No studies have examined the relationship between endogenous polyunsaturated fatty acids (PUFAs) levels and treatment response to PUFAs. We conducted a 12-week, double-blind, placebo-controlled trial ...comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.2 g) and placebo on cognitive function (continuous performance test) in n = 92 youth (age 6-18-years-old) with Attention Deficit Hyperactivity Disorder (ADHD). Blood erythrocytes PUFAs were measured before and after treatment, to examine the effects of baseline endogenous EPA levels on treatment response and the effects of EPA treatment on PUFAs levels. Secondary measures included other ADHD symptoms, emotional symptoms, and levels of plasma high-sensitivity c-reactive protein (hs-CRP) and brain-derived neurotrophic factor (BDNF). Overall, EPA group improved more than placebo group on focused attention (variability, Effect size (ES) = 0.38, p = 0.041); moreover, within youth with the lowest baseline endogenous EPA levels, EPA group improved more than placebo group in another measure of focused attention (hit reaction time, HRT, ES = 0.89, p = 0.015) and in vigilance (HRT interstimulus interval changes, HRTISIC, ES = 0.83, p = 0.036). Interestingly, EPA group improved less than placebo group in impulsivity (commission errors), both overall and in youth with the highest baseline EPA levels, who also showed less improvement in other ADHD and emotional symptoms. EPA increased blood erythrocytes EPA by 1.6-fold but not DHA levels, and did not affect hs-CRP and BDNF plasma levels. In conclusion, EPA treatment improves cognitive symptoms in ADHD youth, especially if they have a low baseline endogenous EPA level, while youth with high EPA levels may be negatively affected by this treatment.
Background Interferon (IFN)-α therapy for chronic hepatitis C virus infection is frequently associated with depression. The routine prophylaxis with antidepressants might expose patients to adverse ...effects, hence, the need for alternative preventive interventions. Omega-3 polyunsaturated fatty acids are safe and effective essential nutritional compounds used for the treatment of depression, putatively through an anti-inflammatory action. In addition, lower erythrocyte levels of omega-3 polyunsaturated fatty acids have been associated with an increased risk of IFN-induced depression. Methods We conducted a 2-week, double-blind, placebo-controlled trial comparing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and placebo for the prevention of IFN-α-induced depression. A total of 162 patients consented to participate and were randomized to the study. All of the patients completed the 2-week trial; 152 participants were followed throughout the 24 weeks of IFN-α treatment and were included in the analysis. Results Compared with placebo, the incident rates of IFN-α-induced depression were significantly lower in EPA-treated but not in DHA-treated patients (10% and 28%, respectively, versus 30% for placebo, p = .037). Both EPA and DHA significantly delayed the onset of IFN-induced depression (week of onset: 12.0 and 11.7, respectively, versus 5.3 for placebo, p = .002). EPA and DHA were both well tolerated in this population. EPA treatment increased both EPA and DHA erythrocyte levels, but DHA only increased DHA erythrocyte levels. Conclusions EPA is effective in the prevention of depression in hepatitis C virus patients received IFN-α therapy. Our study confirms the notion that anti-inflammatory strategies are effective antidepressants in the context of depression associated with inflammation.
The side effects of cisplatin (CDDP), notably nephrotoxicity, greatly limited its use in clinical chemotherapy. HuangQi Injections (HI), a commonly used preparation of the well-known Chinese herbal ...medicine Astragali radix, appeared to be promising treatment for nephrotoxicity without compromising the anti-tumor activity of CDDP. In this study, the urinary metabolomics approach using liquid chromatography time of flight mass spectrometry (LC-TOF/MS) was developed to assess the toxicity-attenuation effects and corresponding mechanisms of HI on CDDP-exposed rats. As a result, successive administration of HI significantly recovered the decline of body weight and downregulated the abnormal increase of serum creatinine and urea. HI partly restored the CDDP-induced alteration of metabolic profiling back into normal condition. Totally 43 toxicity-attenuation potential biomarkers were screened and tentatively identified, which were involved in important metabolic pathways such as amino acid metabolism, TCA cycle, fatty acid metabolism, vitamin B6 metabolism and purine metabolism. The results clearly revealed that HI could alleviate CDDP-induced nephrotoxicity and improve the disturbed metabolic balance induced by repeated CDDP exposure. The present study provided reliable evidence for the protective effect of HI on CDDP-induced toxicity with the multi-target pharmacological characteristics.
Background
Three‐dimensional (3D) printing has become an available technology to fabricate customized tissue engineering scaffolds with delicate architecture. This exploratory study aimed to evaluate ...the potential of a 3D‐printed hydroxyapatite‐based scaffold as a biomaterial for obtaining guided bone regeneration (GBR) in vivo.
Methods
Scaffolds composed of 90% hydroxyapatite and 10% poly(lactic‐co‐glycolic acid) were printed using a microextrusion process to fit 4 mm diameter and 0.5 mm thick through‐and‐through osseous defects on the mandibular ramus of rats, with unfilled defects serving as controls. Specimens were analyzed for regeneration‐associated gene expression on day 7, and micro‐computed tomography (micro‐CT) and histology assessments were carried out on day 28.
