Esketamine for Unipolar Major Depression With Psychotic Features: A Retrospective Chart Review and Comparison With Nonpsychotic Depression.

PURPOSES/BACKGROUND: The aims of the study were to assess subanesthetic esketamine as an antidepressant for major depressive disorder with psychotic features (PMDD) and to compare posttreatment symptoms among those with PMDD to a sample of nonpsychotic depression (major depressive disorder [MDD]). METHODS/PROCEDURES: This study is a retrospective chart review of patients with major depression and current psychotic symptoms, treated with a single parenteral 0.5-mg/kg dose of esketamine. Depression symptoms were assessed at baseline and 24-hour posttreatment with the Montgomery-Åsberg Depression Rating Scale. Individuals with PMDD were matched in a 1:2 ratio to nonpsychotic MDD patients from a randomized, noninferiority clinical trial of esketamine. FINDINGS/RESULTS: A total of 15 individuals with PMDD were included, which had higher baseline depression scores (PMDD = 40.9, MDD = 33.6, P = 0.004). A statistically significant change in depressive symptoms was found for the PMDD sample (ß = -16.20 [95% confidence interval, -23.30 to -9.10], P < 0.001), and no difference between PMDD and MDD groups was observed in the matched-sample analysis (ß = -2.2 [95% confidence interval, -9.32 to 4.58], P = 0.537). Treatment-induced dissociative symptoms were present for both groups, self-contained to within 2 hours after treatment, and no exacerbation of psychotic symptoms was found in clinical assessments. IMPLICATIONS/CONCLUSIONS: Results suggest a single 0.5-mg/kg dose of esketamine may benefit individuals with PMDD, and the symptom reduction may be comparable with esketamine's effects for MDD. Furthermore, esketamine may induce an antidepressant response in those with PMDD without complication of psychotic symptoms. Future research with controlled designs is warranted.

Clinical predictors of depressive symptom remission and response after racemic ketamine and esketamine infusion in treatment-resistant depression.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide and most people do not achieve symptom remission. Treatment-resistant depression (TRD) is characterized by the failure of at least one adequate trial of a major class of antidepressant, with adequate time and dosage. We aimed to identify clinical predictors of depressive symptom remission and response 24 h and 7 days after racemic ketamine and esketamine infusions. METHODS: A randomized, double-blind, active-controlled, non-inferiority trial using ketamine and esketamine in TRD. Individuals diagnosed with MDD according to Diagnostic and Statistical Manual of Mental Disorders version IV and fulfilling TRD criteria were recruited from March 2017 to June 2018. Participants received a single subanesthetic dose of ketamine (0.5 mg/kg) or esketamine (0.25 mg/kg) for 40 min. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and symptom remission was defined as a MADRS score ≤7 and response defined as ≥50% reduction in depressive symptom severity, 24 h and 7 days after the infusion. Clinical variables were selected based on previous clinical trials. Stepwise backward logistic regression was used, considering a confidence level of 95%. RESULTS: 61 subjects were included: 39 (63.9%) were females with a mean age of 47.2 ± 14.9. Higher number of therapeutic failures (Odds Ratio (OR) = 0.677; 95% confidence interval (CI): 0.47-0.97) and higher severity of illness (OR = 0.912; 95% CI: 0.83-0.99) were associated with fewer remissions of depressive symptoms 7 days after intervention, and with fewer response in 24 h (OR = 0.583; 95% CI: 0,40; 0,84 and OR = 0.909; 95% CI: 0,83; 0,99, respectively). CONCLUSION: Number of treatment failures and severity of illness were predictors of fewer remissions and responses of depressive symptoms in this TRD population. Study of predictors of remission may contribute to better selection patients that may benefit from receiving ketamine.

Neuropsychological effects of direct-acting antiviral treatment for Hepatitis C virus subjects: A systematic review.

