The aim of the study was to evaluate two widely studied biomarkers: MMP-9 and S100B in blood serum in healthy people after physical exercise mimicking physical activity during bi-lateral tonic-clonic seizures. Both biomarkers have been shown to increase after seizures, and their serum levels tend to be higher in epilepsy patients compared to individuals without epi-lepsy. To achieve this goal, we have developed two sets of exercises, each consisting of a tonic contrac-tion phase and a phase of alternating muscle work, lasting a total of approximately 5 minutes. Both sets of motor exercises were performed in the same group of healthy volunteers 6 months apart. Serum samples were collected before exercise, 3 hours after exercise, and the next day (time points 0, 3 hours, and 24 hours). Our results demonstrated that both sets of motor exercises led to a similar increase in MMP-9 levels, while neither while neither affected S100B levels. No significant differences in MMP-9 levels were observed due to muscle failure. We propose that the increase in MMP-9 is primarily induced by muscle contraction and additional mechanisms observed during exercise, such as neutrophil degranulation. S100B appears to be a promising biomarker in epilepsy, as it is not induced by physical activity but does increase following seizures.

Introduction: The association between epilepsy and myasthenia gravis has rarely been reported, and only in small case series. Objective: To report the frequency of epilepsy and myasthenia gravis and to describe a case series of patients with myasthenia gravis and epilepsy, focusing on their clinical characteristics and searching for a possible physiopathological mechanism. Methods: A retrospective, observational, adult center study was conducted in 2022. Patients were recruited from the database of the outpatient clinic of the Myasthenia Gravis unit and Epilepsy unit. Results: Five patients were included. Frequency of epilepsy in the myasthenia gravis cohort was 5/469 (1.1%), and of myasthenia gravis in the epilepsy cohort was 5/1432 (0.35%). All patients suffered focal epilepsy, mainly fronto-central, and drug-resistant in half of them. Myasthenia gravis was generalized and with exacerbations in half of them. Three patients were thymectomized. Other autoimmune diseases were found in 2 (40%). Epilepsy onset preceded myasthenia gravis onset in all patients. Both diseases were considered autoimmune-related in 3/5 (60%). Conclusion: Epilepsy and myasthenia gravis are only infrequently associated. In adult patients, epilepsy onset precedes myasthenia onset in most cases. In some cases, epilepsy has an autoimmune aetiology and coexists with other autoimmune conditions.

Mesial temporal lobe epilepsy (mTLE) is one of the most common and refractory focal epilepsy syndromes. The molecular mechanisms of TLE are not completely understood. The aim of this study was to investigate the expression and potential function of plasma exosomal miRNAs (miR-483-5p, miR-671-5p, and miR-150-3p) in a mouse mode and in temporal lobe epilepsy patients. It was found that exosomal miRNAs were differentially expressed in three phases of the mouse mode, and exosomal miRNAs were down-regulated in mTLE patients compared with healthy controls. A bioinformatics analysis showed that target genes of exosomal miRNAs were significantly involved in the apoptotic process, cell adhesion, nervous system development, neurotrophin signaling pathway, PI3K-Akt signaling pathway, and metabolic pathways. The areas under the curve of miR-483-5p and miR-150-3p were 0.8714 (sensitivity = 75.00%, specificity = 91.65%) and 0.8213 (sensitivity = 67.50%, specificity = 90.00%), respectively. More importantly, the exosomal miRNAs were significantly associated with clinical parameters. Exosomal miRNAs may have the potential to become diagnostic and therapeutic biomarkers.

Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut-brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this and other rare neurological diseases.

High rates of phosphorus (P) currently being applied to soils for the production of vegetables in the Mekong Delta, Vietnam has led to the concern of its negative effect on the economics and the environment. This research presents a comprehensive study on the determination of P supplying capacity in this region of Vietnam to examine the possibility of reducing P fertilizer input. One hundred twenty (120) soil samples were collected to evaluate total P and Bray 1 available P in the soils. Phosphorus maximum sorption, degree of P saturation, P release, and the effect of P fertilizer on corn (Zea mays L.) yield in greenhouse and fields were also determined. Total P concentrations of 56.7% soil samples evaluated yielded high P concentrations (>560 mg P/kg), while 74.2% of the samples had high Bray 1 available P concentrations (>20 mg P/kg soil). Maximum P sorption ranged from 149 to 555 mg P/kg soil, respectively and has negative correlation to available P (r = - 0.63*), degrees of P saturation ranged from 0.63 to 5.46% correlated to available P (r = 0.98**) and maximum P release ranged from 1.2 to 61.9 mg P/kg soil, respectively correlated to available P (r = 0.96**). Corn grown in soils with available P concentrations >15 mg P/kg did not respond to P fertilizer in greenhouse or field experiments. We conclude that many farmers in this region can reduce P fertilizer input, thus increasing their profits and reducing negative environmental impacts associated with excess soil P for sustainable agriculture.

Background/Objectives: Determining the outcome of epilepsy is crucial for making proactive and timely treatment decisions, as well as for counseling patients. Recent research efforts have focused on using various imaging techniques and EEG for prognostication; however, there is insufficient evidence regarding the role of blood parameters. Our study aimed to investigate the additional prognostic value of routine blood parameters in predicting epilepsy outcomes. Methods: We analyzed data from 1,782 patients who underwent routine blood tests within 90 days of their first visit and had a minimum follow-up duration of three years. The etiological types were structural (35.1%), genetic (14.2%), immune (4.7%), infectious (2.9%), and unknown (42.6%). The outcome was defined as the presence of seizures in the last year. Results: Initially, a multivariate analysis was conducted based on clinical variables, MRI, and EEG data. This analysis revealed that sex, age of onset, epileptiform discharge, structural etiology, and the number of antiseizure medications were related to the outcome, with an area under curve (AUC) of 0.708. Among the blood parameters, fibrinogen, bilirubin, uric acid, and aPTT were significant, with AUCs of 0.602, 0.597, 0.455, and 0.549, respectively. Including these blood parameters in the analysis slightly improved the AUC to 0.713. Conclusions: Some blood parameters were found to be related to the final outcome, potentially paving the way to understanding the mechanisms of epileptogenesis and drug resistance.

SUDEP is a sudden death in a person with epilepsy, without evidence of a seizure before death. While its cause is still unclear, various factors have been linked to seizure onset and cardiopulmonary function. Studies have shown that although 91.3% of epilepsy patients want information on premature death, only 31% of them receive it. The numbers emphasize the need for open and sensitive communication by medical professionals. It is important to choose the appropriate moment for the conversation, avoiding periods of stress and ensuring emotional stability in the patient, as well as clear, appropriate and easy to comprehend information about SUDEP. To facilitate this, knowing the patient's level of knowledge is essential. Education on the warning signs of seizures and SUDEP can help take precautions and can decrease the incidence of the phenomenon itself. Effective epilepsy care requires a comprehensive plan, including medication adherence and lifestyle changes. Regular communication and collaboration between the patient, caregiver and health professionals are essential for the effective management of epilepsy, so just as epilepsy has a fluid, changeable course of disease and follow-up appointments are very important, the topic of SUDEP is not a one-time conversation either.

Orthostatic hypotension (OH) is a condition marked by a significant drop in blood pressure upon standing, resulting from impaired autonomic regulation of vascular tone and blood volume. This study investigates the prevalence, physiological mechanisms, and occupational risk factors for OH among high-risk professions in Nepal, such as traffic police, security guards, and shopkeepers. Using a cross-sectional design, participants were evaluated for blood pressure variability, autonomic function, and fluid balance. The findings reveal a high incidence of OH, linked to reduced baroreceptor sensitivity and impaired sympathetic activation due to prolonged standing and inadequate hydration. This study highlights the need for tailored clinical interventions and workplace modifications to mitigate OH in vulnerable occupational groups.

Sewage sludge is an organic waste generated in waste-water treatment plants with certain content of nutrients, what may potentially be used as a source of slow release fertilizer, especially as phosphorus (P) source, but it demands some pre-treatment and the content of P is much lower compared to soluble mineral fertilizers. For these reasons, composted sewage sludge was used to manufacture pelletized organomineral fertilizers, mixing it with the inorganic sources monoammonium phosphate (MAP) and AshDec® (ASD) (thermochemically incinerated sewage sludge). The fertilizers were physiochemically characterized and evaluated as to the dynamics of soil P solubilization, and the forms of P remaining according to its lability. The sources evaluated were: organic compost of sewage sludge powder (SSC), pelletized SSC (SCP), pelletized organominerals SSC+MAP (S+MAP) and SSC+ASD (S+ASD), ASD alone, all compared to a soluble mineral fertilizer (MAP), and a control without P fertilizer. A test was conducted in leaching columns with 50 g of soil (Oxisol), where the fertilizers were applied at a dose of 100 mg P/column, and 30 mL of water or 2% citric acid were added daily for 30 consecutive days. The collected leachates had pH measured and P content determined. Pelletizing process resulted in denser products and promoted more gradual P release. The organomineral S+MAP was the most water-soluble recycled source, solubilizing about 70% of the total P, while the others presented much lower solubilization (<20%). In contrast, all fertilizers showed high solubility in 2% citric acid (except for S+ASD). After leaching, the greatest amount of P remaining in the soil as labile and moderately labile. Composting and the AshDec process produced materials with slow P solubilization, which would be favoured to solubilize in acidic soils and acidic rhizosphere conditions. In turn, the organomineral mixture of SSC with a highly soluble mineral fertilizer (MAP) resulted in a promising product with intermediate nutrient solubility, better synchronized with crop demand, thus increasing efficiency in P use.

Even brief epileptic seizures can lead to activity-dependent structural remodeling of neural circuitry. Animal models show that the functional plasticity of synapses and changes in the intrinsic excitability of neurons can be crucial for epileptogenesis. However, the exact mechanisms underlying epileptogenesis remain unclear. We induced epileptiform activity in rat hippocampal slices for 15 min using a 4-aminopyridine (4-AP) in vitro model and observed hippocampal hyperexcitability for at least 1 hour. We tested several possible mechanisms of this hyperexcitability, including changes in intrinsic membrane properties of neurons, presynaptic and postsynaptic alterations. Neither input resistance nor other essential biophysical properties of hippocampal CA1 pyramidal neurons were affected by epileptiform activity. The glutamate release probability also remained unchanged, as the frequency of miniature EPSCs and the paired amplitude ratio of evoked responses did not change after epileptiform activity. However, we found an increase in the AMPA/NMDA ratio, suggesting alterations in the properties of postsynaptic glutamatergic receptors. Thus, the increase in excitability of hippocampal neural networks is realized through postsynaptic mechanisms. In contrast, the intrinsic membrane properties of neurons and the probability of glutamate release from presynaptic terminals are not affected in a 4-AP model.

A seroepidemiological study conducted from 2020 to 2022 in Guangzhou, China, aimed to evaluate varicella antibody levels. We measured varicella antibody concentrations using an enzyme-linked immunosorbent assay (ELISA) in a cohort of 3,300 subjects. The mean varicella IgG-specific antibody level was 171.2 mIU/mL (95% CI: 158.9, 184.4), with an overall positivity rate of 67.00% (95% CI: 65.37, 68.60). Varicella antibody levels were found to be influenced by age, vaccination dosage, and history of varicella infection. Notably, antibody concentrations increased with age and the number of vaccinations. Subjects with a vaccination history maintained positive antibody levels six years post-vaccination. We recommend two doses of the varicella vaccine for both children and adults. Before incorporating the varicella vaccine into Guangzhou's routine immunization programs, a comprehensive assessment of disease burden and the economic viability of vaccination strategies is essential.

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p<0.001, Duncan’s new multiple range test) and their total duration (p<0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p<0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

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.

