Thalamocortical Dysconnectivity in Treatment-Resistant Depression.

Thalamocortical connectivity is associated with cognitive and affective processing. The role of thalamocortical connectivity in the pathomechanism of treatment-resistant depression (TRD) remains unclear. This study included 48 patients with TRD and 48 healthy individuals. We investigated thalamocortical connectivity by performing resting-state functional MRI with the bilateral thalamus as the seed. In addition, patients with TRD were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS). Compared with the healthy individuals, the patients with TRD exhibited increased functional connectivity (FC) of the thalamus with the insula and superior temporal cortex and reduced the FC of the thalamus with the anterior paracingulate cortex and cerebellum crus II. Our study may support the crucial role of thalamocortical dysconnectivity in the TRD pathomechanism. However, the small sample size may limit the statistical power. A future study with a large sample size of patients with TRD would be required to validate our findings.

Familial Coaggregation of Suicide, Accidental Death, and Major Psychiatric Disorders in First-Degree Relatives of Individuals Dying Accidentally.

OBJECTIVE: To investigate the risks of suicide, accidental death, and major psychiatric disorders in first-degree relatives (FDRs) of people who die accidentally. Evidence has shown that the endophenotypes of impulsivity and risk-taking are known to coaggregate with major psychiatric disorders, suicide, and accidental deaths within families. METHODS: In total, 136,011 FDRs of individuals who died from accidents and 544,044 individuals matched for age and sex who served as a control group were included in the present study. The relative risks of accidental death and suicide were assessed between these groups. Differences in the frequencies of major psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention deficit hyperactivity disorder (ADHD) between the groups were also identified. RESULTS: The FDRs of individuals who died from accidents were more likely to themselves die from accidents (relative risk [RR] = 4.62) and by suicide (RR = 1.54) compared with individuals in the control group. The FDRs of individuals who died from accidents had an increased risk of developing schizophrenia (RR = 1.24), bipolar disorder (RR = 1.18), major depressive disorder (RR = 1.26), and attention deficit hyperactivity disorder (RR = 1.10) compared with the FDRs of individuals who did not die from accidents. CONCLUSION: Our findings may serve as a reminder to public health officials and clinicians to monitor closely the mental health of the FDRs of individuals who die from accidents.

Association of Titin Polymorphisms with the Progression of Oral Squamous Cell Carcinoma and Its Clinicopathological Characteristics.

This study examined the correlation of titin (TTN) polymorphisms with the sensitivity of oral squamous cell cancer (OSCC) and clinical characteristics. Six TTN SNPs, including rs10497520, rs12463674, rs12465459, rs2042996, rs2244492, and rs2303838, were evaluated in 322 control groups and 606 patients with oral cancer. We then investigated whether the SNP genotypes rs10497520 had associations with clinical pathological categories. Our data showed that the TC + CC genotype of rs10497520 was associated with moderate/poor tumor cell differentiation. The carriers of TTN rs10497520 polymorphic variant "TC + CC" in OSCC patients with cigarette smoking were linked with poor tumor differentiation (p = 0.008). Our results suggest that the TTN SNP rs10497520 is a possible genetic marker for oral cancer patients in the cigarette-smoking population. The TTN rs10497520 polymorphisms may be essential biomarkers to predict the onset and prognosis of oral cancer disease.

Distinct Effects of Major Affective Disorder Diagnoses and Suicidal Symptom Severity on Inhibitory Control Function and Proinflammatory Cytokines: Single-Site Analysis of 800 Adolescents and Adults.

