Development and validation of a nomogram for predicting the occurrence of renal dysfunction after treatment of immune checkpoint inhibitor: a retrospective case-control study.

PURPOSE: The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of renal dysfunction after ICIs therapy, a retrospective case-control study was conducted. METHODS: Clinical information on ICIs-treated patients was collected. Multivariable logistic regression was applied to identify risk factors for renal dysfunction after ICIs treatment. Moreover, a nomogram model was developed and validated internally. RESULTS: A total of 442 patients were included, among which 35 (7.9%) experienced renal dysfunction after ICIs treatment. Lower baseline estimated glomerular filtration rate (eGFR) (OR 0.941; 95% CI 0.917 to 0.966; p<0.001), concurrent exposure of platinum(OR 4.014; 95% CI 1.557 to 10.346; p=0.004), comorbidities of hypertension (OR 3.478; 95% CI 1.600 to 7.562; p=0.002) and infection (OR 5.402; 95% CI 1.544 to 18.904; p=0.008) were found to be independent associated with renal dysfunction after ICIs treatment. To develop a predictive nomogram for the occurrence of renal dysfunction after ICIs treatment, the included cases were divided into training and validation groups in a ratio of 7:3 randomly. The above four independent risk factors were included in the model. The area under the receiver operating characteristic curves of the predictiive model were 0.822 (0.723-0.922) and 0.815 (0.699-0.930) in the training and validation groups, respectively. CONCLUSIONS: Lower baseline eGFR, platinum exposure, comorbidities of hypertension and infection were predictors of renal dysfunction in ICIs-treated patients with cancer. A nomogram was developed to predict the probability of renal dysfunction after ICIs treatment, which might be operable and valuable in clinical practice.

Comparison of Dosage of Glucocorticoid in Idiopathic Membranous Nephropathy: A Systematic Review and Network Meta-Analysis.

PURPOSE: Idiopathic membranous nephropathy (IMN) with moderate risk or above was recommended to receive immunosuppressive therapy. We attempted to evaluate the optimal dose of glucocorticoid when combined with evidence-proven effective immunosuppressants by network meta-analysis. METHODS: A systematic review of the literature was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until January 2022. Randomized controlled trials (RCTs) in IMN limited to supportive care, glucocorticoids, cyclophosphamide, chlorambucil, calcineurin inhibitors (CNIs), and rituximab were screened. RESULTS: Twenty-eight RCTs of 1,830 patients were included. Therapeutic regimens were divided as follows: moderate- to high-dose glucocorticoids plus CNIs (HMSCn), moderate- to high-dose glucocorticoids plus cyclophosphamide (HMSCt), moderate- to high-dose glucocorticoids plus chlorambucil (HMSCh), zero- to low-dose glucocorticoids plus CNIs (LNSCn), zero- to low-dose glucocorticoids plus cyclophosphamide (LNSCt), rituximab alone (R), glucocorticoids alone (SE), and supportive care alone (SP). Compared with SP, HMSCh (risk ratio [RR]: 1.77, 95% confidence interval [CI]: 1, 3.18), HMSCn (RR: 2.5, 95%CI: 1.25, 5.11), HMSCt (RR: 2.15, 95%CI: 1.29, 3.64), LNSCn (RR: 2.16, 95%CI: 1.25, 3.95), and R (RR: 2.07, 95%CI: 1, 4.39) had a higher probability of total remission rate, while HMSCn represented the highest probability depending on the surface under the cumulative ranking area (SUCRA) ranking values. Regarding infection, no significant difference was found between different doses of glucocorticoids plus the same immunosuppressant. HMSCn and HMSCt showed superiority in reducing 24-hour urine total protein compared with HMSCh, LNSCn, SE, and SP, while HMSCn seemed to be the most effective regimen through the ranking of SUCRA value. CONCLUSION: Moderate- to high-dose glucocorticoids showed superiority in proteinuria remission when combined with CNIs in IMN, with no increasing risk of infection.

Efficacy and safety of the integration of traditional Chinese medicine and western medicine in the treatment of diabetes-associated cognitive decline: a systematic review and meta-analysis.

