Thalamocortical functional connectivity and rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression.

Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.

Chiral anomaly and Weyl orbit in three-dimensional Dirac semimetal Cd3As2grown on Si.

Preparing Cd3As2, which is a three-dimensional (3D) Dirac semimetal in certain crystal orientation, on Si is highly desirable as such a sample may well be fully compatible with existing Si CMOS technology. However, there is a dearth of such a study regarding Cd3As2films grown on Si showing the chiral anomaly. Here,for the first time, we report the novel preparation and fabrication technique of a Cd3As2(112) film on a Si (111) substrate with a ZnTe (111) buffer layer which explicitly shows the chiral anomaly with a nontrivial Berry's phase ofπ. Despite the Hall carrier density (n3D≈9.42×1017cm-3) of our Cd3As2film, which is almost beyond the limit for the portents of a 3D Dirac semimetal to emerge, we observe large linear magnetoresistance in a perpendicular magnetic field and negative magnetoresistance in a parallel magnetic field. These results clearly demonstrate the chiral magnetic effect and 3D Dirac semimetallic behavior in our silicon-based Cd3As2film. Our tailoring growth of Cd3As2on a conventional substrate such as Si keeps the sample quality, while also achieving a low carrier concentration.

Clinical characteristics and immune profiles of patients with immune-mediated alopecia associated with COVID-19 vaccinations.

BACKGROUND: The clinical characteristics and pathomechanism for immune-mediated alopecia following COVID-19 vaccinations are not clearly characterized. OBJECTIVE: We investigated the causality and immune mechanism of COVID-19 vaccines-related alopecia areata (AA). STUDY DESIGN: 27 new-onset of AA patients after COVID-19 vaccinations and 106 vaccines-tolerant individuals were enrolled from multiple medical centers for analysis. RESULTS: The antinuclear antibody, total IgE, granulysin, and PARC/CCL18 as well as peripheral eosinophil count were significantly elevated in the patients with COVID-19 vaccines-related AA compared with those in the tolerant individuals (P = 2.03 × 10-5-0.039). In vitro lymphocyte activation test revealed that granulysin, granzyme B, and IFN-γ released from the T cells of COVID-19 vaccines-related AA patients could be significantly increased by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P = 0.002-0.04). CONCLUSIONS: Spike protein and excipients of COVID-19 vaccines could trigger T cell-mediated cytotoxicity, which contributes to the pathogenesis of immune-mediated alopecia associated with COVID-19 vaccines.

Inhibitory effect of host ocular microenvironmental factors on chlorhexidine digluconate activity.

Acanthamoeba spp. are free-living protozoan that cause a serious human eye disease called Acanthamoeba keratitis (AK). Several new and effective medical therapy for AK patients remains highly debated and therefore, CHG is still considered one of the first lines of treatment for AK patients. We hypothesized that ocular microenvironmental factors are responsible for Acanthamoeba drug resistance and clinical AK treatment failure. To investigate the influence of the ocular surface on CHG treatment, we tested the effect of several ocular elements on the anti-amoeba activity of CHG. The suspected inhibitory elements, including mucin, albumin, human and amoeba cell lysates, live and heat-killed bacteria, and cornea, were added to the amoebicidal activity platform, where amoeba was incubated with CHG at varying concentrations. Mucin showed a significant inhibitory effect on CHG activity against Acanthamoeba castellanii In contrast, albumin did not affect CHG treatment. Furthermore, human and amoeba cell lysates as well as live and heat-killed bacterial suspensions also significantly inhibited CHG activity. Additionally, we found that pig corneas also reduced CHG activity. In contrast, dry eye drops and their major component, propylene glycol, which is commonly used as eyewash material, did not have an impact on CHG activity. Our results demonstrate the effect of ocular microenvironmental factors on CHG activity and suggest that these factors may play a role in the development of amoeba resistance to CHG and treatment failure.

Homeostasis of cellular amino acids in Acanthamoeba castellanii exposed to different media under amoeba-bacteria coculture conditions.

