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.

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.

Impact of superimposed Clostridium difficile infection in Crohn's or ulcerative colitis flares in the outpatient setting.

PURPOSE: The prospective assessment of Clostridium difficile infection (CDI) impact in inflammatory bowel disease (IBD) flare in outpatient setting has been poorly investigated. We aimed to evaluate the prevalence and the associated factors with CDI in IBD outpatients presenting colitis flares as well as the outcomes following treatment. METHODS: In this prospective cohort study, conducted from October, 2014, to July, 2016, 120 IBD patients (55% presenting colitis flare) and 40 non-IBD controls were assessed for CDI. Multivariate regression analysis was performed to identify predictors of CDI. Outcome analysis was estimated for recurrent CDI, hospitalization, colectomy, and CDI-associated mortality. RESULTS: The number of patients with CDI was significantly higher in IBD patients experiencing flares than in both inactive IBD and non-IBD groups (28.8 vs. 5.6 vs. 0%, respectively; p = 0.001). Females (OR = 1.39, 95% CI, 1.13-17.18), younger age (OR = 0.77, 95% CI, 0.65-0.92), steroid treatment (OR = 7.42, 95% CI, 5.17-40.20), and infliximab therapy (OR = 2.97, 95% CI, 1.99-24.63) were found to be independently associated with CDI. There was a dose-related increase in the risks of CDI on patients which had taken prednisone. Those treated with vancomycin had a satisfactory response to therapy, but 21% presented recurrent CDI and 16% were hospitalized. Neither necessity of colectomy nor mortality was noticed in any patient during the investigation. CONCLUSIONS: In IBD outpatients presenting colitis flares, CDI is highly prevalent. Females, younger age, infliximab, and notably steroid therapy were independently associated with CDI. Most patients with CDI experienced mild-to-moderate disease, and prompt treatment with vancomycin was highly effective, which seems to reduce the serious complication risks.

Compound profiling and 3D-QSAR studies of hydrazone derivatives with activity against intracellular Trypanosoma cruzi.

Chagas disease is a tropical disease caused by the parasite Trypanosoma cruzi, which is endemic in Central and South America. Few treatments are available with effectiveness limited to the early (acute) stage of disease, significant toxicity and widespread drug resistance. In this work we report the outcome of a HTS-ready assay chemical library screen to identify novel, nontoxic, small-molecule inhibitors of T. cruzi. We have selected 50 compounds that possess hydrazone as a common group. The compounds were screened using recombinant T. cruzi (Tulahuen strain) expressing beta-galactosidase. A 3D quantitative structure-activity relationship (QSAR) analysis was performed using descriptors calculated from comparative molecular field analysis (CoMFA). Our findings show that of the fifty selected hydrazones, compounds LpQM-19, 28 and 31 displayed the highest activity against T. cruzi, leading to a selectivity index (SI) of 20-fold. The 3D-QSAR analysis indicates that a particular electrostatic arrangement, where electron-deficient atoms are aligned along the molecule main axis positively correlates with compound biological activity. These results provide new candidate molecules for the development of treatments against Chagas disease.

Lipidomics analysis of follicular fluid by ESI-MS reveals potential biomarkers for ovarian endometriosis.

PURPOSE: The aim of the present study was to analyze the lipid profile of follicular fluid from patients with endometriosis and endometrioma who underwent in vitro fertilization treatment (IVF). METHODS: The control group (n = 10) was composed of women with tubal factor or minimal male factor infertility who had positive pregnancy outcomes after IVF. The endometriosis group consisted of women with endometriosis diagnosed by videolaparoscopy (n = 10), and from the same patients, the endometriomas fluids were collected, which composed the endometrioma group (n = 10). From the follicular fluid and endometriomas, lipids were extracted by the Bligh and Dyer method, and the samples were analyzed by tandem mass spectrometry. RESULTS: We observed phosphatidylglycerol phosphate, phosphatidylcholine, phosphatidylserine, and phosphatidylnositol bisphosphate in the control group. In the endometriosis group, sphingolipids and phosphatidylcholines were more abundant, while in the endometrioma group, sphingolipids and phosphatidylcholines with different m/z from the endometriosis group were found in high abundance. CONCLUSION: This analysis demonstrated that there is a differential representation of these lipids according to their respective groups. In addition, the lipids found are involved in important mechanisms related to endometriosis progress in the ovary. Thus, the metabolomic approach for the study of lipids may be helpful in potential biomarker discovery.

Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro fertilization (IVF) treatment. This study aimed to identify potential lipid biomarkers for women with PCOS and a hyper response to controlled ovarian stimulation. METHODS: Follicular fluid samples were collected from patients who underwent IVF, including normal responder women who became pregnant (control group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS group, n = 7) and women with only hyper response to gonadotropins (HR group, n = 7). A lipidomic analysis was performed by electrospray ionization mass spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry experiment. RESULTS: The lipid profiles indicated particularities related to differences in phosphatidylcholine (PCOS and HR), phosphatidylserine, phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and phosphatidylethanolamine (control and HR). CONCLUSIONS: These findings contribute to the understanding of the molecular mechanisms associated with lipid metabolism in the PCOS-related hyper response, and strongly suggest that these lipids may be useful as biomarkers, leading to the development of more individualized treatment for pregnancy outcome.

Potential of NIR spectroscopy for predicting cellulose nanofibril quality in commercial bleached Kraft pulp of Eucalyptus.

Multivariate models were developed to classify cellulose nanofibril (CNF) fibrillation by a quality index from near infrared (NIR) spectra. Commercial pulps of Eucalyptus spp. were used to produce cellulose nanofibrils by means of a fibrillator mill. After each of the five passes through the mill, samples were collected and analyzed for energy consumption and fiber classification. As a standard, pulps were oxidized with TEMPO reagent followed by a single pass through the mill to compare the resulting quality of CNFs produced by each method. NIR spectra of CNFs were associated with quality indices determined by conventional laboratory analyses that included morphology, turbidity, mechanical properties, X-ray diffraction and quality index measurements. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were applied to the spectral and experimental data. Fibrillator milling to obtain CNFs was efficient and resulted in gel formation following the third pass through the mill. NIR spectroscopy combined with PLS-DA was used successfully to create a model to classify quality of CNFs with 96 % certainty in 3 wt% solutions. These findings suggest that NIR spectroscopy holds promise for estimating CNF quality in suspension, particularly in real-time industrial applications where reliable estimates are crucial.

MicroRNAs as Diagnostic Biomarkers and Predictors of Antidepressant Response in Major Depressive Disorder: A Systematic Review.

Despite the hardships of major depressive disorder (MDD), biomarkers for the diagnosis and pharmacological management of this condition are lacking. MicroRNAs are epigenetic mechanisms that could provide promising MDD biomarkers. Our aim was to summarize the findings and provide validation for the selection and use of specific microRNAs as biomarkers in the diagnosis and treatment of MDD. A systematic review was conducted using the PubMed/Medline, Cochrane, PsycINFO, Embase, and LILACS databases from March 2022 to November 2023, with clusters of terms based on "microRNA" and "antidepressant". Studies involving human subjects, animal models, and cell cultures were included, whereas those that evaluated herbal medicines, non-pharmacological therapies, or epigenetic mechanisms other than miRNA were excluded. The review revealed differences in the expression of various microRNAs when considering the time of assessment (before or after antidepressant treatment) and the population studied. However, due to the heterogeneity of the microRNAs investigated, the limited size of the samples, and the wide variety of antidepressants used, few conclusions could be made. Despite the observed heterogeneity, the following microRNAs were determined to be important factors in MDD and the antidepressant response: mir-1202, mir-135, mir-124, and mir-16. The findings indicate the potential for the use of microRNAs as biomarkers for the diagnosis and treatment of MDD; however, more homogeneous studies are needed.

Gastaut type idiopathic childhood occipital epilepsy.

Gastaut type idiopathic childhood occipital epilepsy is an uncommon epileptic syndrome characterised by frequent seizures, most commonly presenting as elementary visual hallucinations or blindness. Other occipital (non-visual) symptoms may also occur. Interictal EEG typically shows occipital paroxysms, often with fixation-off sensitivity. Ictal EEG is usually characterised by interruption by paroxysms and sudden appearance of low-voltage, occipital, fast rhythm and/or spikes. Despite well described clinical and EEG patterns, to our knowledge, there are very few reports in the literature with video-EEG recording of either seizure semiology or fixation-off phenomena. We present a video-EEG recording of a 12-year-old girl with Gastaut type epilepsy, illustrating the interictal and ictal aspects of this syndrome. Our aim was to demonstrate the clinical and neurophysiological pattern of a typical seizure of Gastaut type epilepsy, as well as the fixation-off phenomena, in order to further clarify the typical presentation of this syndrome. [Published with video sequences].

