Genotype-genotype interactions of the OXTR gene polymorphisms are associated with self-reported daytime dysfunction, sleep latency and personal distress.

The oxytocin receptors located in the corticotropin-releasing factor neurons of the paraventricular nucleus are stimulated by oxytocin. Oxytocin functions as the regulator of the corticotropin-releasing factor system and in turn promotes sleep quality. The objective of this study was to examine the main and genotype-genotype interactive effects of the oxytocin receptor gene (OXTR) polymorphisms on sleep quality. A total of 324 participants were randomly recruited from a university in Beijing, China. Sleep quality was measured with the Pittsburgh Sleep Quality Index. The OXTR single-nucleotide polymorphisms (rs2254298, rs2268498, rs13316193, rs2268490 and rs2268491) were genotyped. The results showed that gender and age were associated with various empathy traits (all p < 0.001). The Pittsburgh Sleep Quality Index was positively correlated with the Personal Distress subscale of empathy (p < 0.001). Both rs2254298 and rs2268491 interacted with rs13316193 to influence daytime dysfunction and Personal Distress (all p < 0.05), indicating that in individuals with rs13316193 CC/CT genotype, those with rs2254298 AA/AG or rs2268491 TT/TC genotypes displayed higher daytime dysfunction and Personal Distress scores than those with rs2254298 GG or rs2268491 CC genotypes. Conversely, among the individuals with rs2254298 GG or rs2268491 CC genotypes, the rs13316193 C allele carriers had lower daytime dysfunction and Personal Distress scores than rs13316193 TT homozygotes. There was also a significant interaction between rs2268490 and rs2268498 on the sleep latency dimension of the Pittsburgh Sleep Quality Index. Our findings reveal for the first time the genotype-genotype interactions of the OXTR gene on sleep quality, which may open new research avenues for studying psychopathology involving sleep problems.

Association of high BMI with subclinical hypothyroidism in young, first-episode and drug-naïve patients with major depressive disorder: a large-scale cross-sectional study.

Thyroid dysfunction is known to be associated with obesity, but the reliability of this relationship is easily affected by drug treatment, age, and subclinical hypothyroidism (SCH) with no apparent symptoms. Our research aims to compare obese and overweight BMI ranges with SCH and without SCH in a large sample of young, first-episode and drug-naïve (FEDN) patients with major depressive disorder (MDD), which has received little systemic investigation. A total of 1289 FEDN MDD young outpatients were recruited for this study. Serum thyroid function and lipid level parameters were measured; HAMD and PANSS scales were used to assess patients' depression and positive symptoms. A self-administered questionnaire collected other clinical and demographic data. The prevalence of SCH in FEDN MDD young patients was 58.26%. Compared to patients without SCH, the patients with SCH had a more prolonged illness duration, higher BMI levels, increased prevalence of overweight and obesity, higher HAMD score and PANSS-positive symptom scores, higher levels of TG, TC, LDL-C, and lower levels of HDL-C. Further logistic regression indicated that overweight BMI, obese BMI, illness duration, HAMD score, HDL-C, and TC were significantly associated with SCH. Our results indicate that obesity and overweight may be associated with SCH in young, FEDN MDD patients. The importance of regular thyroid function assessment in young FEDN MDD patients with high BMI should be taken into account.

Current curricular trends after the COVID-19 pandemic: A national survey of psychiatry residency programs.

OBJECTIVES: During the COVID-19 pandemic, many psychiatry residencies (academic, community, and hybrid programs) have adopted different learning modalities to preserve a high quality of educational training. There is minimal data on specific program adaptations, related change perspectives, and program type stratification. This study sought to examine trends in curriculum changes in accredited psychiatry residency programs in the United States. METHODS: Program directors of accredited general psychiatry programs in the United States were surveyed to assess both general program details and changes in educational content, delivery, and perspectives with regard to program curricula. RESULTS: A total of 63 program directors out of 264 eligible programs completed the questionnaire (23.9%). There was a significant shift to integrate virtual learning post-pandemic (98.5%) compared to pre-pandemic (3%). However, there was no association between these modality changes and program type (p = 0.13). Furthermore, changes were noted with respect to didactic content (60%), decreased rotation sites (38%), and increased telemedicine exposure (84%) with no change of wellness days (67%) or protected time (97%). Again, the above changes had no association with program type. Use of virtual educational platforms was described as positive (59.7%) with 9 programs noting a future transition to a hybrid learning model for didactics and grand rounds. CONCLUSIONS: The findings suggest that pandemic-related curriculum adaptations occurred in all different types of psychiatry residencies and suggest a national trend to continue virtual educational platforms with regard to psychiatry didactics. However, future investigation of effectiveness of virtual learning programs in psychiatry residencies is warranted.