The involvement of the prefrontal cortical dopaminergic system in psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or nonconvulsive epilepsies. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive forms, and KM strain was a model for convulsive epilepsy comorbiding with ASD-like behavioral phenotype. Prefrontal cortex of rats with any of epileptic pathology studied, demonstrated profound decreases in binding densities to both D1DR, D2DR; the effects were localized in the primary and secondary anterior cingulate cortexi, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent (not correlated) from each other. The particular group of epileptic rats with ASD-like phenotype (KM strain), displayed changes in the lateral prefrontal cortex and adjacent regions: D1DR were lowered, but those to D2DR elevated, in anterior dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of rat archeocortex were localized in the medial regions, whereas ASD-related candidates were seen in the lateral aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

In this paper, we introduce the (ρ,q)-analogue of the p-adic factorial function. By utilizing some properties of (ρ,q)-numbers, we obtain several new and interesting identities and formulas. We then construct the p-adic (ρ,q)-gamma function by means of the mentioned factorial function. We investigate several properties and relationships belonging to the foregoing gamma function, some of which are given for the case p = 2. We also derive more representations of the p-adic (ρ,q)-gamma function in general case. Moreover, we consider the p-adic (ρ,q)-Euler constant derived from the derivation of p-adic (ρ,q)-gamma function at x = 1. Furthermore, we provide a limit representation of aforementioned Euler constant based on (ρ,q)-numbers. Finally, we consider (ρ,q)-extension of the p-adic beta function via the p-adic (ρ,q)-gamma function and we then investigate various formulas and identities.

The gap junction-coupled astroglial network plays a central role in the regulation of neuronal activity and synchronization, but its involvement in the pathogenesis of neuronal diseases is not yet understood. Here we present the current state of knowledge about the impact of impaired glial coupling in the development and progression of epilepsy and discuss whether astrocytes represent alternative therapeutic targets. We focus mainly on temporal lobe epilepsy (TLE), which is the most common form of epilepsy in adults, characterized by high therapy resistance. Functional data from TLE patients and corresponding experimental models point to a complete loss of astrocytic coupling, but preservation of the gap junction forming proteins connexin43 (Cx43) and connexin30 (Cx30) in hippocampal sclerosis. Several studies further indicate that astrocyte uncoupling represents a causal event in the initiation of TLE, as it occurs very early in epileptogenesis, clearly preceding dysfunctional changes in neurons. However, more research is needed to fully understand the role of gap junction channels in epilepsy and to develop safe and effective therapeutic strategies targeting astrocytes.

Introduction: Early childhood caries is a significant public health problem among preschool children. The COVID-19 pandemic, which restricted dental services, altered family dynamics, affected child development, and created new demands on caregivers, may have exacerbated this issue. Objective: Analyze the occurrence and severity of caries and identify associated factors in preschool children attending public municipal daycare centers in Salvador, Bahia, Brazil, Methodology: A cross-sectional epidemiological study was conducted to investigate caries in children aged 2 to 5 years in 2022 and 2023. Caries was assessed using the decayed, extracted, filled, and missing teeth (DEFT) index, and prevalence was calculated. Sociodemographic, family dynamic, dietary, and healthcare utilization data were obtained through a questionnaire. After descriptive and exploratory analyses, robust Poisson multivariable regression was conducted at a 5% significance level, considering socioeconomic, psychosocial, and behavioral aspects. Results: A total of 440 preschoolers participated, with a mean age of 55 months. The majority were Black or mixed race (88.86%) and female (52.73%). The prevalence of caries was 30.91% and the mean DEFT score was 1.1. In the multivariable analysis, low family income (up to one minimum wage) and not playing outdoors during the pandemic were associated with a higher prevalence of caries. Conclusion: The prevalence and severity of caries remain high, and the pandemic has contributed to the maintenance of this epidemiological scenario. Public health measures and policies promoting social justice should be planned to improve oral health conditions in childhood.

In this study, we propose a conservative and compact finite difference scheme designed to preserve both the mass change rate and energy for solving the sixth-order Boussinesq equation with the surface tension. Theoretical analysis confirms that the proposed scheme achieves second-order accuracy in temporal discretization and fourth-order accuracy in spatial discretization. The solvability, convergence, and stability of the difference scheme are rigorously established through the application of the discrete energy method. Additionally, a series of numerical experiments are conducted to illustrate the effectiveness and reliability of the conservative scheme for long-time simulations.

In this paper, we introduce a new class of $(p,q)$-analogue type of Fubini numbers and polynomials and investigate some properties of these polynomials. We establish summation formulas of these polynomials by summation techniques series. Furthermore, we consider some relationships for $(p,q)$-Fubini polynomials associated with $(p,q)$-Bernoulli polynomials, $(p,q)$-Euler polynomials and $(p,q)$-Genocchi polynomials and $(p,q)$-Stirling numbers of the second kind.

Febrile seizures (FSs) are defined as seizures occurring in children aged 6 months to 5 years with a background of elevated body temperature. It is one of the most common neurological disorders of childhood, emphasizing the importance of understanding the causes of FSs and their impact on the developing nervous system. However, there are significant limitations to the technologies currently available for studying the etiology and pathophysiology of seizures in humans. It is currently not possible to adequately capture the subtle molecular and structural rearrangements of the nervous system that can occur after seizures in humans. The use of animal models can be invaluable for these purposes. The most commonly used models in modern research are hyperthermic models in rats and mice aged 10-12 days. While these models can reproduce many of the characteristics of FSs, they have certain limitations. This review outlines the key considerations when working with models of FSs, provides an overview of current approaches to producing seizures in different model subjects, and presents a summary of key findings regarding morphological and functional changes in the brain, as well as behavioral alterations, that have been identified in studies using animal models of FSs.

This study explores the intriguing phenomenon of action potentials reverberating and propagating in high-resistance tissues, such as gliosis, leading to the emergence of short circuits within the brain. Gliosis, characterized by increased tissue resistance, presents a unique environment for electrical signals. My research investigates the possible mechanisms behind these reverberations and their role in the creation of self-empowering short circuits that can potentially affect the entire brain's functionality. Understanding these processes may have significant implications for the treatment and management of neurological disorders associated with gliosis and abnormal electrical activity in the brain.

Metabolic syndrome (MetS) refers to the group of several interconnected risk factors that collectively double the risk of cardiovascular disease. Epilepsy is linked to MetS across all age groups, though its prevalence differs across various studies. This can be understood from the perspective of seizure-related metabolic abnormalities, long-term antiepileptic drugs (AEDs) use, and a more sedentary lifestyle due to epilepsy. The factors that are considered in developing MetS for patients with epilepsy (PWE) are age, residence, level of physical activity, food intake status, epilepsy subtype, epilepsy duration, current (AEDs) use, drug responsiveness status, body-mass index (BMI), total cholesterol and LDL-cholesterol levels. A deeper understanding of the epilepsy-AED-MetS connection and the exploration of lifestyle interventions hold the promise of significantly improving the overall health and well-being of PWE. Clinicians managing PWE should closely monitor various risk factors for developing MetS and consider them when selecting AED treatment.

Background: Platelets are increasingly recognised for their multifaceted roles in inflammation beyond their traditional involvement in haemostasis. This review consolidates knowledge on platelets as critical players in inflammatory responses. Methods: This study did an extensive search of electronic databases and identified studies on platelets in inflammation, focusing on molecular mechanisms, cell interactions, and clinical implications, emphasising recent publications. Results: Platelets contribute to inflammation via surface receptors, release of mediators, and participation in neutrophil extracellular trap formation. They are implicated in diseases like atherosclerosis, rheumatoid arthritis, and sepsis, highlighting their interaction with immune cells as pivotal in the onset and resolution of inflammation. Conclusion: Platelets are central to regulating inflammation, offering new therapeutic targets for inflammatory diseases. Future research should explore specific molecular pathways of platelets in inflammation for therapeutic intervention.

Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties, Stroke and Epilepsy in particular, clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence (AI) can predict the expected neurological impairment from an AIS (Acute Ischemic Stroke), the possibility of ICH (IntraCranial Hemorrhage) expansion, and the clinical outcomes of comatose patients. This review article informs readers of artificial intelligence principles and methods. The article introduces the basic terminology of artificial intelligence before reviewing current and developing AI applications in neurology practice. AI holds promise as a tool to ease a neurologist’s daily workflow and supply unique diagnostic insights by analyzing data simultaneously from several sources, including neurological history and examination, blood and CSF laboratory testing, CNS electrophysiologic evaluations, and CNS imaging studies. AI-based methods are poised to complement the other tools neurologists use to make prompt and precise decisions that lead to favorable patient outcomes.

Epilepsy, a disorder of unprovoked recurring seizures, continues to be seen as a growing medical concern worldwide. It represents the most common, non-communicable brain disorder, affecting persons of all ages. Every year over five million persons are formally diagnosed with epilepsy when seeking medical care. Often diagnosed as a young child, most persons can live a seizure-free life once there is an early diagnosis, proper patient education, and keen clinical management. However, the reoccurrence of status epilepticus, a neurological emergency, can be linked to untreated underlying causes and lead to serious morbidity and even early mortality if not properly managed. The prognosis is heavily reliant on the discovery of the underlying cause. Epilepsy, in recent times, provides a terminology for ease of identification of the associated clinical symptomology. Epilepsy, an umbrella term, can manifest differently as either idiopathic, symptomatic, or cryptogenic. However, distinguishing epilepsy from other seizure mimics is critical to preventing complications. Epilepsy research, like many other neurological symptoms, is limited in low-resource areas. Therefore, through greater awareness of epilepsy and public education campaigns, better health outcomes can be achieved. There is huge utility in clear communication of medical information among healthcare providers as well as in optimizing treatment plans.

(1) Background: Hemispherotomy is the generally accepted treatment for hemispheric drug resistant epilepsy (DRE). Lateral or vertical approaches are performed according to the surgeon's preference. Multiples technical variations have been proposed since Delalande first described his vertical technique. We propose a sub-insular variation of the vertical parasagittal hemispherotomy (VPH) and describe our case series of patients operated on with this procedure. (2) Methods: a continuous series of patients operated on by the senior author (CR) with the modified sub-insular VPH was retrospectively analyzed. We report the demographic pre-operative characteristics, epilepsy and functional outcome as well as the surgical complications.(3) Results: Twenty-five patients were operated on between August 2008 and August 2023, twenty-three of them have at least a 3-month follow-up. On this last group 86,3% of patients were seizure-free. Only two patients developed post-operative hydrocephalus (8.7%), all patients with autonomous preoperative walk and 86,3% of the total series were able to walk without assistance (86.3%) and perform adapted social activities at last follow-up.(4) Conclusion: The modified vertical parasagittal sub-insular hemispherotomy is a successful surgical technique for hemispheric DRE with seizure freedom rates similar to the biggest series reported in the literature. Compared to other series, patients operated with our modified technique had a lower rate of postoperative hydrocephalus and excellent long-term motor and cognitive outcome.

Aim: The majority of medicines used in Poland are generic drugs – substitutions of the original. Objective of the study was to obtain information on the current knowledge about generic medicines among Polish patients with epilepsy. Material and Methods: The study was conducted based on a self-developed questionnaire. The questionnaire consisted of 25 questions, including questions regarding their knowledge about generics, their previous experience and the factors behind these choices. Results: Overall, 1220 questionnaires were analyzed. Among all patients, 66.39% reportedly heard about generics. Of these 61.48% of patients had used the generic drugs in past. A significant proportion of participants had never been recommended to switch to a generic medicine by their health care professional (22.95% physician and 13.93% pharmacist). Statistically relevant differences were observed regarding the respondents’ kind and level of education, place of residence, and net income per household. Conclusions: Significant gaps were identified in the knowledge and perceptions among patients regarding generic medicines especially in relation to efficacy and safety of generic medicines. Efforts must be directed towards increasing public awareness of generic medicines and should also focus on educating patients about generic medicines.

