Enhancing Early Diagnosis of Bipolar Disorder in Adolescents through Multimodal Neuroimaging.

BACKGROUND: Bipolar Disorder (BD), a severe neuropsychiatric condition, often appears during adolescence. Traditional diagnostic methods, which primarily relying on clinical interviews and single-modal MRI techniques, may have limitations in accuracy. This study aimed to improve adolescent BD diagnosis by integrating behavioral assessments with multimodal MRI. We hypothesized that this combination would enhance diagnostic accuracy for at-risk adolescents. METHODS: A retrospective cohort of 309 subjects, including BD patients, offspring of BD patients (with and without subthreshold symptoms), non-BD offspring with subthreshold symptoms, and healthy controls, was analysed. Behavioral attributes were integrated with MRI features from T1, rsfMRI, and DTI. Three diagnostic models were developed using GLMNET multinomial regression: a clinical diagnosis model based on behavioral attributes, an MRI-based model, and a comprehensive model integrating both datasets. RESULTS: The comprehensive model achieved a prediction accuracy of 0.83 (CI: [0.72, 0.92]), significantly higher than the clinical (0.75) and MRI-based (0.65) models. Validation with an external cohort showed high accuracy (0.89, AUC=0.95). Structural equation modelling revealed that Clinical Diagnosis (ß=0.487, p<0.0001), Parental BD History (ß=-0.380, p<0.0001), and Global Function (ß=0.578, p<0.0001) significantly impacted Brain Health, while Psychiatric Symptoms showed only a marginal influence (ß=-0.112, p=0.056). CONCLUSION: This study highlights the value of integrating multimodal MRI with behavioral assessments for early diagnosis in at-risk adolescents. Combining neuroimaging enables more accurate patient subgroup distinctions, facilitating timely interventions and improving health outcomes. Our findings suggest a paradigm shift in BD diagnostics, advocating for incorporating advanced imaging techniques in routine evaluations.

Establishment of a corneal ulcer prognostic model based on machine learning.

Corneal infection is a major public health concern worldwide and the most common cause of unilateral corneal blindness. Toxic effects of different microorganisms, such as bacteria and fungi, worsen keratitis leading to corneal perforation even with optimal drug treatment. The cornea forms the main refractive surface of the eye. Diseases affecting the cornea can cause severe visual impairment. Therefore, it is crucial to analyze the risk of corneal perforation and visual impairment in corneal ulcer patients for making early treatment strategies. The modeling of a fully automated prognostic model system was performed in two parts. In the first part, the dataset contained 4973 slit lamp images of corneal ulcer patients in three centers. A deep learning model was developed and tested for segmenting and classifying five lesions (corneal ulcer, corneal scar, hypopyon, corneal descementocele, and corneal neovascularization) in the eyes of corneal ulcer patients. Further, hierarchical quantification was carried out based on policy rules. In the second part, the dataset included clinical data (name, gender, age, best corrected visual acuity, and type of corneal ulcer) of 240 patients with corneal ulcers and respective 1010 slit lamp images under two light sources (natural light and cobalt blue light). The slit lamp images were then quantified hierarchically according to the policy rules developed in the first part of the modeling. Combining the above clinical data, the features were used to build the final prognostic model system for corneal ulcer perforation outcome and visual impairment using machine learning algorithms such as XGBoost, LightGBM. The ROC curve area (AUC value) evaluated the model's performance. For segmentation of the five lesions, the accuracy rates of hypopyon, descemetocele, corneal ulcer under blue light, and corneal neovascularization were 96.86, 91.64, 90.51, and 93.97, respectively. For the corneal scar lesion classification, the accuracy rate of the final model was 69.76. The XGBoost model performed the best in predicting the 1-month prognosis of patients, with an AUC of 0.81 (95% CI 0.63-1.00) for ulcer perforation and an AUC of 0.77 (95% CI 0.63-0.91) for visual impairment. In predicting the 3-month prognosis of patients, the XGBoost model received the best AUC of 0.97 (95% CI 0.92-1.00) for ulcer perforation, while the LightGBM model achieved the best performance with an AUC of 0.98 (95% CI 0.94-1.00) for visual impairment.

A Preliminary Study of Brain Developmental Features of Bipolar Disorder Familial Risk and Subthreshold Symptoms.