Gender differences in empathy and clinical symptoms in chronic schizophrenia patients: a large sample study based on a Chinese Han population.

BACKGROUND: Empathy is social cognition and reduced empathy in schizophrenia (SCZ) has been noted; however, whether there are gender differences in empathy remains unclear. Therefore, the purpose of this study was to explore this issue by examining a large sample of the population with SCZ. METHODS: We recruited 987 SCZ patients (M/F = 638/349). The empathy was assessed by The Interpersonal Reactivity Index (IRI). The Positive and Negative Syndrome Scale (PANSS) was adopted to assess their clinical psychiatric symptoms and their ability to recognise the facial emotions of others was assessed by the Pictures Of Facial Affect (POFA). RESULTS: Female SCZ patients had higher IRI total score than male patients. In male patients, Pearson correlation analysis showed that empathy was negatively correlated with PANSS total score and negative symptom subscale scores, but positively correlated with anger identification. In female patients, IRI total score was negatively correlated with PANSS total score as well as its positive and negative symptom subscale scores (all p < 0.05). CONCLUSION: There are gender differences in the empathy of SCZ patients, with female patients having greater empathy and a correlation with their clinical symptoms. This gender difference may provide potential clinical value for the treatment of SCZ.KEY POINTSFemale SCZ were more likely to empathise than males;Female patients had more severe clinical symptoms than males;There were gender differences in the association between certain specific clinical presentations and empathy.In future studies, it may be useful to investigate gender differences in schizophrenia empathy for the diagnosis and treatment of the disorder.

Suicide attempt rate and the risk factors in young, first-episode and drug-naïve Chinese Han patients with major depressive disorder.

BACKGROUND: In recent years, the rates of suicide among young people have been increasing, and major depressive disorder (MDD) is regarded to be its main cause. Many factors such as thyroid dysfunction and metabolic abnormalities are thought to mediate this process, but the conclusions are inconsistent. This study investigated the rate of suicide attempts and associated risk factors among young, first-episode and drug-naïve Chinese Han patients with MDD. METHODS: A total of 917 patients with MDD (aged 18 ~ 35 years) were recruited. Demographic and clinical data were collected and thyroid function, fasting blood glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), positive symptom subscale of Positive and Negative Syndrome Scale (PANSS) and clinical global impression of severity scale (CGI-S) were adopted to assess depression, anxiety, psychotic symptoms and disease severity respectively. RESULTS: The rate of suicide attempts was 19.5% in young MDD patients. There were significant differences in age (p = 0.003), education level (p = 0.001), age of onset (p = 0.004) and disease duration (p = 0.001) between patients with and without suicide attempts. Compared with patients without suicide attempts, patients with suicide attempts had significantly higher scores on the HAMD-17, HAMA, PANSS positive symptom subscale and CGI-S (all p < 0.001). Patients with suicide attempts had significantly higher levels of TSH (p < 0.001), TgAb (p = 0.004), TPOAb (p < 0.001), TG (p = 0.016), TC (p < 0.001), LDL (p < 0.001), and fasting glucose (p < 0.001), but significantly lower levels of HDL (p < 0.001). Logistic regression analysis showed that marital status (OR = 0.515, 95%CI: 0.280-0.950, p = 0.515), disease duration (OR = 1.100, 95%CI: 1.013-1.194, p = 0.024), HAMA score (OR = 1.313, 95%CI: 1.205-1.430, p < 0.001), CGI-S score (OR = 1.875, 95%CI: 1.339-2.624, p < 0.001), levels of FT3(OR = 0.717, 95%CI: 0.536-0.959, p = 0.025), TPOAb (OR = 1.004, 95%CI: 1.002-1.006, p < 0.001), TC (OR = 1.330, 95%CI: 1.011-1.750, p = 0.042) and LDL (OR = 0.736, 95%CI: 0.558-0.971, p = 0.030) were all independently associated with suicide attempts in young MDD patients. CONCLUSIONS: In China, the rate of suicide attempts in young patients with MDD is quite high and thyroid dysfunction and metabolic abnormalities may be implicated in its pathogenesis.