BACKGROUND: Inhibitory control function and proinflammatory cytokines play a role in the pathomechanisms underlying major affective disorders and suicidal behavior. However, the distinct or interactive effects of major affective disorders and suicidal symptom severity on inhibitory control function and proinflammatory cytokines remain unclear. METHODS: This study included 287 patients with bipolar disorder, 344 with major depressive disorder, and 169 healthy controls. We categorized the participants into 3 groups based on Montgomery-Åsberg Depression Rating Scale (MADRS) item 10 (suicidal symptoms) score: 0, 2 or 3, and ≥4. The participants completed the go/no-go task and the measurements for C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) levels. RESULTS: Errors in the go/no-go task were associated with suicidality (P = .040), regardless of the severity of suicidal symptoms and diagnosis. An elevated CRP level was especially associated with a Montgomery-Åsberg Depression Rating Scale item 10 score ≥4 (P = .001). An increased TNF-α level could distinguish bipolar disorder from major depressive disorder (P < .001). DISCUSSION: Our study indicated the distinct effects of major affective disorder diagnosis and suicide symptom severity on inhibitory control function and CRP and TNF-α levels. Importantly, individuals with the poorest inhibitory control function and highest CRP levels had more severe suicidal symptoms.

Obsessive-compulsive disorder and suicide: a longitudinal study in Taiwan.

AIMS: Research evidence has established an association of obsessive-compulsive disorder (OCD) with suicidal thoughts and suicide attempts. However, further investigation is required to determine whether individuals with OCD have higher risk of death by suicide compared with those without OCD. METHODS: Of the entire Taiwanese population, between 2003 and 2017, 56,977 individuals with OCD were identified; they were then matched at a 1:4 ratio with 227,908 non-OCD individuals on the basis of their birth year and sex. Suicide mortality was assessed between 2003 and 2017 for both groups. Time-dependent Cox regression models were used to investigate the difference in suicide risk between individuals with versus without OCD. RESULTS: After adjustment for major psychiatric comorbidities (i.e., schizophrenia, bipolar disorder and major depressive disorder), the OCD group had higher risk of suicide (hazard ratio: 1.97, 95% confidence interval: 1.57-2.48) during the follow-up compared with the comparison group. Furthermore, OCD severity, as indicated by psychiatric hospitalizations due to OCD, was positively correlated with suicide risk. CONCLUSIONS: Regardless of the existence of major psychiatric comorbidities, OCD was found to be an independent risk factor for death by suicide. A suicide prevention program specific to individuals with OCD may be developed in clinical practice in the future.

Congenital hypothyroidism and risk of subsequent autism spectrum disorder and attention-deficit/hyperactivity disorder in Taiwan.

AIM: Evidence suggests an association between maternal hypothyroidism and risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in offspring. We examined the risk of ASD and ADHD in individuals with congenital hypothyroidism (CHT). METHODS: A nationwide population-based cohort study enrolled a total of 1260 children younger than 12 years with a confirmed diagnosis of CHT and no prior diagnosis of any neurodevelopmental disorders, selected from the National Health Insurance Research Database of Taiwan between 1998 to 2013. In addition, 12,600 controls matched for sex, age, and residence were selected. Cox proportional hazards analysis was used to investigate the association among CHT, ASD, and ADHD. RESULTS: Children with CHT were associated with a higher incidence of ASD (7.1‰ vs 1.3‰, P < 0.001) and ADHD (39.7‰ vs 18.7‰, P < 0.001) than the control group. Cox regression analyses demonstrated that children with CHT were associated with elevated risks of ASD (hazard ratio [HR], 4.72 [95% confidence interval (CI), 2.08-10.70]) and ADHD (HR, 2.03 [95% CI, 1.49-2.77]), after adjusting for demographic data and family history of major psychiatric disorders, compared with the control group. CONCLUSION: Children with CHT were associated with approximately a two-fold increased risk of ADHD and a four-fold increased risk of ASD than the control group. Our study highlights the need for future research to elucidate the potential pathophysiology among CHD, ASD, and ADHD.

The I4790K mutation of the ryanodine receptor is responsible for anthranilic diamide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae).

