A Ten-Minute Bioassay to Test Metal Toxicity with the Freshwater Flagellate Euglena agilis.

A chemical analysis of water quality cannot detect some toxicants due to time constraints, high costs, and limited interactions for detection. Bioassays would offer a complementary means to assess pollution levels in water. Euglena is a flagellate green alga and an excellent system for toxicity testing thanks to its ease of culture, rapid growth, and quick response to environmental stresses. Herein, we examined the sensitivity of E. agilis to seven heavy metals by analyzing six end-point parameters: motility, velocity, cell compactness, upward swimming, r-value, and alignment. Notably, the velocity of E. agilis was most sensitive to cadmium (96.28 mg·L-1), copper (6.51 mg·L-1), manganese (103.28 mg·L-1), lead (78.04 mg·L-1), and zinc (101.90 mg·L-1), while r-values were most sensitive to arsenic (12.84 mg·L-1) and mercury (4.26 mg·L-1). In this study, velocity and r-values are presented as useful biomarkers for the assessment of metal toxicity in Euglena. The metals As, Cd, Cu, and Pb were suitable for this test. The advantages of the ecotoxicity test are its rapidity: It takes 10 min to obtain results, as opposed to the typical 3-4 d of exposure time with intensive labor. Moreover, this test can be performed at room temperature under dark conditions.

Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes.

Achieving remission following initial antidepressant therapy in patients with major depressive disorder (MDD) is an important clinical result. Making predictions based on genetic markers holds promise for improving the remission rate. However, genetic variants found in previous genetic studies do not provide robust evidence to aid pharmacogenetic decision-making in clinical settings. Thus, the objective of this study was to perform whole-genome sequencing (WGS) using genomic DNA to identify genetic variants associated with the treatment outcomes of selective serotonin reuptake inhibitors (SSRIs). We performed WGS on 100 patients with MDD who were treated with escitalopram (discovery set: 36 remitted and 64 non-remitted). The findings were applied to an additional 553 patients with MDD who were treated with SSRIs (replication set: 185 remitted and 368 non-remitted). A novel loss-of-function variant (rs3213755) in keratin-associated protein 1-1 (KRTAP1-1) was identified in this study. This rs3213755 variant was significantly associated with remission following antidepressant treatment (p = 0.0184, OR 3.09, 95% confidence interval [CI] 1.22-7.80 in the discovery set; p = 0.00269, OR 1.75, 95% CI 1.22-2.53 in the replication set). Moreover, the expression level of KRTAP1-1 in surgically resected human temporal lobe samples was significantly associated with the rs3213755 genotype. WGS studies on a larger sample size in various ethnic groups are needed to investigate genetic markers useful in the pharmacogenetic prediction of remission following antidepressant treatment.

Safety of epidural steroids: a review.

Spine disease is one of the most common musculoskeletal diseases, especially in an aging society. An epidural steroid injection (ESI) is a highly effective treatment that can be used to bridge the gap between physical therapy and surgery. Recently, it has been increasingly used clinically. The purpose of this article is to review the complications of corticosteroids administered epidurally. Common complications include: hypothalamic-pituitary-adrenal (HPA) axis suppression, adrenal insufficiency, iatrogenic Cushing's syndrome, hyperglycemia, osteoporosis, and immunological or infectious diseases. Other less common complications include psychiatric problems and ocular ailments. However, the incidence of complications related to epidural steroids is not high, and most of them are not serious. The use of nonparticulate steroids is recommended to minimize the complications associated with epidural steroids. The appropriate interval and dosage of ESI are disputed. We recommend that the selection of appropriate ESI protocol should be based on the suppression of HPA axis, which reflects the systemic absorption of the corticosteroid.

Large-Area Nonfullerene Organic Solar Cell Modules Fabricated by a Temperature-Independent Printing Method.

Despite recent breakthroughs in the fabrication of spin-coated small-area devices (≤0.1 cm2) with power conversion efficiencies (PCEs) of more than 17%, printed large-area organic solar cells (OSCs) are significantly less efficient because of the intrinsic differences between the coating dynamics of the two types of OSCs. The PCEs of printed large-area (∼100 cm2) OSCs have typically been decreased compared with those of small-area spin-coated devices. In this work, an efficient low-temperature printing method to fabricate high-efficiency large-area nonfullerene-based OSC modules is successfully demonstrated. A systematic study of the relationship between the concentration of the photoactive solution and the resulting film properties reveals that the large-area modules (85 cm2) produced in this work deliver excellent performance, yielding PCEs of up to 8.18% with a geometric fill factor of 85%. These novel OSC modules are ∼87% as efficient as small-area printed single cells (cell PCE ∼9.43% with 1 cm2).

Coprescription of mood stabilizers in schizophrenia, dosing, and clinical correlates: An international study.