Objective: In order to offer possible therapeutic treatment evidence for diabetes-associated cognitive decline (DACD), we thoroughly evaluated the effectiveness and safety of combining Traditional Chinese Medicine (TCM) and Western Medicine (WM) in the current study. Methods: The present study employed a comprehensive search strategy across multiple databases, namely, PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Scientific Journals Database (VIP), and Chinese Biomedical Literature Database (CBM), to identify relevant articles published until July 2023. Subsequently, a systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the efficacy and safety of integrating TCM with WM for the treatment of DACD. The literature included in this study was assessed using the GRADE criteria and the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was conducted using RevMan 5.4 software. Results: A total of 20 RCTs involving 1,570 patients were ultimately included in this meta-analysis. The pooled results demonstrated that the integration of TCM and WM therapy significantly enhanced the overall effectiveness rate compared to WM therapy alone [OR = 4.94, 95% CI (3.56, 6.85), p < 0.00001]. Additionally, the combination therapy resulted in reductions in fasting blood glucose [MD = -0.30, 95% CI (-0.49, -0.10), p = 0.003], HbA1c [MD = -0.71, 95%CI (-1.03, -0.40), p < 0.00001], TNF-α levels [MD = -8.28, 95%CI (-13.12, -3.44), p = 0.0008], and TCM Syndrome Score [MD = -5.97, 95%CI (-9.06, -2.88), p = 0.0002]. Meanwhile, the combination therapy had a positive effect on MoCA Score [MD = 2.52, 95% CI (1.75, 3.30), p < 0.00001], and MMSE Score [MD = 2.31, 95% CI (1.33, 3.29), p < 0.00001]. In addition, the safety of the combination therapy was comparable to that of the WM alone [OR = 0.40, 95% CI (0.12, 1.31), p = 0.13]. Conclusion: The integration of TCM and WM therapy outperformed WM alone in DACD treatment. Simultaneously, the combination therapy could improve the therapeutic effect on blood glucose, cognitive function, and inflammation to a certain extent with few adverse effects. However, given the constraints imposed by the quality limitations of the incorporated studies, as well as the potential presence of reporting bias, it is imperative that our findings be substantiated through rigorous, large-scale, randomized controlled trials of superior quality in the future.

Validation of the Thai Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) among young adults.

BACKGROUND: The Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) is a consistent and comprehensive instrument to assess symptoms of specific internet-use disorders including those related to gaming, shopping, pornography use disorder, social networks use and gambling considering criteria in the eleventh revision of the International Classification of Diseases (ICD-11). However, to date, there is little evidence supporting instruments assessing major types of specific internet use disorders in Thailand. The aim of this present study was to assess the psychometric properties of the ACSID-11 among Thai young adults. METHODS: A total of 612 participants were recruited. A confirmatory factor analysis (CFA) examined construct validity of the ACSID-11. Cronbach's α and McDonald's ω were used to assess reliability of the ACSID-11. Pearson correlations examined relationships between ACSID-11 domains and Internet Gaming Disorder Scale-Short Form (IGDS9-SF) scores. RESULTS: The CFA supported validity of the Thai version of the ACSID-11 and a four-factor structure. Specific domains of the Thai ACSID-11, particularly gaming, were positively and significantly correlated with IGDS9-SF scores. CONCLUSIONS: Data indicate that the Thai version of the ACSID-11 is a valid and reliable instrument to assess major types of specific internet use disorders. Additional studies are needed to further examine the validity and reliability of the Thai ACSID-11.

The Role of Iron Overload in Diabetic Cognitive Impairment: A Review.

It is well documented that diabetes mellitus (DM) is strongly associated with cognitive decline and structural damage to the brain. Cognitive deficits appear early in DM and continue to worsen as the disease progresses, possibly due to different underlying mechanisms. Normal iron metabolism is necessary to maintain normal physiological functions of the brain, but iron deposition is one of the causes of some neurodegenerative diseases. Increasing evidence shows that iron overload not only increases the risk of DM, but also contributes to the development of cognitive impairment. The current review highlights the role of iron overload in diabetic cognitive impairment (DCI), including the specific location and regulation mechanism of iron deposition in the diabetic brain, the factors that trigger iron deposition, and the consequences of iron deposition. Finally, we also discuss possible therapies to improve DCI and brain iron deposition.

Problematic smartphone use and two types of problematic use of the internet and self-stigma among people with substance use disorders.