BACKGROUND: Risk for bipolar disorder (BD) is increased among individuals with a family history or subthreshold mood symptoms. However, the brain structural developments associated with these BD risks remain unknown. METHODS: This longitudinal cohort study examined the brain gray matter volume (GMV) developmental features of familial and symptomatic risks for BD and their associations with participants' global function levels. We recruited unaffected BD offspring with (n = 26, 14 female, mean ± SD age = 14.9 ± 2.9 years) or without (n = 35, 19 female, age = 15.3 ± 2.7 years) subthreshold manic or depressive symptoms and unaffected non-BD offspring with (n = 49, 30 female, age = 14.5 ± 2.2 years) or without (n = 68, 37 female, age = 15.0 ± 2.3 years) symptoms. The offspring had no mood disorder diagnosis prior to the study. The average follow-up duration was 2.63 ± 1.63 years. RESULTS: At baseline, we found significant interactive effects of familial risk and subthreshold symptoms that indicated that the symptomatic offspring exhibited markedly large GMV in the brain affective and cognitive circuitries. During follow-up, the combined group of BD offspring (symptomatic and nonsymptomatic) displayed a more accelerated GMV decrease than BD nonoffspring in the hippocampus and anterior cingulate cortex. In contrast, the combined group of symptomatic participants (offspring and nonoffspring) displayed a slower GMV decrease than nonsymptomatic participants in the ventromedial prefrontal cortex. Larger GMV at baseline and accelerated GMV decrease during follow-up prospectively and longitudinally predicted positive global function changes. All results survived multiple testing correction. CONCLUSIONS: These findings indicated that familial and symptomatic risks of BD are associated with distinct brain structural developments and unraveled key brain developmental features of particularly vulnerable high-risk individuals to subsequent functional deterioration.

DivIVA Interacts with the Cell Wall Hydrolase MltG To Regulate Peptidoglycan Synthesis in Streptococcus suis.

Bacterial morphology is largely determined by the spatial and temporal regulation of peptidoglycan (PG) biosynthesis. Ovococci possess a unique pattern of PG synthesis different from the well studied Bacillus, and the mechanism of the coordination of PG synthesis remains poorly understood. Several regulatory proteins have been identified to be involved in the regulation of ovococcal morphogenesis, among which DivIVA is an important one to regulate PG synthesis in streptococci, while its mechanism is largely unknown. Here, the zoonotic pathogen Streptococcus suis was used to investigate the regulation of DivIVA on PG synthesis. Fluorescent d-amino acid probing and 3D-structured illumination microscopy found that DivIVA deletion caused abortive peripheral PG synthesis, resulting in a decreased aspect ratio. The phosphorylation-depleted mutant (DivIVA3A) cells displayed a longer nascent PG and became longer, whereas the phosphorylation-mimicking mutant (DivIVA3E) cells showed a shorter nascent PG and became shorter, suggesting that DivIVA phosphorylation is involved in regulating peripheral PG synthesis. Several DivIVA-interacting proteins were identified, and the interaction was confirmed between DivIVA and MltG, a cell wall hydrolase essential for cell elongation. DivIVA did not affect the PG hydrolysis activity of MltG, while the phosphorylation state of DivIVA affected its interaction with MltG. MltG was mislocalized in the ΔdivIVA and DivIVA3E cells, and both ΔmltG and DivIVA3E cells formed significantly rounder cells, indicating an important role of DivIVA phosphorylation in regulating PG synthesis through MltG. These findings highlight the regulatory mechanism of PG synthesis and morphogenesis of ovococci. IMPORTANCE The peptidoglycan (PG) biosynthesis pathway provides a rich source of novel antimicrobial drug targets. However, bacterial PG synthesis and its regulation is a very complex process involving dozens of proteins. Moreover, unlike the well studied Bacillus, ovococci undergo unusual PG synthesis with unique mechanisms of coordination. DivIVA is an important regulator of PG synthesis in ovococci, while its exact role in regulating PG synthesis remains poorly understood. In this study, we determined the role of DivIVA in regulating lateral PG synthesis of Streptococcus suis and identified a critical interacting partner, MltG, in which DivIVA influenced the subcellular localizations of MltG through its phosphorylation. Our study characterizes the detailed role of DivIVA in regulating bacterial PG synthesis, which is very helpful for understanding the process of PG synthesis in streptococci.