Results
The scaffolds were 3.56 ± 0.43 mm (x‐axis) and 4.02 ± 0.44 mm (y‐axis) in diameter and 0.542 ± 0.035 mm thick (z‐axis), with a mean pore size of 0.420 ± 0.028 × 0.328 ± 0.005 mm2. Most scaffolds fit the defects well. Type I collagen, VEGF, and Cbfa1 were upregulated in the scaffold‐treated defects by day 7. By day 28, de novo osteogenesis and scaffold–tissue integration were evident in the scaffold‐treated defects, and entire mineralized tissue, as well as newly formed bone, was significantly promoted, as seen in the micro‐CT and histologic analyses.
Conclusion
The 3D‐printed hydroxyapatite‐based scaffold showed acceptable dimensional stability and demonstrated favorable osteoregenerative capability that fulfilled the need for GBR.
Cinnamomum plants (Lauraceae) are a woody species native to South and Southeast Asia forests, and are widely used as food flavors and traditional medicines. This study aims to evaluate the chemical ...constituents of Cinnamomum osmophloeum ct. linalool leaf oil, and its antidepressant and motor coordination activities and the other behavioral evaluations in a rodent animal model. The major component of leaf oil is linalool, confirmed by GC-MS analysis. Leaf oil would not induce the extra body weight gain compared to the control mice at the examined doses after 6 weeks of oral administration. The present results provide the first evidence for motor coordination and antidepressant effects present in leaf oil. According to hypnotic, locomotor behavioral, and motor coordination evaluations, leaf oil would not cause side effects, including weight gain, drowsiness and a diminishment in the motor functions, at the examined doses. In summary, these results revealed C. osmophloeum ct. linalool leaf essential oil is of high potential as a therapeutic supplement for minor/medium depressive syndromes.
•Patients with CVDs with comorbid MDD often comorbid somatic and fatigue symptoms.•N-3 PUFAs reduced fatigue symptoms in patients with CVDs comorbid MDD.•N-3 PUFAs reduced somatic symptoms in younger ...patients with CVDs comorbid MDD.•Changes of EPA and n-3 PUFAs correlate negatively with changes of somatic symptoms.•Changes of BDNF correlate negatively with changes of somatic symptoms.
Cardiovascular diseases (CVDs) and major depressive disorder (MDD) are the two most disabling diseases. Patients with CVDs comorbid depression had somatic and fatigue symptoms and were associated with chronic inflammation and omega-3 polyunsaturated fatty acid (n-3 PUFA) deficits. However, there have been limited studies on the effects of n-3 PUFAs on somatic and fatigue symptoms in patients with CVDs comorbid MDD.
Forty patients with CVDs comorbid MDD (58% males, mean age of 60 ± 9 years) were enrolled and randomised to receive either n-3 PUFAs (2 g of eicosapentaenoic acid EPA and 1 g of docosahexaenoic acidDHA per day) or placebo in a 12-week double-blind clinical trial. We assessed the somatic symptoms with Neurotoxicity Rating Scale (NRS) and fatigue symptoms with Fatigue Scale at baseline, weeks 1, 2, 4, 8 and 12, as well as blood levels of Brain-Derived Neurotrophic Factor (BDNF), inflammatory biomarkers and PUFAs, at the baseline and week 12.
The n-3 PUFAs group had a greater reduction in Fatigue scores than the placebo group at Week 4 (p =.042), while there were no differences in the changes of NRS scores. N-3 PUFAs group also had a greater increase in EPA (p =.001) and a greater decrease in total n-6 PUFAs (p =.030). Moreover, in the subgroup analyses in the younger age group (age < 55), the n-3 PUFAs group had a greater reduction on NRS total scores at Week 12 (p =.012) and NRS Somatic scores at Week 2 (p =.010), Week 8 (p =.027), Week 12 (p =.012) than the placebo group. In addition, the pre- and post-treatment changes of EPA and total n-3 PUFAs levels were negatively associated with the changes of NRS scores at Weeks 2, 4, and 8 (all p <.05), and the changes of BDNF levels were negatively associated with NRS scores at Weeks 8 and 12 (both p <.05) in the younger age group. In the older age group (age ≥ 55), there were a lesser reduction on NRS scores at Weeks 1, 2 and 4 (all p <.05), but a greater reduction on Fatigue score at Week 4 (p =.026), compared to the placebo group. There was no significant correlation between the changes of blood BDNF, inflammation, PUFAs and NRS and Fatigue scores in general and in the older age group.
Overall, n-3 PUFAs improved the fatigue symptoms in patients with CVDs comorbid MDD and the general somatic symptoms in specific subpopulation of younger age patients, and perhaps via the interplay between BDNF and EPA. Our findings provide promising rationales for future studies to investigate the treatment effects of omega-3 fatty acids on fatigue and somatic symptoms of chronic mental and medical diseases.