BACKGROUND AND AIMS: Guided by the Interaction of Person-Affect-Cognition-Execution (I-PACE) model and a self-stigma framework, this study aimed to investigate relationships between cognitive and affective self-stigma and behavioral self-stigma, problematic use of internet (PUI), and problematic smartphone use (PSU) among people with substance use disorders (SUDs). It also examined mediating roles for affective self-stigma in the relationships between cognitive self-stigma and behavioral self-stigma/PUI/PSU. METHODS: Using a cross-sectional design, 530 participants diagnosed with SUDs in Taiwan were recruited from a psychiatric center in Taiwan. Mediation models were investigated using the Hayes' Process Macro Model 4. RESULTS: Mediation analyses indicated that cognitive self-stigma was directly associated with behavioral self-stigma (p < 0.001), but not with either types of PUI or PSU (p-values ranging from 0.41 to 0.76). Affective self-stigma was directly related to behavioral self-stigma (p < 0.001), two types of PUI, and PSU (ß = 0.24-0.30; all p < 0.001); cognitive self-stigma was indirectly associated with behavioral self-stigma (ß = 0.53; 95  % bootstrapping CI = 0.46, 0.60), two types of PUI, and PSU (ß = 0.20-0.25; 95  % bootstrapping CI = 0.08-0.14, 0.31-0.37) via a mediating effect of affective self-stigma. DISCUSSION AND CONCLUSION: Findings support the I-PACE model in a self-stigma context. The findings also suggest that addressing affective self-stigma may help prevent or reduce behavioral self-stigma, PUI, and PSU among people with SUDs. Longitudinal studies are warranted to investigate over time relationships between self-stigma and PUI/PSU in people with SUDs.

Effects of liraglutide on astrocyte polarization and neuroinflammation in db/db mice: focus on iron overload and oxidative stress.

Neuroinflammation plays a crucial role in the occurrence and development of cognitive impairment in type 2 diabetes mellitus (T2DM), but the specific injury mechanism is not fully understood. Astrocyte polarization has attracted new attention and has been shown to be directly and indirectly involved in neuroinflammation. Liraglutide has been shown to have beneficial effects on neurons and astrocytes. However, the specific protection mechanism still needs to be clarified. In this study, we assessed the levels of neuroinflammation and A1/A2-responsive astrocytes in the hippocampus of db/db mice and examined their relationships with iron overload and oxidative stress. First, in db/db mice, liraglutide alleviated the disturbance of glucose and lipid metabolism, increased the postsynaptic density, regulated the expression of NeuN and BDNF, and partially restored impaired cognitive function. Second, liraglutide upregulated the expression of S100A10 and downregulated the expression of GFAP and C3, and decreased the secretion of IL-1ß, IL-18, and TNF-α, which may confirm that it regulates the proliferation of reactive astrocytes and A1/A2 phenotypes polarize and attenuate neuroinflammation. In addition, liraglutide reduced iron deposition in the hippocampus by reducing the expression of TfR1 and DMT1 and increasing the expression of FPN1; at the same time, liraglutide by up-regulating the levels of SOD, GSH, and SOD2 expression, as well as downregulation of MDA levels and NOX2 and NOX4 expression to reduce oxidative stress and lipid peroxidation. The above may attenuate A1 astrocyte activation. This study preliminarily explored the effect of liraglutide on the activation of different astrocyte phenotypes and neuroinflammation in the hippocampus of a T2DM model and further revealed its intervention effect on cognitive impairment in diabetes. Focusing on the pathological consequences of astrocytes may have important implications for the treatment of diabetic cognitive impairment.

Neonatal and pregnancy complications following maternal depression or antidepressant exposure: A population-based, retrospective birth cohort study.

OBJECTIVES: Depression is common during pregnancy, and antidepressants are often prescribed for treatment. However, depression and antidepressant use both increase the risk of neonatal and pregnancy complications. To separately evaluate the effects of antidepressant use and the underlying depression on pregnancy and neonatal complications by using a robust statistical method to control for confounding by indication. METHODS: All study data were obtained from Taiwan's National Health Insurance Research Database. Pregnant women were divided into three groups: those with no depression and no antidepressant exposure(n = 1619,198), depression and no antidepressant exposure(n = 2006), and depression and antidepressant exposure(n = 7857). Antidepressant exposure was further divided into that before pregnancy and during each trimester. RESULTS: Mothers with depression but no antidepressant exposure exhibited increased risks of intrauterine growth restriction and preterm delivery, compared with mothers without depression. In mothers with depression, antidepressant exposure before pregnancy or during the first trimester conferred increased risks of gestational diabetes mellitus, malpresentation, preterm delivery and cardiovascular anomalies, compared with no antidepressant exposure. Moreover, antidepressant exposure during the second or third trimester conferred increased risks of anemia, a low Apgar score, preterm delivery and genitourinary defects. However, antidepressants administered before pregnancy and during all trimesters did not increase the risk of stillbirth. CONCLUSION: Depression and antidepressant treatment for depression during pregnancy may individually increase the risks of some neonatal and pregnancy complications. Physicians should thoroughly consider the risks and benefits for both the mother and fetus when treating depression during pregnancy by using antidepressants.