OBJECTIVE: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses). METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates. RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses. CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

Interface Engineering for Fabricating Semitransparent and Flexible Window-Film-Type Organic Solar Cells.

We fabricated window-film-type organic photovoltaics with flexible transparent electrodes (FTEs). By overcoming the poor adhesion between layers, we created ultrathin metal electrodes (bottom FTE) on flexible substrates and transferred conducting polymers onto the photoactive layer (top FTE), providing power conversion efficiencies of 4.9% (7.4%) with average visible transmittances of 38% (18%).

Patterns of long acting injectable antipsychotic use and associated clinical factors in schizophrenia among 15 Asian countries and region.

INTRODUCTION: Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established. METHODS: Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region. RESULTS: Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications. DISCUSSION: These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.

Full recovery of near complete tear of anterior cruciate ligament without surgery: a case report.

INTRODUCTION: The anterior cruciate ligament (ACL) is the region where spraining or tearing is most prevalent when the knee is injured. Complete ACL ruptures have a much less favorable outcome without surgical intervention. Polydeoxyribonucleotide (PDRN) is a relatively safe substance widely used for regenerative therapy. PATIENT CONCERNS: A 43-year-old female patient visited our clinic with Rt. knee pain after slipping, which she rated as 7/10 on a numeric rating scale. DIAGNOSIS: She was diagnosed as having a near complete tear of the ACL at the femoral attachment, partial tear of the lateral collateral ligament. INTERVENTIONS: Ultrasound-guided PDRN injections were carried out 5 times at intervals of about 2 weeks. OUTCOMES: At 3-month follow-up, the patient demonstrated an improvement in knee symptoms (numeric rating scale 0) and ROM without any complications. Even after 2 years and 5 months since the diagnosis, she has been doing her daily life well without any pain. CONCLUSION: This is the first report of successful PDRN injection for near complete tear of ACL and partial tear of lateral collateral ligament without surgery.

Remifentanil Alleviates Propofol-Induced Burst Suppression without Affecting Bispectral Index in Female Patients: A Randomized Controlled Trial.

The bispectral index is affected by various factors, such as noxious stimuli and other drugs, such as muscle relaxants. The burst suppression ratio from bispectral index monitoring is correlated with electroencephalographic burst suppression, which is associated with deep anesthesia, metabolic disorders, and brain injury. We assessed patients undergoing total intravenous anesthesia and examined the effects of remifentanil on the bispectral index, burst suppression ratio, and hemodynamic changes immediately after loss of consciousness with propofol. Seventy American Society of Anesthesiologists physical status class I and II Korean female patients scheduled for general anesthesia were administered propofol with an effect-site concentration of 5 µg/mL, using a target-controlled infusion (TCI). After losing consciousness, patients received either saline or remifentanil at an effect-site concentration of 5 ng/mL for 10 min. During this period, we recorded the bispectral index values, including burst suppression ratio, blood pressure, and heart rate. With remifentanil infusion, burst suppression ratios were lower (p < 0.01) but bispectral values were not different. The burst suppression ratio was significantly different at 6, 7, 8, and 10 min after remifentanil infusion (p < 0.05). In female patients with propofol-induced unconsciousness, remifentanil alleviated the burst suppression ratio without affecting the bispectral value.

Analgesic Effect of Low Dose Nefopam Hydrochloride after Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

Arthroscopic rotator cuff repair causes acute postoperative hyperalgesia. Multimodal analgesia is preferable to opioid-based intravenous patient-controlled analgesia (IV-PCA) due to postoperative nausea and vomiting (PONV). We evaluated the effect of nefopam as a postoperative non-opioid analgesic after shoulder surgeries. A total of 180 adult patients were enrolled for arthroscopic rotator cuff repair. They were randomly assigned to nefopam (N) or control (C) groups and each group was reclassified according to the interscalene block (B) into NB, CB and NX, CX. Nefopam was applied at a constant dose intravenously during recovery. Pain scores were measured with a Visual Analogue Scale (VAS) before (T0), immediately after (T1), 30 min (T2) and 12 h (T3), 24 h (T4) and 48 h (T5) after surgery. There was no significant difference in demographic data. The overall VAS scores did not differ with regard to nefopam use, except for the NB group at T4 in intention to treat (ITT) analysis (p < 0.05). PONV occurred more frequently in the N group than in the C group (p < 0.05). Neither individual nor all risk factors were associated with PONV occurrence (p > 0.10). In conclusion, nefopam alone did not show a definite decrease in postoperative pain. It instead increased PONV regardless of risk factors.

Psychotropic drug-prescribing correlates of disorganized speech in Asians with schizophrenia: The REAP-AP study.

