Self-Limited Epilepsy With Autonomic Seizures: A Case Report.

This case report describes a six-year-old girl without relevant personal or family history, who had a seizure at awakening with loss of muscle tone, sialorrhea and ocular retroversion. The episode lasted >5 minutes, with vomiting and post-ictal confusion. Upon the hospital visit, she was misdiagnosed with acute gastroenteritis and discharged with symptomatic treatment. After another seizure, she was diagnosed with Panayiotopoulos syndrome and started receiving treatment. Since then, the child has been followed up through neuropediatric appointments and by her family doctor. The psychological assessment revealed normal general intellectual functioning with vulnerability in the language area.

Caffeine Protects Keratinocytes from Trichophyton mentagrophytes Infection and Behaves as an Antidermatophytic Agent.

Caffeine affords several beneficial effects on human health, acting as an antioxidant, anti-inflammatory agent, and analgesic. Caffeine is widely used in cosmetics, but its antimicrobial activity has been scarcely explored, namely against skin infection agents. Dermatophytes are the most common fungal agents of human infection, mainly of skin infections. This work describes the in vitro effect of caffeine during keratinocyte infection by Trichophyton mentagrophytes, one of the most common dermatophytes. The results show that caffeine was endowed with antidermatophytic activity with a MIC, determined following the EUCAST standards, of 8 mM. Caffeine triggered a modification of the levels of two major components of the fungal cell wall, ß-(1,3)-glucan and chitin. Caffeine also disturbed the ultrastructure of the fungal cells, particularly the cell wall surface and mitochondria, and autophagic-like structures were observed. During dermatophyte-human keratinocyte interactions, caffeine prevented the loss of viability of keratinocytes and delayed spore germination. Overall, this indicates that caffeine can act as a therapeutic and prophylactic agent for dermatophytosis.

A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid ß (Aß)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aß in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential to be a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.

Integrated Design and Fabrication of Pneumatic Soft Robot Actuators in a Single Casting Step.

Bio-inspired soft robots have already shown the ability to handle uncertainty and adapt to unstructured environments. However, their availability is partially restricted by time-consuming, costly, and highly supervised design-fabrication processes, often based on resource-intensive iterative workflows. Here, we propose an integrated approach targeting the design and fabrication of pneumatic soft actuators in a single casting step. Molds and sacrificial water-soluble hollow cores are printed using fused filament fabrication. A heated water circuit accelerates the dissolution of the core's material and guarantees its complete removal from the actuator walls, while the actuator's mechanical operability is defined through finite element analysis. This enables the fabrication of actuators with non-uniform cross-sections under minimal supervision, thereby reducing the number of iterations necessary during the design and fabrication processes. Three actuators capable of bending and linear motion were designed, fabricated, integrated, and demonstrated as 3 different bio-inspired soft robots, an earthworm-inspired robot, a 4-legged robot, and a robotic gripper. We demonstrate the availability, versatility, and effectiveness of the proposed methods, contributing to accelerating the design and fabrication of soft robots. This study represents a step toward increasing the accessibility of soft robots to people at a lower cost.

Synthesis and Cytotoxic Activity of Friedelinyl Esters.

Commonly isolated from plants of Celastraceae family, pentacyclic triterpenoids have a broad spectrum of biological activities, such as antitumor, anti-inflammatory, antinociceptive properties, among others. Structural modifications in these triterpenoids can enhance their biological activity, as well as their selectivity, while improving their physicochemical and pharmacokinetic aspects. In this study, eight novel esters were synthesized: four derivatives of 3α-friedelinol (friedelan-3α-yl p-bromobenzoate (1a); friedelan-3α-yl naproxenate (1b); friedelan-3α-yl pent-4-ynoate (1c); friedelan-3α-yl undec-10-ynoate (1d)) and four derivatives of 3ß-friedelinol (friedelan-3ß-yl p-bromobenzoate (2a); friedelan-3ß-yl naproxenate (2b); friedelan-3ß-yl pent-4-ynoate (2c); friedelan-3ß-yl undec-10-ynoate (2d)). Overall, 3α-friedelinol showed greater reactivity when compared to the ß-epimer. The esters 1b-d and 2b-c were tested for antileukemic activity against THP-1 and K-562 cells but showed low cytotoxicity for both cell lines. The most active against THP-1 cells was friedelan-3ß-yl naproxenate (2b, IC50=266±6 µM), and the most active against K-562 cells was friedelan-3α-yl pent-4-ynoate (1c, IC50=267±5 µM).