Insecticide resistance in Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae) is a major constraint on the global production of cruciferous crops. For effective management of insecticide resistance, it is necessary to develop a molecular detection tool for predicting insecticide resistance levels based on the mutation frequency of target sites. In this study, a susceptible strain (SHggt) of P. xylostella was subjected to chlorantraniliprole and tetraniliprole selection under laboratory conditions to obtain the CHLSel and TETSel strains, respectively, to determine their resistance development, cross-resistance and mutation frequencies of the P. xylostella ryanodine receptor (PxRyR). In addition, the tetraniliprole resistance and the mutation frequencies of the PxRyR from 7 field populations were evaluated. Continuous selection over 30 generations resulted in resistance ratios (RRs) of 7,073.2-fold and 6,971.0-fold for the CHLSel and TETSel strains, respectively, and thousandfold increases in cross-resistance to unexposed diamides, e.g., cyantraniliprole and flubendiamide, were observed. For the field populations, three out of seven populations have developed more than thousandfold resistance to tetraniliprole. Among the three investigated target site mutations in PxRyR, only I4790K was detected in both laboratory-selected strains. However, 2 mutations, I4790K and G4946E, were detected in field populations. A positive correlation between RRs and K allele frequencies was observed in the laboratory-selected/relaxed strains and field populations of P. xylostella. These results suggest a possible link between the development of anthranilic diamide resistance and the frequency of the PxRyR I4790K mutation, which can be used to develop effective strategies for diamide resistance management in P. xylostella.

Cognitive impairment and depression precede increased HDL-C levels in middle-aged and older Chinese adults: cross-lagged panel analyses.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.

Familial coaggregation of major psychiatric disorders and neurodevelopmental disorders among first-degree relatives of individuals with generalized anxiety disorder.

BACKGROUND: Anxiety disorders, major psychiatric disorders (e.g., schizophrenia and major affective disorders), and neurodevelopmental disorders (e.g., autism and attention-deficit/hyperactivity disorder [ADHD]) may cluster together within families. However, whether the first-degree relatives (FDRs) of individuals with generalized anxiety disorder (GAD) are at an elevated risk of neurodevelopmental or major psychiatric disorders remains unknown. METHODS: We identified 2,378,190 FDRs of patients with GAD and 9,512,760 birth year-matched and sex-matched controls from Taiwan's National Health Insurance Research Database. Neurodevelopmental disorders, including autism and ADHD, and major psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, and GAD, were identified. RESULTS: The FDRs-parents, offspring, and siblings-of individuals with GAD were more likely to be diagnosed as having schizophrenia (relative risk: 1.22), bipolar disorder (1.36), major depressive disorder (1.29), autism (1.20), ADHD (1.52), obsessive-compulsive disorder (1.21), and GAD (1.61) than are the FDRs of individuals without GAD. CONCLUSION: Our findings support the notion of a familial coaggregation between GAD, major psychiatric disorders, and neurodevelopmental disorders. Future studies should elucidate the definitive genetic etiology of this familial coaggregation.

All-cause and suicide mortality after first psychiatric admission in adolescents and young adults: A longitudinal follow-up study.

BACKGROUND: This study investigated all-cause and suicide mortality rates in adolescents and young adults following an initial psychiatric admission to elucidate the long-term outcomes for this vulnerable group by focusing on the risks associated with various psychiatric diagnostic categories. METHODS: This study involved 9762 adolescents and young adults discharged from their first psychiatric admission and matched 1:1 with 9762 individuals discharged following a diagnosis of appendicitis on the basis of birth year and sex by using Taiwan's National Health Insurance Research Database. Both stratified (model 1) and standard (model 2) Cox regression analyses were conducted to assess variations in all-cause and suicide mortality between the groups. RESULTS: Over the 15-year follow-up period, the adolescents and young adults discharged from their first psychiatric admission exhibited an approximately 3-fold increased risk of death from any cause (hazard ratio [HR]: 2.97 in model 1, 2.83 in model 2) and an approximately ten times higher risk of suicide (11.13 in model 1, 9.23 in model 2) compared with those discharged with a diagnosis of appendicitis. Those discharged with alcohol use disorder or major depressive disorder exhibited higher hazard ratios for both all-cause and suicide compared with the reference group. CONCLUSIONS: The findings reveal a considerable risk of all-cause and suicide mortality in adolescents and young adults following discharge from their first psychiatric admission. These results highlight an urgent need for tailored interventions and continued support for this demographic.