BACKGROUND: Acanthamoeba castellanii is a free-living protist that feeds on diverse bacteria. A. castellanii has frequently been utilized in studies on microbial interactions. Grazing bacteria also exhibit diverse effects on the physiological characteristics of amoebae, such as their growth, encystation, and cytotoxicity. Since the composition of amoebae amino acids is closely related to cellular activities, it can indicate the overall responses of A. castellanii to various stimuli. METHOD: A. castellanii was exposed to different culture conditions in low-nutrient medium with heat-killed DH5α to clarify their effects. A targeted metabolomic technique was utilized to evaluate the concentration of cellular amino acids. The amino acid composition and pathways were analyzed by two web-based tools: MetaboAnalyst and Pathview. Then, long-term exposure to A. castellanii was investigated through in silico and in vitro methods to elucidate the homeostasis of amino acids and the growth of A. castellanii. RESULTS: Under short-term exposure, all kinds of amino acids were enriched in all exposed groups. In contrast to the presence of heat-killed bacteria, the medium exhibited obvious effects on the amino acid composition of A. castellanii. After long-term exposure, the amino acid composition was more similar to that of the control group. A. castellanii may achieve amino acid homeostasis through pathways related to alanine, aspartate, citrulline, and serine. DISCUSSION: Under short-term exposure, compared to the presence of bacteria, the type of medium exerted a more powerful effect on the amino acid composition of the amoeba. Previous studies focused on the interaction of the amoeba and bacteria with effective secretion systems and effectors. This may have caused the effects of low-nutrient environments to be overlooked. CONCLUSION: When A. castellanii was stimulated in the coculture system through various methods, such as the presence of bacteria and a low-nutrient environment, it accumulated intracellular amino acids within a short period. However, different stimulations correspond to different amino acid compositions. After long-term exposure, A. castellanii achieved an amino acid equilibrium by downregulating the biosynthesis of several amino acids.

Association of Neurofilament Light Chain With the Antidepressant Effects of Low-Dose Ketamine Infusion Among Patients With Treatment-Resistant Depression.

BACKGROUND: The role of neurofilament light chain (NFL) in treatment-resistant depression (TRD) is unclear. Whether baseline NFL concentrations are associated with the antidepressant effects of low-dose ketamine infusion has not been determined. METHODS: The NFL concentrations of 71 patients with TRD and 17 healthy controls were assessed. Patients with TRD were randomly administered a single infusion of 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were assessed before infusion and sequentially at postinfusion timepoints (after 240 minutes and after 2-7 and 14 days) using the Hamilton Depression Rating Scale (HDRS). RESULTS: After adjustment for age, sex, and body mass index, patients with TRD were more likely to have higher concentrations of NFL than healthy controls (P < .001). A generalized estimating equation model with adjustments for infusion group, age, sex, body mass index, and baseline HDRS scores showed that baseline NFL concentrations were positively associated with subsequent HDRS scores following low-dose ketamine infusion (P = .038). DISCUSSION: Higher concentrations of NFL were observed among patients with TRD compared with healthy controls. Baseline NFL concentrations may predict the antidepressant effects of low-dose ketamine infusion.

A Randomized, Double-Blind, Midazolam-Controlled Trial of Low-Dose Ketamine Infusion in Patients With Treatment-Resistant Depression and Prominent Suicidal Ideation.

BACKGROUND: The benefits of low-dose ketamine for patients with treatment-resistant depression (TRD) and prominent suicidal ideation require further investigation. The effects of treatment refractoriness, the duration of the current depressive episode, and the number of prior antidepressant failures on ketamine efficacy also require clarification. METHODS: We recruited 84 outpatients with TRD and prominent suicidal ideation-defined as a score ≥4 on item 10 of the Montgomery-Åsberg Depression Rating Scale (MADRS)-and randomized them into 2 groups to receive 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. We assessed depressive and suicidal symptoms prior to infusion; 240 minutes post infusion; and 2, 3, 5, 7, and 14 days post infusion. RESULTS: According to the MADRS scores, the antidepressant effect (P = .035) was significantly noted in the ketamine group up to 14 days than in the midazolam group. However, the antisuicidal effect of ketamine, as measured by the Columbia-Suicide Severity Rating Scale Ideation Severity Subscale (P = .040) and MADRS item 10 (P = .023), persisted only 5 days post infusion. Furthermore, the antidepressant and antisuicidal effects of ketamine infusion were noted particularly in patients whose current depressive episode lasted <24 months or whose number of failed antidepressants was ≤4. CONCLUSIONS: Low-dose ketamine infusion is a safe, tolerable, and effective treatment for patients with TRD and prominent suicidal ideation. Our study highlights the importance of timing; specifically, ketamine is more likely to achieve therapeutic response when the current depressive episode lasted <24 months and the number of failed antidepressants is ≤4.

