Partial Activity Research Articles

Investigating the Synergistic Effect of Decoration and Doping in Silver/Strontium Titanate for Air Remediation.

Strontium titanate (STO) and its variants have emerged as leading materials in photocatalysis, particularly for degrading nitrogen oxides (NOx), due to their non-toxic nature, structural adaptability, and exceptional thermal stability. Although the one-pot sol-gel method leads to high-quality photocatalysts, areas remain for improvement. This study examines the impact of ethanol as a cosolvent in STO synthesis, focusing on optimizing the water-to-ethanol volume ratio. The findings reveal that a 1:3 ratio significantly enhances macropore formation and photocatalytic efficiency, achieving 42% NOx degradation under LED within three hours. Furthermore, incorporating 8.0 wt.% Ag into STO substantially improves visible light absorption and enables complete NOx elimination, thanks to enhanced charge separation and localized surface plasmon resonance. Even at high temperatures (1100 °C), the Ag-STO photocatalyst maintains partial activity, despite exceeding silver's melting point. These results highlight the potential of STO-based materials for industrial applications, positioning them as a promising solution for effective NOx mitigation.

Physiological monitoring of movement and manoeuvrability during a military skiing exercise

IntroductionMilitary forces receive training in various high-altitude warfare techniques to safeguard border regions and lives. Skiing is one of such practices where research evidences are limited. Therefore, a study was...

Therapeutic Options for Crigler–Najjar Syndrome: A Scoping Review

Crigler–Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in the following forms: CNS type 1 (CNS1), the more severe form with the complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. This narrative review aims to provide a detailed overview of CNS, highlighting its clinical significance and the need for new, more effective treatments. By summarizing current knowledge and discussing future treatments, this article seeks to encourage further research and advancements that can improve outcomes for CNS patients. The literature analysis showed that CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients responding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risk of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interventions.

Biodegradation of the Antiretroviral Tenofovir Disoproxil by a Cyanobacteria/Bacterial Culture.

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug extensively used by people living with HIV. The TDF molecule is hydrolysed in vivo and liberates tenofovir, the active part of the molecule. Tenofovir is a very stable drug and the discharge of its residues into the environment can potentially lead to risk for aquatic species. This study evaluated the TDF biodegradation and removal by cultures of Microcystis novacekii with the bacteria Pseudomonas pseudoalcaligenes. Concentrations of TDF of 12.5, 25.0, and 50.0 mg/L were used in this study. The process occurred in two stages. In the first 72 h, TDF was de-esterified, forming the tenofovir monoester intermediate by abiotic and enzymatic processes associated in an extracellular medium. In a second step, the monoester was removed from the culture medium by intracellular processes. The tenofovir or other by-products of TDF were not observed in the test conditions. At the end of the experiment, 88.7 to 94.1% of TDF and its monoester derivative were removed from the culture medium over 16 days. This process showed higher efficiency of TDF removal at the concentration of 25 mg/L. Tenofovir isoproxil monoester has partial antiviral activity and has shown to be persistent, maintaining a residual concentration after 16 days in the culture medium, therefore indicating the need to continue research on methods for total removal of this product from the aquatic environment.

Ornithine lipid is a partial TLR4 agonist and NLRP3 activator

Gram-negative bacterial lipopolysaccharides (LPSs) trigger inflammatory reactions through Toll-like receptor 4 (TLR4) and prime myeloid cells for inflammasome activation. In phosphate-limited environments, bacteria reduce LPS and other phospholipid production and synthesize phosphorus-free alternatives such as amino-acid-containing lipids like the ornithine lipid (OL). This adaptive strategy conserves phosphate for other essential cellular processes and enhances bacterial survival in host environments. While OL is implicated in bacterial pathogenicity, the mechanism is unclear. Using primary murine macrophages and human mononuclear cells, we elucidate that OL activates TLR4 and induces potassium efflux-dependent nucleotide-binding domain and leucine-rich repeat-containing pyrin protein 3 (NLRP3) activation. OL upregulates the expression of NLRP3 and pro-interleukin (IL)-1β and induces cytokine secretion in primed and unprimed cells. By contrast, in the presence of LPS, OL functions as a partial TLR4 antagonist and reduces LPS-induced cytokine secretion. We thus suggest that in phosphate-depleted environments, OL replaces LPS bacterial immunogenicity, while constitutively present OL may allow bacteria to escape immune surveillance.