Discovery of a highly efficient TylF methyltransferase via random mutagenesis for improving tylosin production.

Macrolides are currently a class of extensively used antibiotics in human and animal medicine. Tylosin is not only one of the most important veterinary macrolides but also an indispensable material for the bio- and chemo-synthesis of new generations of macrolide antibiotics. Thus, improving its production yield is of great value. As the key rate-limiting enzyme catalyzing the terminal step of tylosin biosynthesis in Streptomyces fradiae (S. fradiae), TylF methyltransferase's catalytic activity directly affects tylosin yield. In this study, a tylF mutant library of S. fradiae SF-3 was constructed based on error-prone PCR technology. After two steps of screening in 24-well plates and conical flask fermentation and enzyme activity assay, a mutant strain was identified with higher TylF activity and tylosin yield. The mutation of tyrosine to phenylalanine is localized at the 139th amino acid residue on TylF (TylFY139F), and protein structure simulations demonstrated that this mutation changed the protein structure of TylF. Compared with wild-type protein TylF, TylFY139F exhibited higher enzymatic activity and thermostability. More importantly, the Y139 residue in TylF is a previously unidentified position required for TylF activity and tylosin production in S. fradiae, indicating the further potential to engineer the enzyme. These findings provide helpful information for the directed molecular evolution of this important enzyme and the genetic modification of tylosin-producing bacteria.

Oral voriconazole monotherapy for fungal keratitis: efficacy, safety, and factors associated with outcomes.

Purpose: To provide preliminary data on the efficacy and safety of oral voriconazole (VCZ) as a primary treatment for fungal keratitis (FK). Method: We performed a retrospective histopathological analysis of data on 90 patients with FK at The First Affiliated Hospital of Guangxi Medical University between September 2018 and February 2022. We recorded three outcomes: corneal epithelial healing, visual acuity (VA) improvement, and corneal perforation. Independent predictors were identified using univariate analysis, and multivariate logistic regression analysis was used to identify independent predictive factors associated with the three outcomes. The area under the curve was used to evaluate the predictive value of these factors. Results: Ninety patients were treated with VCZ tablets as the only antifungal drug. Overall, 71.1% (n = 64) of the patients had extreme corneal epithelial healing, 56.7% (n = 51) showed an improvement in VA, and 14.4% (n = 13) developed perforation during treatment. Non-cured patients were more likely to have large ulcers (≥5 × 5 mm2) and hypopyon. Conclusion: The results indicated that oral VCZ monotherapy was successful in the patients with FK in our study. Patients with ulcers larger than 5 × 5 mm2 and hypopyon were less likely to respond to this treatment.

Anti-oomycete ability of scopolamine against Phytophthora infestans, a terrible pathogen of potato late blight.

BACKGROUND: Phytophthora infestans causes late blight, threatening potato production. The tropane alkaloid scopolamine from some industrial plants (Datura, Atropa, etc.) has a broad-spectrum bacteriostatic effect, but its effect on P. infestans is unknown. RESULTS: In the present study, scopolamine inhibited the mycelial growth of phytopathogenic oomycete P. infestans, and the half-maximal inhibitory concentration (IC50 ) was 4.25 g L-1 . The sporangia germination rates were 61.43%, 16.16%, and 3.99% at concentrations of zero (control), 0.5 IC50 , and IC50 , respectively. The sporangia viability of P. infestans was significantly reduced after scopolamine treatment through propidium iodide and fluorescein diacetate staining, speculating that scopolamine destroyed cell membrane integrity. The detached potato tuber experiment demonstrated that scopolamine lessened the pathogenicity of P. infestans in potato tubers. Under stress conditions, scopolamine showed good inhibition of P. infestans, indicating that scopolamine could be used in multiple adverse conditions. The combination effect of scopolamine and the chemical pesticide Infinito on P. infestans was more effective than the use of scopolamine or Infinito alone. Moreover, transcriptome analysis suggested that scopolamine leaded to a downregulation of most P. infestans genes, functioning in cell growth, cell metabolism, and pathogenicity. CONCLUSION: To our knowledge, this is the first study to detect scopolamine inhibitory activity against P. infestans. Also, our findings highlight the potential of scopolamine as an eco-friendly option for controlling late blight in the future. © 2023 Society of Chemical Industry.

