Concomitant urea stabilization and phosphorus recovery from source-separated fresh urine in magnesium anode-based peroxide-producing electrochemical cells.

In this study, we investigated the recovery of nitrogen (N) and phosphorus (P) from fresh source-separated urine with a novel electrochemical cell equipped with a magnesium (Mg) anode and carbon-based gas-diffusion cathode. Recovery of P, which exists primarily as phosphate (PO43-) in urine, was achieved through pH-driven precipitation. Maximizing N recovery requires simultaneous approaches to address urea and ammonia (NH3). NH3 recovery was possible through precipitation in struvite with soluble Mg supplied by the anode. Urea was stabilized with electrochemically synthesized hydrogen peroxide (H2O2) from the cathode. H2O2 concentrations and resulting urine pH were directly proportional to the applied current density. Concomitant NH3 and PO43- precipitation as struvite and urea stabilization via H2O2 electrosynthesis was possible at lower current densities, resulting in urine pH under 9.2. Higher current densities resulted in urine pH over 9.2, yielding higher H2O2 concentrations and more consistent stabilization of urea at the expense of NH3 recovery as struvite; PO43- precipitation still occurred but in the form of calcium phosphate and magnesium phosphate solids.

Effect of fluoride or chitosan toothpaste and at-home bleaching in enamel roughness, tooth color, and staining susceptibility.

PURPOSE: To evaluate how fluoride- or chitosan-based toothpaste used during at-home bleaching affects enamel roughness, tooth color, and staining susceptibility. METHODS: Bovine enamel blocks were submitted to a 14-day cycling regime considering a factorial design (bleaching agent x toothpaste, 2 x 3), with n=10: (1) bleaching with 16% carbamide peroxide (CP) or 6% hydrogen peroxide (HP), and (2) daily exposure of a fluoride (1,450 ppm F-NaF) toothpaste (FT), chitosan-based toothpaste (CBT), or distilled water (control). Then, 24 hours after the last day of bleaching procedure the samples were exposed to a coffee solution. Color (ΔEab, ΔE00, L*, a*, b*) and roughness (Ra, µm) analyses were performed to compare the samples initially (baseline), after bleaching, and after coffee staining. The results were evaluated by linear models for repeated measures (L*, a*, b*, and Ra), 2-way ANOVA (ΔEab, ΔE00) and Tukey's test (α= 0.05). RESULTS: After the at-home bleaching procedure (toothpaste vs. time, P< 0.0001), the toothpaste groups presented a statistically lower Ra than the control (CBT 0.05). After coffee exposure, CBT presented lower ΔEab and ΔE00 values in the HP groups (toothpaste, P< 0.0001), and lower b* and a* values in the CP groups (toothpaste vs. time, P= 0.004). CLINICAL SIGNIFICANCE: Fluoride or chitosan delivered by toothpaste can reduce surface alterations of the enamel during at-home bleaching, without affecting bleaching efficacy.

Chemical Annealing Restructures RNA for Nanopore Detection.

RNA is a key biochemical marker, yet its chemical instability and complex secondary structure hamper its integration into DNA nanotechnology-based sensing platforms. Relying on the denaturation of the native RNA structure using urea, we show that restructured DNA/RNA hybrids can readily be prepared at room temperature. Using solid-state nanopore sensing, we demonstrate that the structures of our DNA/RNA hybrids conform to the design at the single-molecule level. Employing this chemical annealing procedure, we mitigate RNA self-cleavage, enabling the direct detection of restructured RNA molecules for biosensing applications.

Conjugated molecularly imprinted polymers based on covalent organic frameworks: Fluorescent sensing platform for specific capture of urea and elimination of ethyl carbamate.

This study described the preparation of an azide covalent organic framework-embedded molecularly imprinted polymers (COFs(azide)@MIPs) platform for urea adsorption and indirect ethyl carbamate (EC) removal from Chinese yellow rice wine (Huangjiu). By modifying the pore surface of COFs using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, COFs(azide) with a high fluorescence quantum yield and particular recognition ability were inventively produced. In order to selectively trap urea, the COFs(azide) were encased in an imprinted shell layer via imprinting technology. With a detection limit (LOD) of 0.016 µg L-1 (R2 = 0.9874), the COFs(azides)@MIPs demonstrated a good linear relationship with urea in the linear range of 0-5 µg L-1. Using real Huangjiu samples, the spiking recovery trials showed the viability of this sensing platform with recoveries ranging from 88.44 % to 109.26 % and an RSD of less than 3.40 %. The Huangjiu processing model system achieved 38.93 % EC reduction by COFs(azides)@MIPs. This research will open up new avenues for the treatment of health problems associated with fermented alcoholic beverages, particularly Huangjiu, while also capturing and removing hazards coming from food.