Underestimating the Risk of an Inconclusive Result in Exercise Treadmill Tests for Patients With Suspected Ischemic Heart Disease.

BACKGROUND: The exercise stress test is a widely used noninvasive test for diagnosing ischemic heart disease. Patients with a "positive" result have a higher risk than those with a "negative" result. However, the outcomes of patients with an "inconclusive" result remain uncertain.Methods and Results: We retrospectively collected the data of patients who underwent an ECG-based treadmill stress test between August 2009 and March 2020. Propensity score matching (PSM) was performed to adjust for confounders. Clinical outcomes were compared in terms of all-cause death and cardiovascular (CV) death. Subgroup analysis evaluated treatment interactions, including medication and examinations. In total, 25,475 patients were recruited, and after exclusion and PSM, 4,847 (1,621 with a positive result, 1,606 with a negative result, and 1,621 with an inconclusive result) remained. Compared with the negative group, the inconclusive group, but not the positive group, had a significantly worse outcome in terms of all-cause death (hazard ratio [HR]: 1.834, 95% confidence interval [CI]: 1.34-2.511 and HR: 1.327, 95% CI: 0.949-1.857, respectively); however, CV death was not significantly different in the inconclusive and positive groups (HR: 1.728, 95% CI: 0.413-7.232 and HR: 2.067, 95% CI: 0.517-8.264, respectively). CONCLUSIONS: Clinicians must not underestimate the potential for worse outcomes in patients with an inconclusive stress test result.

Antidepressant effects of prolonged intermittent theta-burst stimulation monotherapy at the bilateral dorsomedial prefrontal cortex for medication and standard transcranial magnetic stimulation-resistant major depression: a three arm, randomized, double blind, sham-controlled pilot study.

The dorsomedial prefrontal cortex (DMPFC) plays a pivotal role in depression and anxiosomatic symptom modulation. However, DMPFC stimulation using a double-cone coil has demonstrated inconsistent results for antidepressant efficacy. No study thus far has investigated the antidepressant and anti-anxiosomatic effects of prolonged intermittent theta-burst stimulation (piTBS) bilaterally over DMPFC. Furthermore, head-to-head comparisons of antidepressant effects between standard iTBS and piTBS warrant investigation. This double-blind, randomized, sham-controlled trial recruited 34 patients with highly treatment-resistant depression (TRD) unresponsive to antidepressants and standard repetitive transcranial magnetic stimulation (rTMS)/piTBS. These patients were randomly assigned to one of three monotherapy groups (standard iTBS, piTBS, or sham), with treatment administered bilaterally over the DMPFC twice per day for 3 weeks. The primary outcome was the overall changes of 17-item Hamilton Depression Rating Scale (HDRS-17) over 3-weeks intervention. The changes in Depression and Somatic Symptoms Scale (DSSS) as the secondary outcome and the anxiosomatic cluster symptoms as rated by HDRS-17 as the post-hoc outcome were measured. Multivariable generalized estimating equation analysis was performed. Although no differences in overall HDRS-17 changes between three groups were found, the antidepressant efficacy based on DSSS was higher in piTBS than in iTBS and sham at week 3 (group effect,p = 0.003, post-hoc: piTBS > iTBS, p = 0.002; piTBS > sham, p = 0.038). In post-hoc analyses, piTBS had more alleviation in anxiosomatic symptoms than iTBS (group effect, p = 0.002; post-hoc, p = 0.001). This first randomized sham-controlled study directly compared piTBS and iTBS targeting the DMPFC using a figure-of-8 coil and found piTBS may fail to demonstrate a significant antidepressant effect on overall depressive symptoms, but piTBS seems superior in alleviating anxiosomatic symptoms, even in depressed patients with high treatment resistance. This Trial registration (Registration number: NCT04037592). URL: https://clinicaltrials.gov/ct2/show/NCT04037592 .