Vaccination status and long COVID symptoms in patients discharged from hospital.

Effective vaccination against coronavirus mitigates the risk of hospitalisation and mortality; however, it is unclear whether vaccination status influences long COVID symptoms in patients who require hospitalisation. The available evidence is limited to outpatients with mild disease. Here, we evaluated 412 patients (age: 60 ± 16 years, 65% males) consecutively admitted to two Hospitals in Brazil due to confirmed coronavirus disease 2019 (COVID-19). Compared with patients with complete vaccination (n = 185) before infection or hospitalisation, those with no or incomplete vaccination (n = 227) were younger and had a lower frequency of several comorbidities. Data during hospitalisation revealed that the no or incomplete vaccination group required more admissions to the intensive care unit (ICU), used more corticosteroids, and had higher rates of pulmonary embolism or deep venous thrombosis than the complete vaccination group. Ninety days after hospital discharge, patients with no or incomplete vaccination presented a higher frequency of symptoms (≥ 1) than patients with complete vaccination (40 vs. 27%; p = 0.013). After adjusting for confounders, no or incomplete vaccination (odds ratio [OR] 1.819; 95% confidence interval [CI] 1.175-2.815), female sex (OR 2.435; 95% CI 1.575-3.764) and ICU admission during hospitalisation (OR 1.697; 95% CI 1.062-2.712) were independently associated with ≥ 1 symptom 90 days after hospital discharge. In conclusion, even in patients with severe COVID-19, vaccination mitigates the probability of long COVID symptoms.

In-hospital and Post-discharge Status in COVID-19 Patients With Acute Respiratory Failure Supported With Extracorporeal Membrane Oxygenation.

Few data from Latin American centers on clinical outcomes in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome who required extracorporeal membrane oxygenation (ECMO) are published. Moreover, clinical and functional status after hospital discharge remains poorly explored in these patients. We evaluated in-hospital outcomes of severe COVID-19 patients who received ECMO support in two Brazilian hospitals. In one-third of the survivors, post-acute COVID-19 syndrome (PACS), quality of life, anxiety, depression, and return to work were evaluated. Eighty-five patients were included and in-hospital mortality was 47%. Age >65 years (HR: 4.8; 95% confidence interval [CI]: 1.4-16.4), diabetes (HR: 6.0; 95% CI: 1.8-19.6), ECMO support duration (HR: 1.08; 95% CI: 1.05-1.12) and dialysis initiated after ECMO (HR: 3.4; 95% CI: 1.1-10.8) were independently associated with higher in-hospital mortality and mechanical ventilation (MV) duration before ECMO was not (HR: 1.18; 95% CI: 0.71-2.09). PACS-related symptoms were reported by two-thirds and half of patients at 30- and 90-days post-discharge, respectively. The median EQ-5D score was 0.85 (0.70-1.00) and 0.77 (0.66-1.00) at 30 and 90 days. Of the 15 responders, all previously working patients, except one, have returned to work at 90 days. In conclusion, in-hospital mortality in a large Latin American cohort was comparable to the Global extracorporeal life support organization registry.

Post-COVID-19 Cardiopulmonary Symptoms: Predictors and Imaging Features in Patients after Hospital Discharge. / Sintomas Cardiopulmonares Pós-COVID-19: Preditores e Características de Imagem de Pacientes após a Alta Hospitalar.

BACKGROUND: Most of the evidence about the impact of the post-acute COVID-19 Syndrome (PACS) reports individual symptoms without correlations with related imaging. OBJECTIVES: To evaluate cardiopulmonary symptoms, their predictors and related images in COVID-19 patients discharged from hospital. METHODS: Consecutive patients who survived COVID-19 were contacted 90 days after discharge. The Clinic Outcome Team structured a questionnaire evaluating symptoms and clinical status (blinded for hospitalization data). A multivariate analysis was performed to address the course of COVID-19, comorbidities, anxiety, depression, and post-traumatic stress during hospitalization, and cardiac rehabilitation after discharge. The significance level was set at 5%. RESULTS: A total of 480 discharged patients with COVID-19 (age: 59±14 years, 67.5% males) were included; 22.3% required mechanical ventilation. The prevalence of patients with PACS-related cardiopulmonary symptoms (dyspnea, tiredness/fatigue, cough, and chest discomfort) was 16.3%. Several parameters of chest computed tomography and echocardiogram were similar in patients with and without cardiopulmonary symptoms. The multivariate analysis showed that PACS-related cardiopulmonary-symptoms were independently related to female sex (OR 3.023; 95% CI 1.319-6.929), in-hospital deep venous thrombosis (OR 13.689; 95% CI 1.069-175.304), elevated troponin I (OR 1.355; 95% CI 1.048-1.751) and C-reactive protein during hospitalization (OR 1.060; 95% CI 1.023-1.097) and depression (OR 6.110; 95% CI 2.254-16.558). CONCLUSION: PACS-related cardiopulmonary symptoms 90 days post-discharge are common and multifactorial. Beyond thrombotic and markers of inflammation/myocardial injury during hospitalization, female sex and depression were independently associated with cardiopulmonary-related PACS. These results highlighted the need for a multifaceted approach targeting susceptible patients.