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.

Background: Immunologic and neuro-inflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. Methods: We performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Results: Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways in-volved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Conclusions: Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.

Introduction: Epilepsy is one of the most common neurological diseases. Epilepsy poses a significant burden on the quality of life of affected individuals and their families. The aim of this study was to determine the psychiatric disorders in epileptic patients. Methods and Materials: This descriptive-analytical study was conducted in 2017 with a simple random sampling method on patients with epilepsy who admitted to the neurology department. Results: Among the 150 examined patients, 88 (58.7%) were female and 63(42%) had epilepsy more than 10 years. The most common psychiatric disorder among epileptic patients was depression (68 patients = 45.3%) and anxiety (65 patients = 43.3%) patients. Conclusion: Most of patients had more than 10 years history of epilepsy. Also, Anxiety and depression were the most common symptoms in epileptic patients. It need to more study to determine the psychiatric disorders in epileptic patients.

Software Engineering education has grown during the past couple of decades as a specialized branch of computer science education to address employment demands. Software Engineering education is constantly evolving because of its dynamic nature. However, there are still some gaps between the skills being taught in the universities and skills required for employment. In this paper, we present our experience of designing and delivering a new module to enhance skills for employment. We have taken a structured approach to analyze the gap through literature review and our personal experiences of engaging with employers of our students. Based on the analysis, we arrived at a set of gaps between what we teach and what the employers of our students need. We prioritized the gaps and envisaged a new module ‘Contemporary Software Engineering’ to address the gaps and subsequently help our students for an easy transition to job. As part of our experience, we present the background, design and delivery of the module and reflect on our journey of delivering the module for a few years.

Polluting discharges are produced at a rate that is inexorably rising in tandem with human activity development. Eutrophication and other matters, such as offensive aquatic life, require wastewater to be treated before being discharged into the environment. Prior releasing into water bodies, the treated waters must to undertake laboratory analysis. For this purpose, an analysis using standard methods was carried out at the Laboratory Waterworks in Debrecen on various samples taken from various wastewater treatment plants (sewage treatment plants) in Hungary. The overall objective of this study was to assess the quality of the effluents from the fourteen (14) wastewater treatment plants and investigate their efficiency by measuring various physicochemical parameters and microbiological parameters as excellent indicators to evaluate the performance of the studied wastewater treatment plants. The microbiological indicator monitored was the heterotrophic count (HPC) by estimating its total number, which provides useful information for the assessment and monitoring of water samples. The determination of physicochemical parameters included biological oxygen demand (BOD5), chemical oxygen demand (COD) and nitrite -N (NO2), ammonia-N (NH3-N), nitrate-N (NO3) total phosphorus (TP), Kjeldahl- Nitrogen (organic N+ammonia-N) (TKN), total inorganic N (TI), total suspended solids (TSS) and total nitrogen (TN). The performance of the wastewater treatment plants examined was checked and the results were conclusive. In the future, solutions should be applied to these wastewater treatment plants and some recommendations are suggested.

Formaldehyde is generated via the biochemical and chemical pathways, and it widely exists in foods. Its chronic exposure causes carcinogenic, neurotoxic, reproductive, allergic, immunological, genetic and respiratory toxicities. However, food-sourced formaldehyde is usually neglected due to its rapid metabolism after intake. Compared with its residual level in processed foods, a large proportion of formaldehyde disappears because of its high reactivity. Nevertheless, its elimination reaction mechanism and the potential consequences remain unclear. In this review, the disappearing pathway of formaldehyde from two aspects, the formation of formaldehyde-derived toxins and aromas, was reviewed. This review article may help food scientists take appropriate strategies to use the beneficial reactions of formaldehyde or divert its harmful effects to beneficial ones.

Employee turnover is a significant issue for financial institutions, impacting productivity, increasing recruitment costs, and disrupting critical operations. In this project, this study aimed to predict employee turnover using a dataset containing attributes such as employee satisfaction, performance, and tenure. By framing the task as a binary classification problem, this study employed CatBoost and XGBoost, two advanced regression-based algorithms, to develop predictive models. This paper's analysis demonstrated that CatBoost outperformed XGBoost across all evaluation metrics, including MAE, MSE, RMSE, and R², making it the more effective model for predicting turnover in the financial sector. The study highlights key factors contributing to employee attrition, such as job satisfaction, tenure, and promotion opportunities, offering actionable insights for retention strategies. Additionally, by predicting probabilities rather than binary outcomes, this study aims to make more detailed decisions about employee retention. This research provides valuable tools for financial institutions to mitigate the risk of turnover, retain critical talent, and ensure operational continuity.

Granular material is one of the most common in nature. Recently, there has been a significant amount of interest in the granular materials, such as powders or sand. It is challenging to describe the motion of such kind of macroscopic size matter, because it behaves like solid, fluid or gas. Size division, pattern formation, avalanches, packing and convection - these are just a few examples from a wide range of observed phenomena that occur during the motion process of granular matter. Most of these processes are based by flow and no wonder that much effort has been devoted to obtain a hydrodynamic description in which granular materials are treated as a continuous medium. During the research of vertically shaken granular medium motion in an opened container it was found that experimental and numerical results are explained by hydrodynamic theory. This paper investigates the motion of a granular matter for a shallow, vertically shaken bed. We assume the Leidenfrost state as initial and the matter resembles a fluid heated up from below.A one-dimensional isothermal and a non-isothermal problem of granular material motion,simulatedby a hydrodynamic model are considered, and the material is assumed to be a continuous medium. The local temporal solvability of isothermal and non-isothermal initial boundary-value problem in Sobolev’s spaces is proved. This work presents a numerical study of the one-dimensional model of granular medium flow. The feature of this model is consideration of the Navier-Stokes equations accounting an interpolation form of VanderWaals constitutive equation for pressure. A finite-difference approximation for numerical solution is proposed.

This bibliometric study analysed breast cancer research trends and outputs from 2014 to 1 2023, utilising data from the Scopus database. The primary objectives include analysing publication 2 growth, citation metrics, document type distribution, leading countries, preferred journals and 3 authorship patterns. The study reveals a significant increase in breast cancer research publications, 4 with a total of 12,073 documents and 216,769 citations over the ten-year period. The United States 5 leads in publication output and citation impact, followed by China and Japan. Articles are the 6 predominant document type for total 73.4% of publications, while reviews and book chapters also 7 contribute notably. The most preferred journals for publishing breast cancer research include Breast 8 Cancer Research and Treatment, Clinical Breast Cancer, and Breast Cancer Research. Authorship 9 patterns show a trend towards multi-authored papers, with a substantial number of papers having 10 more than five authors. The study underscores the global collaborative effort in advancing breast 11 cancer research and highlights key areas for future exploration.

Introduction: This study aims to elucidate the clinical diagnostic value of S100 Calcium Binding Protein beta (S100B) in epilepsy, a topic of ongoing debate among European and Asian epilepsy research centres.Methods and analysis: A structured long-term research plan was developed, comprising three phases. Phase one involves observational studies investigating the correlation between S100B levels in serum or cerebrospinal fluid and epilepsy. Phase two integrates observational and randomised controlled data to establish baseline S100B levels across diverse epilepsy demographics, underpinning the predictive value of S100B for epilepsy. Phase three focuses on randomised controlled trials to evaluate the diagnostic accuracy of S100B as an epilepsy biomarker.Ethics and dissemination: All enrolled patients will provide written consent. The ethics committee of the Second People’s Hospital of Gansu Province, Affiliated Hospital of Northwest Minzu University, China, approved the study (GSSEY2022-KY009-01).Registration: The study is registered with PROSPERO (CRD42023425431).

Abstract: Background: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic etiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish the effectiveness of the treatment. All patients showed improvements in QoL, EEG tracing and postural-motor development. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and tolerability of pulse IVMP treatment in pediatric patients with EE, especially with genetic etiology and ESES. The fourth month of therapy was the minimum time point to establish its effectiveness. QoL, EEG and postural-motor development also showed improvement.

Epilepsy is a common neurological condition, typically diagnosed using Electroencephalogram (EEG). Large scale EEG datasets have recently been made publicly available, allowing the use of advanced Machine Learning (ML) algorithms to analyze EEG patterns associated with epilepsy. While most existing studies focus on identifying seizures in the EEG, few have tried to identify preictal EEG segments. Identifying preictal EEG segments are not only useful in developing early warning systems but also helps inform the course of treatment for the patient. In this study, we propose to represent EEG segments as images, instead of time-series data, and identify preictal EEG segments using a preexisting ML algorithm (YOLOv8) designed for image processing. Multiplexed images (containing the original EEG signal represented on a 2D grid, kurtosis, and spectral entropy) achieve the best accuracy of 95.75% on the dataset while images just containing the EEG signal result in an accuracy of 91.25%. Using only spectrograms, generated from the original EEG signal, results in an accuracy of 90.15%.

Imaging-based biomarkers have developed as an effective tool in neurology, providing vital understandings of the structural, functional, and molecular changes associated with neurological disorders. Imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) have been widely employed to record disease-related alterations in the brain. These techniques provide a wide range of biomarkers, such as functional connectivity patterns, volumetric measurements, molecular imaging agents, and perfusion parameters, enabling the correct identification of neurological disorders. These biomarkers have proven useful in early diagnosis, disease progression tracking, therapy response prediction, and surgical planning. This review emphasizes the various obstacles and limitations that are associated with imaging-based biomarkers. Technical constraints, standardization obstacles, ethical concerns, regulatory challenges, and cost-effectiveness concerns all offer substantial barriers to wider use. It is vital to overcome these challenges if imaging biomarkers are to be successfully integrated into routine clinical practice. Imaging technology advancements like high-resolution imaging, multimodal imaging, and artificial intelligence-based analysis hold immense promise for imaging-based biomarkers in the future. While more study and standardization are needed, their ongoing development and integration into clinical practice have the potential to revolutionize the diagnosis, treatment, and management of neurological disorders, resulting in better patient care and outcomes.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

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.

Epilepsy and Alzheimer's disease (AD) incidence increase with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age and abnormal AD biomarkers in PET and or CSF are frequently found in late onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes including neuronal hyperexcitability and an early excitatory-inhibitory dysregulation leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both β-amyloid and tau protein aggregates, the anatomopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epileptiform activity and electroclinical seizures in AD appears to accelerate progression of cognitive decline and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASM). There is also a potential role for ASMs to be used as disease-modifying drugs in AD.

A two phase survey of epilepsy was conducted in selected villages in Mundri West and East Counties (26 June−8 July, 2021), an onchocerciasis-endemic area in Western Equatoria State in South Sudan. In the first phase, households were visited by a trained research team to identify persons suspected to have epilepsy. In the second phase, persons suspected to have epilepsy were interviewed and examined by a clinician to confirm the diagnosis. A total of 364 households agreed to participate in the survey, amounting to 2,588 individuals. The epilepsy screening questionnaire identified 91 (3.5%) persons suspected to have epilepsy, of whom in 86 (94.5%) the diagnosis of epilepsy was confirmed by a clinician. The overall prevalence of confirmed epilepsy was 3.3% (95% CI: 2.7-4.1%), and of nodding syndrome 0.9% (95% CI: 0.6-1.4%). In 61 (16.8%) households there was at least one person with epilepsy. Only 1,212 (46.9%) of 2,583 people took ivermectin during the last distribution round in 2021. The annual epilepsy incidence was 77.3/100.000 (95% CI: 9.4-278.9/100,000) and the annual epilepsy mortality 251.2/100,000 (95% CI: 133.8-428.7/100,000). In conclusion, a high prevalence and incidence of epilepsy was observed in villages in Mundri. Urgent action is needed to prevent children from developing onchocerciasis-associated epilepsy by strengthening the local onchocerciasis elimination programme.

Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4αR subunit. Blockade of IL-4/13 is effective in reducing Th2-oriented response including the release of proinflammatory cytokines, chemokines, and IgE. These mechanisms are known as mediators in the pathogenesis of atopic dermatitis, food allergy, allergic rhinitis with and without polyposis, and asthma. We report the clinical case of a patient in which the Th2-mediated inflammatory substrate is evident in comorbid allergic manifestations who show a good response after treatment with Dupilumab for moderate atopic dermatitis.

Breast cancer is among the most prevalent cancers in Indonesia. One of the methods for early detection of breast cancer is utilizing ultrasound images to classify breast conditions into normal, benign tumors, or cancer. The advent of deep learning technology facilitates the image analysis process, such as the use of Transfer Learning Convolutional Neural Networks (CNNs). Generally, CNN models require large and balanced datasets to perform well in classification tasks. However, medical datasets like breast ultrasound images tend to be limited and imbalanced. The Wasserstein GAN (WGAN) is a generative data augmentation method capable of producing synthetic images by learning the pattern of the distribution of real image data. The implementation of the Wasserstein distance results in the training process of WGAN demonstrating stability from epochs 3000, 2500, and 3000 out of a total of 5000 epochs. The quality of the synthetic images improves with an increasing number of training iterations. By using WGAN, all of the evaluation metrics of each classifier are increasing, with the best accuracy score is achieved by VGG16 model with 83.33% accuracy.

Background: Nanotechnology has emerged as a promising field of study, aiming to revolutionize healthcare through the innovative development of drugs, diagnostic tools, and medical devices. As a result, healthcare professionals in training are constantly faced with the challenge of understanding and applying these emerging technologies. The objective of this study is to determine the factors to consider for including the teaching of nanotechnological tools in medical specialty postgraduate programs. Methods: A study based on the Nominal Group Technique (NGT) was conducted to identify the factors that promote and hinder the implementation of nanotechnology in certain postgraduate programs where nanotechnology is employed, such as Internal Medicine, Critical Care Medicine, Family Medicine, and Clinical Pharmacology at the School of Medicine of Universidad de La Sabana. A framework analysis was used to analyze the collected data. Results: Based on the two research questions, several aspects were identified for the inclusion of nanotechnology in the medical practice of specialties. Key challenges include lack of knowledge and resource availability, misinformation, and lack of knowledge, as well as paradigmatic analysis as the main obstacles to the use of nanotechnology. Conclusions: The findings provide a first-time study on nanotechnology curricula within medical specialty programs in Colombia, with potential extrapolation to similar situations in other medical schools.

The species and bio-availability of phosphorus (P) in primary, secondary and digested sludge were fractionated and further analyzed in this study. Results showed that inorganic P (IP) was the primary P fraction in the secondary sludge and digested sludge, in which non-apatite IP (NAIP) amounted to 91.6% and 69.3% of IP, respectively. Organic P (OP), accounting for about 71.7% of total P (TP), was the dominant P composition in primary sludge. The content of bio-available P was about 9.7, 43.4, 29.8 mg-P/g-TS in primary sludge, secondary sludge and digested sludge, respectively, suggesting secondary sludge is the optimal choice when land application of sewage sludge is taken into consideration, followed by digested sludge and primary sludge. Polyphosphate and orthophosphate, comprising approximately 54.3% and 89.2% of TP, was the dominant P species in the secondary sludge and digested sludge, respectively. Monoester-P (54.6% of TP in extract) and diester- P (24.1%) were identified as OP species in primary sludge by Phosphorus-31 nuclear magnetic resonance (31PNMR). The present results would be helpful for P recovery and recycle from sewage sludge in wastewater treatment plant.

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S), a gasotransmitter, promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures and during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS subsequent to acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the corneal kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels in whole brain homogenate and expression of related genes in corneal kindled mice were not altered. However, plasma H2S and MeSH levels were significantly lower during kindling, but not after established kindling. Morever, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, Opa1, Mfn2, Drp1, and Mff during kindling, which did not correlate with gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.

We conducted a comparative study on the development of two synthetic methods. The solvent-free synthesis is a green chemistry method developed in a bid to ameliorate environmental adverse effects of the conventional solvent-based synthesis. The synthesis of novel dichloro and polymethoxy p-nitrophenylhydrazones through solvent free technique gave moderate to high yields which were however lower than those of the solvent-based method. The established solvent-free approach has several benefits, including universality and simplicity of the approach, catalyst-free conditions, non-use of an organic solvent, quick reaction time, fast and efficient workup, and un-solvated pure products in moderate to high yields.

Recent research has demonstrated that endophytes, or non-pathogenic fungi found in plant bi-omes, can dramatically alter the expression of host plants. Our natural ecology is burdened by an increasing amount of chemicals owing to the rapid modernization of agricultural sector. This study examined the use of natural pesticides in place of chemical pesticides to eradicate patho-genic fungi that destroy cabbage crops every year. Agrochemicals-, or pesticides-, are used in ag-ricultural land and crops to protect plants from various diseases. The cabbage crop was treated using the appropriate methodology. In an effort to identify endophytic fungi that can stop the growth of pathogenic fungi, samples are gathered from markets and farms to find solutions at the source of the issue. The outcome revealed a number of fungal endophytes that have the ability to suppress fungal infections and act as a defense against crops. Because plants have endophytic fungi, which act as a barrier to protect plants, in addition to harmful fungi, fungi play a critical role in the discussion of natural pesticides. These findings also indicate that market samples were more contaminated with microorganisms. These endophytes can be the main source of materials for producing natural insecticides for crops;-, thus, further research on them can be conducted. Furthermore, farmers may be able to overcome obstacles and find a potential solution with the use of numerous more potent strategies in the field of microorganism development.

Reaction of the phosphonated hydrazone (2-hydrazineylidenepropyl) diphenylphosphine oxide 1 with p-fluorophenyl-isothiocyanate yields as major product the thiosemicarbazone Ph2P(=O)CH2{C=N-NH(C=S)-N(H)C6H4F}CH3 (2-(1-(diphenylphosphoryl)propan-2-ylidene)-N-(4-fluorophenyl)hydrazine-1-carbothioamide) 2 along with bis(N-p-fluorophenylthiourea) 3 as minor product. This latter product 3 was isolated as main product by direct treatment of p-FC6H4N=C=S with hydrazine in a 2:1 ratio. Both 2 and 3 were characterized by NMR. Furthermore, the molecular structure of 3 was elucidated by an X-ray diffraction study. A conformational DFT study, at the B3LYP/6311 G++ (d, p) level of theo-ry, confirmed a good match between the calculated structure and the experimental one.

The design and control of lower limb rehabilitation robots for patients after a stroke has gained significant attention. This paper presents the dynamic analysis and control of a 3-degree-of-freedom lower limb rehabilitation robot using combined position-force control based on the force feed-forward and compensate gravity proportional derivative method. In the lower limb rehabilitation robot, the interaction force between the patient with the joints and links of the robot is uncertain and nonlinear due to the disturbance effect of Coriolis force, centrifugal force, gravitational force, and friction force. During recovery stages, forces exerted by the patient's lower limb are considered disturbances. Therefore, to meet the quality requirements in using the rehabilitation robot with different recovery stages of patient training, combining position control and force control is essential. In this paper, we proposed a combinations of proportional-derivative gravity compensation motion control and force feed-forward control to form an advanced combined controller (Position-Force Feedforward Control - PFFC) for a 3 DOF lower limb functional rehabilitation robot. The forces can be sensed using a 3-axis force sensor. In addition, the robot's position parameters are also measured by encoders. The control algorithm is implemented on the STM32F4 Discovery board. Verified test of the proposed control method is shown in the experiments and shown good performance of the system.

This paper presents an approach to assess and improve the cybersecurity infras- tructure of developing countries. We have highlighted and addressed the critical gaps through a hybrid approach encompassing SWOT analysis, benchmarking using Data Envelopment Analysis (DEA) and, Root Cause Analysis (RCA). This approach has provided a strong basis for evaluating cybersecurity performance by combining qualitative insights with quantitative metrics. As a case study, we have compared an underdeveloped country’s (Pakistan) cybersecurity pos- ture to five highly developed countries (Lithuania, Estonia, Singapore, Spain,and Norway). Our analysis has identified cybersecurity shortcomings and pro- vided actionable recommendations within a flexible framework, applicable for all developing countries to identify and address vulnerabilities, and align their cybersecurity infrastructure with international standards.

The increasing energy consumption and industrial activities that release carbon dioxide (CO2) emissions into the atmosphere have become one of the most serious environmental issues of today. This article discusses the current status in Azerbaijan regarding the development of effective approaches to reduce carbon emissions and ensure sustainable development, and it proposes relevant strategies for managing the carbon footprint. By exploring the interrelationship between the economy and the environment, it aims to contribute to the formation of more effective policies for managing CO2 emissions in Azerbaijan. According to the results of the econometric model established within the research for the period of 1990-2023, as the Azerbaijan economy grows, per capita CO2 emissions tend to increase, which can be linked to rising industrial activity, energy consumption, and other factors driving economic growth. The presence of a positive long-term relationship between population growth and per capita CO2 emissions can be attributed to higher overall energy consumption, increased demand for goods and services, and rising transportation needs. The strong correlation between economic growth and CO2 emissions suggests that it may be too early to assert the validity of the Kuznets curve for Azerbaijan economy as a developing country.

Fluctuations in kynurenic acid (KYNA) and brain-derived neurotrophic factor (BDNF) levels in the brain reflect its neurological status. The aim of the study was to investigate the effect of transiently elevated KYNA concentration in the cerebroventricular circulation on the expression of BDNF and its high-affinity tropomyosin-related kinase receptor B (TrkB) in specific structures of the sheep brain. Intracerebroventricularly cannulated anestrous sheep were subjected to a series of four 30-min infusions of KYNA: 4×5 μg/60 μL/30 min (KYNA20, n=6) and 4×25 μg/60 μL/30 min (KYNA100, n=6) or a control infusion (n=6), at 30-min intervals. Sections of the hippocampal CA3 field, amygdala (AMG), prefrontal cortex (PCx), and the hypothalamic medial-basal (MBH) and preoptic (POA) areas were dissected from the brain immediately after the experiment. The highest concentration of BDNF protein was found in the CA3 field (P<0.01), which was 8-fold higher than in the AMG and 12-fold higher than that in the PCx (MBH and POA were not analyzed). The most pronounced BDNF mRNA expression was observed in the MBH followed by the PCx, POA, AMG and CA3, while the highest abundance of TrkB mRNA was recorded in the AMG followed by the MBH, PCx, CA3 and POA. KYNA increased (P<0.05-P<0.01) BDNF protein levels and the expression of its gene in the brain structures examined, with the effect varying by dose and brain region. KYNA, particularly at the KYNA100 dose, also increased (P<0.01) TrkB gene expression, except for the AMG, where the lower KYNA20 dose was more effective (P<0.01). These findings suggest a positive relationships between KYNA levels in the cerebroventricular circulation and BDNF-TrkB expression in specific brain regions in a sheep model. This indicates that a transient increase in CSF KYNA concentration can potentially restore BDNF production, whose deficiency underlies numerous neurological disorders.

Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves extracts contain high amounts of flavonoids and terpenoids, endowed with potential antioxidant, anti-inflammatory, anticancer, antidiabetic and antimicrobial effects. Re-cently, many in vitro and in vivo studies have assessed different potential health benefits of per-simmon leaves; however, its anticancer activity towards colorectal cancer (CRC), the second deadliest cancer in Western countries, has not been investigated in depth. Since CRC current therapies are associated with serious side effects and show no efficacy towards patients carrying RAS/BRAF mutations, the search for new and more effective therapies has turned to plant extracts, which could help reduce conventional drugs dosages and toxicity. The effect of Diospyros kaki al-coholic extract has been investigated on E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS activating mutation. This extract is effective in reducing tumor cells viability, without affecting the healthy mucosa cell line CCD 841, and it triggers apoptosis in CRC cells, by disrupting mitochondrial functionality and increasing oxidative stress.

Pre-transport management activities can cause stress, injuries, and mortality in poultry. This study aimed to gather information about the current pre-transport practices (selection of unfit chickens, catching preparations, catching, and crating) for spent hens and broilers by questioning Flemish poultry farmers. The results showed that catching preparations such as an extra selection of chickens unfit for transport was performed by a minority of the poultry farmers, and that layer farmers were less in line with the EU-legislation for water and feed withdrawal than broiler farmers. All birds were caught inverted except for one broiler farmer who used mechanical catching (not yet common in Flanders). Additionally, mechanical catching may involve extra costs, increased biosecurity risks, and specific recommendations for the stable (height and width). The broiler farmers preferred mechanical catching for broiler catchers' well-being, while upright catching was considered better for animal welfare than catching more than three chickens by one/two legs, mechanically, or by wings. Awareness of the need to perform an extra selection by the poultry farmers before catching is required. Preparations like closing areas under the aviary system and removing litter (layers) can further streamline the process and reduce animal suffering.

This stability analysis method is simply represented and understood on a Bode plot of two impedances without complex equations. The external impedance of the charging system is properly quantified and designed based on the stability criteria by analyzing.

Arbutus unedo (strawberry tree) is a small Mediterranean tree capable of vigorous regrowth after disturbances like fire. Traditionally used for biomass fuel, its bark and branches hold potential for higher-value products through ecovalorisation into liquid mixtures that could replace petro-leum-based materials. This study aimed to explore the chemical composition of various compo-nents of Arbutus unedo and to produce a liquefied material from its internal (IB) and external bark (EB). Chemical compositions of internal and external bark were determined using TAPPI standards including ash, extractive content, lignin, and cellulose. Metal cations were analyzed by ICP. Liquefaction of bark was optimized in a PARR reactor, evaluating factors such as particle size, temperature, and time and the best polyols were monitored by FTIR-ATR. Polyurethane foams were made with internal and external bark liquefied materials by polymerization with isocyanate, a catalyst and water as blowing agent. Results showed that EB has a higher extractive and lignin content, while IB contains more cellu-lose. Liquefaction yields were higher for IB (74%) than EB (68%), with IB yielding polyols that produced stronger and more resilient foams. Mechanical properties of the foams were influenced by the NCO/OH ratio and catalyst levels. Overall, the internal bark demonstrated superior performance for foam production, highlighting its potential as an eco-friendly alternative to petroleum-derived materials.

Introduction: Leptin and ghrelin are two hormones that play a role in weight homeostasis. Leptin, which is produced primarily by adipocytes and is dependent on body fat mass, suppresses appetite and increases energy expenditure. Conversely, ghrelin is the “hunger hormone”, it stimulates appetite and promotes fat storage. Bariatric surgery significantly alters the levels and activity of these hormones, contributing to weight loss and metabolic improvements. Clarifying the interplay between bariatric surgery, weight loss, physical exercise, leptin, and ghrelin is essential for developing comprehensive strategies for optimizing long-term outcomes for candidates for bariatric surgery, especially sarcopenic patients. Methods: This was a randomized controlled study with two groups (n=22). The patients in both groups have obesity and sarcopenia. A Roux-en-Ygastric bypass (RYGB) procedure was performed in all patients. The intervention group participated in a structured exercise program three times per week beginning one month after surgery and lasting 16 weeks. Patient assessment was performed before surgery (baseline) and after completion of the exercise program. The control group received the usual standard of care and was assessed similarly. Results: After surgery, weight, BMI and lean mass decreased significantly in both groups from baseline to the second assessment. Leptin was not significantly different from baseline to the second assessment in the physical exercise group but was significantly lower in the control group (p=0.05). Ghrelin increased over time in both groups, but the differences were not significant. When we associated leptin (the dependent variable) with weight (the independent variable), we found that lower weight was associated with lower leptin levels. A similar relationship was also observed between leptin and sarcopenia parameters (muscle strength and mass), as well as with bone health parameters (bone mineral density and t-score). Higher ghrelin levels were significantly associated with higher t-scores and z-score (p<0.05). Conclusion: Exercise has been shown to have a significant effect on leptin and ghrelin levels after bariatric surgery. By incorporating regular physical activity into their lifestyle, bariatric patients can optimize their weight loss outcomes and improve their overall health. After the physical exercise protocol, patients in the intervention group revealed more established leptin levels, which may indicate a protected pattern concerning decreased leptin levels. An unfavorable profile was evidenced, according to which greater weight loss, sarcopenia, and osteoporosis were associated with lower leptin levels.

Among the theoretical problems with the prevailing theory of cosmology, Lambda Cold Dark Matter (λCDM), the most serious appears to be the twofold problem with the cosmological constant lambda: Dark Energy and Hubble Tension. Despite a two-decade search for systematic errors in astrometry the problems have not been resolved. This paper posits a potential source of error that may have affected astrometry related to the current and past measurements of lambda.

Differential beamforming has attracted much research since it can utilize the array with small aperture size to form frequency-invariant beampatterns and achieve high directional gains. It has recently been applied to the linear loudspeaker array to produce a broadside frequency-invariant radiation pattern. However, designing steerable frequency-invariant beampatterns for the linear loudspeaker array has yet to be explored. This paper proposes a method to design the steerable differential beamformer with the linear loudspeaker array. We first determine the target differential beampatterns according to the desired direction, the main lobe width, and the beampattern order. Then, we transform the target beampattern into the modal domain for representation. The Jacobi-Anger expansion is subsequently used to design the beamformer so that the resulting beam pattern matches the target differential beam pattern. Furthermore, based on the criterion of minimizing the mean square error between the synthesized beam pattern and the ideal one, a multi-constraint optimization problem is formulated to calculate the optimal desired weighting vector. Simulations and experimental results show that the proposed method can achieve steerable frequency-invariant beamforming over 300 Hz – 4 kHz.

N-(diisopropylphosphanyl)benzamide, PhC(O)NHPiPr2, has been synthesized in good yield following two alternative procedures that employ benzamide as the starting material. The first one is a two-step preparation, in which N-(trimetilsilyl)benzamide is reacted with PiPr2Cl, to give the title compound in good yield, whereas the second one is a straightforward synthesis which converts benzamide into N-(diisopropylphosphanyl)benzamide by reaction with PiPr2Cl in the presence of N,N-dimethylpyridin-4-amine (DMAP) and triethylamine. NMR spectroscopy and X-ray diffraction analyses have been performed to characterize the new compound and elucidate its molecular structure in the solid state. N-(diisopropylphosphanyl)benzamide adds to the limited family of amido-substituted phosphines, RC(O)NHPR’2, which can be classified as bidentate hybrid P,O-ligands, both in their neutral and anionic forms, the latter achievable by deprotonation of the NH group.

Detection of adverse events, for example convulsive epileptic seizures, can be critical for the patients suffering from variety of pathological syndromes. Algorithms using remote sensing modalities, such as video camera input, can be effective for real-time alerting but the broad variability of environments and numerous non-stationary factors may limit their precision. In this work, we address the issue of adaptive reinforcement that can provide flexible application of the alerting devices. The generic concept of our approach is the topological reinforced adaptive algorithm (TOREADA. Three essential steps, embedding, assessment and envelope act iteratively during the operation of the system, providing thus a continuous, on the fly reinforced learning. We apply this concept on the case of detecting convulsive epileptic seizures where three parameters define the decision manifold. Monte-Carlo type simulations validate the effectiveness and robustness of the approach. We show that the adaptive procedure finds the correct detection parameters, providing optimal accuracy, from a large variety of initial states. With respect to the separation quality between simulated seizure and normal epochs, the detection reinforcement algorithm is robust within broad margins of signal generation scenarios. We conclude that our technique is applicable to a large variety of event-detection systems.

In the contest of childhood epilepsies, the concept of continuous spike-waves during slow sleep (CSWS) includes several childhood-onset heterogeneous conditions, sharing an electroencephalogram (EEG) characterized by a high frequency of paroxysmal abnormalities during sleep which are attributed negative effects on the cognitive development and behavior of the child. These negative effects may have the characteristics of a clear regression or of a slowdown in development. Seizures are very often present, but not constantly. The above makes it clear why CSWS have been included in epileptic encephalopathies, in which by definition the frequent EEG paroxysmal abnormalities have an unfavorable impact on the cognitive functions, including socio-communicative skills causing autistic features, even regardless of the presence of clinically overt seizures. Although several decades have passed since the original descriptions of the electroclinical condition of CSWS, there are still many areas that are little known and deserve to be further studied, including the EEG diagnostic criteria, the most effective electrophysiological parameter for monitoring the evolution, the role of the thalamus in the CSWS pathogenesis, the long-term evolution, the nosographic location of Landau-Kleffner syndrome, the standardized neuropsychological and behavioral assessment, the pharmacological and non-pharmacological therapies.

Background: Epileptic patients frequently encounter cognitive impairment. Functions that are mostly affected involve memory, attention and executive function; however this is mainly dependant on the location of the epileptic activity. The aim of the study is to assess cognitive functions in MRI-negative epilepsy patients by means of neurophysiological and neuropsychological measures. Methods: The patients were enrolled from the outpatient Epilepsy/Clinical Neurophysiology clinic over a time period of 6 months. The study sample comprised 20 MRI negative epilepsy patients [mean age ± standard deviation (SD), 30.3 ± 12.56 years; age range 16-60 years; average disease duration, 13.95 years) and 10 age-matched controls (mean age ± SD, 24.22 ± 15.39 years), that were also education-matched (p>0.05) Patients with epileptogenic lesions were excluded from the study. Informed consent was obtained from all subjects involved in the study. Auditory ERPs and the cognitive screening tool EpiTrack, were administered to all subjects. Results: Latencies of P300 and slow waves were prolonged in patients compared to controls (p<0.05). ASM load and the patients’ performance in the EpiTrack maze subtest were the most significant predictors of P300 latency. A decline in memory, attention, and speed of information processing has been observed in patients with cryptogenic epilepsy compared to age-matched controls, as reflected by P300 latency and EpiTrack scores.

Pretreatment with non-convulsive dose of methionine sulfoximine (MSO) attenuated lithi-um-pilocarpine-induced (Li-Pilo) seizures in young rats [1]. We hypothesized that the effect of MSO results from a) glutamine synthetase block-mediated inhibition of conversion of Glu/Gln precursors to neurotransmitter Glu, and/or from b) altered synaptic Glu release. Pilo was admin-istered 60 min prior to sacrifice, MSO at 75 mg/kg, i.p., 2.5 h earlier. [1,2-13C]acetate and [U-13C]glucose were i.p.-injected either together with Pilo (onset) or 15 min before sacrifice (final phase). Their conversion to Glu and Gln in hippocampus and entorhinal cortex was followed us-ing [13C] gas chromatography-mass spectrometry. Release of in vitro loaded [3H]D-Asp from ex vi-vo brain slices was measured in continuously collected superfusates. Protein and mRNA expres-sion were measured by Western Blot and real-time PCR techniques, respectively. At no time point nor brain region did MSO modify incorporation of [13C] to Glu or Gln in Pilo-treated rats. MSO pretreatment decreased by ~37% high potassium-induced [3H]D-Asp release and reduced by ~50% the synaptic vesicular Glu transporter VGLUT1 protein, but not mRNA content in the hippo-campus. The results indicate that MSO at non-convulsive dose mitigates the initial Pilo-induced seizures by interfering with synaptic Glu-release but not with neurotransmitter Glu recycling.