Effects of Intravenous Lidocaine on Quality of Recovery After Laparoscopic Bariatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis aimed to assess the effects of pre and intraoperative lidocaine infusion on short-term recovery quality after laparoscopic bariatric surgeries. In the search across MEDLINE, Embase, and Cochrane databases, we considered randomized controlled trials comparing intravenous lidocaine vs placebo (saline) for patients with obesity undergoing laparoscopic bariatric surgery. Seven studies (640 patients) were included. The lidocaine group had a significantly higher recovery quality score, a lower morphine consumption, and a notably reduced rate of nausea and vomiting compared with the placebo group. Additionally, Lidocaine infusion was associated with a shorter hospital stay, while no significant difference was observed in the time to bowel function recovery between both groups. In conclusion, lidocaine infusion before and during laparoscopic bariatric surgery contributes to an enhanced quality of recovery.

Leveraging large-scale biobank EHRs to enhance pharmacogenetics of cardiometabolic disease medications.

Electronic health records (EHRs) coupled with large-scale biobanks offer great promises to unravel the genetic underpinnings of treatment efficacy. However, medication-induced biomarker trajectories stemming from such records remain poorly studied. Here, we extract clinical and medication prescription data from EHRs and conduct GWAS and rare variant burden tests in the UK Biobank (discovery) and the All of Us program (replication) on ten cardiometabolic drug response outcomes including lipid response to statins, HbA1c response to metformin and blood pressure response to antihypertensives (N = 740-26,669). Our findings at genome-wide significance level recover previously reported pharmacogenetic signals and also include novel associations for lipid response to statins (N = 26,669) near LDLR and ZNF800. Importantly, these associations are treatment-specific and not associated with biomarker progression in medication-naive individuals. Furthermore, we demonstrate that individuals with higher genetically determined low-density and total cholesterol baseline levels experience increased absolute, albeit lower relative biomarker reduction following statin treatment. In summary, we systematically investigated the common and rare pharmacogenetic contribution to cardiometabolic drug response phenotypes in over 50,000 UK Biobank and All of Us participants with EHR and identified clinically relevant genetic predictors for improved personalized treatment strategies.

Lineage-specific changes in mitochondrial properties during neural stem cell differentiation.

Neural stem cells (NSCs) reside in discrete regions of the adult mammalian brain where they can differentiate into neurons, astrocytes, and oligodendrocytes. Several studies suggest that mitochondria have a major role in regulating NSC fate. Here, we evaluated mitochondrial properties throughout NSC differentiation and in lineage-specific cells. For this, we used the neurosphere assay model to isolate, expand, and differentiate mouse subventricular zone postnatal NSCs. We found that the levels of proteins involved in mitochondrial fusion (Mitofusin [Mfn] 1 and Mfn 2) increased, whereas proteins involved in fission (dynamin-related protein 1 [DRP1]) decreased along differentiation. Importantly, changes in mitochondrial dynamics correlated with distinct patterns of mitochondrial morphology in each lineage. Particularly, we found that the number of branched and unbranched mitochondria increased during astroglial and neuronal differentiation, whereas the area occupied by mitochondrial structures significantly reduced with oligodendrocyte maturation. In addition, comparing the three lineages, neurons revealed to be the most energetically flexible, whereas astrocytes presented the highest ATP content. Our work identified putative mitochondrial targets to enhance lineage-directed differentiation of mouse subventricular zone-derived NSCs.

Uncovering microplastics contamination in canned seafood.

There is limited research on the occurrence of microplastics (MPs) in canned seafood. All types of canned seafood investigated in the present study were contaminated. After sample digestion in 30 % hydrogen peroxide, a total of 40 MPs were recovered. Fibers were the most common type, blue was the dominant colour, and Fourier Transform Infrared Spectroscopy (FTIR) identified polyester as the most common polymer. Considering all samples, an average of 3.5 ± 5.2 MPs/can was obtained, with octopus in tomato sauce and tuna in olive oil presenting the highest contamination (5.2 ± 7.5 MPs/can and 5.2 ± 5.1 MPs/can, respectively). Also, significant differences between the number of MPs in the seafood tissues and immersion liquids were verified. The present study demonstrates MPs occurrence in canned seafood, a potential contamination pathway for humans. More research on the different stages of the canning processing is vital for understanding MPs contamination in cans.

Exercise-induced potentiation of the acute hypoxic ventilatory response: Neural mechanisms and implications for cerebral blood flow.