Effects of Charge Sequence Pattern and Lysine-to-Arginine Substitution on the Structural Stability of Bioinspired Polyampholytes.

A comprehensive study focusing on the combined influence of the charge sequence pattern and the type of positively charged amino acids on the formation of secondary structures in sequence-specific polyampholytes is presented. The sequences of interest consisting exclusively of ionizable amino acids (lysine, K; arginine, R; and glutamic acid, E) are (EKEK)5, (EKKE)5, (ERER)5, (ERRE)5, and (EKER)5. The stability of the secondary structure was examined at three pH values in the presence of urea and NaCl. The results presented here underscore the combined prominent effects of the charge sequence pattern and the type of positively charged monomers on secondary structure formation. Additionally, (ERRE)5 readily aggregated across a wide range of pH. In contrast, sequences with the same charge pattern, (EKKE)5, as well as the sequences with the equivalent amino acid content, (ERER)5, exhibited no aggregate formation under equivalent pH and concentration conditions.

Enhanced Hydrogen Bonding by Urea Functionalization Tunes the Stability and Biological Properties of Peptide Amphiphiles.

Self-assembled nanostructures such as those formed by peptide amphiphiles (PAs) are of great interest in biological and pharmacological applications. Herein, a simple and widely applicable chemical modification, a urea motif, was included in the PA's molecular structure to stabilize the nanostructures by virtue of intermolecular hydrogen bonds. Since the amino acid residue nearest to the lipid tail is the most relevant for stability, we decided to include the urea modification at that position. We prepared four groups of molecules (13 PAs in all), with varying levels of intermolecular cohesion, using amino acids with distinct ß-sheet promoting potential and/or containing hydrophobic tails of distinct lengths. Each subset contained one urea-modified PA and nonmodified PAs, all with the same peptide sequence. The varied responses of these PAs to variations in pH, temperature, counterions, and biologically related proteins were examined using microscopic, X-ray, spectrometric techniques, and molecular simulations. We found that the urea group contributes to the stabilization of the morphology and internal arrangement of the assemblies against environmental stimuli for all peptide sequences. In addition, microbiological and biological studies were performed with the cationic PAs. These assays reveal that the addition of urea linkages affects the PA-cell membrane interaction, showing the potential to increase the selectivity toward bacteria. Our data indicate that the urea motif can be used to tune the stability of a wide range of PA nanostructures, allowing flexibility on the biomaterial's design and opening a myriad of options for clinical therapies.

High-confidence structural annotation of substances via multi-layer molecular network reveals the system-wide constituent alternations in milk interfered with diphenylolpropane.

The spectral database-based mass spectrometry (MS) matching strategy is versatile for structural annotating in ingredient fluctuation profiling mediated by external interferences. However, the systematic variability of MS pool attributable to aliasing peaks and inadequacy of present spectral database resulted in a substantial metabolic feature depletion. An amended procedure termed multiple-charges overlap peaks extraction algorithm (MCOP) was proposed involving identifying collision-trigged dissociation precursor ions through iteratively matching mass features of fragmentations to expand the spectral reference library. We showcased the versatility and utility of established strategy in an investigation centered on the stimulation of milk mediated by diphenylolpropane (BPA). MCOP enabled efficient unknown annotations at metabolite-lipid-protein level, which elevated the accuracy of substance annotation to 85.3% after manual validation. Arginase and α-amylase (|r| > 0.75, p < 0.05) were first identified as the crucial issues via graph neural network-based virtual screening in the abnormal metabolism of urea triggered by BPA, resulting in the accumulation of arginine (original: 1.7 µg kg-1 1.7 times) and maltodextrin (original: 6.9 µg kg-1 2.9 times) and thus, exciting the potential dietary risks. Conclusively, MCOP demonstrated generalisation and scalability and substantially advanced the discovery of unknown metabolites for complex matrix samples, thus deciphering dark matter in multi-omics.