Impact of Harmonic Voltage on the Partial Discharge Properties of Eco-Friendly Nanofluid

The Insulation is crucial in transformers to maintain electrical isolation between components and windings, ensuring safe and efficient operation. Mineral oil acts as both insulation and coolant in transformers. It is a substance that does not naturally degrade and can persist in the environment for an extended period if accidentally released. Therefore, Sunflower oil is used as a substitute for mineral oil. However, harmonic distortion is a common issue in power systems, leading to increased dielectric loss and partial discharge activity, ultimately causing insulation failure and equipment damage. Hence, it is vital to analyze the partial discharge performance of pure Sunflower oil under varying harmonic AC voltages to ensure the reliable operation of electrical devices. The study examines the partial discharge characteristics of a sunflower oil-based nanofluid under harmonic AC voltages, which is a blend of pure sunflower oil and SiO2 nanoparticles. Two nanofluid mixtures were created, one with a 0.01% mass ratio and the other with 0.05% sunflower oil. Various PD characteristics were evaluated, including Partial Discharge significance, starting voltage, duration of increase, maximum amplitude, Phase-Resolved PD sample, and frequency and time graphs of the Partial Discharge signal. All tests were carried out under IEC regulations. A comparison was made between the outcomes of Nano blended sunflower oil and natural sunflower edible oil. Experiments were conducted on partial discharges in Sunflower oil using specific harmonic superimposed AC Voltages, utilizing the third and fifth harmonics. The findings reveal that: a) PDIV value decreases with increasing harmonic order when using AC voltage with superimposed harmonics, b) PD characteristics are closely related to the voltage waveform, and the addition of Silica to sunflower oil results in reduced PD amplitude, pulse duration, and time duration compared to pure sunflower oil.

Cd loop fusion enhances the immunogenicity and the potential transmission blocking activity of Plasmodium falciparum generative cell specific 1 (GCS1) antigen

TBVs are suggested to inhibit parasite transmission from humans to Anopheles mosquitoes. For the transmission of Plasmodium parasite, a variety of factors are included in gametes fusion phase. In this step, conserved male-specific generative cell specific 1 antigen is necessary for fusion of cytoplasmic membranes of micro- and macro-gametocytes and zygot formation. The partial blocking activities of elicited antibodies against either the HAP2-GCS1 domain or the cd loop of this antigen have been recorded to hinder the transmission of Plasmodium species in Anopheles mid-gut. Thus, the objective of the present study was to investigate if the cd loop-fusion can enhance the quantity and quality of humoral and cellular immune responses against Plasmodium falciparum GCS1 in comparison to non-fusion antigen (without cd loop), in the adjuvanted and non-adjuvanted mouse groups. The immunogenicity of two constructs of P. falciparum generative cell specific 1 antigen, a fusion protein composed of cd loop and HAP2-GCS1 domain (cd-HAP) and another recombinant PfGCS1 containing solo HAP2-GCS1 domain (HAP2) were assessed to impede Plasmodium gametocytes integration before zygote formation. The antibodies profiling, titer, and avidity of induced antibodies were measured by the immunized mice sera, and the released cytokines (IL-5, TNF, and INF-γ) were analyzed in the supernatants of stimulated splenocytes. Furthermore, the inhibitory potency of the elicited antibodies against HAP2 and cd-HAP was measured during oocyst development by Standard Membrane Feeding Assay (SMFA). The comparative results in the present study showed the higher titer of IgG antibodies and IgG2a subclass, avidity, and transmission-reducing activity (TRA = 72.5 %) when mice were immunized by cd-HAP rather than HAP2. Moreover, our findings confirmed intensified Th1-directed immune responses in group 4 received cd-HAP/Poly(I:C). These findings declared the potential ability of cd loop fusion (cd-HAP) to upsurge humoral and cellular immune responses. However, the immune responses may switch to stronger Th1-type using alternative formulations. Explicitly, the cd-HAP-based vaccine may enhance the overall efficiency of immune responses and present a promising implementation in aiming malaria transmission.