A given dose of hypoxia causes a greater increase in pulmonary ventilation during physical exercise than during rest, representing an exercise-induced potentiation of the acute hypoxic ventilatory response (HVR). This phenomenon occurs independently from hypoxic blood entering the contracting skeletal muscle circulation or metabolic byproducts leaving skeletal muscles, supporting the contention that neural mechanisms per se can mediate the HVR when humoral mechanisms are not at play. However, multiple neural mechanisms might be interacting intricately. First, we discuss the neural mechanisms involved in the ventilatory response to hypoxic exercise and their potential interactions. Current evidence does not support an interaction between the carotid chemoreflex and central command. In contrast, findings from some studies support synergistic interactions between the carotid chemoreflex and the muscle mechano- and metaboreflexes. Second, we propose hypotheses about potential mechanisms underlying neural interactions, including spatial and temporal summation of afferent signals into the medulla, short-term potentiation and sympathetically induced activation of the carotid chemoreceptors. Lastly, we ponder how exercise-induced potentiation of the HVR results in hyperventilation-induced hypocapnia, which influences cerebral blood flow regulation, with multifaceted potential consequences, including deleterious (increased central fatigue and impaired cognitive performance), inert (unchanged exercise) and beneficial effects (protection against excessive cerebral perfusion).

Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates.

Understanding the immunological control of pathogens requires a detailed evaluation of the mechanistic contributions of individual cell types within the immune system. While knockout mouse models that lack certain cell types have been used to help define the role of those cells, the biological and physiological characteristics of mice do not necessarily recapitulate that of a human. To overcome some of these differences, studies often look towards nonhuman primates (NHPs) due to their close phylogenetic relationship to humans. To evaluate the immunological role of select cell types, the NHP model provides distinct advantages since NHP more closely mirror the disease manifestations and immunological characteristics of humans. However, many of the experimental manipulations routinely used in mice (e.g., gene knock-out) cannot be used with the NHP model. As an alternative, the in vivo infusion of monoclonal antibodies that target surface proteins on specific cells to either functionally inhibit or deplete cells can be a useful tool. Such depleting antibodies have been used in NHP studies to address immunological mechanisms of action. In these studies, the extent of depletion has generally been reported for blood, but not thoroughly assessed in tissues. Here, we evaluated four depleting regimens that primarily target T cells in NHP: anti-CD4, anti-CD8α, anti-CD8ß, and immunotoxin-conjugated anti-CD3. We evaluated these treatments in healthy unvaccinated and IV BCG-vaccinated NHP to measure the extent that vaccine-elicited T cells - which may be activated, increased in number, or resident in specific tissues - are depleted compared to resting populations in unvaccinated NHPs. We report quantitative measurements of in vivo depletion at multiple tissue sites providing insight into the range of cell types depleted by a given mAb. While we found substantial depletion of target cell types in blood and tissue of many animals, residual cells remained, often residing within tissue. Notably, we find that animal-to-animal variation is substantial and consequently studies that use these reagents should be powered accordingly.

cMPL-Based Purification and Depletion of Human Hematopoietic Stem Cells: Implications for Pre-Transplant Conditioning.

The transplantation of gene-modified autologous hematopoietic stem and progenitor cells (HSPCs) offers a promising therapeutic approach for hematological and immunological disorders. However, this strategy is often limited by the toxicities associated with traditional conditioning regimens. Antibody-based conditioning strategies targeting cKIT and CD45 antigens have shown potential in mitigating these toxicities, but their long-term safety and efficacy in clinical settings require further validation. In this study, we investigate the thrombopoietin (TPO) receptor, cMPL, as a novel target for conditioning protocols. We demonstrate that high surface expression of cMPL is a hallmark feature of long-term repopulating hematopoietic stem cells (LT-HSCs) within the adult human CD34+ HSPC subset. Targeting the cMPL receptor facilitates the separation of human LT-HSCs from mature progenitors, a delineation not achievable with cKIT. Leveraging this finding, we developed a cMPL-targeting immunotoxin, demonstrating its ability to selectively deplete host cMPLhigh LT-HSCs with a favorable safety profile and rapid clearance within 24 hours post-infusion in rhesus macaques. These findings present significant potential to advance our understanding of human hematopoiesis and enhance the therapeutic outcomes of ex vivo autologous HSPC gene therapies.

Do organisms need an impact factor? Citations of key biological resources including model organisms reveal usage patterns and impact.