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.

In June 2020, a door-to-door household survey was conducted in Mvolo County, an onchocerciasis endemic area in South Sudan. A total of 2,357 households containing 15,699 individuals agreed to participate in the study. Of these, 5,046 (32.1%, 95%CI: 31.4-32.9%) had skin itching and 445 (2.8%, 95% CI: 2.6-3.1%) were blind. An epilepsy screening questionnaire identified 813 (5.1%) persons suspected to have epilepsy. Of them, 804 (98.9%) were seen by a medical doctor and in 798 (98.1%) the diagnosis of epilepsy was confirmed. The overall epilepsy prevalence was 50.8/1000 (95% CI: 47.6-54.4/1000) and prevalence of nodding syndrome was 22.4/1000 (95% CI: 20.1-24.9/1000). Younger age, being male, skin itching, blindness and living in a village close to the Naam river were risk factors for epilepsy. The annual incidence of epilepsy was 82.8/100,000 (95% CI: 44.1-141.6/100,000). In conclusion, a high prevalence and incidence of epilepsy was observed in Mvolo, South Sudan. Strengthening the onchocerciasis elimination programme is urgently needed to prevent epilepsy in this region.

A 12 year old boy was diagnosed with temporal lobe epilepsy (TLE) along with mesial temporal sclerosis based on MRI (magnetic resonance imaging) results. The diagnosis was further confirmed by genetic analysis. He also had minor psychiatric symptoms of obsessive-compulsive disorders and mood swings. After 4 years of treatment with Sodium Valproate no change in symptoms was observed. Genetic testing along with deep phenotyping revealed altered glutamate pathway and metabolism. Post genetic testing the patient was put on a combination of Sodium Valproate and Valproic acid along with supplementation of N-acetylcysteine (NAC), Cyanocobalamin, Pyridoxine and Cholecalciferol. Within three months of this combined therapy the patient experienced complete elimination of seizures and drastic improvement in mood and social behaviour. The case report highlights the importance of precision diagnosis in understanding the underlying perturbed pathways in structural epilepsy like TLE and demonstrates the importance of non-invasive targeted therapy in such cases.

Background/Objectives: The function of adipokines, which play an important role in the etiopathogenesis of critical illness, has not been fully elucidated. We aim to investigate the sequential changes in serum adipokines and their association with clinical outcomes and nutritional parameters in ICU patients with SARS-CoV-2. Methods: This observational study was conducted prospectively in a Medical ICU. Blood samples were collected on admission and on the 7th day for analysis of adiponectin, GLP-1, resistin, visfatin, acyl ghrelin (AG), IGF-1, and leptin levels using ELISA kits. Results: This study included 30 critically ill patients and 10 healthy controls. Baseline and day 7 serum adiponectin, GLP-1, resistin, visfatin, baseline AG and day 7 IGF-1 levels are significantly lower in critically ill patients compared to the control group (p<0.05). A negative correlation was observed between time to initiate nutrition and serum adipokine levels (p<0.05). Patients with high mNUTRIC scores had elevated serum adiponectin and IGF-1 levels on day 7 (p<0.05). Positive correlations were found between MV duration and day 7 AG levels (p<0.05). Conclusions: This pilot study provides insights into serum adipokine dynamics in critically ill COVID-19 patients. Lower adiponectin, GLP-1, resistin, visfatin, AG, and IGF-1 levels suggest dysregulation in these pathways.

The positive relationship between species richness and area is a fundamental principle in ecology. However, this pattern deviates on small islands, where species richness either changes independently of area or increases at a slower rate—a phenomenon known as the Small-Island Effect (SIE). While the SIE has been well-documented in natural ecosystem, its presence in highly fragmented and disturbed urban ecosystem remains unexplored, posing challenges for urban vegetation conservation. Urban remnant vegetation, isolated by surrounding infrastructures, preserves intact zonal vegetation characteristics, serves as a benchmark for restoring near-natural habitats and offers ideal conditions to test the existence of SIE in human-altered landscapes. In this study, we surveyed 17 remnant vegetation patches in Qingdao City, China. In total of 331 plants attributed to 255 genus in 81 families been recorded. Firstly, by using six species-area relationship regression models tested SIE for remnant vegetation with different life form (i.e. annual herb, perennial herb, shrub and tree), we found SIE detected in only woody plants, with area threshold ranging from 6.38 ha (tree) to 11.91 ha (shrub). According to stepwise and generalized linear regression mode analysis we found SIE detected in only woody plants, with area threshold 6.38 ha for tree and 11.91 ha for shrub. Further analysis revealed that the SIE in shrub was driven by landscape shape index, perimeter-area ratio, and the proportion of sealed surface within patch. For trees, the SIE was influenced by the distance to the source of species, GDP, night light intensity and perimeter-area ratio. This finding justifies that conservation in urban planning, construction and development should focus not only on protecting large areas, but also on maintaining and promoting diverse habitats within these areas. At the same time, reducing anthropogenic disturbance and enhancing the connectivity of green spaces are important for the persistence of metacommunities and can contribute to the local species pool, thus potentially improving the ecological resilience of urban environments.

Cybersecurity threats pose a significant challenge to the operational resilience and sustainability of Small and Medium Enterprises (SMEs) globally, with distinct implications for regional business ecosystems. This research presents an in-depth investigation into the impact of cybersecurity threats on SMEs within the unique context of Kajiado County, Kenya. Against the backdrop of an increasingly digitized business environment, this study aims to comprehensively assess the challenges SMEs face in mitigating cyber risks and their consequent impact on performance. The research employed a mixed methods approach, combining quantitative and qualitative analyses to elucidate the multifaceted nature of cybersecurity challenges encountered by SMEs in Kajiado County. Utilizing interviews, and document analysis, the study gathered empirical data to identify prevalent cybersecurity threats, their frequency, and the subsequent repercussions on SMEs' operational efficiency, financial stability, and overall performance metrics. Initial findings reveal a diverse spectrum of cybersecurity threats SMEs face in Kajiado County, ranging from phishing attacks and data breaches to ransomware incidents. These threats significantly impede business operations, resulting in financial losses, service delivery disruptions, and customer trust erosion. Moreover, the study examined the cybersecurity measures adopted by SMEs, highlighting the challenges in implementing effective preventive strategies within resource-constrained environments. Notably, the research addresses the identified gap by offering a nuanced understanding of the interplay between cybersecurity threats and SME performance in Kajiado County. The study intends to propose tailored and pragmatic recommendations to fortify SMEs' cybersecurity resilience by contextualizing global best practices within the regional business landscape. The anticipated outcomes of this research endeavor extend beyond academic discourse, aiming to provide actionable insights to SME stakeholders, policymakers, and industry practitioners. The findings aspire to empower SMEs in Kajiado County to enhance their cybersecurity posture, enabling them to navigate the evolving threat landscape more effectively and bolster their long-term sustainability within the digital economy.

Background/Objectives: Recent advancements in artificial intelligence (AI) have spurred interest in developing computer-assisted analysis for imaging examinations. However, the lack of high-quality datasets remains a significant bottleneck. Labeling instructions are critical to improving dataset quality but are often lacking. This study aimed to establish a liver MRI segmentation protocol and assess its impact on annotation quality and inter-reader agreement; Methods: This retrospective study included 20 patients with chronic liver disease. Manual liver segmentations were performed by a radiologist in training and a radiology technician on T2 weighted imaging (wi) and T1wi at the portal venous phase. Based on the inter-reader discrepancies identified after the first segmentation round, a segmentation protocol was established, guiding the second round of segmentation, resulting in a total of 160 segmentations. Dice Similarity Coefficient (DSC) assessed inter-reader agreement pre- and post-protocol with a Wilcoxon signed-rank test. Slice selection at extreme cranial or caudal liver positions was evaluated using the McNemar test; Results: The per-volume DSC significantly increased after protocol implementation for both T2wi (p<0.001) and T1wi (p=0.03). Per-slice DSC also improved significantly for both T2wi and T1wi (p<0.001). The protocol reduced the number of liver segmentations with a non-annotated slice on T1wi (p=0.04), but the change was not significant on T2wi (p=0.16); Conclusions: Establishing a liver MRI segmentation protocol improves annotation robustness and reproducibility, paving the way for advanced computer-assisted analysis. Moreover, segmentation protocols could be extended to other organs and lesions and incorporated into guidelines, thereby expanding the potential applications of AI in daily clinical practice.

At the time of accession, Ukraine will be covered by the full CAP instrumentarium, the system of direct payments included. Due to the size of the country, including agricultural land, the total amount of payments to Ukraine may reach the amount of EUR 96.5 billion (over 7 years) according to some estimates. The purpose of the article is to try to verify this amount. This will be done by reviewing the latest analyses, made in EU countries, on the estimates of future direct payments in Ukraine. At the same time, author’s own account of the amount of payments to agricultural producers in this country shall be presented. Unlike other studies, the calculation takes into account two elements that significantly reduce the amount of subsidies. Firstly, after accession, Ukrainian farmers will probably receive only part of the payments, which will be gradually increased (phasing-in mechanism), as was the case with Poland and other countries joining the European Union in 2004. Secondly, the calculation attempts to count the effects of the so-called capping, i.e. a ceiling for the amount of direct payments, which will probably also be applied. The result shows a smaller amount of future payments than the other studies.

Chikungunya is mosquito born disease that is spread across continents. This research provides valuable insights into the potential functional significance of the hydrophobic tail and cysteine-rich regions in E2 proteins. These findings lay the groundwork for future investigations into the specific roles of the C-terminal domain and post-translational modifications, which could ultimately lead to a better understanding of viral mechanisms and potential therapeutic targets.

Fanconi syndrome is a disorder of renal proximal tubule transport characterized by metabolic acidosis, amino aciduria, glucosuria, and phosphaturia. There are acquired and hereditary forms of this disorder. Fanconi syndrome in Basenjis was first described in 1976 and is now recognized as an inherited disease in these dogs. Linkage analysis within a large family of Basenjis that included both affected and unaffected individuals was performed to localize the causative variant within the genome. Significant linkage was identified between chromosome 3 (CFA3) makers and the disease phenotype. Fine mapping restricted the region to a 2.7 Mb section of CFA3. A whole genome sequence of a Basenji affected with Fanconi syndrome was generated, and the sequence data were examined for the presence of potentially deleterious homozygous variants within the mapped region. A homozygous 317 bp deletion was identified in the last exon of FAN1 of the proband. 78 Basenjis of known disease status were genotyped for the deletion variant. Among these dogs, there was almost complete concordance between genotype and phenotype. The only exception was one dog that was homozygous for the deletion variant but did not exhibit signs of Fanconi syndrome. These data indicate that the disorder is very likely the result of FAN1 deficiency. The mechanism by which this deficiency causes the disease signs remains to be elucidated. FAN1 has endonuclease and exonuclease activity that catalyzes incisions in regions of double-stranded DNA containing interstrand crosslinks. FAN1 inactivation may cause Fanconi syndrome in Basenjis by sensitization of kidney proximal tubule cells to toxin-mediated DNA crosslinking resulting in accumulation of genomic and mitochondrial DNA damage in the kidney. Differential exposure to environmental toxins that promote DNA crosslink formation may explain the wide age-at-onset variability for the disorder in Basenjis.