Direct-acting antivirals (DAAs) have been approved in recent years to treat patients infected by the Hepatitis C virus (HCV). The DAAs treatment is well tolerated and increases sustained virological responses, but there is no consensus about the neuropsychological functioning related to the treatment. This systematic review aims to provide an overview of the recent findings exploring the cognitive effects of DAAs treatment in patients with HCV. After a systematic search on PubMed, Embase, Scopus and LILACS, studies that assessed neuropsychological data related to DAAs treatment were included. We found nine articles, considering the inclusion and exclusion criteria. Three other manuscripts were included after searching for the references listed in the previously mentioned articles. We observed methodological heterogeneity in terms of neuropsychological tests used, cognitive domain explored and the sample characteristic presented between the studies. Studies presented data from HCV subjects monoinfected with or without cirrhosis, advanced liver disease and post-transplant patients; and HCV subjects coinfected with human immunodeficiency virus (HIV). Most results from the 12 studies that explored the effect of DAAs treatment in HCV subjects' neurocognitive functioning demonstrated cognitive improvement following treatment. In general, HCV and HCV/HIV subjects improved processing speed, verbal fluency and verbal/visual episodic memory. The DAAs treatment is effective for neurocognitive functioning in HCV monoinfected and coinfected subjects, with or without advanced liver disease, since neuropsychological scores increased after treatment. Further studies, however, are needed to confirm these findings.

Intravenous arketamine for treatment-resistant depression: open-label pilot study.

We aimed to analyze the efficacy and safety of arketamine, the R(-)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion to 10.4 after one day, a mean difference of 20.3 points [CI 95% 13.6-27.0; p < 0.001]; dissociation was nearly absent. Arketamine might produce fast-onset and sustained antidepressant effects in humans with favorable safety profile, like previously reported with animals; further controlled-trials are needed.

A combined injectable contraceptive improves plasma redox status and does not induce vascular changes in female rats.

This study aimed to investigate the effects of the combined injectable contraceptive (CIC) containing estradiol valerate (EV) and norethisterone enanthate (NET-EN) on aorta function and morphology, as well as on redox status, of female Wistar rats. Female rats (9-10 weeks of age) received intramuscular injections of CIC (0.1 mg EV plus 1 mg NET-EN) or castor oil (control group, CTL) for 8 weeks, once a week. Food intake, body weight and systolic blood pressure were measured during the treatment period. Thoracic aortic segments were prepared for isometric tension recording and morphological analysis. Redox status was evaluated by total oxidant status (TOS) and lipid peroxidation (LP) on plasma and reduced glutathione (GSH) on whole blood. CIC group presented lower food intake and lower total weight gain compared to CTL group. There was no change in systolic blood pressure, vascular response of aorta to phenylephrine and acetylcholine and aorta thickness. Plasma TOS and LP values were reduced in CIC group, although GSH was not altered. It was shown that the long-term treatment with the CIC containing EV plus NET-EN does not induce endothelial dysfunction and histomorphometric changes of vascular wall, as well as improves redox status on female Wistar rats.

An In Vitro Pipeline for Screening and Selection of Citrus-Associated Microbiota with Potential Anti-"Candidatus Liberibacter asiaticus" Properties.

Huanglongbing (HLB) is a destructive citrus disease that is lethal to all commercial citrus plants, making it the most serious citrus disease and one of the most serious plant diseases. Because of the severity of HLB and the paucity of effective control measures, we structured this study to encompass the entirety of the citrus microbiome and the chemistries associated with that microbial community. We describe the spatial niche diversity of bacteria and fungi associated with citrus roots, stems, and leaves using traditional microbial culturing integrated with culture-independent methods. Using the culturable sector of the citrus microbiome, we created a microbial repository using a high-throughput bulk culturing and microbial identification pipeline. We integrated an in vitro agar diffusion inhibition bioassay into our culturing pipeline that queried the repository for antimicrobial activity against Liberibacter crescens, a culturable surrogate for the nonculturable "Candidatus Liberibacter asiaticus" bacterium associated with HLB. We identified microbes with robust inhibitory activity against L. crescens that include the fungi Cladosporium cladosporioides and Epicoccum nigrum and bacterial species of Pantoea, Bacillus, and Curtobacterium Purified bioactive natural products with anti-"Ca. Liberibacter asiaticus" activity were identified from the fungus C. cladosporioides Bioassay-guided fractionation of an organic extract of C. cladosporioides yielded the natural products cladosporols A, C, and D as the active agents against L. crescens This work serves as a foundation for unraveling the complex chemistries associated with the citrus microbiome to begin to understand the functional roles of members of the microbiome, with the long-term goal of developing anti-"Ca Liberibacter asiaticus" bioinoculants that thrive in the citrus holosystem.IMPORTANCE Globally, citrus is threatened by huanglongbing (HLB), and the lack of effective control measures is a major concern of farmers, markets, and consumers. There is compelling evidence that plant health is a function of the activities of the plant's associated microbiome. Using Liberibacter crescens, a culturable surrogate for the unculturable HLB-associated bacterium "Candidatus Liberibacter asiaticus," we tested the hypothesis that members of the citrus microbiome produce potential anti-"Ca Liberibacter asiaticus" natural products with potential anti-"Ca Liberibacter asiaticus" activity. A subset of isolates obtained from the microbiome inhibited L. crescens growth in an agar diffusion inhibition assay. Further fractionation experiments linked the inhibitory activity of the fungus Cladosporium cladosporioides to the fungus-produced natural products cladosporols A, C, and D, demonstrating dose-dependent antagonism to L. crescens.

