Gradient Harmonization in Unsupervised Domain Adaptation.

Unsupervised domain adaptation (UDA) intends to transfer knowledge from a labeled source domain to an unlabeled target domain. Many current methods focus on learning feature representations that are both discriminative for classification and invariant across domains by simultaneously optimizing domain alignment and classification tasks. However, these methods often overlook a crucial challenge: the inherent conflict between these two tasks during gradient-based optimization. In this paper, we delve into this issue and introduce two effective solutions known as Gradient Harmonization, including GH and GH++, to mitigate the conflict between domain alignment and classification tasks. GH operates by altering the gradient angle between different tasks from an obtuse angle to an acute angle, thus resolving the conflict and trade-offing the two tasks in a coordinated manner. Yet, this would cause both tasks to deviate from their original optimization directions. We thus further propose an improved version, GH++, which adjusts the gradient angle between tasks from an obtuse angle to a vertical angle. This not only eliminates the conflict but also minimizes deviation from the original gradient directions. Finally, for optimization convenience and efficiency, we evolve the gradient harmonization strategies into a dynamically weighted loss function using an integral operator on the harmonized gradient. Notably, GH/GH++ are orthogonal to UDA and can be seamlessly integrated into most existing UDA models. Theoretical insights and experimental analyses demonstrate that the proposed approaches not only enhance popular UDA baselines but also improve recent state-of-the-art models.

Metformin treatment improves depressive symptoms associated with type 2 diabetes: A 24-week longitudinal study.

OBJECTIVE: Metformin is a medication that is widely used for lowering blood sugar in patients with type 2 diabetes. Metformin was shown to have significant antidepressant effects; however, it is not clear whether metformin treatment improves outcomes in patients with type 2 diabetes who have concomitant depressive symptoms. METHODS: A total of 475 patients with type 2 diabetes mellitus with depressive symptoms were included in this study and divided into metformin and nonmetformin groups according to whether they were taking metformin. The DASS-21 was used to assess patients' depression and anxiety scores before and after a 24-week intervention. In addition, general information about whether the patients had developed complications from diabetes and whether they had been diagnosed with other diseases was assessed. RESULTS: (1) After 24 weeks, anxiety and depression scores were significantly lower in the metformin group than in the nonmetformin group. (2) The prevalence of depressive symptoms was significantly greater in female type 2 diabetic patients than in male patients (OR = 2.039, 95 % CI = 1.160-3.568). (3) People with type 2 diabetes who develop complications from diabetes (OR = 1.794, 95 % CI = 1.015-3.171) and those diagnosed with other conditions are more likely to experience depressive symptoms. CONCLUSION: Metformin has an ameliorative effect on type 2 diabetes. However, women, those with diabetes complications, and those with type 2 diabetes who are also diagnosed with other conditions are more likely to experience depressive symptoms.

Effect of long-term use of antipsychotics on the ventricular repolarization index.

BACKGROUND: The risk of arrhythmia is usually assessed by the length of the corrected QT interval (QTc) when patients use antipsychotics. Prolonged QTc intervals are thought to increase the probability of malignant ventricular arrhythmias, and if we focus only on the QTc interval, we may be influenced by a single factor and make decisions that are not conducive to effective treatment. The index of cardiac electrophysiological balance (iCEB) is considered more valuable than the QTc for predicting drug-induced arrhythmias. It has been used in clinical practice, but no studies have observed changes in this index after the use of antipsychotics. OBJECTIVE: To investigate the changes in ventricular repolarization indices and the occurrence of arrhythmias in patients who have been using antipsychotic drugs for a long time, to compare the changes in iCEBc and QTc and to predict abnormal iCEBc values. METHODS: Patients with schizophrenia who had been hospitalized for more than 4 years and who were receiving atypical antipsychotics underwent a 12-lead synchronized electrocardiogram (ECG) every 2-4 weeks. The baseline data were measured at admission, defined as the baseline (time0), and the most obvious abnormal changes in ventricular depolarization and repolarization measured every 12 months were one-year follow-up (time1), two-year follow-up (time2), three-year follow-up (time3), and four-year follow-up (time4). Repeated measures analysis of variance was used for comparisons. The types and doses of drugs taken at 5 time points were recorded and converted into chlorpromazine equivalents for comparison. The incidence of arrhythmia during the observation cycle was recorded. RESULTS: The patients had been treated with antipsychotic medication for 4 years, and the duration of the QRS wave was longer in males than in females. TpTe, TpTe/QRS, TpTe/QT, TpTe/QTc, iCEB, and iCEBc increased significantly with hospital stay, while TpTe, TpTe/QRS, TpTe/QT, and TpTe/QTc exhibited more obvious changes in these indicators in female patients (P < 0.01). The changes in iCEB and iCEBc were more significant in males (P < 0.01). The incidences of arrhythmia (arrhythmic events included premature ventricular beats and premature atrial beats) within 5 time points were 2.5%, 6.25%, 6.25%, 6.25% and 5%, respectively. More than 90% of patients treated with antipsychotics did not have any arrhythmias. No TdP syncope or other cardiovascular symptoms were found in any of the patients. CONCLUSION: After long-term use of antipsychotics, the ventricular repolarization index gradually increased with time. The new ventricular repolarization indices iCEB and iCEBc were more sensitive than the QTc at predicting arrhythmia. According to the abnormal QTc values in men and women, we predict that the abnormal value of the iCEBc in males is 4.528 and that in females is 5.315.