Background: Patients undergoing brain tumor resection experience neurological and cognitive (i.e., neurocognitive) changes reflected in altered performance on neuropsychological tests. These changes can be difficult to explain or predict. Brain connectivity, measured with neuroimaging, offers one potential model for examining these changes. In this study, we evaluated whether longitudinal changes in brain connectivity correlated with changes in neurocognitive abilities in patients before and after brain tumor resection. Methods: Patients underwent functional and diffusion MR scanning and neuropsychological evaluation before tumor resection followed by repeat scanning and evaluation two weeks post-resection. Using this functional and diffusion imaging data, we measured changes in the topology of the functional and structural networks. From the neuropsychological testing scores, we derived a composite score that described a patient’s overall level of neurocognitive functioning. We then used a multiple linear regression model to test whether structural and functional connectivity measures were correlated with changes in composite scores. Results: Multiple linear regression on 21 subjects showed that connectivity changes were highly correlated with changes in neuropsychological evaluation scores (R² adjusted = 0.79, p<0.001). Changes in functional local efficiency (p<0.001) and global efficiency (p<0.05) were inversely correlated with changes in composite score, while changes in modularity (p<0.01) as well as the patient’s age (p<0.05) were directly correlated with changes in composite score. Conclusion: Short interval changes in brain connectivity markers were strongly correlated with changes in the composite neuropsychological test scores in brain tumor resection patients. Our findings support the need for further exploration of brain connectivity as a biomarker relevant to brain tumor patients.

The gut, often referred to as the "second brain," has significant contributions in the maintaining of the good bacteria contribute enormous role such as digestion, produce essential vitamins, support the immune system, and protect against harmful bacteria. The beneficial flora including Akkermansia muciniphila, Adlercreutzia equolifasciens, Barnesiella, Christensenella minuta, and Oxalobacter formigenes, along with their derived bioactive metabolites emerged as a key player in maintaining host metabolic and immune health. Dietary choices such as blending of prebiotic, fermented, symbiotic, anti-inflammatory foods, and secondary metabolites from a wide variety of plants and fruits promotes the diversity, composition, and stability of beneficial intestinal microbes. The colourful plant foods rich in phytochemicals bioactive compounds such as carotenoids, flavonoids, polyphenols, alkaloids, anthocyanins, and capsaicin offer a wide array of unique properties such as analgesics, antioxidants, anti-inflammatory, antimicrobials effect and promoting the abundance of beneficial gut bacteria and their bioactive metabolites confer numerous health-promoting effects. Here, we present knowledge about most beneficial gut bacteria and their derived metabolites in terms of their sources and health benefits. Finally, we discuss best foods that skew towards promoting healthy intestinal microbes.

This article presents a method for detecting P, QRS, T, and U waves in electrocardiogram (ECG) signals through advanced signal processing techniques, including a Butterworth bandpass filter and peak finding algo- rithms. The results are evaluated against the voltage ranges recommended in the literature, underscoring the importance of accurate wave detection for the diagnosis of various cardiac conditions.

Additive Manufacturing (AM) methods are increasingly beign abopted in the industry as an alternative for mass production. In particular, Fused Deposition Modeling (FDM) technology is leading the way in this field. However, the adhesion of layers in products produced using FDM technology is an important issue. These products are particularly vulnerable to forces acting parallel to the layers and specially to impact strength. This study aims to optimize the impact strength against loads acting parallel to the layers (ZX orientation) of PA6, one of the most widely used materials in the industry. This orientation is critical in term of mechanical properties, and the mechanical characteristics are significantly lower compared to other orientation. In this study, filaments containing pure PA6 with 15% short carbon fiber and 30% glass fiber were utilized. Additionally, printing temperature, layer thickness and heat treatment duration were used as independent variables. An L9 orthogonal array was employed in this study, and each experiment was repeated three times to conduct impact strength tests. Characterization, Taguchi optimization, a factor analyses were performed, followed by fracture surface characterization by SEM. As a result, the highest impact strength was achieved with pure PA6 at 8.9 kJ/m2, followed by PA6 GF30 at 8.1 kJ/m2 and the lowest impact strength was obtained with PA6 CF15 at 6.258 kJ/m2. When compared to the literature and manufacturer datasheets, it was concluded that the impact strength values have significantly increased, and the chosen experimental factors and their levels, particularly nozzle temperature, were effective.

For Sir Ronald Fisher, it is important to consistently obtain significant p-values to support an experimental hypothesis. So, replicating experiments to obtain independent p-values is a legitimate and desirable research practice. Several simple statistics have been proposed to meta-analyze p-values, all assuming that they are genuine, i.e. observations from independent standard Uniform random variables. But, as publication bias favors the studies that report "significant" p-values, when a p&gt;0.05 is obtained for the outcome of an experiment, some researchers will "fall into temptation" and decide to replicate the experiment in the hope of getting a smaller second p-value, ideally a significant one. Consequently, if the smallest of two p-values is reported, this is a Beta(1,2) distributed "fake" p-value, not a uniformly distributed genuine p-value. This is an unacceptable scientific research practice, and moreover the detection of fake p-values is unpractical. Even when it is possible, the analytic results to accommodate their existence in combined tests are cumbersome. For an informed decision, inclusive when the presence of fake p-values in a sample of p-values to be meta-analyzed is probable, tables with simulated critical values for the usual combined testing are supplied. This will also allow comparisons to be made between several combined tests.

The global malaria community has picked up the theme of malaria elimination in greater than 90 % of the world’s population in the next decade. The recent reports of P. vivax in all sub-Saharan Africa, including Duffy negative individuals, threaten the efforts to achieve elimination. This is not only in view of strategies that are tailored only to P. falciparum elimination, but also due to currently revealed biological characteristics of P. vivax concerning the relapse patterns of hypnozoites and conservation of a large biomass at cryptic sites in the bone marrow and spleen. A typical scenario has been observed in Botswana from the period between 2008 to 2018, which palpably projects how P. vivax could endanger efforts at malaria elimination where the two parasites co-exist. The need for the global malaria community, NMPs, funding agencies and relevant stakeholders to engage in a forum to discuss and recommend clear pathways for sub-Saharan Africa regarding malaria elimination including P. vivax, is warranted.

Academic and corporate research has been focusing on analyzing stock performances, financial markets, and investment strategies for decades. According to Lynch and Rothchild (1989), certain investments can be described as plays. In this work, the authors use the term for investments in value stocks, spin-offs, and turnarounds to analyze the long-term stock performance and risk-adjusted excess returns of up to five years for those stocks. Additionally, stocks with a supe-rior return performance are identified within an investment play based on low P/E and P/B mul-tiples. The study finds that value stocks, spin-offs, and turnarounds outperform the S&P 500 on average on a one-, three- and five-year investment horizon. The analysis of the three investment plays confirms earlier studies that investment plays constitute a profitable investment opportunity. Moreover, the research exemplifies that private investors could achieve an excess return (alpha) through a passive buy-and-hold investment strategy. Overall, the analysis provides a deeper in-sight into the long-term performance of value stocks, spin-offs, and turnarounds.

Purpose: This study evaluates the impact of Medicaid expansion under the Affordable Care Act (ACA) on melanoma staging at diagnosis, treatment utilization, and 3-year mortality outcomes. The objective is to determine whether Medicaid expansion led to earlier melanoma diagnosis and improved survival rates among non-elderly adults (ages 40-64) by analyzing data from the National Cancer Database (NCDB). Methods: A total of 12,667 patients, aged 40-64, diagnosed with melanoma from 2010 to 2020 were identified using the NCDB. Difference-in-difference (DID) analysis was performed to analyze tumor staging at presentation between Medicaid expansion states and non-Medicaid expansion states both prior to the expansion and after the expansion. Results: Of the total patients 2,307 were from the pre-expansion time period residing in Medicaid Expansion states (MES) and 1,804 in non-Medicaid expansion states. In the post-expansion time period there were 5,571 residing in the MES and 2,985 in the non-MES. DID analysis revealed a decrease in stage IV melanoma at diagnosis (DID -0.222, p <0.001) between MES and non-MES before and after Medicaid expansion. After expansion, in stage IV, the occurrence of primary surgery was 0.42 in non-MES and 0.44 (difference 0.02), DID analysis was not statistically significant. The use of immunotherapy in MES was significantly higher than non-MES after expansion (p<0.001), although DID analysis did not reveal a statistically significant difference. DID analysis showed a statistically significant decrease in 3-year mortality (DID -0.05, p=0.001) between MES and non-MES before and after Medicaid expansion. Conclusions: This study revealed the positive impact of the ACA’s Medicaid expansion on melanoma stage at presentation showing improved access to healthcare services can facilitate the diagnosis of early-stage melanoma and decrease mortality rate.

Background: An accurate diagnosis of thyroid nodules is crucial for avoiding unnecessary surgical procedures and making timely treatment possible. The objective of the present study was to evaluate the diagnostic accuracy of FNAB (fine-needle aspiration biopsy) using histopathological findings as the reference standards. Patients with the diagnostic categories (DCs) III, IV, V were subjected to a special analysis. In addition, the authors assessed whether other factors, i.e. age, gender, BMI (body mass index), obesity and histopathologically confirmed lymphocytic thyroiditis had an impact on the occurrence of malignant tumors. Methods: A retrospective analysis was conducted on 535 patients who underwent thyroid surgery between October 2022 and September 2023. To assess the FNAB reliability, the result obtained using the Bethesda classification was compared with the histopathological result. Results: The ROM (risk of malignancy) values for DCs I-VI were 38.1%, 15.6%, 29.8%, 18.6%, 91.0%, 93.2%, respectively. DC V (OR 62.34, p< 0.0001) and age≤50 (OR=2.31, p<0.006) had a statistically significant effect on the risk of thyroid cancer. DCs III and IV were not statistically significantly associated with the risk of malignancy (OR=1.68,p=0.16; OR=1.51,p=0.3,respectively). There were no statistically significant differences in sex, BMI and obesity between the patients with benign and malignant lesions. Conclusion: DC V is associated with a high likelihood of malignancy, especially in patients under 50 years of age, and therefore surgery is indicated in this category of subjects. In the DCs III and IV categories, the risk of malignancy is lower and conservative management with active clinical and ultrasound surveillance can be considered. In patients < 50 years of age, with the Bethesda categories III and IV, surgical treatment should be considered.

Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach for a wide variety of diseases, offering the potential to modulate gene expression with a high degree of specificity. These small, synthetic nucleic acid-like molecules provide unique advantages over traditional pharmacological treatments, including the ability to target previously "undruggable" genes. Despite this promise, several biological barriers severely limit their clinical efficacy Upon administration, ASOs primarily enter cells through endocytosis, becoming trapped inside membrane-bound vesicles known as endosomes. Studies estimate that only 1-2% of ASOs successfully escape endosomal compartments to reach the cytosol, and ultimately the nucleus, where they bind target mRNA and exert their therapeutic effect. Endosomal entrapment and inefficient nuclear localization are therefore critical bottlenecks in the therapeutic application of ASOs. This review explores the current understanding of endosomal escape, and nuclear transport of ASOs. Furthermore, we examine strategies aimed at overcoming these challenges, including the use of endosomal escape agents, peptide-ASO conjugates, non-viral delivery vehicles, and nuclear localization signals. By improving both endosomal escape and nuclear localization, significant advances in ASO-based therapeutics can be realized, ultimately enhancing their potency and expanding their clinical utility

Rhynchocypris kumgangensis, endemic to Korea, is limited to the upper Hangang River and Gucheondongcheon Stream. As a key and climate-sensitive biological indicator species in Deogyusan National Park, it has a southern range limit in the Gucheondong Valley. Due to climate change, notable shifts in the activity, vertical distribution, and population of R. kumgangensis in the Gucheondongcheon Stream are expected. Owing to the rapidly changing climate, significant changes in the activity, vertical distribution, and population size of R. kumgangensis in the Gucheondongcheon Stream are anticipated, and continuous surveys of the distribution of R. kumgangensis in this river area have been conducted. This study assessed the habitat of R. kumgangensis at 13 sites, including five in the Gucheondongcheon Stream, from July to October 2020 and compared the results with historical data to evaluate the impacts of climate change. At the five Gucheondongcheon Stream sites, 102 individuals were recorded from April to October 2020, and 378 were recorded between June 2018 and July 2019. Additionally, the subdominant species shifted from R. kumgangensis (2014–2018) to Zacco koreanus (2020). In the two southernmost Gucheondongcheon Stream sites, only 18 R. kumgangensis were observed in 2020 compared to 82 in 2019, indicating a significant population decline.