Gender-specific association between blood cell parameters and hyperuricemia in high-altitude areas.

Background: Hyperuricemia is a common metabolic disorder linked to various health conditions. Its prevalence varies among populations and genders, and high-altitude environments may contribute to its development. Understanding the connection between blood cell parameters and hyperuricemia in high-altitude areas can shed light on the underlying mechanisms. This study aimed to investigate the relationship between blood cell parameters and hyperuricemia in high-altitude areas, with a particular focus on gender differences. Methods: We consecutively enrolled all eligible Tibetan participants aged 18-60 who were undergoing routine medical examinations at the People's Hospital of Chaya County between January and December 2022. During this period, demographic and laboratory data were collected to investigate the risk factors associated with hyperuricemia. Results: Among the participants, 46.09% were diagnosed with hyperuricemia. In the male cohort, significant correlations were found between serum uric acid (SUA) levels and red blood cell (RBC) count, creatinine (Cr). Urea, alanine transaminase (ALT), and albumin (ALB). Notably, RBC exhibited the strongest association. Conversely, in the female cohort, elevated SUA levels were associated with factors such as white blood cell (WBC) count. Urea, ALT, and ALB, with WBC demonstrating the most significant association. Further analysis within the female group revealed a compelling relationship between SUA levels and specific white blood cell subtypes, particularly neutrophils (Neu). Conclusion: This study revealed gender-specific associations between SUA levels and blood cell parameters in high-altitude areas. In males, RBC count may play a role in hyperuricemia, while in females, WBC count appears to be a significant factor. These findings contribute to our understanding of metabolic dynamics in high-altitude regions but require further research for comprehensive mechanistic insights.

Genetic and functional correction of argininosuccinate lyase deficiency using CRISPR adenine base editors.

Argininosuccinate lyase deficiency (ASLD) is a recessive metabolic disorder caused by variants in ASL. In an essential step in urea synthesis, ASL breaks down argininosuccinate (ASA), a pathognomonic ASLD biomarker. The severe disease forms lead to hyperammonemia, neurological injury, and even early death. The current treatments are unsatisfactory, involving a strict low-protein diet, arginine supplementation, nitrogen scavenging, and in some cases, liver transplantation. An unmet need exists for improved, efficient therapies. Here, we show the potential of a lipid nanoparticle-mediated CRISPR approach using adenine base editors (ABEs) for ASLD treatment. To model ASLD, we first generated human-induced pluripotent stem cells (hiPSCs) from biopsies of individuals homozygous for the Finnish founder variant (c.1153C>T [p.Arg385Cys]) and edited this variant using the ABE. We then differentiated the hiPSCs into hepatocyte-like cells that showed a 1,000-fold decrease in ASA levels compared to those of isogenic non-edited cells. Lastly, we tested three different FDA-approved lipid nanoparticle formulations to deliver the ABE-encoding RNA and the sgRNA targeting the ASL variant. This approach efficiently edited the ASL variant in fibroblasts with no apparent cell toxicity and minimal off-target effects. Further, the treatment resulted in a significant decrease in ASA, to levels of healthy donors, indicating restoration of the urea cycle. Our work describes a highly efficient approach to editing the disease-causing ASL variant and restoring the function of the urea cycle. This method relies on RNA delivered by lipid nanoparticles, which is compatible with clinical applications, improves its safety profile, and allows for scalable production.

BREAST CANCER-MODULATED OMENTIN AND VASPIN PLASMA LEVELS.

Omentin and vaspin levels have been shown to change in many inflammatory diseases, the present study aimed to evaluate the omentin and vaspin levels in breast cancer patients. To do so serum samples were collected and analysed for omentin, vaspin, renal and liver function tests. The levels of creatinine (p<0.01) and urea (p<0.05) showed substantial increases, while omentin and Vaspin levels notably decreased (p<0.05). Additionally, breast cancer patients exhibited significantly higher levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine transaminase (ALT) compared to the control group (p<0.05). In comparison to the control group, individuals with breast cancer demonstrated reduced blood concentrations of omentin and vaspin and elevated levels of creatinine and urea. Additionally, liver function testing indicated lower levels of Alanine transaminase (ALT), Alkaline phosphatase (ALP), and Aspartate aminotransferase (AST) in breast cancer patients. Breast cancer patients had lower levels of omentin and vaspin, and higher levels of creatinine and urea compared to the control group. Liver function tests also indicated lower levels of AST, ALP, and ALT in breast cancer patients compared to the control group.