Halogenated retinoid derivatives as dual RARα and RXRα modulators for treating acute promyelocytic leukemia cells

Acute promyelocytic leukemia (APL), a distinctive subtype of acute myeloid leukemia (AML), is characterized by the t(15; 17) translocation forming the PML-RARα fusion protein. Recent studies have revealed a crucial role of retinoid X receptor α (RXRα) in PML-RARα′s tumorigenesis. This necessitates the development of dual RARα and RXRα targeting compounds for treating APL. Here, we developed a pair of brominated retinoid isomers, 5a and 5b, exhibiting RARα agonistic selectivity among the RAR subtypes and RXRα partial agonistic activities. In the treatment of APL cells, low doses (RARα activation range) of 5a and 5b degrade PML-RARα and strongly induce differentiation, while higher doses (RXRα activation range) induce G2/M arrest and apoptosis in both all-trans retinoic acid (ATRA)-sensitive and resistant cells. We replaced the bromine in 5a with chlorine or iodine to obtain compounds 7 or 8a. Interestingly, the chlorinated compound 7 tends to activate RXRα and induce G2/M arrest and apoptosis, while the iodinated compound 8a tends to activate RARα and induce differentiation. Together, our work underscores several advantages and characteristics of halogens in the rational design of RARα and RXRα ligands, offering three promising drug candidates for treating both ATRA-sensitive and resistant APL.

Partial discharge characteristics from polymer insulator under various contaminant

The performance of polymer insulators can be significantly compromised by the presence of contaminants, resulting in damage, structural alterations, and accelerated aging. Hence, this research aimed to investigate the discharge behavior of polymer insulators when exposed to various types of contaminants. Three distinct contaminants, namely fly ash, salt, and algae, were prepared for the study. In order to assess the characteristics of these insulators, measurements of inception and surface breakdown voltages were conducted for each sample. Additionally, partial discharge measurements were performed at two different applied voltages to observe the patterns of partial discharge under different contaminants. To aid in distinguishing the characteristics of partial discharge, a statistical method based on graphical analysis was employed. Furthermore, visual inspection was carried out after the occurrence of partial discharge activity to provide an explanation for these phenomena. The findings of the study revealed that each contaminant produced a unique pattern, which was influenced by the specific elements present in the respective contaminant. It was observed that contaminants exhibit varying effects on partial discharge depending on their nature. Salt was found to induce faster stress propagation, fly ash inhibited stress propagation, and algae had a degrading effect on the surface of the polymer insulators.

Domoic Acid as a Lead for the Discovery of the First Selective Ligand for Kainate Receptor Subtype 5 (GluK5).

Twenty-one simplified analogues of the natural product domoic acid were designed, synthesized, and then characterized at homomeric kainic acid (KA) receptors (GluK1-3,5). LBG20304 displays a high affinity for homomeric GluK5 receptors (IC50 = 432 nM) with a >40-fold selectivity over homomeric GluK1-3 subtypes and ≫100-fold selectivity over native AMPA and N-methyl d-aspartate receptors. Functional studies of LBG20304 on heteromeric GluK2/5 receptors show no agonist or antagonist functional response at 10 μM, while a concentration of 100 μM at neuronal slices (rat) shows low agonist activity. A molecular dynamics simulation of LBG20304, in a homology model of GluK5, suggests specific interactions with the GluK5 receptor and an occluded ligand binding domain, which is translated to agonist or partial agonist activity. LBG20304 is a new compound for the study of the role and function of the KA receptors with the aim of understanding the involvement of these receptors in health and disease.