Global trends and prospects in research of artificial cornea over past 20 years: a bibliometric and visualized analysis.

BACKGROUND: Many studies have been focused on the area of the artificial cornea. In our study, a bibliometric analysis was performed on the artificial cornea to identify the global key research fields and trends over the past 20 years. METHODS: Publications about artificial cornea were retrieved and downloaded from the Web of Science Core Collection from 2002 to 2021. CiteSpace and VOSviewer were used to analyze countries, institutions, authors, and related research areas. RESULTS: A total of 829 eligible publications were analyzed. The USA was the most productive country for the artificial cornea, followed by China and Canada. Harvard University was the most prolific institution in this field. Cornea published most of the studies in this area and Dohlman CH was the most cited author. CONCLUSIONS: Bibliometric analysis in our study first provides a general perspective on the artificial cornea, which can be helpful to further explore the issues in the rapidly developing area.

Global hippocampus functional connectivity as a predictive neural marker for conversion to future mood disorder in unaffected offspring of bipolar disorder parents.

OBJECTIVES: Hippocampus-related functional alteration in genetically at-risk individuals may reflect an endophenotype of a mood disorder. Herein, we performed a prospective study to investigate whether baseline hippocampus functional connectivity (FC) in offspring of patients with bipolar disorder (BD) would predict subsequent conversion to mood disorder. METHODS: Eighty bipolar offspring and 40 matched normal controls (NC) underwent resting state functional MRI (rsfMRI) scanning on a 3.0 Tesla MR scanner. The offspring were subdivided into asymptomatic offspring (AO) (n = 41) and symptomatic offspring (SO) (n = 39) according to whether they manifested subthreshold mood symptoms. After identifying the different hippocampus FCs between the AO and SO, a logistic regression analysis was conducted to investigate whether the baseline hippocampus FCs predicted a future mood disorder during a 6-year follow-up. RESULTS: We identified seven baseline para/hippocampus FCs that showed differences between AO and SO, which were entered as predictive features in the logistic regressive model. Of the 80 bipolar offspring entering the analysis, the FCs between left hippocampus and left precuneus, and between right hippocampus and left posterior cingulate, showed a discriminative capacity for predicting future mood disorder (area-under-curve, or AUC=75.76 % and 75.00 % respectively), and for predicting BD onset (AUC=77.46 % and 81.63 %, respectively). CONCLUSIONS: The present findings revealed high predictive utility of the hippocampus resting state FCs for future mood disorder and BD onset in individuals at familial risk. These neural markers can potentially improve early detection of individuals carrying particularly high risk for future mood disorder.

Differential Relationships Among C-Reactive Protein, Attention Functioning, and Brain Structure in Bipolar Offspring With and Without Subthreshold Mood Symptoms.

Background: Bipolar disorder (BD) is a highly heritable mood disorder. Activated low-grade inflammation may not only play an adverse role in the pathophysiology of BD, but also contribute to a resilience process. The neuroinflammatory processes may underlie the attention deficit and alteration of gray matter volume (GMV) in the early stage and premorbid period of BD. Also, the differential inflammation-brain relationship may be identified as biological markers for BD pathology or resilience.Methods: The present data were collected between March 2013 and June 2016. Sixty-four offspring of BD patients were recruited and subdivided into asymptomatic (n = 33, mean age = 17.8 years) and symptomatic (n = 31, mean age = 16.2 years) groups according to whether they manifested subthreshold mood symptoms. The diagnosis of BD was confirmed according to DSM-IV criteria. C-reactive protein (CRP) level, attention functioning, and GMV data were measured by ELISA, the Continuous Performance Test-Identical Pair test (CPT-IP), and 3.0 T magnetic resonance imaging, respectively. Their relationships were examined with mediation and moderation analyses.Results: We observed a higher level of CRP and poorer attention in the symptomatic group than the asymptomatic group and found a significant group × CRP interactive effect on GMV in regions spanning right precentral and postcentral gyri (P = .043). CRP levels negatively mediated the relationship between the group and CPT-IP scores, and the group marginally moderated the relationship between pre/postcentral gyri volumes and CPT-IP scores (P = .05).Conclusions: Symptomatic and asymptomatic bipolar offspring manifested differential inflammation-GMV-attention relationships, which may represent, respectively, an endophenotype or a resilience process for BD.