Research resources like transgenic animals and antibodies are the workhorses of biomedicine, enabling investigators to relatively easily study specific disease conditions. As key biological resources, transgenic animals and antibodies are often validated, maintained, and distributed from university based stock centers. As these centers heavily rely largely on grant funding, it is critical that they are cited by investigators so that usage can be tracked. However, unlike systems for tracking the impact of papers, the conventions and systems for tracking key resource usage and impact lag behind. Previous studies have shown that about 50% of the resources are not findable, making the studies they are supporting irreproducible, but also makes tracking resources difficult. The RRID project is filling this gap by working with journals and resource providers to improve citation practices and to track the usage of these key resources. Here, we reviewed 10 years of citation practices for five university based stock centers, characterizing each reference into two broad categories: findable (authors could use the RRID, stock number, or full name) and not findable (authors could use a nickname or a common name that is not unique to the resource). The data revealed that when stock centers asked their communities to cite resources by RRID, in addition to helping stock centers more easily track resource usage by increasing the number of RRID papers, authors shifted from citing resources predominantly by nickname (~50% of the time) to citing them by one of the findable categories (~85%) in a matter of several years. In the case of one stock center, the MMRRC, the improvement in findability is also associated with improvements in the adherence to NIH rigor criteria, as determined by a significant increase in the Rigor and Transparency Index for studies using MMRRC mice. From this data, it was not possible to determine whether outreach to authors or changes to stock center websites drove better citation practices, but findability of research resources and rigor adherence was improved.

Technological Advances and Market Developments of Solid-State Batteries: A Review.

Batteries are essential in modern society as they can power a wide range of devices, from small household appliances to large-scale energy storage systems. Safety concerns with traditional lithium-ion batteries prompted the emergence of new battery technologies, among them solid-state batteries (SSBs), offering enhanced safety, energy density, and lifespan. This paper reviews current state-of-the-art SSB electrolyte and electrode materials, as well as global SSB market trends and key industry players. Solid-state electrolytes used in SSBs include inorganic solid electrolytes, organic solid polymer electrolytes, and solid composite electrolytes. Inorganic options like lithium aluminum titanium phosphate excel in ionic conductivity and thermal stability but exhibit mechanical fragility. Organic alternatives such as polyethylene oxide and polyvinylidene fluoride offer flexibility but possess lower ionic conductivity. Solid composite electrolytes combine the advantages of inorganic and organic materials, enhancing mechanical strength and ionic conductivity. While significant advances have been made for composite electrolytes, challenges remain for synthesis intricacies and material stability. Nuanced selection of these electrolytes is crucial for advancing resilient and high-performance SSBs. Furthermore, while global SSB production capacity is currently below 2 GWh, it is projected to grow with a >118% compound annual growth rate by 2035, when the potential SSB market size will likely exceed 42 billion euros.

A mixed-ligand Co metal-organic framework and its carbon composites as excellent electrocatalysts for the oxygen evolution reaction in green-energy devices.

Oxygen evolution reaction (OER) electrocatalysts are frequently made from noble metal-based oxides like ruthenium/iridium oxides. However, because of their scarcity and high price, researchers are now focusing on creating innovative OER catalysts based on affordable transition metals that have improved electrical conductivity and accessibility to active sites. Metal-organic frameworks (MOFs), a unique class of inorganic materials with excellent physical and chemical properties, have witnessed significant progress in promising green energy systems. In this work, a novel mixed-ligand metal-organic framework [Co(µ-1κN,2κN'-BDP)(µ3-1κoo',2κo''2κo'''-BTC)]n·nH2O (BDP = boron-dipyrromethene or BODIPY; BTC = benzene tricarboxylate) denoted as CoBDPMOF has been synthesized, and its composites with different carbon materials have been designed. Compared to the pristine MOF, the composites showed enhanced electrocatalytic activity toward the oxygen evolution reaction (OER) in alkaline media. In addition, the CoBDPMOF with activated carbon showed the highest OER performance with a low Tafel slope (82 mV dec-1) and the highest j600 (59.8 mA cm-2), outperforming noble metal IrO2, the OER benchmark electrocatalyst. This study presents new insights into the design and application of CoBDPMOF-based materials for energy conversion and suggests promising avenues for further research and development in electrocatalysis.

Thimet oligopeptidase (THOP 1) distribution in cane toad (Bufo Marinus, Linnaeus, 1758) brain.