Risk factors of immune checkpoint inhibitor-associated acute kidney injury: evidence from clinical studies and FDA pharmacovigilance database.

BACKGROUND: Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study. METHODS: We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR). RESULTS: A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78-2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24-1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01-1.65), diuretics (OR = 2.00, 95%CI 1.38-2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04-1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15-1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25-2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96-3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91-2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95-3.57), NSAIDs (ROR = 3.06, 95%CI 2.81-3.32) or diuretics (ROR = 2.82, 95%CI 2.50-3.19) were observed significant signals associated with AKI in ICIs-treated patients. CONCLUSIONS: Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

Examining the association between neuropsychiatric symptoms among people with dementia and caregiver mental health: are caregiver burden and affiliate stigma mediators?

BACKGROUND: Neuropsychiatric disturbances are common manifestations of dementia disorders and are associated with caregiver burden and affiliate stigma. The present study investigated affiliate stigma and caregiver burden as mediators for the association between neuropsychiatric symptoms of people with dementia (PWD) and caregiver mental health such as depression and anxiety. METHODS: A cross-sectional survey study was carried out with 261 dyads of PWD and informal caregivers from the outpatient department of a general hospital in Taiwan. The survey included the Caregiver Burden Inventory (CBI), the Affiliate Stigma Scale (ASS), the Taiwanese Depression Questionnaire (TPQ), and the Beck Anxiety Inventory (BAI). Mediation models were tested using the Hayes' PROCESS macro (Model 4 for parallel mediation model; Model 6 for sequentially mediation model). RESULTS: Caregiver burden, affiliate stigma, caregiver depression, and caregiver anxiety were significantly associated with neuropsychiatric symptoms. After controlling for several potentially confounding variables, it was found that PWD's neuropsychiatric symptoms, caregiver burden and affiliate stigma significantly explained 52.34% of the variance in caregiver depression and 37.72% of the variance in caregiver anxiety. The parallel mediation model indicated a significantly indirect path from PWD's neuropsychiatric symptoms to caregiver mental health through caregiver burden and affiliate stigma, while the direct effect was not significant. Moreover, there was a directional association between caregiver burden and affiliate stigma in the sequential mediation model. CONCLUSIONS: These findings show that it is imperative to improve caregivers' perception of those with dementia to reduce internalized stigma and to improve caregivers' mental health. Implementation of affiliate stigma assessment in clinical practice would allow distinctions to be made between the impact of affiliate stigma and the consequences of caregiver burden to help inform appropriate intervention.

Quality of life and care burden among family caregivers of people with severe mental illness: mediating effects of self-esteem and psychological distress.

BACKGROUND: Family caregivers are important allies for healthcare providers in facilitating the recovery process among people with mental illness (PWMI). The present study examined the factors associated with quality of life (QoL) among family caregivers of PWMI. METHODS: A multi-center cross-sectional survey was conducted. Family caregivers of people with schizophrenia, major depressive disorder, and bipolar disorder were recruited using convenience sampling. A survey assessing their QoL, depression, anxiety, and self-esteem was completed with self-rated psychometric scales including the Rosenberg Self-Esteem Scale, Caregiver Burden Inventory, Taiwanese Depression Questionnaire, Beck Anxiety Inventory, and World Health Organization Quality of Life Instrument Short Form. A mediation model was constructed with QoL as the dependent variable, care burden as the independent variable, and psychological distress (including depression and anxiety) with self-esteem as mediating variables. RESULTS: Family caregivers of people with schizophrenia had worse QoL compared with counterparts of people with major depression and bipolar disorder. The sociodemographic of both caregivers and PWMI had less impact on QoL when psychological factors were considered. Caregivers with lower self-esteem, higher levels of psychological distress, and heavier care burdens had poorer QoL. Care burden had a significant total effect on QoL. Both self-esteem and psychological distress were significant mediators. CONCLUSION: The findings indicated that caregivers' psychological health and care burden influenced their QoL. Interventions that target family caregivers' self-esteem and psychological distress may attenuate the effect from care burden, and further improve their QoL.