A survey of the participants' learning outcomes after finishing the dental radiology course for the continuing education of medical radiation technologists in Taiwan.

Background/purpose: In Taiwan, there are very few dental radiology curricula in medical radiation education system. This study assessed the participants' learning outcomes after finishing the dental radiology course for the continuing education of medical radiation technologists in Taiwan. Materials and methods: This study used the questionnaire survey to evaluate the participants' learning outcomes after finishing the dental radiology course for the continuing education of medical radiation technologists in Taiwan. Results: In this study, 85 participants filled out the questionnaires completely after finishing the dental radiology course. The majority of participants agreed that dental radiology courses were rare in the medical radiation school curricula and the continuing education courses of medical radiation technologists. Moreover, most of participants found this course to be helpful in raising their basic knowledge about the dental radiology, their attitude towards the dental radiology, and their interest in further learning of the dental radiology. They were satisfied with the courses. The degree of agreement for each question was high with all the mean scores for each question being between 3.87 and 4.61. The numbers (rates) of respondents who answered as agree were between 58 (68.24%) and 84 (98.82%). Conclusion: The dental radiology course for the continuing education of medical radiation technologists is found to increase the participants' basic knowledge about the dental radiology, and their awareness and understanding of the radiation protection in dental radiography. Thus, this model can be further used for the dental radiology course for the continuing education of medical radiation technologists in Taiwan.

Pyrocurzerenone suppresses human oral cancer cell metastasis by inhibiting the expression of ERK1/2 and cathepsin S proteins.

Pyrocurzerenone is a natural compound found in Curcuma zedoaria and Chloranthus serratus. However, the anticancer effect of pyrocurzerenone in oral cancer remains unclear. Using the MTT assay, wound healing assay, transwell assay and western blot analysis, we investigated the impact of pyrocurzerenone on antimetastatic activity, as well as the critical signalling pathways that underlie the processes of oral cancer cell lines SCC-9, SCC-1 and SAS in this work. Our findings suggested that pyrocurzerenone inhibits cell migration and invasion ability in oral cancer cell lines. Furthermore, phosphorylation of ERK1/2 had significant inhibitory effects in SCC-9 and SCC-1 cell lines. Combining ERK1/2 inhibitors with pyrocurzerenone decreased the migration and invasion activity of SCC-9 and SCC-1 cell lines. We also found that the expressed level of cathepsin S decreased under pyrocurzerenone treatment. This study showed that pyrocurzerenone reduced ERK1/2 expression of the proteins and cathepsin S, suggesting that it could be a valuable treatment to inhibit human oral cancer cell metastasis.

Risk of Neurodevelopmental Disorders in Offspring of Parents with Major Depressive Disorder: A Birth Cohort Study.

Studies have reported inconsistent results regarding associations between parental depression and offspring neurodevelopmental disorders, such as developmental delay and autism spectrum disorder (ASD). In all, 7,593 children who were born between 1996 and 2010 in Taiwan and had at least one parent with major depressive disorder and 75,930 birth-year- and sex-matched children of parents without major depressive disorder were followed from 1996 or time of birth to the end of 2011. Intergroup differences in neurodevelopmental conditions-including ASD, attention-deficit hyperactivity disorder (ADHD), tic disorder, developmental delay, and intellectual disability (ID)-were assessed. Compared with the children in the control group, the children of parents with major depression were more likely [hazard ratio (HR), 95% confidence interval (CI)] to develop ADHD (1.98, 1.80-2.18), ASD (1.52, 1.16-1.94), tic disorder (1.40, 1.08-1.81), developmental delay (1.32, 1.20-1.45), and ID (1.26, 1.02-1.55). Parental depression was associated with offspring neurodevelopmental disorders, specifically ASD, ADHD, developmental delay, ID, and tic disorder. Therefore, clinicians should closely monitor the neurodevelopmental conditions of children of parents with depression.

Nonlocal meta-lens with Huygens' bound states in the continuum.