Advances in Pompe Disease Treatment: From Enzyme Replacement to Gene Therapy.

Pompe disease is a neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), hydrolyzing glycogen to glucose. Pathological glycogen storage, the hallmark of the disease, disrupts the metabolism and function of various cell types, especially muscle cells, leading to cardiac, motor, and respiratory dysfunctions. The spectrum of Pompe disease manifestations spans two main forms: classical infantile-onset (IOPD) and late-onset (LOPD). IOPD, caused by almost complete GAA deficiency, presents at birth and leads to premature death by the age of 2 years without treatment. LOPD, less severe due to partial GAA activity, appears in childhood, adolescence, or adulthood with muscle weakness and respiratory problems. Since 2006, enzyme replacement therapy (ERT) has been approved for Pompe disease, offering clinical benefits but not a cure. However, advances in early diagnosis through newborn screening, recognizing disease manifestations, and developing improved treatments are set to enhance Pompe disease care. This article reviews recent progress in ERT and ongoing translational research, including the approval of second-generation ERTs, a clinical trial of in utero ERT, and preclinical development of gene and substrate reduction therapies. Notably, gene therapy using intravenous delivery of adeno-associated virus (AAV) vectors is in phase I/II clinical trials for both LOPD and IOPD. Promising data from LOPD trials indicate that most participants met the criteria to discontinue ERT several months after gene therapy. The advantages and challenges of this approach are discussed. Overall, significant progress is being made towards curative therapies for Pompe disease. While several challenges remain, emerging data are promising and suggest the potential for a once-in-a-lifetime treatment.

Effect of Environmental and Operating Conditions on Partial Discharge Activity in Electrical Machine Insulation: A Comprehensive Review

Electrical machines for transportation applications are subjected to harsh environmental conditions during their operations. Partial discharge (PD), which is one of the main reasons for insulation failure, is greatly affected by ambient conditions (i.e., temperature, pressure, and humidity). Countless efforts are made for a comprehensive understanding of the physics of PD under variable environmental factors. This paper aims to review recent works addressing temperature, pressure, and humidity impact on PD activity. The main content of the paper is organized into three sections dealing with each environmental factor. In every section, relevant publications are reviewed considering the type of samples tested, voltage waveform applied, mutual effects, and the most common PD modeling strategies used. The applicability of the PD measurements for PD risk assessment is also discussed. Based on the review, the current progress in understanding the environmental effects on the PD inception mechanism and PD characteristics is presented and discussed in detail, and future research trends in this field are outlined.

Study on the effect of volatile organic compounds on the treatment of high-salt wastewater by low-temperature evaporation

ABSTRACT High-salinity wastewater, owing to its intricate composition and challenging treatment requirements, poses a significant hurdle in water environmental governance. In this study, low-temperature evaporation technology is used to tackle wastewater containing the volatile organic compound such as N,N-dimethylacetamide (DMAC). Utilisation of comprehensive approaches involving experimental testing, mathematical modelling, and Aspen Plus software simulations, The influence of DMAC on evaporation efficiency is researched through the following factors which encompassing its effects on boiling point elevation, partial molar activation energy, and the formation of by-products. Additionally, the comparation of the impact of temperature, ionic strength, intermolecular interactions on the evaporation rate and the concentration of the volatile component DMAC in the condensate is also conducted in this study. After conducting a multiple linear regression analysis of evaporation efficiency using the Statistical Product and Service Solutions (SPSS) tool, it was discovered that temperature serves as the primary determinant influencing the evaporation rate. Additionally, ionic strength impacts solution viscosity, intermolecular interactions, and saturated vapour pressure by altering the intermolecular forces, thereby indirectly influencing both the evaporation rate and the quality of condensate water. The comparative analysis of single-effect and double-effect evaporation indicates that the optimal operating condition for double-effect evaporation yields an evaporation rate of 70%, with a remarkable 88% reduction in steam consumption compared to single one. Based on heat and mass balance principles, the mathematical model for double-effect evaporation is established to offer crucial data support for practical industrial applications.