FUNDAMENTO: A maioria da evidência sobre o impacto da síndrome COVID pós-aguda (PACS, do inglês, post-acute COVID-19 syndrome) descreve sintomas individuais sem correlacioná-los com exames de imagens. OBJETIVOS: Avaliar sintomas cardiopulmonares, seus preditores e imagens relacionadas em pacientes com COVID-19 após alta hospitalar. MÉTODOS: Pacientes consecutivos, que sobreviveram à COVID-19, foram contatados 90 dias após a alta hospitalar. A equipe de desfechos clínicos (cega quanto aos dados durante a internação) elaborou um questionário estruturado avaliando sintomas e estado clínico. Uma análise multivariada foi realizada abordando a evolução da COVID-19, comorbidades, ansiedade, depressão, e estresse pós-traumático durante a internação, e reabilitação cardíaca após a alta. O nível de significância usado nas análises foi de 5%. RESULTADOS: Foram incluídos 480 pacientes (idade 59±14 anos, 67,5% do sexo masculino) que receberam alta hospitalar por COVID-19; 22,3% necessitaram de ventilação mecânica. A prevalência de pacientes com sintomas cardiopulmonares relacionados à PACS (dispneia, cansaço/fadiga, tosse e desconforto no peito) foi de 16,3%. Vários parâmetros de tomografia computadorizada do tórax e de ecocardiograma foram similares entre os pacientes com e sem sintomas cardiopulmonares. A análise multivariada mostrou que sintomas cardiopulmonares foram relacionados de maneira independente com sexo feminino (OR 3,023; IC95% 1,319-6,929), trombose venosa profunda durante a internação (OR 13,689; IC95% 1,069-175,304), nível elevado de troponina (OR 1,355; IC95% 1,048-1,751) e de proteína C reativa durante a internação (OR 1,060; IC95% 1,023-1,097) e depressão (OR 6,110; IC95% 2,254-16,558). CONCLUSÃO: Os sintomas cardiopulmonares relacionados à PACS 90 dias após a alta hospitalar são comuns e multifatoriais. Além dos marcadores trombóticos, inflamatórios e de lesão miocárdica durante a internação, sexo feminino e depressão foram associados independentemente com sintomas cardiopulmonares relacionados à PACS. Esses resultados destacaram a necessidade de uma abordagem multifacetada direcionada a pacientes susceptíveis.

Ninety-day outcomes in patients diagnosed with COVID-19 in São Paulo, Brazil: a cohort study.

OBJECTIVE: COVID-19 has been associated with a significant burden to those who survive the acute phase. We aimed to describe the quality of life and symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) at 90 days after hospital discharge of COVID-19 patients. METHODS: Patients with COVID-19 admitted to a private hospital in the city of São Paulo, Brazil, between April of 2020 and April of 2021 were interviewed by telephone at 30 and 90 days after discharge to assess the quality of life and symptoms of depression, anxiety, and PTSD. RESULTS: A total of 2,138 patients were included. The mean age was 58.6 ± 15.8 years, and the median length of hospital stay was 9.0 (5.0-15.8) days. Between the two time points, depression increased from 3.1% to 7.2% (p < 0.001), anxiety increased from 3.2% to 6.2% (p < 0.001), and PTSD increased from 2.3% to 5.0% (p < 0.001). At least one physical symptom related to COVID-19 diagnosis persisted in 32% of patients at day 90. CONCLUSIONS: Persistence of physical symptoms was high even at 90 days after discharge. Although the prevalence of symptoms of anxiety, depression, and PTSD was low, these symptoms persisted for three months, with a significant increase between the time points. This finding indicates the need to identify at-risk patients so that they can be given an appropriate referral at discharge.

Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine and esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial.

BACKGROUND: Ketamine and esketamine have both shown significant antidepressant effects in treatment-resistant depression (TRD), and conflicting evidence suggests that induced dissociation by these drugs can be a clinical predictor of esketamine/ketamine's efficacy. METHODS: This study is a secondary analysis from a bi-center, randomized, controlled trial. Participants were randomly assigned 1:1 to receive an IV infusion of esketamine (.25 mg/kg) or racemic ketamine (.50 mg/kg) over 40 minutes. Dissociative symptoms were assessed using the Clinician-Administered Dissociative State Scale (CADSS) 40 minutes following the beginning of the infusion. The variation in depression scores was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), which was administered before the intervention as a baseline measure and 24 hrs, 72 hrs, and 7 days following infusion. RESULTS: Sixty-one patients were included in the analysis. Examining CADSS scores of 15 or below, for every 1-point increment in the CADSS score, there was a mean change of -0.5 (SD = 0.25; p-value 0.04) of predicted MADRS score from baseline to 24 hrs. The results for 72 hrs and 7 days following infusion were not significant. Limitations: This study was not designed to assess the relationship between ketamine or esketamine-induced dissociation and antidepressant effects as the main outcome, therefore confounding variables for this relationship were not controlled. CONCLUSION: We suggest a positive relationship between dissociation intensity, measured by CADSS, and antidepressant effect 24 hours after ketamine and esketamine infusion for a CADSS score of up to 15 points.

Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study.

BACKGROUND: Racemic ketamine is a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), with the latter regarded as the main isomer for antidepressant effects. However, preclinical data and one open-label human trial suggest arketamine might exert a more potent and longer-lasting antidepressant effect with fewer side effects. We aimed to explore the feasibility of a randomized controlled trial of arketamine for treatment-resistant depression (TRD) and to assess its efficacy and safety compared to placebo. METHODS: This is a, randomized, double-blind, crossover, pilot trial (n = 10). All participants received saline and arketamine (0.5 mg/kg) with a one-week interval. Treatment effects were analyzed with a linear mixed effects (LME) model. RESULTS: Our analysis suggested the presence of a carryover effect, so the main efficacy analysis was limited to the first week, which demonstrated a main effect of time (p = 0.038) but not for treatment (p = 0.40) or their interaction (p = 0.95). This indicates that depression improved over time, but without significant difference between arketamine and placebo. Analyzing the two weeks together, findings were the same. Dissociation and other adverse events were minimal. LIMITATIONS: This was a pilot study with a small sample and underpowered. CONCLUSIONS: Arketamine was not superior to placebo for TRD but demonstrated to be extremely safe. Our findings reinforce the importance of continuing studies with this drug, with better powered clinical trials, perhaps considering a parallel design with higher or flexible doses and repeated administrations.

Good practices with injectables: digital technology for nursing education to control infections.

OBJECTIVES: to build, validate, implement, and evaluate an educational strategy for nursing professionals and students aiming at good practices in administrating injectable medications. METHODS: methodological study for the development of an open course, without tutoring, in a virtual learning environment about good practices with injectable medications. RESULTS: ten evaluators validated the educational material that supported the course "Good Practices with Injectables: actions for infection control" regarding objectives, structure, and relevance for the e-book and podcast. The evaluation by the target population (17 individuals) suggests that it is relevant and motivating. However, the forum may be the least attractive tool, and other studies should be conducted to identify its effectiveness as a tool for content retention in open courses. CONCLUSIONS: the course is open and has no mentoring for students and nursing professionals with validated educational material for this purpose may be used for nursing education in formal or informal settings.

Metabolomics of Major Depressive Disorder: A Systematic Review of Clinical Studies.

