosentan 100 mg/kg/day per os. 3) ATG: atorvastatin 20mg/kg/day per os). 4) BO+ATG: Combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations were determined. The percentage of lumen stenosis significantly decreased across all treated groups: BOG: 19.5±2.2%, ATG: 12.8±4.8%, BO+ATG: 9.1±2.7% compared to controls (24.6±4.8%, p&lt;0.001). Both atorvastatin and bosentan significantly increased collagen content and fibrous cap thickness versus COG (p&lt;0.01). All intervention groups reduced the relative intra-plaque concentrations of MCP-1, MMP-3,-9, and increased TIMP-1 compared to COG (p&lt;0.001). Importantly, bosentan showed modest but additive to atorvastatin effects on the latter parameters compared COG (p&lt;0.05). Bosentan treatment in diabetic, atherosclerotic apoE-/- mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but complementary effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

Crown of thorns starfish (Acanthaster planci) are coral predators with advantages of having toxicity in their venom and tissue regeneration capabilities. With all these characteristics, only a handful of studies have highlighted the association of microorganisms with this organism. Crown of thorns starfish are common in Fiji and their analyses of microbial diversity for secondary metabolites could be of great interest to the scientific community. This study is an attempt to investigate Fijian-based A. planci for their venom and associated actinomycetes antibacterial activity and further identify the type of enzymes present in the crude venom extract. The CoTS venom extract (0.192 g) harbor enzymes such as gelatinase, caesinase, and amylase. An abundant and potent actinomycete strain, represented as FJA1 showed antibacterial activity against Enterococcus faecium with an inhibition zone of 10 mm. Moreover, all pathogenic test microorganisms were resistant against concentrations of 500 µg and 1 mg of A. planci venom extract.

Coffee is rich in caffeine (CF), chlorogenic acid (CGA) and phenolics. Differing types of coffee beverages and brewing procedures may result in differences in total phenolic contents (TPC) and biological activities. Inflammation and increases of platelet activation and aggregation can lead to thrombosis. We focused on determining the chemical composition, antioxidant activity and inhibitory effects on agonist-induced platelet aggregation and cyclooxygenase (COX) of coffee beverages in relation to their preparation method. We prepared instant coffee and brewed coffee beverages using drip, espresso and boiling techniques. Coffee extracts were assayed for their CF and CGA contents using HPLC, TPC using colourimetry, platelet aggregation with an aggregometer and COX activity using ELISA. The findings have shown all coffee extracts, except the decaffeinated types, contained nearly equal amounts of CF, CGA and TPC. Inhibitory effects of coffee extracts on platelet aggregation differed depending on the activation pathways induced by different agonists. All espresso, drip and boiled coffee extracts caused dose dependent inhibition of platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid (ARA). The most marked inhibition was seen at low doses of collagen or ARA. Espresso and drip extracts inhibited collagen-induced platelet aggregation more than purified caffeine or CGA. Espresso, boiled and drip coffee extracts were also a more potent inhibitors of COX-1 and COX-2 than purified caffeine or CGA. We conclude that inhibition of platelet aggregation and COX-1 and COX-2 may contribute to anti-platelet and anti-inflammatory effects of espresso and drip coffee extracts.

Functional gastro-intestinal disorders (FGID) including irritable bowel syndrome (IBS) are frequently handled by self-management with over the counter (OTC) products such as hyoscine butylbromide (HBB), alone or in combination with paracetamol, and natural products such as peppermint oil. To obtain real-world information, we have performed an anonymous pharmacy-based patient survey among 1686 users of HBB, HBB + paracetamol and peppermint oil. Based on the distinct but overlapping indications for the three OTC products, multiple logistic regression was applied to compare them in users reporting gastrointestinal cramps and pain, bloating, flatulence, or IBS as cardinal symptom. All three treatments reduced symptoms and associated impairments of work/daily chores, leisure activities, and sleep by approximately 50%. Based on the four cardinal symptoms and the four dependent continuous variables of interest (change of intensity of symptoms and of the three impairment domains) a total of 16 logistic regression models were applied. HBB, HBB + paracetamol, and peppermint oil had similar reported overall effectiveness in those models. Gender, age, baseline symptom severity and impairment in one of three domains had small and inconsistent effects on perceived treatment success. We provide evidence that HBB, HBB + paracetamol, and peppermint oil have comparable effectiveness in their approved indications under real-world conditions in an OTC setting.