P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria.

A complete understanding of the mechanisms underlying the acquisition of protective immunity is crucial to improve vaccine strategies to eradicate malaria. However, it is still unclear whether recognition of damage signals influences the immune response to Plasmodium infection. Adenosine triphosphate (ATP) accumulates in infected erythrocytes and is released into the extracellular milieu through ion channels in the erythrocyte membrane or upon erythrocyte rupture. The P2X7 receptor senses extracellular ATP and induces CD4 T cell activation and death. Here we show that P2X7 receptor promotes T helper 1 (Th1) cell differentiation to the detriment of follicular T helper (Tfh) cells during blood-stage Plasmodium chabaudi malaria. The P2X7 receptor was activated in CD4 T cells following the rupture of infected erythrocytes and these cells became highly responsive to ATP during acute infection. Moreover, mice lacking the P2X7 receptor had increased susceptibility to infection, which correlated with impaired Th1 cell differentiation. Accordingly, IL-2 and IFNγ secretion, as well as T-bet expression, critically depended on P2X7 signaling in CD4 T cells. Additionally, P2X7 receptor controlled the splenic Tfh cell population in infected mice by promoting apoptotic-like cell death. Finally, the P2X7 receptor was required to generate a balanced Th1/Tfh cell population with an improved ability to transfer parasite protection to CD4-deficient mice. This study provides a new insight into malaria immunology by showing the importance of P2X7 receptor in controlling the fine-tuning between Th1 and Tfh cell differentiation during P. chabaudi infection and thus in disease outcome.

Efficient Extraction of Carotenoids from Sargassum muticum Using Aqueous Solutions of Tween 20.

The replacement of synthetic compounds by natural products witnesses an increasing demand from the pharmaceutical, cosmetic, food and nutraceutical industries. Included in the set of natural raw materials that are poorly explored are the macroalgae. Despite the detailed characterization and identification of most relevant biomolecules that are present in the main macroalgae species, there remains a lack of efficient and economically viable processes available to meet the needs of the markets. In this work, an efficient and single-step process, based on aqueous solutions of Tween 20, to recover carotenoids from Sargassum muticum, an invasive brown macroalgae species present in the Portuguese coast, is proposed and optimized allowing an extraction yield of 2.78 ± 0.4 mgcarotenoids.gdried mass-1, which is shown to increase the extraction efficiency by 38% when compared with traditional methods.

Technical Quality of Complete Dentures: Influence on Masticatory Efficiency and Quality of Life.

PURPOSE: To evaluate the effect of the technical quality of conventional complete dentures (CD) on masticatory efficiency and quality of life (QoL) of denture wearers during a 1-year follow-up. MATERIALS AND METHODS: A prospective clinical trial with 32 edentulous patients (mean age of 60.2 years) wearing mandibular and maxillary dentures was conducted. All patients were evaluated wearing their preexisting dentures and after 3, 6, and 12 months postinsertion of new dentures. A reproducible method for objective evaluation of the technical quality of CDs was employed. Masticatory efficiency was evaluated by the colorimetric method using beads as artificial testing food. The oral health impact on patient QoL was measured using the OHIP-EDENT (Oral Health Impact Profile in Edentulous Adults) questionnaire. The nonparametric Wilcoxon test was applied to reveal any differences in technical quality between the preexisting and new dentures. The Friedman test was used to detect differences in masticatory efficiency and oral health impact on QoL. Spearman's correlation was applied to reveal correlation between the variables. RESULTS: Comparing preexisting and new dentures, significant improvement was found in technical quality between the dentures (p < 0.001). There was no statistically significant difference in masticatory efficiency. A significant decrease was found in the total OHIP-EDENT scores after denture replacement. A positive correlation was found between technical quality and OHIP in the new denture wearers (p = 0.011). CONCLUSIONS: According to the results of this study, denture quality significantly improved patients' oral health-related QoL; however, insertion of new dentures did not influence masticatory efficiency.