Although the understanding of the pathophysiology of major depressive disorder (MDD) has advanced greatly, this has not been translated into improved outcomes. To date, no biomarkers have been identified for the diagnosis, prognosis, and therapeutic management of MDD. Thus, we aim to review the biomarkers that are differentially expressed in MDD. A systematic review was conducted in January 2022 in the PubMed/MEDLINE, Scopus, Embase, PsycINFO, and Gale Academic OneFile databases for clinical studies published from January 2001 onward using the following terms: "Depression" OR "Depressive disorder" AND "Metabolomic." Multiple metabolites were found at altered levels in MDD, demonstrating the involvement of cellular signaling metabolites, components of the cell membrane, neurotransmitters, inflammatory and immunological mediators, hormone activators and precursors, and sleep controllers. Kynurenine and acylcarnitine were identified as consistent with depression and response to treatment. The most consistent evidence found was regarding kynurenine and acylcarnitine. Although the data obtained allow us to identify how metabolic pathways are affected in MDD, there is still not enough evidence to propose changes to current diagnostic and therapeutic actions. Some limitations are the heterogeneity of studies on metabolites, methods for detection, analyzed body fluids, and treatments used. The experiments contemplated in the review identified increased or reduced levels of metabolites, but not necessarily increased or reduced the activity of the associated pathways. The information acquired through metabolomic analyses does not specify whether the changes identified in the metabolites are a cause or a consequence of the pathology.

Effects of GRIN2B , GRIA1 , and BDNF Polymorphisms on the Therapeutic Action of Ketamine and Esketamine in Treatment-Resistant Depression Patients: Secondary Analysis From a Randomized Clinical Trial.

OBJECTIVE: This study aimed to evaluate the effect of genetic variants in glutamate ionotropic receptor N-methyl- d -aspartate type subunit 2B ( GRIN2B ), glutamate ionotropic receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type subunit 1 ( GRIA1 ), and brain-derived neurotrophic factor ( BDNF ) genes on therapeutic response, remission, and total Montgomery-Åsberg Depression Rating Scale scores after treatment with ketamine or esketamine in treatment-resistant depression (TRD) patients. METHODS: Participants (N = 60) are from a double-blind, randomized, noninferiority clinical trial comparing single-dose intravenous ketamine (0.5 mg/kg) to esketamine (0.25 mg/kg) for TRD. Montgomery-Åsberg Depression Rating Scale was applied at baseline, 24 hours, 72 hours, and 7 days postinfusion to assess depressive symptoms. Blood samples were collected to evaluate single nucleotide polymorphisms rs1805502 ( GRIN2B ), rs1994862 ( GRIA1 ), and rs6265 ( BDNF ). RESULTS: There was no association between rs1805502, rs1994862, or rs6265 polymorphisms and antidepressant response ( P = 0.909, P = 0.776, and P = 0.482, respectively), remission P = 0.790, P = 0.086, and P = 0.669), or Montgomery-Åsberg Depression Rating Scale scores at each time point ( P = 0.907, P = 0.552, and P = 0.778). CONCLUSIONS: We found no association between the studied single nucleotide polymorphisms (rs6265, rs1805502, and rs1994862) and ketamine's therapeutic action in TRD patients. Further studies with larger samples are needed to clarify the utility of these genes of interest as predictors for antidepressant treatment.

Membrane interactions of the anuran antimicrobial peptide HSP1-NH2: Different aspects of the association to anionic and zwitterionic biomimetic systems.

Studies have suggested that antimicrobial peptides act by different mechanisms, such as micellisation, self-assembly of nanostructures and pore formation on the membrane surface. This work presents an extensive investigation of the membrane interactions of the 14 amino-acid antimicrobial peptide hylaseptin P1-NH2 (HSP1-NH2), derived from the tree-frog Hyla punctata, which has stronger antifungal than antibacterial potential. Biophysical and structural analyses were performed and the correlated results were used to describe in detail the interactions of HSP1-NH2 with zwitterionic and anionic detergent micelles and phospholipid vesicles. HSP1-NH2 presents similar well-defined helical conformations in both zwitterionic and anionic micelles, although NMR spectroscopy revealed important structural differences in the peptide N-terminus. 2H exchange experiments of HSP1-NH2 indicated the insertion of the most N-terminal residues (1-3) in the DPC-d38 micelles. A higher enthalpic contribution was verified for the interaction of the peptide with anionic vesicles in comparison with zwitterionic vesicles. The pore formation ability of HSP1-NH2 (examined by dye release assays) and its effect on the size and surface charge as well as on the lipid acyl chain ordering (evaluated by Fourier-transform infrared spectroscopy) of anionic phospholipid vesicles showed membrane disruption even at low peptide-to-phospholipid ratios, and the effect increases proportionately to the peptide concentration. On the other hand, these biophysical investigations showed that a critical peptide-to-phospholipid ratio around 0.6 is essential for promoting disruption of zwitterionic membranes. In conclusion, this study demonstrates that the binding process of the antimicrobial HSP1-NH2 peptide depends on the membrane composition and peptide concentration.