Recent Advances in representative small-molecule DRD2 inhibitors: Synthetic Routes and clinical applications

The dopamine D2 receptor (DRD2) represents a pivotal target for therapeutic intervention in the treatment of neuropsychiatric disorders, including schizophrenia, bipolar disorder, and Parkinson's disease. The successful discovery of numerous effective DRD2 inhibitors has led to their clinical application and ongoing evaluation in various clinical trials. This review explores the synthetic approaches and clinical applications of prototypical small-molecule DRD2 inhibitors that have received approval or are currently undergoing clinical trials, highlighting their therapeutic potential and challenges. The synthesis of these inhibitors employs various chemical strategies, including modifications of phenothiazine and butyrophenone structures, which have yielded significant antipsychotic agents like chlorpromazine and haloperidol. Additionally, newer classes of inhibitors, such as aripiprazole, exhibit partial agonist activity at DRD2, offering a unique therapeutic profile. Clinically, DRD2 inhibitors demonstrate efficacy in managing positive symptoms of schizophrenia, manic episodes in bipolar disorder, and dopaminergic imbalance in Parkinson's disease. However, the emergence of adverse effects, including tardive dyskinesia, extrapyramidal symptoms and metabolic syndrome, presents substantial challenges. Advances in the development of second-generation antipsychotics aim to balance efficacy with a better side effect profile by targeting additional neurotransmitter receptors. This review aims to deliver an overview of the synthesis and clinical applications of representative small-molecule DRD2 inhibitors across various clinical phases, thereby offering strategic insights for the advancement of DRD2 inhibitor development.

Evidence of isochorismate channeling between the Escherichia coli enterobactin biosynthetic enzymes EntC and EntB.

Enterobactin is a high-affinity iron chelator produced and secreted by Escherichia coli and Salmonella typhimurium to scavenge scarce extracellular Fe3+ as a micronutrient. EntC and EntB are the first two enzymes in the enterobactin biosynthetic pathway. Isochorismate, produced by EntC, is a substrate for EntB isochorismatase. By using a competing isochorismate-consuming enzyme (the E. coli SEPHCHC synthase MenD), we found in a coupled assay that residual EntB isochorismatase activity decreased as a function of increasing MenD concentration. In the presence of excess MenD, EntB isochorismatase activity was observed to decrease by 84%, indicative of partial EntC-EntB channeling (16%) of isochorismate. Furthermore, addition of glycerol to the assay resulted in an increase of residual EntB isochorismatase activity to approximately 25% while in the presence of excess MenD. These experimental outcomes supported the existence of a substrate channeling surface identified in a previously reported protein-docking model of the EntC-EntB complex. Two positively charged EntB residues (K21 and R196) that were predicted to electrostatically guide negatively charged isochorismate between the EntC and EntB active sites were mutagenized to determine their effects on substrate channeling. The EntB variants K21D and R196D exhibited a near complete loss of isochorismatase activity, likely due to electrostatic repulsion of the negatively charged isochorismate substrate. Variants K21A, R196A, and K21A/R196A retained partial EntB isochorismatase activity in the absence of EntC; in the presence of EntC, isochorismatase activity in all variants increased to near wild-type levels. The MenD competition assay of the variants revealed that while K21A channeled isochorismate as efficiently as wild-type EntB (~ 15%), the variants K21A/R196A and R196A exhibited an approximately 5-fold loss in observed channeling efficiency (~3%). Taken together, these results demonstrate that partial substrate channeling occurs between EntC and EntB via a leaky electrostatic tunnel formed upon dynamic EntC-EntB complex formation and that EntB R196 plays an essential role in isochorismate channeling.