Effects of melancholic features on positive and negative suicidal ideation in patients with treatment-resistant depression and strong suicidal ideation receiving low-dose ketamine infusion.

The role of melancholic features on the antisuicidal effect of 0.5 mg/kg ketamine infusion has remained unclear in patients with treatment-resistant depression (TRD) and strong suicidal ideation (SI). Whether ketamine diminishes suicidal ideation in patients with TRD-SI was also unknown. We enrolled 84 patients with TRD-SI, including 27 with melancholic features and 57 without, and then randomly administered a single infusion of 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. The clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) item 10, Columbia Suicide Severity Rating Scale-Ideation Severity Subscale (CSSRS-ISS), and self-reported Positive and Negative Suicide Ideation Inventory (PANSI) were used to assess suicidal symptoms from baseline to day 7. Generalized estimating equation models showed that only patients without melancholic features (MADRS item 10: infusion group effect, p = 0.017; CSSRS-ISS: infusion group × time effect, p = 0.008; PANSI-negative suicidal ideation: infusion group effect, p = 0.028) benefited from the antisuicidal effect of low-dose ketamine. The PANSI-positive ideation scores were higher in the ketamine group than in the midazolam group (p = 0.038) for patients with melancholic features. Additional studies are necessary to clarify the neuromechanisms underlying the ketamine-related positive effect against SI and antisuicidal effects among patients with TRD-SI. Additional studies are necessary to clarify the neuromechanisms underlying the ketamine-related positive effect against SI and antisuicidal effects among patients with TRD-SI.

Comparative prevalence of oral bacteria and protozoa in patients with periodontitis in Taiwan.

OBJECTIVES: Periodontitis is an inflammatory disease caused by bacteria present in the dental biofilm. However, the presence of two oral protozoans, Entamoeba gingivalis and Trichomonas tenax, in patients with the periodontal disease remains largely unknown in Taiwan. Therefore, we investigated the prevalence of oral microbial infections between the sites with mild gingivitis and chronic periodontitis in patients. MATERIALS AND METHODS: We collected 60 dental biofilm samples from sites with mild gingivitis (probing depth <5 mm) and chronic periodontitis (probing depth ≥5 mm) from 30 patients at the National Cheng Kung University Hospital. The samples were analyzed via polymerase chain reaction and gel electrophoresis. RESULTS: Among oral protozoans, E. gingivalis and T. tenax were detected in 44 (74.07%) and 14 (23.33%) of all samples, respectively. Among oral bacteria, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia were detected in 50 (83.33%), 47 (78.33%), and 48 (80.0%) samples, respectively. CONCLUSIONS: This study, which is the first to analyze E. gingivalis and T. tenax presence among patients with periodontitis in Taiwan, revealed an association between periodontitis and oral microbes.