Prevalence and Incidence of Dry Eye Disease in Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Dry eye disease (DED) is the most common ocular surface disease, which severely affects the quality of life. An overall estimate of the prevalence, incidence, and risk factors of DED in Asia would help in planning and implementing appropriate public health strategies. OBJECTIVES: The present study aimed to study the epidemiology of DED in Asia. METHODS: A comprehensive and systematic search was performed using several databases, including PubMed, Cochrane Library, and Web of Science, in January 2021. A random-effects meta-analysis was performed on logit-transformed prevalence and incidence rates to calculate pooled prevalence and incidence estimates. Meta-regression and subgroup analyses were performed to explain the heterogeneity. RESULTS: Among the 6,742 articles identified, 23 were included in the analysis, with a total sample size of 1,488,935 subjects. Twenty studies reported the prevalence of DED in Asia, two studies reported the incidence, and one study reported both prevalence and incidence. The estimated pooled prevalence of DED in any population in Asia was 20.1% (95% confidence interval [Ozdemir et al., Acta Ophthalmol. 2019;97(1):e91-6]: 13.9-28.3%), and the incidence 16.7% (95% CI: 0-34.9%). The prevalence rate of DED in males and females was 16.4% (95% CI: 10.0-25.8%) and 21.7% (95% CI: 14.7-30.8%; p < 0.001), respectively. In general, the prevalence increased with age. The risk factors considered for specific populations were not significant, and the prevalence in the general population, excluding the populations considered at risk, was similar at 20.9% (95% CI: 12.8-32.1%). CONCLUSIONS: DED is common in Asian populations and causes a significant disease burden. Its prevalence is higher in females than that in males, and it tends to increase in severity with age. Further research on additional risk factors is needed to adequately explain the epidemiology of DED in Asia.

Development and Application of Two Inducible Expression Systems for Streptococcus suis.

Streptococcus suis is an important zoonotic bacterial pathogen posing a threat to the pig industry as well as public health, for which the mechanisms of growth and cell division remain largely unknown. Developing convenient genetic tools that can achieve strictly controlled gene expression is of great value for investigating these fundamental physiological processes of S. suis. In this study, we first identified three strong constitutive promoters, Pg, Pt, and Pe, in S. suis. Promoter Pg was used to drive the expression of repressor genes tetR and lacI, and the operator sequences were added within promoters Pt and Pe. By optimizing the insertion sites of the operator sequence, we successfully constructed an anhydrotetracycline (ATc)-inducible expression system and an isopropyl-ß-d-thiogalactopyranoside (IPTG)-inducible expression system in S. suis. We showed that these two systems provided inducer-concentration- and induction-time-dependent expression of the reporter gene. By using these tools, we investigated the subcellular localization of a key cell division protein, FtsZ, which showed that it could be correctly localized to the midcell region. In addition, we constructed a conditional knockout strain for the glmS gene, which is an essential gene, and showed that our ATc-inducible promoter could provide strictly controlled expression of glmS in trans, suggesting that our inducible expression systems can be used for deletion of essential genes in S. suis. Therefore, for the first time we developed two inducible expression systems in S. suis and showed their applications in the study of an important cell division protein and an essential gene. These genetic tools will further facilitate the functional study of other important genes of S. suis. IMPORTANCE Streptococcus suis is an important zoonotic bacterial pathogen. Studying the mechanisms of cell growth and division is important for the identification of novel antimicrobial drug targets. Inducible expression systems can provide strictly controlled expression of the protein of interest and are useful tools to study the functions of physiologically important proteins. However, there is a lack of convenient genetic tools that can achieve inducible protein expression in S. suis. In this study, we developed two (ATc-inducible and IPTG-inducible) inducible expression systems and showed their applications in a subcellular localization study of a cell division protein and the construction of conditional knockout of essential genes in S. suis. These systems will be useful for functional studies of important proteins of S. suis.

IPA-3: An Inhibitor of Diadenylate Cyclase of Streptococcus suis with Potent Antimicrobial Activity.