Structural basis for the full and partial agonist activities of retinoid X receptor α ligands with an iso-butoxy and an isopropyl group

Retinoid X receptors (RXRs) belong to a retinoid-binding subgroup of the nuclear receptor family, and their synthetic agonists have been developed as therapeutics for glucose and lipid metabolism, inflammation, and inflammatory bowel disease, although RXR agonists could cause side effects such as hypothyroidism, hypertriglyceridemia, and hepatomegaly. We previously reported novel full and partial agonists, NEt–3IB and NEt–4IB, which reduce the side effects, but the molecular basis of their different activity was not clear. In this study, we report the crystal structures of the ligand-binding domain of human RXRα complexed with NEt–3IB and NEt–4IB. Detailed comparisons of the two structures showed that the full agonist, NEt–3IB, is more stably accommodated in the ligand-binding pocket due to the interactions of the bulky iso-butoxy group with helices 5 and 7. The stabilization of these helices led to the stabilization of helix 12, which is important for formation of the coactivator-binding site. The structures shed light on the novel mechanism of the regulation of RXR activity through the interaction between the bound agonist and helix 7, an interaction that was not previously considered important.

Forward osmosis zwitterionic membranes for platelet concentration – Evaluation of the feasibility of the concept

This study focuses on the development of forward osmosis (FO) membranes tailored for platelet and growth factor enrichment applications while maintaining minimal activation throughout the process. The FO membrane structure comprises a polyacrylonitrile (PAN) layer, fabricated using vapor-induced phase separation (VIPS), atop a polyethylene terephthalate (PET) substrate. Then, a polyamide (PA) layer was formed through interfacial polymerization (IP) at the PAN layer interface. The PET side of the membrane was further enhanced with coatings of antifouling copolymers, based on poly(ethylene glycol) methyl ether methacrylate (PEGMA) alone or both PEGMA and zwitterionic sulfobetaine methacrylate (SBMA). In a first step, the formation of each layer was optimized. The structure of the PAN layer was adjusted through the polymer concentration (15 wt%) and the exposure time to vapors (15 min) during the VIPS step. The PA layer was optimized by adjusting the curing temperature to 70 °C. The antifouling copolymer was selected by conducting protein adsorption tests. Subsequently, these tailored FO membranes were employed in the enrichment of plasma proteins, growth factors, and platelets from platelet-rich plasma. It is shown that the membrane modified with a copolymer made of butyl methacrylate (BMA), PEGMA and SBMA, referred to as poly(BMA-r-PEGMA-r-SBMA), enabled to reach a Human Serum Albumin concentration factor of 1.32 and a platelet concentration using PRP of 2.4. Despite partial platelet activation (12 %) due to the high cell concentration, the platelet content is much higher than in PRP or whole blood, which could benefit platelet-based therapies. In addition, the system can be applied to the concentration of growth factors, with PDGF and VEGF concentration factors of 1.92 and 2.58, respectively, which could contribute to the advancement of regenerative medicine.

Peri active site catalysis of proline isomerisation is the molecular basis of allomorphy in β-phosphoglucomutase

Metabolic regulation occurs through precise control of enzyme activity. Allomorphy is a post-translational fine control mechanism where the catalytic rate is governed by a conformational switch that shifts the enzyme population between forms with different activities. β-Phosphoglucomutase (βPGM) uses allomorphy in the catalysis of isomerisation of β-glucose 1-phosphate to glucose 6-phosphate via β-glucose 1,6-bisphosphate. Herein, we describe structural and biophysical approaches to reveal its allomorphic regulatory mechanism. Binding of the full allomorphic activator β-glucose 1,6-bisphosphate stimulates enzyme closure, progressing through NAC I and NAC III conformers. Prior to phosphoryl transfer, loops positioned on the cap and core domains are brought into close proximity, modulating the environment of a key proline residue. Hence accelerated isomerisation, likely via a twisted anti/C4-endo transition state, leads to the rapid predominance of active cis-P βPGM. In contrast, binding of the partial allomorphic activator fructose 1,6-bisphosphate arrests βPGM at a NAC I conformation and phosphoryl transfer to both cis-P βPGM and trans-P βPGM occurs slowly. Thus, allomorphy allows a rapid response to changes in food supply while not otherwise impacting substantially on levels of important metabolites.