Impact of the COVID-19 pandemic on inflammatory bowel disease care in Taiwan: A multicenter study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a great impact on healthcare system and patients. This study aimed to evaluate the effect of the COVID-19 pandemic on the perceptions of patients with inflammatory bowel disease (IBD). METHODS: This prospective multicenter study was conducted between July 2021 and December 2021. Patients with IBD answered a structured questionnaire, and their degree of anxiety was assessed using a visual analogue scale (VAS) before and after reading educational materials. RESULTS: A total of 225 (47.67%) patients with Crohn's disease, 244 (51.69%) with ulcerative colitis and 3 (0.64%) with indeterminate colitis were enrolled. Common concerns were adverse events from vaccination (20.34%), and higher risks of developing severe COVID-19 (19.28%) and COVID-19 infection (16.31%) than the general population. Medications deemed by the patients to increase the risk of COVID-19 were immunomodulators (16.10%), anti-tumor necrosis factor-α antagonists (9.96%), and corticosteroids (9.32%). Thirty-five (7.42%) patients self-discontinued IBD medication, of whom 12 (34.28%) had worse symptoms. Older age (>50 years) (OR 1.10, 95% CI 1.01-1.19, p = 0.03), IBD-related complications (OR 1.16, 95% CI 1.04-1.28, p = 0.01), education status below senior high school (OR 1.22, 95% CI 1.08-1.37, p = 0.001), and residing in north-central Taiwan (OR 1.21, 95% CI 1.10-1.34, p < 0.001) were associated with more anxiety. None of the enrolled patients contracted COVID-19. The anxiety VAS score (mean ± SD) improved after reading the educational materials (3.84 ± 2.33 vs. 2.81 ± 1.96, p < 0.001). CONCLUSION: The medical behavior of IBD patients was influenced by the COVID-19 pandemic, and their anxiety could be mitigated after education.

Intestinal Ultrasound in Inflammatory Bowel Disease: A Novel and Increasingly Important Tool.

New and efficacious medical therapies have become available that have greatly enhanced clinicians' ability to manage inflammatory bowel diseases (IBDs). IBD activity should be assessed regularly in scheduled examinations as the part of a treat-to-target strategy for IBD care. The gold-standard approach to investigating IBD is colonoscopy, but this is an invasive procedure. Intestinal ultrasound (IUS) has played a crucial role in recent years regarding the assessment of IBD activity because it is noninvasive, safe, reproducible, and inexpensive. IUS findings could inform changes in therapeutic interventions for IBDs; this would necessitate fewer endoscopies and enable faster decision-making processes. Furthermore, patients are accepting and tolerant of IUS examinations. This review outlines the current evidence and gives indication regarding the use of IUS in the management of IBDs.

Cancer risk in patients with bipolar disorder and unaffected siblings of such patients: A nationwide population-based study.

Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than in the general population. However, the overall cancer risk in the unaffected siblings of such patients remains unknown. From the National Health Insurance Research Database of Taiwan, 25 356 patients with bipolar disorder, 25 356 age-matched unaffected siblings of patients with bipolar disorder and 101 422 age-matched controls without severe mental disorders between 1996 and 2010 were enrolled in our study. Patients who developed cancer between the time of enrollment and the end of 2011 were identified. Cancers were divided into three subgroups based on the related layer of embryonic development: ectodermal, mesodermal and endodermal cancers. Patients with bipolar disorder (odds ratio [OR] = 1.22, 95% confidence interval [CI]: [1.06, 1.40]) and unaffected siblings of such patients (OR = 1.17, 95% CI [1.02, 1.34]) had greater risk of developing malignant cancer than did controls. Furthermore, only those aged <50 years, for both patients with bipolar disorder (OR = 1.90, 95% CI [1.38, 2.61]) and unaffected siblings (OR = 1.65, 95% CI [1.19, 2.28]), were more likely to develop the ectodermal cancer, especially breast cancer, than the control group. The associations of bipolar disorder and susceptibility to bipolar disorder with increased cancer risk in the younger population may imply a genetic overlap in neurodevelopment and malignancy pathogenesis. Our findings may encourage clinicians to monitor cancer risk factors and warning signs closely in patients with bipolar disorder and unaffected siblings of such patients.

Localized Surface Plasmon Resonance-Based Colorimetric Assay Featuring Thiol-Capped Au Nanoparticles Combined with a Mobile Application for On-Site Parathion Organophosphate Pesticide Detection.