Antimicrobial resistance (AMR) poses a huge threat to public health. The development of novel antibiotics is an effective strategy to tackle AMR. Cyclic diadenylate monophosphate (c-di-AMP) has recently been identified as an essential signal molecule for some important bacterial pathogens involved in various bacterial physiological processes, leading to its synthase diadenylate cyclase becoming an attractive antimicrobial drug target. In this study, based on the enzymatic activity of diadenylate cyclase of Streptococcus suis (ssDacA), we established a high-throughput method of screening for ssDacA inhibitors. Primary screening with a compound library containing 1133 compounds identified IPA-3 (2,2'-dihydroxy-1,1'-dinapthyldisulfide) as an ssDacA inhibitor. High-performance liquid chromatography (HPLC) analysis further indicated that IPA-3 could inhibit the production of c-di-AMP by ssDacA in vitro in a dose-dependent manner. Notably, it was demonstrated that IPA-3 could significantly inhibit the growth of several Gram-positive bacteria which harbor an essential diadenylate cyclase but not E. coli, which is devoid of the enzyme, or Streptococcus mutans, in which the diadenylate cyclase is not essential. Additionally, the binding site in ssDacA for IPA-3 was predicted by molecular docking, and contains residues that are relatively conserved in diadenylate cyclase of Gram-positive bacteria. Collectively, our results illustrate the feasibility of ssDacA as an antimicrobial target and consider IPA-3 as a promising starting point for the development of a novel antibacterial.

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study.

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049-0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.

Alterations in resting-state global brain connectivity in bipolar I disorder patients with prior suicide attempt.

BACKGROUND: Bipolar I disorder (BD-I) is associated with a high risk of suicide attempt; however, the neural circuit dysfunction that confers suicidal vulnerability in individuals with this disorder remains largely unknown. Resting-state functional magnetic resonance imaging (rs-fMRI) allows non-invasive mapping of brain functional connectivity. The current study used an unbiased voxel-based graph theory analysis of rs-fMRI to investigate the intrinsic brain networks of BD-I patients with and without suicide attempt. METHODS: A total of 30 BD-I patients with suicide attempt (attempter group), 82 patients without suicide attempt (non-attempter group), and 67 healthy controls underwent rs-fMRI scan, and then global brain connectivity (GBC) was computed as the sum of connections of each voxel with all other gray matter voxels in the brain. RESULTS: Compared with the non-attempter group, we found regional differences in GBC values in emotion-encoding circuits, including the left superior temporal gyrus, bilateral insula/rolandic operculum, and right precuneus (PCu)/cuneus in the bipolar disorder (BD) attempter group, and these disrupted hub-like regions displayed fair to good power in distinguishing attempters from non-attempters among BD-I patients. GBC values of the right PCu/cuneus were positively correlated with illness duration and education in the attempter group. CONCLUSIONS: Our results indicate that abnormal connectivity patterns in emotion-encoding circuits are associated with the increasing risk of vulnerability to suicide attempt in BD patients, and global dysconnectivity across these emotion-encoding circuits might serve as potential biomarkers for classification of suicide attempt in BD patients.

Treating Fungal Keratitis with Oral Voriconazole Only: A Case Series.

BACKGROUND: To report the clinical effect of oral voriconazole only as a treatment for fungal keratitis. HISTORY AND SIGNS: Three patients (1 female and 2 males) with culture-proven fungal keratitis (1 Mucoraceae, 1 Aspergillus, 1 Fusarium) were included in this study. The patients were treated with oral voriconazole 200 mg twice daily to observe the clinical response in the treatment of fungal keratitis. THERAPY AND OUTCOME: The mean age of the patients was 51 years and the average treatment duration was 6 weeks. The corneal inflammation in these three patients was eliminated by oral voriconazole only. CONCLUSIONS: This is the first reported case of oral voriconazole only as a treatment for fungal keratitis. We found that oral voriconazole has a significant clinical effect on the treatment of fungal keratitis.

Aerobic exercise impacts the anterior cingulate cortex in adolescents with subthreshold mood syndromes: a randomized controlled trial study.