Intralesional uridine-5'-triphosphate (UTP) treatment induced resistance to Leishmania amazonensis infection by boosting Th1 immune responses and reactive oxygen species production.

Leishmania amazonensis is the etiologic agent of cutaneous leishmaniasis, an immune-driven disease causing a range of clinical symptoms. Infections caused by L. amazonensis suppress the activation and function of immune cells, including macrophages, dendritic cells, and CD4+ T cells. In this study, we analyzed the course of infection as well as the leishmanicidal effect of intralesional UTP treatment in L. amazonensis-infected BALB/c mice. We found that UTP treatment reduced the parasitic load in both footpad and lymph node sites of infection. UTP also boosted Th1 immune responses, increasing CD4+ T cell recruitment and production of IFN-γ, IL-1ß, IL-12, and TNF-α. In addition, the role of UTP during innate immune response against L. amazonensis was evaluated using the air pouch model. We observed that UTP augmented neutrophil chemoattraction and activated microbicidal mechanisms, including ROS production. In conclusion, our data suggested an important role for this physiological nucleotide in controlling L. amazonensis infection, and its possible use as a therapeutic agent for shifting immune responses to Th1 and increasing host resistance against L. amazonensis infection.

Can Coloured Fluoride Gel Stain Demineralised Enamel?

PURPOSE: This study evaluated the colour changes of demineralized enamel after treatment with coloured fluoride gel. MATERIALS AND METHODS: Enamel blocks obtained from bovine incisors were submitted to artificial caries induction by pH cycling followed by fluoride gel applications (2% sodium fluoride, pH 6.8) using a colourless gel (control group), pink or blue gels. The enamel optical properties were evaluated by spectrophotometry, using the CIE L*a*b* system at baseline (sound enamel), after artificial caries induction (demineralised enamel) and after each of the five fluoride gel applications (weekly intervals). Changes in enamel optical properties (ΔE) were analysed by two-way ANOVA and Tukey's test (α = 0.05). RESULTS: No significant differences were found among fluoride gels (p = 0.476) regardless of the presence of pigments in the gel. ΔE values were significantly different (p < 0.001) between baseline evaluation and treated enamel (after fluoride gel application). CONCLUSION: This in vitro study demonstrated that colour changes in enamel do not occur during fluoride gel treatment, regardless of the presence or absence of coloured pigments in the gel.

Serologic and Molecular Evidence of Vaccinia Virus Circulation among Small Mammals from Different Biomes, Brazil.

Vaccinia virus (VACV) is a zoonotic agent that causes a disease called bovine vaccinia, which is detected mainly in milking cattle and humans in close contact with these animals. Even though many aspects of VACV infection have been described, much is still unknown about its circulation in the environment and its natural hosts/reservoirs. To investigate the presence of Orthopoxvirus antibodies or VACV DNA, we captured small rodents and marsupials in 3 areas of Minas Gerais state, Brazil, and tested their samples in a laboratory. A total of 336 animals were tested; positivity ranged from 18.1% to 25.5% in the 3 studied regions located in different biomes, including the Atlantic Forest and the Cerrado. Analysis of nucleotide sequences indicated co-circulation of VACV groups I and II. Our findings reinforce the possible role played by rodents and marsupials in VACV maintenance and its transmission chain.

Expression of miR-155 associated with Toll-like receptors 3, 7, and 9 transcription in the olfactory bulbs of cattle naturally infected with BHV5.