In this study, we employed a dual strategy for parathion organophosphate pesticide (parathion) detection; first, we used a localized surface plasmon resonance (LSPR)-based colorimetric sensor featuring thiol-capped Au NPs, namely cysteine (Cys)@Au NPs, 11-mercaptoundecanoic acid (11-MUA)@Au NPs, and glutathione (GSH)@Au NPs, via acetylcholinesterase (ACHE) and acetylthiocholine (ATCH) enzyme-mediated hydrolysis reactions; second, we developed a color analysis toxicity-sensing app (Toxin APP). Positively charged thiocholine (TCH) molecules, which were continuously generated via hydrolysis, subsequently conjugated with thiol-capped Au NPs, causing Au NP aggregation through electrostatic attractions. The degree of aggregation of the thiol-capped Au NPs was influenced by parathion concentrations in the range 0 to 108 ppt, because parathion acted as an ACHE inhibitor by controlling the amount of TCH generated. Based on the values of LSPR absorbance ratio, the limits of detection (LODs) of three types thiol-capped Au NPs were determined to be 100 ppt using ultraviolet-visible spectroscopy measurements. However, the aggregation efficiency of GSH@Au NPs was lower than that of the others regarding gradual changes in their color and LSPR absorbance band. Furthermore, we designed Toxin APP for color analysis which consists of three modules: processing, database collection, and communication. Toxin APP could on-site and precisely detect the color changes of GSH@Au NPs at parathion concentrations in the ranges of 100 ppt to 1, 10, and 100 ppm and could distinguish between OP and non-OP pesticides (e.g., fipronil) in tap water samples with high sensitivity and selectivity. Moreover, the concentration of residual parathion in real samples (tomato and strawberry) was quantified based on the color changes of GSH@Au NPs detected using Toxin APP. Therefore, the combination of an LSPR-based colorimetric assay and Toxin APP can be a reliable method for the facile and rapid detection of parathion in food and water samples.

Identifying common and distinct subcortical volumetric abnormalities in 3 major psychiatric disorders: a single-site analysis of 640 participants.

BACKGROUND: Subcortical volumetric abnormalities in schizophrenia, bipolar disorder and major depressive disorder (MDD) have been consistently found on a single-diagnosis basis in previous studies. However, whether such volumetric abnormalities are specific to a particular disorder or shared by other disorders remains unclear. METHODS: We analyzed the structural MRIs of 160 patients with schizophrenia, 160 patients with bipolar disorder, 160 patients with MDD and 160 healthy controls. We calculated the volumes of the thalamus, hippocampus, amygdala, accumbens, putamen, caudate, pallidum and lateral ventricles using FreeSurfer 7.0 and compared them among the groups using general linear models. RESULTS: We found a significant group effect on the volumes of the thalamus, hippocampus, accumbens and pallidum. Further post hoc analysis revealed that thalamic volumes in patients with schizophrenia, bipolar disorder and MDD were significantly reduced compared to those in healthy controls, but did not differ from one another. Patients with schizophrenia and bipolar disorder also shared a significant reduction in hippocampal volumes. Among the 3 clinical groups, patients with schizophrenia showed significantly lower hippocampal volumes and higher pallidal volumes than patients with bipolar disorder and MDD. LIMITATIONS: Differences in psychotropic use and duration of illness among the patient groups may limit the interpretation of our findings. CONCLUSION: Our findings indicate that decreased thalamic volume is a common feature of schizophrenia, bipolar disorder and MDD. Smaller hippocampal and larger pallidal volumes differentiate schizophrenia from bipolar disorder and MDD and may provide clues to the biological basis for the Kraepelinian distinction between these illnesses.

Low-dose ketamine infusion in treatment-resistant double depression: Revisiting the adjunctive ketamine study of Taiwanese patients with treatment-resistant depression.

BACKGROUND: Whether a single low-dose ketamine infusion may have rapid antidepressant and antisuicidal effects in patients with treatment-resistant double depression remains unclear. METHODS: This study enrolled 35 patients with treatment-resistant double depression, 12 of whom received 0.5 mg/kg ketamine, 11 received 0.2 mg/kg ketamine, and 12 received normal saline as a placebo. The patients were assessed using the 17-item Hamilton Rating Scale for Depression (HDRS) prior to the initiation of infusions, at 40 and 240 min post-infusion, and sequentially on Days 2-7 and on Day 14 after ketamine or placebo infusions. RESULTS: A single 0.5 mg/kg ketamine infusion had rapid antidepressant (p = 0.031, measured by the HDRS) and antisuicidal (p = 0.033, measured by the HDRS item 3 scores) effects in patients with treatment-resistant double depression. However, 0.2 mg/kg ketamine was insufficient to exert rapid antidepressant and antisuicidal effects in this patient population with severe and chronic illness. DISCUSSION: In this patient population, the commonly used dose of 0.5 mg/kg was sufficient. Additional studies are required to investigate whether repeated infusions of low-dose ketamine may also maintain antidepressant and antisuicidal effects in patients with treatment-resistant double depression.