Brexpiprazole for Agitation Associated With Dementia Due to Alzheimer's Disease

Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by progressive cognitive and functional decline. Nearly all patients with AD develop neuropsychiatric symptoms (NPSs). Agitation is one of the most distressing and challenging NPS. Brexpiprazole is an oral antipsychotic and is the first approved pharmacologic agent in the United States for the treatment of agitation associated with dementia due to AD. Its effect is thought to be from its partial serotonin 5-HT1A and dopamine D2 receptor agonist activity and serotonin 5-HT2A receptor antagonism. Brexpiprazole is a maintenance medication, and it should not be used “as needed” or as a “PRN” treatment for breakthrough agitation. Brexpiprazole is a major substrate of CYP2D6 and CYP3A4. Dose adjustments may be required for drug interactions or impaired renal or hepatic function. Clinical trials found brexpiprazole 2 to 3 mg/d demonstrated significant improvements in agitation, with brexpiprazole showing an approximate 5-point greater reduction on change in the Cohen-Mansfield Agitation Inventory total score at week 12 from baseline compared with placebo. Brexpiprazole is generally well tolerated and safe, and common adverse reactions when used for this indication include dizziness, headaches, insomnia, nasopharyngitis, somnolence, and urinary tract infections. Like other antipsychotics used for agitation in AD, brexpiprazole is associated with higher mortality rates compared with placebo. In a long-term care setting, there are several considerations for its use. Benefits include an oral agent that is well tolerated and clinical data showing statistically significant effects on agitation. However, brexpiprazole has not been studied in head-to-head clinical trials against other antipsychotics, and there are differing opinions if the agitation score reductions translate to a clinically meaningful difference. The approval of brexpiprazole signals favorably for upcoming agents for this indication, including escitalopram and dextromethorphan-bupropion. Both escitalopram and dextromethorphan-bupropion are currently undergoing clinical trials.

Acaricidal activity of Egyptian crude plant extracts against Haemaphysalis longicornis ticks.

Haemaphysalis longicornis is a common Ixodida tick species found in temperate areas of Asian countries. An anti-tick assay was conducted on adult female H. longicornis ticks. Plant extract solutions were prepared at concentrations of 50, 25, and 10 mg/mL. Tick survival and mortality were assessed by counting the number of dead and live ticks at 24 h, 48 h, 72 h, and 96 h posttreatment. Out of 11 plant extracts screened, Artemisia judaica extract exhibited the highest potency with 100% mortality (5/5) at 48 h when applied at high and moderate concentrations (50 and 25 mg/mL). Similar results were observed at 96 h for the 10 mg/mL group compared to the untreated ticks. Cleome droserifolia extract demonstrated partial activity with 60% (3/5) and 20% (1/5) mortality at 96 h posttreatment at concentrations of 50 and 25 mg/mL, respectively. Forsskaolea tenacissima extract showed a weak effect with 100% tick mortality (5/5) only at the highest treatment concentration after 96 h. To confirm the activity of A. judaica, trial 2 was conducted. A. judaica demonstrated potency within 48 h in high dose and 72 h in moderate dose, with 100% mortality (15/15) at 96 h posttreatment compared to untreated ticks. The median lethal time 50 (LT50) values were 30.37 h for the high and 55.08 h for the moderate doses. Liquid chromatography‒mass spectrometry was performed on the most potent candidate (A. judaica) to identify its phytochemical components. The results revealed the presence of 9 compounds identified through manual annotation and 74 compounds from the Global Natural Products Social library. These compounds included terpenoids, steroids, phenylpropanoids, flavonoid glycosides, flavonoids, and benzenoids. Camphor was identified as the major component via both approaches. These findings suggest the potential use of A. judaica extract in the future development of acaricidal therapeutics.