Peripheral Interleukin-18 is negatively correlated with abnormal brain activity in patients with depression: a resting-state fMRI study.

BACKGROUND: Interleukin-18 (IL-18) may participate in the development of major depressive disorder, but the specific mechanism remains unclear. This study aimed to explore whether IL-18 correlates with areas of the brain associated with depression. METHODS: Using a case-control design, 68 subjects (34 patients and 34 healthy controls) underwent clinical assessment, blood sampling, and resting-state functional Magnetic Resonance Imaging (fMRI). The total Hamilton depression-17 (HAMD-17) score was used to assess depression severity. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-18 levels. Rest-state fMRI was conducted to explore spontaneous brain activity. RESULTS: The level of IL-18 was higher in patients with depression in comparison with healthy controls. IL-18 was negatively correlated with degree centrality of the left posterior cingulate gyrus in the depression patient group, but no correlation was found in the healthy control group. CONCLUSION: This study suggests the involvement of IL-18 in the pathophysiological mechanism for depression and interference with brain activity.

Gender differences in prevalence and clinical correlates of anxiety symptoms in first-episode and drug-naïve patients with major depressive disorder.

AIM: Gender differences in major depressive disorder (MDD) are commonly reported; however, gender differences in first-episode and drug-naïve (FEDN) patients with major depressive disorder remain unclear. This study aimed to examine potential gender differences in the prevalence and clinical correlates of comorbid anxiety in FEDN patients with MDD. METHODS: A cross-sectional study was conducted with1718 FEDN patients with MDD. Patients' demographic and clinical data were collected and analyzed using standardized clinical evaluation forms. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depression, anxiety and psychotic symptoms, respectively. RESULTS: There were no gender-based differences in the comorbidity rates of MDD and anxiety disorders (male: 10.2% vs. female:12.7%, P = 0.123). The prevalence of MDD with severe anxiety symptoms in male patients was similar to that of female patients (80.8%vs. 80.1%, P = 0.749). Male MDD patients were younger, had earlier age of onset, and were less likely to be married. In both the male and female groups, HAMD scores, HAMA scores, suicide attempts, and psychotic symptoms in patients with severe anxiety symptoms were higher than those patients without severe anxiety symptoms (all p ≤ 0.001). Furthermore, binary logistic regression analysis showed that psychotic symptoms and suicide attempts significantly predicted severe anxiety symptoms in both male and female patients with MDD, while body mass index(BMI)significantly predicted severe anxiety symptoms in MDD females only. CONCLUSION: Our study showed that there were no gender differences in the prevalence of comorbid anxiety in FEDN patients with MDD. Suicide attempts and psychiatric symptoms were associated with severe anxiety symptoms in both men and women with MDD, whereas BMI was only correlated with severe anxiety symptoms in women.

Image of Electroconvulsive Therapy in YouTube Videos.

OBJECTIVES: Image of electroconvulsive therapy (ECT) in TV shows and movies have been studied before. However, there is no study about image of ECT on YouTube as one of the most commonly used social media platforms for disseminating health information. Our study aims to study the image of ECT in YouTube videos. METHODS: Key word "Electroconvulsive therapy and ECT" were used to search on Youtube.com and only videos over 50,000 view counts and in English were selected. Above videos were reviewed by an ECT physician and were classified into neutral, negative, and positive groups based on the image of ECT. RESULTS: There were 41 YouTube videos selected based on the criteria as stated above, among which 14 were unrelated with ECT treatment, 8 were neutral, 9 were positive, and 10 were reflecting negative image about ECT. There was no significant difference among view counts of the positive, negative and neutral videos (χ = 2.746, P = 0.253). Furthermore, the most viewed 3 videos showed negative image of ECT. Additionally, only 6 videos showed the modified ECT and one showed both modified and nonmodified ECT. CONCLUSIONS: This is the first study conducted on image of ECT in YouTube videos. We found the stigma against ECT may persist in digital video platforms, such as YouTube.