Aerobic exercise is effective in alleviating mood symptoms while the mechanism is poorly understood. There are limited clinical trials that investigated the effect of exercise on the anterior cingulate cortex (ACC), a key brain region involved in mood regulations, in adolescents with subthreshold mood syndromes. This randomized controlled trial (RCT) of aerobic exercise was undertaken in a middle school in Guangzhou, China. Participants were adolescents aged 12-14 with subthreshold mood syndromes including depressive and manic symptoms and were randomly assigned to an aerobic exercise intervention or a psychoeducation control group. Participants in the exercise group received moderate-intensity exercise intervention, consisting of 30 mins running, 4 days per week for 3 months. The primary outcome in this study was structural changes in the ACC from baseline to post intervention. The trial was registered with ClinicalTrial.gov (NCT03300778). Of 56 participants who met the criteria for subthreshold mood syndromes, 39 (41.03% males) had complete MRI data, with 20 and 19 subjects in the exercise and control group, respectively. At baseline, demographic information (e.g., age and sex), clinical symptoms, and the gray matter volume and cortical thickness of ACC were matched between the two groups. After 12 weeks of treatment, participants in the exercise group displayed increased gray matter volume of the left rostral ACC (F1,30 = 5.73, p = 0.02) and increased cortical thickness of the right rostral ACC (F1,30 = 7.83, p = 0.01) when compared with the control group. No significant differences were found for caudal ACC cortical thickness and gray matter volume. Our data demonstrate that 12-week, moderate-intensity aerobic exercise can induce structural changes in the rostral ACC in adolescents with subthreshold mood syndromes.

CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania.

BACKGROUND: The ß2 subunit of the voltage-gated l-type calcium channel gene(CACNB2) rs11013860 polymorphism is a putative genetic susceptibility marker for bipolar disorder (BD). However, the neural effects of CACNB2 rs11013860 in BD are largely unknown. METHODS: Forty-six bipolar patients with first-episode mania and eighty-three healthy controls (HC) were genotyped for CACNB2 rs11013860 and were scanned with a 3.0 Tesla structural magnetic resonance imaging system to measure cortical thickness of prefrontal cortex (PFC) components (superior frontal cortex, orbitofrontal cortex, middle and inferior frontal gyri). RESULTS: Cortical thickness was thinner in patients on all PFC measurements compared to HC (p < 0.050). Moreover, we found a significant interaction between CACNB2 genotype and diagnosis for the right superior frontal cortical thickness (F = 8.190, p = 0.040). Bonferroni corrected post-hoc tests revealed that, in CACNB2 A-allele carriers, patients displayed thinner superior frontal thickness compared to HC (p < 0.001). In patients, CACNB2 A-allele carriers also exhibited reduced superior frontal thickness compared to CACNB2 CC-allele carriers (p = 0.016). LIMITATIONS: Lithium treatment may influence our results, and the sample size in our study is relatively small. CONCLUSIONS: Our results suggest that the CACNB2 rs11013860 might impact PFC thickness in patients with first-episode mania. These findings provide evidence to support CACNB2 rs11013860 involvement in the emotion-processing neural circuitry abnormality in the early stage of BD, which will ultimately contribute to revealing the link between the variation in calcium channel genes and the neuropathological mechanism of BD.

Inflammation, brain structure and cognition interrelations among individuals with differential risks for bipolar disorder.

Neuro-inflammation might impact on clinical manifestations and cognition function via changing the volumes of key brain structures such as the anterior cingulate cortex (ACC) in bipolar disorder (BD). In this study, we investigated the interrelations among interleukin (IL)-6 cytokine level, grey matter (GM) volume of the anterior cingulated cortex (ACC), and attention function among offspring of parents diagnosed with BD. The offspring were categorized as being either asymptomatic or symptomatic based on whether they manifested pre-defined sub-threshold mood symptoms. We found that the symptomatic offspring showed significantly higher serum levels of IL-6 than the asymptomatic offspring (F(1, 59) = 67.65, p < 0.001). On the brain level, we obtained significant interactive effect of group and IL6 level on the ACC GM (PFWE = 0.017). Specifically, the GM volume of the rostral ACC was negatively associated with the levels of IL-6 in the asymptomatic offspring (PFWE = 0.021), but not the symptomatic offspring (PFWE > 0.05). Mediation analyses revealed that the GM volume of the rostral ACC significantly mediated the negative association between the IL-6 levels and attention performance in the asymptomatic offspring (bootstrapping Confidence Interval (CI) = -6.0432 to -0.0731) but not the symptomatic offspring (bootstrapping CI = -0.3197 to 1.3423). Our data suggest that the asymptomatic and symptomatic bipolar offspring may exhibit different neurocognitive-inflammatory profiles, which could be further validated as viable biosignatures for BD risk and resilience.