Thimet oligopeptides (THOP 1) is a metal-dependent peptidase involved in the metabolism of neuropeptides and the presentation of peptides via MHC-1. It has been shown to play a role in the regulation of protein-protein interactions and the metabolism of intracellular peptides. THOP 1 is associated with important biological processes such as metabolism and neurodegenerative diseases, among others. The objective of this study is to elucidate the distribution of THOP 1 in the Bufo marinus brain. The analysis of THOP 1 amino acid sequences indicates that they have been conserved throughout evolution, with significant homology observed across various phyla. When comparing amphibians with other species, more than 70% identity can be identified. Immunohistochemistry analysis of the toad's brain has demonstrated that the enzyme has a ubiquitous distribution, consistent with previous findings in mammals. THOP 1 can be found in important areas of the brain, such as bulb, thalamic nuclei, striatum, hypothalamus, and among others. Nonetheless, THOP 1 is consistently localized within the nucleus, a pattern also observed in the rat brain. Therefore, based on these results, the toad appears to be an excellent model for studying the general biology of THOP 1, given the substantial homology of this enzyme with mammals and its similarity in distribution within the brain.

Applications of Polymer Electrolytes in Lithium-Ion Batteries: A Review.

Polymer electrolytes, a type of electrolyte used in lithium-ion batteries, combine polymers and ionic salts. Their integration into lithium-ion batteries has resulted in significant advancements in battery technology, including improved safety, increased capacity, and longer cycle life. This review summarizes the mechanisms governing ion transport mechanism, fundamental characteristics, and preparation methods of different types of polymer electrolytes, including solid polymer electrolytes and gel polymer electrolytes. Furthermore, this work explores recent advancements in non-aqueous Li-based battery systems, where polymer electrolytes lead to inherent performance improvements. These battery systems encompass Li-ion polymer batteries, Li-ion solid-state batteries, Li-air batteries, Li-metal batteries, and Li-sulfur batteries. Notably, the advantages of polymer electrolytes extend beyond enhancing safety. This review also highlights the remaining challenges and provides future perspectives, aiming to propose strategies for developing novel polymer electrolytes for high-performance Li-based batteries.

Unravelling a novel role for cannabidivarin in the modulation of subventricular zone postnatal neurogenesis.

Postnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis. Using the neurosphere assay, SVZ-derived neural stem/progenitor cells (NSPCs) were incubated with CBDV and/or 5'-Iodoresinferotoxin (TRPV1 antagonist), and their role on cell viability, proliferation, and differentiation were dissected. CBDV was able to promote, through a TRPV1-dependent mechanism, cell survival, cell proliferation and neuronal differentiation. Furthermore, pulse-chase experiments revealed that CBDV-induced neuronal differentiation was a result of cell cycle exit of NSPCs. Regarding oligodendrocyte differentiation, CBDV inhibited oligodendrocyte differentiation and maturation. Since our data suggested that the CBDV-induced modulation of NSPCs acted via TRPV1, a sodium-calcium channel, and that intracellular calcium levels are known regulators of NSPCs fate and neuronal maturation, single cell calcium imaging was performed to evaluate the functional response of SVZ-derived cells. We observed that CBDV-responsive cells displayed a two-phase calcium influx profile, being the initial phase dependent on TRPV1 activation. Taken together, this work unveiled a novel and untapped neurogenic potential of CBDV via TRPV1 modulation. These findings pave the way to future neural stem cell biological studies and repair strategies by repurposing this non-psychoactive cannabinoid as a valuable therapeutic target.

Bipolar Membranes for Direct Borohydride Fuel Cells-A Review.

Direct liquid fuel cells (DLFCs) operate directly on liquid fuel instead of hydrogen, as in proton-exchange membrane fuel cells. DLFCs have the advantages of higher energy densities and fewer issues with the transportation and storage of their fuels compared with compressed hydrogen and are adapted to mobile applications. Among DLFCs, the direct borohydride-hydrogen peroxide fuel cell (DBPFC) is one of the most promising liquid fuel cell technologies. DBPFCs are fed sodium borohydride (NaBH4) as the fuel and hydrogen peroxide (H2O2) as the oxidant. Introducing H2O2 as the oxidant brings further advantages to DBPFC regarding higher theoretical cell voltage (3.01 V) than typical direct borohydride fuel cells operating on oxygen (1.64 V). The present review examines different membrane types for use in borohydride fuel cells, particularly emphasizing the importance of using bipolar membranes (BPMs). The combination of a cation-exchange membrane (CEM) and anion-exchange membrane (AEM) in the structure of BPMs makes them ideal for DBPFCs. BPMs maintain the required pH gradient between the alkaline NaBH4 anolyte and the acidic H2O2 catholyte, efficiently preventing the crossover of the involved species. This review highlights the vast potential application of BPMs and the need for ongoing research and development in DBPFCs. This will allow for fully realizing the significance of BPMs and their potential application, as there is still not enough published research in the field.