Objective tools to track medication adherence are lacking. A tool to monitor pill intake that can be implemented in mHealth apps without the need for additional devices was developed. We propose a pill intake detection tool that uses digital image processing to analyze images of a blister to detect the presence of pills. The tool uses the circular Hough transform as a feature extraction technique and is therefore primarily useful for the detection of pills with a round shape. This pill detection tool is composed of two steps. First, the registration of a full blister and storing of reference values in a local database. Second, the detection and classification of taken and remaining pills in similar blisters, to determine the actual number of untaken pills. In the registration of round pills in full blisters, 100% of pills in gray blisters or blisters with a transparent cover were successfully detected. In counting of untaken pills in partially opened blisters, 95.2% of remaining and 95.1% of taken pills were detected in gray blisters, while 88.2% of remaining and 80.8% of taken pills were detected in blisters with a transparent cover. The proposed tool provides promising results for the detection of round pills. However, the classification of taken and remaining pills need to be further improved, in particular for the detection of pills with non-oval shapes.

Barcode medication administration (BCMA) is advocated as a technology that reduces medication errors relating to incorrect patient identity, drug or dose. Little is known, however, about the impact it has on nursing workflow. Our aim was to investigate the impact of BCMA on nursing activity and workflow. A comparative study was conducted on two similar surgical wards within an acute UK hospital. We observed nurses during drug rounds on a non-BCMA ward and a BCMA ward. Data were collected on drug round duration, timeliness of medication administration, patient identification, medication verification and general workflow patterns. BCMA appears not to alter drug round duration, although it may reduce the administration time per dose. Workflow was streamlined, with a reduction in use of the medicines room. The rate of patient identification increased from 74% (of 47) patients to 100% (of 43), with 95% of 255 scannable medication doses verified using the system. This study suggests that BCMA does not affect drug round duration; further research is required to determine the impact it has on timeliness of medication administration. There was reduced variability in the medication administration workflow of nurses, along with an increased patient identification rate and high medication scan rate, representing potential benefits to patient safety.

The increasing environmental awareness and carbon-storing capability of wood have amplified its relevance as a building material. The demand for high-quality wood species necessitates exploring alternative, underutilized wood sources due to limited forest areas and premium wood volume. Consequently, the veneer-based industry is considering lower-value hardwood species like grey alder, black alder, and aspen as substitutes for high-quality birch. Initially less appealing due to their lower density and mechanical properties, these species show promise through densification, which enhances their density, strength, and hardness. This study aims to enhance plywood screw withdrawal capacity and surface hardness by densifying low-density wood species and using them in plywood face veneer layers or all layers. The relationship between wood density, surface hardness, and screw withdrawal capacity of plywoods made of low-value species like aspen and black alder is examined. Experimental work with a pilot-scale veneer and plywood production line demonstrates improved surface hardness (65% and 93% for aspen and black alder, respectively) and screw withdrawal capacity (16% and 35% for aspen and black alder, respectively) in face veneer densified low-value hardwood plywood. This research highlights the potential of densified low-value wood species to meet construction requirements, expanding their practical applications.

Intelligent fault diagnosis techniques have replaced the time-consuming and unreliable human analysis, increasing the efficiency of fault diagnosis. Deep learning model can improve the accuracy of intelligent fault diagnosis with the help of its multilayer nonlinear mapping ability. This paper has proposed a novel method named Deep Convolutional Neural Networks with Wide First-layer Kernels (WDCNN). The proposed method uses raw vibration signals as input (data augmentation is used to generate more inputs), and uses the wide kernels in first convolutional layer for extracting feature and suppressing high frequency noise. Small convolutional kernels in the preceding layers are used for multilayer nonlinear mapping. AdaBN is implemented to improve the domain adaptation ability of the model. The proposed model addresses the problem that currently, the accuracy of CNN applied to fault diagnosis is not very high. WDCNN can not only achieve 100% classification accuracy on normal signals, but also outperform state of the art DNN model which is based on frequency features under different working load and noisy environment.

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles in tumor development by regulating cell adhesion, survival, proliferation, and stemness, it has been considered a target for tumor therapy. Anti-CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody-drug conjugates and chimeric antigen receptor-T cell therapy. We previously developed anti‐pan-CD44 mAbs, C₄₄Mab-5 and C₄₄Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG_2a version of the anti-pan-CD44 mAbs (5-mG_2a-f and C₄₄Mab-46-mG_2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG_2a-f and C₄₄Mab-46-mG_2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG_2a. These results indicate that 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.

Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are described in the neurological context as well as in autoimmune diseases. However, a deeper understanding of these differences in peripheral immune cells remains limited. In this study, we investigated the effects of dopaminergic stimulation on activation and cytokine secretion of peripheral blood mononuclear cells from women and men using flow cytometry, ELISA and multiplex assay. We found a B cell-driven downregulation in cytokine secretion of monocytes exclusively from women under physiological conditions. Moreover, B cells from men showed higher dopamine receptor (DR) expression, which was shown to be further increased by sex hormones only in men. In monocytes from women, an acute inflammatory stimulus via CpG combined with dopaminergic stimulation caused a switch to a proinflammatory phenotype, which was less pronounced in men. These novel findings in sex-specific responses to dopaminergic stimulation are crucial for understanding DA’s function in the healthy and activated immune system and provide evidence to treat DA-related pathologies in a sex-specific manner.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.