Urea promoted soil microbial community and reduced the residual ciprofloxacin in soil and its uptake by Chinese flowering cabbage.

Antibiotics in agricultural soil can be accumulated in crops and might pose a potential risk to human health. Nevertheless, there is a lack of knowledge about the impact of nitrogen fertilizers on the dissipation and uptake of antibiotics in soils. Therefore, our aim in this study is to investigate the effects of urea fertilizer on the residues of ciprofloxacin and its uptake by Chinese flowering cabbage (Brassica parachinensis L.) as affected by the associated changes on the soil microbial community. A pot experiment has been conducted using spiked soil with 20 mg ciprofloxacin /kg soil and fertilized with urea at dosages equal to 0, 0.2, 0.4, 0.8 t/ha. Application urea especially at 0.4 t/ha decreased the residue of ciprofloxacin in the soil and its uptake by the roots and its translocation to the shoots of Chinese flowering cabbage. The translocation factors (TFs) for ciprofloxacin were significantly decreased (P < 0.05) only at the treatment of 0.4 t/ha, while no significant difference of bio-concentration factors (BCFs). The average well color development (AWCD) values, Shannon diversity, and richness index were higher in the fertilized than the un-fertilized soils, and all such indicators were greater at the treatment of 0.4 t/ha than at 0.2 and 0.8 t/ha. The carbon substrate utilization of phenolic acids at the treatments of 0.4 t/ha were greater than with other levels of urea fertilizer. In conclusion, moderate urea addition significantly increased soil microbial activity and abundance, which in turn promoted the ciprofloxacin dissipation in soil and plant tissue. The present study provides an economical and operational strategy for the remediation of ciprofloxacin contaminated soils.

Nitrogen Forms Regulate the Response of Microcystis aeruginosa to Nanoplastics at Environmentally Relevant Nitrogen Concentrations.

As essential primary producers, cyanobacteria play a major role in global carbon and nitrogen cycles. Though the influence of nanoplastics on the carbon metabolism of cyanobacteria is well-studied, little is known about how nanoplastics affect their nitrogen metabolism, especially under environmentally relevant nitrogen concentrations. Here, we show that nitrogen forms regulated growth inhibition, nitrogen consumption, and the synthesis and release of microcystin (MC) in Microcystis aeruginosa exposed to 10 µg/mL amino-modified polystyrene nanoplastics (PS-NH2) with a particle size of 50 nm under environmentally relevant nitrogen concentrations of nitrate, ammonium, and urea. We demonstrate that PS-NH2 inhibit M. aeruginosa differently in nitrate, urea, and ammonium, with inhibition rates of 51.87, 39.70, and 36.69%, respectively. It is caused through the differences in impairing cell membrane integrity, disrupting redox homeostasis, and varying nitrogen transport pathways under different nitrogen forms. M. aeruginosa respond to exposure of PS-NH2 by utilizing additional nitrogen to boost the production of amino acids, thereby enhancing the synthesis of MC, extracellular polymeric substances, and membrane phospholipids. Our results found that the threat of nanoplastics on primary producers can be regulated by the nitrogen forms in freshwater ecosystems, contributing to a better understanding of nanoplastic risks under environmentally relevant conditions.

PHB Production by Bacillus megaterium LSRB 0103 Using Cornstarch and Urea.

Polyhydroxybutyrates (PHBs) are biopolymers that are good green alternative for synthetic carbon-based polymers, and are also one of the most researched members of the Polyhydroxyalkanoates (PHA) family. In this study, a gram-positive bacterial strain Bacillus megaterium LSRB 0103 was isolated from Pallikaranai Marshland, Chennai, India. Primary screening using Sudan Black dye revealed the presence of intracellular PHB granules. Minimal Davis Media (MDM) which was used or PHB production gave a yield of 0.7107 g/L. Subsequently, using response surface methodology (RSM), a central composite design (CCD) model was designed for media optimization having cornstarch, urea, and pH as independent variables. The findings of the CCD model were fitted into a second-order polynomial equation. The RSM model predicted the maximum PHB yield of 0.93 g/L, at these independent variable levels, cornstarch, 5 g/L; urea, 2.1 g/L; and pH 7.0; while the experimental PHB yield was 0.94 g/L, with a percentage error of 1.1%. This study is the first-time report of production of PHB by Bacillus megaterium using cornstarch and urea as substrate.