Peptidols were prepared through the reductive cleavage of benzotriazole intermediates obtained from the on‐bead activation of 3,4‐diaminobenzoyl linkers. Remarkably, this method used commercially ...available amino acid residues and resins without further modification. Pure peptidols were collected with only filtration in 49%–87% yield. Only the derivatives with aspartic acid as the first C‐terminal residue required sophisticated chromatography purification. Esters and carboxylic acids were identified as side products and were suppressed by additional reduction or reduction in DMF. Remarkably, the reduction of peptides with the first aspartic acid residue at the C‐terminal afforded a C‐terminal lactone, which could be reduced by deprotection at 0 °C. For the synthesis of branched peptidols, the bulky wedge structures of the branched peptides resulted in low total yields, which were improved to 23%–28% by using peripheral Boc groups and SPPS on the Tental gel resin. In addition, this method gave two peptaibols, SPF‐5506‐A4 and Ac‐Gramicidin A, in 11% and 46% yields, respectively.
•Cardiovascular diseases (CVDs) commonly comorbid with depression.•Omega-3 fatty acids (n-3 PUFAs) are compared with placebo in CVDs with depression.•N-3 PUFAs did not improve total HAMD or BDI ...scores in CVDs with depression.•N-3 PUFAs did not have an effect on CVDs markers as secondary outcome.•N-3 PUFAs improved Core depression symptoms in the severe depression group.
Cardiovascular diseases (CVDs) and major depressive disorder (MDD) will be the two most disabling diseases by 2030. Patients with CVDs comorbid depression had lower levels of total omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), and a higher omega-6 to omega-3 ratio. However, there have been limited studies on the effects n-3 PUFAs on MDD in patients with CVDs.
We have enrolled a total of 59 patients (64% males, mean age of 61.5 ± 9.0 years and mean education of 10.2 ± 4.2 years) with CVDs comorbid MDD. They were randomized into either receiving n-3 PUFAs (2 g per day of eicosapentaenoic acid (EPA) and 1 g of DHA) or placebo for 12 weeks. We assessed depression symptom severity with Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI), as well as blood fatty acid levels, electrocardiogram and blood biochemistry, at the baseline and at the endpoint.
There were no differences between the n-3 PUFAs and placebo group in the changes of HAMD and BDI total scores, while PUFAs group had a greater reduction in HAMD Cognition subscale scores than the placebo group at week 8 (p < 0.05). Moreover, subgroup analyses found that the n-3 group had a greater reduction of HAMD Core subscale scores than the placebo group at the end of week 12 (p < 0.05) for the very severe DEP group (HAMD ≥ 23).
Overall, n-3 PUFAs did not show a beneficial effect on depressive symptoms when compared with placebo. However, when stratified with depression severity, n-3 PUFAs supplementation improved core depression symptoms in the very severe MDD group. N-3 PUFAs supplementation may provide a treatment option for a subpopulation of patients with CVDs comorbid MDD.
This study conducted a psychometric examination into the application of positive behavior support (PBS) principles, focusing on how its trajectory differs between Taiwan and the United States. ...Eighteen items from the Beliefs about Behavior Survey were adapted to gauge educators' perception of implementing PBS strategies within different cultural contexts. The sample comprised 643 educators, split between northern Taiwan (N = 267) and a mid‐mountain region in the United States (N = 376). Results from the confirmatory factor analysis suggest that the previously identified four‐factor model determined using a US sample presents a satisfactory fit with the Taiwanese data set. Furthermore, reliability estimates vouch for the internal consistency of the model. Interestingly, it was observed that general education teachers reported the least supportive beliefs across all four factors, relative to their colleagues. In a direct comparison with the US sample, the Taiwanese respondents scored significantly lower on two out of the four PBS belief factors. This trend could be attributed to a relative scarcity of exposure to, and training in, PBS principles in Taiwan, particularly beyond tertiary remedial services. The revised survey questionnaire presents a useful tool for informing the design of professional development initiatives and system‐wide changes in Taiwanese schools. The study concludes with a discussion on the impact of differing cultural contexts and the potential directions for future research.
Practitioner points
Taiwanese school educators showed lower supportive beliefs than the US counterparts on positive behavior support principles probably due to their overall lack of exposure and training.
General education teachers in Taiwan held the lowest level of supportive beliefs about positive behavior support principles compared with administrators, school counselors, and special education teachers.
The translated belief survey can be used to identify educational philosophies and discipline practices among Taiwanese school educators for preparing professional development.
•Systemic review and meta-analysis assessing the efficacy of tocilizumab for treatment of severe COVID-19.•All-cause mortality was similar between tocilizumab and control groups (16.3% vs. 24.1%; ...RR = 0.62).•Risk of ICU admission was similar between tocilizumab and control groups (35.0% vs. 15.8%; RR = 1.51).•Requirement for mechanical ventilation was similar between tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82).•There is no conclusive evidence that tocilizumab provides any additional benefit to patients with severe COVID-19.
This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31–1.22; I2 = 68%. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33–6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14–4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.
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