Bovine herpesvirus 5 (BHV5) infection of young cattle is frequently associated with fatal neurological disease and, as such, represents an attractive model for studying the pathogenesis of viral-induced meningoencephalitis. Following replication in the nasal mucosa, BHV5 invades the central nervous system (CNS) mainly through the olfactory pathway. The innate immune response triggered by the host face to virus replication through the olfactory route is poorly understood. Recently, an upregulation of conserved pathogen-associated molecular pattern, as Toll-like receptors (TLRs), has been demonstrated in the CNS of BHV5 experimentally infected cows. A new perspective to understand host-pathogen interactions has emerged elucidating microRNAs (miRNAs) network that interact with innate immune response during neurotropic viral infections. In this study, we demonstrated a link between the expression of TLRs 3, 7, and 9 and miR-155 transcription in the olfactory bulbs (OB) of 16 cows suffering from acute BHV5-induced neurological disease. The OBs were analyzed for viral antigens and genome, miR-155 and TLR 3, 7, and 9 expression considering three major regions: olfactory receptor neurons (ORNs), glomerular layer (GL), and mitral cell layer (ML). BHV5 antigens and viral genomes, corresponding to glycol-C gene, were detected in all OBs regions by fluorescent antibody assay (FA) and PCR, respectively. TLR 3, 7, and 9 transcripts were upregulated in ORNs and ML, yet only ORN layers revealed a positive correlation between TLR3 and miR-155 transcription. In ML, miR-155 correlated positively with all TLRs studied. Herein, our results evidence miR-155 transcription in BHV5 infected OB tissue associated to TLRs expression specifically ORNs which may be a new window for further studies.

Bovine herpesviruses induce different cell death forms in neuronal and glial-derived tumor cell cultures.

Oncolytic viruses have the ability to infect tumor cells and leave healthy cells intact. In this study, bovine herpesvirus 1 (BHV1; Los Angeles, Cooper, and SV56/90 strains) and bovine herpesvirus 5 (BHV5; SV507/99 and GU9457818 strains) were used to infect two neuronal tumor cell lineages: neuro2a (mouse neuroblastoma cells) and C6 (rat glial cells). BHV1 and BHV5 strains infected both cell lines and positively correlated with viral antigen detection (p < 0.005). When neuro2a cells were infected by Los Angeles, SV507/99, and GU9457818 strains, 40 % of infected cells were under early apoptosis and necroptosis pathways. Infected C6 cells were >40 % in necroptosis phase when infected by BHV5 (GU9457818 strain). Blocking caspase activation did not interfere with cell death. However, when necroptosis was blocked, 60-80 % of both infected cells with either virus switched to early apoptosis pathway with no interference with virus replication. Moreover, reactive oxygen species production and mitochondrial membrane dysfunction were detected at high levels in both infected cell lines. In spite of apoptosis and necroptosis blockage, tumor necrosis factor alpha (TNFA) and virus transcription were positively correlated for all viral strains studied. Thus, these results contribute to the characterization of BHV1 and BHV5 as potential oncolytic viruses for non-human cells. Nonetheless, the mechanisms underlying their oncolytic activity in human cells are still to be determined.

Waterborne toxoplasmosis investigated and analysed under hydrogeological assessment: new data and perspectives for further research.

We present a set of data on human and chicken Toxoplasma gondii seroprevalence that was investigated and analysed in light of groundwater vulnerability information in an area endemic for waterborne toxoplasmosis in Brazil. Hydrogeological assessment was undertaken to select sites for water collection from wells for T. gondii oocyst testing and for collecting blood from free-range chickens and humans for anti-T. gondii serologic testing. Serologic testing of human specimens was done using conventional commercial tests and a sporozoite-specific embryogenesis-related protein (TgERP), which is able to differentiate whether infection resulted from tissue cysts or oocysts. Water specimens were negative for the presence of viable T. gondii oocysts. However, seroprevalence in free-range chickens was significantly associated with vulnerability of groundwater to surface contamination (p < 0.0001; odds ratio: 4.73, 95% confidence interval: 2.18-10.2). Surprisingly, a high prevalence of antibodies against TgERP was detected in human specimens, suggesting the possibility of a continuous contamination of drinking water with T. gondii oocysts in this endemic setting. These findings and the new proposed approach to investigate and analyse endemic toxoplasmosis in light of groundwater vulnerability information associated with prevalence in humans estimated by oocyst antigens recognition have implications for the potential role of hydrogeological assessment in researching waterborne toxoplasmosis at a global scale.

Rehabilitation of individuals with intestinal ostomy.