Interaction of BDNF with cytokines in chronic schizophrenia.

Brain-derived neurotrophic factor (BDNF) interacts with cytokines. Although both BDNF and cytokines occur at abnormal levels in schizophrenia patients, their interactions have not yet been examined. We therefore compared serum BDNF, TNF-α, interleukin (IL)-2, IL-6, and IL-8 levels in 92 chronically medicated schizophrenia patients and 60 healthy controls. We correlated these serum levels within these subject groups with each other and with clinical symptoms assessed according to the Positive and Negative Syndrome Scale (PANSS). Compared to the control group, the schizophrenia patients had significantly lower BDNF and TNF-α levels, and higher IL-2, IL-6, and IL-8 levels. The patients also showed a significant positive correlation between BDNF and both IL-2 and IL-8 levels, and low BDNF and TNF-α levels together were associated with poor performance on the PANSS cognitive factor. Thus, an interaction between cytokines and neurotrophic factors may be implicated in the pathophysiology of chronic schizophrenia. In particular, the cytokine TNF-α may interact with BNDF causing cognitive impairment.

Hospital length of stay in individuals with schizophrenia with and without cocaine-positive urine drug screens at hospital admission.

Despite the high prevalence of cocaine use disorder (CUD) in individuals with schizophrenia, current understanding of the effect of cocaine on psychiatric hospital length of stay (LOS) in individuals with schizophrenia is limited. We therefore retrospectively examined the medical records of 5106 hospital admissions due to exacerbation of schizophrenia. Linear regression and t-test were used to compare LOS between individuals with schizophrenia with cocaine-positive urine drug test results and those with negative test results. Individuals with schizophrenia who were also positive for cocaine had shorter LOS from both unadjusted (geometric mean LOS, 8.07 ± 1.92 vs. 11.83 ± 1.83 days; p < 0.001) and adjusted (ß = 0.69; confidence interval, 0.63-0.76; p < 0.001) analyses. Our results suggest that individuals with schizophrenia who also have comorbid CUD may require shorter inpatient treatment during periods of exacerbation of symptoms. Replication of this finding has relevance in treatment planning and resource allocation for the subpopulation of individuals with schizophrenia who also have stimulant use disorders.

Antipsychotic medication-induced dysphoria: its meaning, association with typical vs. atypical medications and impact on adherence.

Antipsychotic medication-induced dysphoria is a relatively under-recognized and understudied effect of antipsychotic medication. Although the term is encountered in clinical practice and in the literature, there is no consensus regarding its exact meaning. This article is a narrative review of the literature on antipsychotic medication and dysphoria based on a pubmed database search. We found that antipsychotic medication-induced dysphoria is a term used to describe a negative and unpleasant affective state which seems to be more often associated with high potency first-generation antipsychotics and could potentially lead to medication non-adherence. Though it is plausible to expect antipsychotic medication-induced dysphoria to be related to extrapyramidal symptoms, most especially akathisia, the nature of the association remains unspecified. Furthermore, there is some evidence that dopamine blockade maybe involved in the pathogenesis of antipsychotic medication-induced dysphoria. However, the limited methods of the currently available studies make it impossible to conclusively address the question of which class of antipsychotic (first- or second-generation) has a higher prevalence and severity of the syndrome.

Evaluation of spontaneous fermentation impact on the physicochemical properties and sensory profile of green and roasted arabica coffee by digital technologies.