Randomized Double-blind Cost-effectiveness Comparison of Two 10% Urea Creams in Patients with Diabetic Foot Syndrome.

OBJECTIVE: To evaluate the cost-effectiveness of two 10% urea creams in patients with diabetic foot syndrome. METHODS: This was a prospective, longitudinal, single-center, randomized, double-blind, prospective clinical trial that evaluated the skin quality of 20 feet belonging to 10 patients with diabetic foot syndrome after the application of two 10% urea creams purchased from pharmacies and supermarkets. RESULTS: At follow-up, 19 (95%) of the participants' feet showed improved skin quality, irrespective of the cream applied. On visual inspection, participants had a decreased presence of xerosis, hyperkeratosis, and preulcerative signs such as subkeratotic bruising and areas of redness on the dorsum of the toes. At the 3-month follow-up, nine (90%) of the participants stated that they had continued to apply the cream as a method of self-management to prevent complications. CONCLUSIONS: Creams containing 10% urea purchased in supermarkets improve foot skin quality in patients with diabetic foot syndrome, regardless of their cost. Based on these findings, the authors recommend creams containing 10% urea as a self-management tool for patients with diabetic foot syndrome.

Design, Synthesis, Computational Studies, and Anti-Proliferative Evaluation of Novel Ethacrynic Acid Derivatives Containing Nitrogen Heterocycle, Urea, and Thiourea Moieties as Anticancer Agents.

In the present work, the synthesis of new ethacrynic acid (EA) derivatives containing nitrogen heterocyclic, urea, or thiourea moieties via efficient and practical synthetic procedures was reported. The synthesised compounds were screened for their anti-proliferative activity against two different cancer cell lines, namely, HL60 (promyelocytic leukaemia) and HCT116 (human colon carcinoma). The results of the in vitro tests reveal that compounds 1-3, 10, 16(a-c), and 17 exhibit potent anti-proliferative activity against the HL60 cell line, with values of the percentage of cell viability ranging from 20 to 35% at 1 µM of the drug and IC50 values between 2.37 µM and 0.86 µM. Compounds 2 and 10 showed a very interesting anti-proliferative activity of 28 and 48% at 1 µM, respectively, against HCT116. Two PyTAP-based fluorescent EA analogues were also synthesised and tested, showing good anti-proliferative activity. A test on the drug-likeness properties in silico of all the synthetised compounds was performed in order to understand the mechanism of action of the most active compounds. A molecular docking study was conducted on two human proteins, namely, glutathione S-transferase P1-1 (pdb:2GSS) and caspase-3 (pdb:4AU8) as target enzymes. The docking results show that compounds 2 and 3 exhibit significant binding modes with these enzymes. This finding provides a potential strategy towards developing anticancer agents, and most of the synthesised and newly designed compounds show good drug-like properties.

Conformation-Associated C···dz2-PtII Tetrel Bonding: The Case of Cyclometallated Platinum(II) Complex with 4-Cyanopyridyl Urea Ligand.

The nucleophilic addition of 3-(4-cyanopyridin-2-yl)-1,1-dimethylurea (1) to cis-[Pt(CNXyl)2Cl2] (2) gave a new cyclometallated compound 3. It was characterized by NMR spectroscopy (1H, 13C, 195Pt) and high-resolution mass spectrometry, as well as crystallized to obtain two crystalline forms (3 and 3·2MeCN), whose structures were determined by X-ray diffraction. In the crystalline structure of 3, two conformers (3A and 3B) were identified, while the structure 3·2MeCN had only one conformer 3A. The conformers differed by orientation of the N,N-dimethylcarbamoyl moiety relative to the metallacycle plane. In both crystals 3 and 3·2MeCN, the molecules of the Pt(II) complex are associated into supramolecular dimers, either {3A}2 or {3B}2, via stacking interactions between the planes of two metal centers, which are additionally supported by hydrogen bonding. The theoretical consideration, utilizing a number of computational approaches, demonstrates that the C···dz2(Pt) interaction makes a significant contribution in the total stacking forces in the geometrically optimized dimer [3A]2 and reveals the dz2(Pt)→π*(PyCN) charge transfer (CT). The presence of such CT process allowed for marking the C···Pt contact as a new example of a rare studied phenomenon, namely, tetrel bonding, in which the metal site acts as a Lewis base (an acceptor of noncovalent interaction).