This article will discuss an ethnographic study interpreting the rehabilitation experience of 15 individuals with an intestinal ostomy in Brazil, analysed using thematic analysis from the perspective of the sociology of health. The decoded meanings included: 'dealing with treatment and intestinal ostomy', and led to the theme 'the rehabilitation experience of patients with intestinal ostomy due to chronic illness', which addressed normality of life before intestinal illness, defining oneself and life, considering personal, family, social and therapeutic difficulties, and preparing to live with an intestinal ostomy, considering both the private and public spheres. This study will contribute to the specialised care provided in the various contexts of healthcare delivery, especially in relation to the humanisation of care of patients and implementation of appropriate strategies to meet the needs of patients.

Phylogenomic analyses and comparative genomics of Pseudomonas syringae associated with almond (Prunus dulcis) in California.

We sequenced and comprehensively analysed the genomic architecture of 98 fluorescent pseudomonads isolated from different symptomatic and asymptomatic tissues of almond and a few other Prunus spp. Phylogenomic analyses, genome mining, field pathogenicity tests, and in vitro ice nucleation and antibiotic sensitivity tests were integrated to improve knowledge of the biology and management of bacterial blast and bacterial canker of almond. We identified Pseudomonas syringae pv. syringae, P. cerasi, and P. viridiflava as almond canker pathogens. P. syringae pv. syringae caused both canker and foliar (blast) symptoms. In contrast, P. cerasi and P. viridiflava only caused cankers, and P. viridiflava appeared to be a weak pathogen of almond. Isolates belonging to P. syringae pv. syringae were the most frequently isolated among the pathogenic species/pathovars, composing 75% of all pathogenic isolates. P. cerasi and P. viridiflava isolates composed 8.3 and 16.7% of the pathogenic isolates, respectively. Laboratory leaf infiltration bioassays produced results distinct from experiments in the field with both P. cerasi and P. syringae pv. syringae, causing significant necrosis and browning of detached leaves, whereas P. viridiflava conferred moderate effects. Genome mining revealed the absence of key epiphytic fitness-related genes in P. cerasi and P. viridiflava genomic sequences, which could explain the contrasting field and laboratory bioassay results. P. syringae pv. syringae and P. cerasi isolates harboured the ice nucleation protein, which correlated with the ice nucleation phenotype. Results of sensitivity tests to copper and kasugamycin showed a strong linkage to putative resistance genes. Isolates harbouring the ctpV gene showed resistance to copper up to 600 µg/ml. In contrast, isolates without the ctpV gene could not grow on nutrient agar amended with 200 µg/ml copper, suggesting ctpV can be used to phenotype copper resistance. All isolates were sensitive to kasugamycin at the label-recommended rate of 100µg/ml.

Genome Sequence and Assembly of 18 Fusarium Isolates from Florida Citrus under High Huanglongbing Disease Pressure and California Citrus under Low Huanglongbing Disease Pressure.

The genomes of eighteen Fusarium isolates cultured from diseased and healthy citrus trees were sequenced, assembled, and annotated. Isolate species identification was confirmed using single marker (TEF1-alpha) phylogenetic assessment. Studies of the traits and genotypes of plant-associated isolates are important to understanding the fungal contribution to phytobiomes of citrus.

Arketamine for bipolar depression: Open-label, dose-escalation, pilot study.

There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this pilot study, we treated six subjects with bipolar disorder types I and II (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria) who had been in a current depressive episode for at least four weeks. Four subjects were female (66.66%), and the mean age was 45.33 (±12.32). Subjects received adjunct treatment with two arketamine intravenous infusions one week apart-0.5 mg/kg first and then 1 mg/kg. The mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score was 36.66, which decreased to 27.83 24h after the first infusion of 0.5 mg/kg of arketamine (p = 0.036). In respect of the 1 mg/kg dose, the mean MADRS total score before the second infusion was 32.0, which dropped to 17.66 after 24h (p < 0.001). Arketamine appears to have rapid-acting antidepressant properties, consistent with previous animal studies on major depression. All individuals tolerated both doses, exhibiting nearly absent dissociation, and no manic symptoms. To the best of our knowledge, this pilot trial is the first to test the feasibility and safety of the (R)-enantiomer of ketamine (arketamine) for bipolar depression.