There is a growing demand for specialty coffee with more pleasant and uniform sensory perception. Wet fermentation could modulate and confer additional aroma notes to final roasted coffee brew. This study aimed to assess differences in volatile compounds and the intensities of sensory descriptors between unfermented and spontaneously fermented coffee using digital technologies. Fermented (F) and unfermented (UF) coffee samples, harvested from two Australia local farms Mountain Top Estate (T) and Kahawa Estate (K), with four roasting levels (green, light-, medium-, and dark-) were analysed using near-infrared spectrometry (NIR), and a low-cost electronic nose (e-nose) along with some ground truth measurements such as headspace/gas chromatography-mass spectrometry (HS-SPME-GC-MS), and quantitative descriptive analysis (QDA ®). Regression machine learning (ML) modelling based on artificial neural networks (ANN) was conducted to predict volatile aromatic compounds and intensity of sensory descriptors using NIR and e-nose data as inputs. Green fermented coffee had significant perception of hay aroma and flavor. Roasted fermented coffee had higher intensities of coffee liquid color, crema height and color, aftertaste, aroma and flavor of dark chocolate and roasted, and butter flavor (p < 0.05). According to GC-MS detection, volatile aromatic compounds, including methylpyrazine, 2-ethyl-5-methylpyrazine, and 2-ethyl-6-methylpyrazine, were observed to discriminate fermented and unfermented roasted coffee. The four ML models developed using the NIR absorbance values and e-nose measurements as inputs were highly accurate in predicting (i) the peak area of volatile aromatic compounds (Model 1, R = 0.98; Model 3, R = 0.87) and (ii) intensities of sensory descriptors (Model 2 and Model 4; R = 0.91), respectively. The proposed efficient, reliable, and affordable method may potentially be used in the coffee industry and smallholders in the differentiation and development of specialty coffee, as well as in process monitoring and sensory quality assurance.

A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of the Acute Antisuicidal and Antidepressant Effects of Intranasal (R,S)-Ketamine in Severe Unipolar and Bipolar Depression With and Without Comorbid Alcohol Use Disorder.

Objective: Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic (R,S)-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior antisuicidal outcomes for patients.Methods: This was a double-blind, randomized, placebo-controlled trial (May 2018 to January 2022) of single administration, fixed-dose (50 mg) IN (R,S)-ketamine (or saline comparator) in unmedicated inpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for a current major depressive episode (bipolar or unipolar), with current suicidal ideation (SI) and past attempt. Patients with and without comorbid AUD were enrolled. Change in Scale for Suicide Ideation score was the primary outcome measure, and change in Montgomery-Åsberg Depression Rating Scale score was the secondary outcome measure.Results: No significant group × time effect was noted for SI (F = 1.1, P = .36). A statistical trend toward superior improvement in suicidality was observed in participants with comorbid AUD. The group × time interaction was significant for improvements in depression (F = 3.06, P = .03) and largely unaffected by comorbid AUD or primary mood disorder type. Within the ketamine group, a significant correlation was observed between improvement in depressive symptoms and SI for patients without comorbid AUD (r =0.927, P = .023) that was absent in patients with AUD (r = 0.39, P = .44).Conclusion: IN ketamine induced rapid antidepressant effects compared to placebo but did not significantly alter SI scores. The treatment was well tolerated. Continued investigation with IN ketamine as a practical alternative to current formulations is warranted.Trial Registration: ClinicalTrials.gov identifier: NCT03539887.

In vitro digestion and colonic fermentation of phenolic compounds and their bioaccessibility from raw and roasted nut kernels.

Roasting and digestion affect nut kernel phenolic compounds' bioaccessibility and bioactivity. In this study, three types of raw and commercially roasted nut kernels (almonds, cashews, and walnuts) were treated by in vitro digestion and colonic fermentation. The objective was to analyze the effect of roasting on their phenolic content, associated antioxidant potential, bioaccessibility, and short chain fatty acid (SCFA) synthesis altering. Among these, raw and roasted walnuts performed best, with significantly higher total phenolic content (TPC), total flavonoid content (TFC), free radical scavenging (2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay) values, and ferric reducing antioxidant power (FRAP) values after completing gastrointestinal digestion. With the exception of cashews, roasting had no significant effect on antioxidant capacity during digestion from oral to small intestinal phase. Almonds showed the highest DPPH values after 16-hour colonic fermentation, reaching above 7.60 mg TE per g. Roasting had a positive effect on the free radical savagery capacity of walnuts within 16-24 hours of fecal fermentation. Significant differences were found in the bioaccessibility of individual compounds in raw and roasted nuts. As for almond and walnut, roasting increases the release and breakdown of phenolic compounds during colonic fermentation and have a positive impact on the bioaccessibility of specific phenolic compounds. The colonic bioaccessibility of most phenolic compounds was the highest. Due to heat polysaccharide breakdown, the total SCFAs produced were limited up to 0.03 mM. Raw almonds produced the most SCFAs at 16-hour fermentation and illustrated more benefits to gut health.