This study presents the experimental and analytical evaluations on an innovative connection class under cyclic loading. The connection was an H- or I-shaped section as a short stub column (SSC) between the end-plate and the column. The stub section was bolted to the column flange on the one side and bolted to the beam along with the welded end-plate on the other side. Stiffeners were installed on the webs and flanges of the beam and stub to ensure the necessary stiffness of the connection. The variables included thickness of stub flange/web and height of stub web. The cyclic loading was applied on a sample of the proposed connection according to AISC ANSI/AISC 341-16 loading protocol. Experimental observations displayed that the proposed connection, one can either employ hot rolling sections or create the connection as a plate girder, in which case the flange thickness and stub web, as well as the distance between two flanges and their height, was obtained according to the demand and performance of the structure. The optimum cross-section of the stub was then obtained. Also, the analytical model was calibrated using the finite element method (FEM), and its performance was confirmed. The effective parameters of the proposed connection were determined by modeling in the FEM software, and the design method was presented.

Objective: In recent years, the field of Essential Thrombocythemia (ET) research has seen a significant accumulation of scientific findings, but comprehensive bibliometric analyses remain lacking. This study aims to fill that gap by performing a thorough bibliometric analysis of ET research, identifying key contributors and collaboration networks, and mapping the development trends to provide insights for future research directions. Methods: A bibliometric analysis of ET-related publications from 2001 to 2024 was conducted using CiteSpace, VOSviewer, and R packages. Data were retrieved from the Web of Science Core Collection, with a focus on publication volume, citation analysis, co-authorship networks, co-citation relationships, and citation bursts. Results: A total of 4,297 studies published in 778 journals were included in the analysis. ET research has seen rapid growth, with researcher clusters in the United States and Europe driving progress through extensive regional and international collaborations. Leading researchers, such as Ayalew Tefferi from the Mayo Clinic and Alessandro M. Vannucchi from the University of Florence, have made significant advances in ET classification, molecular mechanisms, targeted therapies, and disease management. The discovery of driver mutations, such as JAK2, has revolutionized the diagnostic and therapeutic approaches to ET. Research focus has shifted from clinical morphological diagnosis to molecular diagnostics, with the field now entering the era of targeted therapies. However, the inherent heterogeneity of ET continues to present challenges for the widespread implementation of personalized precision treatment. Conclusion: Bibliometric analysis demonstrates significant advances in ET research, particularly in molecular pathology and targeted therapies. However, the heterogeneity of ET remains a major obstacle to personalized treatment. Future research should focus on further elucidating the pathogenesis of ET and improving stratified management approaches to achieve individualized precision therapy.

Phosphorus (P) is an essential element in food production, but it is often largely unavailable for plants as it persists in soils in immobilized forms. Farmers have been using P fertilizers extensively to overcome this unavailability, leading to the exhaustion of non-renewable deposits of phosphorite, rising fertilizers prices and causing several environmental impacts such as eutrophication. Its large-scale utilization is also inefficient since most of the added P becomes quickly unavailable for the plants. Therefore, farming solutions that improve P uptake, P use efficiency of plants and P mobilization in soils are highly important. In this narrative review, we summarized and explored the link between the Silicon (Si) and P cycles in soils. Silicon is quasi-essential for plants, and it has been established that its presence in soil and uptake by plants has several benefits, especially in toxic and nutrient-deficient conditions. Here, we established that Si in soils can affect crop production in P-deficient conditions through: 1) the pH effect – Si improves organic matter decomposition and decreases Al3+ availability; the Si uptake effect – the deposited Si in the plant improves its photosynthetic performance, improves the root ability to uptake P, improves organic matter decomposition and increases P/Mn ration in plant, improving P use; and 3) the Si soil effect – Si stimulates phosphorite rocks weathering and competes with P for the binding places at the surface of Ak and Fe hydroxides, releasing P into soil solution. This positive effect of Si on P mobilization in soils and consequent use by crops should be further disseminated to farmers and other relevant stakeholders.

Cystic fibrosis (CF) diagnosis can be a challenge due to the large spectrum of pathogenic variants in the CFTR gene and the effects of complex alleles. Next-generation sequencing has improved our understanding of the contribution of these complex alleles to the wide spectrum of CF clinical symptoms and to the response to medications. Herein, we studied nine CF patients from six unrelated families carrying the complex allele p.[Ile148Thr;Ile1023_Val1024del] with a frequency of 0.18%. All the patients were from Central Mexico. This complex allele was found in trans with Class I and II pathogenic variants (PVs) such as [c.1521_1523del, p.(Phe508del), and c.3231_3232del, p.(Phe1078Profs*77)]. A targeted search of a dataset of 2,217 exomes from healthy individuals revealed that eight individuals (0.18%) carried the p.(Ile148Thr) variant, but only one (0.022%), who was also born in Central Mexico, was a carrier of the complex allele. These findings led us to hypothesize a founder effect for the p.[Ile148Thr;Ile1023_Val1024del] complex allele in Mexican patients with CF, probably through migration from the French-Canadian population in Mexico. Finally, protein modeling revealed that this complex allele disrupts the secondary structure of the CFTR protein and might alter the ion flow.

In this paper, various Ni-P composite coatings containing toner, MoS2, and nano-SiO2 particles were deposited on steel substrates by the electroless method. Then, the electrochemical properties of these coatings after a heat treatment process were compared. The microstructural evaluations were also done by using the optical and electron microscopy methods. Both Tafel polarization and electrochemical impedance spectroscopy techniques were utilized to survey the electrochemical behavior of such coatings. The surface morphology of all coatings contained cauliflower-like nodules. The X-ray diffraction patterns showed the crystalline phases of Ni and Ni3P for all coatings after the heat-treatment step. Obtained results showed that all composite coatings exhibited lower corrosion rates with respect to Ni-P coatings. Such a reduction was about 21.6-92.2%. This behavior was attributed to the presence of reinforcement as barriers for corrosive ion diffusion through the coating plus the changes in detected phases and thickness. Electrochemical impedance spectroscopy test results also demonstrated that the increase in the polarization resistance for composites coatings was about 18.4-85.3% after 1 h immersion in a 0.6M NaCl solution; however, when the immersion time increased to 24 h, such increased resistance changed to 18.1 to 73.1%. Totally, despite the lower deposition rate, the presence of MoS2 and nano-SiO2 particles were more effective than toner particles to raise the corrosion rate of the Ni-P coating.

In this paper, we investigate p-adic q-integral (q-Volkenborn integral) on Z_p of p-adic gamma function via their Mahler expansions. We also derived two q-Volkenborn integrals of p-adic gamma function in terms of q-Daehee polynomials and numbers and q-Daehee polynomials and numbers of the second kind. Moreover, we discover q-Volkenborn integral of the derivative of p-adic gamma function. We acquire the relationship between the p-adic gamma function and Stirling numbers of the first kind. We finally develop a novel and interesting representation for the p-adic Euler constant by means of the q-Daehee polynomials and numbers.

It is known that the class of p-normed spaces (0 < p ≤ 1) is an important generalization of usual normed spaces with rich topological and geometrical structure, but the most of tools and general principles in nature with nonlinearity have not been developed yet, thus the main goal of this paper is to develop tools for nonlinear analysis under the framework of p-vector spaces. In particular, we first develop the general fixed point theorems which provide solutions to answer Schauder conjecture since 1930’s in the affirmative for p-vector spaces when p = 1 (which is just general topological vector spaces); then the one best approximation result for upper semi-continuous mappings is given, which is used as a powerful tool to establish fixed points for non-self set-valued mappings with either inward or outward set conditions; and finally we establish comprehensive existence results of solutions for Birkhoff-Kellogg Problems, and the general principle of nonlinear alternative by including Leray-Schauder alternative and related results. The results given in this paper not only include the corresponding results in the existing literature as special cases, but also expected to be useful tools for the study of nonlinear problems arising from theory to practice.

Anticonvulsant drugs are widely used in the management of epilepsy and other neurological disorders. However, their concomitant use with other medications can lead to significant drug interactions, impacting both efficacy and safety. This article aims to provide a comprehensive overview of common anticonvulsant interactions with other frequently used drugs. It discusses the mechanisms of these interactions, their clinical implications, and strategies for managing them. The article also highlights the importance of monitoring and patient education in minimizing adverse outcomes.

Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) who suffer from ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies have suggested a high efficacy with unusually high seizure-free rates. We sought to investigate the serum trough levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. We analyzed samples from 101 PWEs treated with adjunct cenobamate under steady-state conditions. In all, 36 PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. We found a linear correlation between the daily doses (range: 100 mg – 400 mg) and the plasma levels (3.8 mg/l – 54.6 mg/l). Neither the daily doses nor the plasma levels differed significantly between seizure-free and non-responding PWEs or between PWEs with a satisfactory tolerability and those who experienced adverse events. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Still, to evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful.

The dentate gyrus (DG) is part of the hippocampal formation and is essential for important cognitive processes such as navigation and memory. The oscillatory activity of the DG network is believed to play a critical role in cognition. DG circuits generate three main rhythms: theta, beta, and gamma, which participate in the specific information processing performed by DG neurons. In the temporal lobe epilepsy (TLE), cognitive abilities are impaired, which may be due to drastic alterations in the DG structure and network activity during epileptogenesis. The theta rhythm and theta coherence are especially vulnerable in dentate circuits; disturbances in DG theta oscillations and their coherence may be responsible for general cognitive impairments observed during epileptogenesis. Some researchers suggested that the vulnerability of DG mossy cells is a key factor in the genesis of TLE, but others did not support this hypothesis. The aim of the review is not only to present the current state of the art in this field of research but to help pave the way for future investigations by highlighting the gaps in our knowledge to completely appreciate the role of DG rhythms in brain functions. Disturbances in oscillatory activity of the DG during TLE development are described in detail that may be a diagnostic marker in the treatment of this disease.

Epilepsy is characterized by repeated spontaneous reactions caused by hyper-excitability and neurons firing in high synchronization in the central nervous system. It seriously affects the quality of life of epileptic patients and nearly 30% of individuals are refractory to treatment of antiepileptic drugs. Therefore, there is an urgent need to develop new medicines to manage and control the refractory epilepsy. Cannabinoid ligands including selective cannabinoid receptor subtype (CB1 or CB2 receptor) ligands and non-selective cannabinoid (synthetic and endogenous) ligands may serve as the novel candidates for this need. Cannabinoid systems appear to regulating seizure activity in the brain through the activation of CB1 and CB2 cannabinoid receptors (CB1R and CB2R). An abundant series of cannabinoid analogues have been tested in various animal models, including a rat pilocarpine model of acquired epilepsy, in vitro hippocampal neuronal culture models of acquired epilepsy and status epilepticus, a pentylenetetrazole model of myoclonic seizures in mice and a penicillin-induced model of epileptiform activity in the rats. The accumulating lines of evidence show that cannabinoid ligands exhibit significant benefits to control seizure activity in different epileptic models. For this reason, we summarize the relationship between brain CB2 receptors and seizures, and emphasize the potential mechanisms of their therapeutic effects involving affecting neurons, astrocytes, and microglia cells. The unique features of CB2Rs, such as lower expression levels under physiological conditions and high inducibility under epileptic conditions, make it an important target for future research on drug-resistant epilepsy.