Acute kidney injury associated with immune checkpoint inhibitors: A pharmacovigilance study.

BACKGROUND: Acute kidney injury (AKI) is a rare but severe adverse event of immune checkpoint inhibitors (ICIs). With the increasing reports of ICIs, it's necessary to put new insights into ICIs-related AKI. We conducted a systematic review of randomized controlled trials(RCTs) and a real-world study by extracting data from the US FDA Adverse Event Reporting System (FAERS) database. METHODS: We explored ICIs-related AKI events in RCTs available in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to August 2021. Meta-analysis was performed by using risk ratios (RRs) with 95 %CIs. In a separate retrospective pharmacovigilance study of FAERs, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC). RESULTS: A total of 79 RCTs (500,09 patients) were included, and ICIs were associated with increased risk of all-grade (RR = 1.37, 95 %CI:1.14-1.65) and high-grade AKI (RR = 1.60, 95 %CI:1.16-2.20). Results of subgroup analysis indicated that RR of ICI-related AKI did not vary significantly by cancer type, treatment regimen (monotherapy or combination of ICIs), study design (double-blind or open-label), individual ICIs and publication status (published or unpublished). FAERS pharmacovigilance data identified 1918 cases of AKI related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of AKI (ROR = 2.38, 95 %CI:2.27-2.49; IC = 1.22, 95 %CI:1.16-1.27). The median onset time of AKI was 48 days, 77.5 % of patients discontinued the use of ICIs, and 15.9 % of patients resulted in death. CONCLUSIONS: These data suggest that ICIs were significantly associated with increased risk of AKI in both trial settings and clinical practice.

Respiratory Arousals in Patients with Very Severe Obstructive Sleep Apnea and How They Change after a Non-Framework Surgery.

Respiratory arousal is the change from a state of sleep to a state of wakefulness following an apnea or hypopnea. In patients with obstructive sleep apnea (OSA), it could have a helpful role to activate upper airway muscles and the resumption of airflow and an opposing role to contribute to greater ventilatory instability, continue cycling, and likely exacerbate OSA. Patients with very severe OSA (apnea-hypopnea index (AHI) ≥ 60 events/h) may have specific chemical (e.g., possible awake hypercapnic hypoxemia) and mechanical (e.g., restricted dilator muscles) stimuli to initiate a respiratory arousal. Little was reported about how respiratory arousal presents in this distinct subgroup, how it relates to AHI, Epworth Sleepiness Scale (ESS), body mass index (BMI), and oxygen saturation, and how a non-framework surgery may change it. Here, in 27 patients with very severe OSA, we show respiratory arousal index was correlated with each of AHI, mean oxyhemoglobin saturation of pulse oximetry (SpO2), mean desaturation, and desaturation index, but not in BMI or ESS. The mean (53.5 events/h) was higher than other reports with less severe OSAs in the literature. The respiratory arousal index can be reduced by about half (45.3%) after a non-framework multilevel surgery in these patients.

Negative impact of the hypopnea index or duration increase after a non-frame work surgery in patients with very severe obstructive sleep apnea.

A non-framework surgery could change the postoperative components of breathing disturbances and increase the frequency or duration of hypopnea in patients with very severe obstructive sleep apnea (OSA). Either an increase of hypopnea index, which increases apnea-hypopnea index (AHI), or an increase of its duration raises the concern of worsening the oxygen desaturation and so morbidity and mortality associated with OSA. It is unclear how the oxygen saturation would change in those having increased frequency or duration of hypopneas after the surgery. Here in 17 patients with AHI ≥ 60 events/h, having increased frequency or duration of hypopneas after the non-framework surgery, the results show that the surgery improved oxygen saturation by reducing obstructive-apnea index (36.1 events/h) and duration (8.6 s/event), despite it increased hypopnea index (16.8 events/h) and duration (9.8 s/event). The surgery improved the average of the mean oxyhemoglobin saturation of pulse oximetry (SpO2) by 2.8% (toward a ceiling mean of 94.3%), mean minimal SpO2 by 7.5%, and mean desaturation by 5%. The results suggest sufficient apnea reduction and shift from apnea to hypopnea may mask the negative impact of the increase of hypopnea index or duration and improve postoperative mean SpO2, minimal SpO2, and mean desaturation.

Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis.

Studies have shown that diabetes is associated with the occurrence of neurodegenerative diseases and cognitive decline. However, there is currently no effective treatment for diabetes-induced cognitive dysfunction. The superior efficacy of liraglutide (LIRA) for cognitive impairment and numerous neurodegenerative diseases has been widely demonstrated. This study determined the effects of LIRA on diabetic cognitive impairment and on the levels of oxidative stress, lipid peroxidation, iron metabolism and ferroptosis in the hippocampus. Mice were injected daily with liraglutide (200 µg/kg/d) for 5 weeks. LIRA could repair damaged neurons and synapses, and it increased the protein expression levels of PSD 95, SYN, and BDNF. Furthermore, LIRA significantly decreased oxidative stress and lipid peroxidation levels by downregulating the production of ROS and MDA and upregulating SOD and GSH-Px in the serum and hippocampus, and the upregulation of SOD2 expression was also proven. The decreased levels of TfR1 and the upregulation of FPN1 and FTH proteins observed in the LIRA-treated db/db group were shown to reduce iron overload in the hippocampus, whereas the increased expression of Mtft and decreased expression of Mfrn in the mitochondria indicated that mitochondrial iron overload was ameliorated. Finally, LIRA was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4; simultaneously, the damage to the mitochondria observed by TEM was also repaired. For the first time, we proved in the T2DM model that ferroptosis occurs in the hippocampus, which may play a role in diabetic cognitive impairment. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetic cognitive disorders and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.

Risk of incident dementia in late-life depression treated with antidepressants: A nationwide population cohort study.

BACKGROUND: Antidepressants are frequently used to treat depression in patients with dementia. In addition, late-life depression is associated with the incidence of subsequent cognitive impairment or dementia. However, the association between exposure to antidepressants in late-life depression and the development of incident dementia remains understudied. METHODS: Through a population-based retrospective cohort design, data were extracted from the Taiwan National Health Insurance Research Dataset of medical claims registered from 1998-2013. We collected data of individuals who had received a new diagnosis of depression between 2000 and 2007. We excluded those who received a diagnosis of depression and were given antidepressants before 2000 and those younger than 60 years. The primary outcome was the occurrence of incident dementia. The time from the prescription of antidepressants or the diagnosis of depression until the outcome or the end of 2013 was calculated as the time to event. A total of 563,918 cases were included and were divided into either antidepressant users or antidepressant nonusers. Cox proportional hazards models were used to calculate the hazard ratio and 95% confidence interval. RESULTS: Exposure to antidepressants did not increase the risk of dementia in patients with late-life depression at either a low exposure dosage (hazard ratio: 1.06, 95% confidence interval: 0.91-1.23) or a high exposure dosage (hazard ratio: 1.07, 95% confidence interval: 0.95-1.20). To confirm the validity of our results, we performed a sensitivity analysis and subgroup analysis, and the post-hoc results were consistent with the main results. CONCLUSION: Antidepressants did not increase the risk of incident dementia in patients with late-life depression.

Comparing generalized and specific problematic smartphone/internet use: Longitudinal relationships between smartphone application-based addiction and social media addiction and psychological distress.

BACKGROUND AND AIMS: The literature has proposed two types of problematic smartphone/internet use: generalized problematic use and specific problematic use. However, longitudinal findings on the associations between the two types of problematic use and psychological distress are lacking among East-Asians. The present study examined temporal associations between both generalized and specific problematic use of the smartphone/internet, and psychological distress. METHODS: Hong Kong University students (N = 308; 100 males; mean age = 23.75 years; SD ± 5.15) were recruited with follow-ups at three, six, and nine months after baseline assessment. All participants completed the Smartphone Application-Based Addiction Scale (for generalized problematic smartphone/internet use), the Bergen Social Media Addiction Scale (for specific problematic smartphone/internet use), and the Hospital Anxiety and Depression Scale (for psychological distress) in each assessment. Latent growth modeling (LGM) was constructed to understand temporal associations between generalized/specific problematic use and psychological distress. RESULTS: The LGM suggested that the intercept of generalized problematic use was significantly associated with the intercept of psychological distress (standardized coefficient [ß] = 0.32; P < 0.01). The growth of generalized problematic use was significantly associated with the growth of psychological distress (ß = 0.51; P < 0.01). Moreover, the intercept of specific problematic use was significantly associated with the intercept of psychological distress (ß = 0.28; P < 0.01) and the growth of psychological distress (ß = 0.37; P < 0.01). CONCLUSION: The initial level of problematic use of smartphone/internet increased the psychological distress among university students. Helping young adults address problematic use of the smartphone/internet may prevent psychological distress.