Insomnia mediates the effect of perceived stress on emotional symptoms during the first wave of the COVID-19 pandemic in China.

The outbreak of the 2019 coronavirus disease (COVID-19) has significant effects on stress, emotion and sleep in the general public. The aim of this study was to explore the relationship between perceived stress and emotional symptoms during the first wave of the COVID-19 pandemic in China and to further determine whether insomnia could serve as a mediator in this relationship. A total of 1178 ordinary citizens living in mainland China conducted anonymous online surveys. The 10-item Perceived Stress Scale, the Insomnia Severity Index, the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale were used to estimate perceived stress, insomnia, depression and anxiety symptoms, respectively. Of the 1171 valid respondents from 132 cities in China, 46.6 % and 33.0 % showed symptoms of depression and anxiety, respectively. Perceived stress and insomnia independently predicted the prevalence of emotional symptoms and were positively correlated with the severity of these emotional symptoms. The mediation analyses further revealed a partial mediation effect of insomnia on the relationship between perceived stress and emotional symptoms during the first wave of the COVID-19 outbreak in China. Our findings can be used to formulate early psychological interventions to improve the mental health of vulnerable groups, specifically those with insomnia, during the COVID-19 pandemic.

Fluidized-bed gasification of dairy manure by Box-Behnken design.

Application of excessive animal manure to the land may cause some environmental problems such as eutrophication of surface waters, degradation of ground water quality, and threats to human health. This paper reports an experimental study on the technology of biomass gasification to treat animal waste by analysing the effects of key operating parameters on gasification. In this research, dairy manure from the University of Nebraska dairy farm was first collected and dried, and then gasified in a fluidized-bed, laboratory-scale gasifier to generate syngas. The effects of three parameters, namely temperature, steam to biomass ratio (SBR) and the equivalence ratio (ER), on the gasification were described by a Box-Behnken design (BBD). Results showed that increasing the temperature favoured the formation of all three combustible gases, but the composition of each gas behaved differently according to the changing parameters. The lower heating value of the syngas varied from 2.0 to 4.7 MJ m(-3), indicating gasification could be used as a waste management option to produce bioenergy, and potentially reduce problems associated with the disposal of animal waste.

Thermogravimetric characterization of dairy manure as pyrolysis and combustion feedstocks.

Thermogravimetric analysis was used to examine the thermal behavior of dairy manure as a pyrolysis and combustion feedstock. Nitrogen and air were used as purging gases to analyze the pyrolysis and combustion reactions, respectively, and heating rates of 20°C min(-1), 40°C min(-1) and 60°C min(-1) were applied. An Arrhenius model was used to estimate the kinetic parameters (activation energy, reaction order and pre-exponential factor). Results showed four steps for both the pyrolysis and the combustion reactions, with the second step being the most critical one and during which most thermal decomposition of cellulose, hemicelluloses, starch and protein occurred. Thermochemical reactions were determined mainly by temperature. Heating rate influenced the start and the end of the thermal conversions. The activation energies for the two major reaction zones were 93.63 kJ mol(-1) and 84.53 kJ mol(-1) for pyrolysis, and 83.03 kJ mol(-1) and 55.65 kJ mol(-1) for combustion. Knowledge of the thermal behavior of dairy manure provides guidelines for future energy utilization.

Comparison of Efficacy and Safety Between Low-Dose Ziprasidone in Combination With Sertraline and Ziprasidone Monotherapy for Treatment-Resistant Patients With Acute Exacerbation Schizophrenia: A Randomized Controlled Trial.

Treatment-resistant schizophrenia (TRS) is a prevalent clinical problem with heterogeneous presentations. However, the clinical trial designs for new treatments are still lacking. This study aimed to assess the efficacy of ziprasidone plus sertraline in TRS patients as compared to ziprasidone monotherapy. We conducted a 24 weeks, randomized, controlled, double-blinded clinical research trial. 62 treatment-resistant patients with acute exacerbation SZ were randomly allocated to receive a usual dose of ziprasidone (120-160 mg/d) monotherapy (Control group) and 53 TRS inpatients were to receive a low dose of ziprasidone (60-80 mg/d) in combination with sertraline (ZS group). Treatment outcomes were measured by the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and Personal and Social Performance Scale (PSP) at baseline, week 4, 8, 12, and 24. Relative to control group, the patients in ZS group showed greater reductions in the following: PANSS positive symptom, negative symptom, total score, and HAMD total score. Additionally, the patients in ZS group had a greater increase in PSP total score. Notably, the reduction in HAMD was positively correlated with the reduction in PANSS total score. The reduction in CGI-S was a predictor for the improvement of psychosocial functioning in patients. Furthermore, the ZS group had a lower rate of side effects compared to the control group. Our findings suggest that a low dose of ziprasidone in combination with sertraline is an effective therapy for the clinical symptoms as compared to a usual dose of ziprasidone in the treatment-resistant patients with acute exacerbation SZ. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04076371.