Baseline Working Memory Predicted Response to Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression.

INTRODUCTION: Pretreatment neurocognitive function may predict the treatment response to low-dose ketamine infusion in patients with treatment-resistant depression (TRD). However, the association between working memory function at baseline and the antidepressant efficacy of ketamine infusion remains unclear. METHODS: A total of 71 patients with TRD were randomized to one of three treatment groups: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HDRS) at baseline and after treatment. Cognitive function was evaluated using working memory and go-no-go tasks at baseline. RESULTS: A generalized linear model with adjustments for demographic characteristics, treatment groups, and total HDRS scores at baseline revealed only a significant effect of working memory function (correct responses and omissions) on the changes in depressive symptoms measured by HDRS at baseline (F=12.862, p<0.05). Correlation analysis further showed a negative relationship (r=0.519, p=0.027) between pretreatment working memory function and changes in HDRS scores in the 0.5 mg/kg ketamine group. DISCUSSION: An inverse relationship between pretreatment working memory function and treatment response to ketamine infusion may confirm that low-dose ketamine infusion is beneficial and should be reserved for patients with TRD.

Potential role of Acanthamoeba Rab7.

Acanthamoeba castellanii is a free-living protozoan that causes several severe human parasitic diseases such as Acanthamoeba keratitis and granulomatous encephalitis. A. castellanii feeds on bacteria, yeasts, and other organic particles as food sources, but the mechanisms of digestion in acanthamoebal cells are unclear. Rab GTPases participate in endosomal delivery in eukaryotes after phagocytosis. This study aimed to determine the potential functions of A. castellanii Rab7 (AcRab7), which is involved in phagocytosis, and the relationship between AcRab7 and further cellular physiological phenomena. In this study, the inhibitor CID1067700 (CID) was used to specifically inhibit the binding of nucleotides to confirm the potential functions of AcRab7. Cellular proliferation and ATP assays were also used to detect underlying cellular physiological functions after blocking the phagocytosis pathway. We found that AcRab7 expression increased as the co-culture time with Escherichia coli increased. Immunofluorescence staining showed that AcRab7 colocalized with lysosomes in its GTP-activating form. In addition, AcRab7 inhibition resulted in a reduction in cell proliferation and ATP levels. Our results suggest that AcRab7 participates in endosomal delivery and dominates energy production and cell growth.

Treatment response to low-dose ketamine infusion for treatment-resistant depression: A gene-based genome-wide association study.

BACKGROUNDS: Evidence suggested the crucial roles of brain-derived neurotrophic factor (BDNF) and glutamate system functioning in the antidepressant mechanisms of low-dose ketamine infusion in treatment-resistant depression (TRD). METHODS: 65 patients with TRD were genotyped for 684,616 single nucleotide polymorphisms (SNPs). Twelve ketamine-related genes were selected for the gene-based genome-wide association study on the antidepressant effect of ketamine infusion and the resulting serum ketamine and norketamine levels. RESULTS: Specific SNPs and whole genes involved in BDNF-TrkB signaling (i.e., rs2049048 in BDNF and rs10217777 in NTRK2) and the glutamatergic and GABAergic systems (i.e., rs16966731 in GRIN2A) were associated with the rapid (within 240 min) and persistent (up to 2 weeks) antidepressant effect of low-dose ketamine infusion and with serum ketamine and norketamine levels. DISCUSSION: Our findings confirmed the predictive roles of BDNF-TrkB signaling and glutamatergic and GABAergic systems in the underlying mechanisms of low-dose ketamine infusion for TRD treatment.