Association Between Family Caregiver Burden and Affiliate Stigma in the Families of People with Dementia.

Family caregivers of people with dementia (PWD) have a heavy care burden. Affiliate stigma is the stigma internalized by individuals associated with PWD. Limited research has addressed the affiliate stigma among caregivers of PWD and its influence on caregiver burden. Thus, our study investigated the burden of caregivers of PWD and its relationship with affiliate stigma. In addition, we examined the factors related to affiliate stigma. This cross-sectional study was conducted in a general hospital in Taiwan. We recruited 270 PWD and their family caregivers from the outpatient department. Relevant demographic and clinical assessment data of the patients and caregivers were evaluated. Regression analysis was performed to examine the factors associated with affiliate stigma. In total, 23.7% of the family caregivers had depression and 37.4% had anxiety. Male caregivers had higher levels of anxiety and heavier care burdens related to affiliate stigma compared with female caregivers. Moreover, characteristics such as younger age and low levels of dependence in daily activities among PWD were associated with increased affiliate stigma. A higher family caregiver burden was related to more severe affiliate stigma. Interventions for decreasing the family caregiver burden might reduce the effect of affiliate stigma.

A prospective study on the link between weight-related self-stigma and binge eating: Role of food addiction and psychological distress.

OBJECTIVES: This prospective study investigated the link between weight-related self-stigma and binge eating by (a) examining the temporal association between weight-related self-stigma and binge eating; (b) investigating the mediating role of food addiction in the association between weight-related self-stigma and binge eating; and (c) examining the mediating role of psychological distress in the association between weight-related self-stigma and binge eating. METHOD: Participants comprised 1,497 adolescents (mean = 15.1 years; SD = 6.0). Body mass index and weight bias were assessed at baseline; psychological distress (i.e., depression, anxiety, and stress) assessed and food addiction at 3 months; and binge eating at 6 months. The mediation model was analyzed using Model 4 in the PROCESS macro for SPSS with 10,000 bootstrapping resamples. RESULTS: There was no significant direct association between weight-related self-stigma and binge eating. However, food addiction and psychological distress significantly mediated the association between weight-related self-stigma and binge eating. DISCUSSION: These findings highlight the indirect association between weight-related self-stigma and binge eating via food addiction and psychological distress. Consequently, intervention programs targeting food addiction and psychological distress among adolescents may have significant positive effects on outcomes for weight-related self-stigma and binge eating. The findings will be beneficial to researchers and healthcare professionals working with adolescents during this critical developmental period.

Correlations And Correlates Of Post-Traumatic Growth And Post-Traumatic Stress Symptoms In Patients With Breast Cancer.

PURPOSE: Although post-traumatic growth (PTG) and post-traumatic stress symptoms (PTSS) might develop and coexist after a major trauma, few studies have simultaneously examined them in patients with breast cancer. This study investigated the correlation between PTG and PTSS and their differential correlates in patients with breast cancer. PATIENTS AND METHODS: Overall, 145 patients with breast cancer were recruited. PTG and PTSS were assessed using the PTG inventory and the Chinese version of startle, physiological arousal, anger, and numbness, respectively. We investigated the effects of demographics, chemotherapy, depression, family support, alexithymia, and anxiety symptoms on PTG and PTSS. Multivariate linear regression analyses were performed to select the independent correlates of PTSS and PTG. RESULT: An association was observed between PTG and PTSS (r = 0.21). Based on multiple regression models, the common correlate of PTG (ß = 0.271) and PTSS (ß = 0.212) was anxiety symptoms. Differential independent correlates were years of education (ß = 0.272), receiving chemotherapy (ß = 0.248), and family support (ß = 0.259) for PTG, and chronic pain (ß = 0.316) and poor cognition (ß = -0.350) for PTSS. CONCLUSION: Differential correlates were observed for PTG and PTSS in patients with breast cancer. Possible mechanisms and relationships between PTG and PTSS were discussed.