Ecological and oral toxicity assessment of urea and camphor oil against Rattus norvegicus rats.

Background: One of the most challenging pests to control is the wild rat (Rattus norvegicus), which poses serious risks to both human health and the economy. Fertilizers are a more recent method of pest management with various action modes and are considered safe control agents when applied at low doses. Aim: The present study aimed to examine the toxicological impacts of the contaminated water with urea and camphor oil individually, post-treatment of rats with camphor oil after the pre-treatment with urea and post-treatment of rats with urea mixed with camphor oil after urea pre-treatment against the wild rats (R. norvegicus). Methods: The study extends to explore the influence of these treatments on the physicochemical parameters of the water administered by rats. Moreover, the effect of the most three toxic treatments was studied on the blood and renal functional parameters and the kidney tissue of rats after 21 days of treatment. Results: The study showed that urea was more potent than camphor oil when applied individually and increasing the concentration of urea in the pre-treatment or when combined with camphor oil in the post-treatment caused a significant increase in the mortality of rats. The post-treatment of rats with camphor oil only or camphor oil mixed with urea after the pre-treatment with urea induced a synergistic activity against rats. In addition, the exposed water to urea and camphor oil has been modified in physicochemical parameters and formed ulcers and harm to the kidneys of the exposed wild rats. Conclusion: This study significantly contributes to the ecological and toxicological potential risk indexes of urea and camphor oil together, which are restricted on the perceptible value relevance in the literature of water quality and renal pathology. Therefore, urea and camphor oil represent successful agents for the wild rat's control.

Tunable Light-Responsive Polyurethane-urea Elastomer Driven by Photochemical and Photothermal Coupling Mechanism.

Light-driven soft actuators based on photoresponsive materials can be used to mimic biological motion, such as hand movements, without involving rigid or bulky electromechanical actuations. However, to our knowledge, no robust photoresponsive material with desireable mechanical and biological properties and relatively simple manufacture exists for robotics and biomedical applications. Herein, we report a new visible-light-responsive thermoplastic elastomer synthesized by introducing photoswitchable moieties (i.e., azobenzene derivatives) into the main chain of poly(ε-caprolactone) based polyurethane urea (PAzo). A PAzo elastomer exhibits controllable light-driven stiffness softening due to its unique nanophase structure in response to light, while possessing excellent hyperelasticity (stretchability of 575.2%, elastic modulus of 17.6 MPa, and strength of 44.0 MPa). A bilayer actuator consisting of PAzo and polyimide films is developed, demonstrating tunable bending modes by varying incident light intensities. Actuation mechanism via photothermal and photochemical coupling effects of a soft-hard nanophase is demonstrated through both experimental and theoretical analyses. We demonstrate an exemplar application of visible-light-controlled soft "fingers" playing a piano on a smartphone. The robustness of the PAzo elastomer and its scalability, in addition to its excellent biocompatibility, opens the door to the development of reproducible light-driven wearable/implantable actuators and lightweight soft robots for clinical applications.

On the Optimal Diagnosis and the Evolving Role of Pimavanserin in Parkinson's Disease Psychosis.

Parkinson's disease (PD) is associated with the development of psychosis (PDP), including hallucinations and delusions, in more than half of the patient population. Optimal PD management must therefore involve considerations about both motor and non-motor symptoms. Often, clinicians fail to diagnosis psychosis in patients with PD and, when it is recognized, treat it suboptimally, despite the availability of multiple interventions. In this paper, we provide a summary of the current guidelines and clinical evidence for treating PDP with antipsychotics. We also provide recommendations for diagnosis and follow-up. Finally, an updated treatment algorithm for PDP that incorporates the use of pimavanserin, the only US FDA-approved drug for the treatment of PDP, was developed by extrapolating from a limited evidence base to bridge to clinical practice using expert opinion and experience. Because pimavanserin is only approved for the treatment of PDP in the US, in other parts of the world other recommendations and algorithms must be considered.