Meta-lenses composed of artificial meta-atoms have stimulated substantial interest due to their compact and flexible wavefront shaping capabilities, outperforming bulk optical devices. The operating bandwidth is a critical factor determining the meta-lens' performance across various wavelengths. Meta-lenses that operate in a narrowband manner relying on nonlocal effects can effectively reduce disturbance and crosstalk from non-resonant wavelengths, making them well-suitable for specialized applications such as nonlinear generation and augmented reality/virtual reality display. However, nonlocal meta-lenses require striking a balance between local phase manipulation and nonlocal resonance excitation, which involves trade-offs among factors like quality-factor, efficiency, manipulation dimensions, and footprint. In this work, we experimentally demonstrate the nonlocal meta-lens featuring Huygens' bound states in the continuum (BICs) and its near-infrared imaging application. All-dielectric integrated-resonant unit is particularly optimized to efficiently induce both the quasi-BIC and generalized Kerker effect, while ensuring the rotation-angle robustness for generating geometric phase. The experimental results show that the single-layer nonlocal Huygens' meta-lens possesses a high quality-factor of 104 and achieves a transmission polarization conversion efficiency of 55%, exceeding the theoretical limit of 25%. The wavelength-selective two-dimensional focusing and imaging are demonstrated as well. This work will pave the way for efficient nonlocal wavefront shaping and meta-devices.

Inhibition of Tumoral VISTA to Overcome TKI Resistance via Downregulation of the AKT/mTOR and JAK2/STAT5 Pathways in Chronic Myeloid Leukemia.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Risk of Periodontitis in Adolescents With Attention Deficit Hyperactivity Disorder: A Cohort Study of 81,055 Participants.

OBJECTIVES: Previous studies have demonstrated poor oral hygiene in children with attention deficit hyperactivity disorder (ADHD). However, the association between ADHD and periodontitis is still unclear. METHODS: In all, 16,211 adolescents with ADHD and 162,110 age- and sex-matched controls participated in the study between 2001 and 2011. To identify the occurrence of periodontitis, the participants were followed up till the end of 2011. Confounding factors, including smoking, diabetes, and depressive disorder, were assessed and adjusted in the Cox regression models. RESULTS: Adolescents with ADHD (HR: 2.29) were more likely to develop periodontitis later in life than controls. We additionally observed the beneficial effect of atomoxetine (HR: 0.42) on the periodontitis risk among adolescents with ADHD. However, this finding should be interpreted cautiously given the small sample (n = 290) of children taking atomoxetine in the present study. CONCLUSIONS: ADHD is an independent risk factor for subsequent periodontitis development. Oral health should be closely monitored in adolescents with ADHD. Future investigation of the shared pathomechanisms between periodontitis and ADHD is warranted.

Raddeanin A augments the cytotoxicity of natural killer cells against chronic myeloid leukaemia cells by modulating MAPK and Ras/Raf signalling pathways.

Natural killer (NK) cell therapy, a developing approach in cancer immunotherapy, involves isolating NK cells from peripheral blood. However, due to their limited number and activity, it is essential to significantly expand these primary NK cells and enhance their cytotoxicity. In this study, we investigated how Raddeanin A potentiate NK activity using KHYG-1 cells. The results indicated that Raddeanin A increased the expression levels of cytolytic molecules such as perforin, granzymes A and granzymes B, granulysin and FasL in KHYG-1 cells. Raddeanin A treatment increased CREB phosphorylation, p65 phosphorylation, NFAT1 and acetyl-histone H3 expression. Raddeanin A elevated caspase 3 and PARP cleavage, increased t-Bid expression, promoting apoptosis in K562 cells. Furthermore, it reduced the expression of HMGB2, SET and Ape1, impairing the DNA repair process and causing K562 cells to die caspase-independently. Additionally, Raddeanin A increased ERK, p38 and JNK phosphorylation at the molecular level, which increased granzyme B production in KHYG-1 cells. Raddeanin A treatment increased Ras, Raf phosphorylation, MEK phosphorylation, NKG2D, NKp44 and NKp30 expression in KHYG-1 cells. Collectively, our data indicate that Raddeanin A enhances the cytotoxic activity of NK cells against different cancer cells.