BACKGROUND: Although disorganized speech is seen as one of the nuclear features of schizophrenia, there have been few reports of disorganized speech-associated psychotropic drug-prescribing patterns in large samples of schizophrenia patients. OBJECTIVE: We aimed to examine the prevalence of disorganized speech and its correlates in terms of psychotropic drug prescribing, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. METHOD: A total of 3744 patients with the ICD-10 diagnosis of schizophrenia were enrolled from 71 survey centers in 15 Asian countries/areas. An essential criterion of disorganized speech was that it was "severe enough to impair substantially effective communication" as defined in the DSM-5. A binary logistic model was fitted to identify the psychotropic drug-prescribing correlates of disorganized speech. RESULTS: After adjusting for the potential effects of confounding variables, the binary logistic regression model showed that the presence of disorganized speech was directly associated with adjunctive use of mood stabilizers (P < 0.001) and cumulative diazepam equivalent dose (P < 0.0001), and inversely associated with adjunctive use of anti-Parkinson drugs (P < 0.0001). CONCLUSION: The association between disorganized speech and adjunctive use of mood stabilizers could perhaps be understood in the context of a relationship with impulsiveness/aggressiveness, or in terms of deconstructing the Kraepelinian dualism.

Concurrent antipsychotic use in older adults treated with antidepressants in Asia.

AIM: Depressive disorders are common in old age. Antipsychotics (APs) are often used as an adjunctive treatment with antidepressants (ADs) in this population but its patterns of use in Asia are not known. This study explored the rate of combination of APs and ADs in older adult psychiatric patients in Asia. METHODS: This is a secondary analysis of the database of a multicentre study which recorded participants' basic demographical and clinical data in standardised format in 10 Asian countries and territories. The data were analysed using univariate and multivariate logistic regression analyses. RESULTS: A total of 955 older adult psychiatric in- and outpatients were included in this study. The proportion of concurrent AP and AD use was 32.0%, ranging from 23.3% in Korea to 44.0% in Taiwan. Multivariate logistic regression analysis found that younger age, inpatient status and diagnosis of schizophrenia, anxiety and other mental disorders were significantly related to a higher proportion of concurrent use of APs and ADs. CONCLUSION: Around a third of older adult psychiatric patients had concurrent AP and AD use in the Asian countries/regions surveyed. Considering the uncertain effectiveness and questionable safety of the AP and AD combination in this patient population, such should be cautiously used.

Concurrent benzodiazepine use in older adults treated with antidepressants in Asia.

ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates. METHODS: The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed. RESULTS: The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants. CONCLUSIONS: Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

Interaction effects of oxytocin receptor gene polymorphism and depression on hippocampal volume.

Many studies have revealed that the oxytocin receptor gene (OXTR) is associated with emotional salience and depression among females. Hippocampus is closely associated with the pathophysiology of major depressive disorder (MDD). However, little is known of the interaction effects of OXTR and MDD on hippocampal volume. We sought to investigate the interaction effects of OXTR (rs53576) allelic variants and MDD on hippocampal volumes which also including subfield volumes. The OXTR rs53576 genotype groups were categorized as minor G allele carriers and A allele homozygotes. A total of 47 female patients with depression and 30 healthy females were included in this study. There were significant interactions between OXTR allele type and diagnosis of MDD on the 7 hippocampal subfield volumes, such as left presubiculum, left subiculum, left molecular, right cornus ammonis 1, right granule cells in the molecular layer of the dentate gyrus, right molecular layer, and right subiculum. There were no differences in the hippocampal volumes between MDD vs healthy controls or OXTR A vs G alleles. Our results demonstrate the importance of the interactions between OXTR and MDD on hippocampal volume. Future studies with large sample size should expand those interactions in the whole brain volumes.

Physical comorbidities in older adults receiving antidepressants in Asia.

BACKGROUND: The present study explored the patterns of physical comorbidities and their associated demographic and clinical factors in older psychiatric patients prescribed with antidepressants in Asia. METHODS: Demographic and clinical information of 955 older adults were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Standardized data collection procedure was used to record demographic and clinical data. RESULTS: Proportion of physical comorbidities in this cohort was 44%. Multiple logistic regression analyses showed that older age (OR = 1.7, P < 0.001), higher number of depressive symptoms (OR = 1.09, P = 0.016), being treated in psychiatric hospital (OR = 0.5, P = 0.002), living in high income countries/territories (OR = 2.4, P = 0.002), use of benzodiazepines (OR = 1.4, P = 0.013) and diagnosis of 'other psychiatric disorders' (except mood, anxiety disorders and schizophrenia) (OR = 2.7, P < 0.001) were significantly associated with physical comorbidities. CONCLUSIONS: Physical comorbidities in older patients prescribed with antidepressants were common in Asia. Integrating physical care into the treatment of older psychiatric patients should be urgently considered.