Role of HOMA-IR and IL-6 as screening markers for the metabolic syndrome in patients with chronic schizophrenia: a psychiatric hospital-based cross-sectional study.

This study starts from the metabolic related indexes and cellular inflammatory factors in patients with chronic schizophrenia to find out that it can be used as an effective screening index of metabolic syndrome. 320 patients with chronic schizophrenia (course of disease > 5 years) and 165 healthy subjects were selected. The mental symptoms of the patients were measured by positive and negative syndrome scale. Blood samples from patients and healthy controls were collected to detect blood glucose, triglyceride, HDL and fasting insulin. The serum levels of IL-1ß, IL-2, IL-6, IL-17, IFN-γ and TNF-α were determined repeatedly by sandwich enzyme-linked immunosorbent assay. The levels of HOMA-IR, plasma inflammatory factors IL-2, IL-6, IL-17 and TNF-α in patient group were higher than those in healthy group. It was found that there were differences in age and related metabolic indexes between patients with chronic schizophrenia with and without metabolic syndrome. In addition, HOMA-IR, plasma cytokines IL-2 and IL-6 still showed differences between groups. In the Spearmen correlation analysis of insulin resistance index, cytokines and metabolic indexes, it was found that there was a significant correlation between HOMA-IR, IL-6 and related metabolic indexes and metabolic syndrome. ROC curve analysis showed that HOMAIR and IL-6 could be used as screening indexes for MS in male and female patients with schizophrenia.Metabolic syndrome is an important risk factor for cardiovascular disease in patients with chronic schizophrenia. HOMA-IR and IL-6 can be used as effective biological indicators to screen MS in patients with chronic schizophrenia.

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/ß-catenin pathway in rats.

Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS), after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively. The sucrose preference test, open field test, and forced swimming test were used to explore the antidepressant-like effects of RES. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the plasma corticosterone concentration and hypothalamic mRNA expression of corticotrophin-releasing hormone. The plasma interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) concentrations were measured by enzyme-linked immunosorbent assay. Hippocampal protein expression of brain-derived neurotrophic factor (BDNF) and the Wnt/ß-catenin pathway were analyzed by western blot. The results showed that RES relieved depression-like behavior of CUMS rats, as indicated by the increased sucrose preference and the decreased immobile time. Rats that received RES treatment exhibited reduced plasma corticosterone levels and corticotrophin-releasing hormone mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by RES. Moreover, after RES treatment, the rats exhibited increased plasma IL-6, CRP, and TNF-α concentrations. Furthermore, RES treatment upregulated the hippocampal protein levels of BDNF and the relative ratio of p-ß-catenin/ß-catenin while downregulating the relative ratio of p-GSK-3ß/GSK-3ß. Our findings suggest that RES improved depressive behavior in CUMS rats by downregulating HPA axis hyperactivity, increasing BDNF expression and plasma IL-6, CRP, and TNF-α concentrations, and regulating the hippocampal Wnt/ß-catenin pathway.