Bioaccessibility and movement of phenolic compounds from tomato (Solanum lycopersicum) during in vitro gastrointestinal digestion and colonic fermentation.

Tomatoes (Solanum lycopersicum) are highly involved in diets consumed worldwide, and are rich in bioactive compounds including phenolics, carotenoids and vitamins. In this study, four different varieties of fresh tomato pulp (Oxheart, Green Zebra, Kumato and Roma) were used to estimate the bioaccessibility of target phenolic compounds during in vitro gastrointestinal digestion and colonic fermentation, and to determine their antioxidant capacity. The production of short chain fatty acids (SCFAs) was also estimated during colonic fermentation. Among these, Roma displayed relatively higher total phenolic content (TPC) and free radical scavenging (2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay) values after gastrointestinal digestion of 0.31 mg gallic acid equivalents (GAE) per g and 0.12 mg Trolox equivalents (TE) per g. Kumato exhibited the highest total flavonoid content (TFC) of 2.47 mg quercetin equivalents (QE) per g after 8 hours of colonic fermentation. Oxheart and Roma showed similar ferric reducing antioxidant power (FRAP) values of around 4.30 mg QE per g after 4 hours of faecal reaction. Catechin was the most bioaccessible phenolic compound in all fresh tomatoes, and could be completely decomposed after intestinal digestion, whereas the release of some bonded phenolic compounds required the action of gut microflora. Kumato and Green Zebra showed higher production of individual and total SCFAs for 16 hours of fermentation, which would provide more gut health benefits.

Identification of Phenolic Compounds in Australian-Grown Bell Peppers by Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time-of-Flight-Mass Spectrometry and Estimation of Their Antioxidant Potential.

Bell peppers are widely considered as healthy foods that can provide people with various phytochemicals, especially phenolic compounds, which contribute to the antioxidant property of bell peppers. Nevertheless, the acknowledgment of phenolic compounds in bell peppers is still limited. Therefore, this study aimed to determine the phenolic content and the antioxidant potential in pulps and seeds of different bell peppers (green, yellow, and red) by several in vitro assays followed by the characterization and quantification of individual phenolics using liquid chromatography coupled with electrospray ionization-quadrupole-time-of-flight-mass spectrometry (LC-ESI-QTOF-MS/MS) and high-performance liquid chromatography photodiode array (HPLC-PDA) quantification, respectively. The captured results showed that the pulp of red bell peppers exhibited the highest phenolic content in the total polyphenol content (1.03 ± 0.07 mg GAE/gf.w.), total flavonoid content (137.43 ± 6.35 µg QE/gf.w.), and total tannin content (0.22 ± 0.01 mg CE/gf.w.) as well as the most antioxidant potential in all antioxidant capacity estimation assays including total antioxidant capacity (3.56 ± 0.01 mg AAE/gf.w.), 2,2'-diphenyl-1-picrylhydrazyl (0.89 ± 0.01 mg AAE/gf.w.), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (1.36 ± 0.12 mg AAE/gf.w.), and ferric reducing antioxidant power (0.15 ± 0.01 mg AAE/gf.w.). LC-ESI-QTOF-MS/MS isolated and identified a total of 59 phenolic compounds, including flavonoids (21), phenolic acids (20), other phenolic compounds (12), lignans (5), and stilbenes (1) in all samples. According to HPLC-PDA quantification, the seed portions showed a significantly higher amount of phenolic compounds. These findings indicated that the waste of bell peppers can be a potential source of phenolic compounds, which can be utilized as antioxidant ingredients in foods and nutritional products.