Efficacy of Tianeptine 25-50 mg in Elderly Patients With Recurrent Major Depressive Disorder: An 8-Week Placebo- and Escitalopram-Controlled Study.

OBJECTIVE: The present placebo-controlled study evaluated the efficacy and safety of 8 weeks of treatment with tianeptine 25-50 mg/d in elderly patients suffering from major depressive disorder (MDD) according to DSM-IV-TR. Escitalopram 5-10 mg/d was used as an active comparator. METHODS: Elderly outpatients aged at least 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD were recruited by psychiatrists in 44 clinical centers in 10 countries from October 2013 to January 2016. Patients were randomly assigned to receive tianeptine (n = 105), placebo (n = 107), or escitalopram (n = 99) for 8 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17) total score. RESULTS: Tianeptine improved depressive symptoms, as evaluated by the HDRS17 total score in terms of absolute change from baseline (week 0) to week 8 (placebo-tianeptine difference [SE] of 3.84 [0.85] points, P < .001, using a last-observation-carried-forward approach) and response to treatment (tianeptine: 46.7%; placebo: 34.0%, estimate [SE] = 12.70% [6.70], P = .06). A sensitivity analysis using a mixed model for repeated measures confirmed the main results on HDRS total s​core. The placebo-tianeptine difference (SE) was 0.66 (0.15) for Clinical Global Impressions-Severity of Illness (95% CI, 0.37 to 0.96; P < .001) and 0.57 (0.14) for Clinical Global Impressions- Improvement (95% CI, 0.30 to 0.83; P < .001). Positive results were also obtained with the active control escitalopram (HDRS17 total score placebo-escitalopram difference of 4.09 ± 0.86 points, P < .001), therefore validating the sensitivity of the studied population. Tianeptine was well tolerated, with only minimal differences in tolerability from placebo. CONCLUSIONS: The present study provides robust evidence that an 8-week treatment period with tianeptine 25-50 mg is efficacious and well tolerated in depressed patients aged 65 years or older. TRIAL REGISTRATION: EudraCT identifier: 2012-005612-26​.

Differential effect of COMT gene methylation on the prefrontal connectivity in subjects with depression versus healthy subjects.

Expression of the catechol-O-methyl transferase (COMT) gene mainly determines prefrontal dopaminergic availability. Deficient prefrontal dopaminergic activity leads to loss of interest, energy, and motivation, which are core symptoms of depression. Given the role of stress-environmental interactions in major depressive disorder (MDD), we investigated the impact of COMT gene methylation status on prefrontal connectivity. We measured COMT gene methylation and polymorphisms (Val158Met) at the rs4468 locus in peripheral blood samples of healthy controls (n = 90) and patients with MDD (n = 90). We used diffusion tensor imaging to calculate the fractional anisotropy (FA) and radial diffusivity (RD) of the white matter tracts related to prefrontal cortex. Finally, we examined the effects of COMT gene methylation on the white matter connectivity in patients with MDD. The FA and RD values in the prefrontal white matter tracts of patients with MDD were positively and negatively associated with COMT gene methylation, respectively. In the control group, on the other hand, the association between white matter connectivity and COMT gene methylation showed opposite pattern to those of MDD. COMT gene methylation has a substantial effect on the prefrontal connectivity in patients with MDD. Moreover, COMT gene methylation and prefrontal connectivity showed opposite relationships in patients and controls. Thus, stress-related alterations in dopaminergic neurotransmission have a differential effect on white matter connectivity according to the microenvironment in the brain.

The effects of 5-HTTLPR and BDNF Val66Met polymorphisms on neurostructural changes in major depressive disorder.

The serotonin-transporter-linked polymorphic region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have been implicated in the pathophysiology of major depressive disorder (MDD). We aimed to investigate the effects of genetic variants of the 5-HTTLPR and BDNF Val66Met polymorphisms and their interactions with MDD on cortical volume and white matter integrity. Ninety-five patients with MDD and 65 healthy participants aged 20-65 years were recruited. The subjects were genotyped for the 5-HTTLPR and BDNF Val66Met polymorphisms and scanned with T1-weighted and diffusion tensor imaging. The gray matter volumes of 24 gyri in the prefrontal and anterior cingulate cortices and the fractional anisotropy values of nine white matter tracts in both hemispheres were determined. In the pooled sample of subjects from both groups, 5-HTTLPR L-allele carriers had significantly decreased cortical volume in the right anterior midcingulate gyrus compared to S-allele homozygotes. A significant effect of the interaction of the BDNF Val66Met polymorphism and MDD on the fractional anisotropy values of the right uncinate fasciculus was observed. Our results suggested that these genetic polymorphisms play important roles in the neurostructural changes of emotion-processing regions in subjects with MDD.